Single-Cell Behavioral Assays For Heterogeneity Studies

Cell heterogeneity is an emerging challenge in cell biology and cancer therapies. Each cell in heterogeneous populations has its own unique behavior, and thus responds differently to the same reagent or drug, making analysis or treatment difficult and complicated. Therefore, it is important to understand the heterogeneity characteristics of cells in phenotypic behavior assays. Although conventional fluorescence-activated cell sorting can separate cells based on markers, most assays simply present the average behavior in a batch of cells sorted by markers. It is important to have a capability to fully characterize individual cell behaviors in a miniaturized, high-throughput platform, distinguishing their heterogeneity and tracking their responses over time. This chapter introduces the technological innovations enabling these assays and the associated biological experiments, including (1) single-cell isolation and tracking schemes to investigate the cell proliferation, cell differentiation and lineage, (2) cell migration platforms to measure cell motility, deformation, and invasiveness, and (3) cell-cell interaction platforms to study the alteration of cell behaviors caused by reciprocal interactions among cells.