Shear-induced platelet aggregation: 3D-grayscale microfluidics for repeatable and localized occlusive thrombosis
Shear-induced platelet aggregation: 3D-grayscale microfluidics for repeatable and localized occlusive thrombosis
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DOI：
10.1063/1.5113508
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发表时间：
2019-09-01
期刊：
影响因子：
3.2
通讯作者：
Ku, David N.
中科院分区：
文献类型：
--
作者：
Griffin, Michael T.;Kim, Dongjune;Ku, David N.
由于剪切诱导的血小板聚集（SIPA），动脉粥样硬化血栓形成导致心肌梗死和中风的并发症。临床医生和研究人员可能会受益于诊断和台式微流体测定，评估个人的血栓形成活动。目前，有几种不同的提出的护理点诊断和微流体血栓形成测定具有不同的设计参数和终点。微流体的几何形状、表面涂层和抗凝剂可能强烈影响这些测定的精度。选定终点的变异性也持续存在，导致结果不明确。本研究旨在评估三个生理相关的外在设计因素对单一终点变异性的影响，为设计参数和终点标准化提供量化的依据。使用实验设计方法，我们表明，通道制造和胶原蛋白表面涂层的方法显着影响猪全血闭塞时间的变异性，而肝素和柠檬酸盐之间的抗凝剂选择没有显着影响的变异性。未确定显著影响试验内平均闭塞时间的因素。闭塞性血栓被发现始终形成在第一个三分之一（333 μ m）的高剪切区，而不是在剪切梯度区。在护理点诊断和实验性SIPA测定的设计中选择这些因素可能导致高剪切血栓形成研究中的精确度和特异性增加。由AIP Publishing授权出版。
Atherothrombosis leads to complications of myocardial infarction and stroke as a result of shear-induced platelet aggregation (SIPA). Clinicians and researchers may benefit from diagnostic and benchtop microfluidic assays that assess the thrombotic activity of an individual. Currently, there are several different proposed point-of-care diagnostics and microfluidic thrombosis assays with different design parameters and end points. The microfluidic geometry, surface coatings, and anticoagulation may strongly influence the precision of these assays. Variability in selected end points also persists, leading to ambiguous results. This study aims to assess the effects of three physiologically relevant extrinsic design factors on the variability of a single end point to provide a quantified rationale for design parameter and end-point standardization. Using a design of experiments approach, we show that the methods of channel fabrication and collagen surface coating significantly impact the variability of occlusion time from porcine whole blood, while anticoagulant selection between heparin and citrate did not significantly impact the variability. No factor was determined to significantly impact the mean occlusion time within the assay. Occlusive thrombus was found to consistently form in the first third (333 mu m) of the high shear zone and not in the shear gradient regions. The selection of these factors in the design of point-of-care diagnostics and experimental SIPA assays may lead to increased precision and specificity in high shear thrombosis studies. Published under license by AIP Publishing.