Advances and Challenges in Membrane-Disruption-Based Microfluidic Intracellular Delivery

Intracellular delivery has widespread applications in biomanufacturing and fundamental research for cellular-level genome editing and modification. However, current limitations, mainly regarding throughput and delivery efficiency, still hinder the development of this technique. Studies on membrane-disruption-based microfluid intracellular delivery methodologies have recently increased due to their potential for large-scale, low-damage molecular transport on versatile cell types. This chapter primarily introduces recent advances in membrane-disruption-based delivery approaches incorporated with microfluidic technologies. The approaches were classified according to their mechanisms, where the microfluid chip design, steps for achieving delivery, highest delivery efficiency, cell viability, and throughput are discussed. Comprehensive comparisons among those technologies for the advantages, disadvantages, and current limitations were presented. Specifically, we emphasized the potential of microfluidic techniques that integrate refined micro/nanostructures for high-throughput and efficient mechanoporation or electroporation. Key challenges and possible solutions for hard-to-transfect cells were discussed at the end of this chapter.