Microchip-based single-cell functional proteomics for biomedical applications.

Cellular heterogeneity has been widely recognized but only recently have single cell tools become available that allow characterizing heterogeneity at the genomic and proteomic levels. We review the technological advances in microchip-based toolkits for single-cell functional proteomics. Each of these tools has distinct advantages and limitations, and a few have advanced toward being applied to address biological or clinical problems that traditional population-based methods fail to address. High-throughput single-cell proteomic assays generate high-dimensional data sets that contain new information and thus require developing new analytical frameworks to extract new biology. In this review article, we highlight a few biological and clinical applications in which microchip-based single-cell proteomic tools provide unique advantages. The examples include resolving functional heterogeneity and dynamics of immune cells, dissecting cell-cell interaction by creating a well-controlled on-chip microenvironment, capturing high-resolution snapshots of immune system functions in patients for better immunotherapy and elucidating phosphoprotein signaling networks in cancer cells for guiding effective molecularly targeted therapies.