Improving Quality of CAR-T Cell Therapy Starting Material with Automated Microfluidic Cell Sorting

Autologous CAR-T cell therapy has demonstrated remarkable clinical efficacy in hematologic malignancies, yet its broader application remains limited by complex, labor-intensive manufacturing and inconsistent product quality. We describe a novel microfluidic cell separation platform based on Deterministic Lateral Displacement (DLD), integrated into a fully automated, closed-system instrument (Curate System), capable of processing full leukopacks in under one hour. Compared to Ficoll(R)-based density gradient centrifugation, DLD processing yielded significantly higher leukocyte recovery (88% vs. 58%), superior platelet and red blood cell depletion, and reduced CD69 T-cell activation. Flow cytometric analysis revealed improved phenotypic preservation across key T-cell subsets, including naive and central memory populations. Cytokine profiling demonstrated enhanced washing efficiency, with markedly lower levels of biologic response modifiers such as RANTES and TGF-{beta}1. DLD-purified T cells exhibited enhanced expansion kinetics and greater yield, supporting improved manufacturing outcomes. These findings position DLD-based processing as a clinically relevant, scalable alternative to conventional methods, with potential to improve consistency, potency, and accessibility of CAR-T therapies.