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

Abstract

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.

[INVITED] New perspectives in photonic crystal fibre sensors

“…The possibility of sensing multiple parameters with multi-core or photonic band gap (PBG) PCFs was demonstrated in recent years [81][82][83]. PBG fibres have a hollow core and guide light with low attenuation within a narrow spectral range which is sufficient to guide the pump laser light and the Raman-scattered photons [82,83].…”

Differential high-resolution stimulated CW Raman spectroscopy of hydrogen in a hollow-core fiber

“…We use a very short integration time of 30 ms for the lock-in amplifier in order to have the SNR of the Raman signal without too much averaging. The differential detector subtracts the DC power of the probe to avoid saturation of the lock-in amplifier, and any background signal from spontaneous Raman scattering of the pump light from silica in the fibre, which could otherwise be problematic [3], only leaves a small constant offset in the lock-in signal which can be subtracted in post-processing. Figure 2 shows the effect of the differential detection scheme.…”

“…With applications in physical, chemical, biological sciences and in a number of different industrial areas [1][2][3] there is growing demand for versatile and highly sensitive optical spectroscopy and microscopy tools. For this, Raman spectroscopy is a popular solution.…”

Spontaneous Raman scattering in hollow core photonic crystal fibres

“…Hollow core photonic crystal fibres (HC-PCFs) [1] have recently been used to overcome this challenge [2][3][4][5][6]. In a HC-PCF, light is guided with low attenuation in an air core.…”