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There is an ever-growing interest in metabolomic profiling using noninvasive, real-time techniques that avoid sample manipulation and are painless for the patients. In this context, breath analysis is gaining much attention, and several ionization techniques have been developed to get insights in real-time into metabolic status by analyzing breath through mass spectrometry, such as Proton transfer reaction mass spectrometry (PTR-MS), Selected ion flow tube mass spectrometry (SIFT-MS), and Secondary electrospray ionization mass spectrometry (SESI-MS). SESI-MS is the most recently developed analytical platform displaying particular adequate characteristics for breath analysis, such as the low detection limits, and the detection of low volatility species, which tend to present a higher biological significance. Here, we review the SESI technology development, the different SESI configurations developed, and the standardization procedures described to translate SESI into the clinical environment. Finally, SESI main applications described in the literature with prompt translation into the clinical environment, namely, biomarker discovery or pharmacokinetics and drug monitoring are revised.

Breath Analysis by Secondary Electro-Spray Ionization - Mass Spectrometry to Interrogate Biologically Significant Metabolites Non-Invasively