Breath analysis using laser spectroscopic techniques: breath biomarkers, spectral fingerprints, and detection limits.

Chuji Wang,Peeyush Sahay

doi:10.3390/s91008230

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.

Highlights

It is generally accepted that modern breath analysis started with the discovery made by Pauling in 1971 that hundreds of volatile organic compounds (VOCs) are present in normal human breath at the levels of parts per billion or lower [1]
Alkanes are present in the case of lung cancer and formaldehyde in the case of breast cancer; the presence of isoprene in human breath is related to blood cholesterol levels; and patients with Type 1 diabetes have excess acetone in their breath
Of the 35 major breath biomarkers listed in Table 1, 14 biomarkers have been detected in actual human breath by the aforementioned laser spectroscopic techniques; some of the breath biomarkers have not been measured in actual breath gases to date, but have been measured in specially calibrated gas samples, which contain the biomarker of interest

Summary

Introduction

It is generally accepted that modern breath analysis started with the discovery made by Pauling in 1971 that hundreds of volatile organic compounds (VOCs) are present in normal human breath at the levels of parts per billion (ppb) or lower [1]. The basic principles of these techniques are briefly described below

Laser Spectroscopic Techniques for Breath Analysis

Breath Biomarkers Detected by the Laser Spectroscopic Techniques

Current Status of Prototype and commercialized Breath Sensors

Challenges and Perspectives

Summary

Findings

65. For example