Using microfluidic devices to study thrombosis in pathological blood flows
Using microfluidic devices to study thrombosis in pathological blood flows
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DOI：
10.1063/1.5021769
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发表时间：
2018-07-01
期刊：
影响因子：
3.2
通讯作者：
Diamond, Scott L.
中科院分区：
文献类型：
--
作者：
Herbig, Bradley A.;Yu, Xinren;Diamond, Scott L.
极端流动可能存在于病理血管几何形状或机械辅助装置内，其产生复杂的力并导致与疾病相关的血栓形成问题。由于小通道中的低雷诺数流动，在微流体中难以获得湍流和边界层分离。然而，拉伸流动，极端的剪切速率和应力，以及停滞点流动是可能的，使用微流体和小灌注体积。在这篇综述中，一系列用于研究病理血流的微流控装置进行了描述。在预先涂有纤维状胶原的极度狭窄的通道中，其从500 μ m迅速变窄至15 μ m，血浆血管性血友病因子（VWF）将伸长并在胶原上组装成厚纤维束。使用微柱撞击装置，撞击在微柱上的等离子体流产生强烈的拉伸应力和壁剪切应力，其触发柱周围的VWF束的生长（不需要胶原蛋白）。使用停滞点装置来模拟流动再附着附近的区域，血液可以直接冲击在胶原蛋白和组织因子的促凝剂表面上。在流动冲击的停滞点处形成的凝块具有经典的核-壳结构，其中核被高度活化（P-选择素阳性血小板和富含纤维蛋白）。最后，在填充微通道的闭塞性凝块内，由Δ P/L> 70 mm Hg/mm凝块驱动的达西流足以驱动截留的中性粒细胞的NETosis，这是一种不需要凝血酶或纤维蛋白的事件。新型微流体装置是进入人类疾病中存在的物理环境的强大工具。由AIP出版社出版。
Extreme flows can exist within pathological vessel geometries or mechanical assist devices which create complex forces and lead to thrombogenic problems associated with disease. Turbulence and boundary layer separation are difficult to obtain in microfluidics due to the low Reynolds number flow in small channels. However, elongational flows, extreme shear rates and stresses, and stagnation point flows are possible using microfluidics and small perfusion volumes. In this review, a series of microfluidic devices used to study pathological blood flows are described. In an extreme stenosis channel pre-coated with fibrillar collagen that rapidly narrows from 500 mu m to 15 mu m, the plasma von Willebrand Factor (VWF) will elongate and assemble into thick fiber bundles on the collagen. Using a micropost-impingement device, plasma flow impinging on the micropost generates strong elongational and wall shear stresses that trigger the growth of a VWF bundle around the post (no collagen required). Using a stagnation-point device to mimic the zone near flow reattachment, blood can be directly impinged upon a procoagulant surface of collagen and the tissue factor. Clots formed at the stagnation point of flow impingement have a classic core-shell architecture where the core is highly activated (P-selectin positive platelets and fibrin rich). Finally, within occlusive clots that fill a microchannel, the Darcy flow driven by Delta P/L> 70 mm-Hg/mm-clot is sufficient to drive NETosis of entrapped neutrophils, an event not requiring either thrombin or fibrin. Novel microfluidic devices are powerful tools to access physical environments that exist in human disease. Published by AIP Publishing.