Ultra-low extracorporeal volume microfluidic leukapheresis is safe and effective in a rat model

Mubasher Iqbal, Alexandra L. McLennan, Anton Mukhamedshin, Mai T. P. Dinh, Qisheng Liu, Jacob J. Junco, Arvind Mohan, Poyyapakkam R. Srivaths, Karen R. Rabin, Thomas P. Fogarty, Sean C. Gifford, Sergey S. Shevkoplyas () and Fong W. Lam ()
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Mubasher Iqbal: Department of Biomedical Engineering; University of Houston
Alexandra L. McLennan: Department of Pediatrics; Baylor College of Medicine
Anton Mukhamedshin: Department of Biomedical Engineering; University of Houston
Mai T. P. Dinh: Department of Biomedical Engineering; University of Houston
Qisheng Liu: Center for Translational Research on Inflammatory Diseases; Michael E. DeBakey Veterans Affairs Medical Center
Jacob J. Junco: Department of Pediatrics; Baylor College of Medicine
Arvind Mohan: Department of Pediatrics; Baylor College of Medicine
Poyyapakkam R. Srivaths: Department of Pediatrics; Baylor College of Medicine
Karen R. Rabin: Department of Pediatrics; Baylor College of Medicine
Thomas P. Fogarty: Department of Pediatrics; Baylor College of Medicine
Sean C. Gifford: Halcyon Biomedical Incorporated
Sergey S. Shevkoplyas: Department of Biomedical Engineering; University of Houston
Fong W. Lam: Department of Pediatrics; Baylor College of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Leukapheresis is a potentially life-saving therapy for children with symptomatic hyperleukocytosis. However, the standard centrifugation-based approach exposes pediatric patients to significant complications due to its large extracorporeal volume, high flow rates, and considerable platelet loss. Here, we tested whether performing cell separation with a high-throughput microfluidic technology could alleviate these limitations. In vitro, our microfluidic devices removed ~85% of large leukocytes and ~90% of spiked leukemic blasts from undiluted human whole blood, while minimizing platelet losses. Multiplexed devices connected in parallel allowed for faster, clinically relevant flow rates in vitro with no difference in leukocyte collection efficiency. When connected to Sprague-Dawley rats, the devices removed large leukocytes with ~80% collection efficiency, reducing the leukocyte count in recirculating blood by nearly half after a 3-hour procedure. Evaluation of plasma biomarkers and end-organ histology revealed no adverse effects compared to sham control. Overall, our study suggests that microfluidics-based leukapheresis is safe and effective at selectively removing leukocytes from circulation, with separation performance sufficiently high to ultimately enable low extracorporeal volume leukapheresis in children.

Date: 2025
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DOI: 10.1038/s41467-025-57003-5

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