Cavity-enhanced mid-infrared frequency comb spectroscopy: application to real-time ultra-sensitive breath analysis

Exhaled breath analysis, by identifying biomarkers that reflect metabolic and physiological processes occurring in a human body, represents a promising approach for rapid, non-invasive medical diagnosis and disease monitoring. While mass-spectrometry-based methods are widely used to identify and quantify exhaled molecules, broadband laser spectroscopic techniques offer the possibility of simultaneous detection of multiple biomarkers with high detection sensitivity and specificity, but without the need for (1) gas chromatography to pre-separate various molecules and/or (2) routine calibration to achieve accurate quantification. This potentially in-situ and real-time analysis tool can become invaluable for medical applications. Here, we demonstrate a cavity-enhanced mid-infrared frequency comb breath analysis system with ultra-high detection sensitivity at parts-per-billion and even parts-per-trillion levels. With a wide spectral coverage from 2810 – 2945 cm^-1, we can potentially detect at least ten clinically relevant biomarkers simultaneously, including CH₃OH, CH₄, H₂CO, C₂H₆, C₂H₄, OCS, CS₂, NH₃, HDO, and H₂O. To demonstrate the feasibility of applying this technique to real-time monitoring of human breath, we have tracked the concentration of molecules present in the exhalations of a volunteer before and after the consumption of ripe fruit, which reveals a consistent ≈ 0.15 ppm temporal increase in methanol concentration on the 1 – 2 hour time scale.