Personalized gene-modified cell immunotherapies exist, but manufacturing has yet to be optimized to increase the broad availability of these life-saving therapies to patients in need. This proposal is focused on meeting this need with the continued development of microfluidic vortex shedding (μVS), a safe and rapid approach to genetically modify patient-derived immune cells. The long term objective of this proposal is to integrate μVS into the manufacturing workflow of cell-based cancer immunotherapies. The goal of this contract proposal to demonstrate the feasibility of μVS technology in generating representative Chimeric Antigen Receptor T cells (CAR-T) and T Cell Receptor T cells (TCR-T) cells. The research and development objectives are to: (1) demonstrate the technical performance of μVS transfection of primary T cells with clinically relevant CAR and TCR constructs, and (2) demonstrate the functionality and safety of transfected T cells generated by μVS in cell based assays. Pending the successful completion of these objectives, CAR-T and TCR-T cells will be engineered using patient-derived T cells, and commercial-scale processing and enrichment of sufficient genetically modified viable cells for clinical applications will be demonstrated.