Integrated microfluidic chip for endothelial cells culture and analysis exposed to a pulsatile and oscillatory shear stress
Integrated microfluidic chip for endothelial cells culture and analysis exposed to a pulsatile and oscillatory shear stress
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用于暴露于脉动和振荡剪切应力下的内皮细胞培养和分析的集成微流控芯片
DOI：
10.1039/b909312e
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发表时间：
2009-01-01
期刊：
影响因子：
6.1
通讯作者：
Zhao, Jianlong
中科院分区：
文献类型：
--
作者：
Shao, Jianbo;Wu, Lei;Zhao, Jianlong
为了全面了解细胞或组织，重要的是在芯片的可控微环境下进行多项研究。在这份报告中，我们提出了一个集成的微流控细胞培养平台，其中内皮细胞（EC）是在静态条件下或暴露于脉动和振荡的剪切应力。通过集成微间隙、自容流动回路、气动泵和阀门，新型微流控芯片实现了多种功能：脉动和振荡流体循环、细胞捕获、细胞培养、形成EC屏障以及对细胞施加剪切力。细胞在重力作用下进入微通道后，在流体动力的作用下沿微间隙沿着排列，并在微通道内生长7天以上。细胞增殖并迁移，在微间隙处形成屏障，模仿血管壁，将微环境分为两个隔室：微通道和微室。一个优化的气动微泵被嵌入到一个独立的回路，诱导在生理水平上的EC在微通道中的脉动和振荡的剪切应力，驱动流动循环。所有分析均在静态或动态条件下进行。通过荧光标记的白蛋白的扩散和分布行为来评价屏障的性能。屏障的渗透性与传统的体外试验相当。在微室中形成的示踪剂的浓度梯度可以潜在地用于研究细胞极化，迁移和通信在未来。此外，还分析了内皮细胞对脉动和振荡切应力反应的形态学和细胞骨架。微流控芯片提供了一个多功能的平台，使血管在细胞或组织水平的全面研究。
For a comprehensive understanding of cells or tissues, it is important to enable multiple studies under the controllable microenvironment of a chip. In this report, we present an integrated microfluidic cell culture platform in which endothelial cells (ECs) are under static conditions or exposed to a pulsatile and oscillatory shear stress. Through the integration of a microgap, self-contained flow loop, pneumatic pumps, and valves, the novel microfluidic chip achieved multiple functions: pulsatile and oscillatory fluid circulation, cell trapping, cell culture, the formation of ECs barrier, and adding shear stress on cells. After being introduced into the chip by gravity, the ECs arranged along the microgap with the help of hydrodynamic forces and grew in the microchannel for more than 7 days. The cells proliferated and migrated to form a barrier at the microgap to mimic the vessel wall, which separated the microenvironment into two compartments, microchannel and microchamber. An optimized pneumatic micropump was embedded to actuate flow circulation in a self-contained loop that induced a pulsatile and oscillatory shear stress at physiological levels on the ECs in the microchannel. All the analyses were performed under either static or dynamic conditions. The performance of the barrier was evaluated by the diffusion and distribution behaviors of fluorescently labeled albumin. The permeability of the barrier was comparable to that in traditional in vitro assays. The concentration gradients of the tracer formed in the microchamber can potentially be used to study cell polarization, migration and communications in the future. Additionally, the morphology and cytoskeleton of the ECs response to the pulsatile and oscillatory shear stress were analyzed. The microfluidic chip provided a multifunctional platform to enable comprehensive studies of blood vessels at the cell or tissue level.