液滴微流控生化分析高通量平台中复合相射流断裂现象的研究

Droplet-based microfluidics enables fast generation and precise manipulation of well-defined droplets from compound fluid phases in a programmable way. These droplets as micro-reactors for chemical and biological assays provide increased screening throughput, reduced consumption of reagents, short reaction time and low costs. Thus droplet-based microfluidics presents a promising platform for applications where multiple reactions performed in parallel are desired, such as high throughput screening. Currently, fluid phase with simple rheological properties (mostly Newtonian fluid with low viscosity similar to water) are employed to generate droplet micro-reactor. However, typical fluid samples in practical clinical applications are with complex rheological properties, such as high viscosity and Non-Newtonian characteristics. For example, bio-fluid (such as blood), and concentrated cell suspensions are Non-Newtonian fluid with non-constant viscosities. The properties of these complex fluids present challenge to form controlled droplets from compound fluid phases. Thus, it is difficult to form droplet micro-reactors from clinical samples in a controlled and programmable manner. This significantly limits the broad application of droplet-based microfluidic platform in practical clinical applications. In this project, we study experimentally and numerically the rheological properties of the complex liquids extensively employed in clinical applications. We investigate the influence of the complex rheological properties on the droplet generation process from a compound jet in microfluidics. Subsequently we systematically characterize the size, frequency and composition of the generated compound droplets. To generate droplet micro-reactor based on requirements of applications, we further control the droplet generation process by external forces. Our aim is to form tailor-designed compound droplet from complex fluids, namely Non-Newtonian fluid, as micro-reactors for the sake of clinical uses. This study will unleash the potential of droplet-based microfluidics in high throughput clinical diagnostics, and facilitate the commercialization of the next generation clinical devices based on droplets.

液滴微流控中的复合相射流可断裂产生尺寸均一的微液滴。用这些微液滴作微反应器具有通量高、成本小、反应速度快、试剂消耗少等优势。因此，液滴微流控是高通量快速生化分析诊断的理想平台。目前，对液滴微流控在生化分析诊断中的应用多处于实验研究阶段。该阶段多采用流变性质简单的流体简化完成概念性验证。但实际临床应用上，许多待验液体（如血液、检测试剂等）具有高粘度、非牛顿特性等复杂的流变性质。这些性质对液滴微流控以复合相射流为基础产生可控液滴带来了影响和挑战。.本课题中，我们将用实验和数值模拟相结合的方法研究征流变性质复杂的流体对复合相射流产生微液滴的影响。并用复合液滴的产生同步性、组成、尺寸对这些影响进行了系统地表征。同时我们引入机械振动、交变电场等，探讨了外力对复合相射流产生微液滴的调控作用。这些研究对液滴微流控高通量平台获得可控液滴用作微反应器具有指导意义，从而对实际临床分析诊断具有重要价值和影响。

液滴微流控中的复合相射流可断裂形成可控的微液滴或延伸成为极细射流，其可做为微反应器或做为制备微颗粒/纤维载体的模板，因此在生物医学应用中有重要价值。实际应用中的多相流体系具有复杂的流变性质，如高浓度的聚合物溶液、细胞或颗粒悬浮液等，研究这些复杂流体在微流控系统中的流态、并探索外场力对复杂流体射流的调控十分关键。为此，本项目通过引入电场力来调控复合相射流的断裂同步性、尺寸等，总结出电场力对复合相射流产生微液滴的调控作用；在实验和模拟的基础上，深入研究了复杂流体复合相射流在电场作用下的不同动态行为，创新性地发现并报道了微流控复合相带电射流的新机制，并总结出新机制与控制参数如电场强度、进样流量等，物性参数如粘度、界面张力、介电常数、导电率等的无量纲关系，为复杂微流体的精准控制提供了理论基础。本项目已申请专利4项(授权1项)；在PNAS(第一标注), Small(第一标注), ACS appl. mater. interfaces(第一标注),Nat. Commun.,等高水平学术期刊上共发表项目相关一作或通讯论文12篇，其中IF>8的论文6篇，共培养硕士研究生7人。参与国内外会议并作报告5次。