An instrument integrating thermal desorption (TD) to selected ion flow tube mass spectrometry (SIFT-MS) is presented, and its application to analyze volatile organic compounds (VOCs) in human breath is demonstrated for the first time. The rationale behind this development is the need to analyze breath samples in large-scale multicenter clinical projects involving thousands of patients recruited in different hospitals. Following adapted guidelines for validating analytical techniques, we developed and validated a targeted analytical method for 21 compounds of diverse chemical class, chosen for their clinical and biological relevance. Validation has been carried out by two independent laboratories, using calibration standards and real breath samples from healthy volunteers. The merging of SIFT-MS and TD integrates the rapid analytical capabilities of SIFT-MS with the capacity to collect breath samples across multiple hospitals. Thanks to these features, the novel instrument has the potential to be easily employed in clinical practice.

Department of Surgery and Cancer Imperial College London London W12 0HS United Kingdom

Element Lab Solutions Wellbrook Court Girton Road Cambridge CB3 0NA United Kingdom

J Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences 182 23 Prague Czechia

Syft Technologies Limited 68 St Asaph Street Christchurch 8011 New Zealand

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Belluomo I.; Boshier P. R.; Myridakis A.; Vadhwana B.; Markar S. R.; Spanel P.; Hanna G. B. Selected ion flow tube mass spectrometry for targeted analysis of volatile organic compounds in human breath. Nat. Protoc 2021, 16 (7), 3419–3438. 10.1038/s41596-021-00542-0. PubMed DOI

Ajibola O. A.; Smith D.; Spanel P.; Ferns G. A. Effects of dietary nutrients on volatile breath metabolites. J. Nutr Sci. 2013, 2, e3410.1017/jns.2013.26. PubMed DOI PMC

Spanel P.; Smith D. Progress in SIFT-MS: breath analysis and other applications. Mass Spectrom Rev. 2011, 30 (2), 236–267. 10.1002/mas.20303. PubMed DOI

Sharma A.; Kumar R.; Varadwaj P. Smelling the Disease: Diagnostic Potential of Breath Analysis. Mol. Diagn Ther 2023, 27 (3), 321–347. 10.1007/s40291-023-00640-7. PubMed DOI PMC

Markar S. R.; Wiggins T.; Antonowicz S.; Chin S. T.; Romano A.; Nikolic K.; Evans B.; Cunningham D.; Mughal M.; Lagergren J.; Hanna G. B. Assessment of a Noninvasive Exhaled Breath Test for the Diagnosis of Oesophagogastric Cancer. JAMA Oncol 2018, 4 (7), 970–976. 10.1001/jamaoncol.2018.0991. PubMed DOI PMC

Woodfield G.; Belluomo I.; Laponogov I.; Veselkov K.; Group C. W.; Cross A. J.; Hanna G. B.; Boshier P. R.; Lin G. P.; Myridakis A.; et al. Diagnostic performance of a non-invasive breath test for colorectal cancer: COBRA1 study. Gastroenterology 2022, 163, 1447.10.1053/j.gastro.2022.06.084. PubMed DOI

Kamal F.; Kumar S.; Edwards M. R.; Veselkov K.; Belluomo I.; Kebadze T.; Romano A.; Trujillo-Torralbo M. B.; Shahridan Faiez T.; Walton R.; et al. Virus-induced Volatile Organic Compounds Are Detectable in Exhaled Breath during Pulmonary Infection. Am. J. Respir Crit Care Med. 2021, 204 (9), 1075–1085. 10.1164/rccm.202103-0660OC. PubMed DOI PMC

Woodfield G.; Belluomo I.; Boshier P. R.; Waller A.; Fayyad M.; von Wagner C.; Cross A. J.; Hanna G. B. Feasibility and acceptability of breath research in primary care: a prospective, cross-sectional, observational study. BMJ. Open 2021, 11 (4), e04469110.1136/bmjopen-2020-044691. PubMed DOI PMC

Weber R.; Haas N.; Baghdasaryan A.; Bruderer T.; Inci D.; Micic S.; Perkins N.; Spinas R.; Zenobi R.; Moeller A. Volatile organic compound breath signatures of children with cystic fibrosis by real-time SESI-HRMS. ERJ. Open Res. 2020, 6 (1), 00171-2019.10.1183/23120541.00171-2019. PubMed DOI PMC

Bruderer T.; Gaisl T.; Gaugg M. T.; Nowak N.; Streckenbach B.; Muller S.; Moeller A.; Kohler M.; Zenobi R. On-Line Analysis of Exhaled Breath Focus Review. Chem. Rev. 2019, 119 (19), 10803–10828. 10.1021/acs.chemrev.9b00005. PubMed DOI

Harshman S. W.; Mani N.; Geier B. A.; Kwak J.; Shepard P.; Fan M.; Sudberry G. L.; Mayes R. S.; Ott D. K.; Martin J. A.; Grigsby C. C. Storage stability of exhaled breath on Tenax TA. J. Breath Res. 2016, 10 (4), 046008.10.1088/1752-7155/10/4/046008. PubMed DOI

Kang S.; Paul Thomas C. L. How long may a breath sample be stored for at −80 degrees C? A study of the stability of volatile organic compounds trapped onto a mixed Tenax:Carbograph trap adsorbent bed from exhaled breath. J. Breath Res. 2016, 10 (2), 026011.10.1088/1752-7155/10/2/026011. PubMed DOI

Stefanuto P. H.; Zanella D.; Vercammen J.; Henket M.; Schleich F.; Louis R.; Focant J. F. Multimodal combination of GC x GC-HRTOFMS and SIFT-MS for asthma phenotyping using exhaled breath. Sci. Rep 2020, 10 (1), 16159.10.1038/s41598-020-73408-2. PubMed DOI PMC

Hryniuk A.; Ross B. M. Detection of acetone and isoprene in human breath using a combination of thermal desorption and selected ion flow tube mass spectrometry. Int. J. Mass Spectrom. 2009, 285 (1–2), 26–30. 10.1016/j.ijms.2009.02.027. DOI

Sovova K.; Spesyvyi A.; Bursova M.; Pasztor P.; Kubista J.; Shestivska V.; Spanel P. Time-integrated thermal desorption for quantitative SIFT-MS analyses of atmospheric monoterpenes. Anal. Bioanal. Chem. 2019, 411 (14), 2997–3007. 10.1007/s00216-019-01782-6. PubMed DOI

Slingers G.; Eede M. V.; Lindekens J.; Spruyt M.; Goelen E.; Raes M.; Koppen G. Real-time versus thermal desorption selected ion flow tube mass spectrometry for quantification of breath volatiles. Rapid Commun. Mass Spectrom. 2021, 35 (4), e8994.10.1002/rcm.8994. PubMed DOI

EMA . Guideline on bioanalytical method validation. European Medical Agency 2012, 58 ( (3), ), 284–289.

Smith D.; Spanel P.; Demarais N.; Langford V. S.; McEwan M. J. Recent developments and applications of selected ion flow tube mass spectrometry (SIFT-MS). Mass Spectrom Rev. 2023, e2183510.1002/mas.21835. PubMed DOI PMC

Spanel P.; Dryahina K.; Smith D. A general method for the calculation of absolute trace gas concentrations in air and breath from selected ion flow tube mass spectrometry data. Int. J. Mass Spectrom. 2006, 249, 230–239. 10.1016/j.ijms.2005.12.024. DOI

Drabinska N.; Flynn C.; Ratcliffe N.; Belluomo I.; Myridakis A.; Gould O.; Fois M.; Smart A.; Devine T.; Costello B. L. A literature survey of all volatiles from healthy human breath and bodily fluids: the human volatilome. J. Breath Res. 2021, 15 (3), 034001.10.1088/1752-7163/abf1d0. PubMed DOI

Behera S. N.; Sharma M.; Aneja V. P.; Balasubramanian R. Ammonia in the atmosphere: a review on emission sources, atmospheric chemistry and deposition on terrestrial bodies. Environ. Sci. Pollut Res. Int. 2013, 20 (11), 8092–8131. 10.1007/s11356-013-2051-9. PubMed DOI

Spanel P.; Spesyvyi A.; Smith D. Electrostatic Switching and Selection of H(3)O(+), NO(+), and O(2)(+*) Reagent Ions for Selected Ion Flow-Drift Tube Mass Spectrometric Analyses of Air and Breath. Anal. Chem. 2019, 91 (8), 5380–5388. 10.1021/acs.analchem.9b00530. PubMed DOI

Kumar S.; Huang J.; Abbassi-Ghadi N.; Mackenzie H. A.; Veselkov K. A.; Hoare J. M.; Lovat L. B.; Spanel P.; Smith D.; Hanna G. B. Mass Spectrometric Analysis of Exhaled Breath for the Identification of Volatile Organic Compound Biomarkers in Esophageal and Gastric Adenocarcinoma. Ann. Surg 2015, 262 (6), 981–990. 10.1097/SLA.0000000000001101. PubMed DOI