Cell pairing for biological analysis in microfluidic devices

Cell pairing at the single-cell level usually allows a few cells to contact or seal in a single chamber and provides high-resolution imaging. It is pivotal for biological research, including understanding basic cell functions, creating cancer treatment technologies, developing drugs, and more. Laboratory chips based on microfluidics have been widely used to trap, immobilize, and analyze cells due to their high efficiency, high throughput, and good biocompatibility properties. Cell pairing technology in microfluidic devices provides spatiotemporal research on cellular interactions and a highly controlled approach for cell heterogeneity studies. In the last few decades, many researchers have emphasized cell pairing research based on microfluidics. They designed various microfluidic device structures for different biological applications. Herein, we describe the current physical methods of microfluidic devices to trap cell pairs. We emphatically summarize the practical applications of cell pairing in microfluidic devices, including cell fusion, cell immunity, gap junction intercellular communication, cell co-culture, and other applications. Finally, we review the advances and existing challenges of the presented devices and then discuss the possible development directions to promote medical and biological research.