用于对流驱动大分子细胞内递送的瞬态细胞体积交换的微流控生成

Liu Anna, Islam Muhymin, Stone Nicholas, Varadarajan Vikram, Jeong Jenny, Bowie Sam, Qiu Peng, Waller Edmund K, Alexeev Alexander, Sulchek Todd

Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.

School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.

Mater Today (Kidlington). 2018 Sep;21(7):703-712. doi: 10.1016/j.mattod.2018.03.002. Epub 2018 Apr 17.

Efficient intracellular delivery of target macromolecules remains a major obstacle in cell engineering and other biomedical applications. We discovered a unique cell biophysical phenomenon of transient cell volume exchange by using microfluidics to rapidly and repeatedly compress cells. This behavior consists of brief, mechanically induced cell volume loss followed by rapid volume recovery. We harness this behavior for high-throughput, convective intracellular delivery of large polysaccharides (2000 kDa), particles (100 nm), and plasmids while maintaining high cell viability. Successful proof of concept experiments in transfection and intracellular labeling demonstrated potential to overcome the most prohibitive challenges in intracellular delivery for cell engineering.

在细胞工程和其他生物医学应用中，将目标大分子高效递送至细胞内仍然是一个主要障碍。我们利用微流控技术快速且反复地压缩细胞，发现了一种独特的细胞生物物理现象——瞬时细胞体积交换。这种行为包括短暂的、机械诱导的细胞体积减小，随后是快速的体积恢复。我们利用这种行为实现了对大分子量多糖（2000 kDa）、颗粒（100 nm）和质粒的高通量、对流式细胞内递送，同时保持了较高的细胞活力。转染和细胞内标记方面成功的概念验证实验表明，该技术有潜力克服细胞工程中细胞内递送方面最严峻的挑战。