Simulation of microfluidic intracellular delivery based on the synergy of cell squeezing and electrical field

In recent years, the microfluidic squeezing method for cell intracellular delivery has demonstrated high efficiency and generalizability. This approach, however, still faces difficulties in effectively transfecting large molecules. Integration of this method with other membrane disruption strategies can enhance intracellular delivery efficiency and cell viability. Notably, the combination of microchannel squeezing and electric fields emerges as the most crucial strategy. The cell membrane is rapidly perforated in a microfluidic device, and then an electric field is introduced to further improve the permeability of the plasma membrane, allowing transmembrane transit of impermeable molecules. Nevertheless, the underlying mechanism of the combined squeezing and electroporation method on cell membrane destabilization and material transport remains unclear. Thus, this paper aims to develop a computational model to investigate the intracellular delivery process influenced by various external stimuli and to examine the implications of mixing external stimuli as well as the distinct effects of electric and squeezing on intracellular delivery. Meanwhile, we modified the squeezing parameters (microchannel size and cell velocity) and the electric field parameters (pulse length, electric field strength, etc.) to optimize the cell’s absorption of foreign substances. The simulation results indicate that a decrease in the contraction width, an increase in the contraction length, and an increase in the average cell velocity could promote the squeezing deformation of the cell as well as the formation of pores on the cell membrane. And the joint action of cell squeezing and electric field enhances cellular absorption of substances. In addition, the change of electrical parameters also affects the results of cell squeezing in conjunction with the electric field. For example, the increased length of electric field pulses improves the cell membrane permeability. However, the electric field intensity must be set in a reasonable range (< several kV/cm) to prevent cell inactivation.