The Future of Disease Detection

Na-Nose

Introducing Na-Nose: A Nanoscale Artificial Nose to Detect Specific Medical Conditions

Breathtec licenses NA-NOSE technology to detect indications of Streptococcus; Methicillin resistant (MRSA); Staphylococcus; Enterococcus; Vancomycin resistant (VRE); Pneumococcus; Hemophilus influenza (HiB); Chickenpox; and the Common Cold.


Lead proponent

Prof. Hossam Haick
Technion – Israel Institute of Technology

technion

Video: Technology Overview. (Example: Cancer): NA-NOSE respiratory infection license offers rapid development opportunity.

Overview

Breathtec Biomedical, Inc. has entered into a license agreement with the Technion Research and Development Foundation Ltd., an Israeli private company and wholly-owned subsidiary of the Technion – Israel Institute of Technology (“Technion”), with respect to NA-NOSE, an advanced stage breath analysis technology for indication detection of Streptococcus; Methicillin resistant (MRSA); Staphylococcus; Enterococcus; Vancomycin resistant (VRE); Pneumococcus; Hemophilus influenza (HiB); Chickenpox; and the common cold.

Detection of Respiratory Infections by Breath Analysis – read more

“Our agreement with the Technion grants us the opportunity to collaboratively leverage their extraordinary expertise in the research phase, years of effort, and millions of Euro’s already invested in the NA-NOSE project in order to move forward with a plan for commercialization of a new application in the area of disease detection thru breath. This is a game changing and disruptive technology that offers great promise, and we look forward to bringing the NA-NOSE Technology to North America and to rapidly advance it through clinical trials and regulatory approval.”

— Kal Malhi, President (Breathtec)

Respiratory infections are a leading cause of mortality and morbidity worldwide. Respiratory pathogenic bacteria, such as Streptococcus pneumoniae and Haemophilus influenza, are the main causes for chronic respiratory conditions, such as Chronic Obstructive Pulmonary Disease (COPD). Advanced stages of these conditions lead to poor quality of life, limited flexibility in practicing daily physical activity, and an increased risk of death. Altogether, these disease conditions lead to considerable healthcare costs, both for the patient and for the healthcare system.

In many instances, routine tests do not allow rapid accurate identification of viruses or bacteria. In the absence of clear surrogate clinical markers that could discriminate between various sources of respiratory infections, over-treatments with antibiotic prescriptions are evidenced in a large portion of the treated cases. On top of that, inappropriate over-use of antibiotics is associated with high healthcare costs and contributes to the development of resistant pathogens and side effects or further health complications. Unfortunately, the available tests and methods does not enhance the detection of many respiratory infections, primarily due to technological limitations and their complexities, leading to delays in diagnosis and/or discrimination between various type of the respiratory infection.

Accordingly, there has been an increasing interest in recent years in improved methods for diagnosis of many metabolic and infectious diseases. These new methods are expected to be non-invasive and inexpensive, while allowing: (1) screening of high-risk populations for emerging diseases; (2) early detection and prediction of diseases; and (3) evaluation and monitoring of therapy efficacy. Furthermore, assimilation of these methods into diagnostic routines should reduce the use of less efficient methods, leading to more rapid and convenient diagnosis, with financial savings in healthcare systems.

Technology

  1. A proto-type of novel, cross-sensitive nanowire-based sensors to be integrated in the ‘NA-NOSE’ trained to detect target disease related mixtures of biomarkers;
  2. Novel algorithms to reduce the dimensionality of the ‘NA-NOSE’ information to safely distinguish between healthy and unhealthy individuals, as well as between different sub-types of disease (e.g. different types of cancer);
  3. Novel, company-manufactured, ready-to-use integrated ‘NA-NOSE’ devices, to be tested in clinical studies/environments for large-scale screening and research;
  4. A method based ‘NA-NOSE’ to detect and improve the outcome of therapies;
  5. A method based ‘NA-NOSE’ to guide surgeons during surgery based on tissue analysis; and
  6. A method for identification of new biomarkers that are related to different stages of target diseases.

Professor Hossam Haick at the Technion – Israel Institute of Technology, has developed and tested the NA-NOSE technology for detecting the volatile biomarkers of diseases. The nanotechnology-based breath test was successfully applied in numerous research phase studies for a wide variety of diseases. In many diseases, the NA-NOSE has shown an ability to distinguish between “healthy” and “disease” states as well as between the different stages of the disease, mainly between the early stages and the advanced stages of the disease. Biomarker-based breath testing using the NA-NOSE technology holds future potential as a cost-effective, fast and reliable diagnostic test for early disease and infection detection as well as ongoing monitoring of disease progression. The NA-NOSE technology would be suitable for use outside of specialist settings and could significantly reduce budgetary burdens at many regional and national healthcare organizations.

Specifics of licensed technology:

  1. Novel, cross-sensitive nanowire-based sensors integrated in the ‘NA-NOSE’ device trained to detect target disease related mixtures of specific biomarkers;
  2. Novel algorithms to reduce the dimensionality of the ‘NA-NOSE’ information to safely distinguish between healthy and unhealthy individuals, as well as between different sub-types of disease (e.g. different biomarkers of conditions per licensing agreement);
  3. ‘NA-NOSE’ prototype devices, to be tested in clinical studies/environments for diagnosis and research;
  4. A method for identification of new biomarkers that are related to different stages of target conditions.

Testing

Breathtec’s entry into a licensing agreement will further investigation and advance development of NA-NOSE disease detection capabilities for the detection of the following indications from exhaled breath: Streptococcus; Methicillin resistant (MRSA); Staphylococcus; Enterococcus; Vancomycin resistant (VRE); Pneumococcus; Hemophilus influenza (HiB); Chickenpox; and the common cold. The testing of the novel ‘NA-NOSE’ prototypes will be carried out in three separate trials:

  1. Outpatient clinic strep throat study.
  2. Hospital inpatient MRSA and lower respiratory infection study.
  3. 2nd outpatient clinic viral infection respiratory infection study.

The easy-to-use (no medical specialists required) ‘NA-NOSE’ technology detects specific disease biomarkers based on a change in the blood chemistry and/or metabolic activity (which is reflected in the chemical composition of the exhaled breath and cell/tissue headspace) rather than by other forms of imaging or invasive blood analysis, thus permitting earliest detection and improved treatment outcomes.

Development

The following outlines general plans for development activities required for pre, launch, and post commercialization activities.

  • Outpatient pilot strep study for detection of throat streptococcus infection and normative data.
  • Design/build for device suitable for outpatient point of care use in accordance with regulations for FDA class II/III device.
  • Batch production of devices in compliance with ISO13485 standard for FDA and Medical Device Directive 93/42/EEC.
  • Start pilot inpatient trail for hospital based infections for MRSA, lower respiratory tract infections (HiB, Pneumococcus, staphylococcus enterococcus and zoster). Tandem outpatient pilot viral study for zoster, and common cold.
  • Wider scale Phase 1 strep study trials as required by FDA for premarket approval (assuming no predicate device for 510(k)*) to demonstrate device is safe and effective for intended use of strep throat infection.
  • Regulatory clearance of the strep device in USA then EU for strep throat.
  • Manufacture point of care device for strep throat.
  • Regulatory clearance of the inpatient device in USA then EU for MRSA and lower respiratory infections.
  • Regulatory clearance of the outpatient viral device in USA and EU for zoster and common cold.
  • Manufacture of point of care device for inpatient and viral device.
  • Post-market surveillance strep, inpatient and viral study tracking (likely required).

*NB this device may be labelled by FDA as a class III device if there is no predicate at the time of application and this would require a petition to lower class or ‘de novo’ 510(k)

Effectiveness

The effectiveness of the ‘NA-NOSE’ in detecting volatile biomarkers specifically and selectively provides a launch pad for identifying other indications of the target conditions which may lead to improvements that could include preventative or ameliorative opportunities prior to full disease onset.

Prof.-Hossam-HaickLead Researcher:  Prof. Hossam Haick

  • The F.M.W. Academic Chair
  • Head, Laboratory for Nanomaterial-Based Devices (LNBD)
  • Director, SNIFFPHOHE: Horizon 2020 ICT Program
  • Director, VOLGACORE: EuroNanoMed II Program
  • Director, LCAOS: FP7 Health Program
  • Department of Chemical Engineering and Russell Berrie Nanotechnology Institute
  • Technion – Israel Institute of Technology, Haifa, Israel

Hossam Haick, an expert in the field of nanotechnology and non-invasive disease diagnosis, is a full professor and the F.M.W. Academic Chair in the Department of Chemical Engineering and the Russell Berrie Nanotechnology Institute at the Technion – Israel Institute of Technology. Prof. Haick received his B.Sc. and Ph.D. (direct track) in Chemical Engineering from the Ben-Gurion University (1998) and the Technion (2002) respectively.  After a two-year period at the Weizmann Institute of Science (2002-2004), he moved to the California Institute of Technology – Caltech (2004-2006) for postdoctoral research, and then to the Technion as an assistant professor in 2006.

In 2007, Hossam appeared on the list of 50 leading Israelis and four saluted Israeli scientists. In 2008, Hossam appeared on the MIT Technology Review list of 35 leading young scientists in the world. In 2010, he was named one of the 10 Most Promising Young Israeli Scientists and one of the Young Israelis of the Year. In 2013, he received a listing of the “50 Sharpest Israeli Minds” by the Marker. In 2015 he received a listing as the world’s top-100 influential innovators in the Digital Technology for 2015 by Nominet Trust (London, UK). In 2016, he received the listing of the world’s top-100 influential scientists in the Medical Field for 2016 by the GOOD Magazine (Los Angeles, USA).

Read More

At the Technion, Prof. Haick has made a significant mark through his development of artificially intelligent nanoarray technology to detect diseases non-invasively.  This work has earned him prestigious grants: the Marie Curie Excellence Grant, the ERC and the Bill & Melinda Gates Foundation Award. Among the many consortia Prof. Haick has coordinated are the FP-7 consortium (LCAOS; 2011-2015), a EuroNanoMed II consortium (VOLGACORE; 2014-2017), and the Horizon2020 ICT consortium (SNIFFPHONE; 2015-2019). Additionally, he has received more than 52 prizes and honors, including:  a Knight of the Order of Academic Palms (Chevalier dans l’Ordres des Palmes Académiques)[i], the Horev Chair for Leaders in Science and Technology, the Halevy Award for Innovative Applied Engineering, the LERMIT’s International Chair of Therapeutic Innovation, the Tenne Prize for Nanoscale Sciences, the Innovation and Entrepreneurship Prize in Chemical Engineering, the OXYGEN Prize (Paris, France), the Bergmann Award for Excellent Scientists, the Herschel Rich Innovation Award, and more. In January 2013, the Technion and INSERM (National Institute of Health Research, France) announced signing an academic agreement between the laboratories of Hossam Haick in the Technion and the Respiratory Diseases Department, led by Professor Marc Humbert, after they were awarded the very competitive LIA (International Associate Laboratory) funding.

Besides Prof. Haick’s achievements in research, he has had considerable success as a lecturer, as expressed by the many prizes he has received for excellence in teaching. Prof. Haick is the recipient of the “Yanai Prize for Academic Excellence”, which is given for exceptional contribution in teaching and academic education.  In 2014, Prof. Haick designed and developed the first massive open online course (MOOC) in the Technion, and is the first person worldwide to do this in two languages: English and Arabic. This MOOC focuses on the fields of nanotechnology, and nanosensors stressing their implications for use in diagnosis and treatment of disease, as well as in personalized medicine. So far, the course has drawn more than 76,000 participants, thus disseminating knowledge about biomedical science and nanotechnology to people in both developed and developing countries, without admissions bureaucracy.

Prof. Haick has also supervised a broad range of talented graduate and undergraduate students worldwide. He serves as an associate editor of the Journal of Translational Engineering in Health and Medicine and member of the editorial board of several peer-reviewed journals, such as the Journal of Nanoscience Letters, Hybrid Materials, Dataset Papers in Physical Chemistry and Frontiers in Respiratory Pharmacology. Prof. Haick serves as an advisory consultant to the Chemical Abstracts Service (CAS) – the world’s authority for chemical information, and is a senior scientific advisory member of several national and international companies and institutes, and a scientific evaluator in the European Commission.

Prof. Haick has published more than 170 publications in top-level journals in the field of nanotechnology and advanced/applied materials/chemistry, and more than five book chapters. Additionally, Prof. Haick holds more than 28 patents for his inventions.

Prof. Haick’s research interests include nano-array devices for screening, diagnosis and monitoring of disease, nanomaterial-based chemical (flexible) sensors, electronic skin, breath analysis, volatile biomarkers, and molecule-based electronic devices.

[1] Established in 1808 by Napoleon Bonaparte, the prestigious Academic Palms is the oldest extant civilian accolade awarded by the French Government. The order was created to honor top, eminent academics and educators. The knights of this order wear a medallion on a ribbon on their left breast.