Cell Culturing BioChips for Pulmonary Vasculature Mimics

描述(申请人提供)：这项SBIR第一阶段项目的重点是开发一种微流体平台，作为研究影响肺动脉高压发病因素的替代微血管。正如设想的那样，由此产生的设备平台将能够筛选多参数空间，以寻找流体剪切、病毒感染和毒素引起的压力与阐明的转化生长因子之间的相关性。概念验证设备将由一个平台组成，在这个平台上原位培养内皮细胞，孵化后，周围液体的化学和物理性质将独立改变。通过微流体创造敏感可控的化学环境的能力，以及通过流体剪切力施加给细胞的应力的细微变化，允许同时控制多个实验参数。在制造过程中赋予通道几何形状的变化将被设计成模拟肺动脉中的分叉点，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。本项目的具体目标是：1)构建和展示有利于微血管内皮细胞黏附和生长的多通道微流控网络。2)使用Met流体流量控制技术调节含有细胞的毛细血管内的化学和物理环境。3)利用该平台作为肺模拟模型，研究几何形状和剪切力对健康微血管内皮细胞转分化为丛状病变的影响。第一阶段的成功将为更大的第二阶段工作奠定基础，重点是开发一种新的“黑匣子”，它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在一起。这一多阶段SBIR项目的成功完成将立即带来一项技术，使人们能够以一种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，这项技术将展示微流控技术生产准确模拟内皮衬里毛细血管形态和功能的系统的潜力，并将适用于不同的医学研究学科。

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.