Detection of an Extended Human Volatome with Comprehensive Two-Dimensional Gas Chromatography Time-of-Flight Mass Spectrometry

Abstract

BackgroundComprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOF MS) has been proposed as a powerful new tool for multidimensional analysis of complex chemical mixtures. We investigated GCxGC-TOF MS as a new method for identifying volatile organic compounds (VOCs) in normal human breath.MethodsSamples of alveolar breath VOCs and ambient room air VOC were collected with a breath collection apparatus (BCA) onto separate sorbent traps from 34 normal healthy volunteers (mean age = 40 yr, SD = 17 yr, male/female = 19/15). VOCs were separated on two serial capillary columns separated by a cryogenic modulator, and detected with TOF MS. The first and second dimension columns were non-polar and polar respectively.ResultsBCA collection combined with GC×GC-TOF MS analysis identified approximately 2000 different VOCs in samples of human breath, many of which have not been previously reported. The 50 VOCs with the highest alveolar gradients (abundance in breath minus abundance in ambient room air) mostly comprised benzene derivatives, acetone, methylated derivatives of alkanes, and isoprene.ConclusionsCollection and analysis of breath VOCs with the BCA-GC×GC-TOF MS system extended the size of the detectable human volatile metabolome, the volatome, by an order of magnitude compared to previous reports employing one-dimensional GC-MS. The size of the human volatome has been under-estimated in the past due to coelution of VOCs in one-dimensional GC analytical systems.

Laser spectroscopy for breath analysis: towards clinical implementation

“…Several methods are currently employed for exhaled volatiles detection, among which mass spectrometry (e.g., gas chromatography mass spectrometry, GC-MS) is the most widely used analytical tool [11][12][13][14]. However, the GC-MSbased instruments are limited to laboratory settings, do not allow online sampling (i.e., exhaling directly into the instrument, usually using an inbuilt system or an external breath sampler for feedback exhaled airflow control, including a flowmeter) and have a relatively long analysis time (in the order of tens of minutes).…”

“…There are already a few optical breath analyzers commercially available for monitoring different biomarkers in clinical applications, e.g., non-dispersive infrared (NDIR) spectrometers for capnography and for measuring 13 C in breath to diagnose Helicobacter pylori (the bacterium that generates gastric ulcers and gastric cancers) [19], an infrared spectrometer for monitoring of CH 4 in breath accompanied by electrochemical sensors to detect H 2 and O 2 for diagnosis of gastrointestinal disorders [20], and a cavity ring-down spectroscopy system for detection of breath acetone which correlates with abnormal metabolic status, such as diabetes [21]. These successful implementations of optical breath analyzers in real-life clinical applications show the bright future of these systems, especially those using lasers as light sources.…”

Exhaled Gas Detection for Medical Diagnosis: Can it be Made a Tool for Self-Screening?

“…Alternate hypotheses were also proposed to explain the biochemical origin of exhaled breath VOCs and their link with cancer [2,9]. More than 3000 VOCs have been reported to be related to different types of cancers [2,10].…”

Normal–Gamma–Bernoulli peak detection for analysis of comprehensive two-dimensional gas chromatography mass spectrometry data

“…Compared with other analytical platforms, GC×GC-MS can significantly increase the separation power by 3–10 folds, depending on the sample complexity and instrument operation (Winnike et al, 2015). Therefore, GC×GC-MS has been increasingly used in metabolomics for biomarker discovery (Phillips et al, 2013; Ralsoton-Hooper et al, 2008; Schmidt et al, 2013; Shi et al, 2014). …”