Abstract

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.

Highlights

  • The basic theories and modeling methods of single-cell impedance sensing have been re-viewed and recent advances in this field have been highlighted with respect to the device design and applications

  • The way to implement electrical impedance measurement in a microfluidic device is categorized into impedance flow cytometry (IFC) and electrical impedance spectroscopy (EIS) sensing

  • IFC features measuring impedance of single frequencies for large number of cells, while EIS sensing is capable of re-al-time monitoring of a few cells over a wide frequency range

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. To characterize the diverse biophysical properties of single cells, analytical methods integrated with microfluidic devices have been widely expanded, such as spectroscopy [19], fluorometry [20], mass spectroscopy [21] and electrochemical probes [22]. Optical characterization methods, such as optical flow cytometry and laser confocal microscopy, are most widely used to acquire biological information in single-cell resolution [20]. These methods require fluorescent labels in cells to characterize cell and subcellular structures. Due to the advantages mentioned above, electrical impedance integrated microfluidic devices have been widely utilized for cell-based assays in single-cell resolution. Advances and prospects on electrical impedance sensing technology for single-cell analysis are discussed

Theory and Modeling
Electrode Configurations
Different designs
Particle Positioning
Trapping of Suspended Single Cells
Advanced Design to Increase the Throughput of EIS Devices
CMOS-Based Impedance Sensing Devices
IFC to Detect Flowing Single Cells
MHz and 40 MHz
Tumor Cells
MHz andthe distinguished them leukocytes classification accuracy
Plant Cells
Microbes
Cell-based assayusing usingEIS
Conclusions
Findings
Methods
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