{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T12:17:47Z","timestamp":1783772267847,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,8]]},"group-title":"Bioengineering","reference-count":22,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH\/NCI"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Adoptive T-cell therapies rely on the identification and expansion of rare tumor-reactive T cells, yet current enrichment strategies are limited by the low abundance of these cells and complexity of their functional enrichment. Here, we present a microfluidic platform that exploits hydrodynamic shear as a controllable parameter for enriching antigen-specific T cells through peptide-major histocompatibility complex (pMHC)-mediated capture. An eight-channel microfluidic device was engineered to simultaneously interrogate a range of wall shear stresses while maintaining uniform cell delivery, enabling systematic identification of shear conditions that maximize antigen-specific enrichment. Using engineered MART-1-specific Jurkat cells, we demonstrate that T-cell capture is jointly regulated by wall shear stress and pMHC density, with intermediate shear preferentially enriching antigen-specific cells over nonspecific binders. Translation of the optimal operating condition to a high-throughput single-shear device enabled approximately 35-fold enrichment of antigen-specific T cells from peripheral blood mononuclear cells containing only 0.05% target cells. We further show that peptide-MHC complexes isolated directly from melanoma whole-cell lysates support shear-dependent enrichment comparable to recombinant pMHCs. Finally, primary MART-1-specific CD8\u207a T cells enriched using tumor-derived pMHCs retained the ability to recognize melanoma cells and upregulated the activation marker CD137 following antigen-specific stimulation. Together, these findings establish hydrodynamic shear as an orthogonal parameter for antigen-specific T-cell enrichment and provide a framework for integrating force-based selection with tumor-derived pMHCs to isolate functional antigen-specific T cells using tumor-derived pMHCs.<\/jats:p>","DOI":"10.64898\/2026.07.08.737133","type":"posted-content","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:40:23Z","timestamp":1783532423000},"source":"Crossref","is-referenced-by-count":0,"title":["Hydrodynamic shear enables enrichment of functional tumor antigen-reactive T cells"],"prefix":"10.64898","author":[{"given":"Prem S.","family":"Subramanian","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Davis, Davis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Davis, Davis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layla C.","family":"Semaan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Davis, Davis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asfa S.","family":"Sher","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Davis, Davis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhupinder S.","family":"Shergill","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Davis, Davis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2263-1914","authenticated-orcid":false,"given":"Steven C.","family":"George","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Davis, Davis, USA"},{"name":"Department of Surgery, University of California, Davis, Davis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4430-2612","authenticated-orcid":false,"given":"Venktesh S.","family":"Shirure","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California, Davis, Davis, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071105050625000_2026.07.08.737133v1.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1076514"},{"key":"2026071105050625000_2026.07.08.737133v1.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa4967"},{"key":"2026071105050625000_2026.07.08.737133v1.3","doi-asserted-by":"crossref","first-page":"4004","DOI":"10.1158\/1078-0432.CCR-25-0880","article-title":"FDA Approval Summary: Lifileucel for Unresectable or Metastatic Melanoma Previously Treated with an Anti-PD-1-Based Immunotherapy Clin","volume":"31","year":"2025","journal-title":"Cancer Res. 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