THz spectroscopy of exhaled gas
Breath tests have been used in medical practice for centuries. For example, bad breath was used as early as the 13th century to diagnose "biliary disorders" in patients suffering from advanced kidney or liver disease. Today, dozens of exhaled gases have been found to be markers of various pathologies (see e.g. [Kazemi S. et al., Diagnostic values of Helicobacter pylori diagnostic tests: stool antigen test, urea breath test, rapid urease test, serology and histology Journal of Research in Medical Sciences 2011 16 1097-104]). Among these, the carbon-13 urease test is the most widely used breath test. It detects the presence of Helicobacter pylori bacteria in the stomach, as it degrades labeled urea and releases carbon-13. But also the nitric oxide (NO) test for the detection of asthma or bronchiectasis, carbon monoxide (CO) for the detection of respiratory infections, ammonia (NH3) for the diagnosis of lung cancer. The table below lists the various breath tests and associated pathologies.
Breath analysis is totally non-invasive and safe for both patient and hospital staff. It can therefore be used for diagnosis, monitoring and therapy selection, as well as for predicting response to specific treatments.
However, commercially available breath analyzers can only be used for a few specific substances, such as the isotopes of carbon dioxide (CO2), nitrous oxide (NO), hydrogen (H2) and methane (CH4). In addition, the technology used in these analyzers (electrochemical sensors, chemiluminescence (see e.g. [Cristescu S M, et al., Methods of NO detection in exhaled breath J. Breath Res. 2013 7 017104/1-11]) is not applicable for the detection of several gases simultaneously, which reduces diagnostic reliability, as a set of biomarkers is required to obtain a conclusive diagnosis.
Internationally, only one model of gas spectrometer operating at THz frequencies has been developed in Russia. This model has a major drawback in that its THz radiation source is based on the specific BWO (backward waves oscillator) tube technology found only in Russia. This poses obvious problems for its development in European countries. Fortunately, in recent years, the development of semiconductor technology has led to the emergence of new THz semiconductor sources with high-frequency stability. To achieve very high selectivity analysis in gases carrying several chemical components to be detected; the spectroscopic characteristics of the radiation sources must achieve Doppler resolution with a frequency measurement accuracy reaching 10-8-10-10times the reference center frequency.
Expected results
- At present, there are two types of radiation source that can satisfy the requirements of breath-air spectroscopy. The first is based on the use of a source containing a photomixer (typically GaAs-BT): the difference frequency of two continuous optical lasers is obtained using a semiconductor mixer. The second type of source is a microwave frequency generator created by multiplying the frequency of a highly stable reference synthesizer. While the former presents a problem in terms of available power, the sources available in the spectroscopy system requested in the project will be capable of covering the frequency range from 50 GHz to 1100 GHz with very high resolution, high temporal stability and significant power.
High-precision THz spectroscopy can fully satisfy the requirements of real-time gas analysis. In fact, the THz frequency range is favored by the presence of strong absorption lines for many exhaled biomarkers (NO, CO, acetone, ammonia, etc.), enabling analysis of gases present in exhaled air.