A critical review of microfluidic electroporation for therapeutic cell engineering

Microfluidic electroporation (MFEP) is emerging as a scalable, non-viral modality for engineering therapeutic cells. This review synthesizes recent progress in MFEP, outlining the key advantages of MFEP, including continuous processing at high throughputs, single-cell manipulation and monitoring, electrolysis mitigation, and automation for rapid multi-parameter screening and minimized cell manufacturing complexity. We then survey the waveforms, pulses, and buffers used in MFEP. In doing so, we highlight the diversity of parameters and uncover the inconsistent reporting of outcomes, calling for standardized reporting of electric-field dose, yield, and efficiency. We additionally note the need for investigation into the effects of MFEP on the long-term perturbation of cells given the effects of bulk electroporation compared to other transfection methods. Finally, we conclude that MFEP has many advantages for cell engineering yet must continue to adopt greater validation of short- and long-term efficiency and effects on cells to accelerate clinical adoption.