Microfluidic separation of particles based upon stiffness

0932510 Sulchek人类细胞的机械刚度可以是揭示细胞疾病状态的关键参数，例如，在各种癌症和疟疾中。然而，为了在诊断环境中利用刚度，我们将需要用于以高通量连续监测细胞刚度的方法。虽然通常采用通过其他参数（例如尺寸或密度）进行分离，但是目前还没有用于通过刚度进行分离的方法。提出的研究的主要目标是开发一种微流体装置，能够通过其机械顺应性连续分离和分选微尺度弹性颗粒、合成微胶囊和生物细胞。我们将结合联合收割机的计算建模和实验研究，以探讨微尺度的顺应性物体在微通道中的运动与周期性收缩，并研究如何动态之间的相互作用，由于粘性流动和通道的几何形状的弹性变形可以利用挑起细胞分离。 我们初步的三维计算机模拟表明，细胞与不同的刚度最初具有相同的横向位置分散到不同的横向位置在一个微通道中的对角收缩，并以这种方式，可以有效地分离他们的顺应性。 在拟议的研究中，我们将首先开发一个全面的计算模型的弹性胶囊和细胞在微流体环境中。我们的流体-结构相互作用计算方法将捕获一个弹性壳代表顺应胶囊，微通道，封装流体和主机解决方案的复杂几何形状之间的动态相互作用。我们将采用我们的数值模型来深入了解通过明确定义的固体收缩推进的顺应性胶体颗粒的物理特性，并建立设计具有对角收缩的稳健和高效的微流体分选机的指导方针。 我们将制定系统参数的最佳范围，导致最有效的分离。这些结果将指导我们的实验研究。 我们将开始我们的实验努力，合成明确的胶囊层由层沉积。机械顺应性可以通过在胶囊壁上包括附加层来可靠地控制，其中颗粒直径的增加可以忽略不计。我们将基于原子力显微镜通过力学测量来评估颗粒刚度。我们将实施所提出的微通道设计到一个实验微流体系统组成的矩形聚（二甲基硅氧烷）通道包含压力驱动的液体流。通道的顶部和底部表面显示具有限定的垂直间隙的偏斜脊。我们将采用实验装置来验证我们的理论模型的预测，并通过跟踪它们的轨迹来进一步研究受限流体通道中微观粒子的动力学。在我们的实验中，我们将收集关于颗粒刚度和通道几何形状对颗粒运动的影响的数据，这对于设计稳健的分选机和建立所提出的方法的准确性至关重要。所提出的协同方法将增强我们对柔性颗粒和受限几何形状中的微流体流动之间的动态相互作用以及弹性在复合物中所起的作用的基本知识微粒流拟议研究的结果可能会改变我们对生物系统弹性影响的认识，包括血管中的流动以及细胞弹性对各种疾病发展的贡献。它还将产生有用的计算和实验工具，用于检查涉及顺应性颗粒和粘性流动的动态过程。更广泛的影响：我们的研究结果将为设计新型微流体设备建立急需的指导方针，用于连续分析和分选生物细胞和合成微胶囊。 这种微流体分选器可以证明对于影响生物细胞的生物力学特性的大量病理的快速和廉价的诊断是非常有价值的，这可能挽救许多人的生命。在教育推广方面，PI将参加CEISMC计划，接待来自亚特兰大公立学校系统的科学教师。教师将从代表性不足的群体中招募2-3名高中生，在拟议研究的框架内现场开展项目。然后，高中生将在国家科学博览会和国家西门子科学竞赛上展示他们的研究成果。

0932510SulchekThe mechanical stiffness of human cells can be a key parameter that reveals the disease state of the cell, for example, in various cancers and in malaria. However, for stiffness to be utilized in diagnostic settings, we will require methods for continuous monitoring of the stiffness of cells in high throughput. Although separation by other parameters, such as size or density, is commonly employed, methods are not currently available for separation by stiffness. The main goal of the proposed studies is to develop a microfluidic device capable of continuous separation and sorting of microscale elastic particles, synthetic microcapsules, and biological cells by their mechanical compliance. We will combine computational modeling and experimental studies to probe the movement of microscale compliant objects in microchannels with periodical constrictions and examine how the dynamical interplay between elastic deformation due to viscous flow and the channel geometry can be harnessed to provoke cell segregation. Our preliminary three dimensional computer simulations reveal that cells with dissimilar stiffness initially having identical lateral positions disperse to distinct lateral locations in a microchannel with diagonal constrictions and, in this way, can be effectively separated by their compliance. In the proposed studies, we will first develop a comprehensive computational model of elastic capsules and cells in a microfluidic environment. Our fluid structure interaction computational approach will capture the dynamic interactions among an elastic shell representing compliant capsules, complex geometry of microchannel, encapsulated fluid, and host solution. We will employ our numerical model to gain insight into the physics of compliant colloidal particles propelled through well defined solid constrictions and establish guidelines for designing robust and efficient microfluidic sorters with diagonal constrictions. We will formulate the optimal range of system parameters leading to the most efficient separation. These results will then guide our experimental studies. We will begin our experimental efforts by synthesizing well-defined capsules made from layer by layer deposition. The mechanical compliance can be reliably controlled by including additional layers to the wall of the capsule, with a negligible increase in particle diameter. We will assess particle stiffness with mechanics measurements based upon atomic force microscopy. We will implement the proposed microchannel design into an experimental microfluidic system composed of a rectangular poly (dimethylsiloxane) channel containing a pressure driven liquid flow. The top and bottom surface of the channel display skewed ridges with a defined vertical gap. We will employ the experimental setup to verify the predictions of our theoretical model and further examine the dynamics of microscopic particles in confined fluidic channels by tracking their trajectories. In our experiments, we will collect data on the effect of particle stiffness and channel geometry upon the particle movement, which is critical for designing robust sorters and establishing the accuracy of the proposed method.Intellectual Merit: The proposed synergetic approach will enhance our basic knowledge on the dynamic interactions between compliant particles and microfluidic flows in constrained geometries and the role that elasticity plays in the complex particulate flows. The results of proposed studies could potentially transform our knowledge on the effect of elasticity in biological systems, including flows in blood vessels and the contribution of cell elasticity to development of various diseases. It will also yield useful computational and experimental tools for examining dynamic processes involving compliant particles and viscous flows.Broader Impact: The results of our studies will establish the much needed guidelines for designing novel microfluidic devices for continuously analyzing and sorting of biological cells and synthetic microcapsules. Such microfluidic sorters could prove extremely valuable for rapid and inexpensive diagnostics of a large number of pathologies affecting the biomechanical properties of biological cells that could potentially save numerous human lives. In terms of educational outreach, the PI's will participate in CEISMC program to host a science teacher from the Atlanta Public School system. The teacher will recruit 2-3 high school students from underrepresented groups to work on site on a project in the framework of the proposed studies. The high-school students will then present their research results at the state science fair and the national Siemens science competition.