Collaborative Research: Efficient Rare Cell Capturing in Microfluidic Devices via Multiscale Surface Design

建议：1264808/1263940PI：Liu/Yang这项建议的目标是通过利哈伊大学和宾夕法尼亚大学的协同研究活动，设计一种能够显著提高稀有细胞捕获效率和选择性的新型表面，包括新型多尺度计算模型、制造3D分层表面和微流体测试平台。具体地说，我们将设计和制造一个由两个不同长度尺度的图案化结构组成的分级表面：微尺度的波纹或人字形结构表面和纳米颗粒或纳米柱阵列。微尺度的正弦波纹和人字形结构将产生微涡，加强细胞与壁的碰撞，提供更大的黏附面积，避免非特异性细胞黏附和可能的细胞损伤，并实现准确的细胞计数；纳米结构将补充细胞膜上的微绒毛，从而提高相互作用的特异性和细胞捕获效率。通过计算和实验相结合的方法，我们期望这项拟议的研究将为临床从血液样本中分离稀有细胞提供重要的见解。多尺度计算模型将首次用于指导细胞在各种三维表面上捕获的研究，同时考虑了流体力学和附着动力学。各种独特的分层表面设计将集成到微流控设备中，以验证计算预测并显著提高稀有细胞捕获性能。具体地说，我们计划：(1)建立细胞捕获过程的多尺度传输和黏附动力学模型，并对不同设计的表面进行细胞捕获分析。描述各种表面设计如何影响细胞捕获效率、吞吐量和选择性。(2)制作由微尺度波纹图案(一维波纹和二维人字形结构)和纳米管或纳米颗粒阵列组成的三维分层曲面库。(3)利用所制作的分层表面对颗粒和细胞捕获进行微流控试验。在捕获效率、吞吐量和选择性方面对各种表面设计进行基准测试(程和刘)。(4)将实验结果与计算模型进行比较，对模型进行了优化，并对分层曲面和稀有细胞捕获器进行了重新设计。跨不同学科的协同方法，包括生物工程、材料科学、纳米制造和生物微机械，带来了一种新的仿生方法来构建用于早期癌症检测的芯片实验室设备，从而使该项目具有变革性。研究成果将创造一个重要的机会，激发公众对生物纳米技术的兴趣，从而激发和吸引他们对科学、技术、工程和数学(STEM)的兴趣。此外，这项工作将为在高度整合的研究和教育环境中招收和培训各级学生提供一个有效的工具。研究成果将通过一个专门的网站和工具共享在NanHub上传播，用于发布从该项目开发的细胞科学、材料制造和计算建模框架的新发现，以及向K-12学生推广。

Proposal: 1264808/1263940PI: Liu/YangThe goal of this proposal is to design a novel surface that could significantly enhance rare cell capture efficacy and selectivity through synergistic research activities between Lehigh University and University of Pennsylvania, including a novel multi-scale computational model, fabrication of a 3D hierarchical surface, and a microfluidic testing platform. Specifically, we will design and fabricate a hierarchical surface consisting of patterned structures at two difference length scales: a micro-scale surface of ripples or herringbone structure and an array of nanoparticles or nanopillars. The micro-scale sinusoidal ripples and herringbone structures will generate micro-vortices to enhance cell-wall collision, provide larger adhesion area, avoid non-specific cell adhesion and possible cell damage, and enable accurate cell counting; the nanostructures will complement microvilli on cell membranes, thus, improve both interaction specificity and cell capturing efficiency. Through a combined computational and experimental approach we expect that the proposed study will provide important insights for clinical isolation of rare cells from a blood sample. The multiscale computational modeling will be applied for the first time to guide the study of cell capture on various 3D surfaces with consideration of both hydrodynamics and adhesion dynamics. Various unique hierarchical surface designs will be integrated into a microfluidic device to validate the computational prediction and significantly improve rare cell capture performance. Specifically, we plan to: (1) Develop a multi-scale transport and adhesion dynamics model for cell capture process and perform cell capture analysis on surfaces of various designs. Characterize how various surface designs influence cell capture efficiency, throughput, and selectivity. (2) Fabricate a library of 3D hierarchical surface consisting of microscale wavy patterns (1D ripples and 2D herringbone structures) and an array of nanopillars or nanoparticles. (3) Perform microfluidic test on particle and cell capture using the fabricated hierarchical surface. Benchmark various surface designs in terms of capture efficiency, throughput, and selectively (Cheng and Liu). (4) Compare the experimental results with the computational model; optimize the model and re-engineer the hierarchical surface and the rare cell capture device. The synergistic approach across diverse disciplines, including bioengineering, materials science, nanofabrication, and BioMEMS brings about a novel biomimetic approach to construct a lab-on-the-chip device for early cancer detection, thus making the project transformative. The research outcome will create a significant opportunity to excite the general public in bio-nanotechnology, thereby provoking and engaging their interest Science, Technology, Engineering, and Mathematics (STEM). In addition, this work will offer an effective tool to recruit and train students at all levels in a highly-integrated research and educational environment. The research outcome will be disseminated through a dedicated website and tool sharing at nanoHub for posting new discoveries in cell science, materials fabrication, and computational modeling frameworks developed from this project, as well as outreach to K-12 students.