National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA and Department of Mechanical Engineering, University of Maryland, College Park, MD, 20742 USA.
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Lab Chip. 2019 Jan 29;19(3):493-502. doi: 10.1039/c8lc01178h.
A multifunctional microfluidic platform combining on-demand aqueous-phase droplet generation, multi-droplet storage, and controlled merging of droplets selected from a storage library in a single integrated microfluidic device is described. A unique aspect of the technology is a microfluidic trap design comprising a droplet trap chamber and lateral bypass channels integrated with a microvalve that supports the capture and merger of multiple droplets over a wide range of individual droplet sizes. A storage unit comprising an array of microfluidic traps operates in a first-in first-out manner, allowing droplets stored within the library to be analyzed before sequentially delivering selected droplets to a downstream merging zone, while shunting other droplets to waste. Performance of the microfluidic trap is investigated for variations in bypass/chamber hydrodynamic resistance ratio, micro-chamber geometry, trapped droplet volume, and overall flow rate. The integrated microfluidic platform is then utilized to demonstrate the operational steps necessary for cell-based assays requiring the isolation of defined cell populations with single cell resolution, including encapsulation of individual cells within an aqueous-phase droplet carrier, screening or incubation of the immobilized cell-encapsulated droplets, and generation of controlled combinations of individual cells through the sequential droplet merging process. Beyond its utility for cell analysis, the presented platform represents a versatile approach to robust droplet generation, storage, and merging for use in a wide range of droplet-based microfluidics applications.
一种多功能微流控平台，结合按需水相液滴生成、多液滴存储以及从存储库中选择的液滴的受控合并，集成在单个微流控装置中。该技术的一个独特方面是微流控阱设计，包括由微阀集成的液滴阱室和侧向旁路通道，该微阀支持在广泛的单个液滴尺寸范围内捕获和合并多个液滴。由微流控阱阵列组成的存储单元以先进先出的方式工作，允许在将选定的液滴顺序输送到下游合并区之前，对库中存储的液滴进行分析，同时将其他液滴分流到废物中。研究了旁路/腔室水动力阻力比、微腔几何形状、捕获的液滴体积和总流速变化对微流控阱性能的影响。然后利用集成微流控平台演示了基于细胞的测定所需的操作步骤，这些测定需要以单细胞分辨率分离定义的细胞群体，包括将单个细胞包封在水相液滴载体中、筛选或孵育固定化的细胞包封液滴，以及通过顺序液滴合并过程生成受控的单个细胞组合。除了用于细胞分析之外，所提出的平台还代表了一种用于生成、存储和合并稳健液滴的通用方法，可用于广泛的基于液滴的微流控应用。
