Microfluidic Chip and Software for Microvascular Studies

用于微血管研究的微流控芯片和软件

• 批准号: 6833765
• 负责人: BALABHASKAR PRABHAKARPANDIAN
• 金额: $ 10万
• 依托单位: CFD RESEARCH CORPORATION
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6833765
• 关键词: bioengineering /biomedical engineering; biomedical equipment development; cell adhesion; computer program /software; computer simulation; fluid flow; fluidity; microcapsule; microcirculation; microprocessor /microchip; technology /technique development; tissue /cell culture; vascular endothelium

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.).

描述（由申请人提供）： 颗粒与组织（血管内皮）的粘附主要取决于颗粒/细胞特性（尺寸、受体）、血管系统的尺度/几何特征（直径、分叉等）。和局部血液动力学因素（应力、扭矩等）。目前的体外流动室受到严重的限制，包括（a）不代表微脉管系统的理想化的大循环缩放（B）不代表几何特征（分叉）、健康与患病的脉管系统和互连网络，以及（c）需要大体积以及它们的非一次性性质。 我们建议开发和展示一种用于研究细胞/药物载体粘附的新型综合工具包，包括（a）基于体内图像的微流体微血管流动网络芯片，具有经过验证的培养细胞的协议和（B）定制的易于使用的基于CFD的软件来模拟这些芯片中的流动，颗粒运输和粘附。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的图像来设计。流动池将使用软光刻技术在一次性廉价塑料（PDMS）基板上微制造。微球的受控实验将用于演示方法和验证模型。将在塑料微芯片上培养内皮细胞的汇合层。先进的流动/颗粒运输模型将适用于微血管动力学分析和易于使用的GUI界面开发。第二阶段将侧重于（a）扩大网络数据库（包括疾病状态）（B）协议，用其他细胞/肿瘤进行实验和（c）软件封装。一个多学科的团队（CFD研究公司和美国。田纳西州健康科学中心），其中包括微血管成像，微细加工，微流体/细胞培养，CFD建模和生物流变学的专家。 预期益处/商业潜力：这种新颖的、解剖学上真实的、基于微血管网络的流式芯片与定制软件集成，可用于在真正模拟微血管环境的受控条件下检查颗粒细胞与组织的相互作用。随附的软件工具将是至关重要的，在促进基本的理解，以及规划的实验。在增加的功能、所用试剂/细胞的大幅减少和一次性使用（与当前简单、昂贵的流动室相比）的刺激下，该技术将被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（封装递送疗法、组织工程、疾病生理过程，如动脉粥样硬化等）。