Multi-Frequency Multi-Parametric Acoustophoretic Microfluidic System for Particle and Cell Separation

PI：Kim，Yong-Joe研究所：德克萨斯农工大学智力优势：该项目的目标是(1)开发新的、变革性的二维和三维数值模拟方法，以分析在多频声激励下微流体系统中颗粒和细胞的声波分离，以及(2)开发用于分离具有不同振动-声学特性的颗粒和细胞的声波微流控平台，并通过实验验证数值模型。可压缩性是一种有趣的物理特性，可用于无标记分离；然而，不存在能够在高通量下基于颗粒和细胞的尺寸和可压缩性连续和同时无标记分离的系统。基于声导引法的微流控分离利用了目标样品在声激励下固有的振动-声学性质的差异，并且可以使用简单的微流控系统来实现，而不需要繁琐的样品制备步骤。因此，这种方法以其强大的作用力、高通量、高特异性、低资本和操作成本而成为最可行的无标记分离方法。然而，最先进的声波微流控系统的设计主要是从一个简单的静态流体介质中的一维分析声学模型推导出来的。因此，不可能考虑二维或三维几何形状、“移动的”流体介质以及显著影响颗粒和细胞运动的粘性边界层的真实世界效应。在这个分析模型中，粒子或细胞也被建模为均匀的、可压缩的球体，以只考虑它们的“静态”物理特性，而不能分析它们的频率相关的振动-声学特性。所提出的方法解决了这些不足之处，以显著提高声光分离的可预测性和特异性。还提出了新的粒子和细胞模型，以了解它们的频率依赖、振动-声学特性。更广泛的影响：一个变革性的、多频率、多参数的微流控平台，通过这些新的建模功能并利用频率相关的振动-声学特性，将允许同时分离复杂样品。这个项目将为本科生和研究生提供一个极好的跨学科研究机会，结合声学、微流体学、芯片实验室、生物学和计算物理。特别是，这项工作将(1)为积极进取的本科生和代表性不足的少数族裔提供研究机会和培训，以及(2)扩大机械和电气工程的正式课堂课程，将微流控实验室芯片系统和声光分离的学习目标包括在内。拟议研究的结果将通过同行评议的期刊出版物和在专业会议上的陈述加以传播，并用于丰富本科生和研究生课程的教材。本文提出的一种公开可用的声学建模方法，通过实现“虚拟现实”原型，将极大地推进声学分离系统的设计。

PI: Kim, Yong-JoeInstitution: Texas A&M University Intellectural Merit: The objectives of this project are (1) to develop novel, transformative, two- and three-dimensional numerical modeling methods to analyze acoustophoretic separation of particles and cells in microfluidic systems under multi-frequency acoustic excitations, and (2) to develop an acoustophoretic microfluidic platform for separating particles and cells having different vibro-acoustic properties and validating the numerical models experimentally. Compressibility is an interesting physical property that can be utilized in label-free separation; however, systems capable of continuous and simultaneous label-free separation of particles and cells based on both their sizes and compressibility at high throughput do not exist. Acoustophoresis-based microfluidic separation utilizes intrinsic differences in vibro-acoustic properties of target samples under acoustic excitations, and can be achieved using simple microfluidic systems without need for cumbersome sample preparation steps. Thus, this approach has gained significant interest as the most viable label-free separation method in terms of its strong force generation, high throughput, high specificity, and low capital and operation cost. However, the design of state-of-the-art acoustophoretic microfluidic systems has been mainly derived from a simplistic one-dimensional analytical acoustic model in a "static" fluid medium. Therefore, it is not possible to consider the real-world effects of two- or three-dimensional geometries, "moving" fluid media, and viscous boundary layers that significantly influence the motion of particles and cells. In this analytical model, particles or cells are also modeled as homogenous, compressible spheres to consider only their "static" physical characteristics, and their frequency-dependent vibro-acoustic characteristics cannot be analyzed. The proposed methods address these deficiencies to significantly improve the predictability and specificity of the acoustophoretic separation. Novel particle and cell models are also proposed to understand their frequency-dependent, vibro-acoustic characteristics. Broader Impact: A transformative, multi-frequency, multi-parametric, acoustophoretic microfluidic platform enabled by these new modeling capabilities and utilizing the frequency-dependent vibro-acoustic properties will allow simultaneous fractionation of complex samples. This project will provide undergraduate and graduate students an excellent interdisciplinary research opportunity combining acoustics, microfluidics, lab-on-a-chip, biology, and computational physics. In particular, this work will (1) provide research opportunities and training for highly motivated undergraduate students and underrepresented minorities, and (2) expand the formal classroom curriculum in mechanical and electrical engineering to include learning objectives in microfluidic lab-chip systems and acoustophoretic separation. The results of the proposed research will be disseminated through peer-reviewed journal publications and presentations at professional conferences and used to enrich teaching materials for undergraduate and graduate courses. A publicly-available, acoustophoretic modeling method as proposed here will significantly advance the design of acoustophoretic separation systems by enabling "virtual reality" prototyping.