Recent advances and typical applications in mass spectrometry-based technologies for single-cell metabolite analysis

Cells are the most basic structural and functional units of biological organisms. Single-cell metabolite analysis can discover the chemical composition and molecular profile at the cellular and even subcellular levels and has attracted increasing research interests due to its crucial role in cellular heterogeneity investigation, fine tissue classification, and new biomarker identification. However, single-cell analysis is extremely challengable due to the minimal cell volume and the wide variety, yet very low concentration of metabolites. Mass spectrometry (MS) has been proven a very promising tool for single-cell analysis with high sensitivity. In this review, the recent advances in MS-based technologies for single-cell metabolite analysis are summarized including electrospray ionization mass spectrometry, laser desorption/ionization mass spectrometry, secondary ion mass spectrometry, and mass cytometry. Their typical applications in cellular heterogeneity , tumor microenvironment, reproductive development, and neuroscience fields are also summed up, and current limitations and future development directions are discussed. • Mass spectrometry (MS) is becoming a highly promising tool for single-cell analysis. • Recent advances in MS-based technologies for single-cell metabolite analysis are overviewed. • Typical applications of single-cell metabolite analysis are summarized. • Limitations and future development trends on single-cell analysis are discussed.