Chemical tagging mass spectrometry: an approach for single-cell omics

Single-cell (SC) analysis offers new insights into the study of fundamental biological phenomena and cellular heterogeneity. The superior sensitivity, high throughput, and rich chemical information provided by mass spectrometry (MS) allow MS to emerge as a leading technology for molecular profiling of SC omics, including the SC metabolome, lipidome, and proteome. However, issues such as ionization suppression, low concentration, and huge span of dynamic concentrations of SC components lead to poor MS response for certain types of molecules. It is noted that chemical tagging/derivatization has been adopted in SCMS analysis, and this strategy has been proven an effective solution to circumvent these issues in SCMS analysis. Herein, we review the basic principle and general strategies of chemical tagging/derivatization in SCMS analysis, along with recent applications of chemical derivatization to single-cell metabolomics and multiplexed proteomics, as well as SCMS imaging. Furthermore, the challenges and opportunities for the improvement of chemical derivatization strategies in SCMS analysis are discussed.