Decoupled Space and Time Gradients for Particle Enrichment, Sorting and Isolation

微纳颗粒的使用，如固体颗粒、胶囊和液体乳剂，在多个行业都有广泛的应用：从化妆品、油漆和农业中的乳剂，到抗菌和高质量光学涂层的金属纳米颗粒，以及用于药物输送和治疗的微纳胶囊。在所有这些应用中，粒度对于确保所需的功能至关重要。例如，给药胶囊的大小确保药物及时靶向递送到体内的适当位置，或者乳剂的大小决定化妆品的稳定性和保质期。在颗粒的制造过程中，颗粒的大小是通过下游的富集和分选过程来控制的。这种富集和分选过程也广泛应用于微流控医疗诊断技术中，用于分离和分离生物细胞，用于个性化癌症治疗和药物发现。这些颗粒加工技术的精度、效率、产量和可扩展性决定了产品的最终质量和成本。发展可扩展颗粒处理技术的一个关键挑战是平衡吞吐量和精度的灵活性。该技术也应该是无标签的，并采用低剪切力，以避免污染和颗粒活力。本研究项目将通过研究一种利用流体流场梯度操纵颗粒的新机制，解决上述颗粒富集、分选和分离方面的挑战。该机制依赖于封闭通道中的低频液体振荡，将用于在流场中产生空间和时间梯度，从而将颗粒驱动到通道中的特定位置。该机制的一个关键特征是这些时空梯度将解耦，这在现有的声学[Wiklund， Lab Chip, 12, 2018-2028(2012)]或基于毛管波的[Agrawal， et al.， Phys]中基本上是不可能的。应用学报，2,064008(2014)]机制（由于波长和频率的耦合）。这种解耦将允许对颗粒的收集和不稳定力进行独立控制，从而提供对过程效率和吞吐量的独立控制。低频振荡的能量密集度也较低，这有助于该机制的可扩展性。我们将结合分析和数值模拟以及实验来研究粒子在这些解耦的时空梯度流场中的运动。研究通道设计、驱动参数和颗粒性质（尺寸、密度和刚度）对不同硬、软颗粒（如固体微纳颗粒、液体乳剂和生物细胞）收集稳定性和收集速度的影响。本研究的一个关键成果将是探索该机制的可扩展性和实用性，以富集颗粒生产中的固体和液滴乳剂等颗粒，并为生物医学分析工具分选和分离生物细胞。这项研究的直接应用将是一种新型的低能耗方法，用于散装、基于尺寸的颗粒富集和分选，作为制造纳米颗粒和乳剂的下游工艺，用于药物输送和涂层。这项研究的支持应用将是开发一种新型的微流体设备，用于分选和分离细胞，这将支持细胞治疗、癌症治疗和个性化医疗的生物医学和临床研究。该项目由在医疗诊断和制药制造方面具有专业知识的公司提供支持，以探索上述应用。

The use of micro-nano particles, such as, solid particles, capsules and liquid emulsions have immense applications in multiple industries: from emulsions in cosmetics, paint and agriculture, metal nanoparticles for anti-bacterial and high-quality optical coatings, and micro-nano capsules for drug delivery and therapeutics. In all these applications particle size is crucial to ensure the desired functionality. For example, size of drug delivery capsules ensures timely targeted delivery of drugs to the appropriate location in the body, or size of an emulsion determines stability and shelf-life of a cosmetic product.During manufacturing of particles, particle sizes are controlled via downstream processes of enrichment and sorting. Such enrichment and sorting processes are also widely used in microfluidic healthcare diagnostic technologies for separation and isolation of biological cells for emerging applications in personalized cancer therapeutics and drug discovery. The precision, efficiency, yield and scalability of these particle processing techniques determines the eventual quality and cost of the product. A key challenge in developing scalable particle processing technologies is the flexibility to balance throughput and precision. The technology should also be label-free and employ low shear forces to avoid contamination and particle viability.This research project will address the above challenges in particle enrichment, sorting and isolation by investigating a new mechanism to manipulate particles using fluid flow field gradients. The mechanism relies on low frequency liquid oscillations in closed channels will be used to create spatial and temporal gradients in the flow field which will drive particles to specific locations in the channel. A key feature of this mechanism is that these spatial and temporal gradients will be de-coupled, which is fundamentally not possible in existing acoustic [Wiklund, Lab Chip, 12, 2018-2028 (2012)] or capillary wave-based [Agrawal, et al., Phys. Rev. App., 2, 064008 (2014)] mechanisms (due to coupled wavelength and frequency). This decoupling will allow an independent control of collection and destabilizing forces on particles providing an independent control of process efficiency and throughput. Low frequency oscillations are also less energy intensive which aids scalability of the mechanism.A combination of analytical and numerical modeling, and experiments will be used to investigate particle motion in these decoupled spatial and temporal gradient flow fields. The effect of channel designs, actuation parameters and particle properties (size, density and stiffness) on collection stability and collection speed will be characterized for different hard and soft particles, such as, solid micro-nano particles, liquid emulsions and biological cells. A key outcome of this research will be to explore the mechanism's scalability and utility to enrich particles like solids and droplet emulsions as a downstream process in particle production, and sort and isolate biological cells for a bio-medical analysis tool.The direct application of this research will be a novel low energy intensive method for bulk, size-based particle enrichment and sorting to be used as a downstream process in manufacturing of nanoparticles and emulsions for drug delivery and coatings. The supported applications of this research will be in developing a new class of microfluidic devices for sorting and isolating cells which will support bio-medical and clinical research in cell therapies, cancer treatment and personalized medicine. The project is supported by companies with an expertise in healthcare diagnostics and pharmaceutical manufacturing to explore the above applications.