LNBD

Interdisciplinary Projects and Clinical Studies

SNIFFPHONE: Smart Phone for Disease Detection from Exhaled Breath

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Screening for early detection of a disease is required to reveal groups of individuals from the general population in whom the likelihood of the disease is increased and who could benefit from further medical evaluation. The ideal screening test is high-accuracy, low-cost, non-invasive, easily repeatable, effortlessly operated by a lay-person and has minimal impact on the person’s daily activities. In the SNIFFPHONE project, we aim to tackle these requirements by integrating heterogeneous micro- and nano-technologies into autonomous smart system that can be attached to a mobile phone and analyze disease markers from exhaled breath. In this approach, an interaction between breath sample and a miniaturized array of highly sensitive nanomaterial-based chemical sensors is recorded, stored and pre-processed by integrated miniature on-chip microfluidics and electronics, and then the relevant electrical signals are transferred wirelessly via the mobile phone’s internet to an external server. Statistical pattern recognition methods are then applied on the received data and a clinical report including the screening results is sent back to the designated receiver (e.g., specialist, family doctor) in case of positive result is revealed. SNIFFPHONE represents a new concept addressing major societal challenges in health and well-being of the general population, while taking into account constituent ethical and security aspects. The SNIFFPHONE end-product will integrate functionalities that are relevant to the health screening applications with decreased size, decreased costs, increased predictive and cognitive functions and full autonomy with energy management as well as with operation/use management.

Schematic illustration of the main components and features of the SNIFFPHONE: exhaled breath, heterogeneous sensors array linked with breath collector and microfluidic cell, and advanced statistical and pattern recognition methods. The expected outcome of the SNIFFPHONE’s project is presented as well.

Schematic illustration of the main components and features of the SNIFFPHONE: exhaled breath, heterogeneous sensors array linked with breath collector and microfluidic cell, and advanced statistical and pattern recognition methods. The expected outcome of the SNIFFPHONE’s project is presented as well. 

LUMASENSE: A Non-Invasive Test for Guiding Follow–up of Patients with CT-Detected Lung Nodules

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This project addresses an urgent clinical need in the field of lung cancer (LC). The rationale behind the project is that CT-based LC screening programs are emerging in many countries worldwide. However, the high false positive rate of these techniques (96% of the 24% positive CT findings are non-cancerous) remains a major challenge. This is due to the fact that non-cancerous CT-detected group has undergone unnecessary invasive procedures that are both costly and associated with significant morbidity and mortality.

This project aims to increase the specificity of the LDCT-based screening program by utilizing an auxiliary noninvasive breath test to distinguish between malignant and non-cancerous CT findings. The lab’s breath test relies on a novel stand-alone device that provides improved speed, sensitivity and portability, as well as simplicity, ease, and low production cost. This project has the potential to immediately become a powerful tool for managing nodule-positive patients. It will both reduce the rate of unnecessary invasive procedures, and prevent treatment delays when cancer exists. This represents a savings of ~$12-16 billion for healthcare systems worldwide.

The stand-alone breath testing system designed, developed, and constructed at Technion during the ERC “DIAG-CANCER” project.

GCE-II: Self-Administered Adhesive Patch for Detection of Tuberculosis - The Bill and Melinda Gates Foundation

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More than two billion people are estimated to be infected with M. tuberculosis (TB), of which 10% progress to active tuberculosis during their lifetimes. About 95% of TB cases occur in developing countries, where individuals live on 1$ per day. This project aims to develop a stand-alone TB test involving an adhesive patch that allows immediate diagnosis of TB from skin samples within two to five minutes, at much lower costs than with current approaches. The novel TB sensing patch is applied on the patient’s chest, either in the clinic or by the patient at home, and will be suitable for children. The possibility of home testing will allow patients to participate actively in the prevention and detection of TB. At-risk populations such as health workers, family members of TB patients, smokers and HIV-carriers will be able to continuously monitor themselves. This two to five minute examination displays a GREEN LIGHT when the user is healthy (i.e., has no TB) or a RED LIGHT when active TB is present.

schematic figure representing Self-Administered Adhesive Patch for Detection of Tuberculosis

The development of rapid, accurate, and affordable sensing patches for diagnosis of ‘active TB pulmonary disease vs. non-TB pulmonary disease and latent TB’ will contribute to a greater survival rate of TB patients, and, also, in arresting transmission of the disease. Successful completion of these short- and long-term goals will provide a TB sensing patch. This patch could be employed at resource-poor central reference laboratories, hospital and clinic laboratories, and/or at the point-of-care, helping increase TB screening, and saving at least 400,000 lives yearly.

Self-Administered Adhesive Patch for Detection of Tuberculosis - The Bill and Melinda Gates Foundation-Figure 1: (a) Schematic illustration of the envisioned adhesive sensing plaster and its main components. (b) Schematic representation of the readout. Photograph illustrating the output of the device in (c) healthy person and in (d) TB volunteers. (e) A demonstration of the flexibility of the sensing device/plaster achieved in GCE Phase I.

 

Estimated TB incidence rates, 2012

 

VOLGACORE: Volatile Biomarkers for Early Detection and Characterization of Gastric and Colorectal Neoplasms

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Gastrointestinal cancers, in particular gastric (GC) and colorectal cancers (CRC) remain important healthcare issues globally. No non-invasive screening marker is available for GC, and currently available screening markers for CRC demand great improvements. Previous research by LNBD researchers  and others suggests that detection of volatile organic components (VOCs) in exhaled breath may be a promising tool for screening for these cancers. Therefore, the objectives of the project are the development and validation of novel, non-invasive, easy to use and low-cost tools for screening, early detection of GC, CRC and the related premalignant lesions. The project brings together the leading centers in nanotechnological breath analysis with clinical, laboratory and epidemiology experts.  Recruitment is done in high-risk regions; involvement of an innovation-oriented SME is planned. VOCs are analyzed by highly sensitive, cross-reactive, nanomaterial-based gas sensors that can identify and separate volatile marker patterns. In addition, particular components are identified with gas chromatography combined with mass spectrometry. A characteristic sensor technique by correlation of the results to GC-MS is developed for the targeted cancer types and the related pre-malignant lesions. Chemiresistors are based on cross-reactive, chemically diverse layers of organically stabilized spherical gold nanoparticles. In addition, a lowcost instrument for VOC testing, based on molecule-terminated nanoparticle films have been developed for use in point-of-care testing settings.

The lab addresses other factors on VOCs.. Researchers give particular attention to gastrointestinal microbiota. They analyze microbiota from biopsies by sequencing a hyper-variable region of the 16S rRNA gene, in combination with sample-specific barcode sequences. The lab thoroughly evaluates  the implications of these findings for population-based cancer screening programs.

Volatile Biomarkers for Early Detection and Characterization of Gastric and Colorectal Neoplasms: Schematic figure representing breath sampling for gastric cancer detection.

BIRAX: Rapid Diagnostic Test for Parkinson's Disease to Determine Underlying Mechanisms and Possible Regenerative Therapies.

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It can take some time for people with Parkinson’s to be diagnosed. One reason for this is that there is no simple test for accurately diagnosing or monitoring Parkinson’s. Earlier-stage diagnosis will result in better patient treatment.

Recently, the LNBD group has developed a breath test that can be used to analyze the molecules linked with Parkinson’s. This breath test can differentiate between people with Parkinson’s and those of a similar age without the condition.

In collaboration with Prof. John Fienberg of the Technion – IIT and Prof. Roger Barker of Cambridge University, the team is working to test this novel method of diagnosing Parkinson’s. LNBD researchers investigate whether the breath test can be used to diagnose and monitor the progression of Parkinson’s over time, by testing it on a larger group of participants. They look for subtle differences between afflicted individuals to gauge if the test is sensitive enough to identify different forms or types the disease.

The lab also analyzes the molecules in breath samples of Parkinson’s patients for new clues of what causes the condition. Researchers hope their findings will contribute to new Parkinson’s treatment.

This research also promises to shed new light on different molecules that play a role in the development of Parkinson’s. This information may well provide scientists with new targets for therapies that could slow or stop the progression of Parkinson’s.

Using a rapid diagnostic test for Parkinson’s disease to determine underlying mechanisms, develop new regenerative therapies and test the efficacy of existing regenerative therapies.

DIAG-CANCER: Diagnosis, Screening and Monitoring of Cancer Diseases via Exhaled Breath Using an Array of Nanosensors

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Cancer is rapidly becoming the greatest health hazard of our days. The most widespread cancers are lung cancer (LC), breast cancer (BC), colorectal cancer (CC), and prostate cancer (PC). The impact of various techniques used for diagnosis, screening and monitoring these cancers is either uncertain and/or inconvenient for patients.

This project aims to create a low-cost, easy-to-use and non-invasive screening method for LC, BC, CC, and PC based on breath testing with a novel nanosensor approach. With this in mind, the lab (a) modifies an array of nanosensors for obtaining highly-sensitive detection levels of breath biomarkers for cancer; and (b) investigates the use of the developed array in a clinical study. Towards this end, researchers collect suitable breath samples from patients and healthy controls in a clinical trial and test the feasibility of the device to detect LC, BC, CC, and PC, also in the presence of other diseases. We then investigate ways to identify the stage of the disease, monitor the response to cancer treatment, and identify cancer subtypes. Further, we use the developed device to monitor cancer patients during and after treatment. The chemical nature of the cancer biomarkers will be identified through spectrometry techniques.

The proposed approach can be used outside specialist settings.   It could considerably lessen the burden on health budgets, both through the low cost of the proposed all-inclusive cancer test, and through earlier and, hence, more cost-effective cancer treatments.

Schematic reviewing the links between the different frameworks of breath marker-prints and the appropriate sensing approach (specific vs cross-reactive approach.

LCAOS: A Nanoscale Artificial Nose to Easily Detect Volatile Biomarkers at Early Stages of Lung Cancer and Related Genetic Mutations

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In LCAOS, the lab aims to enable the earliest possible detection of lung cancer (LC) using volatile biomarkers present in exhaled breath and/or headspace of LC tissues/cells by applying a novel, non-invasive, easy-to-use tool. This tool will be based on an artificial (electronic) nose, which makes use of cross-selective and sensitive sensor arrays trained in their ensemble [R1] to detect LC biomarkers.

In LCAOS LNBD researchers uniquely modify this artificial nose concept by using 3D silicon nanowire- (Si NW) based field effect transistors (FETs) that show increased sensitivity to LC biomarkers. They term this new Nano Artificial NOSE concept ‘NA-NOSE’ throughout the proposal. This ‘NA-NOSE’ will be used to screen and identify high risk groups for LC, and monitor the therapy provided to people with LC to establish point-of-care diagnostics and less invasive treatments. Testing of the novel ‘NA-NOSE’ for early detection of LC, essentially from breath and tissue headspace samples, is conducted by:

(a)Lab-track evaluation – carried out using simulated compositions of clinical samples and, also, real clinical samples, which will be provided by clinical partners.
(b)Clinical-track evaluation of an integrated, professionalized, easy-to-use ‘NA-NOSE’ tool that is carried out at clinical institutes.

The ‘NA-NOSE’ would be suitable for use outside specialist settings and would significantly reduce costs in health budgets. In addition, the ‘NA-NOSE’ could be used for immediate diagnosis of fresh LC tissues in operating rooms, where a dichotomic diagnosis is crucial to guide surgeons. The easy-to-use — no medical specialists required – ‘NA-NOSE’ technology detects cancer based on a change in the blood chemistry and/or metabolic activity. This change is reflected in the chemical composition of the exhaled breath (and cell/tissue headspace) rather than by tumor imaging, thus permitting the earliest cancer detection –. before a tumor of detectable size has formed.  The effectiveness of the ‘NA-NOSE’ in detecting LC volatile biomarkers specifically and selectively will provide a launching pad for identifying other types of cancer including breast, colon, and prostate cancers from simple analysis of clinical samples. . Biomarkers that indicate other diseases, such as heart failure, kidney disease and liver disease, can be also tested with the same easy-to-use ‘NA-NOSE’ approach.

Overview of the processes involved in breathe testing.