Creation of a High‐Throughput Microfluidic Platform for Single‐Cell Transcriptome Sequencing of Cell‐Cell Interactions

Abstract Cell‐cell interaction is one of the major modalities for transmitting information between cells and activating the effects of functional cells. However, the construction of high‐throughput analysis technologies from cell omics focusing on the impact of interactions of functional cells on targets has been relatively unexplored. Here, they propose a droplet‐based microfluidic platform for cell‐cell interaction sequencing (c‐c‐seq) and screening in vitro to address this challenge. A class of interacting cells is pre‐labeled using cell molecular tags, and additional single‐cell sequencing reagents are introduced to quickly form functional droplet mixes. Lastly, gene expression analysis is used to deduce the impact of the interaction, while molecular sequence tracing identifies the type of interaction. Research into the active effect between antigen‐presenting cells and T cells, one of the most common cell‐to‐cell interactions, is crucial for the advancement of cancer therapy, particularly T cell receptor‐engineered T cell therapy. As it allows for high throughput, this platform is superior to well plates as a research platform for cell‐to‐cell interactions. When combined with the next generation of sequencing, the platform may be able to more accurately evaluate interactions between epitopes and receptors and verify their functional relevance.