Optical Sensing Strategies for Probing Single-Cell Secretion

Measuring cell secretion events is crucial to understand the fundamental cell biology that underlies cell–cell communication, migration, proliferation, and differentiation. Although strategies targeting cell populations have provided significant information about live cell secretion, they yield ensemble profiles that obscure intrinsic cell-to-cell variations. Innovation in single-cell analysis has made breakthroughs allowing accurate sensing of a wide variety of secretions and their release dynamics with high spatiotemporal resolution. This perspective focuses on the power of single-cell protocols to revolutionize cell-secretion analysis by allowing real-time and real-space measurements on single live cell resolution. We begin by discussing recent progress on single-cell bioanalytical techniques, specifically optical sensing strategies such as fluorescence-, surface plasmon resonance-, and surface-enhanced Raman scattering-based strategies, capable of in situ real-time monitoring of single-cell released ions, metabolites, proteins, and vesicles. Single-cell sensing platforms which allow for high-throughput high-resolution analysis with enough accuracy are highlighted. Furthermore, we discuss remaining challenges that should be addressed to get a more comprehensive understanding of secretion biology. Finally, future opportunities and potential breakthroughs in secretome analysis that will arise as a result of further development of single-cell sensing approaches are discussed.