Cellular heterogeneity is of significance in cell-based assays for life science, biomedicine and clinical diagnostics. Electrical impedance sensing technology has become a powerful tool, allowing for rapid, non-invasive, and label-free acquisition of electrical parameters of single cells. These electrical parameters, i.e., equivalent cell resistance, membrane capacitance and cytoplasm conductivity, are closely related to cellular biophysical properties and dynamic activities, such as size, morphology, membrane intactness, growth state, and proliferation. This review summarizes basic principles, analytical models and design concepts of single-cell impedance sensing devices, including impedance flow cytometry (IFC) to detect flow-through single cells and electrical impedance spectroscopy (EIS) to monitor immobilized single cells. Then, recent advances of both electrical impedance sensing systems applied in cell recognition, cell counting, viability detection, phenotypic assay, cell screening, and other cell detection are presented. Finally, prospects of impedance sensing technology in single-cell analysis are discussed.

High‐resolution microscopic imaging may cause intensive image processing and potential impact of light irradiation on yeast replicative lifespan (RLS). Electrical impedance spectroscopy (EIS) could be alternatively used to perform high‐throughput and label‐free yeast RLS assays. Prior to fabricating EIS‐integrated microfluidic devices for yeast RLS determination, systematic modeling and theoretical investigation are crucial for device design and optimization. Here, we report three‐dimensional (3D) finite‐element modeling and simulations of EIS measurement in a microfluidic single yeast in situ impedance array (SYIIA), which is designed by patterning an electrode matrix underneath a cell‐trapping array. SYIIA was instantiated and modeled as a 5 × 5 sensing array comprising 25 units for cell immobilization, culturing, and time‐lapse EIS recording. Simulations of yeast growing and budding in a sensing unit demonstrated that EIS signals enable the characterization of cell growth and daughter‐cell dissections. In the 5 × 5 sensing array, simulation results indicated that when monitoring a target cell, daughter dissections in its surrounding traps may induce variations of the recorded EIS signals, which could cause mistakes in identifying target daughter‐cell dissections. To eliminate the mis‐identifications, electrode array pitch was optimized. Therefore, the results could conduct the design and optimization of microfluidic electrode‐array‐integrated devices for high‐throughput and accurate yeast RLS assays.

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