Department of Mechanical and Manufacturing Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
Center for Bioengineering Research and Education, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
Sci Rep. 2019 Apr 30;9(1):6723. doi: 10.1038/s41598-019-43056-2.
Microinjection is an effective actuation technique used for precise delivery of molecules and cells into droplets or controlled delivery of genes, molecules, proteins, and viruses into single cells. Several microinjection techniques have been developed for actuating droplets and cells. However, they are still time-consuming, have shown limited success, and are not compatible with the needs of high-throughput (HT) serial microinjection. We present a new passive microinjection technique relying on pressure-driven fluid flow and pulsative flow patterns within an HT droplet microfluidic system to produce serial droplets and manage rapid and highly controlled microinjection into droplets. A microneedle is secured within the injection station to confine droplets during the microinjection. The confinement of droplets on the injection station prevents their movement or deformation during the injection process. Three-dimensional (3D) computational analysis is developed and validated to model the dynamics of multiphase flows during the emulsion generation. We investigate the influence of pulsative flows, microneedle parameters and synchronization on the efficacy of microinjection. Finally, the feasibility of implementing our microinjection model is examined experimentally. This technique can be used for tissue engineering, cells actuation and drug discovery as well as developing new strategies for drug delivery.
微注射是一种有效的驱动技术，用于将分子和细胞精确地递送到液滴中，或控制地将基因、分子、蛋白质和病毒递送到单个细胞中。已经开发了几种微注射技术来驱动液滴和细胞。然而，它们仍然耗时，成功率有限，并且与高通量（HT）连续微注射的需求不兼容。我们提出了一种新的被动微注射技术，该技术依赖于压力驱动的流体流动和在 HT 液滴微流控系统内的脉动流动模式，以产生连续的液滴，并对液滴内的快速和高度受控的微注射进行管理。在注射站中固定一个微针，以在微注射过程中限制液滴。在注射站限制液滴可防止它们在注射过程中移动或变形。开发并验证了三维（3D）计算分析来模拟乳液生成过程中多相流的动力学。我们研究了脉动流、微针参数和同步对微注射效果的影响。最后，实验检验了实施我们的微注射模型的可行性。该技术可用于组织工程、细胞驱动和药物发现，以及开发新的药物输送策略。
