{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:31:31Z","timestamp":1793363491891,"version":"4.5.0"},"posted":{"date-parts":[[2026,7,31]]},"group-title":"Bioengineering","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH","award":["K25HL169816"],"award-info":[{"award-number":["K25HL169816"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Treatment with chimeric antigen receptor (CAR) T cells has emerged as a promising immune therapy for relapsed and refractory hematologic malignancies. The CAR T cells are manufactured in a series of steps that involve isolating T cells from the patient\u2019s leukapheresis product, genetically modifying them to express the CAR against the target antigen, and reinfusing them into the patient. Efficient T-cell enrichment from leukapheresis products is critical to the success of these therapies. Current methods for T-cell sorting on a clinical scale involve several washing steps to remove red blood cells and platelets, followed by T-cell selection and activation. These multi-step processes result in cell loss during processing and involve several handling steps. Here, we utilize fluidically assembled micromagnetic lenses to develop a high-throughput, continuous-flow microfluidic T-cell sorter, designated as the T-Chip, for sorting magnetic bead-labeled CD3\n                  <jats:sup>+<\/jats:sup>\n                  T cells in a single step. Our approach allows direct sorting of T cells in expansion media from leukopaks without any washing steps, effectively removing 99.999% of RBCs and platelets from the leukapheresis product. A single 1-inch x 3-inch T-Chip can process leukapheresis product at a throughput of 60 mL\/hr and 2.56 \u00b1 0.12 billion cells\/hr. Using this optimized workflow, we demonstrate clinical-scale enrichment of highly pure CD3\n                  <jats:sup>+<\/jats:sup>\n                  T cells (97.7 \u00b1 1.3%) with high viability (97.0 \u00b1 1.1%) and recovery (87.3 \u00b1 14.8%) in a functionally closed manner. Downstream processing of T cells isolated using the T-Chip yielded potent anti-mesothelin CAR T cells with demonstrated anti-tumor efficacy. Overall, by exploiting precisely engineered magnetic forces and laminar flow, the microfluidic T-Chip overcomes bottlenecks caused by low throughput and enables single-step large-scale T-cell purification for the rapid development of CAR T cells.\n                <\/jats:p>","DOI":"10.64898\/2026.07.30.741793","type":"posted-content","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:55:28Z","timestamp":1785491728000},"source":"Crossref","is-referenced-by-count":1,"title":["Microfluidic T-Chip enables one-step clinical-scale T-cell purification from blood products for CAR T-cell manufacturing"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9954-3205","authenticated-orcid":false,"given":"Maheen","family":"Rana","sequence":"first","affiliation":[{"name":"Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Charlestown, MA 02129, USA"},{"name":"Krantz Family Center for Cancer Research, Massachusetts 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