Significance One of the most critical factors for the survival of living organisms is their gas exchange with the environment. Gas exchange is primarily to absorb oxygen and exhale carbon dioxide (CO₂), water vapor, and other gases. The main gases exhaled by the human body are nitrogen (78%), oxygen (15%--18%), water vapor (5%), carbon dioxide (4%--5%), and argon (1%). In addition, there are more than 3000 other gases and volatile organic compounds in the exhaled breath, and their emissions are much less than those of water vapor and CO₂ (with volume fractions of less than 1×10 ^-6). Many of these gaseous compounds have been identified as biomarkers for specific diseases or metabolic disorders. Breath diagnosis involves the detection of traces of gaseous components in exhaled breath that can be used as biomarkers. It can diagnose diseases without traumatic detection such as blood drawing.

The methods used for breath diagnosis can be divided into non-optical and optical methods. Gas chromatography, electrochemical sensors, and chemiluminescence are the common non-optical methods. Optical methods include non-dispersive infrared spectroscopy, cavity ring-down spectroscopy, Fourier-transform infrared spectroscopy, and tunable diode laser absorption spectroscopy (TDLAS). Compared with other breath diagnosis methods, TDLAS has many advantages: high spectral resolution, good gas selectivity, non-invasive measurement, high detection sensitivity (up to 10^-9 level), online measurement, and fast response. Thus, its devices are easy to obtain and low cost, and its detection system is easy to miniaturize and suitable for practical applications.

TDLAS has been widely used in breath diagnosis, and it is necessary to introduce and summarize the main TDLAS technologies, the types and latest developments of lasers and gas cells, as well as the application status of TDLAS technology in common breathing gases, to guide follow-up researches.

Progress Many gases that can be used for breath diagnosis, the common exhaled breath, and related diseases are summarized in Table 1. The laser wavelengths and corresponding detection limits for common exhaled gases estimated by the HITRAN database are shown in Table 2. At the same time, the normal concentration of the exhaled gases is obtained. TDLAS technology can meet the concentration measurement requirements of most exhaled gases, and the detection limit can be further reduced by increasing the absorption optical path of the gas cell. Direct absorption spectroscopy and wavelength modulation spectroscopy are the most widely used TDLAS technologies, a brief introduction of their principles is described in section 2.2 and section 2.3. The types of laser and gas cells commonly used in TDLAS technology are summarized in section 2.5 and section 2.6, respectively. Hollow waveguide is a new type of gas cell, which can achieve a long optical path in a small gas inflation volume.

In the current study on the measurement of ¹³CO₂ and ¹²CO₂ isotopes for human breath based on TDLAS, the wavelength of most lasers used is 4.3 μm, the Herriott cell is usually used, the accuracy of ratio measurement can reach 0.5‰, and the appearance of a hollow optical waveguide causes the inflation volume to decrease further and the measurement time to be significantly reduced. For CO breath detection, quantum cascade lasers with wavelengths at 4.6--5 μm are usually used, most of the systems can realize online measurement, the sensitivity of concentration detection can reach 10^-9 level, circular multi-pass cell proposed by Ghorbani and coworkers can reduce the gas volume to 38 mL. There are many types of laser wavelengths used to measure acetone based on TDLAS. Since many absorption peaks of acetone in the infrared are broadband, it is necessary to exclude the influence of other gases during the measurement.

Conclusion and Prospect To improve the accuracy of concentration detection, for existing breath detection based on TDLAS, mid-infrared quantum cascade laser is commonly used, in combination with the Herriott multi-path gas cell. The volume of the multi-pass cell used in the existing researches is relatively large. Therefore, strict pressure control is required to shorten the inflation time and reduce the volume of gas to be measured in the online breath diagnosis. In the future, smaller and longer path gas cells can be used in breath diagnosis to further improve the detection speed and accuracy. For some gases, such as isotopes of CO₂, CO, and NO, the laboratory research is relatively mature.The key research directions of the breath detection are to further improve the air intake device, collect respiratory data, give the quantitative corresponding relationship between the measured gas concentration and specific diseases, and integrate and commercialize the measurement system. When TDLAS is applied to the breath detection with broadband absorption, the absorption interference between different gases will affect the accuracy of the concentration measurement of the gas to be measured. Exploring new data processing methods, using wavelength locking technology, or other related technologies to achieve a single line gas measurement, and removing interference from other gases are important directions for future research. In addition, the existing TDLAS technology cannot achieve simultaneous measurement of a variety of exhaled gases. It is also important to improve the laser, gas cell, modulation technology, and data processing, and simultaneously measure more types of exhaled gas concentration through TDLAS.