A matrix-centered view of mass spectrometry platform innovation for volatilome research

Abstract

Volatile organic compounds (VOCs) are carbon-containing molecules with high vapor pressure and low water solubility that are released from biotic and abiotic matrices. Because they are in the gaseous phase, these compounds tend to remain undetected when using conventional metabolomic profiling methods. Despite this omission, efforts to profile VOCs can provide useful information related to metabolic status and identify potential signaling pathways or toxicological impacts in natural or engineered environments. Over the past several decades mass spectrometry (MS) platform innovation has instigated new opportunities for VOC detection from previously intractable matrices. In parallel, volatilome research linking VOC profiles to other forms of multi-omic information (DNA, RNA, protein, and other metabolites) has gained prominence in resolving genotype/phenotype relationships at different levels of biological organization. This review explores both on-line and off-line methods used in VOC profiling with MS from different matrices. On-line methods involve direct sample injection into the MS platform without any prior compound separation, while off-line methods involve chromatographic separation prior to sample injection and analyte detection. Attention is given to the technical evolution of platforms needed for increasingly resolved VOC profiles, tracing technical progress over time with particular emphasis on emerging microbiome and diagnostic applications.

Keywords: comprehensive two-dimensional gas chromatography; high resolution multi-reflecting time-of-flight mass spectrometry; ion mobility spectrometry-mass spectrometry; proton transfer reaction-mass spectrometry; secondary electrospray ionization-mass spectrometry; selected ion flow tube-mass spectrometry; time-of-flight mass spectrometry; volatile organic compounds.

FIGURE 1

Summary of mass spectrometry platform innovation over the past 60 years in relation to volatile organic compound detection (TOF, time-of-flight; SIFT, selected ion flow tube; IMS-MS, ion mobility spectrometry mass spectrometry; PTR-MS, proton transfer reaction mass spectrometry; SESI-MS, secondary electrospray ionization mass spectrometry; MALDI, matrix-assisted laser desorption ionization; GC, gas chromatography; GCxGC, comprehensive two-dimensional gas chromatography; GC-MS, gas chromatography mass spectrometry; GC-MS/MS, gas chromatography triple quadrupole mass spectrometry; HR-TOF-MS, high resolution time-of-flight mass spectrometry).

FIGURE 2

Increasing number of publications related to volatile organic compound detection over the past 20 years for different matrices, methods, and platforms based on PubMed searches. (A) various matrices, (B) extraction methods (SPME, solid phase microextraction; TD, thermal desorption; LE, liquid extraction; HS, headspace; SHS, static headspace; DHS, dynamic headspace), (C) GC-MS (gas chromatography mass spectrometry), (D) other mass spectrometry (MS) platforms (TOF, time-of-flight; PTR-MS, proton transfer reaction MS; IMR-MS, ion molecule reaction MS; IMS-MS, ion mobility spectrometry MS; SIFT-MS, selected ion flow tube MS; GCxGC-MS, comprehensive two-dimensional gas chromatography MS; GC-MS/MS, gas chromatography triple quadrupole MS; SESI-MS, secondary electrospray ionization MS).

FIGURE 3

An emerging paradigm for volatilome research integrating multi-omic data (DNA, RNA, protein, and metabolites) spanning different levels of biological organization to resolve volatile organic compound (VOC) profiles emerging from biological matrices sourced from natural or engineered environments including our own bodies. This paradigm includes enrichment and isolation methods to more closely link specific VOCs with specific individuals or populations of microorganisms as well as community-level analysis that define emergent patterns of VOC production and signaling among and between different taxonomic lineages. The development of more extensive regulatory-compliant repositories, e.g., Wiley Registry/National Institute of Standards and Technology (NIST) Mass Spectral Library compound reference libraries and integrative methods linking identified VOCs onto the background metabolic network at scale remain ongoing challenges (Created with BioRender.com).