Advances in single-cell electrochemical analysis: From micro-nano electrodes to nanoscale sensing

Single-cell is important target in bioelectrochemical analysis because essential life processes, such as the production, storage, and secretion of neurotransmitters and other key biomolecules, occur at the cellular and subcellular levels. Owing to the small cell volume, low intracellular analyte concentrations, rapid reaction kinetics, and the inherent fragility of living cells, efficient single-cell detection requires analytical techniques with high sensitivity, high spatiotemporal resolution, and minimal invasiveness. As an emerging approach, single-cell electrochemical analysis offers unique advantages in probing cellular heterogeneity and dynamic biological processes due to its excellent sensitivity and real-time monitoring capability. This review systematically summarizes recent advances in electrode based single-cell electrochemical analysis, with a focus on micro-nanoelectrode technologies, nanocapillaries, nanopores, nanopipette probes, and nanoscale electrochemical sensing platforms. Key fabrication strategies, including laser pulling, etching methods, and chemical vapor deposition, are discussed. In addition, representative applications of these techniques in the analysis of nucleic acids, neurotransmitters, and reactive oxygen and nitrogen species are reviewed. However, challenges remain in areas such as micro-nanofabrication technologies and multi-analyte detection. • Micro-nano electrodes, microscopic imaging, and nanopore technologies support single-cell electrochemical analysis. • Research progress of single-cell electrochemical analysis methods in detecting intracellular biomolecules. • Challenges and prospects of single-cell electrochemical analysis in biomedical applications are discussed.