The intracellular delivery of macromolecules is a critical process in cell transfection, gene therapy, and cell-based therapeutics. However, existing microfluidics-based mechanoporation strategies are generally limited by the need to redesign device architectures for specific cell types and sizes, making it difficult to accommodate cellular heterogeneity while maintaining high-throughput operation and thereby limiting the translational potential of these architectures. In this work, we present a zero-net mass-flux (ZNMF) jet-based microfluidic delivery platform driven by electromagnetic actuation, in which periodic suction and expulsion through an orifice yield ZNMF over each actuation cycle while imparting momentum to the surrounding fluid. The oscillation of a magnetic composite membrane generates highly controllable microjets within a microchamber that transiently deform the cell membrane, producing short-lived permeable openings that enable the efficient delivery of macromolecules (4 kDa fluorescein isothiocyanate-dextran). Unlike conventional cell squeezing, this approach does not rely on precise dimensional matching between cells and microchannel constrictions, requires no sheath flow assistance, and exhibits high adaptability, high tunability, and reduced clogging risk. In experiments, we achieved efficient delivery across multiple cell types, including HL-60, MS1, and β-TC-6 cells. Under optimized operating conditions (main-channel flow rate of 10 μl/min, excitation frequency of 88.5 Hz, and current of 2.5 A), HL-60 cells exhibited a delivery efficiency of approximately 43% while maintaining a viability above 85%. Notably, effective delivery and high viability were preserved even when the cell diameter differed by more than 40%. Numerical simulations further revealed that the device can instantaneously amplify the dominant elastic stress by more than fourfold within the jet region, thus establishing a highly localized mechanical environment that facilitates transient membrane permeabilization.
Xu et al. (Sun,) studied this question.