Microfluidics-Enabled High-Throughput Screening of Plasma Cells for Therapeutic Antibody Development
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Conventional antibody discovery methods such as hybridoma and phage display are limited by low throughput and labor-intensive workflows. In contrast, single-cell approaches offer faster access to naturally paired heavy- and light-chain sequences, which are essential for developability and safety. Among antibody-secreting cells, plasma cells are particularly valuable due to their high affinity and advanced maturation, but efficient, antigen-specific enrichment remains technically challenging. Here we present a scalable, microfluidics-based platform for high-throughput discovery of plasma cell–derived antibodies, integrated with parallelized expression and epitope binning analysis. This system enables enrichment of 1–2 million plasma cells in one day, recovery of hundreds to thousands of unique antibody sequences within a week, and functional validation—including specificity and epitope classification—within three to four weeks. Applying this platform, we rapidly identified PD-1-targeting antibodies with distinct biological activities, including both blockers and agonists. Our integrated workflow accelerates the identification of diverse, functional antibodies and is broadly applicable to a wide range of targets and therapeutic mechanisms, providing a robust foundation for next-generation antibody discovery and development.
