Fast and Highly Sensitive Fiber-Enhanced Raman Spectroscopic Monitoring of Molecular H₂ and CH₄ for Point-of-Care Diagnosis of Malabsorption Disorders in Exhaled Human Breath

Breath gas analysis is a novel powerful technique for noninvasive, early-stage diagnosis of metabolic disorders or diseases. Molecular hydrogen and methane are biomarkers for colonic fermentation, because of malabsorption of oligosaccharides (e.g., lactose or fructose) and for small intestinal bacterial overgrowth. Recently, the presence of these gases in exhaled breath was also correlated with obesity. Here, we report on the highly selective and sensitive detection of molecular hydrogen and methane within a complex gas mixture (consisting of H₂, CH₄, N₂, O₂, and CO₂) by means of fiber-enhanced Raman spectroscopy (FERS). An elaborate FERS setup with a microstructured hollow core photonic crystal fiber (HCPCF) provided a highly improved analytical sensitivity. The simultaneous monitoring of H₂ with all other gases was achieved by a combination of rotational (H₂) and vibrational (other gases) Raman spectroscopy within the limited spectral transmission range of the HCPCF. The HCPCF was combined with an adjustable image-plane aperture pinhole, in order to separate the H₂ rotational Raman bands from the silica background signal and improve the sensitivity down to a limit of detection (LOD) of 4.7 ppm (for only 26 fmol H₂). The ability to monitor the levels of H₂ and CH₄ in a positive hydrogen breath test (HBT) was demonstrated. The FERS sensor possesses a high dynamic range (∼5 orders of magnitude) with a fast response time of few seconds and provides great potential for miniaturization. We foresee that this technique will pave the way for fast, noninvasive, and painless point-of-care diagnosis of metabolic diseases in exhaled human breath.