An accurate, tunable size filter for particles in microfluidics

在微流体中，根据大小和其他特性对小颗粒进行高效可靠的分选是细胞分选、遗传细胞测定或处理液滴和悬浮液的芯片实验室设备中遇到的一个挑战。本研究的目的是开发一种(i)被动的分选装置，即它不依赖于粒子的主动反馈；（ii）可调，即临界粒径可随意选择；并且（iii）不会因引入障碍而影响通过设备的有效吞吐量。该装置的核心是一个由超声波驱动的振荡微泡，它建立了一个稳定的流场，可以与通过该装置的外部流叠加。通过改变流量和超声振幅，装置被调整到一个临界尺寸的颗粒：如果一个颗粒的直径低于这个值，它将通过装置；如果它高于这个值，它的轨迹将（被动地）使它偏离气泡，在二次流回路中被收集。没有物理收缩引入通道，颗粒在流动最快的地方分离，而不是在传统的被动分选设备中最慢的地方。同样的装置也可以应用于根据可变形性对颗粒进行分类，包括具有构象变化的大分子。在微观层流中，所提出的气泡流表现出全新的特性。它们展示了虚拟流动约束的概念：为装载货物的流体制造狭窄的管道，既不会减慢流动速度，也不会对货物产生过大的剪切力。此外，这些流动可以通过易于调节的外部参数进行定量、非侵入性控制，并且在比任何规模的软光刻制造都小得多的规模上显示尺寸特异性。在设置中使用大分子为盘绕或拉伸大分子（如DNA）的动力学以及盘绕和拉伸状态之间的过渡提供了新的基本见解。这项工作的更广泛的影响是社会和教育：至关重要的应用受益于提高吞吐量，尺寸选择性的微流控颗粒运输，包括细胞术和细胞分选，癌症和血液疾病诊断中的细胞变形性测定，或生物医学样品的纯化和富集。大分子的分类和纯化在生物技术、DNA遗传分析或高效生产纯蛋白质方面同样具有巨大的重要性，这是目前使许多治疗性蛋白质价格过高的一个主要挑战。这项工作的跨学科性质将吸引来自生物工程和工程科学背景的本科生，他们将与研究生一起组成一个研究团队，分析实验数据并帮助进行模拟。该项目将通过针对大学生团队的重点研究项目和针对高中生的示范项目的开发，与伊利诺伊州现有的跨学科计划（如新的In3创新计划和K-12外展计划）联系起来。

1236141HilgenfeldtIn microfluidics, the efficient and reliable sorting of small particles by size and other properties is a challenge encountered in cell sorting, genetic cell assays, or lab-on-a-chip devices handling droplets and suspensions. The objective of the research is to develop a sorting device that is (i) passive, i.e., it does not rely on active feedback from the particles; (ii) tunable, i.e., a critical particle size can be selected at will; and (iii) does not compromise an efficient throughput through the device by introducing obstacles. The centerpiece of this device is an oscillating microbubble, driven by ultrasound, which establishes a steady streaming flow field that can be superimposed with an external flow through the device. By varying flow rate and ultrasound amplitude, the device is tuned to a critical size of particle: if a particle's diameter is below this value, it will pass through the device; if it is above this value, its trajectory will (passively) deflect it off the bubble to be collected in a secondary flow circuit. No physical constriction is introduced into the channel, and the particles are separated where the flow is fastest, not where it is slowest, as in traditional passive sorting devices. The same device can also be applied to sort particles by deformability, including macromolecules with conformational changes.Among laminar flows on the microscale, the proposed bubble streaming flows show fundamentally novel qualities. They demonstrate the concept of virtual flow confinement: narrow conduits for cargo-laden fluid are produced that neither slow the flow down nor lead to excessive shear forces on the cargo. Moreover, these flows are under quantitative, non- invasive control from easily adjustable external parameters and show size specificity on scales much smaller than any scale of soft-lithography manufacturing. Using macromolecules in the set-up gives new fundamental insight into the dynamics of coiled or stretched macromolecules (such as DNA) and the transition between coiled and stretched states.The broader impact of the work is societal and educational: Crucially important applications profit from improved-throughput, size-selective microfluidic particle transport, including cytometry and cell sorting, assays of cell deformability in diagnostics of cancer and blood diseases, or purification and enrichment of biomedical samples. The classification and purification of macromolecules is likewise of enormous importance in biotechnology, in genetic assays of DNA, or in the efficient production of pure proteins, a major challenge that at present makes many therapeutic proteins prohibitively expensive. The interdisciplinary nature of the work will attract undergraduate students from both bioengineering and engineering science backgrounds, who will form a research team together with the graduate student on this project, analyzing experimental data and helping with simulations. This project will be connected to existing interdisciplinary initiatives at Illinois, such as the new In3 Innovation Initiative and K-12 outreach, through the development of both focused research projects for university student teams and demonstration projects for high-school students.