Breath Analysis Using Laser Spectroscopic Techniques: Breath Biomarkers, Spectral Fingerprints, and Detection Limits

Abstract

Breath analysis, a promising new field of medicine and medical instrumentation, potentially offers noninvasive, real-time, and point-of-care (POC) disease diagnostics and metabolic status monitoring. Numerous breath biomarkers have been detected and quantified so far by using the GC-MS technique. Recent advances in laser spectroscopic techniques and laser sources have driven breath analysis to new heights, moving from laboratory research to commercial reality. Laser spectroscopic detection techniques not only have high-sensitivity and high-selectivity, as equivalently offered by the MS-based techniques, but also have the advantageous features of near real-time response, low instrument costs, and POC function. Of the approximately 35 established breath biomarkers, such as acetone, ammonia, carbon dioxide, ethane, methane, and nitric oxide, 14 species in exhaled human breath have been analyzed by high-sensitivity laser spectroscopic techniques, namely, tunable diode laser absorption spectroscopy (TDLAS), cavity ringdown spectroscopy (CRDS), integrated cavity output spectroscopy (ICOS), cavity enhanced absorption spectroscopy (CEAS), cavity leak-out spectroscopy (CALOS), photoacoustic spectroscopy (PAS), quartz-enhanced photoacoustic spectroscopy (QEPAS), and optical frequency comb cavity-enhanced absorption spectroscopy (OFC-CEAS). Spectral fingerprints of the measured biomarkers span from the UV to the mid-IR spectral regions and the detection limits achieved by the laser techniques range from parts per million to parts per billion levels. Sensors using the laser spectroscopic techniques for a few breath biomarkers, e.g., carbon dioxide, nitric oxide, etc. are commercially available. This review presents an update on the latest developments in laser-based breath analysis.

Trace species detection in the near infrared using Fourier transform broadband cavity enhanced absorption spectroscopy: initial studies on potential breath analytes

“…Levels of isoprene have been reported at ~ 200 ppb [30,31], while those of acetone and methane can reach tens of ppm, depending upon the condition of the subject [31][32][33][34][35]. To simulate the relative concentrations possible in breath of isoprene and acetone, a mixture was made of 0.5 % of isoprene and 5 % acetone, buffered in air.…”

Cavity-enhanced absorption using an atomic line source: application to deep-UV measurements

“…25 The estimated limit of detection for acetone is higher than the range found in healthy breath (390 to 850 ppbv), but further improvements in sensitivity could make this approach practical for breath analysis. Other applications include detectors for chromatography, for which both CRDS 26,27 and CEAS 28 have previously been proposed.…”

Low Power Greenhouse Gas Sensors for Unmanned Aerial Vehicles

“…As such, no laser-based trace gas sensors have been developed specifically for small UAVs. Laser-based optical detection is widely used in various atmospheric, industrial and biomedical applications [6][7][8][9]. Laser-based sensors are selective, sensitive, fast, compact, and consume low power (specifically, tunable diode lasers)-essential requirements for deployment on small UAVs as well as obtaining scientifically-robust measurements.…”