Abstract

Lab on a Particle Technology for Functional Discovery of Rare and Unconventional T-Cell Receptors

Dino Di Carlo, Armond and Elena Hairapetian Chair in Engineering and Medicine, Professor and Vice Chair of Bioengineering, University of California Los Angeles

Lab on a particle technologies are emerging as a rapidly adopted platform for performing single-cell functional screening leveraging standard instrumentation, such as flow cytometers and microfluidic single-cell sequencing platforms. Each cell and its secreted products can be analyzed and sorted using widely available fluorescence activating cell sorters operating at up to a 1000 cells per second, promising to democratize single-cell technologies. The platform enables sorting cells based on secreted products for the discovery of antibodies, the development of cell lines producing recombinant products, and the selection of functional cells for cell therapies. Here, I will describe our progress in using nanovial particles for the characterization and discovery of antigen-specific and metabolite-specific T cells. Nanovials enable selective binding, functional characterization of secretion of cytokines and other effector molecules, and sorting of T cells for downstream T-cell receptor sequencing and functional annotation. We apply oligo barcoding technology to both multiplex target antigens and functional performance and link this to the TCR sequence information. Nanovials can enable more rapid discovery of cancer-specific TCRs and TCRs against metabolites presented by unconventional MHC-like molecules, with high accuracy, promising to transform the discovery of critical recognition elements for improved T cell therapies.