Microfluidic Chip and Software for Microvascular Studies

描述(由申请人提供)： 颗粒与组织(血管内皮细胞)的黏附在很大程度上取决于颗粒/细胞特性(大小、受体)、血管系统的尺度/几何特征(直径、分叉等)。局部血流动力学因素(应力、扭矩等)。目前，体外流动室受到严重的限制，包括(A)理想化的大循环尺度不能代表微血管系统(B)没有几何特征(分叉)、健康与患病的血管系统和互联网络以及(C)大容量的要求及其不可丢弃的性质。 我们建议开发和展示一种用于研究细胞/药物载体黏附的新的、全面的工具包，包括：(A)基于体内图像的微流控微血管流动网络芯片，具有成熟的细胞培养协议；以及(B)基于CFD的定制、易于使用的软件来模拟这些芯片中的流动、颗粒传输和黏附。微通道网络将基于使用ANET技术收集的小动物体内微血管图像进行设计。流动单元将使用软光刻技术在一次性廉价塑料(PDMS)基板上进行微细加工。微球的对照实验将用于演示方法和验证模型。将融合层的内皮细胞培养在塑料芯片上。将采用先进的流动/颗粒传输模型来分析微血管动力学，并开发出易于使用的图形用户界面。第二阶段将集中于(A)扩展网络数据库(包括患病状态)(B)协议、其他细胞/肿瘤实验和(C)软件封装。已经组建了一个多学科团队(CFD研究公司和田纳西健康科学中心大学)，其中包括微血管成像、微制造、微流体/细胞培养、CFD建模和生物流变学方面的专家。 预期效益/商业潜力：这种新颖的、解剖学上逼真的、基于微血管网络的流动芯片与定制的软件相集成，可用于在受控条件下检查粒子细胞与组织的相互作用，从而真正模拟微血管环境。随附的软件工具将对促进对实验的基本理解和规划至关重要。由于增加了功能，大大减少了试剂/细胞的使用和一次性(与目前简单、昂贵的流动室相比)，这项技术将销售给各种生物医学和药物发现研究领域的研究人员，并有望被他们采用。

DESCRIPTION (provided by applicant): Particle adhesion to tissue (vascular endothelium) depends critically upon particle/cell property (size, receptors), scale/geometric features of vasculature (diameter, bifurcation etc.) and local hemodynamic factors (stress, torque etc.). Current, in-vitro flow chambers suffer from serious limitations including (a) idealized, macrocirculatory scaling not representative of microvasculature (b) no representation of geometric features (bifurcations), healthy versus diseased vasculature and network of interconnects and (c) requirement of large volumes together with their non-disposable nature. We propose to develop and demonstrate a novel, comprehensive toolkit for studying cell/drug carrier adhesion comprising of (a) microfluidic, microvascular flow network chip, based on in-vivo images, with proven protocols to culture cells and (b) customized, easy-to-use CFD-based software to model flow, particle transport and adhesion in these chips. The microchannel network will be designed based on images of in-vivo microvascular images of small animals collected using ANET technique. The flow cell will be microfabricated using soft lithography techniques on disposable, inexpensive plastic (PDMS) substrate. Controlled experiments with microspheres will be used to demonstrate methodology and verify models. Confluent layer of endothelial cells will be cultured on the plastic microchip. Advanced models of flow/particle transport will be adapted for analysis of microvascular dynamics and an easy-to-use GUI interface developed. Phase II will focus on (a) expanding the network databases (include diseased states) (b) protocols, experiments with other cells/tumors and (c) software encapsulation. A multidisciplinary team (CFD Research Corp. and U. of Tennessee Health Science Center) has been assembled, which includes experts in microvascular imaging, microfabrication, microfluidics/cell-culture, CFD modeling and biorheology. Anticipated Benefits/Commercial Potential: The novel, anatomically realistic, microvascular network based flow-chip integrated with customized software can be used to examine particle cell -tissue interactions under controlled conditions that truly mimic the microvascular environment. The accompanying software tool will be critical in furthering fundamental understanding as well as planning of experiments. Spurred by the added functionality, drastic reduction in reagents/cells used and disposability (compared to the current simplistic, expensive flow chambers) the technology will be marketed to and expected to be adopted by researchers in a variety of biomedical & drug discovery research fields (encapsulated delivery therapies, tissue engineering, disease physiologic processes such as atherosclerosis etc.).