Ultrasensitive multispecies spectroscopic breath analysis for real-time health monitoring and diagnostics

Significance Determining the identity and concentration of the molecules present in breath is a powerful tool to assess the overall health of a person, analogous to blood testing in clinical medicine, but in a faster and less invasive manner. The presence of a particular molecule (or combination of molecules) can indicate the presence of a certain health condition or infection, facilitating a diagnosis. Monitoring the concentration of the molecules of interest over time can help track the development (or recurrence) of a condition, as well as the effectiveness of the administered treatment. To make breath analysis more accessible and widely adopted, we explore a technique to perform breath analysis with high resolution, wide spectral coverage, high specificity, and high sensitivity. Breath analysis enables rapid, noninvasive diagnostics, as well as long-term monitoring of human health, through the identification and quantification of exhaled biomarkers. Here, we demonstrate the remarkable capabilities of mid-infrared (mid-IR) cavity-enhanced direct-frequency comb spectroscopy (CE-DFCS) applied to breath analysis. We simultaneously detect and monitor as a function of time four breath biomarkers—CH3OH, CH4, H2O, and HDO—as well as illustrate the feasibility of detecting at least six more (H2CO, C2H6, OCS, C2H4, CS2, and NH3) without modifications to the experimental apparatus. We achieve ultrahigh detection sensitivity at the parts-per-trillion level. This is made possible by the combination of the broadband spectral coverage of a frequency comb, the high spectral resolution afforded by the individual comb teeth, and the sensitivity enhancement resulting from a high-finesse cavity. Exploiting recent advances in frequency comb, optical coating, and photodetector technologies, we can access a large variety of biomarkers with strong carbon–hydrogen-bond spectral signatures in the mid-IR.