An accurate, tunable size filter for particles in microfluidics

用于微流体中颗粒的精确、可调尺寸过滤器

• 批准号: 1236141
• 负责人: Sascha Hilgenfeldt
• 金额: $ 29.99万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1236141&HistoricalAwards=false
• 关键词: accurate; tunable; size; filter; particles

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.

在微流体中，通过尺寸和其他性质对小颗粒进行有效和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上实验室装置中遇到的挑战。本研究的目的是开发一种分选装置，该分选装置是（i）无源的，即，它不依赖于来自粒子的主动反馈;（i i）可调谐，即，可以随意选择临界颗粒尺寸;和（iii）不会由于引入障碍物而损害通过装置的有效通过量。该装置的核心是由超声驱动的振荡微泡，其建立稳定的流动流场，该流动流场可以与通过装置的外部流叠加。通过改变流速和超声振幅，装置被调整到颗粒的临界尺寸：如果颗粒的直径低于该值，则其将通过装置;如果颗粒的直径高于该值，则其轨迹将（被动地）使其偏离气泡以被收集在二次流回路中。没有物理收缩被引入到通道中，并且颗粒在流动最快的地方被分离，而不是在流动最慢的地方，如在传统的被动分选装置中。同样的装置也可以应用于通过变形性对颗粒进行分选，包括具有构象变化的大分子。在微观尺度的层流中，所提出的气泡流流动显示出根本上新颖的品质。他们展示了虚拟流动限制的概念：产生用于装载货物的流体的狭窄管道，既不会减缓流动，也不会导致货物上的过度剪切力。此外，这些流动处于来自容易调节的外部参数的定量、非侵入性控制下，并且在比软光刻制造的任何规模小得多的规模上显示出尺寸特异性。使用大分子的设置提供了新的基本洞察力的动态卷曲或拉伸大分子（如DNA）和卷曲和拉伸状态之间的转变。这项工作的更广泛影响是社会和教育：至关重要的应用得益于改进的通量、尺寸选择性微流体颗粒运输，包括细胞计数和细胞分选，在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的遗传分析或纯蛋白质的有效生产中同样具有巨大的重要性，这是目前使许多治疗性蛋白质过于昂贵的主要挑战。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，他们将与该项目的研究生一起组成一个研究团队，分析实验数据并帮助模拟。该项目将连接到现有的跨学科的举措在伊利诺伊州，如新的In 3创新倡议和K-12推广，通过两个重点研究项目的大学生团队和示范项目为高中生的发展。