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.
Keywords: Single cell; bioanalysis; fluorescence; optical sensing; secretion; surface plasmon resonance; surface-enhanced Raman scattering.