Microfluidic impedance cytometry for single-cell sensing: Review on electrode configurations

Single-cell analysis has gained considerable attention for disease diagnosis, drug screening, and differentiation monitoring. Compared to the well-established flow cytometry, which uses fluorescent-labeled antibodies, microfluidic impedance cytometry (MIC) offers a simple, label-free, and noninvasive method for counting, classifying, and monitoring cells. Superior features including a small footprint, low reagent consumption, and ease of use have also been reported. The MIC device detects changes in the impedance signal caused by cells passing through the sensing/electric field zone, which can extract information regarding the size, shape, and dielectric properties of these cells. According to recent studies, electrode configuration has a remarkable effect on detection accuracy, sensitivity, and throughput. With the improvement in microfabrication technology, various electrode configurations have been reported for improving detection accuracy and throughput. However, the various electrode configurations of MIC devices have not been reviewed. In this review, the theoretical background of the impedance technique for single-cell analysis is introduced. Then, two-dimensional, three-dimensional, and liquid electrode configurations are discussed separately; their sensing mechanisms, fabrication processes, advantages, disadvantages, and applications are also described in detail. Finally, the current limitations and future perspectives of these electrode configurations are summarized. The main aim of this review is to offer a guide for researchers on the ongoing advancement in electrode configuration designs.