Next-Gen Wearables Unlocking Chemical Secrets

Published: February 2024

Authors: Haick, H.

Years: 2024

Published in: Adv. Sensor Res, https://doi.org/10.1002/adsr.202300203

In recent years, wearable technology has transcended its initial emphasis on fitness and lifestyle applications, expanding its horizons to encompass a critical role in healthcare and environmental monitoring. This remarkable evolution has been propelled by the advancement of wearable chemical sensors, a burgeoning field that has piqued the interest of both the scientific community and the general public. Wearable chemical sensors are distinct in their unparalleled ability to offer direct and precise insights into our health and surroundings. This trait is crucial in providing real-time insights into various personalised healthcare, environmental safety, and ubiquity of Internet of Things (IoT) that cannot be matched by other sensor types. For instance, these sensors can identify biomarkers in sweat or monitor air quality, yielding critical information that can lead to early disease detection or the identification of environmental risks.

A 10-micrometer- thick nanomesh-reinforced gas-permeable hydrogel skin sensor for long-term electrophysiological monitoring

Published: January 2024

Authors: Zhang, Z.; Yang, J.; Wang H.; Wang C.; Gu, Y.; Xu, Y.; Lee S.; Yokota T.; Haick, H.; Someya T.; Wang, Y.

Years: 2024, 2024

Published in: Science Advances, http:// DOI: 10.1126/sciadv.adj538

Hydrogel-enabled skin bioelectronics that can continuously monitor health for extended periods is crucial for early disease detection and treatment. However, it is challenging to engineer ultrathin gas-permeable hydrogel sensors that can self-adhere to the human skin for long-term daily use (>1 week). Here, we present a ~10-micrometer-thick polyurethane nanomesh–reinforced gas-permeable hydrogel sensor that can self-adhere to the human skin for continuous and high-quality electrophysiological monitoring for 8 days under daily life conditions. This research involves two key steps: (i) material design by gelatin-based thermal-dependent phase change hydrogels and (ii) robust thinness geometry achieved through nanomesh reinforcement. The resulting ultrathin hydrogels exhibit a thickness of ~10 micrometers with superior mechanical robustness, high skin adhesion, gas permeability, and anti-drying performance. To highlight the potential applications in early disease detection and treatment that leverage the collective features, we demonstrate the use of ultrathin gas-permeable hydrogels for long-term, continuous high-precision electrophysiological monitoring under daily life conditions up to 8 days.

AI-Driven Wearable Mask-Inspired Self-Healing Sensor Array for Detection and Identification of Volatile Organic Compounds

Published: October 2023

Authors: Chen, M.; Zhang, M.; Yang.Z.; Zhou, C.; Cui, D.; Haick, H.; Tang, N.

Years: 2023

Published in: Adv. Func. Mater., https://doi.org/10.1002/adfm.202309732

Volatile organic compounds (VOCs) sensor arrays have garnered considerable attention due to their potential to provide real-time information for monitoring pollution levels and personal health associated concerning VOCs in the ambient environment. Here, an AI-driven wearable mask-inspired self-healing sensor array (MISSA), created using a simplified single-step stacking technique for detecting and identifying VOCs is presented. This wearable MISSA comprises three vertically placed breathable self-healing gas sensors (BSGS) with linear response behavior, consistent repeatability, and reliable self-healing abilities. For wearable and portable monitoring, the MISSA is combined with a flexible printed circuit board (FPCB) to produce a mobile-compatible wireless system. Due to the distinct layers of MISSA, it creates exclusive code bars for four distinct VOCs over three concentration levels. This grants precise gas identification and concentration prognoses with excellent accuracy of 99.77% and 98.3%, respectively. The combination of MISSA with artificial intelligence (AI) suggests its potential as a successful wearable device for long-term daily VOC monitoring and assessment for personal health monitoring scenarios.

Self-Powered Freestanding Multifunctional Microneedle-Based Extended Gate Device for Personalized Health Monitoring

Published: October 2023

Authors: Omar, R.; Yuan, M.; Wang, J.; Sublaban.M.; Saliba, W.; Zheng, Y.; Haick, H.

Years: 2023

Published in: Sensors and Actuators, https://doi.org/10.1016/j.snb.2023.134788

Online monitoring of prognostic biomarkers is critically important when diagnosing disorders and assessing individuals’ health, especially for chronic and infectious diseases. Despite this, current diagnosis techniques are time-consuming, labor-intensive, and performed offline. In this context, developing wearable devices for continuous measurements of multiple biomarkers from body fluids has considerable advantages including availability, rapidity, convenience, and minimal invasiveness over the conventional painful and time-consuming tools. However, there is still a significant challenge in powering these devices over an extended period, especially for applications that require continuous and long-term health monitoring. Herein, a new freestanding, wearable, multifunctional microneedle-based extended gate field effect transistor biosensor is fabricated for online detection of multiple biomarkers from the interstitial fluid including sodium, calcium, potassium, and pH along with excellent electrical response, reversibility, and precision. In addition, a hybrid powering system of triboelectric nanogenerator and solar cell was developed for creating a freestanding, closed-loop platform for continuous charging of the device’s battery and integrated with an Internet of Things technology to broadcast the measurements online, suggesting a stand-alone, stable multifunctional tool which paves the way for advanced practical personalized health monitoring and diagnosis.

Continuous Monitoring of Psychosocial Stress by Non-Invasive Volatilomics

Published: July 2023

Authors: Mansour, E.; Saliba, W.; Broza, Y. Y.; Frankfurt, O.; Zuri, L.; Ginat, K.; Palzur, E.; Shamir, A.; Haick, H.

Years: 2023

Published in: ACS Publications, https://doi.org/10.1021/acssensors.3c00945

Stress is becoming increasingly commonplace in modern times, making it important to have accurate and effective detection methods. Currently, detection methods such as self-evaluation and clinical questionnaires are subjective and unsuitable for long-term monitoring. There have been significant studies into biomarkers such as HRV, cortisol, electrocardiography, and blood biomarkers, but the use of multiple electrodes for electrocardiography or blood tests is impractical for real-time stress monitoring. To this end, there is a need for non-invasive sensors to monitor stress in real time. This study looks at the possibility of using breath and skin VOC fingerprinting as stress biomarkers. The Trier social stress test (TSST) was used to induce acute stress and HRV, cortisol, and anxiety levels were measured before, during, and after the test. GC–MS and sensor array were used to collect and measure VOCs. A prediction model found eight different stress-related VOCs with an accuracy of up to 78%, and a molecularly capped gold nanoparticle-based sensor revealed a significant difference in breath VOC fingerprints between the two groups. These stress-related VOCs either changed or returned to baseline after the stress induction, suggesting different metabolic pathways at different times. A correlation analysis revealed an association between VOCs and cortisol levels and a weak correlation with either HRV or anxiety levels, suggesting that VOCs may include complementary information in stress detection. This study shows the potential of VOCs as stress biomarkers, paving the way into developing a real-time, objective, non-invasive stress detection tool for well-being and early detection of stress-related diseases.

Spin-Induced Nanomaterials for Detection of Chiral Volatile Organic Compounds

Published: July 2023

Authors: Maity, A.; Haick, H.

Years: 2023

Published in: Appl. Phys. Rev., https://doi.org/10.1063/5.0146656

The capacity to recognize chiral Volatile Organic Compounds (VOCs) is a noteworthy element in many areas, for example, chemistry, pharmacology, and ecological observing. This review centers around the recent advancements in the field of spin-based chiral recognition, with the potential to improve the detection and classification of chiral VOCs in wearable, convenient, low-power, and with least human contribution. It will present and discuss the utilization of chiral molecules and helical structures to impact the spin course of electrons going through them, offering another way for chiral recognition of VOCs. Different dimensionalities of nano materials and related hypothetical leaps forward will be presented and discussed, which could pave the way for smart and miniaturized chiral recognition devices. These devices would empower quicker and more precise location of chiral VOCs in different settings, making them advantageous for a scope of applications later on.

Controlling Fluidic Behavior for Ultra-Sensitive Volatile Sensing

Published: June 2023

Authors: Liu, T.; Zhu, Y.; Guo, L.; Dong, H.; Zhang, M.; Guo, H.; Su, C.; Wang, D.; Hu, W.; Haick, H.; Wu, W.

Years: 2023

Published in: Appl. Phys. Rev., doi.org/10.1063/5.0141840

Volatile organic compounds detection technology, electronic nose, is promising in various applications such as health management, environmental monitoring, public safety, agriculture, and food production. The critical point of electronic nose to achieve good recognition ability, the fundament for applications, is the generation of high-quality signal characteristics that are transduced from each sensor unit, and aided with algorithm. However, chamber without uniform fluidic state introduce sensors’ locations caused artificial characteristics to make the recognition difficult, even incredible. Inspired by the structure of the nasal cavity, a small volume chamber with well-controlled fluidic behavior is designed and fabricated according to theoretical simulation. All the expected fluidic features, including uniform flow field and concentration field, are achieved, which are experimentally demonstrated by humidity and 2-hexanone detection using sensors arrays. The well controlled fluidic behaviors of volatile analytes help achieving the ultra-sensitive volatile organic compounds detection, which might shed a new light for e-nose technology to go over the gap between academics and industry.

Non-Contact Immunological Signaling for Highly-Efficient Regulation of the Transcriptional Map of Human Monocytes

Published: April 2023

Authors: Hashoul, D.; Saliba, W.; Broza, Y. Y.; Haick, H.

Years: 2023

Published in: AIChE, doi.org/10.1002/btm2.10519

The different immune system cells communicate and coordinate a response using a complex and evolved language of cytokines and chemokines. These cellular interactions carry out multiple functions in distinct cell types with numerous developmental outcomes. Despite the plethora of different cytokines and their cognate receptors, there is a restricted number of signal transducers and activators to control immune responses. Herein, we report on a new class of immunomodulatory signaling molecules based on volatile molecules (VMs, namely, volatile organic compounds [VOCs]), by which they can affect and/or control immune cell behavior and transcriptomic profile without any physical contact with other cells. The study demonstrates the role of VMs by analyzing non-contact cell communication between normal and cancerous lung cells and U937 monocytes, which are key players in the tumor microenvironment. Integrated transcriptome and proteome analyses showed the suggested regulatory role of VMs released from normal and cancer cells on neighboring monocytes in several molecular pathways, including PI3K/AKT, PPAR, and HIF-1. Presented data provide an initial platform for a new class of immunomodulatory molecules that can potentially mirror the genomic and proteomic profile of cells, thereby paving the way toward non-invasive immunomonitoring.

Wearable Clinic: From Microneedle-Based Sensors to Next-Generation Healthcare Platforms

Published: March 2023

Authors: Sun, H.; Zheng, Y.; Shi, G.; Haick, H.; Zhang, M.

Years: 2023

Published in: Small, https://doi.org/10.1002/smll.202207539

The rapid development of wearable biosensing calls for next-generation devices that allow continuous, real-time, and painless monitoring of health status along with responsive medical treatment. Microneedles have exhibited great potential for the direct access of dermal interstitial fluid (ISF) in a minimally invasive manner. Recent studies of microneedle-based devices have evolved from conventional off-line detection to multiplexed, wireless, and integrated sensing. In this review, the classification and fabrication techniques of microneedles are first introduced, and then the representative examples of microneedles for transdermal monitoring with different sensing modalities are summarized. State-of-the-art advances in therapeutic and closed-loop systems are presented to formulate guidelines for the development of next-generation microneedle-based healthcare platforms. The potential challenges and prospects are discussed to pave a new avenue toward pragmatic applications in the real world.

Artificial Intelligence-Based Medical Sensors for Healthcare System

Published: March 2023

Authors: Chen, M.; Cui, D.; Haick, H.; Tang, N.

Years: 2023

Published in: Adv. Sensor Res, https://doi.org/10.1002/adsr.202300009

The aging population and the prevalence of infectious diseases have impacted the traditional medical order, significantly increasing the burden on healthcare and adversely affecting the socio-economic system. Medical sensors based on artificial intelligence (AI) provide new ideas for modern medical data collection to monitor the health status of individuals and environmental changes. Meanwhile, with the aid of AI algorithms, the big data processing capabilities of sensor systems have been greatly improved, further realizing early predictions and timely diagnoses. In this paper, a brief overview is offered on the development status of AI-enabled medical sensors for off-body detection, near-body monitoring, disease prediction, and clinical decision support system, and the ongoing challenges and future prospects to move from concept to implementation are discussed. In the foreseeable future, breakthroughs in the combination of medical sensors and AI algorithms are expected to pave the way for early detection and clinical decision support and improve the accuracy and efficiency for disease diagnosis.

Liquid Biopsy-Based Volatile Organic Compounds from Blood and Urine and Their Combined Data Sets for Highly Accurate Detection of Cancer

Published: March 2023

Authors: Einoch-Amor, R.; Levy, J.; Broza, Y. Y.; Vangravs, R.; Rapoport, S.; Zhang, M.; Wu, W.; Leja, M.; A. Behar, J.; Haick, H.

Years: 2023

Published in: ACS Sens., https://doi.org/10.1021/acssensors.2c02422

Liquid biopsy is seen as a prospective tool for cancer screening and tracking. However, the difficulty lies in effectively sieving, isolating, and overseeing cancer biomarkers from the backdrop of multiple disrupting cells and substances. The current study reports on the ability to perform liquid biopsy without the need to physically filter and/or isolate the cancer cells per se. This has been achieved through the detection and classification of volatile organic compounds (VOCs) emitted from the cancer cells found in the headspace of blood or urine samples or a combined data set of both. Spectrometric analysis shows that blood and urine contain complementary or overlapping VOC information on kidney cancer, gastric cancer, lung cancer, and fibrogastroscopy subjects. Based on this information, a nanomaterial-based chemical sensor array in conjugation with machine learning as well as data fusion of the signals achieved was carried out on various body fluids to assess the VOC profiles of cancer. The detection of VOC patterns by either Gas Chromatography−Mass Spectrometry (GC−MS) analysis or our sensor array achieved >90% accuracy, >80% sensitivity, and >80% specificity in different binary classification tasks. The hybrid approach, namely, analyzing the VOC datasets of blood and urine together, contributes an additional discrimination ability to the improvement (>3%) of the model’s accuracy. The contribution of the hybrid approach for an additional discrimination ability to the improvement of the model’s accuracy is examined and reported.

Noninvasive Detection of Stress by Biochemical Profiles from the Skin

Published: February 2023

Authors: Mansour, E.; Palzur, E.; Broza, Y. Y.; Saliba, W.; Kaisari, S.; Goldstein, P.; Shamir, A.; Haick, H.

Years: 2023

Published in: ACS Sens., 8, 3, 1339–1347

Stress is a leading cause of several disease types, yet it is underdiagnosed as current diagnostic methods are mainly based on self-reporting and interviews that are highly subjective, inaccurate, and unsuitable for monitoring. Although some physiological measurements exist (e.g., heart rate variability and cortisol), there are no reliable biological tests that quantify the amount of stress and monitor it in real time. In this article, we report a novel way to measure stress quickly, noninvasively, and accurately. The overall detection approach is based on measuring volatile organic compounds (VOCs) emitted from the skin in response to stress. Sprague Dawley male rats (n = 16) were exposed to underwater trauma. Sixteen naive rats served as a control group (n = 16). VOCs were measured before, during, and after induction of the traumatic event, by gas chromatography linked with mass spectrometry determination and quantification, and an artificially intelligent nanoarray for easy, inexpensive, and portable sensing of the VOCs. An elevated plus maze during and after the induction of stress was used to evaluate the stress response of the rats, and machine learning was used for the development and validation of a computational stress model at each time point. A logistic model classifier with stepwise selection yielded a 66–88% accuracy in detecting stress with a single VOC (2-hydroxy-2-methyl-propanoic acid), and an SVM (support vector machine) model showed a 66–72% accuracy in detecting stress with the artificially intelligent nanoarray. The current study highlights the potential of VOCs as a noninvasive, automatic, and real-time stress predictor for mental health.

Spin-Controlled Helical Quantum Sieve Chiral Spectrometer

Published: February 2023

Authors: Maity, A.; Hershkovitz Pollak, Y.; Gupta, R.; Wu, W.; Haick, H.

Years: 2023

Published in: Adv. Mater., https://doi.org/10.1002/adma.202209125

This article reports on a molecular-spin-sensitive-antenna (MSSA) that is based on stacked layers of organically functionalized graphene on a fibrous helical cellulose network for carrying out spatiotemporal identification of chiral enantiomers. The MSSA structures combine three complementary features: (i) chiral separation via a helical quantum sieve for chiral trapping, (ii) chiral recognition by a synthetically implanted spin-sensitive center in a graphitic lattice; and (iii) chiral selectivity by a chirality-induced-spin mechanism that polarizes the local electronic band-structure in graphene through chiral-activated Rashba spin–orbit interaction field. Combining the MSSA structures with decision-making principles based on neuromorphic artificial intelligence shows fast, portable, and wearable spectrometry for the detection and classification of pure and a mixture of chiral molecules, such as butanol (S and R), limonene (S and R), and xylene isomers, with 95–98% accuracy. These results can have a broad impact where the MSSA approach is central as a precautionary risk assessment against potential hazards impacting human health and the environment due to chiral molecules; furthermore, it acts as a dynamic monitoring tool of all parts of the chiral molecule life cycles.

Room Temperature Humidity Tolerant Xylene Sensor Using a Sn-SnO2 Nanocomposite

Published: January 2023

Authors: Verma,M.; Bahuguna,G.; Saharan, A.; Gaur, S.; Haick, H.; Gupta, R.

Years: 2023

Published in: ACS Publications, https://doi.org/10.1021/acsami.2c22417

Xylene is one of the representative indoor pollutants, even in ppb levels, that affect human health directly. Due to the non-polar and less reactive nature of xylene, its room temperature detection is challenging. This work demonstrates a metallic tin-doped Sn-SnO2 nanocomposite under controlled pH conditions via a simple solvothermal route. The Sn nanoparticles are uniformly distributed inside the SnO2 nanospheres of ∼70 nm with a high specific surface area of 118.8 m2/g. The surface of the Sn-SnO2 nanocomposite exhibits strong affinity toward benzene, toluene, ethylbenzene, and xylene (BTEX) compared to other polar volatile organic compounds (VOCs) such as ethanol, acetone, isopropyl alcohol, formaldehyde, and chloroform tested in this study. The sensor’s response is highest for xylene among BTEX molecules. Under ambient room temperature conditions, the sensor exhibits a linear response to xylene in the 1–100 ppm range with a sensitivity of ∼255% at 60 ppm within ∼1.5 s and recovers in ∼40 s. The sensor is hardly affected by humidity variations (40–70%), leading to enhanced reliability and repeatability under dynamic environmental conditions. The meso and microporous nanosphere morphology act as a nanocontainer for non-polar VOCs to diffuse inside the nanostructures, providing easy accessibility. The metallic Sn increases the affinity for less reactive xylene at room temperature. Thus, the nanocatalytic Sn-SnO2 nanocomposite is an active gas/VOC sensing material and provides an effective solution for sensing major indoor pollutants under humid conditions.

Identification of Key Volatile Organic Compounds Released by Gastric Tissues as Potential Non-Invasive Biomarkers for Gastric Cancer

Published: January 2023

Authors: Mochalski, P.; Leja, M.; Slefarska-Wolak, D.; Mezmale, L.; Patsko, V.; Ager, C.; Krolicka, A.; Mayhew, C.A.; Shani, G.; Haick, H.

Years: 2023

Published in: Diag., Journals Diagnostics Volume 13 Issue 3 10.3390/diagnostics13030335

Background: Volatilomics is a powerful tool capable of providing novel biomarkers for medical diagnosis and therapy monitoring. The objective of this study is to identify potential volatile biomarkers of gastric cancer. Methods: The volatilomic signatures of gastric tissues obtained from two distinct populations were investigated using gas chromatography with mass spectrometric detection. Results: Amongst the volatiles emitted, nineteen showed differences in their headspace concentrations above the normal and cancer tissues in at least one population of patients. Headspace levels of seven compounds (hexanal, nonanal, cyclohexanone, 2-nonanone, pyrrole, pyridine, and phenol) were significantly higher above the cancer tissue, whereas eleven volatiles (ethyl acetate, acetoin, 2,3-butanedione, 3-methyl-1-butanol, 2-pentanone, γ-butyrolactone, DL-limonene, benzaldehyde, 2-methyl-1-propanol, benzonitrile, and 3-methyl-butanal) were higher above the non-cancerous tissue. One compound, isoprene, exhibited contradictory alterations in both cohorts. Five compounds, pyridine, ethyl acetate, acetoin, 2,3-butanedione, and 3-methyl-1-butanol, showed consistent cancer-related changes in both populations. Conclusions: Pyridine is found to be the most promising biomarker candidate for detecting gastric cancer. The difference in the volatilomic signatures can be explained by cancer-related changes in the activity of certain enzymes, or pathways. The results of this study confirm that the chemical fingerprint formed by volatiles in gastric tissue is altered by gastric cancer.

Toward a New Generation of Permeable Skin Electronics

Published: January 2023

Authors: Yang, J.; Zhang, Z.; Zhou, P.; Zhang, Y.; Liu, Y.; Xu, Y.; Gu, Y.; Qin, S.; Haick, H.; Wang, Y.

Years: 2023

Published in: Nanoscale, https://doi.org/10.1039/D2NR06236D

Skin-mountable electronics are considered to be the future of the next generation of portable electronics, due to their softness and seamless integration with human skin. However, impermeable materials limit device comfort and reliability for long-term, continuous usage. The recent emergence of permeable skin-mountable electronics has attracted tremendous attention in the soft electronics field. Herein, we provide a comprehensive and systematic review of permeable skin-mountable electronics. Typical porous materials and structures are first highlighted, followed by discussion of important device properties. Then, we review the latest representative applications of breathable skin-mountable electronics, such as bioelectrical sensors, temperature sensors, humidity and hydration sensors, strain and pressure sensors, and energy harvesting and storage devices. Finally, a conclusion and future directions for permeable skin electronics are provided.

From Conventional to Microfluidic: Progress in Extracellular Vesicle Separation and Individual Characterization

Published: December 2022

Authors: Chen, M.; Lin, S.; Zhou, C.; Cui, D.; Haick, H.; Tang, N.

Years: 2022

Published in: Adv. Healthc. Mater., https://doi.org/10.1002/adhm.202202437

Extracellular vesicles (EVs) are nanoscale membrane vesicles, which contain a wide variety of cargo such as proteins, miRNAs, and lipids. A growing body of evidence suggests that EVs are promising biomarkers for disease diagnosis and therapeutic strategies. Although the excellent clinical value, their use in personalized healthcare practice is not yet feasible due to their highly heterogeneous nature. Taking the difficulty of isolation and the small size of EVs into account, the characterization of EVs at a single-particle level is both imperative and challenging. In a bid to address this critical point, more research has been directed into a microfluidic platform because of its inherent advantages in sensitivity, specificity, and throughput. This review discusses the biogenesis and heterogeneity of EVs and takes a broad view of state-of-the-art advances in microfluidics-based EV research, including not only EV separation, but also the single EV characterization of biophysical detection and biochemical analysis. To highlight the advantages of microfluidic techniques, conventional technologies are included for comparison. The current status of artificial intelligence (AI) for single EV characterization is then presented. Furthermore, the challenges and prospects of microfluidics and its combination with AI applications in single EV characterization are also discussed. In the foreseeable future, recent breakthroughs in microfluidic platforms are expected to pave the way for single EV analysis and improve applications for precision medicine.

Gate-Controlled Chiral Recognition and Spin Assessment with All-Electric Hybrid Quantum Wire-Based Transistors

Published: December 2022

Authors: Maity, A.; Rapoport, S.; Haick, H.

Years: 2022

Published in: Small, https://doi.org/10.1002/smll.202205038

The search for inexpensive and all-electric tunable methods for portable and fast recognition and discrimination between various chiral enantiomers, mainly those found in the gas phase, has been one of the most challenging tasks in the field of analytical chemistry. The current article reports on a chiral sensitive electric architecture (CSEA) of a helical polyaniline (PANI)@carbon nanotube (CNT) hybrid quantum-wire based field effect transistor (FET) platform. The CSEA architecture exhibits gate-controlled-channel-chirality modulation for the selective distinction of Limonene (S(+)/R(−)) at ≈12 V intervals. Typical gate-modulated selectivity of S(+)-Limonene and R(−)-Limonene using two opposite helically turned hybrids, namely as, S-PANI@CNT and R-PANI@CNT are 6.5 and 2.8, respectively. Theoretical analysis and modelling relates the gas-phase chiral quantum probe with spin-channel modulation in CNT by Rashba spin-orbit interaction. This is achieved by applied gate voltage, CNT’s unique curved surface, adsorbed chiral adatom induced scattering center on the curved graphitic lattice and helicoid field from a synthetically prepared helical PANI@CNT hybrid interface.

Microneedle Sensors for Multiplex Applications: Toward Advanced Biomedical and Environmental Analysis

Published: November 2022

Authors: Omar, R.; Zheng, Y.; Wang, J.; Haick, H.

Years: 2022

Published in: Adv. Sensor Res, DOI: 10.1002/adsr.202200032

Microneedles (MNs) are versatile tiny devices that have attracted interest in various fields including medicine, environment, food and agriculture due to their unique properties, such as low-cost, simplicity, pain-free application and minimally invasive penetration, therapeutic efficacy, biosensing ability, and biocompatibility. These properties along with the MNs distinctive geometry including dimension control, material type and fabrication techniques have enabled the optimization of MNs based on each desired application. This review summarizes the latest advances in MN-based sensors in a variety of fields and provides a bird’s eye view over the wide range of applications, starting from material and fabrication techniques to advanced sensor types in the biomedical and environmental fields for both sensing and treatment, and showing the profound advantages of this emerging tool in clinical and sustainable fields.

Ultra-Fast Portable and Wearable Sensing Design for Continuous and Wide-Spectrum Molecular Analysis and Diagnostics

Published: October 2022

Authors: Maity, A.; Milyutin, Y.; Darsa Maidantchik, V.; Hershkovitz Pollak, Y.; Broza, Y. Y.; Omar, R.; Zheng, Y.; Saliba, W.; Huynh, T. P.; Haick, H.

Years: 2022

Published in: Adv. Science, https://doi.org/10.1002/advs.202203693

The design and characterization of spatiotemporal nano-/micro-structural arrangement that enable real-time and wide-spectrum molecular analysis is reported and demonestrated in new horizons of biomedical applications, such as wearable-spectrometry, ultra-fast and onsite biopsy-decision-making for intraoperative surgical oncology, chiral-drug identification, etc. The spatiotemporal sesning arrangement is achieved by scalable, binder-free, functionalized hybrid spin-sensitive (<↑| or <↓|) graphene-ink printed sensing layers on free-standing films made of porous, fibrous, and naturally helical cellulose networks in hierarchically stacked geometrical configuration (HSGC). The HSGC operates according to a time-space-resolved architecture that modulate the mass-transfer rate for separation, eluation and detection of each individual compound within a mixture of the like, hereby providing a mass spectrogram. The HSGC could be used for a wide range of applictions, including fast and real-time spectrogram generator of volatile organic compounds during liquid-biopsy, without the need of any immunochemistry-staining and complex power-hungry cryogenic machines; and wearable spectrometry that provide spectral signature of molecular profiles emiited from skin in the course of various dietry conditions.

Modular Assembly of MXene Frameworks for Noninvasive Disease Diagnosis via Urinary Volatiles

Published: October 2022

Authors: Ding, X.; Zhang, Y.; Zhang, Yu.; Ding Xuf.; Zhang, H.; Cao, T.; Qu, Z.; Ren, J.; Li, L.; Guo, Z.; Xu, F.; Wang, Q.; Wu, X.; Shi, G.; Haick, H.; Zhang, M.

Years: 2022

Published in: ACS Publications, https://doi.org/10.1021/acsnano.2c08266

Volatile organic compounds (VOCs) in urine are valuable biomarkers for noninvasive disease diagnosis. Herein, a facile coordination-driven modular assembly strategy is used for developing a library of gas-sensing materials based on porous MXene frameworks (MFs). Taking advantage of modules with diverse composition and tunable structure, our MFs-based library can provide more choices to satisfy gas-sensing demands. Meanwhile, the laser-induced graphene interdigital electrodes array and microchamber are laser-engraved for the assembly of a microchamber-hosted MF (MHMF) e-nose. Our MHMF e-nose possesses high-discriminative pattern recognition for simultaneous sensing and distinguishing of complex VOCs. Furthermore, with the MHMF e-nose being a plug-and-play module, a point-of-care testing (POCT) platform is modularly assembled for wireless and real-time monitoring of urinary volatiles from clinical samples. By virtue of machine learning, our POCT platform achieves noninvasive diagnosis of multiple diseases with a high accuracy of 91.7%, providing a favorable opportunity for early disease diagnosis, disease course monitoring, and relevant research.

Biomimetic Self-Assembling Metal−Organic Architectures with Non-Iridescent Structural Coloration for Synergetic Antibacterial and Osteogenic Activity of Implants

Published: August 2022

Authors: Zhang, C.; Chu, G.; Ruan, Z.; Tang, N.; Song, C.; Li, Q.; Zhou, W.; Jin, J.; Haick, H.; Chen, Y.; Cui, D.

Years: 2022

Published in: ACS Publications, doi.org/10.1021/acsnano.2c06030

Materials in nature feature versatile and programmable interactions to render macroscopic architectures with multiscale structural arrangements. By rationally combining metal–carboxylate and metal–organophosphate coordination interactions, Au25(MHA)18 (MHA, 6-mercaptohexanoic acid) nanocluster self-assembled structural color coating films and phytic acid (PA)–metal coordination complexes are sequentially constructed on the surface of titanium implants. The Lewis acid–base coordination principle applies for these metal–organic coordination networks. The isotropic arrangement of nanoclusters with a short-range order is investigated via grazing incidence wide-angle X-ray scattering. The integration of robust M–O (M = Ti, Zr, Hf) and labile Cu–O coordination bonds with high connectivity of Au25(MHA)18 nanoclusters enables these artificial photonic structures to achieve a combination of mechanical stability and bacteriostatic activity. Moreover, the colorless and transparent PA–metal complex layer allows the viewing of the structural color and surface wettability switching to hydrophilic and makes feasible the interfacial biomineralization of hydroxyapatite. Collectively, these modular metal–organic coordination-driven assemblies are predictive and rational material design strategies with tunable hierarchy and diversity. The complete metal–organic architectures will not only help improve the physicochemical properties of the bone–implant interface with synergistic antibacterial and osseointegration activities but also can boost surface engineering of medical metal implants.

Debonding-On-Demand Polymeric Wound Patches for Minimal Adhesion and Clinical Communication

Published: August 2022

Authors: Zeng, Q.; Wang, F.; Hu, R.; Ding, X.; Lu, Y.; Shi, G.; Haick, H.; Zhang, M.

Years: 2022

Published in: Adv. Science, https://doi.org/10.1002/advs.202202635

Herein, a multifunctional bilayer wound patch is developed by integrating a debonding-on-demand polymeric tissue adhesive (DDPTA) with an ionic conducting elastomer (ICE). As a skin adhesive layer, the DDPTA is soft and adherent at skin temperature but hard and non-tacky when cooled, so it provides unique temperature-triggered quick adhesion and non-forced detachment from the skin. During use, the dense surface of the DDPTA prevents blood infiltration and reduces unnecessary blood loss with gentle pressing. Moreover, its hydrophobic matrix helps to repel blood and prevents the formation of clots, thus precluding wound tearing during its removal. This unique feature enables the DDPTA to avoid the severe deficiencies of hydrophilic adhesives, providing a reliable solution for a wide range of secondary wound injuries. The DDPTA is versatile in that it can be covered with ICE to configure a DDPTA@ICE patch for initiating non-verbal communication systems by the fingers, leading toward sign language recognition and a remote clinical alarm system. This multifunctional wound patch with debonding-on-demand can promote a new style of tissue sealant for convenient clinical communication.

Hierarchical Graphene-Dye Bilayers for Multimodal Optoelectronic Sensing and Decoupling of Complex Stimuli

Published: August 2022

Authors: Khatib, M.; Rapoport, S.; Zohar, O,; Mansour, E.; Zheng, Y.; Tang, N.; Saliba, W.; Milyutin, Y.; Huynh, T. P.; Haick, H.

Years: 2022

Published in: Adv. Mater., https://doi.org/10.1002/admt.202200920

Signals obtained by chemical or calorimetric sensors are highly coupled and complex, making it very challenging to precisely detect and discriminate between simultaneous stimuli. The development of sensors that provide multiple sensory outputs is a good way to tackle such a long-lasting challenge. Herein, a new design of multimodal sensors capable of generating both colorimetric and electrical sensory outputs is introduced. This is achieved by coupling two functional nanolayers, graphene (electrically active) and dyes (colorimetric) in which each layer can work either autonomously or in conjugation with the other sensing layer. It is shown that the interfacial interaction of graphene with the wide variety of dyes creates unique interfacial sensing sites for the detection of chemicals. This endows each sensor or sensor array, in the format of (opto)electronic nose, with a “fingerprint” of varying bonding possibilities, enlarging the spectrum of gas–sensor interactions. Furthermore, it is shown that the hierarchical nanobilayer structure allows the separation and discrimination of volatile organic compounds (VOCs) based on their diffusion kinetics. Taken together, the bilayer design qualifies as a superior sensor compared to unimodal devices by offering improved detection limits, wider dynamic ranges, and higher sensitivity and selectivity in the binary discrimination of a wide range of stimuli (temperature, relative humidity, and VOCs).

Artificially Intelligent Olfaction for Fast and Noninvasive Diagnosis of Bladder Cancer from Urine

Published: May 2022

Authors: Jian, Y.; Zhang, N.; Liu, T.; Zhu, Y.; Wang, D.; Dong, H.; Guo, L.; Qu, D.; Jiang, X.; Du, T.; Zheng, Y.; Yuan, M.; Fu, X.; Liu, J.; Dou, W.; Niu, F.; Ning, R.; Zhang, G.; Fan, J.; Haick, H.; Wu, W.

Years: 2022

Published in: ACS Publications, doi.org/10.1021/acssensors.2c00467

Globally, bladder cancer (BLC) is one of the most common cancers and has a high recurrence and mortality rate. Current clinical diagnostic approaches are either invasive or inaccurate. Here, we report on a cost-efficient, artificially intelligent chemiresistive sensor array made of polyaniline (PANI) derivatives that can noninvasively diagnose BLC at an early stage and maintain postoperative surveillance through ″smelling″ clinical urine samples at room temperature. In clinical trials, 18 healthy controls and 76 BLC patients (60 and 16 at early and advanced stages, respectively) are assessed by the artificial olfactory system. With the assistance of a support vector machine (SVM), very high sensitivity and accuracy from healthy controls are achieved, exceeding those obtained by the current techniques in practice. In addition, the recurrences of both early and advanced stages are diagnosed well, with the effect of confounding factors on the performance of the artificial olfactory system found to have a negligible influence on the diagnostic performance. Overall, this study contributes a novel, noninvasive, easy-to-use, inexpensive, real-time, accurate method for urine disease diagnosis, which can be useful for personalized care/diagnosis and postoperative surveillance, resulting in saving more lives.

Synthesis, Characterization, and Humidity-Responsiveness of Guar Gum Xanthate and its Nanocomposite with Copper Sulfide Covellite

Published: May 2022

Authors: Le, T.A.; Zouheir, M.; Nikiforow, K.; Khatib, M.; Zohar, O,; Haick, H.; Huynh, T. P.

Years: 2022

Published in: Int. J. Biological Macro., 105-114

A novel conjugation of guar gum with xanthate groups via facile aqueous xanthation reaction has been reported. Density of grafted xanthate on guar gum product (GG-X) is as high as 4.4%, thus GG-X is conceivably characterized and confirmed by various spectrometric, electrochemical, thermogravimetric, and microscopic methods. Complexation of GG-X with numerous borderline and soft metal ions (e.g. Fe2+, Co2+, Ni2+, Cu2+, Pb2+, Pt2+ and Cd2+) yields hydrophilic gel-like materials and shows good agreement with hard and soft acid and base (HSAB) theory. This indicates tremendous potential of GG-X in metal ion extraction, removal and hydrogel cross-linking. GG-X is also employed to formulate an aqueous colloidal dispersion of copper sulfide covellite (GG-X/CuS) nanocomposites. GG-X therefore behaves as a surfactant, allowing formation of electronically conductive nanocomposites. XRD indicates apparent beneficial effects of GG-X in the synthesis of CuS with a crystallite size of 15.6 nm. This novel nanocomposite is a promising material for humidity sensing, showing reversible linear responses to relative humidity changes within 10 to 80% range. The interaction between GG-X and water might cause changes in electrical permittivity of GG-X/CuS nanocomposite and/or electrical hopping conductivity between CuS nanoparticles.

Controlling Response of Polyaniline Towards Humidity by Self- Assembly Fatty Acids

Published: March 2022

Authors: Wang, B.; Jian, Y.; Jiang, X.; Liu, T.; Yang, D.; Zhao, Z.; Liang, Y.; Feng, H.; Yao, X.; Xie, P.; Tang, N.; Haick, H.; Hu, W.; Wu, W.

Years: 2022

Published in: ECS, 11, 037001

Conductive polymers based sensors are potentially a powerful tool for detecting a variety of analytes in gas phase [1-2]. However, the accuracy and reliability of such sensors are threatened by the humidity interference, which limits their use in demanding applications of air-quality monitoring and healthcare [3]. Thus, there is an urgent need to suppress the response of conductive polymers based sensors to humidity [4]. However, it is difficult to fabricate sensors with anti-humidity interference ability.

In this work, a method to control the humidity response of polyaniline (PANI) chemi-resistor based sensors is proposed. The key principle of the method is to self-assemble a fatty acid layer on the surface of PANI to decrease the surface energy and shield the water vapour to adsorb on PANI polymer chains. As a result, the response of PANI sensors towards water vapour is suppressed. To study the relationship between the humidity responses and the chain length of fatty acids, a series of fatty acids with different chain lengths were employed to assemble on PANI surface (Fig.1).

The surface properties of fatty acids modified PANI films were characterized by ATR-FTIR spectra and contact angle test. The results show that the long chain alkyl acid can form more densely packed hydrophilicmolecule layer, which can prevent the water molecular diffuse and adsorb on PANI surface. In addition, the contact angle of fatty acid modified PANI films aredepended on the chain length of surface modified alkyl acid. The fatty acid with a longer chain is more hydrophobic than the shorter ones.

The unmodified and fatty acid modified PANI chemi-resistors were electrically tested under exposure to different concentration of humidity. To further investigate the effect of fatty acid modification on the humidity sensing responses of the PANI gas sensors, the statistical response upon water vapour were summarized in Table 1. The results show that the humidity response suppression effect is depending on the chain length of surface modified alkyl acid. The long chain alkyl acid modified PANI sensors exhibit great suppression of the humidity sensing response; while the short chain modified PANI sensors have weak suppression of the humidity sensing response. Not only the sensor responses at certain water vapourconcentration, but also the concentration depend water vapour response (slopes of linearly fitted lines) were gradually decreased with the surface modified fatty chain length increasing. In specific, the Behenic acid (C22) modified PANI sensors are not sensitive to change of the humidity concentration with a concentration depend water vapour response as low as 0.008 %/ppm, which is only 1/5 of the unmodified PANI sensors.

In summary, we have developed a fatty acids modification based approach to suppress the humidity response on the PANI gas sensors. The effects of chain length of fatty acids on the sensing performance of PANI based gas sensors to a serial concentration of water vapour were studied. The results showed that the sensing response towards water vapour decreased asincreasing the chain length fatty acids. In addition, the concentration depend response, namely the slopes of linearly fitted lines, were gradually decreased with the surface modified fatty chain length increasing. These results indicated that the long chain fatty acid modification on PANI surface can efficiently suppress the humidity response. Furthermore, the surface analysis by contact angle testament showed that the suppression of the humidity response was due to the hydrophobic nature of fatty acid modified PANI surface. This approach to suppress humidity response by hydrophobic surface modification could also be applied on other types of gas sensors.

Biodiagnostics in an Era of Global Pandemics—from Biosensing Materials to Data Management

Published: March 2022

Authors: Broza, Y. Y.; Haick, H.

Years: 2022

Published in: VIEW, https://doi.org/10.1002/VIW.20200164

The novel corona virus SARS-CoV-2 (COVID-19) has exposed the world to challenges never before seen in fast diagnostics, monitoring, and prevention of the outbreak. As a result, different approaches for fast diagnostic and screening are made and yet to find the ideal way. The current mini-review provides and examines evidence-based innovative and rapid chemical sensing and related biodiagnostic solutions to deal with infectious disease and related pandemic emergencies, which could offer the best possible care for the general population and improve the approachability of the pandemic information, insights, and surrounding contexts. The review discusses how integration of sensing devices with big data analysis, artificial Intelligence or machine learning, and clinical decision support system, could improve the accuracy of the recorded patterns of the disease conditions within an ocean of information. At the end, the mini-review provides a prospective on the requirements to improve our coping of the pandemic-related biodiagnostics as well as future opportunities.

Modular Point-of-Care Breath Analyzer and Shape Taxonomy-Based Machine Learning for Gastric Cancer Detection

Published: February 2022

Authors: Polaka, I.; Bhandari, M.P.; Mezmale, L.; Anarkulova, L.; Veliks, V.; Sivins, A.; Lescinska, A.M.; Tolmanis, I.; Vilkoite, I.; Ivanovs, I.; Padilla, M.; Mitrovics, J.; Shani, G.; Haick, H.; Leja, M.

Years: 2022

Published in: Diag., 12, 2, 491

Background: Gastric cancer is one of the deadliest malignant diseases, and the non-invasive screening and diagnostics options for it are limited. In this article, we present a multi-modular device for breath analysis coupled with a machine learning approach for the detection of cancer-specific breath from the shapes of sensor response curves (taxonomies of clusters). Methods: We analyzed the breaths of 54 gastric cancer patients and 85 control group participants. The analysis was carried out using a breath analyzer with gold nanoparticle and metal oxide sensors. The response of the sensors was analyzed on the basis of the curve shapes and other features commonly used for comparison. These features were then used to train machine learning models using Naïve Bayes classifiers, Support Vector Machines and Random Forests. Results: The accuracy of the trained models reached 77.8% (sensitivity: up to 66.54%; specificity: up to 92.39%). The use of the proposed shape-based features improved the accuracy in most cases, especially the overall accuracy and sensitivity. Conclusions: The results show that this point-of-care breath analyzer and data analysis approach constitute a promising combination for the detection of gastric cancer-specific breath. The cluster taxonomy-based sensor reaction curve representation improved the results, and could be used in other similar applications.

Dynamics of Light-Induced Charge Transfer between Carbon Nanotube and CdSe/CdS Core/Shell Nanocrystals

Published: January 2022

Authors: Zeevi, G.; Dehnel, J.; Budniak, A.,K.; Milyutin, Y.; Ankonina, G.; Haick, H.; Lifshitz, E.; Yaish. Y.,E.

Years: 2022

Published in: Nano Fut., 6, 015001

The integration of semiconducting colloidal nanocrystals (NCs) with carbon nanotubes (CNTs) in a single device presents a unique platform that combines optical flexibility with high charge carrying capability. These qualities are desirable in many applications such as photovoltaic cells, photocatalysis, and light sensors. Here, we present hybrid devices that incorporate various CdSe/CdS core/shell NCs, such as seeded quantum dots and asymmetric seeded nanorods (a-sNRs), with a single-wall CNT in a field-effect transistor geometry. We used electrical measurements to probe a light-induced charge transfer (LICT) between the CdSe/CdS NCs and the CNT. We investigate the effect of gate voltage on the LICT magnitude and temporal characteristics. Surprisingly, the measured photo-response depends on the gate voltage, and we observe both electrons and holes transfer from the a-sNRs to the CNT. Furthermore, a comparison between LICT measurements on different devices with different CNTs and NC types reveals that the charge transfer time is directly proportional to the shell-thickness around the CdSe core and inversely correlated with the NCs size. The recovery of the charge trapped inside the CdSe/CdS NCs is characterized by two distinct fast and slow relaxation times, which depend on the NCs size and CNT type. Although, the charge relaxation time is similar between the symmetric QDs and the asymmetric sNRs, the overall percentage of the remaining charge in the QDs is significantly larger than in the sNRs. Understanding both gate voltage and NCs size effect on the LICT processes can optimize the performance of optoelectronic devices.

Wound Dressing: From Nanomaterials to Diagnostic Dressings and Healing Evaluations

Published: January 2022

Authors: Zeng, Q.; Qi, X.; Shi, G.; Zhang, M.; Haick, H.

Years: 2022

Published in: ACS Nano., 16, 2, 1708–1733

Wound dressings based on nanomaterials play a crucial role in wound treatment and are widely used in a whole range of medical settings, from minor to life-threatening tissue injuries. This article presents an educational review on the accumulating knowledge in this multidisciplinary area to lay out the challenges and opportunities that lie ahead and ignite the further and faster development of clinically valuable technologies. The review analyzes the functional advantages of nanomaterial-based gauzes and hydrogels as well as hybrid structures thereof. On this basis, the review presents state-of-the-art advances to transfer the (semi)blind approaches to the evaluation of a wound state to smart wound dressings that enable real-time monitoring and diagnostic functions that could help in wound evaluation during healing. This review explores the translation of nanomaterial-based wound dressings and related medical aspects into real-world use. The ongoing challenges and future opportunities associated with nanomaterial-based wound dressings and related clinical decisions are presented and reviewed.

Wearable Microneedle-Based Extended Gate Transistor for Real-Time Detection of Sodium in Interstitial Fluids

Published: December 2021

Authors: Zheng, Y.; Omar, R.; Zhang, Q.; Tang, N.; Khatib, M.; Xu, Q.; Milyutin, Y.; Saliba, W.; Broza, Y. Y.; Wu, W.; Yuan, M.; Haick, H.

Years: 2021

Published in: Adv. Mater., https://doi.org/10.1002/adma.202108607

Sodium is a prominent prognostic biomarker for assessing health status, such as dysnatremia. As of now, detection and monitoring of sodium levels in the human body is carried out by means of laborious and bulky laboratory equipmentand/or by offline analysis of various body fluids. Herein, an innovative stretchable, skin-conformal and fast-response microneedle extended-gate FET biosensor is reported for real-time detection of sodium in interstitial fluids for minimally invasive health monitoring along with high sensitivity, low limit of detection, excellent biocompatibility, and on-body mechanical stability. The integration of the reported device with a wireless-data transmitter and the Internet-of-Things cloud for real-time monitoring and long-term analysis is reported and discussed. This platform would eventually help bringing unlimited possibilities for effecient medical care and accurate clinical decision-making.

Online vs. On-Campus Higher Education: Exploring Innovation in Students’ Self-Reports and Students’ Learning Products

Published: December 2021

Authors: Usher, M.; Barak, M.; Haick, H.

Years: 2021

Published in: Think. Skills and Cre., 42, 100965

Innovation is an essential competency in the 21st century workplace, and hence, a required skill for higher education students. Studies on innovation in higher education examined the way students perceive themselves as innovators, while others examined the level of innovation in learning products. Research has yet to address the association between innovation as expressed in students’ self-reports and in students’ learning products. Moreover, since due to the COVID-19 outbreak, many faculties rely primarily on online platforms to deliver courses, there is a growing need to identify students’ innovation in online learning environments. This study aimed to examine higher education students’ innovation as expressed in their self-reports and in their learning products, while comparing two formats of the same engineering course: an on-campus synchronous face-to-face (F2F) course, and a fully online asynchronous course. The participants were divided into two groups: F2F students (n = 103), and online students (n = 108). Applying the quasi-experimental design, data were collected via a pre- and post-questionnaire, and students’ mean scores on the innovation level of their learning products. Findings indicated that both F2F and online students self-reported similar levels of innovative behavioral tendencies. Yet, the F2F students received higher mean scores on innovation, compared with the online students, in both individual assignments and team projects. We conclude by suggesting guidelines to better promote students’ innovation in higher education courses delivered online.

Techniques for Wearable Gas Sensors Fabrication

Published: November 2021

Authors: Zhou, C.; Shi, N.; Jiang, X.; Chen, M.; Jiang, J.; Zheng, Y.; Wu, W.; Cui, D.; Haick, H.; Tang, N.

Years: 2021

Published in: Sensors and Actuators, 353, 131133

With the progress of intelligent and digital healthcare, wearable sensors are attracting considerable attention due to their portable and real-time monitoring capabilities. Among them, wearable gas sensors, which can detect both gas markers from the human body and hazardous gas from the environment, are particularly gaining tremendous interest. To ensure the gas sensors can be worn and carried easily, most of them were fabricated on flexible substrates. However, some traditional fabrication techniques of gas sensors such as lithography and chemical vapor deposited, are incompatible with most flexible substrates due to the flexible substrates cannot endure the harsh fabricated conditions, for instance, high temperature. Therefore, fabrication techniques for wearable gas sensors are extremely limited, thus a summary of which is necessary. Here, recent advances in the fabrication techniques of wearable gas sensors are presented. Fabrication techniques included coating techniques, printing techniques, spinning techniques, and transferring techniques are discussed in detail, respectively.

A flexible Dual-Structured MXene for Ultra-Sensitive and Ultra-Wide Monitoring of Anatomical and Physiological Movements

Published: November 2021

Authors: Guo, L.; Li, Z.; Hu, W.; Liu, T.; Zheng, Y.; Yuan, M.; Dai, Y.; Ning, R.; Zhu, Y.; Tao, K.; Zhang, M.; Du, T.; Zhang, L.; Su, C.; Haick, H.; Wu, W.

Years: 2021

Published in: J. Mater. Chem. A., 9, 26867-26874

Flexible devices for capturing anatomical and physiological movements are essential for improving the quality of life in, e.g., disease monitoring, physical rehabilitation, and assistance for people with cognitive disorders. They require high sensitivity, wide detection range, multi-functional applicability, etc. Nevertheless, the current devices and technologies face the challenge of simultaneous achievement of these features, mainly sensitivity and detection range, and thus their utility and applications are limited. Herein we report on the design and production of dual-microstructures of surface micro-bumps and internal hollow pores in a conductive material, an MXene, for obtaining a multifunctional high-performance pressure sensor. The designed sensor has ultra-high sensitivity (401.01 kPa−1, 0–12 kPa), a wide detection range (1.96 Pa to 100 kPa), and stability in a wide range of human physiological and anatomical movement types, including wide range movement (joint movement and gesture), slight movement (muscle movement and wrist pulse), and synchronous movement (respiration, carotid artery, and head movement). With data-mining methods, we show an ultra-sensitive ability to extract gesture behavioral information and physiological information from the sensor signals, and its implications for human health. These performances could be used as a shuttling pad for motor function assessment and dexterous human–robot interaction for rehabilitation robots and intelligent prosthetics.

Highly Efficient Self-Healing Multifunctional Dressing with Antibacterial Activity for Sutureless Wound Closure and Infected Wound Monitoring

Published: November 2021

Authors: Tang, N.; Zhang, R.; Zheng, Y.; Wang, J.; Khatib, M.; Jiang, X.; Zhou, C.; Omar, R.; Saliba, W.; Wu, W.; Yuan, M.; Cui, D.; Haick, H.

Years: 2021

Published in: Adv. Mater., https://doi.org/10.1002/adma.202106842

Wound healing represents a major clinical and public healthcare problem that is frequently challenged by infection risks, detrimental consequences on the surrounding tissues, and difficulties to monitor the healing process. Here we report on a novel self-healing, antibacterial, and multifunctional wound dressing for sutureless wound closure and real-time monitoring of the healing parameters. The self-healing elastomer contains cetyltrimethylammonium bromide (CTAB) and has high mechanical toughness (35 MJ m−3), biocompatibility, and outstanding antibacterial activity (bactericidal rate is ≈90% in 12 h), enabling the wound dressing to effectively inhibit bacterial growth and accelerate infected wound healing. In vivo tests based on full-thickness skin incision model shows that the multifunctional wound dressing can help in contracting wound edges and facilitate wound closure and healing, as could be evidenced by notably dense and well-organized collagen deposition. The test provides an evidence that the integrated sensor array within the multifunctional wound dressing can monitor temperature, pH, and glucose level of the wound area in real-time, providing reliable and timely information of the condition of the wound. Ultimately, the reported multifunctional dressing would be of high value in managing the burden associated with wound healing via personalised monitoring and treatment approaches, digital and other people-centred solutions for health care.

An Organic Solvent-Assisted Intercalation and Collection (OAIC) for Ti3C2Tx MXene with Controllable Sizes and Improved Yield

Published: September 2021

Authors: Qu, D.; Jian, Y.; Guo, L.; Su, C.; Tang, N.; Zhang, X.; Hu, W.; Wang, Z.; Zhao, Z.; Zhong, P.; Li, P.; Du, T.; Haick, H.; Wu, W.

Years: 2021

Published in: Nano-Micro Lett., 13, 188

A good method of synthesizing Ti3C2Tx (MXene) is critical for ensuring its success in practical applications, e.g., electromagnetic interference shielding, electrochemical energy storage, catalysis, sensors, and biomedicine. The main concerns focus on the moderation of the approach, yield, and product quality. Herein, a modified approach, organic solvent-assisted intercalation and collection, was developed to prepare Ti3C2Tx flakes. The new approach simultaneously solves all the concerns, featuring a low requirement for facility (centrifugation speed < 4000 rpm in whole process), gram-level preparation with remarkable yield (46.3%), a good electrical conductivity (8672 S cm−1), an outstanding capacitive performance (352 F g−1), and easy control over the dimension of Ti3C2Tx flakes (0.47–4.60 μm2). This approach not only gives a superb example for the synthesis of other MXene materials in laboratory, but sheds new light for the future mass production of Ti3C2Tx MXene.

Stretchable and Highly Permeable Nanofibrous Sensors for Detecting Complex Human Body Motion

Published: August 2021

Authors: Horev, Y.D.; Maity, A.; Zheng, Y.; Milyutin, Y.; Khatib, M.; Yuan, M.; Suckeveriene, R.Y.; Tang, N.; Wu, W.; Haick, H.

Years: 2021

Published in: Adv. Mater., https://doi.org/10.1002/adma.202102488

Wearable strain sensors have been attracting special attention in the detection of human posture and activity, as well as for the assessment of physical rehabilitation and kinematics. However, it is a challenge to fabricate stretchable and comfortable-to-wear permeable strain sensors that can provide highly accurate and continuous motion recording while exerting minimal constraints and maintaining low interference with the body. Herein, covalently grafting nanofibrous polyaniline (PANI) onto stretchable elastomer nanomeshes is reported to obtain a freestanding ultrathin (varying from 300 to 10 000 nm) strain sensor that has high gas permeability (10–33 mg h–1). The sensor demonstrates a low weight and can be directly laminated onto the dynamic human skin for long periods of time. The sensor, which produces an intimate connection with solid or living objects, has a stable performance with excellent sustainability, linearity, durability, and low hysteresis. It exibits excellent performance for continuous interrogation of complex movements, mimicking muscle activities, and resembling brain activity. This includes a very precise discrimination of bending and twisting stimuli at different angles (1–180°) and speeds (3–18 rpm) and very low exertion of counter-interference. These results imply the utility of this appraoch for advanced developments of robotic e-skins or e-muscles.

Multifunctional Dressing for Wound Diagnosis and Rehabilitation

Published: July 2021

Authors: Tang, N.; Zheng, Y.; Cui, D.; Haick, H.

Years: 2021

Published in: Adv. Healthc. Mater., https://doi.org/10.1002/adhm.202101292

A wound dressing is a sterile pad or compress that is used in direct contact with a wound to help it heal and prevent further issues or complications. Though wound healing is an intricate dynamic process that involves multiple biomolecular species, conventional wound dressings have a limited ability to provide timely information of abnormal conditions, missing the best time for early treatment. The current perspective presents and discusses the design and development of smart wound dressings that are integrated with multifunctional materials, wearable sensors and drug delivery systems as well as their application ranging from wound monitoring to timely application of therapeutics. The perspective also discusses the ongoing challenges and exciting opportunities associated with the development of wearable sensor-based smart wound dressing and provide critical insights into wound healing monitoring and management.

Profiles of Volatile Biomarkers Detect Tuberculosis from Skin

Published: June 2021

Authors: Vishinkin, R.; Busool, R.; Mansour, E.; Fish, F.; Esmail, A.; Kumar, P.; Gharra, A.; Cancilla, J.C.; Torrecilla, J.S.; Skenders, G.; Leja, M.; Dheda, K.; Singh, S.; Haick, H.

Years: 2021

Published in: Adv. Science, 2100235,1-13

Tuberculosis (TB) is an infectious disease that threatens >10 million people
annually. Despite advances in TB diagnostics, patients continue to receive an
insufficient diagnosis as TB symptoms are not specific. Many existing
biodiagnostic tests are slow, have low clinical performance, and can be
unsuitable for resource-limited settings. According to the World Health
Organization (WHO), a rapid, sputum-free, and cost-effective triage test for
real-time detection of TB is urgently needed. This article reports on a new
diagnostic pathway enabling a noninvasive, fast, and highly accurate way of
detecting TB. The approach relies on TB-specific volatile organic compounds
(VOCs) that are detected and quantified from the skin headspace. A
specifically designed nanomaterial-based sensors array translates these
findings into a point-of-care diagnosis by discriminating between active
pulmonary TB patients and controls with sensitivity above 90%. This fulfills
the WHO’s triage test requirements and poses the potential to become a TB
triage test.

Fabricating and Printing Chemiresistors Ased on Monolayer-Capped Metal Nanoparticles

Published: May 2021

Authors: Milyutin, Y.; Abud-Hawa, M.; Kloper, V.; Mansour, E.; Broza, Y. Y.; Shani, G.; Haick, H.

Years: 2021

Published in: Nat. protocols, 16, 2968–2990

Chemiresistors that are based on monolayer-capped metal nanoparticles (MCNPs) have been used in a wide variety of innovative sensing applications, including detection and monitoring of diagnostic markers in body fluids, explosive materials, environmental contaminations and food quality control. The sensing mechanism is based on reversible swelling or aggregation and/or changes in dielectric constant of the MCNPs. In this protocol, we describe a procedure for producing MCNP-based chemiresistive sensors that is reproducible from device to device and from batch to batch. The approach relies on three main steps: (i) controlled synthesis of gold MCNPs, (ii) fabrication of electrodes that are surrounded with a microbarrier ring to confine the deposited MCNP solution and (iii) a tailor-made drying process to enable evaporation of solvent residues from the MCNP sensing layer to prevent a coffee-ring effect. Application of this approach has been shown to produce devices with ±1.5% variance—a value consistent with the criterion for commercial sensors—as well as long shelf life and stability. Fabrication of chemical sensors based on dodecanethiol- or 2-ethylhexanethiol-capped MCNPs with this approach provides high sensitivity and accuracy in the detection of volatile organic compounds (e.g., octane and decane), toxic gaseous species (e.g., HCl and NH3) in air and simulated mixtures of lung and gastric cancer from exhaled breath.

Sensing gastric cancer via point-of-care sensor breath analyzer

Published: April 2021

Authors: Leja, M.; Kortelainen, J.M.; Polaka, I.; Turppa, E.; Mitrovics, J.; Padilla, M.; Mochalski, P.; Shuster, G.; Pohle, R.; Kashanin, D.; Klemm, R.; Ikonen, V.; Mezmale, L.; Broza, Y. Y.; Shani, G.; Haick, H.

Years: 2021

Published in: Cancer, 127(8),1286-1292

Background: Detection of disease by means of volatile organic compounds from breath samples using sensors is an attractive approach to fast, noninvasive and inexpensive diagnostics. However, these techniques are still limited to applications within the laboratory settings. Here, we report on the development and use of a fast, portable, and IoT–connected point-of-care device (so-called, SniffPhone) to detect and classify gastric cancer to potentially provide new qualitative solutions for cancer screening. Methods: A validation study of patients with gastric cancer, patients with high-risk precancerous gastric lesions, and controls was conducted with 2 SniffPhone devices. Linear discriminant analysis (LDA) was used as a classifying model of the sensing signals obatined from the examined groups. For the testing step, an additional device was added. The study group included 274 patients: 94 with gastric cancer, 67 who were in the high-risk group, and 113 controls. Results: The results of the test set showed a clear discrimination between patients with gastric cancer and controls using the 2-device LDA model (area under the curve, 93.8%; sensitivity, 100%; specificity, 87.5%; overall accuracy, 91.1%), and acceptable results were also achieved for patients with high-risk lesions (the corresponding values for dysplasia were 84.9%, 45.2%, 87.5%, and 65.9%, respectively). The test-phase analysis showed lower accuracies, though still clinically useful. Conclusion: Our results demonstrate that a portable breath sensor device could be useful in point-of-care settings. It shows a promise for detection of gastric cancer as well as for other types of disease. Lay Summary: A portable sensor-based breath analyzer for detection of gastric cancer can be used in point-of-care settings. The results are transferrable between devices via advanced IoT technology. Both the hardware and software of the reported breath analyzer could be easily modified to enable detection and monitirng of other disease states.

Wearable Sensors and Systems for Wound Healing-Related pH and Temperature Detection

Published: April 2021

Authors: Tang, N.; Zheng, Y.; Jiang, X.; Zhou, C.; Jin, H.; Jin, K.; Wu, W.; Haick, H.

Years: 2021

Published in: Micromachines, DOI: 10.3390/mi12040430

Wound healing is a complex tissue regeneration process involving many changes in multiple physiological parameters. The pH and temperature of a wound site have long been recognized as important biomarkers for assessing wound healing status. For effective wound management, wound dressings integrated with wearable sensors and systems used for continuous monitoring of pH and temperature have received much attention in recent years. Herein, recent advances in the development of wearable pH and temperature sensors and systems based on different sensing mechanisms for wound status monitoring and treatment are comprehensively summarized. Challenges in the areas of sensing performance, infection identification threshold, large-area 3-dimensional detection, and long-term reliable monitoring in current wearable sensors/systems and emerging solutions are emphasized, providing critical insights into the development of wearable sensors and systems for wound healing monitoring and management.

Biodiagnostics in an Era of Global Pandemics—From Biosensing Materials to Data Management

Published: April 2021

Authors: Broza, Y. Y.; Haick, H.

Years: 2021

Published in: VIEW, DOI: 10.1002/VIW.20200164

The novel corona virus SARS-CoV-2 (COVID-19) has exposed the world to challenges never
before seen in fast diagnostics, monitoring, and prevention of the outbreak. As a result, different
approaches for fast diagnostic and screening are made and yet to find the ideal way. The current
mini-review provides and examines evidence-based innovative and rapid chemical sensing and
related biodiagnostic solutions to deal with infectious disease and related pandemic
emergencies, which could offer the best possible care for the general population and improve the
approachability of the pandemic information, insights, and surrounding contexts. The review
discusses how integration of sensing devices with big data analysis, artificial Intelligence or
machine learning, and clinical decision support system, could improve the accuracy of the recorded
patterns of the disease conditions within an ocean of information. At the end, the
mini-review provides a prospective on the requirements to improve our coping
of the pandemic-related biodiagnostics as well as future opportunities.

Biointerfaced Sensors for Biodiagnostics

Published: April 2021

Authors: Zohar, O,; Khatib, M.; Omar, R.; Vishinkin, R.; Broza, Y. Y.; Haick, H.

Years: 2021

Published in: VIEW, https://doi.org/10.1002/VIW.20200172

Biointerfaced sensors have emerged as a new paradigm for medical applications that require an interface and/or intimate contact with biological components/systems such as cells, tissues, and whole organs. This article provides a review of the concept, design, and device characteristics of biointerfaced sensors needed for successful implementation of biodiagnostics and monitoring. It begins by presenting and discussing the different considerations that arise from artificial interfaces with different biological environments. It then explores the main strategies for sensor and material design, while highlighting the required chemistry, structure, and mechanical properties needed to maintain an unperturbed interface with the surrounding biological environment. Finally, the review discusses successful state-of-the-art demonstrations of body monitoring and biodiagnostics, focusing on the brain, heart, muscles, skin, teeth, and other tissues for medical purposes. Insights, perspectives, and recommendations for future research are presented.

Detection of Single Cancer Cells in Blood with Artificially Intelligent Nanoarray

Published: March 2021

Authors: Einoch-Amor, R.; Broza, Y. Y.; Haick, H.

Years: 2021

Published in: ACS Nano., 15, 4, 7744–7755

Detection and monitoring of single cancer cells (SCCs), such as circulating tumor cells (CTCs), would be of aid in an efficient early detection of cancer, a tailored (personalized) therapy, and in a fast bedside assessment of treatment efficacy. Nevertheless, currently available techniques, which mostly rely on the isolation of SCCs based on their physical or biological properties, suffer from low sensitivity, complicated technical procedures, low cost-effectiveness, and being unsuitable for continuous monitoring. We report here on the design and use of an artificially intelligent nanoarray based on a heterogeneous set of chemisensitive nanostructured films for the detection of SCCs using volatile organic compounds emanating in the air trapped above blood samples containing SCCs. For demonstration purposes, we have focused on samples containing A549 lung cancer cells (hereafter, SCCA549). The nanoarray developed to detect SCCA549 has >90% accuracy, >85% sensitivity, and >95% specificity. Detection works irrespective of the medium and/or the environment. These results were validated by complementary mass spectrometry. The ability to continuously record, store, and preprocess the signals increases the chances that this nanotechnology might also be useful in the early detection of cancer cells in the blood and continuous monitoring of their possible progression.

CuS-Carrageenan Composite Grown from the Gel/Liquid Interface

Published: March 2021

Authors: Zouheir, M.; Le, T.A.; Torop, J.; Nikiforow, K.; Khatib, M.; Zohar, O,; Haick, H.; Huynh, T. P.

Years: 2021

Published in: ChemSysChem, 3, 1-11

The aim of this study is to highlight novel CuS‐carrageenan nanocomposites grown from the interface between sulfide solutions (liquid phases) and Cu‐ι‐carrageenan gels. Several parameters including pH, copper and carrageenan concentration of the hydrogel that influence the growth of the nanocomposite have been examined. The most effective parameter is the initial pH of the liquid phase, hence, three growing samples at pH 7, 10 and 13 were selected for further studies and referred as LPH7, LPH10 and LPH13. Three CuS‐carrageenan nanocomposites obtained from the three pH conditions were purified and examined in detail using several characterization techniques such as X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and X‐ray photoelectron spectroscopy (XPS). The structure, composition, properties as well as the growth mechanism of the nanocomposite have been studied. Additionally, the electrical conductivity of the nanocomposite was exploited to be used as a sensor of relative humidity and temperature.

Artificial Intelligence in Medical Sensors for Clinical Decisions

Published: February 2021

Authors: Haick, H.; Tang, N.

Years: 2021

Published in: ACS Nano., 15, 3, 3557–3567

Due to the limited ability of conventional methods and the limited perspective of human diagnostics, patients are often diagnosed incorrectly or at a late stage as their disease condition progresses. They may then undergo unnecessary treatments due to inaccurate diagnoses. In this Perspective, we offer a brief overview on the integration of nanotechnology-based medical sensors and artificial intelligence (AI) for advanced clinical decision support systems to help decision-makers and healthcare systems improve how they approach information, insights, and the surrounding contexts, as well as to promote the uptake of personalized medicine on an individualized basis. Relying on these milestones, wearable sensing devices could enable interactive and evolving clinical decisions that could be used for evidence-based analysis and recommendations as well as for personalized monitoring of disease progress and treatment. We present and discuss the ongoing challenges and future opportunities associated with AI-enabled medical sensors in clinical decisions.

Self‐Healing Soft Sensors: From Material Design to Implementation

Published: February 2021

Authors: Khatib, M.; Zohar, O,; Haick, H.

Years: 2021

Published in: Adv. Mater., 2004190, 1-32

The demand for interfacing electronics in everyday life is rapidly accelerating, with an ever‐growing number of applications in wearable electronics and electronic skins for robotics, prosthetics, and other purposes. Soft sensors that efficiently detect environmental or biological/physiological stimuli have been extensively studied due to their essential role in creating the necessary interfaces for these applications. Unfortunately, due to their natural softness, these sensors are highly sensitive to structural and mechanical damage. The integration of natural properties, such as self‐healing, into these systems should improve their reliability, stability, and long‐term performance. Recent studies on self‐healing soft sensors for varying chemical and physical parameters are herein reviewed. In addition, contemporary studies on material design, device structure, and fabrication methods for sensing platforms are also discussed. Finally, the main challenges and future perspectives in this field are introduced, while focusing on the most promising examples and directions already reported.

Multiplexed Nanomaterial-Based Sensor Array for Detection of COVID-19 in Exhaled Breath

Published: August 2020

Authors: Shan, B.; Broza, Y. Y.; Li, W.; Wang, Y.; Wu, S.; Liu, Z.; Wang, J.; Gui, S.; Wang, L.; Zhang, Z.; Liu, W.; Zhou, S.; Jin, W.; Zhang, Q.; Hu, D.; Lin, L.; Zhang, Qiu; Li, Wen; Wang, Jin; Li, H.; Pan, Y.; Haick, H.

Years: 2020

Published in: ACS Nano., 14, 9, 12125–12132

This article reports on a noninvasive approach in detecting and following-up individuals who are at-risk or have an existing COVID-19 infection, with a potential ability to serve as an epidemic control tool. The proposed method uses a developed breath device composed of a nanomaterial-based hybrid sensor array with multiplexed detection capabilities that can detect disease-specific biomarkers from exhaled breath, thus enabling rapid and accurate diagnosis. An exploratory clinical study with this approach was examined in Wuhan, China, during March 2020. The study cohort included 49 confirmed COVID-19 patients, 58 healthy controls, and 33 non-COVID lung infection controls. When applicable, positive COVID-19 patients were sampled twice: during the active disease and after recovery. Discriminant analysis of the obtained signals from the nanomaterial-based sensors achieved very good test discriminations between the different groups. The training and test set data exhibited respectively 94% and 76% accuracy in differentiating patients from controls as well as 90% and 95% accuracy in differentiating between patients with COVID-19 and patients with other lung infections. While further validation studies are needed, the results may serve as a base for technology that would lead to a reduction in the number of unneeded confirmatory tests and lower the burden on hospitals, while allowing individuals a screening solution that can be performed in PoC facilities. The proposed method can be considered as a platform that could be applied for any other disease infection with proper modifications to the artificial intelligence and would therefore be available to serve as a diagnostic tool in case of a new disease outbreak.

Exhaled Breath Diagnostics of Lung and Gastric Cancers in China using Nanosensors

Published: June 2020

Authors: Gharra, A.; Broza, Y. Y.; Yu, G.; Mao, W.; Shen, D.; Deng, L.; Wu, C.; Wang, Q.; Sun, X.; Huang, J.; Xuan, Z.; Huang, B.; Wu, S.; Milyutin, Y.; Kloper, V.; Haick, H.

Years: 2020

Published in: Cancer Comm., https://doi.org/10.1002/cac2.12030

Breath analysis is a promising diagnostic approach for various conditions [12]. It is based on the identification of volatile organic compounds (VOCs) emitted in the breath, which creates a unique volatolomic signature [3]. Owing to their characteristics, VOCs can be measured non‐intrusively from the breath or other body sources [34]. Several studies have shown the diagnostic potential for a variety of conditions based on VOC analysis [59]. Malignant diseases, where early detection is crucial, are the main focus of VOC analysis, with lung cancer (LC) and gastric cancer (GC) being the most studied. LC and GC together were responsible for approximately 2.5 million deaths globally in 2018 [10]. The aim of VOC analysis of the breath using sensors is to identify a “VOC‐print” comprising the total abundances and ratios of the compounds in the breath, giving an overall unique chemical pattern [11]. This technology can help to address specific challenges concerning LC screening and GC mortality [1213]. To facilitate real‐world applications, different ethnic‐ and culture‐based populations should be sampled. Here, we carried out a VOC‐based clinical trial for GC and LC detection in China to classify these two major malignancies with different genetic and cultural backgrounds, using our developed sensors [1] with newly‐developed sensor‐printing and sampling methods.

Highly Aligned Nanowire-Based Strain Sensor for Ultrasensitive Monitoring of Subtle Human Motion-Cover Page

Published: May 2020

Years: 2020

Published in: Small

Highly Efficient and Water-Insensitive Self-Healing Elastomer for Wet and Underwater Electronics

Published: April 2020

Authors: Khatib, M.; Zohar, O,; Saliba, W.; Srebnik, S.; Haick, H.

Years: 2020

Published in: Adv. Func. Mater., 1910196, 1-8

Integrating self‐healing capabilities into soft electronic devices increases their durability and long‐term reliability. Although some advances have been made, the use of self‐healing electronics in wet and/or (under)water environments has proven to be quite challenging, and has not yet been fully realized. Herein, a new highly water insensitive self‐healing elastomer with high stretchability and mechanical strength that can reach 1100% and ≈6.5 MPa, respectively, is reported. The elastomer exhibits a high (>80%) self‐healing efficiency (after ≈ 24 h) in high humidity and/or different (under)water conditions without the assistance of an external physical and/or chemical triggers. Soft electronic devices made from this elastomer are shown to be highly robust and able to recover their electrical properties after damages in both ambient and aqueous conditions. Moreover, once operated in extreme wet or underwater conditions (e.g., salty sea water), the self‐healing capability leads to the elimination of significant electrical leakage that would be caused by structural damages. This highly efficient self‐healing elastomer can help extend the use of soft electronics outside of the laboratory and allow a wide variety of wet and submarine applications.

A Multifunctional Electronic Skin Empowered with Damage Mapping and Autonomic Acceleration of Self-Healing in Designated Locations

Published: March 2020

Authors: Khatib, M.; Zohar, Orr; Saliba, W.; Haick, H.

Years: 2020

Published in: Adv. Mater., 2000246, 1-7

Integrating self‐healing capabilities into soft electronic devices and sensors is important for increasing their reliability, longevity, and sustainability. Although some advances in self‐healing soft electronics have been made, many challenges have been hindering their integration in digital electronics and their use in real‐world conditions. Herein, an electronic skin (e‐skin) with high sensing performance toward temperature, pressure, and pH levels—both at ambient and/or in underwater conditions is reported. The e‐skin is empowered with a novel self‐repair capability that consists of an intrinsic mechanism for efficient self‐healing of small‐scale damages as well as an extrinsic mechanism for damage mapping and on‐demand self‐healing of big‐scale damages in designated locations. The overall design is based on a multilayered structure that integrates a neuron‐like nanostructured network for self‐monitoring and damage detection and an array of electrical heaters for selective self‐repair. This system has significantly enhanced self‐healing capabilities; for example, it can decrease the healing time of microscratches from 24 h to 30 s. The electronic platform lays down the foundation for the development of a new subcategory of self‐healing devices in which electronic circuit design is used for self‐monitoring, healing, and restoring proper device function.

A Multifunctional Electronic Skin Empowered with Damage Mapping and Autonomic Acceleration of Self-Healing in Designated Locations-Cover Page

Published: March 2020

Years: 2020

Published in: Adv. Mater.

Gas Sensors Based on Chemi‑Resistive Hybrid Functional Nanomaterials

Published: March 2020

Authors: Jian, Y.; Hu, W.; Zhao, Z.; Cheng, P.; Haick, H.; Yao, M.; Wu, W.

Years: 2020

Published in: Nano-Micro Lett., 12, 71 (2020)

Chemi-resistive sensors based on hybrid functional materials are promising candidates for gas sensing with high responsivity, good selectivity, fast response/recovery, great stability/repeatability, room-working temperature, low cost, and easy-to-fabricate, for versatile applications. This progress report reviews the advantages and advances of these sensing structures compared with the single constituent, according to five main sensing forms: manipulating/constructing heterojunctions, catalytic reaction, charge transfer, charge carrier transport, molecular binding/sieving, and their combinations. Promises and challenges of the advances of each form are presented and discussed. Critical thinking and ideas regarding the orientation of the development of hybrid material-based gas sensor in the future are discussed.

Disease Detection with Molecular Biomarkers: From Chemistry of Body Fluids to Nature-Inspired Chemical Sensors

Published: November 2019

Authors: Broza, Y. Y.; Zhou, X.; Yuan, M.; Qu, D.; Zheng, Y.; Vishinkin, R.; Khatib, M.; Wu, W.; Haick, H.

Years: 2019

Published in: Chem. Rev., 119, 22, 11761-11817

This article aims to review nature-inspired chemical sensors for enabling fast, relatively inexpensive, and minimally (or non-) invasive diagnostics and follow-up of the health conditions. It can be achieved via monitoring of biomarkers and volatile biomarkers, that are excreted from one or combination of body fluids (breath, sweat, saliva, urine, seminal fluid, nipple aspirate fluid, tears, stool, blood, interstitial fluid, and cerebrospinal fluid). The first part of the review gives an updated compilation of the biomarkers linked with specific sickness and/or sampling origin. The other part of the review provides a didactic examination of the concepts and approaches related to the emerging chemistries, sensing materials, and transduction techniques used for biomarker-based medical evaluations. The strengths and pitfalls of each approach are discussed and criticized. Future perspective with relation to the information and communication era is presented and discussed.

Quantitative Measures of Reliability and Sensitivity of NanoparticleBased Sensors in Detecting Volatile Organic Compounds

Published: November 2019

Authors: Sagiv, A.; Mansour, E.; Semiat, R.; Haick, H.

Years: 2019

Published in: ACS OMEGA, 4, 22, 19983–19990

We herein provide quantitative measures of sensors’ reliability and sensitivity as a function of the sensor’s capacity (maximum detection signal or saturation state) in addition to other adsorption–desorption parameters that define the detection signals toward volatile organic compounds (VOCs). The measures we have developed show differentiation between irregular dispersed points of sensors with low and high capacities. We show that the sharpest capacity that separates between the two types of distribution points, viz the reliability limit (RL), is tightly linked with the desorption constant kd. Less sharp RLs give interpretations of other reliability indicators. RL also provides information about the reliability of detecting signals of VOCs for a given sensor and sensors for a particular VOC. We show that sensors with high capacities are more reliable and sensitive to detecting signals of VOCs than sensors with lower capacities.

Measurement of Temperature and Relative Humidity in Exhaled Breath

Published: November 2019

Authors: Mansour, E.; Vishinkin, R.; Rihet, S.; Saliba, W.; Fish, F.; Sarfati, P.; Haick, H.

Years: 2019

Published in: Sensors and Actuators, https://doi.org/10.1016/j.snb.2019.127371

Temperature and relative humidity are two of the most important variables in breath analysis. Several studies have investigated the temperature range of exhaled breath, mostly in the context of respiratory disease diagnostics, but none of them inspected the correlation with clinical parameters, nor the effect of different geographic locations. In this study, we have built a tailor-made device for measuring temperature and relative humidity in exhaled breath. With it, we have carried out 340 measurements (265 in Paris/France and 75 in Haifa/Israel) from 31 participants. The results show that the temperature range of exhaled breath is 31.4-35.4 °C for Haifa’s participants and 31.4-34.8 °C for Parisian participants and the range of exhaled breath relative humidity is 65.0-88.6% and 41.9-91.0% for Haifa and Paris participants, respectively. Clinical and environmental effects were also inspected to give more information on the confounding factors. The results presented in this study contribute to the definition of the ranges of temperature and relative humidity of exhaled breath in individuals, in addition to their correlation with clinical and environmental factors such as gender, BMI and age. These factors must be taken into consideration in order to increase the reproducibility and reliability of a wide variety of measurements in this particular field.

Volatile Compounds Are Involved in Cellular Crosstalk and Upregulation

Published: October 2019

Authors: Serasanambati, M.; Broza, Y. Y.; Haick, H.

Years: 2019

Published in: Adv. Biosystems, DOI: 10.1002/adbi.201900131

Cell–cell cross talk is of great importance in cancer research due to its major role in proliferation, differentiation, migration, and influence on the apoptotic pathway. Different cell–cell communication mechanisms have come mainly from proteomic and genomic approaches. In this paper, a new route is reported for cross talk between cancer cells that occurs, even when they are far away from each other. Single‐cell and culture analysis shows that upregulation of cancer cells emits hundreds of volatile organic compounds (VOCs) into their headspace. Part of the VOCs remains without any change, disregarding the biological environment around it. The other part of the VOCs is exchanged between monocultures of the cells as well as between co‐cultures of the cells with no physical contact between them, leading to different changes in growth than when left on their own. The chemical nature and composition of these VOCs have been determined and are discussed herein. Cell‐to‐cell cross talk has the advantage of being suitable for transfer/diffusion over relatively long distances. It would thus be expected to serve as a shuttling pad toward the development of advanced approaches that could enable very early detection of cancer and/or monitoring of metastasis and related cancer therapy.

Cell‐Cell Cross Talk: Volatile Compounds Are Involved in Cellular Crosstalk and Upregulation-Cover Page

Published: October 2019

Years: 2019

Published in: Adv. Biosystems

Screening for Gastric Cancer using Exhaled Breath Samples

Published: August 2019

Authors: Broza, Y. Y.; Khatib, S.; Gharra, A.; Krilaviciute, A.; Amal, H.; Polaka, I.; Parshutin, S.; Kikuste, I.; Gasenko, E.; Skapars, R.; Brenner, H.; Leja, M.; Haick, H.

Years: 2019

Published in: BJS, 106(9), 1122-1125

Background: The aim was to derive a breath-based classifier for gastric cancer using a nanomaterial-based sensor array, and to validate it in a large screening population.

Methods: A new training algorithm for the diagnosis of gastric cancer was derived from previous breath samples from patients with gastric cancer and healthy controls in a clinical setting, and validated in a blinded manner in a screening population.

Results: The training algorithm was derived using breath samples from 99 patients with gastric cancer and 342 healthy controls, and validated in a population of 726 people. The calculated training set algorithm had 82 per cent sensitivity, 78 per cent specificity and 79 per cent accuracy. The algorithm correctly classified all three patients with gastric cancer and 570 of the 723 cancer-free controls in the screening population, yielding 100 per cent sensitivity, 79 per cent specificity and 79 per cent accuracy. Further analyses of lifestyle and confounding factors were not associated with the classifier.

Conclusion: This first validation of a nanomaterial sensor array-based algorithm for gastric cancer detection from breath samples in a large screening population supports the potential of this technology for the early detection of gastric cancer.

Interface-Regulated Contact Electrification for Power-Free and Highly Selective Gas Sensing

Published: July 2019

Authors: Wu, C.; Liang, Y.; Hu, W.; Yuan, M.; Bai, X.; Liu, F.; Zheng, Y.; Zhao, Z.; Zhang, M.; Haick, H.; Wang, B.; Wu, W.

Years: 2019

Published in: Adv. Int. Sys., https://doi.org/10.1002/aisy.201900066

The detection of volatile organic compounds (VOCs) is critical in various applications, e.g., medical care, environmental monitoring, public security, agriculture, the food industry, etc., requiring high sensitivity, good selectivity, fast response/recovery, multivariate data treatment, anti‐interferon, and wide tolerance of gas temperature. Herein, taking advantage of the interface inside the composite thin film of contact electrification‐based sensors, a “fill two needs with one deed” strategy is successfully demonstrated and developed to selectively detect VOCs without a power source, which may shed a new light on VOCs’ sensing in the future sensor network.

Time‐Resolved and Self‐Adjusting Hybrid Functional Fabric Sensor for Decoupling Multiple Stimuli from Bending

Published: June 2019

Authors: Sun, J.,J.; Zhang, M.; Khatib, M.; Milyutin, Y.; Saliba, W.; Kloper, V.; Gharra, A.; Wu, W.; Jin, H.; Segev-Bar, M.; Deng, Y.; Horev, Y.D.; Vishinkin, R.; Haick, H.

Years: 2019

Published in: Adv. Mater., https://doi.org/10.1002/admt.201900290

Multi‐parametric sensing fabrics have the potential to lead a new generation of applications in a wide variety of fields. Nevertheless, the use of these devices in complex environments depends on the ability of the sensing fabrics to decouple between various stimuli co‐existing in a complex environment. Fabric backbones with dispersed single‐wall carbon nanotubes and molecularly modified gold nanoparticles in elastomer outerwear of styrene–ethylene–butylene–styrene for multifunctional detection of complex physical and chemical stimuli are presented. This feature of the fabric–elastomer structure endows time‐resolved insensitivity to strain; furthermore, it enables decoupling pressure/relative humidity from curving surfaces. It is also shown that applying incompatible regression models to the time‐resolved output signals gives excellent discrimination between various stimuli collected from a complex environment.

Non-Contact Breath Sampling for Sensor-Based Breath Analysis

Published: April 2019

Authors: Mochalski, P.; Shuster, G.; Leja, M.; Unterkofler, K.; Jaeschke, C.; Skapars, R.; Gasenko, E.; Polaka, I.; Vasiljevs, E.; Shani, G.; Mitrovics, J.; Mayhew, C.A.; Haick, H.

Years: 2019

Published in: J. Breath Res., 13, (2019) 036001

Breath analysis holds great promise for real-time and non-invasive medical diagnosis. Thus, there is a considerable need for simple-in-use and portable analyzers for rapid detection of breath indicators for different diseases in their early stages. Sensor technology meets all of these demands. However, miniaturized breath analyzers require adequate breath sampling methods. In this context, we propose non-contact sampling; namely the collection of breath samples by exhalation from a distance into a miniaturized collector without bringing the mouth into direct contact with the analyzing device. To evaluate this approach different breathing maneuvers have been tested in a real-time regime on a cohort of 23 volunteers using proton transfer reaction mass spectrometry. The breathing maneuvers embraced distinct depths of respiration, exhalation manners, size of the mouth opening and different sampling distances. Two inhalation modes (normal, relaxed breathing and deep breathing) and two exhalation manners (via smaller and wider lips opening) forming four sampling scenarios were selected. A sampling distance of approximately 2 cm was found to be a reasonable trade-off between sample dilution and requirement of no physical contact of the subject with the analyzer. All four scenarios exhibited comparable measurement reproducibility spread of around 10%. For normal, relaxed inspiration both dead-space and end-tidal phases of exhalation lasted approximately 1.5 s for both expiration protocols. Deep inhalation prolongs the end-tidal phase to about 3 s in the case of blowing via a small lips opening, and by 50% when the air is exhaled via a wide one. In conclusion, non-contact breath sampling can be considered as a promising alternative to the existing breath sampling methods, being relatively close to natural spontaneous breathing.

Time-Space-Resolved Origami Hierarchical Electronics for Ultrasensitive Detection of Physical and Chemical Stimuli

Published: March 2019

Authors: Zhang, M.; Sun, J.; Khatib, M.; Lin, Z.Y.; Chen, Z.H.; Saliba, W.; Gharra, A.; Horev, Y.D.; Kloper, V.; Milyutin, Y.; Huynh, T. P.; Brandon, S.; Shi, G.; Haick, H.

Years: 2019

Published in: Nat. Communications, 10, Article number: 1120 (2019)

Recent years have witnessed thriving progress of flexible and portable electronics, with very high demand for cost-effective and tailor-made multifunctional devices. Here, we report on an ingenious origami hierarchical sensor array (OHSA) written with a conductive ink. Thanks to origami as a controllable hierarchical framework for loading ink material, we have demonstrated that OHSA possesses unique time-space-resolved, high-discriminative pattern recognition (TSR-HDPR) features, qualifying it as a smart sensing device for simultaneous sensing and distinguishing of complex physical and chemical stimuli, including temperature, relative humidity, light and volatile organic compounds (VOCs). Of special importance, OSHA has shown very high sensitivity in differentiating between structural isomers and chiral enantiomers of VOCs – opening a door for wide variety of unique opportunities in several length scales.

Associations of Diet and Lifestyle Factors with Common Volatile Organic Compounds in Exhaled Breath of Average-Risk Individuals

Published: March 2019

Authors: Krilaviciute, A.; Leja, M.; Kopp-Schneider, A.; Barash, O.; Khatib, S.; Amal, H.; Broza, Y. Y.; Polaka, I.; Parshutin, S.; Rudule, A.; Haick, H.; Brenner, H.

Years: 2019

Published in: J. Mater. Res., 13 (2019), 026006

Background: Detection of diseases via exhaled breath remains an attractive idea despite persisting gaps in understanding the origin of volatile organic compounds (VOCs) and their relationship with the disease of interest. Data on factors potentially influencing the results of breath analysis remain rather sparse and often controversial. In this study, we aimed to investigate the associations of common VOCs in exhaled breath of average-risk individuals with socio-demographic and lifestyle factors, medical conditions as well as diet. Methods: Alveolar breath samples of 1447 men and women were collected in the morning after fasting and were analyzed using gas-chromatography linked with mass-spectrometry. Study participants were 40–64 years old, cancer-free, with overall good health status. The associations between selected VOCs and various factors determined from the questionnaire data were assessed using two-part-Wilcoxon test and Jonckheere–Terpstra trend test. Results: Fifteen VOCs where each of them was detected in at least 80% of the study population were included in this analysis. Statistically significant associations with various VOCs were demonstrated for gender and consumption of certain foods, such as coffee, leeks and garlic, while smoking was not associated with any of the analyzed compounds. Conclusion: Factors potentially modifying the composition of exhaled breath, such as dietary factors, deserve careful attention in the design and analysis of studies accessing the use of VOCs as diagnostic markers.

Profiling Single Cancer Cells with Volatolomics Approach

Published: January 2019

Authors: Serasanambati, M.; Broza, Y. Y.; Marmur, A.; Haick, H.

Years: 2019

Published in: iScience, 11, 178-188

Single-cell analysis is a rapidly evolving to characterize molecular information at the individual cell level. Here, we present a new approach with the potential to overcome several key challenges facing the currently available techniques. The approach is based on the identification of volatile organic compounds (VOCs), viz. organic compounds having relatively high vapor pressure, emitted to the cell’s headspace. This concept is demonstrated using lung cancer cells with various p53 genetic status and normal lung cells. The VOCs were analyzed by gas chromatography combined with mass spectrometry. Among hundreds of detected compounds, 18 VOCs showed significant changes in their concentration levels in tumor cells versus control. The composition of these VOCs was found to depend, also, on the sub-molecular structure of the p53 genetic status.
Analyzing the VOCs offers a complementary way of querying the molecular mechanisms of cancer as well as of developing new generation(s) of biomedical approaches for personalized screening and diagnosis.

Profiling Single Cancer Cells with Volatolomics Approach-Cover Page

Published: January 2019

Years: 2019

Published in: iScience

Learning from an Intelligent Mechanosensing System of Plants

Published: November 2018

Authors: Huynh, T. P.; Haick, H.

Years: 2018

Published in: Adv. Mater. Tech., DOI: 10.1002/admt.201800464

Mechanosensing in plants affords sensing a wide variety of mechanical stimuli (e.g., gravity, touch, wind, or turgor pressure); therefore, it helps some of them to sense, trap, and devour nutritious animals and/or track water. A glimpse on how learning from the plants’ mechanosensing could be beneficial for real‐world applications in the 21st century is provided herein, starting with an overview of the molecular mechanism behind the mechanotransduction; viz., the change of Ca2+ concentration across the membrane of mechanosensory cells. Details on the mechanosensory organs that characterize the vascular plants are then presented. How scientists apply the current knowledge to plant‐mimetic mechanosensors via advanced materials and technologies is also discussed, ending with a supplementing perspective on the future of plant‐inspired mechanosensing research.

Breath Volatolomics for Diagnosing Chronic Rhinosinusitis

Published: August 2018

Authors: Broza, Y. Y.; Braverman, I.; Haick, H.

Years: 2018

Published in: Int. J. Nanomedicine, 13, 4661–4670

Purpose: Chronic rhinosinusitis (CRS) is one of the most common chronic diseases treated by primary care physicians. It is increasingly recognized that CRS and nasal polyposis (NP) comprise several disease processes with diverse causes. Hence, subgroups of sinusitis need to be differentiated so that patients can be screened appropriately and personalized medical treatment provided.
Patients and methods: To address this need, we use a cross-reactive nanoarray based on either molecularly modified gold nanoparticles or molecularly modified single-walled carbon nanotubes, combined with pattern recognition for analyzing breath samples. Breath samples were collected from three groups of volunteers (total 71) at the Hillel Yaffe Medical Center: CRS, NP, and control.
Results: Nanoarray results discriminated between patients with sinusitis and the control group with 87% sensitivity, 83% specificity, and 85% accuracy. The system also discriminated well between the subpopulations: 1) CRS vs control (76% sensitivity, 90% specificity); 2) CRS vs NP (82% sensitivity, 71% specificity); and 3) NP vs control (71% sensitivity, 90% specificity).
Conclusion: This preliminary study shows that a nanoarray-based breath test for screening population for sinusitis-related conditions is feasible.

Keywords: volatile organic compound, breath analysis, sensor, chronic sinusitis, nasal polyposis

Ex vivo Emission of Volatile Organic Compounds from Gastric Cancer and Non-Cancerous Tissue

Published: July 2018

Authors: Mochalski, P.; Leja, M.; Gasenko, E.; Skapars, R.; Santare, D.; Sivins, A.; Aronsson, DE.; Ager, C.; Jaeschke, C.; Shani, G.; Mitrovics, J.; Mayhew, C.A.; Haick, H.

Years: 2018

Published in: J. Breath Res., doi: 10.1088/1752-7163/aacbfb.

The presence of certain volatile organic compounds (VOCs) in the breath of patients with gastric cancer has been reported by a number of research groups; however, the source of these compounds remains controversial. Comparison of VOCs emitted from gastric cancer tissue to those emitted from non-cancerous tissue would help in understanding which of the VOCs are associated with gastric cancer and provide a deeper knowledge on their generation. Gas chromatography with mass spectrometric detection (GC-MS) coupled with head-space needle trap extraction (HS-NTE) as the pre-concentration technique, was used to identify and quantify VOCs released by gastric cancer and non-cancerous tissue samples collected from 41 patients during surgery. Excluding contaminants, a total of 32 VOCs were liberated by the tissue samples. The emission of four of them (carbon disulfide, pyridine, 3-methyl-2-butanone and 2-pentanone) was significantly higher from cancer tissue, whereas three compounds (isoprene, γ-butyrolactone and dimethyl sulfide) were in greater concentration from the non-cancerous tissues (Wilcoxon signed-rank test, p < 0.05). Furthermore, the levels of three VOCs (2-methyl-1-propene, 2-propenenitrile and pyrrole) were correlated with the occurrence of H. pylori; and four compounds (acetonitrile, pyridine, toluene and 3-methylpyridine) were associated with tobacco smoking. Ex vivo analysis of VOCs emitted by human tissue samples provides a unique opportunity to identify chemical patterns associated with a cancerous state and can be considered as a complementary source of information on volatile biomarkers found in breath, blood or urine.

Sensor Array for Detection of Early Stage Parkinson’s Disease before Medication

Published: July 2018

Authors: Finberg, J.P.M.; Schwartz, M.; Jeries, R.; Badarny, S.; Nakhleh, K. M.; Daoud, E.A.; Ayubkhanov, Y.; Aboud-Hawa, M.; Broza, Y. Y.; Haick, H.

Years: 2018

Published in: ACS Chem. Neurosci., 9 (11), 2548–2553

Early diagnosis of Parkinson’s disease (PD) is important because it affects the choice of therapy and is subject to a relatively high degree of error. In addition, early detection of PD can potentially enable the start of neuroprotective therapy before extensive loss of dopaminergic neurons of the substantia nigra occurs. However, until now, studies for early detection of PD using volatile biomarkers sampled only treated and medicated patients. Therefore, there is a great need to evaluate untreated patients for establishing a real world screening and diagnostic technology. Here we describe for the first time a clinical trial to distinguish between de novo PD and control subjects using an electronic system for detection of volatile molecules in exhaled breath (sensor array). We further determine for the first time the association to other common tests for PD diagnostics as smell, ultrasound, and nonmotor symptoms. The test group consisted of 29 PD patients after initial diagnosis by an experienced neurologist, compared with 19 control subjects of similar age. The sensitivity, specificity, and accuracy values of the sensor array to detect PD from controls were 79%, 84%, and 81% respectively, in comparison with midbrain ultrasonography (93%, 90%, 92%) and smell detection (62%, 89%, 73%). The results confirm previous data showing the potential of sensor arrays to detect PD.

Detection of Halitosis in Breath: Between the Past, Present, and Future

Published: June 2018

Authors: Nakhleh, K. M.; Quatredeniers, M.; Haick, H.

Years: 2018

Published in: Oral Dis., DOI: 10.1111/odi.12699

To develop a new generation of diagnostics for halitosis, replacing the subjective organoleptic assessment, a series of exhaled breath analyzers has been developed and assessed. All three devices rely on the assessment of exhaled volatile sulfuric compounds (VSCs), which are mainly generated in and emitted from the oral cavity, contributing to the malodor. Portable, on-site and easy to use, these devices have potential for non-invasive diagnosis of halitosis. However, global assessment of exhaled VSCs alone has two main drawbacks: (i) the absence of VSCs does not rule out halitosis; (ii) non-sulfuric volatile compounds that could be biomarkers of systemic diseases, found in up to 15% of halitosis cases, are neglected. In this article, we review and discuss progress to date in the field of oral/exhaled volatile compounds as potential non-invasive diagnostics for halitosis. We will briefly describe the generation of these compounds both from local (oral) and distal (extra-oral) sources. In addition, we debate the different analytical approaches in use and discuss the potential value of bio-inspired artificially intelligent olfaction in diagnosing and classifying oral and systemic diseases by analyzing exhaled breath.

Synergy between Nanomaterials and Volatile Organic Compounds for Non-Invasive Medical Evaluation

Published: June 2018

Authors: Broza, Y. Y.; Vishinkin, R.; Barash, O.; Nakhleh, K. M.; Haick, H.

Years: 2018

Published in: Chem. Soc. Rev., 47, 4781-4859

This article is an overview of the present and ongoing developments in the field of nanomaterial-based sensors for enabling fast, relatively inexpensive and minimally (or non-) invasive diagnostics of health conditions with follow-up by detecting volatile organic compounds (VOCs) excreted from one or combination of human body fluids and tissues (e.g., blood, urine, breath, skin). Part of the review provides a didactic examination of the concepts and approaches related to emerging sensing materials and transduction techniques linked with the VOC-based non-invasive medical evaluations. We also present and discuss diverse characteristics of these innovative sensors, such as their mode of operation, sensitivity, selectivity and response time, as well as the major approaches proposed for enhancing their ability as hybrid sensors to afford multidimensional sensing and information-based sensing. The other parts of the review give an updated compilation of the past and currently available VOC-based sensors for disease diagnostics. This compilation summarizes all VOCs identified in relation to sickness and sampling origin that links these data with advanced nanomaterial-based sensing technologies. Both strength and pitfalls are discussed and criticized, particularly from the perspective of the information and communication era. Further ideas regarding improvement of sensors, sensor arrays, sensing devices and the proposed workflow are also included.

Chemically-Modified Polyaniline for the Detection of Volatile Biomarkers of Minimal Sensitivity to Humidity and Bending-Cover Page

Published: May 2018

Years: 2018

Published in: Adv. Healthc. Mater.

Materials and Wearable Devices for Autonomous Monitoring of Physiological Markers

Published: March 2018

Authors: Wu, W.; Haick, H.

Years: 2018

Published in: Adv. Mater., 10.1002/adma.201705024

Wearable devices are gaining considerable attention owing to the ease with which they can collect crucial information in real-time, both continuously and noninvasively, regarding a wearer’s health. A concise summary is given of the three main elements that enable autonomous detection and monitoring of the likelihood or the existence of a health-risk state in continuous and real-time modes, with an emphasis on emerging materials and fabrication techniques in the relevant fields. The first element is the sensing technology used in the noninvasive detection of physiological markers relevant to the state of health. The second element is self-powered devices for longer periods of use by drawing energy from bodily movement and temperature. The third element is the self-healing properties of the materials used in the wearable devices to extended usage if they become scratched or cut. Promises and challenges of the separately reviewed parts and the combined parts are presented and discussed. Ideas regarding further improvement of skin-based wearable devices are also presented and discussed.

Materials and Wearable Devices for Autonomous Monitoring of Physiological Markers-Cover Page

Published: March 2018

Years: 2018

Published in: Adv. Mater.

Detection of Lung Cancer and EGFR Mutation by Electronic Nose System

Published: October 2017

Authors: Dekel, S.; Abud-Hawa, M.; Liran, O.; Bar, J.; Gai-Mor, N.; Ilouze, M.; Onn, A.; Ben-Nun, A.; Haick, H.; Peled, N.

Years: 2017

Published in: J. Thorac. Oncol., 12(10), 1544-1551

Early detection of lung cancer (LC) has been well established as a significant key point in patient survival and prognosis. New highly sensitive nanoarray sensors for exhaled volatile organic compounds that have been developed and coupled with powerful statistical programs may be used when diseases such as LC are suspected. Detection of genetic aberration mutation by nanoarray sensors is the next target.

Breath samples were taken from patients who were evaluated for suspicious pulmonary lesions. Patients were classified as those with benign nodules, as patients with LC with or without the EGFR mutation, and according to their smoking status. Breath prints were recognized by nanomaterial-based sensor array, and pattern recognition methods were used.

A total of 119 patients participated in this study, 30 patients with benign nodules and 89 patients with LC (16 with early disease and 73 with advanced disease). Patients with LC who harbored the EGFR mutation (n = 19) could be discriminated from those with wild-type EGFR (n = 34) with an accuracy of 83%, sensitivity of 79%, and specificity of 85%. Discrimination of early LC from benign nodules had 87% accuracy and positive and negative predictive values of 87.7 and 87.5% respectively. Moderate discrimination (accuracy of 76%) was found between LC of heavy smokers and that of never-smokers or distant past light smokers.

Breath analysis could discriminate patients with LC who harbor the EGFR mutation from those with wild-type EGFR and those with benign pulmonary nodules from those patients with early LC. A positive breath print for the EGFR mutation may be used in treatment decisions if tissue sampling does not provide adequate material for definitive mutation analysis.

Exhaled Breath Markers for Nonimaging and Noninvasive Measures for Detection of Multiple Sclerosis

Published: August 2017

Authors: Broza, Y. Y.; Har-Shai, L.; Jeries, R.; Cancilla, J.C.; Glass-Marmor, L.; Lejbkowicz, I.; Torrecilla, J.S.; Yao, X.; Feng, X.; Narita, A.; Müllen, K.; Miller, A.; Haick, H.

Years: 2017

Published in: ACS Chem. Neurosci., 8, 2402−2413

Multiple sclerosis (MS) is the most common chronic neurological disease affecting young adults. MS diagnosis is based on clinical characteristics and confirmed by examination of the cerebrospinal fluids (CSF) or by magnetic resonance imaging (MRI) of the brain or spinal cord or both. However, neither of the current diagnostic procedures are adequate as a routine tool to determine disease state. Thus, diagnostic biomarkers are needed. In the current study, a novel approach that could meet these expectations is presented. The approach is based on noninvasive analysis of volatile organic compounds (VOCs) in breath. Exhaled breath was collected from 204 participants, 146 MS and 58 healthy control individuals. Analysis was performed by gas-chromatography mass-spectrometry (GC-MS) and nanomaterial-based sensor array. Predictive models were derived from the sensors, using artificial neural networks (ANNs). GC-MS analysis revealed significant differences in VOC abundance between MS patients and controls. Sensor data analysis on training sets was able to discriminate in binary comparisons between MS patients and controls with accuracies up to 90%. Blinded sets showed 95% positive predictive value (PPV) between MS-remission and control, 100% sensitivity with 100% negative predictive value (NPV) between MS not-treated (NT) and control, and 86% NPV between relapse and control. Possible links between VOC biomarkers and the MS pathogenesis were established. Preliminary results suggest the applicability of a new nanotechnology-based method for MS diagnostics.

Controlling Marangoni Flow Directionality: Patterning Nano-Materials Using Sessile and Sliding Volatile Droplets

Published: May 2017

Authors: Abo-Jabal, M.; Homede, E.; Pismen, L.M.; Haick, H.; Leshansky, A.M.

Years: 2017

Published in: Eur. Phys. J. Special Topics, 226, 1307-1324

Controlling the droplet shape and the corresponding deposition patterns is pivotal in a wide range of processes and applications based on surface phenomena, such as self-assembly of different types of nanomaterials and fabrication of functional electronic devices. In this paper we study different flow regimes and deposition patterns from volatile sessile droplets and droplets sliding over inclined solid substrates. The directionality and intensity of the Marangoni flow was controlled by vapor composition in a sealed chamber enclosing the evaporating droplets. Two types of volatile droplets are investigated: single component droplets and binary solution droplets. Binary solution droplets can exhibit either inward or outward Marangoni soluto-capillary flow, depending on a surface tension dependence on the concentration of the fast evaporating component. We carried out a detailed experimental study of the micro-rivulet (μ-R) regime in different binary solutions. The μ-R formation in a certain range of Ca proved to be a universal phenomenon subject to the occurrence of inward Marangoni flow. We propose a simplified mathematical model for the shape of μ-R based on the lubrication approximation. The resulting μ-R profile shows a good agreement with the experimental results.

Diketopyrrolopyrrole Copolymers Based Chemical Sensors for the Detection and Discrimination of Volatile Organic Compounds

Published: April 2017

Authors: Wang, B.; Sonar, P.; Manzhos, S.; Haick, H.

Years: 2017

Published in: Sens. Actuat. B, 251, 49-56

With their high charge carrier mobility and easy solution processability, diketopyrrolopyrrole (DPP) copolymers are considered as very promising active organic semiconducting materials for a wide range of organic electronic devices. This class of materials has already successfully demonstrated a very high mobility in organic thin film transistors (OFETs) and impressive performance in organic photovoltaic (OPV) devices. Apart from OFET and OPV, there are very few reports about these materials for other organic electronic devices such as chemical sensors. In the present work, we have used these high mobility DPP copolymers as active semiconductors in OFET device based chemical sensors for sensing of volatile organic compounds (VOCs) in air. Combined with a pattern recognition algorithm and sensor data obtained from an array of DPP copolymer OFETs, VOCs with similar structure can be discriminated from each other. This opens up a novel opportunity to use promising DPP based polymers as active semiconductors for chemical sensors.

Multi-Parametric Sensing Platforms Based on Nanoparticles

Published: January 2017

Authors: Segev-Bar, M.; Bachar, N.; Wolf, Y.; Ukrainsky, B.; Sarraf, L.; Haick, H.

Years: 2017

Published in: Adv. Mater., 2, 1-14

Multi-parametric sensing platforms offer the possibility to measure simultaneously several stimuli, and potentially to differentiate between the different signals. They have advantages in fields that include wearable systems, humanoid robotics, structural health monitoring and precision agriculture, since a complex stimuli from the environment is usually an integrated component in these examples. In the current progress report, we present and discuss new avenues in nanoparticle-based multi-parametric sensing platforms for the detection, classification and separation of common stimuli, e.g., temperature, humidity, strain/pressure and volatile organic compounds (VOCs). New data involving multi-parametric sensing with nanoparticle-based sensors are given for each topic. Future prospects are discussed.

Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules

Published: December 2016

Authors: Nakhleh, K. M.; Amal, H.; Jeries, R.; Broza, Y. Y.; Abud-Hawa, M.; Gharra, A.; Ivgi, H.; Khatib, S.; Badarneh, S.; Har-Shai, L.; Glass-Marmor, L.; Lejbkowicz, I.; Miller, A.; Badarny, S.; Winer, R.; Finberg, J.; Cohen-Kaminsky, S.; Perros, F.; Montani, D.; Girerd, B.; Garcia, G.; Simonneau, G.; Nakhoul, F.; Baram, S.; Salim, R.; Hakim, M.; Gruber, M.; Ronen, O.; Marshak, T.; Doweck, I.; Nativ, O.; Bahouth, Z.; Shi, D. Y.; Zhang, W.; Hua, Q.L.; Pan, Y.Y.; Tao, L.; Liu, H.; Karban, A.; Koifman, E.; Rainis, T.; Skapars, R.; Sivins, A.; Ancans, G.; Liepniece-Karele, I.; Kikuste, I.; Lasina, I.; Tolmanis, I.; Johnson, D.; Millstone, S.Z.; Fulton, J.; Wells, J.W.; Wilf, L.H.; Humbert, M.; Leja, M.; Peled, N.; Haick, H.

Years: 2016

Published in: ACS Nano., DOI: 10.1021/acsnano.6b04930

We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others. Cluster analysis showed a reasonable classification power of diseases from the same categories. The effect of confounding clinical and environmental factors on the performance of the nanoarray did not significantly alter the obtained results. The diagnosis and classification power of the nanoarray was also validated by an independent analytical technique, i.e., gas chromatography linked with mass spectrometry. This analysis found that 13 exhaled chemical species, called volatile organic compounds, are associated with certain diseases, and the composition of this assembly of volatile organic compounds differs from one disease to another. Overall, these findings could contribute to one of the most important criteria for successful health intervention in the modern era, viz. easy-to-use, inexpensive (affordable), and miniaturized tools that could also be used for personalized screening, diagnosis, and follow-up of a number of diseases, which can clearly be extended by further development.

Advanced Materials for Use in Soft Self-Healing Devices

Published: November 2016

Authors: Huynh, T. P.; Sonar, P.; Haick, H.

Years: 2017

Published in: Adv. Mater., DOI: 10.1002/adma.201604973

 Devices integrated with self-healing ability can benefit from long-term use as well as enhanced reliability, maintenance and durability. This progress report reviews the developments in the field of self-healing polymers/composites and wearable devices thereof. One part of the progress report presents and discusses several aspects of the self-healing materials chemistry (from non-covalent to reversible covalent-based mechanisms), as well as the required main approaches used for functionalizing the composites to enhance their electrical conductivity, magnetic, dielectric, electroactive and/or photoactive properties. The second and complementary part of the progress report links the self-healing materials with partially or fully self-healing device technologies, including wearable sensors, supercapacitors, solar cells and fabrics. Some of the strong and weak points in the development of each self-healing device are clearly highlighted and criticized, respectively. Several ideas regarding further improvement of soft self-healing devices are proposed.

Volatolomics of Breath as an Emerging Frontier in Pulmonary Arterial Hypertension

Published: November 2016

Authors: Nakhleh, K. M.; Haick, H.; Humbert, M.; Cohen-Kaminsky, S.

Years: 2017

Published in: Eur Respir J., 49, 1-9

There is accumulating evidence in support of the significant improvement in survival rates and clinical outcomes when pulmonary arterial hypertension (PAH) is diagnosed at early stages. Nevertheless, it remains a major clinical challenge and the outcomes are dependent on invasive right heart catheterisation.

Resulting from pathophysiological processes and detectable in exhaled breath, volatile organic compounds (VOCs) have been proposed as noninvasive biomarkers for PAH. Studies have confirmed significant alterations of the exhaled VOCs among PAH patients when compared to controls and/or patients with other respiratory diseases. This suggests exhaled breath analysis as a potential noninvasive medical application in the field of PAH.

In this article, we review and discuss the progress made so far in the field of exhaled volatolomics (the omics of VOCs) as a potential noninvasive diagnostics of PAH. In addition, we propose a model including possible biochemical pathways on the level of the remodelled artery, in which specific VOCs could be detectable in exhaled breath during the early phases of PAH. We debate the different analytical approaches used and recommend a diagram including a “bottom–top” strategy, from basic to translational studies, required for promoting the field.

Composites of Polymer and Carbon Nanostructures for Self-Healing Chemical Sensors

Published: October 2016

Authors: Huynh, T. P.; Khatib, M.; Srour, R.; Plotkin, M.; Wu, W.; Vishinkin, R.; Hayek, N.; Jin, H.; Gazit, O.M.; Haick, H.

Years: 2016

Published in: Adv. Mater., 1, 1-8

Despite recent dramatic development of materials with self-healing ability, fabrication of a self-healing devices remains challenging. In this paper, truly self-healing composites consisting polymers and carbon nanostructures are reported. Using a modified fabrication technique – called “layer-by-layer stamping” – chemical sensors are produced and characterized by infrared spectroscopy and various microscopy techniques. As a demonstration of the ability of the developed sensors to coexist with harsh operation conditions, the performance of the sensors under exposure to volatile organic compounds that are derived from human breath/skin is evaluated under different conditions of cutting and self-healing cycles. The results show a discrimination ability of the selected sensors to return to an operation level of 70%–100% after cutting and 24 h healing of the composite film. From this analysis, the discriminative power of the self-healing sensor array remains high for the majority of analyte discrimination even after mechanical injury, thus strengthening the potential of such arrays for use in health monitoring applications based on detection of analyte patterns.

Programmed Nanoparticles for Tailoring the Detection of Inflammatory Bowel Diseases and Irritable Bowel Syndrome Disease via Breathprint

Published: September 2016

Authors: Karban, A.; Nakhleh, K. M.; Cancilla, J.C.; Vishinkin, R.; Rainis, T.; Koifman, E.; Jeries, R.; Ivgi, H.; Torrecilla, J.S.; Haick, H.

Years: 2016

Published in: Adv. Healthc. Mater., 5 (18), 2339-2344

Chemical sensors based on programmable molecularly modified gold nanoparticles are tailored for the detection and discrimination between the breathprint of irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD). The sensors are examined in both lab- and real-world clinical conditions. The results reveal a discriminative power accuracy of 81% between IBD and IBS and 75% between Crohn’s and Colitis states.

Printing Ultrasensitive Artificially Intelligent Sensors Array with a Single Self-Propelled Droplet Containing Nanoparticles

Published: July 2016

Authors: Homede, E.; Abo-Jabal, M.; Ionescu, R.; Haick, H.

Years: 2016

Published in: Adv. Func. Mater., 26 (35), 6359-6370

The fabrication and implementation of artificially intelligent sensor arrays has faced serious technical and/or cost-effectiveness challenges. Here, a new printing method is presented to produce a fully functional array of sensors based on monolayer-capped gold nanoparticles. The proposed printing technique is based on the so-called self-propelled antipinning ink droplet, from which evaporative deposition takes place along the path of motion. By applying actuating forces, different deposition line patterns with different thicknesses and morphology from a single droplet are generated. The functionality of the produced sensors is demonstrated by their ability to detect different representative volatile organic compounds (VOCs) belonging to different chemical families, including alcohols, alkanes, ethers, and aromatics, and under extremely different humidity levels resembling those encountered in real-world conditions. The results show that the sensors exhibit ultrasensitive sensing features, with an ability to detect and differentiate between different VOCs at low ppb levels. Additionally, the results show that the sensors are able to accurately predict VOC concentrations, viz. enable quantification capabilities, while nevertheless being inexpensive, do not need complicated and expensive printing equipment and prepatterning processes, allow low voltage operation, and provide a platform for multifunctional applications.

Printing Ultrasensitive Artificially Intelligent Sensors Array with a Single Self-Propelled Droplet Containing Nanoparticles-Cover Page

Published: July 2016

Years: 2018

Published in: Adv. Func. Mater.

Silicon Nanowire Sensors Enable Diagnosis of Patients via Exhaled Breath

Published: July 2016

Authors: Shehada, N.; Cancilla, J.C.; Torrecilla, J.S.; Pariente, E.S.; Brönstrup, G.; Christiansen, S.; Johnson, D.W.; Leja, M.; Davies, M.; Liran, O.; Peled, N.; Haick, H.

Years: 2016

Published in: ACS Nano., 10, 7047-7057

Two of the biggest challenges in medicine today are the need to detect diseases in a noninvasive manner and to differentiate between patients using a single diagnostic tool. The current study targets these two challenges by developing a molecularly modified silicon nanowire field effect transistor (SiNW FET) and showing its use in the detection and classification of many disease breathprints (lung cancer, gastric cancer, asthma, and chronic obstructive pulmonary disease). The fabricated SiNW FETs are characterized and optimized based on a training set that correlate their sensitivity and selectivity toward volatile organic compounds (VOCs) linked with the various disease breathprints. The best sensors obtained in the training set are then examined under real-world clinical conditions, using breath samples from 374 subjects. Analysis of the clinical samples show that the optimized SiNW FETs can detect and discriminate between almost all binary comparisons of the diseases under examination with >80% accuracy. Overall, this approach has the potential to support detection of many diseases in a direct harmless way, which can reassure patients and prevent numerous unpleasant investigations.

Analysis of the Effects of Microbiome-Related Confounding Factors on the Reproducibility of the Volatolomic Test

Published: June 2016

Authors: Leja, M.; Amal, H.; Lasina, I.; Skapars, R.; Sivins, A.; Ancans, G.; Tolmanis, I.; Vanags, A.; Kupcinskas, J.; Ramonaite, R.; Khatib, S.; Bdarneh, S.; Natour, R.; Ashkar, A.; Haick, H.

Years: 2016

Published in: J. Breath Res., 10, 037101

Volatile organic compound (VOC) testing in breath has potential in gastric cancer (GC) detection. Our objective was to assess the reproducibility of VOCs in GC, and the effects of conditions modifying gut microbiome on the test results. Ten patients with GC were sampled for VOC over three consecutive days; 17 patients were sampled before and after H. pylori eradication therapy combined with a yeast probiotic; 61 patients were sampled before and after bowel cleansing (interventions affecting the microbiome). The samples were analyzed by: (1) gas chromatography linked to mass spectrometry (GC-MS), applying the non-parametric Wilcoxon test (level of significance p  <  0.05); (2) by cross-reactive nanoarrays combined with pattern recognition. Discriminant function analysis (DFA) was used to build the classification models; and leave-one-out cross-validation analysis was used to classify the findings. Exhaled VOCs profiles were stable for GC patients over a three day period. Alpha pinene (p  =  0.028) and ethyl acetate (p  =  0.030) increased after the antibiotic containing eradication regimen; acetone (p  =  0.0001) increased following bowel cleansing prior to colonoscopy. We further hypothesize that S. boulardii given with the standard eradication regimen to re-establish the gut microbiome was the source for long-term ethyl acetate production. Differences between the initial and the follow-up sample were also revealed in the DFA analysis of the sensor data. VOC measurement results are well-reproducible in GC patients indicating a useful basis for potential disease diagnostics. However, interventions with a potential effect on the gut microbiome may have an effect upon the VOC results, and therefore should be considered for diagnostic accuracy.

Self-Healable Sensors Based Nanoparticles for Detecting Physiological Markers via Skin and Breath: Toward Disease Prevention via Wearable Devices

Published: June 2016

Authors: Jin, H.; Huynh, T. P.; Haick, H.

Years: 2016

Published in: Nano Lett., 16 (7), 4194–4202

Flexible and wearable electronic sensors are useful for the early diagnosis and monitoring of an individual’s health state. Sampling of volatile organic compounds (VOCs) derived from human breath/skin or monitoring abrupt changes in heart-beat/breath rate should allow noninvasive monitoring of disease states at an early stage. Nevertheless, for many reported wearable sensing devices, interaction with the human body leads incidentally to unavoidable scratches and/or mechanical cuts and bring about malfunction of these devices. We now offer proof-of-concept of nanoparticle-based flexible sensor arrays with fascinating self-healing abilities. By integrating a self-healable polymer substrate with 5 kinds of functionalized gold nanoparticle films, a sensor array gives a fast self-healing (<3 h) and attractive healing efficiency in both the substrate and sensing films. The proposed platform was used in sensing pressure variation and 11 kinds of VOCs. The sensor array had satisfactory sensitivity, a low detection limit, and promising discrimination features in monitoring both of VOCs and pressure variation, even after full healing. These results presage a new type of smart sensing device, with a desirable performance in the possible detection and/or clinical application for a number of different purposes.

UV Regulation of Non-Equilibrated Electrochemical Reaction for Detecting Aromatic Volatile Organic Compounds

Published: June 2016

Authors: Jin, H.; Haick, H.

Years: 2016

Published in: Sensors and Actuators, B 237, 30-40

Analysis of aromatic volatile organic compounds (VOCs) by gas sensors is of utmost important for envi-ronmental monitoring and human health. Nevertheless, most of the reported sensors suffer the problemof undesirable detection limit & poor performance in high humid conditions. We have studied the impactof UV illumination on non-equilibrium electrochemical reactions. Such a principle was applied to yttria-stabilized zirconia-based gas sensors, which have been used in many practical applications. Typically,2 fold increase in the sensing magnitude and sensitivity was achieved with UV illumination. With thecontribution of UV light, the sensor also maintains its high-performance even at relative low operatingtemperatures. Besides, the performance of the sensor was hardly affected by a change in humidity evenwithout upon the UV illumination. These results disclose a new type of sensing principle based on thesolid-state sensing device, with desirable performance for a variety of possible detection and/or clinic applications.

Cancerous Glucose Metabolism in Lung Cancer—Evidence from Exhaled Breath Analysis

Published: June 2016

Authors: Feinberg, T.; Alkoby-Meshulam, L.; Herbig, J.; Cancilla, J.C.; Torrecilla, J.S.; Gai-Mor, N.; Bar, J.; Ilouze, M.; Haick, H.; Peled, N.

Years: 2016

Published in: J. Breath Res., 7, 10(2), 1-8

Cancer cells prefer hyperglycolysis versus oxidative phosphorylation, even in the presence of oxygen. This phenomenon is used through the FDG-PET scans, and may affect the exhaled volatile signature. This study investigates the volatile signature in lung cancer (LC) before and after an oral glucose tolerance test (OGTT) to determine if tumor cells’ hyperglycolysis would affect the volatile signature. Blood glucose levels and exhaled breath samples were analyzed before the OGTT, and 90 min after, in both LC patients and controls. The volatile signature was measured by proton transfer reaction mass spectrometry (PTR-MS). Twenty-two LC patients (age 66.6  ±  12.7) with adenocarcinoma (n  =  14), squamous (n  =  6), small cell carcinoma (n  =  2), and twenty-one controls (age 54.4  ±  13.7; 10 non-smokers and 11 smokers) were included. All LC patients showed a hyperglycolytic state in their FDG-PET scans. Both baseline and post OGTT volatile signatures discriminate between the groups. The OGTT has a minimal effect in LC (a decrease in m/z 54 by 39%, p v  =  0.0499); whereas in the control group, five masses (m/z 64, 87,88, 142 and 161) changed by  -13%, -49%, -40% and  -29% and 46% respectively. To conclude, OGTT has a minimal effect on the VOC signature in LC patients, where a hyperglycolytic state already exists. In contrast, in the control group the OGTT has a profound effect in which induced hyperglycolysis significantly changed the VOC pattern. We hypothesized that a ceiling effect in cancerous patients is responsible for this discrepancy.

A Highly Sensitive Diketopyrrolopyrrole-Based Ambipolar Transistor for Selective Detection and Discrimination of Xylene Isomers

Published: June 2016

Authors: Wang, B.; Huynh, T. P.; Wu, W.; Hayek, N.; Do, T.T.; Cancilla, J.C.; Torrecilla, J.S.; Nahid, M.M.; Colwell, M.M.; Gazit, O.M.; Puniredd, S. R.; McNeill, C.R.; Sonar, P.; Haick, H.

Years: 2016

Published in: Adv. Mater., 28, 4012-4018

An ambipolar poly(diketopyrrolopyrrole-terthiophene)-based field-effect transistor (FET)sensitively detects xylene isomers at low ppm levels with multiple sensing features. Combined with pattern-recognition algorithms, a sole ambipolar FET sensor, rather than arrays of sensors, can discriminate highly similar xylene structural isomers from one another.

Highly Sensitive Ambipolar Field Effect Transistor-Based Diketopyrrolopyrrole Copolymer for Selective Detection and Discrimination of Xylene Isomers-Cover Page

Published: March 2016

Years: 2016

Published in: Adv. Mater.

Exhaled Breath Analysis for Monitoring Response to Treatment in Advanced Lung Cancer-Cover Page

Published: March 2016

Years: 2016

Published in: J. Thorac. Oncol.

Exhaled Breath Analysis for Monitoring Response to Treatment in Advanced Lung Cancer

Published: March 2016

Authors: Nardi-Agmon, I.; Abud-Hawa, M.; Liran, O.; Gai-Mor, N.; Ilouze, M.; Onn, A.; Bar, J.; Shlomi, D.; Haick, H.; Peled, N.

Years: 2016

Published in: J. Thorac. Oncol., 11 ( 6), 827-837

The Response Evaluation Criteria in Solid Tumors (RECIST) serve as the accepted standard to monitor treatment efficacy in lung cancer. However, the time intervals between consecutive computerized tomography scans might be too long to allow early identification of treatment failure. This study examines the use of breath sampling to monitor responses to anticancer treatments in patients with advanced lung cancer.

A total of 143 breath samples were collected from 39 patients with advanced lung cancer. The exhaled breath signature, determined by gas chromatography/mass spectrometry and a nanomaterial-based array of sensors, was correlated with the response to therapy assessed by RECIST: complete response, partial response, stable disease, or progressive disease.

Gas chromatography/mass spectrometry analysis identified three volatile organic compounds as significantly indicating disease control (PR/stable disease), with one of them also significantly discriminating PR/stable disease from progressive disease. The nanoarray had the ability to monitor changes in tumor response across therapy, also indicating any lack of further response to therapy. When one-sensor analysis was used, 59% of the follow-up samples were identified correctly. There was 85% success in monitoring disease control (stable disease/partial response).

Breath analysis, using mainly the nanoarray, may serve as a surrogate marker for the response to systemic therapy in lung cancer. As a monitoring tool, it can provide the oncologist with a quick bedside method of identifying a lack of response to an anticancer treatment. This may allow quicker recognition than does the current RECIST analysis. Early recognition of treatment failure could improve patient care.

Breath Testing as Potential Colorectal Cancer Screening Tool

Published: January 2016

Authors: Amal, H.; Leja, M.; Skapars, R.; Sivins, A.; Ancans, G.; Kikuste, I.; Vanags, A.; Tolmanis, I.; Kirsners, A.; Kupcinskas, L.; Haick, H.

Years: 2016

Published in: Int. J. Cancer, 138 (1), 229-236

Although colorectal cancer (CRC) screening is included in organized programs of many countries worldwide, there is still a place for better screening tools. In this study, 418 breath samples were collected from 65 patients with CRC, 22 with advanced or nonadvanced adenomas, and 122 control cases. All patients, including the controls, had undergone colonoscopy. The samples were analysed with two different techniques. The first technique relied on gas chromatography coupled with mass spectrometry (GC-MS) for identification and quantification of volatile organic compounds (VOCs). The T-test was used to identify significant VOCs (p values < 0.017). The second technique relied on sensor analysis with a pattern recognition method for building a breath pattern to identify different groups. Blind analysis or leave-one-out cross validation was conducted for validation. The GC-MS analysis revealed four significant VOCs that identified the tested groups; these were acetone and ethyl acetate (higher in CRC), ethanol and 4-methyl octane (lower in CRC). The sensor-analysis distinguished CRC from the control group with 85% sensitivity, 94% specificity and 91% accuracy. The performance of the sensors in identifying the advanced adenoma group from the non-advanced adenomas was 88% sensitivity, 100% specificity, and 94% accuracy. The performance of the sensors in identifying the advanced adenoma group was distinguished from the control group was 100% sensitivity, 88% specificity, and 94% accuracy. For summary, volatile marker testing by using sensor analysis is a promising noninvasive approach for CRC screening.

Nanoscale Sensor Technologies for Disease Detection via Volatolomics

Published: December 2015

Authors: Vishinkin, R.; Haick, H.

Years: 2015

Published in: Small, 11 (46), 6142–6164

The detection of many diseases is missed because of delayed diagnoses or the low efficacy of some treatments. This emphasizes the urgent need for inexpensive and minimally invasive technologies that would allow efficient early detection, stratifying the population for personalized therapy, and improving the efficacy of rapid bed-side assessment of treatment. An emerging approach that has a high potential to fulfill these needs is based on so-called “volatolomics”, namely, chemical processes involving profiles of highly volatile organic compounds (VOCs) emitted from body fluids, including breath, skin, urine and blood. This article presents a didactic review of some of the main advances related to the use of nanomaterial-based solid-state and flexible sensors, and related artificially intelligent sensing arrays for the detection and monitoring of disease with volatolomics. The article attempts to review the technological gaps and confounding factors related to VOC testing. Different ways to choose nanomaterial-based sensors are discussed, while considering the profiles of targeted volatile markers and possible limitations of applying the sensing approach. Perspectives for taking volatolomics to a new level in the field of diagnostics are highlighted.

Motivation to Learn in Massive Open Online Courses: Examining Aspects of Language and Social Engagement

Published: November 2015

Authors: Barak, M.; Watted, A.; Haick, H.

Years: 2015

Published in: Computers & Education, 94, 49-60

 Learning is mediated by language of instruction and social engagement. Both factors may play a significant role in understanding motivation to learn in massive open online courses (MOOCs). Therefore, the goal of this study was threefold: a. to compare motivation patterns of MOOC participants who study the same course but in a different language of instruction; b. to examine relationships between motivation gain and diverse modes of engagement; and c. to characterize MOOC completers according to their learning motivation. An exploratory case-study was conducted in the settings of a MOOC in Nanotechnology and Nanosensors, delivered in two languages: English and Arabic. The research sample included 325 participants from the English (N = 289) and Arabic (N = 36) MOOCs. The study applied the mixed methods approach, collecting data via pre- and post-questionnaires, forum posts, and email messages. Findings indicated that regardless the language of instruction, MOOC participants were driven to learn by similar goals, emphasizing intrinsic motivation and self-determination. Findings indicated a positive relationship between motivation gain, the number of messages posted to the online forums, and the number of members in the online study groups. Five types of MOOC completers were identified: problem-solvers, networkers, benefactors, innovation-seekers, and complementary-learners.

In Situ and Real-Time Inspection of Nanoparticle Average Size in Flexible Printed Sensors

Published: November 2015

Authors: Segev-Bar, M.; Ukrainsky, B.; Konvalina, G.; Haick, H.

Years: 2015

Published in: J. Phys. Chem. C., 119 (49), 27521−27528

Nanoparticles play an integral part for the production of contacts and active sensing layers in the fast-developing printed electronic technology on flexible devices. Unfortunately, all currently available techniques for nanoparticle characterization are limited to ex situ and/or off-line processing. Here, we describe a new approach composed of two complementary parts for in situ and real-time estimation of the nanoparticles’ effective diameter on flexible substrates. The first part of the approach is based on measurements of electrical resistance of the device in response to strain, and correlation of the response with the nanoparticles’ diameter. The second part takes place only when measuring the electrical resistance is unfeasible. It is based on UV–vis absorption of the device and correlation of the absorption peak with the nanoparticle diameter based on previous calibration data from strain sensitivity. The new approach shows excellent estimations of the nanoparticle diameter (2.5–20 nm) on the substrate with the advantages of being online, in situ, and inexpensive. In addition, the estimated nanoparticle diameter is in excellent agreement with atomic force microscopy (AFM) measurements. These capabilities are expected to improve the process of “quality control” of the nanoscale-enabled flexible devices, which, until now, has been considered to be one of the most annoying issues that inhibits the commercialization of nanotechnology-based flexible products.

Differentiation Between Genetic Mutations of Breast Cancer by Breath Volatolomics

Published: November 2015

Authors: Barash, O.; Zhang, W.; Halpern, J.M.; Hua, Q.L.; Pan, Y.Y.; Kayal, H.; Khoury, K.; Liu, H.; Davies, M.; Haick, H.

Years: 2015

Published in: Oncotarget, 6, 42, 44864-44876

Mapping molecular sub-types in breast cancer (BC) tumours is a rapidly evolving area due to growing interest in, for example, targeted therapy and screening high-risk populations for early diagnosis. We report a new concept for profiling BC molecular sub-types based on volatile organic compounds (VOCs). For this purpose, breath samples were collected from 276 female volunteers, including healthy, benign conditions, ductal carcinoma in situ (DCIS) and malignant lesions. Breath samples were analysed by gas chromatography mass spectrometry (GC-MS) and artificially intelligent nanoarray technology. Applying the non-parametric Wilcoxon/Kruskal- Wallis test, GC-MS analysis found 23 compounds that were significantly different (p < 0.05) in breath samples of BC patients with different molecular sub-types. Discriminant function analysis (DFA) of the nanoarray identified unique volatolomic signatures between cancer and non-cancer cases (83% accuracy in blind testing), and for the different molecular sub-types with accuracies ranging from 82 to 87%, sensitivities of 81 to 88% and specificities of 76 to 96% in leave-one-out cross-validation. These results demonstrate the presence of detectable breath VOC patterns for accurately profiling molecular sub-types in BC, either through specific compound identification by GC-MS or by volatolomic signatures obtained through statistical analysis of the artificially intelligent nanoarray responses.

Self-Healing, Fully Functional, and Multiparametric Flexible Sensing Platform

Published: November 2015

Authors: Huynh, T. P.; Haick, H.

Years: 2015

Published in: Adv. Mater., 28, 138–143

A non-biological and flexible self-healing platform has tailored sensitivity toward one or a combination of pressure, strain, gas analytes, and temperature. For demonstration, a complete self-healing device is described in the form of a bendable and stretchable chemiresistor, where every part is self-healing.

Dynamic Nanoparticle-Based Flexible Sensors: Diagnosis of Ovarian Carcinoma from Exhaled Breath

Published: October 2015

Authors: Kahn, N.; Lavie, O.; Paz, M.; Segev, Y.; Haick, H.

Years: 2015

Published in: Nano Lett., 15 (10), 7023–7028

Flexible sensors based on molecularly modified gold nanoparticles (GNPs) were integrated into a dynamic cross-reactive diagnostic sensing array. Each bending state of the GNP-based flexible sensor gives unique nanoparticle spatial organization, altering the interaction between GNP ligands and volatile organic compounds (VOCs), which increases the amount of data obtainable from each sensor. Individual dynamic flexible sensor could selectively detect parts per billion (ppb) level VOCs that are linked with ovarian cancers in exhaled breath and discriminate them from environmental VOCs that exist in exhaled breath samples, but do not relate to ovarian cancer per se. Strain-related response successfully discriminated between exhaled breath collected from control subjects and those with ovarian cancer, with data from a single sensor being sufficient to obtain 82% accuracy, irrespective of important confounding factors, such as tobacco consumption and comorbidities. The approach raises the hope of achieving an extremely simple, inexpensive, portable, and noninvasive diagnostic procedure for cancer and other diseases.

Detection of Cancer through Exhaled Breath: A Systematic Review

Published: September 2015

Authors: Krilaviciute, A.; Heiss, J.; Leja, M.; Kupcinskas, J.; Haick, H.; Brenner, H.

Years: 2015

Published in: Oncotarget, 17, 6 (36) 38643-38657


Timely diagnosis of cancer represents a challenging task; in particular, there is a need for reliable non-invasive screening tools that could achieve high levels of adherence at virtually no risk in population-based screening. In this review, we summarize the current evidence of exhaled breath analysis for cancer detection using standard analysis techniques and electronic nose.

Relevant studies were identified searching Pubmed and Web of Science databases until April 30, 2015. Information on breath test performance, such as sensitivity and specificity, was extracted together with volatile compounds that were used to discriminate cancer patients from controls. Performance of different breath analysis techniques is provided for various cancers together with information on methodological issues, such as breath sampling protocol and validation of the results.

Overall, 73 studies were included, where two-thirds of the studies were conducted on lung cancer. Good discrimination usually required a combination of multiple biomarkers, and area under the receiver operating characteristic curve or accuracy reached levels of 0.9 or higher in multiple studies. In 25% of the reported studies, classification models were built and validated on the same datasets. Huge variability was seen in different aspects among the studies.

Analyses of exhaled breath yielded promising results, although standardization of breath collection, sample storage and data handling remain critical issues. In order to foster breath analysis implementation into practice, larger studies should be implemented in true screening settings, paying particular attention to standardization in breath collection, consideration of covariates, and validation in independent population samples.

Hybrid Volatolomics and Disease Detection

Published: September 2015

Authors: Broza, Y. Y.; Mochalski, P.; Ruzsanyi, V.; Amann, A.; Haick, H.

Years: 2015

Published in: Angew. Chem. Int Ed Engl., 54 (38),11036-11048

This Review presents a concise, but not exhaustive, didactic overview of some of the main concepts and approaches related to “volatolomics”-an emerging frontier for fast, risk-free, and potentially inexpensive diagnostics. It attempts to review the source and characteristics of volatolomics through the so-called volatile organic compounds (VOCs) emanating from cells and their microenvironment. It also reviews the existence of VOCs in several bodily fluids, including the cellular environment, blood, breath, skin, feces, urine, and saliva. Finally, the usefulness of volatolomics for diagnosis from a single bodily fluid, as well as ways to improve these diagnostic aspects by “hybrid” approaches that combine VOC profiles collected from two or more bodily fluids, will be discussed. The perspectives of this approach in developing the field of diagnostics to a new level are highlighted.

Hybride Volatolomik und der Nachweis von Krankheiten

Published: September 2015

Authors: Broza, Y. Y.; Mochalski, P.; Ruzsanyi, V.; Amann, A.; Haick, H.

Years: 2015

Published in: Angew. Chem., 127, (38): 11188–11201

Hier stellen wir einige der Hauptkonzepte und Ansätze der Volatolomik, einem sich rasch entwickelnden Gebiet der schnellen, risikofreien und wahrscheinlich preisgünstigen Diagnostik, vor. Wir versuchen, einen Überblick über die Herkunft und die Eigenschaften der Volatolomik anhand von flüchtigen organischen Verbindungen (“volatile organic compounds”, VOCs), die von Zellen und ihrer Mikroumgebung freigesetzt werden, zu geben. Wir beschreiben außerdem das Vorkommen von VOCs in verschiedenen Körperflüssigkeiten, darunter die zelluläre Umgebung, Blut, Atemluft, Haut, Faeces, Urin und Speichel. Schließlich diskutieren wir den Nutzen der Volatolomik für eine Diagnosestellung auf Basis einer einzelnen Körperflüssigkeit ebenso wie die Verbesserung der Diagnosesicherheit durch den “Hybrid”-Ansatz, bei dem die VOC-Profile von zwei oder mehr Körperflüssigkeiten erstellt und kombiniert werden. Die Perspektiven dieser Verfahrensweise zur Weiterentwicklung der Diagnostik werden aufgezeigt.

Application of Organophosphonic Acids by One-Step Supercritical CO2 on 1D and 2D Semiconductors: Toward Enhanced Electrical and Sensing Performances

Published: July 2015

Authors: Bhartia, B.; Bachar, N.; Jayaraman, S.; Khatib, S.; Song, J.; Guo, S.; Troadec, C.; Puniredd, S. R.; Haick, H.

Years: 2015

Published in: Acs Appl. Mater. Interf., 7 (27), 14885–14895

Formation of dense monolayers with proven atmospheric stability using simple fabrication conditions remains a major challenge for potential applications such as (bio)sensors, solar cells, surfaces for growth of biological cells, and molecular, organic, and plastic electronics. Here, we demonstrate a single-step modification of organophosphonic acids (OPA) on 1D and 2D structures using supercritical carbon dioxide (SCCO2) as a processing medium, with high stability and significantly shorter processing times than those obtained by the conventional physisorption-chemisorption method (2.5 h vs 48-60 h).The advantages of this approach in terms of stability and atmospheric resistivity are demonstrated on various 2D materials, such as indium-tin-oxide (ITO) and 2D Si surfaces. The advantage of the reported approach on electronic and sensing devices is demonstrated by Si nanowire field effect transistors (SiNW FETs), which have shown a few orders of magnitude higher electrical and sensing performances, compared with devices obtained by conventional approaches. The compatibility of the reported approach with various materials and its simple implementation with a single reactor makes it easily scalable for various applications.

Controlling the Sensing Properties of Silicon Nanowires via the Bonds Nearest to the Silicon Nanowire Surface

Published: May 2015

Authors: Halpern, J.M.; Wang, B.; Haick, H.

Years: 2015

Published in: Acs Appl. Mater. Interf., 7 (21), 11315-11321

Controlling the sensing properties of a silicon nanowire field effect transistor is dependent on the surface chemistry of the silicon nanowire. A standard silicon nanowire has a passive oxide layer (native oxide), which has trap states that cause sensing inaccuracies and desensitize the surface to nonpolar molecules. In this paper, we successfully modified the silicon nanowire surface with different nonoxide C3 alkyl groups, specifically, propyl (Si-CH2-CH2-CH3), propenyl (Si-CH═CH-CH3), and propynyl (Si-C≡C-CH3) modifications. The effect of the near surface bond on the sensor sensitivity and stability was explored by comparing three C3 surface modifications. A reduction of trap-states led to greater sensor stability and accuracy. The propenyl-modified sensor was consistently the most stable and sensitive sensor, among the applied sensors. The propenyl- and propynyl-modified sensors consistently performed with the best accuracy in identifying specific analytes with similar polarity or similar molecular weights. A combination of features from different sensing surfaces led to the best rubric for specific analytes identification. These results indicate that nonoxide sensor surfaces are useful in identifying specific analytes and that a combination of sensors with different surfaces in a cross-reactive array can lead to specific analytes detection.

Printing Nanostructures with a Propelled Anti-​Pinning Ink Droplet

Published: April 2015

Authors: Konvalina, G.; Leshansky, M.A.; Haick, H.

Years: 2015

Published in: Adv. Func. Mater., 25(16), 2411-2419.

Striving for cheap and robust manufg. processes has prompted efforts to adapt and extend methods for printed electronics and biotechnol. A new “direct-​write” printing method for patterning nanometeric species in addressable locations has been developed, by means of evaporative deposition from a propelled anti-​pinning ink droplet (PAPID) in a manner analogous to a snail-​trail. Three velocity-​controlled deposition regimes have been identified; each spontaneously produces distinct and well-​defined self-​assembled deposition patterns. Unlike other technologies that rely on overlapping droplets, PAPIDs produce continuous patterns that can be formed on rigid or flexible substrates, even within 3D concave closed shapes, and have the ability to control the thickness gradient along the pattern. This versatile low cost printing method can produce a wide range of unusual electronic systems not attainable by other methods.

Detection of Precancerous Gastric Lesions and Gastric Cancer through Exhaled Breath

Published: April 2015

Authors: Amal, H.; Leja, M.; Funka, K.; Skapars, R.; Sivins, A.; Ancans, G.; Liepniece-Karele, I.; Kikuste, I.; Lasina, I.; Haick, H.

Years: 2015

Published in: Gut., 65, 400–407 (2016)

Objectives Timely detection of gastric cancer (GC) and the related precancerous lesions could provide a tool for decreasing both cancer mortality and incidence.

Design 968 breath samples were collected from 484 patients (including 99 with GC) for two different analyses. The first sample was analysed by gas chromatography linked to mass spectrometry (GCMS) while applying t test with multiple corrections (p value<0.017); the second by cross-reactive nanoarrays combined with pattern recognition. For the latter, 70% of the samples were randomly selected and used in the training set while the remaining 30% constituted the validation set. The operative link on gastric intestinal metaplasia (OLGIM) assessment staging system was used to stratify the presence/absence and risk level of precancerous lesions. Patients with OLGIM stages III–IV were considered to be at high risk.

Results According to the GCMS results, patients with cancer as well as those at high risk had distinctive breath-print compositions. Eight significant volatile organic compounds (p value<0.017) were detected in exhaled breath in the different comparisons. The nanoarray analysis made it possible to discriminate between the patients with GC and the control group (OLGIM 0–IV) with 73% sensitivity, 98% specificity and 92% accuracy. The classification sensitivity, specificity, and accuracy between the subgroups was as follows: GC versus OLGIM 0–II—97%, 84% and 87%; GC versus OLGIM III–IV—93%, 80% and 90%; but OLGIM I–II versus OLGIM III–IV and dysplasia combined—83%, 60% and 61%, respectively.

Conclusions Nanoarray analysis could provide the missing non-invasive screening tool for GC and related precancerous lesions as well as for surveillance of the latter.

High-Resolution Unpixelated Smart Patches with Antiparallel Thickness Gradients of Nanoparticles

Published: March 2015

Authors: Segev-Bar, M.; Konvalina, G.; Haick, H.

Years: 2015

Published in: Adv. Mater., 27 (10), 1779-1784

A new concept for high-resolution sensing of touch/load and location in which the number of pixels can be significantly diminished is presented. The technology is based on a flexible substrate with two parallel gold-nanoparticle strips with antiparallel sensitivity gradients for an unpixelated skin strip. The approach exhibits high location and load resolutions.

Role of Silicon Nanowire Diameter for Alkyl (Chain Lengths C₁-C₁₈) Passivation Efficiency through Si-C Bonds

Published: March 2015

Authors: Bashouti, M. Y.; Garzuzi, C.A.; de la Mata, M.; Arbiol, J.; Ristein, J.; Haick, H.; Christiansen, S.

Years: 2015

Published in: Langmuir, 31 (8), 2430-2437

The effect of silicon nanowire (Si NW) diameter on the functionalization efficiency as given by covalent Si-C bond formation is studied for two distinct examples of 25 ± 5 and 50 ± 5 nm diameters (Si NW25 and Si NW50, respectively). A two-step chlorination/alkylation process is used to connect alkyl chains of various lengths (C1-C18) to thinner and thicker Si NWs. The shorter the alkyl chain lengths, the larger the surface coverage of the two studied Si NWs. Increasing the alkyl chain length (C2-C9) changes the coverage on the NWs: while for Si NW25 90 ± 10% of all surface sites are covered with Si-C bonds, only 50 ± 10% of all surface sites are covered with Si-C bonds for the Si NW50 wires. Increasing the chain length further to C14-C18 decreases the alkyl coverage to 36 ± 6% in thin Si NW25 and to 20 ± 5% in thick Si NW50. These findings can be interpreted as being a result of increased steric hindrance of Si-C bond formation for longer chain lengths and higher surface energy for the thinner Si NWs. As a direct consequence of these findings, Si NW surfaces have different stabilities against oxidation: they are more stable at higher Si-C bond coverage, and the surface stability was found to be dependent on the Si-C binding energy itself. The Si-C binding energy differs according to (C1-9)-Si NW > (C14-18)-Si NW, i.e., the shorter the alkyl chain, the greater the Si-C binding energy. However, the oxidation resistance of the (C2-18)-Si NW25 is lower than for equivalent Si NW50 surfaces as explained and experimentally substantiated based on electronic (XPS and KP) and structure (TEM and HAADF) measurements.

Distinguishing Idiopathic Parkinson’s Disease from Other Parkinsonian Syndromes by Breath Test

Published: February 2015

Authors: Nakhleh, K. M.; Winer, R.; Jeries, R.; Finberg, J.P.M.; Haick, H.

Years: 2015

Published in: Parkinsonism Relat Disord., 21 (2), 150-153

Diagnosis of different parkinsonian syndromes is linked with high misdiagnosis rates and various confounding factors. This is particularly problematic in its early stages. With this in mind, the current pilot study aimed to distinguish between Idiopathic Parkinson’s Disease (iPD), other Parkinsonian syndromes (non-iPD) and healthy subjects, by a breath test that analyzes the exhaled volatile organic compounds using a highly sensitive nanoarray.
Breath samples of 44 iPD, 16 non-iPD patients and 37 healthy controls were collected. The samples were passed over a nanoarray and the resulting electrical signals were analyzed with discriminant factor analysis as well as by a K-fold cross-validation method, to test the accuracy of the model.
Comparison of non-iPD with iPD states yielded 88% sensitivity, 88% accuracy, and 88% Receiver Operating Characteristic area under the curve in the training set samples with known identity. The validation set of this comparison scored 81% sensitivity and accuracy and 92% negative predictive value. Comparison between atypical parkinsonism states and healthy subjects scored 94% sensitivity and 85% accuracy in the training set samples with known identity. The validation set of this comparison scored 81% sensitivity and 78% accuracy. The obtained results were not affected by l-Dopa or MAO-B inhibitor treatment.
Exhaled breath analysis with nanoarray is a promising approach for a non-invasive, inexpensive, and portable technique for differentiation between different Parkinsonian states. A larger cohort is required in order to establish the clinical usefulness of the method.

Detecting Lung Infections in Breathprints: Empty Promise or Next Generation Diagnosis of Infections

Published: January 2015

Authors: Haick, H.; Cohen-Kaminsky, S.

Years: 2015

Published in: Eur Respir J., 45 (1), 21-24

Comment on
Breathprints of model murine bacterial lung infections are linked with immune response. [Eur Respir J. 2015]

A discussion of evidence on the link between breathprints of bacterial lung infections and the immune response

Assessment of Ovarian Cancer Conditions from Exhaled Breath

Published: September 2014

Authors: Amal, H.; Shi, D. Y.; Ionescu, R.; Zhang, W.; Hua, Q.L.; Pan, Y.Y.; Tao, L.; Liu, H.; Haick, H.

Years: 2014

Published in: Int. J. Cancer, 136, E614–E622

ABSTRACT: Most patients with ovarian cancer (OC) are diagnosed with advanced disease stages (III to IV) and have a 5-year survival rate less than 30%. Detecting OC in its early stages before it has metastasized could increase the 5-year survival rate to 85% to 90%. Previous studies have investigated a novel approach for the detection of OC based on measuring volatile organic compounds (VOCs) in exhaled breath; these disease-specific compounds evaporate from cancer cells and enter the surrounding environment. Using this principle, trained dogs showed an ability to distinguish OC tissues or blood samples from equivalent controls with almost 100% sensitivity and specificity. Because canine OC detection is not practical for widespread clinical use, scientists developed suitably sensitive analytical instrumentation for rapid detection of OC with similar accuracy as found with dogs.
This pilot study examined the possibility that exhaled breath samples can noninvasively detect and discriminate women with OC from women that have no tumor(s) and from women that have benign genital tract neoplasia. The study population was composed of 3 groups: women with OC (n = 48), tumor-free control subjects (n = 48), and women with benign genetic tract neoplasia (n = 86). Gas chromatography linked with mass spectrometry was used to determine the chemical composition of the VOCs in the breath samples. Elevated concentrations of 5 compounds (decanal, nonanal, styrene, 2-butanone, and hexadecane) were found in the VOC samples from patients with cancer compared with the cancer-free volunteers.
Analysis of the same samples with tailor-made nanoarrays showed good discrimination between women with OC and women who had either no tumor or benign genital tract neoplasia (71% for accuracy, sensitivity, and specificity). Conversely, nanoarray analysis was able to distinguish between the OC patients and the tumor-free control subjects (79% sensitivity, 100% specificity, and 89% accuracy).
These preliminary findings show that a negative result with nanorray analysis could identify tumor-free women and avoid unnecessary complicated or expensive tests for OC in these patients. In patients with a positive result, the test will indicate the presence of OC with high probability. Further studies are needed with larger and more diverse populations to confirm and improve these promising results.

Monolayer-Capped Gold Nanoparticles for Disease Detection from Breath

Published: September 2014

Authors: Nakhleh, K. M.; Broza, Y. Y.; Haick, H.

Years: 2014

Published in: Nanomedicine (Lond)., 9(13), 1991–2002

The recognition of volatile organic compounds in breath samples is a promising approach for noninvasive safe diagnosis of disease. Spectrometry and spectroscopy methods used for breath analysis suffer from suboptimal accuracy, are expensive and are unsuitable for diagnostics. This article presents a concise review on arrays of monolayer-capped gold nanoparticle (GNP) sensors in conjugation with pattern recognition methods for cost-effective, fast and high-throughput point-of-care diagnostic results from exhaled breath samples. The article starts with a general introduction to the rationale and advantages of breath analysis as well as with a presentation of the utility of monolayer-capped GNP sensors in this field. The article continues with a presentation of the main fabrication and operation principles of these GNP sensors and concludes with selected examples regarding their utility in different fields of medicine, particularly in neurology, infectiology, respiratory medicine and oncology.

Unique Volatolomic Signatures of TP53 and KRAS in Lung Cells

Published: July 2014

Authors: Davies, M.; Barash, O.; Jeries, R.; Peled, N.; Ilouze, M.; Hyde, R.; Marcus, M.W.; Field, J.K.; Haick, H.

Years: 2014

Published in: Br. J. Cancer, 111, 1213–1221

Volatile organic compounds (VOCs) are potential biomarkers for cancer detection in breath, but it is unclear if they reflect specific mutations. To test this, we have compared human bronchial epithelial cell (HBEC) cell lines carrying the KRASV12 mutation, knockdown of TP53 or both with parental HBEC cells.
VOC from headspace above cultured cells were collected by passive sampling and analysed by thermal desorption gas chromatography mass spectrometry (TD-GC–MS) or sensor array with discriminant factor analysis (DFA).
In TD-GC–MS analysis, individual compounds had limited ability to discriminate between cell lines, but by applying DFA analysis combinations of 20 VOCs successfully discriminated between all cell types (accuracies 80–100%, with leave-one-out cross validation). Sensor array detection DFA demonstrated the ability to discriminate samples based on their cell type for all comparisons with accuracies varying between 77% and 93%.
Our results demonstrate that minimal genetic changes in bronchial airway cells lead to detectable differences in levels of specific VOCs identified by TD-GC–MS or of patterns of VOCs identified by sensor array output. From the clinical aspect, these results suggest the possibility of breath analysis for detection of minimal genetic changes for earlier diagnosis or for genetic typing of lung cancers.

Analysis of Exhaled Breath for Diagnosing Head and Neck Squamous Cell Carcinoma:A Feasibility Study

Published: July 2014

Authors: Tisch, U.; Jeries, R.; Amal, H.; Hakim, M.; Gruber, M.; Ronen, O.; Marshak, T.; Zimmerman, D.; Israel, O.; Amiga, E.; Doweck, I.; Haick, H.

Years: 2014

Published in: Br. J. Cancer, 111, 790–798

Squamous cell carcinoma of the head and neck (HNSCC) are wide-spread cancers that often lead to disfigurement and loss of important functions such as speech and ingestion. To date, HNSCC has no adequate method for early detection and screening.

Exhaled breath samples were collected from 87 volunteers; 62 well-defined breath samples from 22 HNSCC patients (larynx and pharynx), 21 patients with benign tumours (larynx and pharynx) and 19 healthy controls were analysed in a dual approach: (i) chemical analysis using gas chromatography/mass spectrometry (GC-MS) and (ii) breath-print analysis using an array of nanomaterial-based sensors, combined with a statistical algorithm.

Gas chromatography/mass spectrometry identified ethanol, 2-propenenitrile and undecane as potential markers for HNSCC and/or benign tumours of the head and neck. The sensor-array-based breath-prints could clearly distinguish HNSCC both from benign tumours and from healthy states. Within the HNSCC group, patients could be classified according to tumour site and stage.

We have demonstrated the feasibility of a breath test for a specific, clinically interesting application: distinguishing HNSCC from tumour-free or benign tumour states, as well as for staging and locating HNSCC. The sensor array used here could form the basis for the development of an urgently needed non-invasive, cost-effective, fast and reliable point-of-care diagnostic/screening tool for HNSCC.

Sensor Arrays Based on Nanoparticles for Early Detection of Kidney Injury by Breath Samples

Published: June 2014

Authors: Nakhleh, K. M.; Amal, H.; Awad, H.; Gharra, A.; Abu-Saleh, N.; Jeries, R.; Haick, H.; Abassi, Z.

Years: 2014

Published in: Nanomedicine, 1767-1776

The outcomes of acute kidney injury (AKI) could be severe and even lethal, if not diagnosed in its early stages and treated appropriately. Blood and urine biomarkers, currently in use as indicators for kidney function, are either inaccurate in various cases or not timely. We report on dramatic changes in exhaled breath composition, associated with kidney dysfunction after ischemic insult in rat models. Gas chromatography linked mass spectrometry examination of breath samples indicated significant elevations in the concentration of three exhaled volatile organic compounds, two to six hours after AKI was surgically induced. Relying on these findings, we introduce an array of sensors, based on organic-layer capped gold nanoparticles, sensitive to odor changes. The ability of the array to detect AKI via breath testing was examined and scored a sensitivity of 96%, only one hour after disease induction.

In this study, organic-layer capped gold nanoparticle-based biosensors are used to analyse breath samples in an acute kidney injury model, capitalizing on the observation that specific volatile organic compounds are present in breath samples in that condition. The authors report excellent sensitivity in as little as one hour after acute kidney injury. This method, if commercialized, may replace the current blood and urine sample analysis-based tests with a more convenient, rapid and accurate nanotechnology-based method.

Detecting Active Pulmonary Tuberculosis with a Breath Test Using Nanomaterial Based Sensors

Published: May 2014

Authors: Nakhleh, K. M.; Jeries, R.; Gharra, A.; Binder, A.; Broza, Y. Y.; Pascoe, M.; Dheda, K.; Haick, H.

Years: 2014

Published in: Eur Respir J., 43, 1519–1522

Combined Volatolomics for Monitoring of Human Body Chemistry

Published: April 2014

Authors: Broza, Y. Y.; Zuri, L.; Haick, H.

Years: 2014

Published in: Sci. Rep., 4, 4611

Analysis of volatile organic compounds (VOCs) is a promising approach for non-invasive, fast and potentially inexpensive diagnostics. Here, we present a new methodology for profiling the body chemistry by using the volatile fraction of molecules in various body fluids. Using mass spectrometry and cross-reactive nanomaterial-based sensors array, we demonstrate that simultaneous VOC detection from breath and skin would provide complementary, non-correlated information of the body’s volatile metabolites profile. Eventually with further wide population validation studies, such a methodology could provide more accurate monitoring of pathological changes compared to the information provided by a single body fluid. The qualitative and quantitative methods presented here offers a variety of options for novel mapping of the metabolic properties of complex organisms, including humans.

Assessment of the Exhalation Kinetics of Volatile Cancer Biomarkers based on their Physicochemical Properties

Published: February 2014

Authors: Amann, A.; Mochalski, P.; Ruzsanyi, V.; Broza, Y. Y.; Haick, H.

Years: 2014

Published in: J. Breath Res., 8, (1), 016003

The current review provides an assessment of the exhalation kinetics of volatile organic compounds (VOCs) that have been linked with cancer. Towards this end, we evaluate various physicochemical properties, such as ‘breath:air’ and ‘blood:fat’ partition coefficients, of 112 VOCs that have been suggested over the past decade as potential markers of cancer. With these data, we show that the cancer VOC concentrations in the blood and in the fat span over 12 and 8 orders of magnitude, respectively, in order to provide a specific counterpart concentration in the exhaled breath (e.g., 1 ppb). This finding suggests that these 112 different compounds have different storage compartments in the body and that their exhalation kinetics depends on one or a combination of the following factors: (i) the VOC concentrations in different parts of the body; (ii) the VOC synthesis and metabolism rates; (iii) the partition coefficients between tissue(s), blood and air; and (iv) the VOCs’ diffusion constants. Based on this analysis, we discuss how this knowledge allows modeling and simulating the behavior of a specific VOC under different sampling protocols (with and without exertion of effort). We end this review by a brief discussion on the potential role of these scenarios in screening and therapeutic monitoring of cancer

Artificial Sensing Intelligence with Silicon Nanowires for Ultraselective Detection in the Gas Phase

Published: January 2014

Authors: Wang, B.; Cancilla, J.C.; Torrecilla, J.S.; Haick, H.

Years: 2014

Published in: Nano Lett., 14, 933−938

The use of molecularly modified Si nanowire field effect transistors (SiNW FETs) for selective detection in the liquid phase has been successfully demonstrated. In contrast, selective detection of chemical species in the gas phase has been rather limited. In this paper, we show that the application of artificial intelligence on deliberately controlled SiNW FET device parameters can provide high selectivity toward specific volatile organic compounds (VOCs). The obtained selectivity allows identifying VOCs in both single-component and multicomponent environments as well as estimating the constituent VOC concentrations. The effect of the structural properties (functional group and/or chain length) of the molecular modifications on the accuracy of VOC detection is presented and discussed. The reported results have the potential to serve as a launching pad for the use of SiNW FET sensors in real-world counteracting conditions and/or applications.

Assessment, Origin, and Implementation of Breath Volatile Cancer Markers

Published: December 2013

Authors: Haick, H.; Broza, Y. Y.; Mochalski, P.; Ruzsanyi, V.; Amann, A.

Years: 2013

Published in: Chem. Soc. Rev., 43, 1423-1449

A new non-invasive and potentially inexpensive frontier in the diagnosis of cancer relies on the detection of volatile organic compounds (VOCs) in exhaled breath samples. Breath can be sampled and analyzed in real-time, leading to fascinating and cost-effective clinical diagnostic procedures. Nevertheless, breath analysis is a very young field of research and faces challenges, mainly because the biochemical mechanisms behind the cancer-related VOCs are largely unknown. In this review, we present a list of 115 validated cancer-related VOCs published in the literature during the past decade, and classify them with respect to their “fat-to-blood” and “blood-to-air” partition coefficients. These partition coefficients provide an estimation of the relative concentrations of VOCs in alveolar breath, in blood and in the fat compartments of the human body. Additionally, we try to clarify controversial issues concerning possible experimental malpractice in the field, and propose ways to translate the basic science results as well as the mechanistic understanding to tools (sensors) that could serve as point-of-care diagnostics of cancer. We end this review with a conclusion and a future perspective.

Volatile Organic Compounds and the Potential for a Lung Cancer Breath Test

Published: November 2013

Authors: Barash, O.; Tisch, U.; Haick, H.

Years: 2013

Published in: Future Medicine, 2, 6

Detecting exhaled volatile organic compounds (VOCs) that are associated with lung cancer (LC) has realistic potential for becoming an integral part of population-based LC screening and monitoring in the near future. Here, we review the main three approaches for profiling VOCs in LC patients and their advantages and pitfalls: first, mass spectrometry techniques for the identification and/or quantification of a wide variety of separate breath VOCs; second, canines that are trained to sniff out LC; and third, cross-reactive chemical sensors in combination with statistical methods for identifying disease-specific patterns. We estimate that the latter would be most suitable for clinical practice. In the short run, breath testing could provide a critically needed adjunct method for detecting nodule malignancy with high specificity during low-dose computed tomography screening. In the long run, breath testing holds potential for entirely revolutionizing LC screening, diagnosis and management.

Detection of Volatile Organic Compounds in Brucella abortus- Seropositive Bison

Published: November 2013

Authors: Bayn, A.; Nol, P.; Tisch, U.; Rhyan, J.; Ellis, C.K.; Haick, H.

Years: 2013

Published in: Anal. Chem., 85, 11146−11152

Brucellosis is of great public health and economic importance worldwide. Detection of brucellosis currently relies on serologic testing of an antibody response to Brucella infection, which suffers from cross-sensitivities to other antibody responses. Here we present a new method for identifying Brucella exposure that is based on profiling volatile organic compounds (VOCs) in exhaled breath. Breath samples from Brucella-seropositive bison and controls were chemically analyzed and demonstrated statistically significant differences in the concentration profiles of five VOCs. A point-of-care device incorporating an array of nanomaterial-based sensors could identify VOC patterns indicative of Brucella exposure with excellent discriminative power, using a statistical algorithm. We show that the patterns were not affected by the animals’ environment and that the discriminative power of the approach was stable over time. The Brucella-indicative VOCs and collective patterns that were identified in this pilot study could lead to the development of a novel diagnostic screening test for quickly detecting infected animals chute-side, pen-side, or even remotely in populations of free-ranging ungulates. The promising preliminary results presented encourage subsequent larger scale trials in order to further evaluate the proposed method.

Geographical Variation in the Exhaled Volatile Organic Compounds

Published: November 2013

Authors: Amal, H.; Leja, M.; Broza, Y. Y.; Tisch, U.; Funka, K.; Liepniece-Karele, I.; Skapars, R.; Xu, Z. Q.; Liu, H.; Haick, H.

Years: 2013

Published in: J. Breath Res., 7, 1-9

Breath-gas analysis has demonstrated that concentration profiles of volatile organic compounds (VOCs) could be used for detecting a variety of diseases, among them gastric cancer (GC) and peptic ulcer disease (PUD). Here, we explore how geographical variation affects the disease-specific changes in the chemical composition of breath samples, as compared to control states (less severe gastric conditions). Alveolar exhaled breath samples from 260 patients were collected at two remotely different geographic locations (China and Latvia), following similar breath-collection protocols. Each cohort included 130 patients that were matched in terms of diagnosis (37 GC/32 PUD/61 controls), average age, gender ratio and smoking habits. Helicobacter Pylori infection, which is a major cause for GC and PUD, was found in part of the patients, as well as in part of the controls, at both locations. The breath samples were analyzed by gas chromatography/mass spectrometry, using the same equipment and protocol-of-experiment. We observed similar characteristic differences in the chemical composition of the breath samples between the study groups at the two locations, even though the exact composition of the breath samples differed. Both in China and Latvia, the GC patients and controls could be distinguished by differences in the average levels of 6-methyl-5-hepten-2-one; PUD patients were distinguished from controls by the levels of aromatic compounds and alcohols; GC and PUD patients could not be distinguished at either site. This pilot study indicates the limitations of chemical breath-gas analysis alone for identifying gastric diseases based on the concentration profiles of separate VOCs in international patient cohorts. We assume that these limitations would apply to other diseases as well. The presented data could potentially be useful for developing an alternative, universally applicable diagnostic method that relies on the detection of changes in the collective patterns of the disease-specific classes of exhaled VOCs.

Sensor Arrays Based on Polycyclic Aromatic Hydrocarbons: Chemiresistors versus Quartz-Crystal Microbalance

Published: October 2013

Authors: Bachar, N.; Liberman, L.; Muallem, F.; Feng, X.; Müllen, K.; Haick, H.

Years: 2013

Published in: Acs Appl. Mater. Interf., 5, 11641−11653

Arrays of broadly cross-reactive sensors are key elements of smart, self-training sensing systems. Chemically sensitive resistors and quartz-crystal microbalance (QCM) sensors are attractive for sensing applications that involve detection and classification of volatile organic compounds (VOCs) in the gas phase. Polycyclic aromatic hydrocarbon (PAH) derivatives as sensing materials can provide good sensitivity and robust selectivity towards different polar and nonpolar VOCs, while being quite tolerant to large humidity variations. Here, we present a comparative study of chemiresistor and QCM arrays based on a set of custom-designed PAH derivatives having either purely nonpolar coronas or alternating nonpolar and strongly polar side chain termination. The arrays were exposed to various concentrations of representative polar and nonpolar VOCs under extremely varying humidity conditions (5–80% RH). The sensor arrays’ classification ability of VOC polarity, chemical class and compound separation was explained in terms of the sensing characteristics of the constituent sensors and their interaction with the VOCs. The results presented here contribute to the development of novel versatile and cost-effective real-world VOC sensing platforms.

Discriminative Power of Chemically Sensitive Silicon Nanowire Field Effect Transistors to Volatile Organic Compounds

Published: October 2013

Authors: Ermanok, R; Assad, O.; Zigelboim, K.; Wang, B.; Haick, H.

Years: 2013

Published in: Acs Appl. Mater. Interf., 5, 11172−11183

We report on the sensing of different polar and nonpolar volatile organic compounds (VOCs) in an atmosphere with background humidity (relative humidity: 40%), using molecularly modified silicon nanowire field effect transistors (SiNW FETs). In this endeavor, a systematic comparative analysis is performed with: (i) SiNW FETs that were functionalized with a series of molecules having different electron-withdrawing and electron-donating end groups; and (ii) SiNW FETs that are functionalized with a series of molecules having similar functional groups but different backbone lengths. The analysis of the sensing signals are focused on three main FET parameters: (i) changes in the threshold voltage, (ii) changes in the carrier mobility, and (iii) changes in the on-current, compared to the baseline values under vacuum. Using discriminant factor analysis, the performance of the molecularly modified SiNW FETs is further analyzed as sensors array. The combination of sensors having the best discriminative power between the various VOCs are identified and discussed in terms of their constituent surface modifications.

A Proof of Concept for the Detection and Classification of Pulmonary Arterial Hypertension through Breath Analysis with a Sensor Array

Published: September 2013

Authors: Cohen-Kaminsky, S.; Nakhleh, K. M.; Perros, F.; Montani, D.; Girerd, B.; Garcia, G.; Simonneau, G.; Haick, H.; Humbert, M.

Years: 2013

Published in: Am. J. Resp. Crit. Care Med., 188, 756-759

Flexible Sensors Based on Nanoparticles

Published: September 2013

Authors: Segev-Bar, M.; Haick, H.

Years: 2013

Published in: ACS Nano., 7, 8366-8378

Flexible sensors can be envisioned as promising components for smart sensing applications, including consumer electronics, robotics, prosthetics, health care, safety equipment, environmental monitoring, homeland security and space flight. The current review presents a concise, although admittedly nonexhaustive, didactic review of some of the main concepts and approaches related to the use of nanoparticles (NPs) in flexible sensors. The review attempts to pull together different views and terminologies used in the NP-based sensors, mainly those established via electrical transduction approaches, including, but, not confined to: (i) strain-gauges, (ii) flexible multiparametric sensors, and (iii) sensors that are unaffected by mechanical deformation. For each category, the review presents and discusses the common fabrication approaches and state-of-the-art results. The advantages, weak points, and possible routes for future research, highlighting the challenges for NP-based flexible sensors, are presented and discussed as well.

Sensors for Breath Testing: From Nanomaterials to Comprehensive Disease Detection

Published: August 2013

Authors: Konvalina, G.; Haick, H.

Years: 2013

Published in: Acc. Chem. Res., 47(1), 66–76

The analysis of volatile organic compounds in exhaled breath samples represents a new frontier in medical diagnostics because it is a noninvasive and potentially inexpensive way to detect illnesses. Clinical trials with spectrometry and spectroscopy techniques, the standard volatile-compound detection methods, have shown the potential for diagnosing illnesses including cancer, multiple sclerosis, Parkinson’s disease, tuberculosis, diabetes, and more via breath tests. Unfortunately, this approach requires expensive equipment and high levels of expertise to operate the necessary instruments, and the tests must be done quickly and use preconcentration techniques, all of which impede its adoption.

Sensing matrices based on nanomaterials are likely to become a clinical and laboratory diagnostic tool because they are significantly smaller, easier-to-use, and less expensive than spectrometry or spectroscopy. An ideal nanomaterial-based sensor for breath testing should be sensitive at very low concentrations of volatile organic compounds, even in the presence of environmental or physiological confounding factors. It should also respond rapidly and proportionately to small changes in concentration and provide a consistent output that is specific to a given volatile organic compound. When not in contact with the volatile organic compounds, the sensor should quickly return to its baseline state or be simple and inexpensive enough to be disposable.

Several reviews have focused on the methodological, biochemical, and clinical aspects of breath analysis in attempts to bring breath testing closer to practice for comprehensive disease detection. This Account pays particular attention to the technological gaps and confounding factors that impede nanomaterial-sensor-based breath testing, in the hope of directing future research and development efforts towards the best possible approaches to overcome these obstacles. We discuss breath testing as a complex process involving numerous steps, each of which has several possible technological alternatives with advantages and drawbacks that might affect the performance of the nanomaterial-based sensors in a breath-testing system. With this in mind, we discuss how to choose nanomaterial-based sensors, considering the profile of the targeted breath markers and the possible limitations of the approach, and how to design the surrounding breath-testing setup. We also discuss how to tailor the dynamic range and selectivity of the applied sensors to detect the disease-related volatile organic compounds of interest. Finally, we describe approaches to overcome other obstacles by improving the sensing elements and the supporting techniques such as preconcentration and dehumidification.

Volatile Fingerprints of Cancer Specific Genetic Mutations

Published: August 2013

Authors: Peled, N.; Barash, O.; Tisch, U.; Ionescu, R.; Broza, Y. Y.; Ilouze, M.; Mattei, J.; Bunn, P. A. Jr.; Hirsch, F. R.; Haick, H.

Years: 2013

Published in: Nanomedicine, 9, (6), 758–766

We report on a new concept for profiling genetic mutations of (lung) cancer cells, based on the detection of patterns of volatile organic compounds (VOCs) emitted from cell membranes, using an array of nanomaterial-based sensors. In this in-vitro pilot study we have derived a volatile fingerprint assay for representative genetic mutations in cancer cells that are known to be associated with targeted cancer therapy. Five VOCs were associated with the studied oncogenes, using complementary chemical analysis, and were discussed in terms of possible metabolic pathways. The reported approach could lead to the development of novel methods for guiding treatments, so that patients could benefit from safer, more timely and effective interventions that improve survival and quality of life while avoiding unnecessary invasive procedures. Studying clinical samples (tissue/blood/breath) will be required as next step in order to determine whether this cell-line study can be translated into a clinically useful tool.

Breath Testing: The Future for Digestive Cancer Detection

Published: July 2013

Authors: Leja, M.; Liu, H.; Haick, H.

Years: 2013

Published in: Expert Rev, 7(5), 389–391

A Non-Oxidative Approach Towards Hybrid Silicon Nanowire-Based Solar Cell Heterojunctions

Published: June 2013

Authors: Bashouti, M. Y.; Ristein, J.; Haick, H.; Christiansen, S.

Years: 2013

Published in: Hybrid Mater., 2-14

A general method for the non-oxidative termination of silicon nanowires (Si NWs) is reviewed. Oxide-free Si NW have been successfully alkylated in the lab using a two-step chlorination/alkylation process. The distinctive properties of the resulting Si NW have been taken advantage of by integrating the Si NWs into functional devices such as solar cells. Moreover, molecularly terminated Si NWs exhibit lower defect density emissions than unmodified Si NWs. This, in part, explains the better performance of the molecularly terminated Si NW-based solar cells. Solar cells that use organic-inorganic hybrid Si NWs as absorbers show an increased open-circuit voltage (Voc), an increased short-circuit current (Jsc) and a higher fill factor (FF). The aim of chemical functionalization is to protect Si NWs from extensive oxidation, add functionality and to adjust surface electronic properties such as the work function, surface Fermi level and band bending. The stability of the terminated of Si NWs was found to be dependent on the molecular chain length, molecular coverage, interaction type (π-π or σ-σ), surface energy and Si NW diameter.

Tunable Touch Sensor and Combined Sensing Platform: Toward Nanoparticle-based Electronic Skin

Published: June 2013

Authors: Segev-Bar, M.; Landman, A.; Nir-Shapira, M.; Shuster, G.; Haick, H.

Years: 2013

Published in: Acs Appl. Mater. Interf., 5 (12), 5531-5541

In this paper, we present touch (or pressure) flexible sensors based on monolayer-capped nanoparticles (MCNPs) that are potentially inexpensive, could allow low-voltage operation, and could provide a platform for multifunctional applications. We show that modifying the mechanical and geometrical properties of the flexible substrates, on which the MCNP films are deposited, allows measuring a large span of loads ranging between tens of mg to tens of grams. All flexible sensors exhibited repeatable responses even after a large number of bending cycles. In addition, we show that modified platforms of those touch (or pressure) sensors allow precise detection and monitoring of environmental temperature and humidity. Relying on their superior characteristics, we were able to build an MCNP-based prototype allowing simultaneous detection and monitoring of multiple environmental parameters of touch (or pressure), humidity, and temperature. The excellent temperature (resolution higher than 1 °C and average error of ∼5%) and relative humidity (resolution higher than 1% RH and average error of ∼9%) sensitivities and the possibility to integrate those sensing abilities makes the suggested platform interesting for potentially inexpensive and low-voltage multifunctional electronic-skin applications.

Effect of Chain Length on the Sensing of Volatile Organic Compounds by means of Silicon Nanowires

Published: June 2013

Authors: Wang, B.; Haick, H.

Years: 2013

Published in: Acs Appl. Mater. Interf., 5 (12), 5748−5756

Molecularly modified silicon nanowire field effect transistors (SiNW FETs) are starting to appear as promising devices for sensing various volatile organic compounds (VOCs). Understanding the connection between the molecular layer structure attached to the SiNWs and VOCs is essential for the design of high performance sensors. Here, we explore the chain length influence of molecular layers on the sensing performance to polar and nonpolar VOCs. SiNW FETs were functionalized with molecular layers that have similar end (methyl) group and amide bridge bond, but differ in their alkyl chain lengths. The resulting devices were then exposed to polar and nonpolar VOCs in various concentrations. Our results showed that the sensing response to changing the threshold voltage (ΔVth) and changing the relative hole mobility (Δμh/μh-a) have a proportional relationship to the VOC concentration. On exposure to a specific VOC concentration, ΔVth response increased with the chain length of the molecular modification. In contrast, Δμh/μh-a did not exhibit any obvious reliance on the chain length of the molecular layer. Analysis of the responses with an electrostatic-based model suggests that the sensor response in ΔVth is dependent on the VOC concentration, VOC vapor pressure, VOC–molecular layer binding energy, and VOC adsorption-induced dipole moment changes of molecular layer.

Nanomaterial-Based Sensors for Detection of Disease by Volatile Organic Compounds

Published: May 2013

Authors: Broza, Y. Y.; Haick, H.

Years: 2013

Published in: Nanomedicine, 8 (5), 785–806

The importance of developing new diagnostic and detection technologies for the growing number of clinical challenges is rising each year. Here, we present a concise, yet didactic review on a new diagnostics frontier based on the detection of disease-related volatile organic compounds (VOCs) by means of nanomaterial-based sensors. Nanomaterials are ideal for such sensor arrays because they are easily fabricated, chemically versatile and can be integrated into currently available sensing platforms. Following a general introduction, we provide a brief description of the VOC-related diseases concept. Then, we focus on detection of VOC-related diseases by selective and crossreactive sensing approaches, through chemical, optical and mechanical transducers incorporating the most important classes of nanomaterials. Selected examples of the integration of nanomaterials into selective sensors and crossreactive sensor arrays are given. We conclude with a brief discussion on the integration possibilities of different types of nanomaterials into sensor arrays, and the expected outcomes and limitations.

Impact of Hemodialysis on Exhaled Volatile Organic Compounds in End-Stage Renal Disease: A Pilot Study

Published: May 2013

Authors: Assady, S.; Marom, O.; Hemli, M.; Ionescu, R.; Jeries, R.; Tisch, U.; Abassi, Z.; Haick, H.

Years: 2013

Published in: Nanomedicine, doi: 10.2217/nnm.13.85., 9(7), 1035-1045


To demonstrate the feasibility of nanomaterial-based sensors for identifying patterns of exhaled volatile organic compound of end-stage renal disease (ESRD) and study the impact of hemodialysis (HD) on these patterns.

Exhaled breath samples were collected from a group of 37 volunteers (26 ESRD HD patients; 11 healthy controls); a third of the samples were randomly blinded for determining the sensitivity/specificity of the method. Discriminant function analysis was used to build a model for discriminating ESRD patients and healthy controls (classification accuracy for blind samples: 80%), based on the signals of the nanomaterial sensors.

The breath pattern of the ESRD patients approached the healthy pattern during the HD treatment, without reaching it completely. Gas chromatography/mass spectrometry identified four volatile organic compounds as potential ESRD biomarkers. Although this pilot study has yielded encouraging results, additional large-scale clinical studies are required to develop a fast, noninvasive breath test for monitoring HD adequacy in real time.
breath test; carbon nanotube; dialysis adequacy; end-stage renal disease; gold nanoparticle; hemodialysis; sensor; volatile organic compound

Field Effect Transistors Based on Polycyclic Aromatic Hydrocarbons for the Detection and Classification of Volatile Organic Compounds

Published: April 2013

Authors: Bayn, A.; Feng, X.; Müllen, K.; Haick, H.

Years: 2013

Published in: Acs Appl. Mater. Interf., 5 (8), 3431−3440

We show that polycyclic aromatic hydrocarbon (PAH) based field effect transistor (FET) arrays can serve as excellent chemical sensors for the detection of volatile organic compounds (VOCs) under confounding humidity conditions. Using these sensors, w/o complementary pattern recognition methods, we study the ability of PAH-FET(s) to: (i) discriminate between aromatic and non-aromatic VOCs; (ii) distinguish polar and non-polar non-aromatic compounds; and to (iii) identify specific VOCs within the subgroups (i.e., aromatic compounds, polar non-aromatic compounds, non-polar non-aromatic compounds). We further study the effect of water vapor on the sensor array’s discriminative ability and derive patterns that are stable when exposed to different constant values of background humidity. Patterns based on different independent electronic features from an array of PAH-FETs may bring us one step closer to creating a unique fingerprint for individual VOCs in real-world applications in atmospheres with varying levels of humidity.

Effect of Functional Groups on the Sensing Properties of Silicon Nanowires toward Volatile Compounds

Published: March 2013

Authors: Wang, B.; Haick, H.

Years: 2013

Published in: Acs Appl. Mater. Interf., 5, 2289-2299

Molecular layers attached to a silicon nanowire field effect transistor (SiNW FET) can serve as antennas for signal transduction of volatile organic compounds (VOCs). Nevertheless, the mutual relationship between the molecular layers and VOCs is still a puzzle. In the present paper, we explore the effect of the molecular layer’s end (functional) groups on the sensing properties of VOCs. Toward this end, SiNW FETs were modified with tailor-made molecular layers that have the same backbone but differ in their end groups. Changes in the threshold voltage (ΔVth) and changes in the mobility (Δμh) were then recorded upon exposure to various VOCs. Model-based analysis indicates that the interaction between molecular layers and VOCs can be classified to three main scenarios: (a) dipole−dipole interaction between the molecular layer and the polar VOCs; (b) induced dipole−dipole interaction between the molecular layers and the nonpolar VOCs; and (c) molecular layer tilt as a result of VOCs diffusion. Based on these scenarios, it is likely that the electron-donating/withdrawing properties of the functional groups control the dipole moment orientation of the adsorbed VOCs and, as a result, determine the direction (or sign) of the ΔVth. Additionally, it is likely the diffusion of VOCs into the molecular layer, determined by the type of functional groups, is the main reason for the Δμh responses. The reported findings are expected to provide an efficient way to design chemical sensors that are based on SiNW FETs to nonpolar VOCs, which do not exchange carriers with the molecular layers.

A Nanomaterial-Based Breath Test for Distinguishing Gastric Cancer from Benign Gastric Conditions

Published: March 2013

Authors: Xu, Z. Q.; Broza, Y. Y.; Ionescu, R.; Tisch, U.; Ding, L.; Liu, H.; Song, Q.; Pan, Y.Y.; Xiong, F.; Gu, K.; Sun, G.; Chen, J.; Leja, M.; Haick, H.

Years: 2013

Published in: Br. J. Cancer, 108 (4), 941–950


Upper digestive endoscopy with biopsy and histopathological evaluation of the biopsy material is the standard method for diagnosing gastric cancer (GC). However, this procedure may not be widely available for screening in the developing world, whereas in developed countries endoscopy is frequently used without major clinical gain. There is a high demand for a simple and non-invasive test for selecting the individuals at increased risk that should undergo the endoscopic examination. Here, we studied the feasibility of a nanomaterial-based breath test for identifying GC among patients with gastric complaints.

Alveolar exhaled breath samples from 130 patients with gastric complaints (37 GC/32 ulcers / 61 less severe conditions) that underwent endoscopy/biopsy were analyzed using nanomaterial-based sensors. Predictive models were built employing discriminant factor analysis (DFA) pattern recognition, and their stability against possible confounding factors (alcohol/tobacco consumption; Helicobacter pylori) was tested. Classification success was determined (i) using leave-one-out cross-validation and (ii) by randomly blinding 25% of the samples as a validation set. Complementary chemical analysis of the breath samples was performed using gas chromatography coupled with mass spectrometry.

Three DFA models were developed that achieved excellent discrimination between the subpopulations: (i) GC vs benign gastric conditions, among all the patients (89% sensitivity; 90% specificity); (ii) early stage GC (I and II) vs late stage (III and IV), among GC patients (89% sensitivity; 94% specificity); and (iii) ulcer vs less severe, among benign conditions (84% sensitivity; 87% specificity). The models were insensitive against the tested confounding factors. Chemical analysis found that five volatile organic compounds (2-propenenitrile, 2-butoxy-ethanol, furfural, 6-methyl-5-hepten-2-one and isoprene) were significantly elevated in patients with GC and/or peptic ulcer, as compared with less severe gastric conditions. The concentrations both in the room air and in the breath samples were in the single p.p.b.v range, except in the case of isoprene.

The preliminary results of this pilot study could open a new and promising avenue to diagnose GC and distinguish it from other gastric diseases. It should be noted that the applied methods are complementary and the potential marker compounds identified by gas-chromatography/mass spectrometry are not necessarily responsible for the differences in the sensor responses. Although this pilot study does not allow drawing far-reaching conclusions, the encouraging preliminary results presented here have initiated a large multicentre clinical trial to confirm the observed patterns for GC and benign gastric conditions

Oxide-Free Hybrid Silicon Nanowires: from Fundamentals to Applied Nanotechnology

Published: February 2013

Authors: Bashouti, M. Y.; Sardashti, K.; Schmitt, S.W.; Pietsch, M.; Ristein, J.; Haick, H.; Christiansen, S.

Years: 2013

Published in: Prog. Surf. Sci., 88, 39–60

The ability to control physical properties of silicon nanowires (Si NWs) by designing their surface bonds is important for their applicability in devices in the areas of nano-electronics, nano-photonics, including photovoltaics and sensing. In principle a wealth of different molecules can be attached to the bare Si NW surface atoms to create e.g. Si–O, Si–C, Si–N, etc. to mention just the most prominent ones. Si–O bond formation, i.e. oxidation usually takes place automatically as soon as Si NWs are exposed to ambient conditions and this is undesired is since a defective oxide layer (i.e. native silicon dioxide – SiO2) can cause uncontrolled trap states in the band gap of silicon. Surface functionalization of Si NW surfaces with the aim to avoid oxidation can be carried out by permitting e.g. Si–C bond formation when alkyl chains are covalently attached to the Si NW surfaces by employing a versatile two-step chlorination/alkylation process that does not affect the original length and diameter of the NWs. Termination of Si NWs with alkyl molecules through covalent Si–C bonds can provide long term stability against oxidation of the Si NW surfaces. The alkyl chain length determines the molecular coverage of Si NW surfaces and thus the surface energy and next to simple Si–C bonds even bond types such as C C and C C can be realized. When integrating differently functionalized Si NWs in functional devices such as field effect transistors (FETs) and solar cells, the physical properties of the resultant devices vary.

Detection of Alzheimer’s and Parkinson’s Disease from Exhaled Breath Using Nanomaterial-Based Sensors

Published: January 2013

Authors: Tisch, U.; Schlesinger, I.; Ionescu, R.; Nassar, M.; Axelrod, N.; Robertman, D.; Tessler, Y.; Azar, F.; Marmur, A.; Aharon-Peretz, J.; Haick, H.

Years: 2012

Published in: Nanomedicine (Lond)., 8(1), 43-56


To study the feasibility of a novel method in nanomedicine that is based on breath testing for identifying Alzheimer’s disease (AD) and Parkinson’s disease (PD), as representative examples of neurodegenerative conditions.

Alveolar breath was collected from 57 volunteers (AD patients, PD patients and healthy controls) and analyzed using combinations of nanomaterial-based sensors (organically functionalized carbon nanotubes and gold nanoparticles). Discriminant factor analysis was applied to detect statistically significant differences between study groups and classification success was estimated using cross-validation. The pattern identification was supported by chemical analysis of the breath samples using gas chromatography combined with mass spectrometry.

The combinations of sensors could clearly distinguish AD from healthy states, PD from healthy states, and AD from PD states, with a classification accuracy of 85, 78 and 84%, respectively. Gas chromatography combined with mass spectrometry analysis showed statistically significant differences in the average abundance of several volatile organic compounds in the breath of AD, PD and healthy subjects, thus supporting the breath prints observed with the sensors.

The breath prints that were identified with combinations of nanomaterial-based sensors have future potential as cost-effective, fast and reliable biomarkers for AD and PD

A nanomaterial-Based Breath Test for Short-Term Follow-Up after Lung Tumor Resection

Published: January 2013

Authors: Broza, Y. Y.; Kremer, R.; Tisch, U.; Gevorkyan, A.; Shiban, A.; Best, LA; Haick, H.

Years: 2013

Published in: Nanomedicine, 9 (1), 15-21

In this case study, we demonstrate the feasibility of nanomaterial-based sensors for identifying the breath-print of early-stage lung cancer (LC) and for short-term follow-up after LC-resection. Breath samples were collected from a small patient cohort prior to and after lung resection. Gas-chromatography/mass-spectrometry showed that five volatile organic compounds were significantly reduced after LC surgery. A nanomaterial-based sensor-array distinguished between pre-surgery and post-surgery LC states, as well as between pre-surgery LC and benign states. In contrast, the same sensor-array could neither distinguish between pre-surgery and post-surgery benign states, nor between LC and benign states after surgery. This indicates that the observed pattern is associated with the presence of malignant lung tumors. The proof-of-concept presented here has initiated a large-scale clinical study for post-surgery follow-up of LC patients.

Volatile Organic Compounds of Lung Cancer and Possible Biochemical Pathways

Published: November 2012

Authors: Hakim, M.; Broza, Y. Y.; Barash, O.; Peled, N.; Phillips, M.; Amann, A.; Haick, H.

Years: 2012

Published in: Chem. Rev., 112 (11), 5949–5966

1. Introduction
2. Volatile Organic Compounds of Lung Cancer
3. Biochemical Pathways of Volatile Organic Compounds of Lung Cancer
3.1. Hydrocarbons
3.2. Alcohols
3.3. Aldehydes
3.4. Ketones
3.5. Esters
3.6. Nitriles
3.7. Aromatic Compounds
4. Conclusions and Outlook

Non-invasive Breath Analysis of Pulmonary Nodules

Published: October 2012

Authors: Peled, N.; Hakim, M.; Bunn, P.,A.; Miller, Y.E.; Kennedy, T.C.; Mattei, J.; Mitchell, J.D.; Hirsch, F. R.; Haick, H.

Years: 2012

Published in: J. Thorac. Oncol., 7 (10), 1528-1533

The search for non-invasive diagnostic methods of lung cancer (LC) has led to new avenues of research, including the exploration of the exhaled breath. Previous studies have shown that LC can, in principle, be detected through exhaled-breath analysis. This study evaluated the potential of exhaled-breath analysis for the distinction of benign and malignant pulmonary nodules (PNs).
Breath samples were taken from 72 patients with PNs in a prospective trial. Profiles of volatile organic compounds were determined by (1) gas chromatography/mass spectrometry (GC-MS) combined with solid-phase microextraction and (2) a chemical nanoarray.
Fifty-three PNs were malignant and 19 were benign with similar smoking histories and comorbidities. Nodule size (mean ± SD) was 2.7 ± 1.7 versus 1.6 ± 1.3 cm (p = 0.004), respectively. Within the malignant group, 47 were non-small-cell lung cancer and six were small-cell lung cancer. Thirty patients had early-stage disease and 23 had advanced disease. Gas chromatography/mass spectrometry analysis identified a significantly higher concentration of 1-octene in the breath of LC, and the nanoarray distinguished significantly between benign versus malignant PNs (p < 0.0001; accuracy 88 ± 3%), between adeno- and squamous-cell carcinomas [LINE SEPARATOR](p < 0.0001; 88 ± 3%) and between early stage and advanced disease (p < 0.0001; 88 ± 2%).
In this pilot study, breath analysis discriminated benign from malignant PNs in a high-risk cohort based on LC-related volatile organic compound profiles. Furthermore, it discriminated adeno- and squamous-cell carcinoma and between early versus advanced disease. Further studies are required to validate this noninvasive approach, using a larger cohort of patients with PNs detected by computed tomography.

Polycyclic Aromatic Hydrocarbon for the Detection of Nonpolar Analytes under Counteracting Humidity Conditions

Published: September 2012

Authors: Bachar, N.; Mintz, L.; Zilberman, Y.; Ionescu, R.; Feng, X.; Müllen, K.; Haick, H.

Years: 2012

Published in: Acs Appl. Mater. Interf., 4 (9), 4960–4965

Real-world samples contain reducing and oxidizing chemical agents as well as large and small (bio)molecules, which are polar or nonpolar in nature. Sensing nonpolar analytes, which is of paramount importance for a wide variety of applications, is generally more difficult to achieve than sensing polar analytes. Here, we report on empirical observations of a unique polycyclic aromatic hydrocarbon derivative, referred as PAH-A, whose structure has a triangular-shaped aromatic core (with a carbon number of 60) and contains hydrophobic mesogens terminated with hydrophobic alkyl chains. We show that films made of PAH-A enable excellent sensitivity to nonpolar analytes, compared to polar analytes, in a setting of 5–40% counteracting relative humidity. This finding is based on monitoring the changes in the physical/optical properties of thin PAH-A films upon exposure to nonpolar and polar analytes, by means of quartz crystal microbalance and spectroscopic ellipsometry measurements. A comparison with other polycyclic aromatic hydrocarbon derivatives with different cores or organic functionalities is provided and discussed.

Field-Effect Transistors Based on Silicon Nanowire Arrays: Effect of the Good and the Bad Silicon Nanowires

Published: August 2012

Authors: Wang, B.; Stelzner, T.; Dirawi, R.; Assad, O.; Shehada, N.; Christiansen, S.; Haick, H.

Years: 2012

Published in: Acs Appl. Mater. Interf., 4, 4251−4258

Aligned arrays of silicon nanowires (aa-Si NWs) allow the exploitation of Si NWs in a scalable way. Previous studies explored the influence of the Si NWs’ number, doping density, and diameter on the related electrical performance. Nevertheless, the origin of the observed effects still not fully understood. Here, we aim to provide an understanding on the effect of channel number on the fundamental parameters of aa-Si NW field effect transistors (FETs). Toward this end, we have fabricated and characterized 87 FET devices with varied number of Si NWs, which were grown by chemical vapor deposition with gold catalyst. The results show that FETs with Si NWs above a threshold number (n > 80) exhibit better device uniformity, but generally lower device performance, than FETs with lower number of Si NWs (3 ≤ n < 80). Complementary analysis indicates that the obtained discrepancies could be explained by a weighted contribution of two main groups of Si NWs: (i) a group of gold-free Si NWs that exhibit high and uniform electrical characteristics; and (ii) a group of gold-doped Si NWs that exhibit inferior electrical characteristics. These findings are validated by a binomial model that consider the aa-Si NW FETs via a weighted combination of FETs of individual Si NWs. Overall, the obtained results suggest that the criterions used currently for evaluating the device performance (e.g., uniform diameter, length, and shape of Si NWs) do not necessarily guarantee uniform or satisfying electrical characteristics, raising the need for new growth processes and/or advanced sorting techniques of electrically homogeneous Si NWs.

Detection of Volatile Organic Compounds in Cattle Naturally Infected with Mycobacterium Bovis

Published: August 2012

Authors: Peled, N.; Ionescu, R.; Nol, P.; Barash, O.; McCollum, M.; VerCauterenc, K.; Koslow, M.; Stahl, R.; Rhyan, J.; Haick, H.

Years: 2012

Published in: Sens. Actuat. B, 171– 172, 588– 594

We report here on a novel methodology in detecting Mycobacterium bovis (M. bovis) infection in cattle, based on identifying unique volatile organic compounds (VOCs) or a VOC profile in the breath of cattle. The study was conducted on an M. bovis-infected dairy located in southern Colorado, USA, and on two tuberculosis-free dairies from northern Colorado examined as negative controls. Gas-chromatography/mass-spectrometry analysis revealed the presence of 2 VOCs associated with M. bovis infection and 2 other VOCs associated with the healthy state in the exhaled breath of M. bovis-infected and not infected animals, yielding distinctly different VOC patterns for the two study groups. Based on these results, a nanotechnology-based array of sensors was then tailored for detection of M. bovis-infected cattle via breath. Our system successfully identified all M. bovis-infected animals, while 21% of the not infected animals were classified as M. bovis-infected. This technique could form the basis for a real-time cattle monitoring system that allows efficient and non-invasive screening for new M. bovis infections on dairy farms.

Effect of Perforation on the Sensing Properties of Monolayer-Capped Metallic Nanoparticle Films

Published: July 2012

Authors: Segev-Bar, M.; Shuster, G.; Haick, H.

Years: 2012

Published in: J. Phys. Chem. C., 116, 15361−15368

We report on the effect of perforation within a monolayer-capped metallic nanoparticle (MCNP) film on sensing of volatile organic compounds (VOCs) and water molecules. Our results show that continuous MCNP film exhibits positive responses on exposure to VOCs and to water, consistent with the swelling and dielectric sensing mechanisms. In contrast, perforated films exhibit positive responses on exposure to VOCs but a high-magnitude negative response on exposure to high levels of water. The negative responses were higher by at least 1 order of magnitude compared with the positive responses. The results are explained in terms of ionization of condensed water and/or SiO2 sites in MCNP-free domains under applied voltage, side-by-side with the tunneling mechanism within the MCNP domains. The controlled morphology afforded by MCNP assemblies, combined with the existence of multiple sensing mechanisms under real-world humidity conditions, would enable a host of new fundamental and applied opportunities.

Structural and Electrical Properties of Single Ga/ZnO Nanofibers Synthesized by Electrospinning

Published: July 2012

Authors: Shmueli, Y.; Shter, E.G.; Assad, O.; Haick, H.; Sonntag. P.; Ricoux, P.; Grader, S.G.

Years: 2012

Published in: J. Mater. Res., 27 (13), 1672-1679

Nanofibers (NFs) of Ga-doped ZnO (GZO) were prepared by electrospinning of polymer–salts solution. Sintering profiles reported in the literature led to loss of the fibrous structure. Hence, the morphology, thermal stability, and phase composition of green and sintered fibers were investigated as function of sintering conditions to elucidate this degradation process. Optimal results were obtained at 400 °C for 30 min. This low temperature sintering of GZO fibers has not been previously reported. The fibers were porous with a significant surface area, making it possible to test their sensitivity to environmental changes. In particular, the response of the GZO NFs to changes in humidity was demonstrated for the first time. The electrical and sensing properties of single NFs prepared at these conditions were studied using a field-effect transistor mode.

Hybrids of Organic Molecules and Flat, Oxide-Free Silicon: High- Density Monolayers, Electronic Properties, and Functionalization

Published: July 2012

Authors: Li, Y.; Calder, S.; Yaffe, O.; Cahen, D.; Haick, H.; Kronik, L.; Zuilhof, H.

Years: 2012

Published in: Langmuir, 28, 9920-9929

Since the first report of Si–C bound organic monolayers on oxide-free Si almost two decades ago, a substantial amount of research has focused on studying the fundamental mechanical and electronic properties of these Si/molecule surfaces and interfaces. This feature article covers three closely related topics, including recent advances in achieving high-density organic monolayers (i.e., atomic coverage >55%) on oxide-free Si(111) substrates, an overview of progress in the fundamental understanding of the energetics and electronic properties of hybrid Si/molecule systems, and a brief summary of recent examples of subsequent functionalization on these high-density monolayers, which can significantly expand the range of applicability. Taken together, these topics provide an overview of the present status of this active area of research.

Spray-Coating Route for Highly Aligned and Large-Scale Arrays of Nanowires

Published: June 2012

Authors: Assad, O.; Leshansky, M.A.; Wang, B.; Stelzner, T.; Christiansen, S.; Haick, H.

Years: 2012

Published in: ACS Nano., 6 (6), 4702–4712

Technological implementation of nanowires (NWs) requires these components to be organized with controlled orientation and density on various substrates. Here, we report on a simple and efficient route for the deposition of highly ordered and highly aligned NW arrays on a wide range of receiver substrates, including silicon, glass, metals, and flexible plastics with controlled density. The deposition approach is based on spray-coating of a NW suspension under controlled conditions of the nozzle flow rate, droplet size of the sprayed NWs suspension, spray angle, and the temperature of the receiver substrate. The dynamics of droplet generation is understood by a combined action of shear forces and capillary forces. Provided that the size of the generated droplet is comparable to the length of the single NW, the shear-driven elongation of the droplets results presumably in the alignment of the confined NW in the spraying direction. Flattening the droplets upon their impact with the substrate yields fast immobilization of the spray-aligned NWs on the surface due to van der Waals attraction. The availability of the spray-coating technique in the current microelectronics technology would ensure immediate implementation in production lines, with minimal changes in the fabrication design and/or auxiliary tools used for this purpose.

Interactive Effect of Hysteresis and Surface Chemistry on Gated Silicon Nanowire Gas Sensors

Published: May 2012

Authors: Paska, Y.; Haick, H.

Years: 2012

Published in: Acs Appl. Mater. Interf., 4, 2604-2617

Gated silicon nanowire gas sensors have emerged as promising devices for chemical and biological sensing applications. Nevertheless, the performance of these devices is usually accompanied by a “hysteresis” phenomenon that limits their performance under real-world conditions. In this paper, we use a series of systematically changed trichlorosilane-based organic monolayers to study the interactive effect of hysteresis and surface chemistry on gated silicon nanowire gas sensors. The results show that the density of the exposed or unpassivated Si–OH groups (trap states) on the silicon nanowire surface play by far a crucial effect on the hysteresis characteristics of the gated silicon nanowire sensors, relative to the effect of hydrophobicity or molecular density of the organic monolayer. Based on these findings, we provide a tentative model-based understanding of (i) the relation between the adsorbed organic molecules, the hysteresis, and the related fundamental parameters of gated silicon nanowire characteristics and of (ii) the relation between the hysteresis drift and possible screening effect on gated silicon nanowire gas sensors upon exposure to different analytes at real-world conditions. The findings reported in this paper could be considered as a launching pad for extending the use of the gated silicon nanowire gas sensors for discriminations between polar and nonpolar analytes in complex, real-world gas mixtures.

Gold Nanoparticle Sensors for Detecting Chronic Kidney Disease and Disease Progression

Published: May 2012

Authors: Marom, O.; Nakhoul, F.; Tisch, U.; Shiban, A.; Abassi, Z.; Haick, H.

Years: 2012

Published in: Nanomedicine (Lond)., 7 (5), 639-650

To study the feasibility of a novel nanomedical method that utilizes breath testing for identifying chronic kidney disease (CKD) and disease progression.
Exhaled breath samples were collected from 62 volunteers. The breath samples were analyzed using sensors based on organically functionalized gold nanoparticles, combined with support vector machine analysis. Sensitivity and specificity with reference to CKD patient classification according to estimated glomerular filtration rate were determined using cross-validation. The chemical composition of the breath samples was studied using gas chromatography linked with mass spectrometry.
A combination of two to three gold nanoparticles sensors provided good distinction between early-stage CKD and healthy states (accuracy of 79%) and between stage 4 and 5 CKD states (accuracy of 85%). A single sensor provided a distinction between early and advanced CKD (accuracy of 76%). Several substances in the breath were identified and could be associated with CKD-related biochemical processes or with the accumulation of toxins through kidney function loss.
Breath testing using gold nanoparticle sensors holds future potential as a cost-effective, fast and reliable diagnostic test for early detection of CKD and monitoring of disease progression.

Volatile Organic Compounds in Exhaled Breath as Biomarkers for the Early Detection and Screening of Lung Cancer

Published: May 2012

Authors: Tisch, U.; Billan, S.; Ilouze, M.; Phillips, M.; Peled, N.; Haick, H.

Years: 2012

Published in: CML – Lung Cancer, 5 (4), 107–117

The article offers information on detection and screening of lung cancer. Staging of this disease can be classified according to the tumor, node and metastasis (TNM). It notes that most lung cancers originate from epithelial cells, and can be classified as small-cell lung carcinoma (SCLC), squamous cell carcinoma or large cell carcinoma. Lung cancer can be diagnosed through computed tomography (CT) and positron emission tomography (PET).

Molecular Gating of Silicon Nanowire Field-Effect Transistors with Nonpolar Analytes

Published: January 2012

Authors: Paska, Y.; Stelzner, T.; Assad, O.; Tisch, U.; Christiansen, S.; Haick, H.

Years: 2012

Published in: ACS Nano., 6 (1), 335-345

Silicon nanowire field-effect transistors (Si NW FETs) have been used as powerful sensors for chemical and biological species. The detection of polar species has been attributed to variations in the electric field at the conduction channel due to molecular gating with polar molecules. However, the detection of nonpolar analytes with Si NW FETs has not been well understood to date. In this paper, we experimentally study the detection of nonpolar species and model the detection process based on changes in the carrier mobility, voltage threshold, off-current, off-voltage, and subthreshold swing of the Si NW FET. We attribute the detection of the nonpolar species to molecular gating, due to two indirect effects: (i) a change in the dielectric medium close to the Si NW surface and (ii) a change in the charged surface states at the functionality of the Si NW surface. The contribution of these two effects to the overall measured sensing signal is determined and discussed. The results provide a launching pad for real-world sensing applications, such as environmental monitoring, homeland security, food quality control, and medicine.

International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 Report

Published: January 2012

Authors: Field, J.K.; Smith, R.A.; Aberle, D.R.; Oudkerk, M.; Baldwin, D.R.; Yankelevitz, D.; Pedersen, J.H.; Swanson, S.J.; Travis, W.D.; Wisbuba, I.I.; Noguchi, M.; Mulshine, J.L.; IASLC CT Screening Workshop 2011 Participants

Years: 2012

Published in: J. Thorac. Oncol., 7,10-19

The International Association for the Study of Lung Cancer (IASLC) Board of Directors convened a computed tomography (CT) Screening Task Force to develop an IASLC position statement, after the National Cancer Institute press statement from the National Lung Screening Trial showed that lung cancer deaths fell by 20%. The Task Force’s Position Statement outlined a number of the major opportunities to further improve the CT screening in lung cancer approach, based on experience with cancer screening from other organ sites.The IASLC CT Screening Workshop 2011 further developed these discussions, which are summarized in this report. The recommendation from the workshop, and supported by the IASLC Board of Directors, was to set up the Strategic CT Screening Advisory Committee (IASLC-SSAC). The Strategic CT Screening Advisory Committee is currently engaging professional societies and organizations who are stakeholders in lung cancer CT screening implementation across the globe, to focus on delivering guidelines and recommendations in six specific areas: (i) identification of high-risk individuals for lung cancer CT screening programs; (ii) develop radiological guidelines for use in developing national screening programs; (iii) develop guidelines for the clinical work-up of “indeterminate nodules” resulting from CT screening programmers; (iv) guidelines for pathology reporting of nodules from lung cancer CT screening programs; (v) recommendations for surgical and therapeutic interventions of suspicious nodules identified through lung cancer CT screening programs; and (vi) integration of smoking cessation practices into future national lung cancer CT screening programs.

Charge Transport Across Metal/Molecular (alkyl) Monolayer-Si Junctions is Dominated by the LUMO Level

Published: January 2012

Authors: Yaffe, O.; Qi, Y.; Scheres, L.; Puniredd, S. R.; Segev, L.; Ely, T.; Haick, H.; Zuilhof, H.; Vilan, A.; Kronik, L.; Kahn, A.; Cahen, D.

Years: 2012

Published in: Phys. Rev. B, 85, 045433/1-045433/8

We compare the charge transport characteristics of heavy-doped p++- and n++-Si-alkyl chain/Hg junctions. Based on negative differential resistance in an analogous semiconductor-inorganic insulator/metal junction we suggest that for both p++- and n++-type junctions, the energy difference between the Fermi level and lowest unoccupied molecular orbital (LUMO), i.e., electron tunneling, controls charge transport. This conclusion is supported by results from photoelectron spectroscopy (ultraviolet photoemission spectroscopy, inverse photoelectron spectroscopy, and x-ray photoemission spectroscopy) for the molecule-Si band alignment at equilibrium, which clearly indicate that the energy difference between the Fermi level and the LUMO is much smaller than that between the Fermi level and the highest occupied molecular orbital (HOMO). Furthermore, the experimentally determined Fermi level – LUMO energy difference, agrees with the non-resonant tunneling barrier height, deduced from the exponential length attenuation of the current.

Molecular Gating of Silicon Nanowire Field-Effect Transistors with Nonpolar Analytes

Published: December 2011

Authors: Paska, Y.; Stelzner, T.; Assad, O.; Tisch, U.; Christiansen, S.; Haick, H.

Years: 2011

Published in: ACS Nano., 6 (1), 335-345

Silicon nanowire field-effect transistors (Si NW FETs) have been used as powerful sensors for chemical and biological species. The detection of polar species has been attributed to variations in the electric field at the conduction channel due to molecular gating with polar molecules. However, the detection of nonpolar analytes with Si NW FETs has not been well understood to date. In this paper, we experimentally study the detection of nonpolar species and model the detection process based on changes in the carrier mobility, voltage threshold, off-current, off-voltage, and subthreshold swing of the Si NW FET. We attribute the detection of the nonpolar species to molecular gating, due to two indirect effects: (i) a change in the dielectric medium close to the Si NW surface and (ii) a change in the charged surface states at the functionality of the Si NW surface. The contribution of these two effects to the overall measured sensing signal is determined and discussed. The results provide a launching pad for real-world sensing applications, such as environmental monitoring, homeland security, food quality control, and medicine.

Detection of Asymptomatic Nigrostriatal Dopaminergic Leison in Rats by Exhaled Air Analysis Using Carbon Nanotube Sensors

Published: December 2011

Authors: Tisch, U.; Aluf, Y.; Ionescu, R.; Nakhleh, K. M.; Bassal, R.; Axelrod, N.; Robertman, D.; Tessler, Y.; Finberg, J.P.M.; Haick, H.

Years: 2011

Published in: ACS Chem. Neurosci., 3, 161-166

The ante-mortem diagnosis of Parkinson’s disease (PD) still relies on clinical symptoms. Biomarkers could in principle be used for the early detection of PD-related neuronal damage, but no validated, inexpensive, and simple biomarkers are available yet. Here we report on the breath-print of presymptomatic PD in rats, using a model with 50% lesion of dopaminergic neurons in substantia nigra. Exhaled breath was collected from 19 rats (10 lesioned and 9 sham operated) and analyzed using organically functionalized carbon nanotube sensors. Discriminant factor analysis detected statistically significant differences between the study groups and a classification accuracy of 90% was achieved using leave-one-out cross-validation. The sensors’ breath-print was supported by determining statistically significant differences of several volatile organic compounds in the breath of the lesioned rats and the sham operated rats, using gas chromatography combined with mass spectrometry. The observed breath-print shows potential for cost-effective, fast, and reliable early PD detection.

Probing the Electrostatics of Self-Assembled Monolayers by Means of Beveled Metal-Oxide-Semiconductor Structures

Published: December 2011

Authors: Kornblum, L.; Paska, Y.; Rothschild, A.J.; Haick, H.; Eizenberg, M.

Years: 2011

Published in: Appl. Phys. Lett., 99, 233508/1-233508/3

A method is proposed for characterization of the electrostatics of self-assembledmonolayers(SAMs). The method is based on the extraction of the metal’s effective work function in metal-oxide-semiconductor capacitors, where the SAM is positioned at the metal-oxide interface. Hexyltrichlorosilane molecules assembled on SiO2 are used as a model system for this method. A band offset of 0.5 ± 0.15 eV is observed in the SAM sample when compared to a reference with no molecules. Spectroscopy is employed to confirm the presence of silane anchoring groups after metal deposition.

Effect of Humidity on NanoParticle-Based Chemiresistors: A Comparison between Synthetic and Real-World Samples

Published: November 2011

Authors: Konvalina, G.; Haick, H.

Years: 2001

Published in: Acs Appl. Mater. Interf., 4, 317-325

Chemiresistors based on metal monolayer-capped nanoparticles (MCNPs) are promising candidates for fast, inexpensive, and portable tracing of (bio)chemical species in the gas phase. However, the sensitivity of such sensors to humidity is problematic, limiting their reliable and reproducible application in real-world environmental conditions. In this work, we employed a compensation method to explore the effect of humidity on a single MCNP chemiresistor as well as on an array of MCNP sensors used to analyze either synthetic or real-world samples. We show that an array of MCNP chemiresistors is able to precisely detect and estimate subtle concentrations of (mixtures of) volatile organic compounds (VOCs) under variable backgrounds of 2–83% relative humidity (RH) only after humidity compensation. Humidity effects were also tested in two clinical trials aimed at detecting prostate cancer and breast cancer through exhaled breath analysis. Analysis of the results showed improved cancer detection capabilities as a result of RH compensation, though less substantial than the impact of RH compensation on synthetic samples. This outcome is attributed to one – or a combination – of the following effects: (i) the RH variance was smaller in the breath samples than that in the synthetic samples; (ii) the VOC composition in the breath samples is less controlled than the synthetic samples; and (iii) the responses to small polar VOCs and water are not necessarily additive in breath samples. Ultimately, the results presented here could assist the development of a cost-effective, low-power method for widespread detection of VOCs in real-world applications, such as breath analysis, as well as for environmental, security, and food applications.

Classification of Lung Cancer Histology by Gold Nanoparticle Sensors

Published: October 2011

Authors: Barash, O.; Peled, N.; Tisch, U.; Bunn, P. A. Jr.; Hirsch, F. R.; Haick, H.

Years: 2011

Published in: Nanomedicine (NY, US)., 8(5), 580-589

We propose a nanomedical device for the classification of lung cancer (LC) histology. The device profiles volatile organic compounds (VOCs) in the headspace of (subtypes of) LC cells, using gold nanoparticle (GNP) sensors that are suitable for detecting LC-specific patterns of VOC profiles, as determined by gas chromatography–mass spectrometry analysis. Analyzing the GNP sensing signals by support vector machine allowed significant discrimination between (i) LC and healthy cells; (ii) small cell LC and non–small cell LC; and between (iii) two subtypes of non–small cell LC: adenocarcinoma and squamous cell carcinoma. The discriminative power of the GNP sensors was then linked with the chemical nature and composition of the headspace VOCs of each LC state. These proof-of-concept findings could totally revolutionize LC screening and diagnosis, and might eventually allow early and differential diagnosis of LC subtypes with detectable or unreachable lung nodules.

Detection of Multiple Sclerosis from Exhaled Breath Using Bilayers of Polycyclic Aromatic Hydrocarbons and Single-Wall Carbon Nanotubes

Published: September 2011

Authors: Ionescu, R.; Broza, Y. Y.; Shaltieli, H.; Sadeh, D.; Zilberman, Y.; Feng, X.; Lejbkowicz, I.; Glass-Marmor, L.; Müllen, K.; Miller, A.; Haick, H.

Years: 2011

Published in: ACS Chem. Neurosci., 2 (12), 687–693

A cross-reactive array of polycyclic aromatic hydrocarbons and single wall carbon nanotube bilayers was designed for the detection of volatile organic compounds (tentatively, hexanal and 5-methyl-undecane) that identify the presence of disease in the exhaled breath of patients with multiple sclerosis. The sensors showed excellent discrimination between hexanal, 5-methyl-undecane, and other confounding volatile organic compounds. Results obtained from a clinical study consisting of 51 volunteers showed that the sensors could discriminate between multiple sclerosis and healthy states from exhaled breath samples with 85.3% sensitivity, 70.6% specificity, and 80.4% accuracy. These results open new frontiers in the development of a fast, noninvasive, and inexpensive medical diagnostic tool for the detection and identification of multiple sclerosis. The results could serve also as a launching pad for the discrimination between different subphases or stages of multiple sclerosis as well as for the identification of multiple sclerosis patients who would respond well to immunotherapy.

Utility of Resistance and Capacitance Response in Sensors Based on Monolayer-Capped Metal Nanoparticles

Published: July 2011

Authors: Shuster, G.; Baltianski, S.; Tsur, Y.; Haick, H.

Years: 2011

Published in: J. Phys. Chem. Lett, 2 (15), 1912–1916

We investigate the utility of resistance and capacitance responses, as derived by impedance spectroscopy, in well-controlled and real-world applications of monolayer-capped metal nanoparticle (MCNP) sensors. Exposure of the MCNP films to well-controlled analytes showed stable sensing responses and low baseline drift of the pertinent capacitance signals, when compared with equivalent resistance signals. In contrast, exposure of the MCNP films to breath of chronic kidney disease patients under dialysis, as a representative example to real-world multicomponent mixtures, showed low baseline drift but relatively scattered signals when compared with the equivalent resistance response. We ascribe these discrepancies to the level and fluctuating concentration of water molecules in the real-world samples.

Enhanced Sensing of Nonpolar Volatile Organic Compounds by Silicon Nanowire Field Effect Transistors

Published: June 2011

Authors: Paska, Y.; Stelzner, T.; Christiansen, S.; Haick, H.

Years: 2011

Published in: ACS Nano., 5 (7), 5620–5626

Silicon nanowire field effect transistors (Si NW FETs) are emerging as powerful sensors for direct detection of biological and chemical species. However, the low sensitivity of the Si NW FET sensors toward nonpolar volatile organic compounds (VOCs) is problematic for many applications. In this study, we show that modifying Si NW FETs with a silane monolayer having a low fraction of Si–O–Si bonds between the adjacent molecules greatly enhances the sensitivity toward nonpolar VOCs. This can be explained in terms of an indirect sensor–VOC interaction, whereby the nonpolar VOC molecules induce conformational changes in the organic monolayer, affecting (i) the dielectric constant and/or effective dipole moment of the organic monolayer and/or (ii) the density of charged surface states at the SiO2/monolayer interface. In contrast, polar VOCs are sensed directly via VOC-induced changes in the Si NW charge carriers, most probably due to electrostatic interaction between the Si NW and polar VOCs. A semiempirical model for the VOC-induced conductivity changes in the Si NW FETs is presented and discussed.

Arrays of Chemisensitive Monolayer-Capped Metallic Nanoparticles for Diagnostic Breath Testing

Published: May 2011

Authors: Tisch, U.; Haick, H.

Years: 2011

Published in: Rev. Chem. Eng., 26,171-179

Arrays of cross-reactive sensors are well suited to detect subtle changes in clinical samples resulting from internal diseases. Monolayer-capped metallic nanoparticles (MCNPs) are ideal base materials for such sensor arrays because they are chemically versatile, easily fabricated, and readily integrated into chemiresistive sensing platforms using microelectrodes. In this review, we present the main concepts and approaches related to the use of MCNPs in chemiresistors and show their applicability to exhaled breath testing, which is a new non-invasive frontier of medical diagnostics.

Diagnosis of Head-and-Neck Cancer from Exhaled Breath

Published: April 2011

Authors: Hakim, M.; Billan, S.; Tisch, U.; Peng, G.; Dvrokind, I.; Marom, O.; Abdah- Brotnyak, R.; Kuten, A.; Haick, H.

Years: 2011

Published in: Br. J. Cancer, 104, 1649–1655

Head-and-neck cancer (HNC) is the eighth most common malignancy worldwide. It is often diagnosed late due to a lack of screening methods and overall cure is achieved in <50% of patients. Head-and-neck cancer sufferers often develop a second primary tumour that can affect the entire aero-digestive tract, mostly HNC or lung cancer (LC), making lifelong follow-up necessary.

Alveolar breath was collected from 87 volunteers (HNC and LC patients and healthy controls) in a cross-sectional clinical trial. The discriminative power of a tailor-made Nanoscale Artificial Nose (NA-NOSE) based on an array of five gold nanoparticle sensors was tested, using 62 breath samples. The NA-NOSE signals were analysed to detect statistically significant differences between the sub-populations using (i) principal component analysis with ANOVA and Student’s t-test and (ii) support vector machines and cross-validation. The identification of NA-NOSE patterns was supported by comparative analysis of the chemical composition of the breath through gas chromatography in conjunction with mass spectrometry (GC-MS), using 40 breath samples.

The NA-NOSE could clearly distinguish between (i) HNC patients and healthy controls, (ii) LC patients and healthy controls, and (iii) HNC and LC patients. The GC-MS analysis showed statistically significant differences in the chemical composition of the breath of the three groups.

The presented results could lead to the development of a cost-effective, fast, and reliable method for the differential diagnosis of HNC that is based on breath testing with an NA-NOSE, with a future potential as screening tool.

Catalyst-Free Functionalization for Versatile Modification of Non-Oxidized Silicon Structures

Published: March 2011

Authors: Puniredd, S. R.; Assad, O.; Stelzner, T.; Christiansen, S.; Haick, H.

Years: 2011

Published in: Langmuir, 27 (8), 4764–4771

Here, we report on a simple, catalyst-free route for obtaining highly versatile subsequent functionalization on Si nanowires and Si(111) substrates. The versatility of this approach allows subsequent functionalization not only for organic species but also for inorganic (nanomaterial) species. The method has the advantage of controlling the density of reactive cross-linkers without affecting the stability of the Si samples and without having metallic (or catalyst) residues on the surface. This method also allows formation of monolayers with a variety of termination groups and is expected to open up a wide range of opportunities for producing stable molecule-based (opto)electronic and (bio)sensing devices. Immobilization of inorganic nanomaterial on the Si samples offers advanced opportunities in molecular switches, (bio)sensors, molecular scale memory, and Si-based nanoelectronic devices.

Classification of Breast Cancer Precursors through Exhaled Breath, Breast Cancer Research and Treatment

Published: December 2010

Authors: Shuster, G.; Gallimidi, Z.; Reiss, A. H.; Dovgolevsky, E.; Billan, S.; Abdah- Brotnyak, R.; Kuten, A.; Engel, A.; Shiban, A.; Tisch, U.; Haick, H.

Years: 2010

Published in: Breast Cancer Res. Treat., 126, 791-796

Certain benign breast diseases are considered to be precursors of invasive breast cancer. Currently available techniques for diagnosing benign breast conditions lack accuracy. The purpose of this study was to deliver a proofof-concept for a novel method that is based on breath testing to identify breast cancer precursors. Within this context, the authors explored the possibility of using exhaled alveolar breath to identify and distinguish between benign breast conditions, malignant lesions, and healthy states, using a small-scale, case-controlled, cross-sectional clinical trial. Breath samples were collected from 36 volunteers and were analyzed using a tailor-made nanoscale artificial NOSE (NA-NOSE). The NA-NOSE signals were analyzed using two independent methods: (i) principal component analysis, ANOVA and Student’s t-test and (ii) support vector machine analysis to detect statistically significant differences between the sub-populations. The NA-NOSE could distinguish between all studied test populations. Breath testing with a NA-NOSE holds future potential as a cost-effective, fast, and reliable diagnostic test for breast cancer risk factors and precursors, with possible future potential as screening method.

Nanomaterials for Cross- Reactive Sensor Arrays

Published: October 2010

Authors: Tisch, U.; Haick, H.

Years: 2010

Published in: Bull. MRS., 35, 797-803

Arrays of cross-reactive sensors for the detection of multi-component chemical and biological agents have been actively developed during the past two decades. The rapid progress in this fi eld has been driven by the need for fast online detection of a wide range of chemical and biological compounds and mixtures in different branches of industry and in medicine. Nanomaterials are ideal base materials for such sensor arrays because they are chemically versatile, can easily be fabricated, and can be integrated into existing sensing platforms to increase the sensitivity to the target agents. We present a concise though non-exhaustive didactic review of the main concepts and approaches related to the use of nanomaterials in cross-reactive sensor arrays. We focus on electronic transducers incorporating the most important classes of nanomaterials: molecularly modifi ed metal nanoparticles, metal oxide nanoparticles, carbon nanotubes, and semiconducting nanowires. Selected examples of their integration into sensors and sensor arrays are given. We conclude with a brief discussion of the possibilities that the integration of the different types of nanomaterials into sensor arrays offer and the expected limitations.

Carbon Nanotube/ Hexa-peri- hexabenzocoronene Bilayers for Discrimination Between Nanopolar Volatile Organic Compounds of Cancer and Humid Atmospheres

Published: October 2010

Authors: Zilberman, Y.; Tisch, U.; Shuster, G.; Pisula, W.; Feng, X.; Müllen, K.; Haick, H.

Years: 2010

Published in: Adv. Mater., 22, 4317-4320

Cancer detection: The development of a cost-effective, portable and non-invasive diagnostic tool for detecting cancer from exhaled breath requires sensors that discriminate well between polar and nonpolar volatile organic compounds in highly humid atmospheres. Here we show that a chemiresistive bilayer comprised of a dense cap layer of discotic hexa-dodecyl-hexa-peri-hexabenzocoronene derivatives (hereby, HBC-C12) and a random network of carbon nanotubes (RN-CNT) as underlayer layer could fulfill these requirements.

Self-Assembly of Organic Monolayers as Protective and Conductive Bridges for Nanometric Surface – Mount Applications

Published: September 2010

Authors: Platzmann, I.; Haick, H.; Tannebaum, R.

Years: 2010

Published in: Acs Appl. Mater. Interf., 2( 9), 2585-2593

In this work, we present a novel surface-mount placement process that could potentially overcome the inadequacies of the currently used stencil-printing technology, when applied to devices in which either their lateral and/or their horizontal dimensions approach the nanometric scale. Our novel process is based on the “bottom-up” design of an adhesive layer, operative in the molecular/nanoscale level, through the use of self-assembled monolayers (SAMs) that could form protective and conductive bridges between pads and components. On the basis of previous results, 1,4-phenylene diisocyanide (PDI) and terephthalic acid (TPA) were chosen to serve as the best candidates for the achievement of this goal. The quality and stability of these SAMs on annealed Cu surfaces (Rrms=0.15-1.1 nm) were examined in detail. Measurements showed that the SAMs of TPA and PDI molecules formed on top of Cu substrates created thermally stable organic monolayers with high surface coverage (∼90%), in which the molecules were closely packed and well-ordered. Moreover, the molecules assumed a standing-up phase conformation, in which the molecules bonded to the Cu substrate through one terminal functional group, with the other terminal group residing away from the substrate. To examine the ability of these monolayers to serve as “molecular wires,” i.e., the capability to provide electrical conductivity, we developed a novel fabrication method of a parallel plate junction (PPJ) in order to create symmetric Cu-SAM-Cu electrical junctions. The current-bias measurements of these junctions indicated high tunneling efficiency. These achievements imply that the SAMs used in this study can serve as conductive molecular bridges that can potentially bind circuital pads/components.

Monolayer- Capped Cubic Platinum Nnoparticles for Sensing Nonpolar Analyst in Highly Humid Atmospheres

Published: July 2010

Authors: Dovgolevsky, E.; Konvalina, G.; Tisch, U.; Haick, H.

Years: 2010

Published in: J. Phys. Chem. C., 114, 14042-14049

We report on the feasibility of cubic Pt nanoparticles (NPs) capped with four representative organic ligands, viz. oleylamine (ODA), 11-mercaptoundecanol, 11-mercaptoundecanoic acid, and benzylmercaptan, for sensing gaseous nonpolar analytes in humid atmospheres. Chemiresistors based on cubic Pt NPs with nonpolar ligands show a very large increase in resistance upon exposure to nonpolar analyte vapors, combined with a low sensitivity to polar analyte vapors, especially to water. The sensing mechanism can be understood in terms of analyte-induced changes in the NP−NP core distance and changes in the permittivity of the medium between the NPs. The sensing capabilities of the Pt NP chemiresistors for nonpolar molecules in highly humid atmospheres are demonstrated by dosing an ODA-capped cubic Pt NP sensor with air mixtures containing low octane concentrations and high humidity levels that are typical for many applications. The simple construction, low cost, stability, fast response, and high sensitivity to nonpolar molecules, together with the low sensitivity to water vapor, are promising features for sensing applications in real confounding atmospheres.

Detection of Lung, Breast, Colorectal and Prostate Cancers from Exhaled Breath Using a Singel Array of Nanosensors

Published: July 2010

Authors: Peng, G.; Hakim, M.; Broza, Y. Y.; Billan, S.; Abdah- Brotnyak, R.; Kuten, A.; Tisch, U.; Haick, H.

Years: 2010

Published in: Br. J. Cancer, 103, 542 – 551


Tumour growth is accompanied by gene and/or protein changes that may lead to peroxidation of the cell membrane species and, hence, to the emission of volatile organic compounds (VOCs). In this study, we investigated the ability of a nanosensor array to discriminate between breath VOCs that characterise healthy states and the most widespread cancer states in the developed world: lung, breast, colorectal, and prostate cancers.

Exhaled alveolar breath was collected from 177 volunteers aged 20-75 years (patients with lung, colon, breast, and prostate cancers and healthy controls). Breath from cancerous subjects was collected before any treatment. The healthy population was healthy according to subjective patient’s data. The breath of volunteers was examined by a tailor-made array of cross-reactive nanosensors based on organically functionalised gold nanoparticles and gas chromatography linked to the mass spectrometry technique (GC-MS).

The results showed that the nanosensor array could differentiate between ‘healthy’ and ‘cancerous’ breath, and, furthermore, between the breath of patients having different cancer types. Moreover, the nanosensor array could distinguish between the breath patterns of different cancers in the same statistical analysis, irrespective of age, gender, lifestyle, and other confounding factors. The GC-MS results showed that each cancer could have a unique pattern of VOCs, when compared with healthy states, but not when compared with other cancer types.

The reported results could lead to the development of an inexpensive, easy-to-use, portable, non-invasive tool that overcomes many of the deficiencies associated with the currently available diagnostic methods for cancer

Systematic Cross-Linking Changes within a Self-Assembled Monolayer in a Nanogap Junction: A Tool for Investigating the Intermolecular Electronic Coupling

Published: February 2010

Authors: Paska, Y.; Haick, H.

Years: 2010

Published in: J. Am. Chem. Soc., 132, 1774–1775

Here, we show that a controllable cross-linking within a self-assembled monolayer can be used as a tool for investigating the (lateral) intermolecular coupling between adjacent organic molecules. We draw this conclusion based on macroscopic electrical experiments with self-assembled hexyltrichlorosilane (HTS) having different degrees of Si-O-Si intermolecular bonds in a planar nanogap junction.

Tuning Electrical Properties of Si Nanowire Field Effect Transistors by Molecular Engineering

Published: December 2009

Authors: Bashouti, M. Y.; Tung, R. T.; Haick, H.

Years: 2009

Published in: Small, 5 (23), 2761-2769

Exposed facets of n-type silicon nanowires (Si NWs) fabricated by a top-down approach are successfully terminated with different organic functionalities, including 1,3-dioxan-2-ethyl, butyl, allyl, and propyl-alcohol, using a two-step chlorination/alkylation method. X-ray photoemission spectroscopy and spectroscopic ellipsometry establish the bonding and the coverage of these molecular layers. Field-effect transistors fabricated from these Si NWs displayed characteristics that depended critically on the type of molecular termination. Without molecules the source-drain conduction is unable to be turned off by negative gate voltages as large as -20 V. Upon adsorption of organic molecules there is an observed increase in the “on” current at large positive gate voltages and also a reduction, by several orders of magnitude, of the “off” current at large negative gate voltages. The zero-gate voltage transconductance of molecule-terminated Si NW correlates with the type of organic molecule. Adsorption of butyl and 1,3-dioxan-2-ethyl molecules improves the channel conductance over that of the original SiO(2)-Si NW, while adsorption of molecules with propyl-alcohol leads to a reduction. It is shown that a simple assumption based on the possible creation of surface states alongside the attachment of molecules may lead to a qualitative explanation of these electrical characteristics. The possibility and potential implications of modifying semiconductor devices by tuning the distribution of surface states via the functionality of attached molecules are discussed.

Sniffing the Unique ”Odor Print” of Non-Small-Cell Lung Cancer with Gold Nanoparticles

Published: November 2009

Authors: Barash, O.; Peled, N.; Hirsch, F. R.; Haick, H.

Years: 2009

Published in: Small, 5 (22), 2618-2624

A highly sensitive and fast-response array of sensors based on gold nanoparticles, in combination with pattern recognition methods, can distinguish between the odor prints of non-small-cell lung cancer and negative controls with 100% accuracy, with no need for preconcentration techniques. Additionally, preliminary results indicate that the same array of sensors might serve as a better tool for understanding the biochemical source of volatile organic compounds that might occur in cancer cells and appear in the exhaled breath, as compared to traditional spectrometry techniques. The reported results provide a launching pad to initiate a bedside tool that might be able to screen for early stages of lung cancer and allow higher cure rates. In addition, such a tool might be used for the immediate diagnosis of fresh (frozen) tissues of lung cancer in operating rooms, where a dichotomic diagnosis is crucial to guide surgeons.

Diagnosing Lung Cancer in Exhaled Breath Using Au Nanoparticles

Published: August 2009

Authors: Peng, G.; Tisch, U.; Adams, O.; Hakim, M.; Shehada, N.; Broza, Y. Y.; Billan, S.; Abdah- Brotnyak, R.; Kuten, A.; Haick, H.

Years: 2009

Published in: Nat. Nanotechnol., 4, 669-673

Conventional diagnostic methods for lung cancer are unsuitable for widespread screening because they are expensive and occasionally miss tumours. Gas chromatography/mass spectrometry studies have shown that several volatile organic compounds, which normally appear at levels of 1–20 ppb in healthy human breath, are elevated to levels between 10 and 100 ppb in lung cancer patients. Here we show that an array of sensors based on gold nanoparticles can rapidly distinguish the breath of lung cancer patients from the breath of healthy individuals in an atmosphere of high humidity. In combination with solid-phase microextraction, gas chromatography/mass spectrometry was used to identify 42 volatile organic compounds that represent lung cancer biomarkers. Four of these were used to train and optimize the sensors, demonstrating good agreement between patient and simulated breath samples. Our results show that sensors based on gold nanoparticles could form the basis of an inexpensive and non-invasive diagnostic tool for lung cancer.

Molecular Electronics at Metal/Semiconductor Junctions. Si Inversion by Sub-Nanometer Molecular Films

Published: May 2009

Authors: Yaffe, O.; Scheres, L.; Puniredd, S. R.; Stein, N.; Biller, A.; Har-Lavan, R.; Shpaisman, H.; Zuilhof, H.; Haick, H.; Cahen, D.; Vilan, A.

Years: 2009

Published in: Nano Lett., 9 (6), 2390–2394

Electronic transport across n-Si-alkyl monolayer/Hg junctions is, at reverse and low forward bias, independent of alkyl chain length from 18 down to 1 or 2 carbons! This and further recent results indicate that electron transport is minority, rather than majority carrier dominated, occurs via generation and recombination, rather than (the earlier assumed) thermionic emission, and, as such, is rather insensitive to interface properties. The (m)ethyl results show that binding organic molecules directly to semiconductors provides semiconductor/metal interface control options, not accessible otherwise.

Detection of Nonpolar Molecules by Means of Carrier Scattering in Random Networks of Carbon Nanotubes: Towards Diagnosis of Diseases via Breath Samples

Published: April 2009

Authors: Peng, G.; Tisch, U.; Haick, H.

Years: 2009

Published in: Nano Lett., 9 (4), 1362-1368

Field effect transistors (FETs) based on random networks (RNs) of single-wall carbon nanotubes (CNTs) have several technological advantages. However, the low sensitivity (or no sensitivity) of RN-CNT sensors to nonpolar molecules is a problematic, negative feature that limits their applications in the detection of a wide variety of diseases via breath samples. In this paper, we show experimental evidence for the detection of both individual nonpolar molecules and patterns of nonpolar molecules, even in the presence of polar molecules in the same environment. We do so by preparing RN-CNT FETs and functionalizing them with organic films that exhibit distinctive electrical and physical (or mechanical) characteristics. Exposing the functionalized RN-CNTs to representative nonpolar breath biomarkers, and, for comparison, to polar molecules in the gas phase, and monitoring the changes in conductance, work function, and organic film thickness show sensitivity toward nonpolar molecules. We explain this observation by carrier scattering as a result of swelling of the organic film upon exposure to (nonpolar) chemical agents. Hence, the sensitivity towards nonpolar molecules can be tailored, even in the presence of polar molecules, by controlling the scattering of charge carrier through deliberate functionalization of CNTs. As examples for the technological impact of our findings, we describe ways to detect lung cancer and kidney disease using specially designed RN-CNT sensor arrays.

Sponge-like Structures of Hexa-peri-hexabenzocoronenes Derivatives Enhances the Sensitivity of Chemiresistive Carbon Nanotubes to Nonpolar Volatile Organic Compounds

Published: April 2009

Authors: Zilberman, Y.; Tisch, U.; Pisula, W.; Feng, X.; Müllen, K.; Haick, H.

Years: 2009

Published in: Langmuir, 25 (9), 5411–5416

Cancer is a leading health hazard, and lung cancer is its most common form. Breath testing is a fast, noninvasive diagnostic method which links specific volatile organic compounds (VOCs) in exhaled breath to medical conditions. Arrays of sensors based on carbon nanotubes (CNTs) could in principle detect cancer by differentiating between the VOCs found in the breath of healthy and sick persons, but the notoriously low sensitivity of CNT sensors to nonpolar VOCs limits their accuracy. In this study, we have achieved a marked improvement of the sensitivity and selectivity of random networks (RNs) of CNT chemiresistors to nonpolar VOCs by functionalizing them with self-assembled, spongelike structures of discotic hexa-peri-hexabenzocoronene (HBC) derivatives. We observed swelling of the organic film by monitoring the changes of organic film thickness during exposure and propose that the expansion of the spongelike organic overlayer creates scattering centers in the underlying RN-CNTs by physically distancing the CNTs at their intersections. The results presented here could lead to the development of robust sensors for nonpolar VOCs of cancer breath, which have hitherto been difficult to trace.

Silicon Nanowires Terminated with Methyl Functionalities Exhibit Stronger Si-C bonds than Equivalent 2D Surfaces

Published: March 2009

Authors: Bashouti, M. Y.; Paska, Y.; Puniredd, S. R.; Stelzner, T.; Christiansen, S.; Haick, H.

Years: 2009

Published in: Phys. Chem. Chem. Phys., 11, 3845–3848

Silicon nanowires (Si NWs) terminated with methyl functionalities exhibit higher oxidation resistance under ambient conditions than equivalent 2D Si(100) and 2D Si(111) surfaces having similar or 10–20% higher initial coverage. The kinetics of methyl adsorption as well as complementary surface analysis by XPS and ToF SIMS attribute this difference to the formation of stronger Si–C bonds on Si NWs, as compared to 2D Si surfaces. This finding offers the possibility of functionalising Si NWs with minimum effect on the conductance of the near-gap channels leading towards more efficient Si NW electronic devices.

Chemically Sensitive Resistors Based on Monolayer-Capped Cubic Nanoparticles: Towards Configurable Nanoporous Sensors

Published: March 2009

Authors: Dovgolevsky, E.; Tisch, U.; Haick, H.

Years: 2009

Published in: Small, 5 (10), 1158-1161

Cube roots: Chemiresistors based on cubic monolayer-capped nanoparticles (MCNPs) produce a higher electrical response upon exposure to volatile organic compounds than those based on spherical MCNPs. These observations are explained in terms of the higher swellability of cubic MCNPs compared to spherical MCNPs

Controlling Surface Energetics of Silicon by Intermolecular Interactions between Parallel Self-Assembled Molecular Dipoles

Published: January 2009

Authors: Paska, Y.; Haick, H.

Years: 2009

Published in: J. Phys. Chem. C., 113 (5), 1993-1997

We show that the electrical properties of Si surfaces can be controlled systematically by the extent of intermolecular interactions between molecular dipoles that self-assemble in parallel on the Si surfaces. We draw this conclusion on the basis of experiments with self-assembled hexyltrichlorosilane molecules on SiOx/Si surfaces, with different degrees of Si−O−Si intermolecular bonds. Our results indicate that systematic control of intermolecular interactions of organic molecules on a semiconductor surface provides an important additional molecular handle, in addition to varying the individual molecule’s dipole, for controlling the surface energetics of semiconductor surfaces and, by extension, of semiconductor- and metal-containing interfaces, thus significantly enhancing the molecular control of electronic surfaces and interfaces.

Direct Observation of the Transition Point between Quasi-Spherical and Cubic Nanoparticles in Two-Step Seed-Mediated Growth Method

Published: October 2008

Authors: Dovgolevsky, E.; Haick, H.

Years: 2008

Published in: Small, 4 (11), 2059-2066

An aqueous seed-mediated growth method is adapted to explore the shape transformation of quasi-spherical Au seeds to nanocubes in a direct and continuous manner. Quenching the growth process at varied reaction-duration times and exploring the intermediate products by high-resolution transmission electron microscopy and UV/vis spectroscopy shows an abrupt cuboctahedral-to-nanocube transition at 25-27 nm without any change in the nanoparticle size. The size of the obtained nanocubes remains constant (25-27 nm) until most (>90%) of the cuboctahedral nanoparticles are transformed to nanocubes. At this point, the (25-27 nm) nanocubes initiate further continuous and homogeneous growth until they reach 50-nm Au cubes. These observations are ascribed to a scenario in which the kinetically controlled growth mode of the nanoparticle is significantly affected by the surface self-diffusion of metal adatoms, especially when the adatom’s self-diffusion distance is comparable with the nanoparticle’s size.

Detecting Simulated Patterns of Lung Cancer Biomarkers by Random Network of Single-Walled Carbon Nanotubes Coated with Nonpolymeric Organic Materials, Nano Lett.

Published: October 2008

Authors: Peng, G.; Trock, E.; Haick, H.

Years: 2008

Published in: Nano Lett., 8 (11), 3631–3635

An array of chemiresistive random network of single-walled carbon nanotubes coated with nonpolymeric organic materials shows a high potential for diagnosis of lung cancer via breath samples. The sensors array shows excellent discrimination between the volatile organic compounds (VOCs) found in the breath of patients with lung cancer, relative to healthy controls, especially if the sensors array is preceded with either water extractor and/or preconcentrator of VOCs. The pattern compositions of the healthy and cancerous states were determined by gas-chromatography linked with mass-spectroscopy (GC-MS) analysis of real exhaled breath.

Highly Stable Organic Monolayers for Reacting Si with Further Functionalities: The Effect of C-C Bond nearby the Si Surface

Published: September 2008

Authors: Puniredd, S. R.; Assad, O.; Haick, H.

Years: 2008

Published in: J. Am. Chem. Soc., 130 (41), 13727-13734

Crystalline Si(111) surfaces have been alkylated in a two-step chlorination/alkylation process using various organic molecules having similar backbones but differing in their C-C bond closest to the silicon surface (i.e., C-C vs C=C vs C[triple bond]C bonds). X-ray photoelectron spectroscopic (XPS) data show that functionalization of silicon surfaces with propenyl magnesium bromide (CH3-CH=CH-MgBr) organic molecules gives nearly full coverage of the silicon atop sites, as on methyl- and propynyl-terminated silicon surfaces. Propenyl-terminated silicon surface shows less surface oxidation and is more robust against solvent attacks when compared to methyl- and propynyl-terminated silicon surfaces. We also show a secondary functionalization process of propenyl-terminated silicon surface with 4′-[3-Trifluoromethyl-3H-diazirin-3-yl]-benzoic acid N-hydroxysuccinimide ester [TDBA-OSu] cross-linker. The Si-CH=CH-CH3 surfaces thus offer a means of attaching a variety of chemical moieties to a silicon surface through a short linking group, enabling applications in molecular electronics, energy conversion, catalysis, and sensing.

Coverage Effect of Self-Assembled Polar Molecules on the Surface Energetics of Silicon

Published: July 2008

Authors: Gozlan, N.; Haick, H.

Years: 2008

Published in: J. Phys. Chem. C., 112 (33), 12599-12601

We show here that optimal control over the work function of Si can be achieved even with half coverage of molecular dipoles, especially when the pinholes present on the surface are smaller than the depletion region of the semiconductor. Higher coverage than an optimal value contributes minor (or, no) further changes in the work function of the same semiconductor. The results imply that the requirements on the molecules used to control the electrical properties of Si are significantly and nearly completely relaxed. Therefore, the ability of the molecules to form pinhole-free coverage will not be important after a specific coverage.

Tailoring the Work Function of Gold Surface by Controlling Coverage and Disorder of Polar Molecular Monolayers

Published: July 2008

Authors: Gozlan, N.; Tisch, U.; Haick, H.

Years: 2008

Published in: J. Phys. Chem. C., 112 (33), 12988-12992

We show here that the work function of Au can be controlled not only by the magnitude and direction of adsorbed polar molecules but also by the molecular coverage and (dis)order within the molecular patterns. Molecular monolayers composed of two types of molecules with opposite dipoles were deposited on Au films containing the changes of the work function due to variation of molecular coverage and disorder were monitored. The results indicate that the requirements on molecular layers covering Au surfaces are significantly relaxed and that partial, disordered monolayers can be used to tailor the work function of metal surfaces.

Highly Stable Organic Modification of Si (111) Surfaces: Towards Reacting Si with Further Functionalities while Preserving the Desirable Chemical Properties of Full Si-C atop Site Terminations

Published: July 2008

Authors: Puniredd, S. R.; Assad, O.; Haick, H.

Years: 2008

Published in: J. Am. Chem. Soc., 130 (29), 9184-9185

Si(111) surfaces modified by covalent Si-CH=CH-CH3 functionality, with no intervening oxide, show coverage of all atop Si sites and superior chemical stability in ambient conditions and water, as compared with molecules that form nearly full coverage (e.g., Si-C C-CH3 and Si-CH3 surfaces).

Making Contact: Connecting Molecules Electrically to the Macroscopic World

Published: June 2008

Authors: Haick, H.; Cahen, D.

Years: 2008

Published in: Prog. Surf. Sci., 83 (4), 217-261

Introducing organic molecules in electronics, in general, and as active electronic transport components, in particular, is to no small degree limited by the ability to connect them electrically to the outside world. Making useful electrical contacts to them requires achieving this either without altering the molecules, or if they are affected, then in a controlled fashion. This is not a trivial task because most known methods to make such contacts are likely to damage the molecules. In this progress report we review many of the various ways that have been devised to make electrical contacts to molecules with minimal or no damage. These approaches include depositing the electronic conducting contact material directly on the molecules, relying on physical interactions, requiring chemical bond formation between molecule and electrode materials, “ready-made” contacts (i.e., contact structures that are prepared in advance), and contacts that are prepared insitu. Advantages and disadvantages of each approach, as well as the possibilities that they can be used practically, are discussed in terms of molecular reactivity, surface and interfacial science.

Contacting Organic Molecules by means of Soft Methods: Towards Molecule-Based Electronic Devices

Published: March 2008

Authors: Haick, H.; Cahen, D.

Years: 2008

Published in: Acc. Chem. Res., 41 (3), 359-366

Can we put organic molecules to use as electronic components? The answer to this question is to no small degree limited by the ability to contact them electrically without damaging the molecules. In this Account, we present some of the methods for contacting molecules that do not or minimally damage them and that allow formation of electronic junctions that can become compatible with electronics from the submicrometer to the macroscale. In “Linnaean” fashion, we have grouped contacting methods according to the following main criteria: (a) is a chemical bond is required between contact and molecule, and (b) is the contact “ready-made”, that is, preformed, or prepared in situ? Contacting methods that, so far, seem to require a chemical bond include spin-coating a conductive polymer and transfer printing. In the latter, a metallic pattern on an elastomeric polymer is mechanically transferred to molecules with an exposed terminal group that can react chemically with the metal. These methods allow one to define structures from several tens of nanometers size upwards and to fabricate devices on flexible substrates, which is very difficult by conventional techniques. However, the requirement for bifunctionality severely restricts the type of molecules that can be used and can complicate their self-assembly into monolayers. Methods that rely on prior formation of the contact pad are represented by two approaches: (a) use of a liquid metal as electrode (e.g., Hg, Ga, various alloys), where molecules can be adsorbed on the liquid metal and the molecularly modified drop is brought into contact with the second electrode, the molecules can be adsorbed on the second electrode and then the liquid metal brought into contact with them, or bilayers are used, with a layer on both the metal and the second electrode and (b) use of preformed metal pads from a solid substrate and subsequent pad deposition on the molecules with the help of a liquid. These methods allow formation of contacts easily and rapidly and allow many types of monolayers and metals to be analyzed. However, in their present forms such approaches are not technologically practical. Direct in situ vacuum evaporation of metals has been used successfully only with bifunctional molecules because it is too invasive and damaging, in general. A more general approach is indirect vacuum evaporation, where the metal atoms and clusters, emitted from the source, reach the sample surface in an indirect line of sight, while cooled by multiple collisions with an inert gas. This method has clear technological possibilities, but more research is needed to increase deposition efficiency and find ways to characterize the molecules at the interface and to prevent metal penetration between molecules or through pinholes, also if molecules lack reactive termination groups. This Account stresses the advantages, weak points, and possible routes for the development of contacting methods. This way it shows that there is at present no one ideal soft contacting method, whether it is because of limitations and problems inherent in each of the methods or because of insufficient understanding of the interfacial chemistry and physics. Hopefully, this Account will present the latter issue as a research challenge to its readers.

Oxidation of Polycrystalline Copper Thin Films at Ambient Conditions

Published: January 2008

Authors: Platzmann, I.; Brener, R.; Haick, H.; Tannebaum, R.

Years: 2008

Published in: J. Phys. Chem. C., 112 (4), 1101-1108

Qualitative and quantitative studies of the oxidation of polycrystalline copper (Cu) thin films upon exposure to ambient air conditions for long periods (on the order of several months) are reported in this work. Thin films of Cu, prepared by thermal evaporation, were analyzed by means of X-ray photoelectron spectroscopy (XPS) to gain an understanding on the growth mechanism of the surface oxide layer. Analysis of high-resolution Cu LMM, Cu2p3/2, and O1s spectra was used to follow the time dependence of individual oxide overlayer thicknesses as well as the overall oxide composite thickness. Transmission electron microscopy (TEM) and spectroscopic ellipsometry (SE) were used to confirm the results obtained from XPS measurements. Three main stages of copper oxide growth were observed:  (a) the formation of a Cu2O layer, most likely due to Cu metal ionic transport toward the oxide−oxygen interface, (b) the formation of a Cu(OH)2 metastable overlayer, due to the interactions of Cu ions with hydroxyl groups present at the surface, and (c) the transformation of the Cu(OH)2 metastable phase to a more stable CuO layer. These three stages were found to occur simultaneously and to be mutually dependent on each other. The findings of this study may provide guidance in choosing the optimal conditions to fabricate and store copper-based ultra-large-scale integrated (ULSI) circuits.

Electrostatic Properties of Ideal and Non-Idea Polar Organic Monolayers: Implications for Electronic Devices

Published: November 2007

Authors: Natan, A.; Kronik, L.; Haick, H.; Tung, R. T.

Years: 2007

Published in: Adv. Mater., 19, 4103-4117

Molecules in (or as) electronic devices are attractive because the variety and flexibility inherent in organic chemistry can be harnessed towards a systematic design of electrical properties. Specifically, monolayers of polar molecules introduce a net dipole, which controls surface and interface barriers and enables chemical sensing via dipole modification. Due to the long range of electrostatic phenomena, polar monolayer properties are determined not only by the type of molecules and/or bonding configuration to the substrate, but also by size, (dis-)order, and adsorption patterns within the monolayer. Thus, a comprehensive understanding of polar monolayer characteristics and their influence on electronic devices requires an approach that transcends typical chemical designs, i.e., one that incorporates long-range effects, in addition to short-range effects due to local chemistry. We review and explain the main uses of polar organic monolayers in shaping electronic device properties, with an emphasis on long-range cooperative effects and on the differences between electrical properties of uniform and non-uniform monolayers.

Chemical Sensors Based Molecularly Modified Metallic Nanoparticles

Published: November 2007

Authors: Haick, H.

Years: 2007

Published in: J. Phys. D, 40, 7173-7186

 This paper presents a concise, although admittedly non-exhaustive, didactic review of some of the main concepts and approaches related to the use of molecularly modified metal nanoparticles in or as chemical sensors. This paper attempts to pull together different views and terminologies used in sensors based on molecularly modified metal nanoparticles, including those established upon electrochemical, optical, surface Plasmon resonance, piezoelectric and electrical transduction approaches. Finally, this paper discusses briefly the main advantages and disadvantages of each of the presented class of sensors.

Controlling Au/n-GaAs Junctions by Partial Molecular Monolayers

Published: November 2006

Authors: Haick, H.; Pelz, J. P.; Ligonzo, T.; Ambrico, M.; Cahen, D.; Cai, W.; Marginean, C.; Tivarus, C.; Tung, R. T.

Years: 2006

Published in: Phys. Status Solidi A, 203 (14), 3438-3451

A dipole-layer approach is adapted to describe the electrostatic potential and electronic transport through metal/semiconductor junctions with a discontinuous monolayer of polar molecules at the metal/semiconductor interface. The effective barrier height of those junctions, which have small pinholes, embedded in a molecular layer, which introduces a negative {positive} dipole (i.e., a dipole whose negative {positive} pole is the one that is closest to the semiconductor surface) on an n-type {p-type} semiconductor, is often “tunable” by the magnitude and density of the dipoles. If the lateral dimensions of a molecule-free pinhole at the interface exceed the semiconductor depletion width, carrier transport is not influenced by the molecular layer and the “effective” barrier height is the nominal metal/semiconductor barrier height. If the molecular layer introduces a positive {negative} dipole on an n-type {p-type} semiconductor, enhanced field emission at edges of small pinholes might lead to a leakage- and/or an edge-current component resulting in an effective barrier height lower than the nominal one. We support these conclusions by direct measurements of the nm-scale electronic behaviour of a Au/n-GaAs diode with a discontinuous monolayer of dicarboxylic acids at the interface, using Ballistic Electron Emission Microscopy

Probing Electrical Properties of Molecule-Controlled, and Plasma Nitrided GaAs Surface: Different Approaches for Modifying Electrical Characteristics of Metal/GaAs Diodes

Published: August 2006

Authors: Ambrico, M.; Losurdo, M.; Capezzuto, P.; Bruno, G.; Ligonzo, T.; Haick, H.

Years: 2006

Published in: Appl. Surf. Sci., 252 (21), 7636-7641

This work shows how partial monolayer of organic molecules or radio-frequency remote plasma surface treatment affects the electrical transport across Au/n-GaAs junctions. In the first case, a series of molecules with systematically varying dipole moment were adsorbed on n-GaAs surfaces, whereas in the second case GaN ultra-thin layers with different thickness were formed by N2–H2 GaAs plasma nitridation, prior to contact deposition. The characteristics of electrical charge transport across the resulting interfaces were studied by current–voltage (I–V), internal photoemission (IPE), and capacitance–voltage (C–V) techniques. In this way, we find that the simplest description for the experimentally observed data is in terms of two different barrier heights, rather than one barrier height, at the interface. The first could be identified with areas free of modified GaAs, and the second with areas controlled by electrostatic effects of adjacent dipolar domains, which affects also semiconductor regions under the film’s pinholes.

Electrical Characteristics and Chemical Stability of Non-Oxidized, Methyl-Terminated Silicon Nanowires

Published: June 2006

Authors: Haick, H.; Hurley, P. T.; Hochbaum, A. I.; Yang, P.; Lewis, N. S.

Years: 2006

Published in: J. Am. Chem. Soc., 128 (28), 8990-8991

Silicon nanowires (Si NWs) modified by covalent Si−CH3 functionality, with no intervening oxide, show atmospheric stability, high conductance values, low surface defect levels, and allow for the formation of air-stable Si NW Field-Effect Transistors (FETs) having on−off ratios in excess of 105 over a relatively small gate voltage swing (±2 V).

Controlling Semiconductor/Metal Junction Barriers by Incomplete, Nonideal Molecular Monolayers

Published: May 2006

Authors: Haick, H.; Ambrico, M.; Ligonzo, T.; Tung, R. T.; Cahen, D.

Years: 2006

Published in: J. Am. Chem. Soc., 128 (21), 6854-6869

We study how partial monolayers of molecular dipoles at semiconductor/metal interfaces can affect electrical transport across these interfaces, using a series of molecules with systematically varying dipole moment, adsorbed on n-GaAs, prior to Au or Pd metal contact deposition, by indirect evaporation or as “ready-made” pads. From analyses of the molecularly modified surfaces, we find that molecular coverage is poorer on low- than on high-doped n-GaAs. Electrical charge transport across the resulting interfaces was studied by current-voltage-temperature, internal photoemission, and capacitance-voltage measurements. The data were analyzed and compared with numerical simulations of interfaces that present inhomogeneous barriers for electron transport across them. For high-doped GaAs, we confirm that only the former, molecular dipole-dependent barrier is found. Although no clear molecular effects appear to exist with low-doped n-GaAs, those data are well explained by two coexisting barriers for electron transport, one with clear systematic dependence on molecular dipole (molecule-controlled regions) and a constant one (molecule-free regions, pinholes). This explains why directly observable molecular control over the barrier height is found with high-doped GaAs: there, the monolayer pinholes are small enough for their electronic effect not to be felt (they are “pinched off”). We conclude that molecules can control and tailor electronic devices need not form high-quality monolayers, bind chemically to both electrodes, or form multilayers to achieve complete surface coverage. Furthermore, the problem of stability during electron transport is significantly alleviated with molecular control via partial molecule coverage, as most current flows now between, rather than via, the molecules.

Effect of Molecular Binding to Semiconductor on a Metal/ Molecule/Semiconductor Junction Behavior

Published: May 2005

Authors: Haick, H.; Ghabboun, J.; Niitsoo, O.; Cohen, H.; Cahen, D.; Vilan, A.; Hwang, J.; Wan, A.; Amy, F.; Kahn, A.

Years: 2005

Published in: J. Phys. Chem. B., 109, 9622-9630

Diodes made by (indirectly) evaporating Au on a monolayer of molecules that are adsorbed chemically onto GaAs, via either disulfide or dicarboxylate groups, show roughly linear but opposite dependence of their effective barrier height on the dipole moment of the molecules. We explain this by Au-molecule (electrical) interactions not only with the exposed end groups of the molecule but also with its binding groups. We arrive at this conclusion by characterizing the interface by in situ UPS-XPS, ex situ XPS, TOF-SIMS, and Kelvin probe measurements, by scanning microscopy of the surfaces, and by current-voltage measurements of the devices. While there is a very limited interaction of Au with the dicarboxylic binding groups, there is a much stronger interaction with the disulfide groups. We suggest that these very different interactions lead to different (growth) morphologies of the evaporated gold layer, resulting in opposite effects of the molecular dipole on the junction barrier height.

Pd versus Au as Evaporated Metal Contacts to Molecules

Published: January 2005

Authors: Haick, H.; Ghabboun, J.; Cahen, D.

Years: 2005

Published in: Appl. Phys. Lett., 86 (4), 042113/1-042113/3

Indirect e-beam evaporation of metal on a cooled substrate that allows making reproducible and gentle electrical contact to molecular films of organic molecules yields strikingly different results with Pd and Au. This is attributed to different growth modes of the metals, which lead to different molecule/metal interactions and to Au penetration in between the molecules. These differences can radically change the effect of the molecules on the resulting junctions.

Discontinuous Molecular Films Can Control Metal/Semiconductor Junctions

Published: December 2004

Authors: Haick, H.; Ambrico, M.; Ligonzo, T.; Cahen, D.

Years: 2004

Published in: Adv. Mater., 16 (23-24), 2145-2151

Molecular control over charge transport across a metal/semiconductor interface persists even if there is only a partial monolayer of polar molecules at the interface. This is because the long-range electrostatic effect of the dipole layer also affects the semiconductor regions under the film’s pinholes. Thus, all types of polar molecules that show average order at the interface can be used.

Contacting Organic Molecules by Metal Evaporation

Published: August 2004

Authors: Haick, H.; Ambrico, M.; Ghabboun, J.; Ligonzo, T.; Cahen, D.

Years: 2004

Published in: Phys. Chem. Chem. Phys., 6, 4538-4541

Reproducible electrical contacts to organic molecules are created non-destructively by indirectelectron beam evaporation of Pd onto molecular films on cooled substrates. In contrast, directlyevaporated contacts damage the molecules seriously. Our conclusions are based on correlating trends in properties of a series of molecules with systematically varying, exposed functional groups, with trends in the electrical behaviour of Pd/molecule/GaAs junctions, where these same molecules are part of the junctions.

Controlled Mass Transport as a Means for Obtaining Selective Photocatalysis

Published: August 2003

Authors: Ghosh, M. S.; Haick, H.; Paz, Y.

Years: 2003

Published in: J. Photochem. Photobiol. A: Chem., 160 (1-2), 77-85

The photoinduced degradation of pollutants in water and air using titanium dioxide attracts an increasing attention. Unfortunately, titanium dioxide has very poor selectivity and cannot differentiate between highly hazardous contaminants that are often non-biodegradable and contaminants of low toxicity that are often very easy to handle biologically. A new approach for enhancing the photocatalytic degradation of specific contaminants in air or water is presented herein. The method is based upon selective physisorption of the contaminants on molecular recognition sites located in the vicinity of titanium dioxide micro-domains, followed by surface-diffusion of the contaminants to the photocatalytic sites. The feasibility of this approach is demonstrated using β-cyclodextrin as the host and 2-methyl-1,4-naphthoquinone and the dye-stuff Chicago Blue as guests. A degradation rate increase of 200 and 70% relative to samples that did not contain the molecular recognition sites was found for the former contaminant and for the latter contaminant, respectively. This was achieved without any significant damage to the organic molecular recognition sites, thus encouraging attempts to materialize this approach on a practical level.

“Dark” Photocatalysis: The Degradation of Organic Molecules Anchored to Dark Microdomains of Titanium Dioxide

Published: June 2003

Authors: Haick, H.; Paz, Y.

Years: 2003

Published in: ChemPhysChem, 4 (6), 617-620

Join the dark side: Titanium dioxide is widely used as a photocatalyst for the degradation of many contaminants in air, in water and on solid surfaces. By anchoring self-assembled monolayers onto “dark” microdomains of titanium dioxide (see picture) and measuring their photodegradation kinetics, it is shown that molecules located on dark areas at the vicinity of illuminated domains of titanium dioxide might be prone to an oxidizing attack by oxidizing species that out-diffuse from the illuminated areas.

Effect of Metallic Microdomains on the Chemisorption of Octadecyltrichlorosilane onto Titanium Dioxide

Published: March 2003

Authors: Haick, H.; Segatelian, Y.; Paz, Y.

Years: 2003

Published in: Langmuir, 19, 2540-2544

The formation of octadecyltrichlorosilane monolayers on titanium dioxide was studied in structures consisting of microdomains of TiO2 and noble metals such as gold and platinum. On the basis of Fourier transform infrared and Auger electron spectroscopies, it was found that the density of the monolayers on the TiO2 surface was significantly higher in these structures than in plain samples that did not contain the metallic microdomains. This effect, whose range was unexpectedly long (up to 80 microns), was found to depend on the stripes’ width and upon the ratio between the width of the metallic domains and that of the titanium dioxide domains. Applying a positive potential bias to the titanium dioxide during the chemisorption of the monolayer had a similar effect.

Long Range Effect of Noble Metals on the Photocatalytic Properties of Titanium Dioxide

Published: February 2003

Authors: Haick, H.; Paz, Y.

Years: 2003

Published in: J. Phys. Chem. B., 107 (10), 2319–2326

Well-defined structures comprised of alternating microstripes of noble metals (Au, Pt) and TiO2, covered with self-assembled monolayers (SAMs), are used to study long-range metallic effects on the photodegradation of the monolayers. It was found that under certain conditions, the presence of a metal in the vicinity of the photocatalyst does not increase its photoefficiency but, in fact, might reduce it significantly, in comparison with a bare photocatalyst. This effect depends on the size of the domains, as well as on humidity and the type of metal. It is suggested that although metal-induced charge separation is beneficial in promoting the production of hydroxyl radicals needed for the first steps of the degradation process, charge separation might also become detrimental under conditions that decrease the back-diffusion of reduced species, such as hydroperoxy radicals, needed at later stages of the degradation process.

Photocatalytic Degradation of Self-Assembled Monolayers Anchored at the Vicinity of Titanium Dioxide

Published: January 2002

Authors: Zemel, E.; Haick, H.; Paz, Y.

Years: 2002

Published in: J. Adv. Oxid. Technol., 5 (1), 27-32

In order to study the photodegradation of molecules located at the vicinity of a titanium dioxide photocatalyst, a well-defined structure comprised of alternating micro-stripes of TiO2 and silicon was prepared on silicon wafers. Onto this structure, a cross-linked self-assembled monolayer (SAM) of Octadecyltrichlorosilane (OTS) was chemisorbed. The kinetics of the photodegradation of the anchored SAM on the hybrid structure was then measured in-situ by FTIR under controlled humidity (8% RH). It was found that the photogenerated oxidizing species, formed on the titanium dioxide well-defined micro-domains, are capable of inducing, within minutes, the mineralization of the aliphatic chains anchored to the inert silicon domains, even when these chains were located as far as 20 microns away from the titanium dioxide micro-zones. Based on complementary experiments with alkanethiols on gold in a Au/TiO2 hybrid system, it was shown that the observed remote mineralization was not based on a diffusion – through – air mechanism. The observation that the oxidizing species can induce mineralization far from the locus of their formation may have large effect on the design and modeling of porous photocatalysts having “dark” pores.

Selective Photocatalysis by Means of Molecular Recognition

Published: January 2001

Authors: Ghosh, M. S.; Haick, H.; Schvartzman, M.; Paz, Y.

Years: 2001

Published in: J. Am. Chem. Soc., 123 (43), 10776-10777

Remote Photocatalytic Activity as Probed by Measuring the Degradation of Self-Assembled Monolayers Anchored Near Micro-Domains of Titanium Dioxide

Published: January 2001

Authors: Haick, H.; Paz, Y.

Years: 2001

Published in: J. Phys. Chem. B., 105, 3045-3051

A cross-linked self-assembled monolayer (SAM) of octadecyltrichlorosilane (OTS) was chemisorbed on well-defined structures, comprised of alternating microstripes of TiO2 and silicon. The kinetics of the photodegradation of the anchored SAM on the hybrid structure was then measured in situ by FTIR under controlled humidity and surface temperature. It was found that mineralization of the aliphatic chains anchored to the inert silicon domains can occur, even when these chains are located as far as 20 μm away from the photocatalytic titanium dioxide microdomains. An apparent first-order kinetics was found for each of the two domain types. Apparent activation energies were calculated on the basis of the temperature-dependent measurements. The observation that the oxidizing species can induce mineralization far from the locus of their formation may have large effect on the design and modeling of porous photocatalysts having “dark” pores and on the developing of hybrid photocatalysts.

Sniffing Chronic Renal Failure in Rat Models via an Array of Random Network of Single-Walled Carbon Nanotubes

Authors: Haick, H.; Hakim, M.; Patrascua, M.; Levenberg, C.; Shehada, N.; Nakhoul, F.; Abassi, Z.

Years: 2009

Published in: ACS Nano., 3 (5), 1258-1266

In this study, we use an experimental model of bilateral nephrectomy in rats to identify an advanced, yet simple nanoscale-based approach to discriminate between exhaled breath of healthy states and of chronic renal failure (CRF) states. Gas chromatography/mass spectroscopy (GC-MS) in conjugation with solid-phase microextraction (SPME) of healthy and CRF breath, collected directly from the trachea of the rats, identified 15 common volatile organic compounds (VOCs) in all samples of healthy and CRF states and 27 VOCs that appear in CRF but not in healthy states. Online breath analysis via an array of chemiresistive random network of single-walled carbon nanotubes (SWCNTs) coated with organic materials showed excellent discrimination between the various breath states. Stepwise discriminate analysis showed that enhanced discrimination capacity could be achieved by decreasing the humidity prior to their analysis with the sensors’ array. Furthermore, the analysis showed the adequacy of using representative simulated VOCs to imitate the breath of healthy and CRF states and, therefore, to train the sensors’ array the pertinent breath signatures. The excellent discrimination between the various breath states obtained in this study provides expectations for future capabilities for diagnosis, detection, and screening various stages of kidney disease, especially in the early stages of the disease, where it is possible to control blood pressure and protein intake to slow the progression.

Controlling Properties of Field Effect Transistors by Intermolecular Cross-linking of Molecular Dipoles

Authors: Paska, Y.; Haick, H.

Years: 2009

Published in: Appl. Phys. Lett., 95, 233103/1-233103/3

In this study, we show that systematic molecular control over a silicon-on-insulator field effect transistor (SOI-FET) device can be achieved by controlling the Si–O–Si intermolecular interactions between adjacent trichlorosilane molecules. This is attributed to the fact that Si–O–Si intermolecular bonds between the parallel molecular dipoles change the overall charge distribution within the organic layer, and, consequently, alter the channel surface potential. Changes in the potential within the formed monolayer close to the channel alter the source-drain current and, consequently, the transistor threshold (turn on) voltage.

The Scent Fingerprint of Hepatocarcinoma: In-Vitro Metastasis Prediction with Volatile Organic Compounds (VOCs)

Authors: Amal, H.; Ding, L.; Liu, B. B.; Tisch, U.; Xu, Z. Q.; Shi, D. Y.; Zhao, Y.; Chen, J.; Sun, R.; Liu, H.; Ye, S. L.; Tang, Z. Y.; Haick, H.

Years: 2012

Published in: Int. J. Nanomedicine, 7, 4135–4146

Hepatocellular carcinoma (HCC) is a common and aggressive form of cancer. Due to a high rate of postoperative recurrence, the prognosis for HCC is poor. Subclinical metastasis is the major cause of tumor recurrence and patient mortality. Currently, there is no reliable prognostic method of invasion.
To investigate the feasibility of fingerprints of volatile organic compounds (VOCs) for the in-vitro prediction of metastasis.
Headspace gases were collected from 36 cell cultures (HCC with high and low metastatic potential and normal cells) and analyzed using nanomaterial-based sensors. Predictive models were built by employing discriminant factor analysis pattern recognition, and the classification success was determined using leave-one-out cross-validation. The chemical composition of each headspace sample was studied using gas chromatography coupled with mass spectrometry (GC-MS).
Excellent discrimination was achieved using the nanomaterial-based sensors between (i) all HCC and normal controls; (ii) low metastatic HCC and normal controls; (iii) high metastatic HCC and normal controls; and (iv) high and low HCC. Several HCC-related VOCs that could be associated with biochemical cellular processes were identified through GC-MS analysis.
The presented results constitute a proof-of-concept for the in-vitro prediction of the metastatic potential of HCC from VOC fingerprints using nanotechnology. Further studies on a larger number of more diverse cell cultures are needed to evaluate the robustness of the VOC patterns. These findings could benefit the development of a fast and potentially inexpensive laboratory test for subclinical HCC metastasis

Ultrasensitive Silicon Nanowire for Real-World Gas Sensing: Noninvasive Diagnosis of Cancer from Breath Volatolome

Authors: Shehada, N.; Brönstrup, G.; Funka, K.; Christiansen, S.; Leja, M.; Haick, H.

Years: 2015

Published in: Nano Lett., 15 (2), 1288–1295

We report on an ultrasensitive, molecularly modified silicon nanowire field effect transistor that brings together the lock-and-key and cross-reactive sensing worlds for the diagnosis of (gastric) cancer from exhaled volatolome. The sensor is able to selectively detect volatile organic compounds (VOCs) that are linked with gastric cancer conditions in exhaled breath and to discriminate them from environmental VOCs that exist in exhaled breath samples but do not relate to the gastric cancer per se. Using breath samples collected from actual patients with gastric cancer and from volunteers who do not have cancer, blind analysis validated the ability of the reported sensor to discriminate between gastric cancer and control conditions with >85% accuracy, irrespective of important confounding factors such as tobacco consumption and gender. The reported sensing approach paves the way to use the power of silicon nanowires for simple, inexpensive, portable, and noninvasive diagnosis of cancer and other disease conditions.