单细胞微流控液滴封装的数值模拟与实验研究

Droplet-based Microfluidic technology can encapsulate single cells into picoliter-sized droplets. The droplet-producing rate can be over thousands per second. Single-cell encapsulations by droplet microfluidics can overcome many challenges in biological single-cell analysis and application. It will bring a breakthrough for biotechnology. Utilizing inertia effect in microchannel for cell sorting and microfluidic droplet-generation technologies, monodispersity of single-cell droplet encapsulation can be realized. However, the theoretical understanding of droplet encapsulation is limited to date. Especially, there is no systematic study on the whole process of droplet encapsulation. This project will be the first try to develop the numerical algorithm of cell membranes based on the Volume of Fluid (VOF) method. Combined with the adaptive grid refinement method for thin region, efficient and reliable numerical simulation method will be developed to couple microscale multiphase flow and cell membrane dynamics. Single-cell droplet encapsulation will be investigated for different droplet-generation microfluidic devices through numerical simulation and experimental measurement. The translation, rotation, deformation and surface stress of cells will be quantified to evaluate their effects on cell viability. The project will examine the influences of encapsulation device geometry and flow parameters on the cell/droplet size ratio, encapsulation tolerance and efficiency. Theoretical basis for the design of single-cell microfluidic encapsulation devices will be provided for different applications. The project will guide the optimization and innovation of encapsulation devices and promote the development of single-cell microfluidic droplet encapsulation technology.

微流控技术可以将单细胞封装在皮升级的液滴中，并进行每秒上千个的高通量操控。单细胞微流控液滴封装技术可克服生物学中单细胞分析与应用的诸多挑战，为生物技术带来突破性进展。利用细胞在微通道中的惯性排序效应和液滴生成技术已可实现单分散性的单细胞液滴封装。但现阶段液滴封装的理论基础匮乏，尤其是对整个液滴封装过程的系统研究还未见报道。本项目将首次在流体体积法的基础上发展细胞膜数值模型，结合对薄区域的自适应网格加密方法，发展多相流/细胞耦合的高效率计算方法。通过数值模拟和实验研究不同液滴生成装置中单细胞微流控封装过程，分析细胞平动、旋转、变形和受力情况，进而量化封装对细胞活力的影响。研究将考察封装装置几何和流动参数对细胞/液滴大小比例、封装容差和效率的影响，从而为不同实际需求的封装装置的设计提供理论基础。研究将指导封装装置的优化和创新，推动单细胞微流控液滴封装技术的发展。

针对单细胞微流控液滴封装基础理论匮乏的问题，本项目在流体体积法的基础上发展细胞膜数值模型和三相界面处理方法，结合对拓扑导向的薄区域自适应网格加密方法，发展了多相流/细胞耦合的高效率计算方法。通过直接数值模拟和高速摄影实验观测研究了不同液滴生成装置中液滴生成过程，考察了封装装置几何和流动参数对液滴大小和封装厚度的影响。利用粘弹性流体的汇聚作用，在方截面直通道中实现了细胞的汇聚，并通过直接数值模拟探索了细胞平衡位置个数及其随雷诺数变化的规律。研究为单细胞液滴封装微流控装置的设计和优化提供了理论基础，也为研究包含细胞和液滴的多相微流控体系的研究提供了重要的工作基础。项目资助发表论文8篇，其中SCI论文6篇，另有在审论文3篇，培养博士研究生3名，并已获得博士学位。