University of California, Los Angeles, California, United States
Abstract: Lab on a particle technologies, such as nanovials, are emerging as an accessible 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 nanovial 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. I will describe our progress in using nanovial particles for discovery of monoclonal antibodies and the characterization and discovery of antigen-specific and metabolite-specific T cells. Nanovials enable selective binding, functional characterization of secretion of antigen-specific antibodies or cytokines and other effector molecules, followed by sorting of plasma B cells, hybridomas, or T cells for downstream sequencing of antibody heavy and light chains or T cell receptor (TCR) alpha and beta chains, with functional annotation. For TCR discovery, we apply oligo barcoding technology to both multiplex target antigens loaded on nanovials as well as label cytokines to link functional performance to the TCR sequence information. Nanovials can enable more rapid discovery of monoclonal antibodies, cancer-specific TCRs, and TCRs against metabolites presented by unconventional MHC-like molecules, with high accuracy, promising to transform the discovery of therapeutic antibodies and critical recognition elements for improved T cell therapies.