Fast and sensitive breath analysis for medical diagnostics – Breath-Diag

The underlying technology of Optical Feedback-Cavity Enhanced Absorption Spectroscopy (OF-CEAS) was invented and patented about ten years ago by LIPhy. It is now licensed to AP2E, who has successfully commercialized OF-CEAS for detection of a number of different molecules in the domains of industrial and air quality monitoring. OF-CEAS enables non-invasive, real-time and fast diagnostics of exhaled air by ultra-sensitive, highly selective, and auto-calibrated trace gas detection. Our objective is to develop exhaled breath analyzers for use by medical staff. In a previous collaborative project, LIPhy and TIMC-IMAG have already identified carbon monoxide (CO) in exhaled air as a biomarker of ischemia-reperfusion injury during ex-vivo perfusion of pig lungs: Endogenous lung production of CO by isolated pig lungs, correlated with ischemia-reperfusion injury, was demonstrated by real-time analysis on the ventilator gas-handling line using an OF-CEAS prototype developed at LIPhy.

After 18 months :
- A CO medical analyzer is developed and ready to be used in medical environment.
- We demonstrate that the OF-CEAS technique can be used with Interband Cascade Lasers (ICL), lasers that recently became commercially available at room temperature in the Mid Infrared region [Richard2016]

Project under development.

L. Richard, I. Ventrillard, G. Chau, K. Jaulin, E. Kerstel, D. Romanini, «Optical-feedback cavity-enhanced absorption spectroscopy with an interband cascade laser : application to SO2 trace analysis«, Appl. Phys. B Lasers Opt., 122:247 (2016)

This innovative project in translational research aims at the development, in the context of lung transplantation, of a novel medical instrumentation for exhaled breath analyses, using state-of-the-art laser spectroscopic techniques. Exploratory measurements to validate the instrument will be done in parallel with clinical research focusing on ex vivo lung graft rehabilitation. A major strength of this ambitious project is that it brings together partners with the required and complementary key skills: physicists of the Laboratory of Interdisciplinary Physics (LIPhy), physicians of the Complex Systems and Health Engineering unit of the Grenoble laboratory of Applied Informatics and Mathematics (TIMC-IMAG) and the Clinical Investigation Center - Innovative Technologies of the Grenoble University Hospital (CIC-IT/CHU), and a private company (AP2E). The underlying technology of Optical Feedback-Cavity Enhanced Absorption Spectroscopy (OF-CEAS) was invented and patented about ten years ago by LIPhy. It is now licensed to AP2E, who has successfully commercialized OF-CEAS for detection of a number of different molecules in the domains of industrial and air quality monitoring. OF-CEAS enables non-invasive, real-time and fast diagnostics of exhaled air by ultra-sensitive, highly selective, and auto-calibrated trace gas detection. Our objective is to develop exhaled breath analyzers for use by medical staff. In a previous collaborative project, LIPhy and TIMC-IMAG have already identified carbon monoxide (CO) in exhaled air as a biomarker of ischemia-reperfusion injury during ex-vivo perfusion of pig lungs: Endogenous lung production of CO by isolated pig lungs, correlated with ischemia-reperfusion injury, was demonstrated by real-time analysis on the ventilator gas-handling line using an OF-CEAS prototype developed at LIPhy.

The primary objective of the current proposal is to enter a new phase of measurements on human lung grafts, under much more stringent conditions and in the considerably more tightly controlled environment of an operating room. Medical qualification of the commercial AP2E analyzer is therefore mandatory. This task will be led by the CIC-IT/CHU, which is specialized in the adaptation and validation of new technologies and devices to the clinical setting.

The second goal is to validate CO as an indicator of the quality of human pulmonary transplants through its endogenous production in an ex-vivo reperfusion system. TIMC-IMAG will validate these OF-CEAS measurements in the tightly controlled clinical setting of organ transplantation within the framework of a larger project that consists in validating an Ex-Vivo Lung Perfusion (EVLP) system for the rehabilitation of initially rejected lung grafts and in searching for new tracers for the evaluation of such grafts. This research field of ex vivo evaluation of organs before transplantation is expected to have a tremendous impact in the context of “extended organ donors”, such as organ donation after cardiac arrest or termination of life support therapies, by increasing (almost doubling) the number of available organs.

The third major goal is the identification and validation of other molecular tracers of the quality of human lung grafts, in particular NO and H2S known to be, with CO, the main endogenous signaling gasotransmitters involved in pulmonary inflammation. Nitric oxide (NO) is a particularly promising candidate that has been studied now for many years. However, its role in pulmonary inflammation is still poorly understood. Detection of NO implies a technological leap in that it requires the use of mid-infrared lasers (MIR), to be implemented by LIPhy, as opposed to the near-infrared lasers used in the AP2E commercial analyzers (NIR). After development and laboratory tests of medical prototype for the detection of NO (MIR) and H2S (NIR), we plan to perform the first OF-CEAS measurements of endogenous NO and H2S production by pig lungs in an EVLP device.