Cardiac-like flow generator for long-term imaging of endothelial cell responses to circulatory pulsatile flow at microscale
Cardiac-like flow generator for long-term imaging of endothelial cell responses to circulatory pulsatile flow at microscale
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DOI：
10.1039/c3lc50123j
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发表时间：
2013-01-01
期刊：
影响因子：
6.1
通讯作者：
Nordon, Robert E.
中科院分区：
文献类型：
--
作者：
Chen, Huaying;Cornwell, James;Nordon, Robert E.
在体外循环血液动力学模型，需要模拟微循环的研究内皮细胞对脉动剪切应力的活细胞成像。本研究报告的设计，制造和表征的微流控装置，产生心脏样流动的连续培养系统中的循环体积只有2-3 μ L。该器械模拟单腔心脏，具有以下心脏阶段：（1）心室入口阀关闭，（2）心室收缩（收缩期），随后打开出口阀，以及（3）心室舒张（舒张期），同时打开入口阀，出口阀保持关闭。周期性瓣膜状态和心室收缩由微处理器控制的气动装置驱动。随时间变化的速度场的特征在于微观粒子图像测速（mu-PIV）。mu-PIV观测用于帮助调整瓣膜状态和心室收缩的电子定时，以合成动脉脉搏波形，从而研究脉动剪切应力对牛动脉内皮细胞（BAEC）的影响。在最大剪切应力为0.42 Pa的脉动波形作用48 h后，BAEC沿剪切应力方向伸长并排列。Kadohama等人（2006年）报告的稳定（非脉动）血流条件下BAEC排列和伸长的阈值为0.7-1.4 Pa。这些细胞响应于瞬时剪切应力，因为产生这种形态响应的脉冲波形的时间平均剪切应力仅为0.09 Pa，远低于稳态流动阈值。微流控脉冲发生器可以模拟循环血液动力学，用于剪切诱导的信号通路的活细胞成像。
In vitro models of circulatory hemodynamics are required to mimic the microcirculation for study of endothelial cell responses to pulsatile shear stress by live cell imaging. This study reports the design, fabrication and characterisation of a microfluidic device that generates cardiac-like flow in a continuous culture system with a circulatory volume of only 2-3 mu L. The device mimics a single chamber heart, with the following cardiac phases: (1) closure of the ventricle inlet valve, (2) contraction of the ventricle (systole) followed by opening of the outlet valve and (3) relaxation of the ventricle (diastole) with opening of the inlet valve whilst the outlet valve remains closed. Periodic valve states and ventricular contractions were actuated by microprocessor controlled pneumatics. The time-dependent velocity-field was characterised by micro-particle image velocimetry (mu-PIV). mu-PIV observations were used to help tune electronic timing of valve states and ventricular contractions for synthesis of an arterial pulse waveform to study the effect of pulsatile shear stress on bovine artery endothelial cells (BAECs). BAECs elongated and aligned with the direction of shear stress after 48 h of exposure to a pulsatile waveform with a maximum shear stress of 0.42 Pa. The threshold for BAECs alignment and elongation under steady (non-pulsatile) flow reported by Kadohama et al. (2006) is 0.7-1.4 Pa. These cells respond to transient shear stress because the time average shear stress of the pulse waveform to generate this morphological response was only 0.09 Pa, well below the steady flow threshold. The microfluidic pulse generator can simulate circulatory hemodynamics for live cell imaging of shear-induced signalling pathways.