Mass cytometry is attracting significant attention for its spatiotemporal high-throughput single-cell analysis. As the first demonstration of 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 cell heterogeneous information. A series of mass probes with online-dissociated mass tags were developed, ensuring the semi-quantification of cell surface proteins and compatibility of endogenous metabolite detection at 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 its applications in distinguishing rare cell phenotypes. As a new generation of mass cytometry, the proposed system is simple, extensible, and promising for cell typing, drug-resistance analysis of tumor cells, and clinical diagnosis and therapy at single-cell level.
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