Microfluidics-Enabled High-Throughput Screening of Plasma Cells for Therapeutic Antibody Development

Microfluidics-Enabled High-Throughput Screening of Plasma Cells for Therapeutic Antibody Development | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Microfluidics-Enabled High-Throughput Screening of Plasma Cells for Therapeutic Antibody Development Haisong Lu, Meng Yu, Liang Wang, Yan Yang, Su Liang, Yiyang Ge, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6702892/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract 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. Biological sciences/Biological techniques/Immunological techniques/Antibody generation Biological sciences/Biological techniques/Immunological techniques/Antibody generation Biological sciences/Biological techniques/Immunological techniques/Antibody generation Biological sciences/Biotechnology/Applied immunology Biological sciences/Biotechnology/Applied immunology single-cell plasma cells micro uidic high-throughput Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6702892","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":460461918,"identity":"b4d83694-d86a-4127-9081-e09ddd3cc6b7","order_by":0,"name":"Haisong 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