Acoustofluidic-mediated molecular delivery to human T cells for improved immunotherapies

Cell-based immunotherapies, such as CAR-T therapy, have recently demonstrated significant efficacy for treatment of blood cancers and other diseases. However, current methods of cell loading and processing for these therapies are time-consuming, expensive, and inefficient, which limits patient access and safety of this potentially life-saving therapy. To address these limitations, we are developing a novel 3-D-printed acoustofluidic system which integrates ultrasound (5 MHz) and a flow chamber to consistently induce molecular delivery to cells as they pass through the system sequentially. We conducted experimental studies to evaluate the efficiency of molecular delivery to human Jurkat T cells using the acoustofluidic system in combination with ultrasound contrast agents. Intracellular delivery of a fluorescent compound, calcein, was measured via flow cytometry. Acoustofluidic treatment significantly enhanced calcein delivery to Jurkat T cells by 51 ± 27% compared to untreated control groups without ultrasound exposure (p = 0.005). Cell viability, as measured with propidium iodide staining, was not compromised by acoustofluidic treatment (93 ± 5% viability). Our experiments revealed enhanced delivery of calcein to human T cells while maintaining cell viability. Further development of this platform technology may lead to improved cell loading and processing methods for cell-based immunotherapies or other applications.