Recent Advances and Perspectives in Microfluidics‐Based Single‐Cell Biosensing Techniques

Abstract

Single‐cell analyses of secretory proteins are essential to fully understand cellular functional heterogeneity and unravel the underlying mechanisms of intercellular signaling and interactions. Retrieving dynamic information of protein secretion at single‐cell resolution reflects the precise, real‐time functional states of individual cells in physiological processes. Such measurements remain very challenging in single‐cell analysis, which requires highly integrated systems capable of performing on‐chip single‐cell isolation and subsequent real‐time protein detection. Here, recent advances in microfluidics‐based single‐cell manipulation and emerging approaches for label‐free single‐cell biosensing are reviewed. The advantages and limitations of these technologies are summarized and challenges to establish the integrated microfluidic biosensing systems for real‐time single‐cell secretomics are discussed. Recent efforts on integrated platforms for on‐chip single‐cell protein assays are highlighted and some perspectives on future directions in this field are provided.

Label‐Free Optofluidic Nanobiosensor Enables Real‐Time Analysis of Single‐Cell Cytokine Secretion

“…This will result in concentrated molecular distribution in the vicinity of the sensor surface. In this regard, microfluidics technology offers a powerful tool to create a highly miniaturized environment with compartmentalization for the analysis . Nevertheless, the optical monitoring of an ultralow volume in cell culture conditions (i.e., 37 °C) introduces a significant evaporation problem.…”

A Self‐Digitization Dielectrophoretic (SD‐DEP) Chip for High‐Efficiency Single‐Cell Capture, On‐Demand Compartmentalization, and Downstream Nucleic Acid Analysis

“…Microfluidic devices, tailored to approximately the size of individual cells with designed unique geometries and precise dimensions, confer inherent advantages over conventional technologies in single cell biology . The capability of integrating the multistep procedures of cell manipulation, lysis, and chemical analysis in a portable and enclosed device could reduce reagent consumption, decrease contamination risk, minimize lysate dilution, and increase assay sensitivity, which is critical for assaying low‐abundance biomolecules in single cells such as mRNA .…”

Research progress of single molecule force spectroscopy technology based on atomic force microscopy in polymer materials: Structure, design strategy and probe modification

“…To a certain extent, the elasticity of polysaccharides can be controlled by the conformational transformation of the pyranose ring. [134,135] In particular, the transition will produce an atomic fingerprint in the force-stretch spectrum, whose characteristics depend on the energy conformation of the pyranose cyclic group and the type of glycosidic bond. [136] Through this method, it was found that the molecules contained in agarose and λcarrageenan produced the force spectrum characteristics of α-(1→4) D-glucan when the AFM is stretched, and thus AFM can be used to identify the components of polysaccharide mixtures at the single-molecule level.…”