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Selected ion flow tube mass spectrometry for targeted analysis of volatile organic compounds in human breath

Nature Protocols volume 16, pages 3419–3438 (2021)Cite this article

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Abstract

The analysis of volatile organic compounds (VOCs) within breath for noninvasive disease detection and monitoring is an emergent research field that has the potential to reshape current clinical practice. However, adoption of breath testing has been limited by a lack of standardization. This protocol provides a comprehensive workflow for online and offline breath analysis using selected ion flow tube mass spectrometry (SIFT-MS). Following the suggested protocol, 50 human breath samples can be analyzed and interpreted in <3 h. Key advantages of SIFT-MS are exploited, including the acquisition of real-time results and direct compound quantification without need for calibration curves. The protocol includes details of methods developed for targeted analysis of disease-specific VOCs, specifically short-chain fatty acids, aldehydes, phenols, alcohols and alkanes. A procedure to make custom breath collection bags is also described. This standardized protocol for VOC analysis using SIFT-MS is intended to provide a basis for wider application and the use of breath analysis in clinical studies.

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Fig. 1: Breath analysis by SIFT-MS.
Fig. 2: Sampling bag types.
Fig. 3: Inlet setups.
Fig. 4: SIFT-MS traces.
Fig. 5: Compromised breath samples.

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Data availability

Examples of data obtained while carrying out this protocol are included in Figs. 3 and 4 and Supplementary Table 2. The data reported in Supplementary Table 2 were obtained during the clinical study described in ref. 4.

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Acknowledgements

The authors acknowledge Q. Wen for figure editing and E. Want for her kind support and precious advice. P.R.B. and S.R.M. are supported by National Institute for Health Research (NIHR) lectureships. I.B. and A.M. are supported by Rosetrees and Stonygates Trusts and NIHR London In Vitro Diagnostics Co-operative. This research was supported by the NIHR Diagnostic Evidence Co-operative London at Imperial College Healthcare NHS Trust. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the Department of Health.

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Authors and Affiliations

  1. Department of Surgery and Cancer, Imperial College London, London, UK

    Ilaria Belluomo, Piers R. Boshier, Antonis Myridakis, Bhamini Vadhwana, Sheraz R. Markar, Patrik Spanel & George B. Hanna

  2. J. Heyrovský Institute of Physical Chemistry, Czech Academy of Sciences, Prague, Czechia

    Patrik Spanel

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Contributions

All the authors discussed the design of the manuscript. I.B., P.R.B., B.V. and S.R.M. carried out the experiments. I.B., P.R.B., A.M. and B.V. wrote the original draft of the manuscript. P.S. and G.B.H. supervised the projects and revised the manuscript.

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Correspondence to George B. Hanna.

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G.B.H. is the founder of VODCA Limited, a company for early detection of cancer.

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Peer review information Nature Protocols thanks James Covington, Jean François Focant, Gudrun Koppen and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

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Key references using this protocol

Markar, S. R. et al. JAMA Oncol. 4, 970-976 (2018): https://doi.org/10.1001/jamaoncol.2018.0991

Vadhwana, B. et al. Rapid Commun. Mass Spectrom. 34, e8706 (2019): https://doi.org/10.1002/rcm.8706

Key data used in this protocol

Markar, S. R. et al. JAMA Oncol. 4, 970-976 (2018): https://doi.org/10.1001/jamaoncol.2018.0991

Supplementary information

Supplementary Information

Supplementary Note 1 and Supplementary Tables 1 and 2.

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Belluomo, I., Boshier, P.R., Myridakis, A. et al. Selected ion flow tube mass spectrometry for targeted analysis of volatile organic compounds in human breath. Nat Protoc 16, 3419–3438 (2021). https://doi.org/10.1038/s41596-021-00542-0

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