Multi‐Dimensional Organic Mass Cytometry: Simultaneous Analysis of Proteins and Metabolites on Single Cells

Abstract Mass cytometry is attracting significant attention for enabling spatiotemporal high‐throughput single‐cell analysis. As the first demonstration of the simultaneous detection of single‐cell proteins and untargeted metabolites, a multi‐dimensional organic mass‐cytometry system was established by a simple microfluidic chip connected to a nanoelectrospray mass spectrometer, providing useful heterogeneous information about the cells. A series of mass probes with online‐dissociated mass tags were developed, ensuring the semi‐quantification of cell‐surface proteins and the compatibility of endogenous metabolite detection at the single‐cell level. Six cell surface antigens and ≈100 metabolites from three ovarian‐cancer cell types and two breast‐cancer cell types were successfully monitored and contributed to highly sensitive and specific cell typing. Doxorubicin‐resistant cancer‐cell analysis confirmed the applications in distinguishing rare cell phenotypes. The proposed system is simple, extensible, and promising for cell typing, drug‐resistance analysis of tumor cells, and clinical diagnosis and therapy at the single‐cell level.