Cell Culturing BioChips for Pulmonary Vasculature Mimics

描述（由申请人提供）：SBIR一期项目的重点是开发一种微流体平台，作为替代微血管系统，用于研究影响肺动脉高压发病的因素。正如设想的那样，最终的设备平台将能够筛选多参数空间，以确定流体剪切、病毒感染和毒素引起的应力之间的相关性，并阐明转化生长因子。概念验证装置将包括一个平台，内皮细胞在平台中原位培养，孵育后，周围液体的化学和物理性质独立改变。通过微流体创建敏感控制的化学环境以及通过流体剪切力传递给细胞的应力的微妙变化的能力允许同时控制多个实验参数。在制造过程中，通道几何形状的变化将被设计成模拟肺动脉的分叉点，Meta-Fluidics开发的流体控制技术将允许完全控制含有细胞的毛细血管内的条件。该项目的具体目标是：1)制造和展示有利于微血管内皮细胞粘附和生长的多通道微流体网络。2)利用Met流体流动控制技术调节细胞毛细血管内的化学和物理环境。3)利用该平台作为肺模拟实验，研究几何和剪切应力对健康微血管内皮细胞向丛状病变转分化的影响。第一阶段的成功将为第二阶段的更大努力奠定基础，第二阶段的重点是开发一种使用“黑匣子”的方法，该方法将以高度并行的方式将几何控制、细胞培养和实验控制结合起来。这个多阶段SBIR项目的成功完成将立即产生一种技术，可以以以前不可能的方式研究肺动脉高压的物理原因。更广泛地说，这项技术将作为微流体技术潜力的展示，用于生产精确模拟内皮血管的形态和功能的系统，并将适用于各种医学研究学科。

DESCRIPTION (provided by applicant): The focus of this SBIR Phase I project is to develop a microfluidic platform that serves as a surrogate microvasculature for studying factors influential in the onset of pulmonary hypertension. As envisioned, the resulting device platform will be capable of screening multi-parameter space for correlations between stresses due to fluid shear, viral infection and toxins and elucidated transforming growth factors. The proof-of- concept device will consist of a platform in which endothelial cells are cultured in situ and, after incubation, the chemical and physical properties of the surrounding fluid altered independently. The ability to create sensitively controlled chemical environments via microfluidics as well as subtle variations in stresses imparted to cells through fluid shear forces allows for control of multiple experimental parameters simultaneously. Variations imparted to channel geometry during fabrication will be designed to mimic bifurcation points in pulmonary arteries and fluid-control technology developed by Meta-Fluidics will allow full control of the conditions within the cell-containing capillaries. The specific aims of this project are to: 1) fabricate and demonstrate a multichannel microfluidic network conducive to microvascular endothelial cell adhesion and growth. 2) regulate the chemical and physical environments within cell-containing capillaries using Met fluidics flow control technology. 3) utilize the platform as a pulmonary mimic to investigate the effects of geometry and shear stress upon the transdifferentiation of healthy microvascular endothelial cells into plexiform lesions. Phase I success will set the stage for a larger Phase II effort focused on developing an to use "black box" that will coalesce geometric control, cell culturing and experimental control in a highly parallel fashion. The successful completion of this multi-phase SBIR project will immediately result in a technology that allows physical causes of pulmonary hypertension to be studied in a manner that has not been previously possible. More broadly, this technology will serve as a demonstration of the potential for microfluidics to produce systems that accurately mimic the morphology and function of endothelial-lined capillaries and will be applicable throughout diverse medical research disciplines.