Innovative Tools and Technology for Analysis of Single Cells and Cell-Cell Interaction.

Heterogeneity in single-cell responses and intercellular interactions results from complex regulation of cell-intrinsic and environmental factors. Single-cell analysis allows not only detection of individual cellular characteristics but also correlation of genetic content with phenotypic traits in the same cell. Technological advances in micro- and nanofabrication have benefited single-cell analysis by allowing precise control of the localized microenvironment, cell manipulation, and sensitive detection capabilities. Additionally, microscale techniques permit rapid, high-throughput, multiparametric screening that has become essential for -omics research. This review highlights innovative applications of microscale platforms in genetic, proteomic, and metabolic detection in single cells; cell sorting strategies; and heterotypic cell-cell interaction. We discuss key design aspects of single-cell localization and isolation in microfluidic systems, dynamic and endpoint analyses, and approaches that integrate highly multiplexed detection of various intracellular species.