Fast Single-Cell Patterning for Study of Drug-Induced Phenotypic Alterations of HeLa Cells Using Time-of-Flight Secondary Ion Mass Spectrometry.

A facile single-cell patterning (ScP) method was developed and integrated with time-of-flight secondary ion mass spectrometry (TOF-SIMS) for the study of drug-induced cellular phenotypic alterations. Micropatterned poly(dimethylsiloxane) (PDMS) stencil film and centrifugation-assisted cell trapping were combined for the preparation of on-surface single-cell microarrays, which exhibited both high site occupancy (>90%) and single-cell resolution (>97%). TOF-SIMS is a surface-sensitive mass spectrometry and is increasingly utilized in biological studies. Here we demonstrated, for the first time, its successful application in high-throughput single-cell analysis. Drug-induced phenotypic alterations of HeLa cells in the early stage of apoptosis were investigated using TOF-SIMS. The major molecular sources of variations were analyzed by principle component analysis (PCA).