THz spectroscopy of exhaled gas
Breath tests have been used in medical practice for centuries. For example, as early as the 13th century, bad breath was used to diagnose “biliary disorders” in patients suffering from advanced kidney or liver disease. Currently, dozens of exhaled gases have been shown 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 is the carbon-13-labeled urease test, which is the most widely used of the breath tests. It detects the presence of the bacterium Helicobacter pylori in the stomach because the bacterium breaks down the labeled urea and releases carbon-13. Other tests include the nitric oxide (NO) test for detecting asthma or bronchiectasis, the carbon monoxide (CO) test for detecting respiratory infections, and the ammonia (NH3) test for diagnosing lung cancer. The table below lists the various exhaled breath tests and their associated conditions.
Exhaled breath analysis is completely noninvasive and safe for both patients and hospital staff. It can therefore be used for diagnosis, monitoring, and treatment selection, as well as for predicting the response to specific treatments.
However, commercially available exhaled breath analyzers can only be used for a few specific substances, such as isotopes of carbon dioxide (CO₂), nitrogen oxide (NO), hydrogen (H₂), and methane (CH₄). Furthermore, 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 suitable for the simultaneous detection of multiple gases, which reduces diagnostic reliability, as a set of biomarkers is required to obtain a conclusive diagnosis.
Internationally, only one model of a gas spectrometer operating at THz frequencies has been developed in Russia. This model has a major drawback, as its THz radiation source is based on proprietary BWO (backward wave oscillator) tube technology that is available only in Russia. This poses obvious challenges for its development in European countries. Fortunately, in recent years, advances in semiconductor technology have led to the emergence of new semiconductor THz sources with high-frequency stability. To achieve highly selective analysis in gases containing multiple chemical components to be detected, the spectroscopic characteristics of the radiation sources must achieve Doppler resolution with a frequency measurement accuracy of 10⁻⁸–10⁻¹⁰ timesthe reference center frequency.
Expected results
- Currently, there are two types of radiation sources that can meet the requirements of exhaled air spectroscopy. The first is based on the use of a source containing a photomixer (typically GaAs-BT): the frequency difference between two continuous-wave 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 first type presents a challenge in terms of available power, the sources available in the spectroscopy system required for the project will be capable of covering the frequency range from 50 GHz to 1100 GHz with very high resolution, high temporal stability, and high power.
High-precision THz spectroscopy can fully meet the requirements of real-time gas analysis. Indeed, the THz frequency range is well-suited for this purpose due to the presence of strong absorption lines from many exhaled biomarkers (NO, CO, acetone, ammonia, etc.), which makes it possible to analyze the gases present in exhaled air.