CAREER: Compact digital biosensing system enabled by localized acoustic streaming

快速、便携和准确的诊断测试对于提高医疗保健的质量和可及性非常重要。然而，现有的快速和便携式检测方法的性能往往不足以检测感染性疾病、癌症和心血管疾病等复杂疾病。CAREER项目的主要目标是开发一种新的数字测试平台，在不牺牲简单性和便携性的情况下，提供高检测灵敏度和定量精度。新的测试平台是由振动毛细管和3D打印微设备引起的独特流体现象实现的。项目成功完成后，将开发出无需专用仪器和实验室空间即可检测低丰度核酸和蛋白质生物标志物的集成设备。这种设备将有很大的潜力向广大人口提供高质量的医疗检测，包括服务不足的社区和资源有限的地区。这个项目是高度多学科的，将生产低成本，紧凑的仪器。因此，它为不同背景的学生创造了独特的教育机会。该提案将使1)通过在课程中实施基于项目和问题的学习理念，提高定量化学分析实验室学生的学习效果；2)面向本科生的新型微尺度分析化学实验，如振动尖头微流控酶分析；3)培养学生运用多学科方法解决研究问题的研究项目。该项目旨在开发一种综合解决方案，在护理点（POC）环境下进行完整的数字生物分析，从而解决开发高性能POC测试的未满足需求。该方法通过控制尖锐尖端的振动来实现，该方法可以在微通道中产生局部和可单独寻址的声流，用于流体控制和液滴生成。为了实现上述影响，将实现三个目标：1)通过数值模拟和流分析阐明尖端液滴的产生过程，并演示POC核酸检测系统；2)开发一种简单的双流液滴生成系统，用于数字ELISA；3)演示了一种由振动尖端和可组合微流控板驱动的集成样品处理系统。该项目将导致一个灵活的生物传感平台，可以很容易地适应测量低丰度核酸或蛋白质生物标志物。它还将促进对非混相流体中声流的基本理解，并扩展声流在复杂流体、液滴和粒子操作中的应用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Rapid, portable, and accurate diagnostic testing is of great importance to improve the quality and accessibility of healthcare. However, the performance of existing rapid and portable testing methods is often not sufficient for complex diseases such as infectious diseases, cancer, and cardiovascular diseases. The major goal of this CAREER project is to develop a new digital testing platform that offers high detection sensitivity and quantification accuracy without sacrificing the simplicity and the portability. The new testing platform is enabled by the unique fluid phenomenon induced by a vibrating capillary and 3D printed microdevices. Upon the successful completion of this project, integrated devices that can detect low abundance nucleic acid and protein biomarkers without the need of dedicated instrument and laboratory space will be developed. Such devices will have great potential to deliver high quality medical testing to a broad population including underserved communities and resource limited regions. This project is highly multidisciplinary and will produce low cost, and compact instrumentation. It therefore creates unique educational opportunities for students with diverse backgrounds. The proposal will enable 1) improved learning outcomes for students in quantitative chemical analysis lab through implementing project- and problem-based learning concepts to the curriculum; 2) novel microscale analytical chemistry experiments for undergraduate students, e.g., vibrating sharp-tip powered microfluidic enzymatic assay; 3) a research program that trains students to solve research problems using multidisciplinary approaches.This project is to develop an integrated solution to perform complete digital bioassays under a point-of-care (POC) setting thereby addressing the unmet need of developing high performance POC tests. The proposed method is enabled by controlling the vibration of sharp tips, which can generate localized and individually addressable acoustic streaming in microchannels for fluid control and droplet generation. To achieve the proposed impact, three aims will be pursued: 1) Elucidate the sharp-tip droplet generation process through numerical modeling and streaming analysis and demonstrate a POC nucleic acids detection system; 2) Develop a simple dual flow droplet generation system for performing digital ELISA; 3) Demonstrate an integrated the sample processing system enabled by vibrating sharp-tip and composable microfluidic plates. This project will lead to a flexible biosensing platform that can be easily adapted to measure either low abundance nucleic acids or protein biomarkers. It will also advance the fundamental understanding of the acoustic streaming in immiscible fluids and expand the utility of acoustic streaming for complex fluid, droplet, and particle manipulations.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.