期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：5
DOI：10.1073/pnas.2110867119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
The study of specific cell–cell interactions at scale would be a significant advancement in single-cell biology with clear utility in immuno-oncology. Our development of Droplet Assembly provides a tool for such studies by extending the benefits of single-cell droplet microfluidics to high-order cell analyses. This technology allows for the construction, sorting, and downstream processing of cell–cell interactions and is compatible with single-cell genomic readouts.
Cell–cell interactions are important to numerous biological systems, including tissue microenvironments, the immune system, and cancer. However, current methods for studying cell combinations and interactions are limited in scalability, allowing just hundreds to thousands of multicell assays per experiment; this limited throughput makes it difficult to characterize interactions at biologically relevant scales. Here, we describe a paradigm in cell interaction profiling that allows accurate grouping of cells and characterization of their interactions for tens to hundreds of thousands of combinations. Our approach leverages high-throughput droplet microfluidics to construct multicellular combinations in a deterministic process that allows inclusion of programmed reagent mixtures and beads. The combination droplets are compatible with common manipulation and measurement techniques, including imaging, barcode-based genomics, and sorting. We demonstrate the approach by using it to enrich for chimeric antigen receptor (CAR)-T cells that activate upon incubation with target cells, a bottleneck in the therapeutic T cell engineering pipeline. The speed and control of our approach should enable valuable cell interaction studies.
