Recent advances in high-throughput biofluid metabotyping by direct infusion and ambient ionization mass spectrometry

Abstract

Biofluid metabolomics is a popular tool for biomarker discovery to decipher disease-, genetics-, and exposure-related metabolic alterations and is an essential component for understanding integrated metabolite-level responses. The conventional metabolomics workflow in mass spectrometry (MS) involves hyphenation with chromatographic separation and represents a valuable analytical tool in both research and clinical settings. However, analytical complexity, relatively low throughput, and high costs often hinder implementation when routine, large-scale analysis with high sample turnover is desired, such as in point-of-care applications. In this context, direct infusion (DI) and ambient ionization (AI) MS, where samples can be analysed directly, rapidly, and with minimal sample handling, offer attractive alternatives to hyphenated methods. Recent technological advances have addressed the typical issues of the AIMS and DIMS methods regarding metabolome coverage, reproducibility, and repeatability encountered during their early development. In this systematic review, we discussed recent (2017–2023) original publications on DIMS- and AIMS-based biofluid metabolomics considering reported biomedical implementations, assets of the workflow, sample and data handling and coherence with the conventional platforms.