Abstract
Intracellular delivery of exogenous biomolecules is crucial in the fields of biology and medicine. However, a significant challenge in intracellular delivery is balancing cell viability with delivery efficiency due to the wide distribution of cell sizes. In this study, we have developed a microfluidic device with viscoelastic fluids to implement highly efficient intracellular delivery and maintain high cell viability after delivery. This method utilizes a micro-constriction array that generates progressive shear forces on the cell membrane via the viscoelastic fluids, facilitating the delivery of exogenous biomolecules into cells. Additionally, the constriction width is greater than the cell diameter to avoid physical squeezing by the device structures, which allows to maintain high cell viability and eliminate channel clogging issue. Without altering the constriction width, we have successfully delivered a wide range of molecule sizes to MDA-MB-231 and Jurkat cells. We have also demonstrated the intracellular delivery of mRNA to Jurkat cells with high efficiency (>99 %), high viability (90 %), and high throughput (500,000 cells/min). This method holds significant potential for applications in biological sciences and medicine.