Microfluidic Platforms for Biological Investigations

这项研究计划将在微观尺度上产生液体与物理和生物标本相互作用的力学方面的新知识。特别是，它试图探索在微通道中具有不同性质的液体中刚性微粒、柔性微粒和柔性微滴的流动诱导聚焦。获得的基本知识支持合作开发微流控设备和芯片上实验室，用于重要的健康和安全应用，如按需检测食品和水、现场环境和安全监测、神经退行性疾病研究和高通量药物筛选。 在生物传感、治疗和药物输送应用中，使用刚性微粒和对其进行分类的方法正在增加。我们将研究(A)流体粘度和密度，(B)颗粒大小和形状，以及(C)通道设计和尺寸对颗粒聚焦的影响。我们将在弯曲的通道中使用模拟血液、复杂水和饮料的合成两相流体，类似于现实生活中的动脉和静脉场景。 柔性颗粒在多相微流体中很常见，但它们在非直流道中的迁移和聚焦还不是很清楚。我们将使用已建立的生物疾病模型生物(蠕虫、果蝇)的小规模胚胎和幼虫作为现实的非球形柔性微粒模型。我们将开发用于测量其力学性能的微型设备，同时探索使用化学物质和电信号来调节其变形性。将研究生物的形状和灵活性对弯曲通道中聚焦的影响。学生将对微流体中具有椭圆形、圆柱形和杆状几何形状的柔性生物对象的流体动力学有基本的了解。 多材料液滴在食品、化妆品和药品等应用中普遍存在，但其具有精确的微米尺寸和材料特性的多功能生产尚未实现。我们将制造一个模块化的装置，其中液滴产生单元将安装在精密打印的可配置夹具上。我们将使用该系统产生具有核壳和滴入配置的双乳化水包油水滴。我们将确定流体性质、通道设计和流速对液滴大小、壳层厚度和液滴形状的影响，并确定液滴的生成机制和形状。将提供有关双乳液滴生成的全面指南。 该项目将在5年内培养10名本科生和8名研究生。他们将获得实验研究方面的技能，包括设计和制造微流控装置，并将其应用于解决多相微流领域的工程问题。此外，学员将通过撰写论文和在会议上发表演讲来获得传播研究成果的软技能。

This research program will generate new knowledge on mechanics of liquids interactions with physical and biological specimens at microscale dimensions. Particularly, it seeks to explore the flow-induced focusing of rigid microparticles, flexible micro-objects, and flexible microdroplets inside liquids with various properties in microchannels. The gained fundamental knowledge supports collaborations to develop microfluidic devices and Lab-on-Chips for important health and safety applications, such as point-of-need food and water testing, field-based environmental and safety monitoring, neurodegenerative disease studies, and high-throughput drug screening. Use of rigid microparticles and methods to sort them are on the rise in biosensing, therapeutic, and drug delivery applications. We will investigate the effects of (a) fluid viscosity and density, (b) particle size and shape, and (c) channel design and size on particle focusing. We will work with synthetic two-phase fluids mimicking blood, complex water and beverages in curved channels similar to real-life scenarios like arteries and veins. Flexible particles are common in multiphase microfluidics, but their migration and focusing in non-straight channels is not well-understood. We will use small-scale embryos and larvae of established biological disease model organisms (worm, fruit fly) as realistic non-spherical flexible microparticle models. We will develop microdevices for measurement of their mechanical properties, while exploring the use of chemicals and electric signal to modulate their deformability. The effects of organisms' shape and flexibility on focusing in curved channels will be studied. Fundamental understanding of hydrodynamics of flexible biological objects with elliptical, cylindrical and rod-shaped geometries in microfluidics will be obtained. Multi-material droplets are ubiquitous in applications like food, cosmetics and pharmaceuticals, but their versatile production with precise micrometric size and material properties is yet to be achieved. We will fabricate a modular setup in which droplet generation units will be mounted onto precision-printed configurable fixtures. We will use the system to generate double-emulsion water-in-oil-in-water droplets with core-shell and drop-in-drop configurations. We will determine the effects of fluid properties, channel design and flow rate on droplet size, shell thickness and droplet configuration, and determine droplet generation regimes and configurations. Comprehensive guidelines for double-emulsion droplet generation will be provided. This program will train 10 undergraduate and 8 post-graduate students in 5yr. They will gain skills in experimental research including design and fabrication of microfluidic devices and applying them to solve engineering problems in the field of multi-phase microflows. Moreover, trainees will gain soft skills in dissemination of research findings via writing papers and giving talks at conferences.