Graphene-Based Confocal Refractive Index Microscopy for Label-Free Differentiation of Living Epithelial and Mesenchymal Cells

Label-free imaging and investigation of living cells are significant for many biomedical studies. It has been challenging to detect the epithelial-mesenchymal transition of cells in situ without affecting cellular activity. Here, we present a common-path differential confocal microscope based on the polarization-sensitive absorption of graphene to realize high-performance refractive index imaging and differentiation of living colorectal cancer cells (HCT116) with large detecting depth (1.29 mu m), excellent refractive index resolution (2.86 X 10(-5) RIU), and high spatial resolution (727 nm) simultaneously. Compared with epithelial (parental HCT116) cells, mesenchymal (paclitaxel-resistant HCT116) cells manifest generally lower refractive index values through the refractive index statistics, which is due to the stronger migration ability and weaker surface adherence of mesenchymal cells. The graphene-based microscopy provides an effective label-free approach to high-resolution imaging and study of living cell kinetics, and we expect it to be widely used in the research fields of pathology, tumorigenesis, and chemotherapy.