T-Probe: An Integrated Microscale Device for Online In Situ Single Cell Analysis and Metabolic Profiling Using Mass Spectrometry

The exploration of single cells reveals cell heterogeneity and biological principle of cellular metabolism. Although a number of mass spectrometry (MS) based single cell MS (SCMS) techniques have been dedicatedly developed with high efficiency and sen-sitivity, limitations still exist. In this work, we introduced a microscale multifunctional device, the T-probe, which integrates cellu-lar contents extraction and immediate ionization, to implement online in situ SCMS analysis at ambient conditions with minimal sample preparation. With high sensitivity and reproducibility, the T-probe was employed for MS analysis of single HeLa cells un-der control and anticancer drug treatment conditions. Intracellular species and xenobiotic metabolites were detected, and changes of cellular metabolic profiles induced by drug treatment were measured. Combining SCMS experiments with statistical data anal-yses, including Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) and two-sample t-test, we provided biolo...