Human exhaled breath consists of more than 3000 volatile organic compounds, many of which are relevant biomarkers for various diseases. Although gas chromatography has been the gold standard for volatile organic compound (VOC) detection in exhaled breath, recent developments in mid-infrared (MIR) laser spectroscopy have led to the promise of compact point-of-care (POC) optical instruments enabling even single breath diagnostics. In this review, we discuss the evolution of MIR sensing technologies with a special focus on photoacoustic spectroscopy, and its application in exhaled breath biomarker detection. While mid-infrared point-of-care instrumentation promises high sensitivity and inherent molecular selectivity, the lack of standardization of the various techniques has to be overcome for translating these techniques into more widespread real-time clinical use.

The broadband photoacoustic spectroscopy (PAS) technique is proposed and demonstrated for measurement of ${\mathrm{CH}}_4$, ${\mathrm{CO}}_2$, and ${\mathrm{H}}_2\mathrm{O}$ vapor in the 1.6 to 2.0 μm wavelength region. The wide spectrum of a supercontinuum light source is used to cover broadband absorption bands of multiple gas species. This sensor works in the off-resonant frequency of the designed photoacoustic cell and exhibits a wide concentration measurement range of parts per billion by volume (ppb-v) to 100%. The PAS sensor is further tested in real time by measuring the concentration of ${\mathrm{CO}}_2$, ${\mathrm{CH}}_4$, and ${\mathrm{H}}_2\mathrm{O}$ vapor in biogas plants.

Online measurement of CO₂, CH₄ and H₂O in a biogas plant using a Supercontinuum laser based off-resonant broadband photoacoustic spectroscopy is realized. The system exhibits a wide dynamic range from ppbv - 100% concentration.

A hollow-core fiber (HCF) combined with a broadband supercontinuum laser-based direct absorption spectroscopy technique is pro- posed and demonstrated for concentration measurements of gas mixtu- res. A dual-wavelength technique is used to eliminate gas interference in multigas sensing. The concentrations of methane (CH ₄ ) in two bands, 1.6 and 2.3 µm, ammonia (NH ₃ ) in two bands, 2 and 2.3 µm, and carbon dioxide (CO ₂ ) in the 2-µm band are measured. The measurements were performed using 0.5, 1, 5, and 10 m long HCF covering multiple absorption lines in the given band. The minimum detection limit (MDL) is improved as the signal-to-noise ratio was enhanced up to 3.9 dB by considering cumulative absorbance obtained from multiple absorption lines in the broadband measurement. The MDL were 13 and 15 parts-per-million (ppm) for CH ₄ at 1.6 and 2.3 µm, respectively; 13 and 17 ppm for NH ₃ at 2 and 2.3 µm, respectively; and 154 ppm for CO ₂ at 2 µm band. The proposed dual-wavelength measurement technique was further extended to measure concentrations of gases in biogas samples. CH ₄ , CO ₂ , and hydrogen sulfide were measured to be 54.7%, 46.1%, and 2.1%, respectively, and atmospheric CO ₂ of 421 ppm was also measured using a 10-m long HCF. The system offers excellent long-term stability for over continuous measurement of 4 h.