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

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.