Towards the determination of isoprene in human breath using substrate-integrated hollow waveguide mid-infrared sensors

Abstract

Selected volatile organic compounds (VOCs) in breath may be considered biomarkers if they are indicative of distinct diseases or disease states. Given the inherent molecular selectivity of vibrational spectroscopy, infrared sensing technologies appear ideally suitable for the determination of endogenous VOCs in breath. The aim of this study was to determine that mid-infrared (MIR; 3-20 µm) gas phase sensing is capable of determining isoprene in exhaled breath as an exemplary medically relevant VOC by hyphenating novel substrate-integrated hollow waveguides (iHWG) with a likewise miniaturized preconcentration system. A compact preconcentrator column for sampling isoprene from exhaled breath was coupled to an iHWG serving simultaneously as highly miniaturized gas cell and light conduit in combination with a compact Fourier transform infrared spectrometer. A gas mixing system enabled extensive system calibration using isoprene standards. After system optimization, a calibration function obtaining a limit of quantification of 106 ppb was achieved. According to the literature, the obtained sensitivity is sufficient for quantifying middle to high isoprene concentrations occurring in exhaled breath. Finally, a volunteer breath sample was analysed proving comparable values of isoprene in a real-world scenario. Despite its fundamental utility, the proposed methodology contains some limitations in terms of sensitivity and temporal resolution in comparison with the readily available measurement techniques that should be addressed during future optimization of the system. Nonetheless, this study presents the first determination of endogenous VOCs in breath via advanced hollow waveguide MIR sensor technology, clearly demonstrating its potential for the analysis of volatile biomarkers in exhaled breath.

Technologies for Clinical Diagnosis Using Expired Human Breath Analysis

“…These can be considered as volatile biomarkers within the exhaled breath matrix. The most concentrated endogenous constituents in breath are isoprene (12–580 ppb), ethanol (13–1000 ppb), methanol (160–2000 ppb), and acetone (1.2–1800 ppb); other alcohols are present in the very low ppb concentration range [ 24 ].…”

iHWG-μNIR: a miniaturised near-infrared gas sensor based on substrate-integrated hollow waveguides coupled to a micro-NIR-spectrophotometer

“…18 iHWGs provide unmatched compactness and exibility for gas sensing with a footprint of only 75 Â 50 Â 12 mm (L Â W Â H). While such devices have been efficiently coupled to spectrometers operating in the mid-infrared region for the detection of e.g., 12 CO 2 / 13 CO 2 , 19 ozone, 20 hydrogen sulphide, 21 and isoprene, 22 iHWGs have not been coupled to a near-infrared sensor system yet.…”

Online monitoring of carbon dioxide and oxygen in exhaled mouse breath via substrate-integrated hollow waveguide Fourier-transform infrared-luminescence spectroscopy

“…A c c e p t e d M a n u s c r i p t mechanical stability[14,[17][18][19][20][21][22][23][24][25][26]. Radiation from the IR spectrometer is focused into the iHWG, and propagated onto the internal DTGS detector of the ALPHA via two gold-coated off-axis parabolic mirrors (OAPM; diam: 1") with an effective focal length of 2" (Janos Technology Inc, Keene/NH, USA).…”