Optical Sensing Strategies for Probing Single-Cell Secretion

Abstract

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.

Advances in self-assembled Au-DNA nanomachines

“… 79 The output signals of optical sensors are mainly composed of fluorescence, SPR, SERS, and other modalities. 80 In particular, fluorescence-based methods are one of the most sensitive biosensing strategies. Together with the progressive development of DNA nanomachines, fluorescence-based Au-DNA nanomachines have become one of the most popular nanomachines.…”

Integration of 2D Nanoporous Membranes in Microfluidic Devices

“…Automation is inherent in microfluidic systems, overcoming the limitations posed by manual handling in microscopic setups . The majority of microfluidic systems are amenable to high-quality optical and electrical investigation in situ, offering real-time and simultaneous measurement, which is impractical in diffusion cells. − The integration can extend to biochemical assays, facilitating a cohesive platform for applications too.…”

Optical Technologies for Single-Cell Analysis on Microchips

“…As three of the most common detection methods, optical, electrochemical, and mass spectrometric techniques have been widely applied for cell analysis and integrated with microfluidic systems [26][27][28][29]. Significantly, optical methods are hugely popular for single-cell analysis because of their ability to directly visualize the response process in cells using super-resolution microscopy, as well as to realize single-cell analysis in a label-free manner [30,31].…”