Methods developments of mass spectrometry based single cell metabolomics

Metabolomics at the single-cell level is of great importance to reveal phenotypic heterogeneity and contribute to disease precision diagnosis. Owing to small sample volume, trace analytes and diverse metabolite species, single-cell metabolomics puts forward high demand for analysis technology and methodology. Mass spectrometry (MS), which combines the advantages of high sensitivity, high throughput and fast analysis speed, has made great progress in single-cell metabolomics during the past decades. In this review, developments of MS-based single-cell metabolomics are categorized and summarized according to different ionization methods. Key parameters such as cell throughput, metabolite coverage and imaging capability are systematically introduced. Finally, challenges and perspectives of MS-based single-cell metabolomics are proposed for further development of techniques, data integration and biological applications. • The overview of single cell metabolomics from the insight of mass spectrometric ionization techniques and their applications. • The summary of the development of different ionization methods for single cell analysis. • The challenges and perspectives of mass spectrometry based single cell metabolomics.