Rapid, label-free enrichment of lymphocytes in a closed system using a flow-through microfluidic device.

Autor: Mukhamedshin A; Department of Biomedical Engineering University of Houston Houston Texas USA., Reddington RC; Halcyon Biomedical, Incorporated Friendswood Texas USA., Dinh MTP; Department of Biomedical Engineering University of Houston Houston Texas USA., Abhishek K; Department of Biomedical Engineering University of Houston Houston Texas USA., Iqbal M; Department of Biomedical Engineering University of Houston Houston Texas USA., Manheim M; Halcyon Biomedical, Incorporated Friendswood Texas USA., Gifford SC; Halcyon Biomedical, Incorporated Friendswood Texas USA., Shevkoplyas SS; Department of Biomedical Engineering University of Houston Houston Texas USA.
Jazyk: angličtina
Zdroj: Bioengineering & translational medicine [Bioeng Transl Med] 2023 Sep 25; Vol. 9 (1), pp. e10602. Date of Electronic Publication: 2023 Sep 25 (Print Publication: 2024).
DOI: 10.1002/btm2.10602
Abstrakt: The majority of adoptive cellular therapies are produced from peripheral mononuclear cells obtained via leukapheresis and further enriched for the cells of interest (e.g., T cells). Here, we present a first-of-its-kind closed system, which effectively removes ~85% of monocytes and ~88% of platelets, while recovering ~88% of concentrated T cells in a separate output stream, as the leukapheresis sample flows through a microfluidic device at 5 mL/min. The system is driven by a common peristaltic pump, enabled by a novel pressure wave dampener, and operates in a closed bag-to-bag configuration, without requiring any specialized, dedicated equipment. When compared to standard density gradient centrifugation on paired samples, the new system demonstrated a 1.5-fold increase in T cell recovery and a 2-fold reduction in inter-sample variability for this separation outcome. The T cell-to-monocyte ratio of the leukapheresis sample was increased to 20:1, whereas with density gradient processing it decreased to 2:1. As a result of superior purity and/or gentler processing, T cells enriched by the system showed a 2.7-times higher fold expansion during subsequent culture, and an overall 3.5-times higher cumulative yield. This centrifugation-free and label-free closed system for enriching lymphocytes could significantly simplify and standardize the manufacturing of life-saving cellular therapies.
Competing Interests: Sean C. Gifford and Sergey S. Shevkoplyas are inventors of U.S. Patent #9,789,235 ‘Separation and concentration of particles’ describing the ‘controlled incremental filtration’ technology, and are co‐founders of Halcyon Biomedical, Incorporated, a company that would benefit from its commercialization. Riley C. Reddington and Marc Manheim are employees of Halcyon Biomedical, Incorporated. SSS has received research funding from Halcyon Biomedical, Incorporated. Anton Mukhamedshin, Mai T. P. Dinh, Kumar Abhishek, and Mubasher Iqbal declare no competing interests.
(© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)
Databáze: MEDLINE
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