Microfluidics Laminar Flow Endothelial Cell Assays

微流体层流内皮细胞分析

• 批准号: 6644644
• 负责人: Rajan Kumar
• 金额: $ 14.02万
• 依托单位: GENOME DATA SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-11 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6644644
• 关键词: biomedical equipment development; cell population study; drug screening /evaluation; fluid flow; gene expression; high throughput technology; method development; microarray technology; shear stress; technology /technique development; vascular endothelium

DESCRIPTION (provided by applicant): Coronary Heart Disease (CHD) and stroke are leading causes of death in the United States. The underlying cause of CHD and stroke is atherosclerosis, which is a chronic inflammatory condition of large arteries. A number of genetic and environmental factors are responsible for development of atherosclerosis. Atherosclerosis does not develop uniformly in arteries; hemodynamic characteristics of blood flow that promote laminar shear stress seem to prevent local atherosclerosis. The goal of this project is to develop a novel microfluidics system for performing laminar shear stress assays on vascular endothelium and developing a high-throughput system for atherosclerosis drug discovery. Parallel plate flow chamber has been the most popular method for simulating physiological flow conditions experienced by endothelial cells (ECs). Recently, a commercially produced flow chamber has been introduced that promises to reduce assay volume. However, for high throughput applications, such as screening for new therapeutics, none of the existing technologies are suitable. Genome Data Systems, Inc. (GDS) has developed an innovative and proprietary chip technology called GeneCard that can overcome the challenges of the existing systems. The characteristic feature of GeneCard technology is a modular approach to microfluidics that allows easy introduction of cells, tissues and other solid phase materials into fluidic devices, as well as their easy removal. During this project, GeneCard designs for efficient culture and laminar flow assay of ECs will be investigated. EC cultures will be established on GeneCard devices, and subjected to controlled laminar shear stress. Gene expression profiles of ECs using microarrays will be generated and genes that are regulated by laminar shear stress will be identified. Finally, the ability of known modulators of EC function to reverse gene expression changes induced by laminar shear stress will be investigated. The proposed method provides a user-friendly approach for investigating effects of laminar flow on EC cultures. Smaller number of cells required reduces cost and enables high throughput assays. At the successful completion of the proposed project, GDS will provide complete systems for drug discovery market as well as use the systems for internal R&D efforts and to provide contract screening service.

描述（由申请人提供）：冠心病（CHD）和中风是美国的主要死亡原因。冠心病和中风的根本原因是动脉粥样硬化，这是大动脉的慢性炎症状况。许多遗传和环境因素负责动脉粥样硬化的发展。动脉粥样硬化在动脉中不一致。促进层状剪切应力的血流的血流动力学特征似乎可以预防局部动脉粥样硬化。该项目的目的是开发一种新型的微流体系统，用于在血管内皮上执行层状剪切应力测定，并开发用于动脉粥样硬化药物发现的高通量系统。平行板流室一直是模拟内皮细胞（ECS）经历的生理流动条件的最流行方法。最近，引入了商业产生的流动室，该流动室有望减少测定量。但是，对于高吞吐量应用，例如筛选新的治疗剂，现有技术都不适合。 Genome Data Systems，Inc。（GDS）开发了一种创新且专有的芯片技术，称为GeneCard，可以克服现有系统的挑战。 GeneCard技术的特征是微流体技术的模块化方法，可轻松将细胞，组织和其他固相材料引入流体设备，并易于去除。在该项目中，将研究用于有效培养的Genecard设计和EC的层流测定法。 EC培养物将在Genecard设备上建立，并受到控制的层状剪切应力。使用微阵列的EC的基因表达谱将产生，并将鉴定受层状剪切应力调节的基因。最后，将研究已知的EC功能调节剂逆转层状剪切应力诱导的基因表达变化的能力。提出的方法提供了一种用户友好的方法来研究层流对EC培养物的影响。较少的单元格会降低成本，并实现高通量测定。在拟议项目的成功完成时，GDS将为药物发现市场提供完整的系统，并将系统用于内部研发工作并提供合同筛查服务。