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使用微孔板微流控装置进行基于剪切力的血栓形成检测。

Using well-plate microfluidic devices to conduct shear-based thrombosis assays.

作者信息

Conant Carolyn G, Nevill J Tanner, Zhou Zhou, Dong Jing-Fei, Schwartz Michael A, Ionescu-Zanetti Cristian

机构信息

Fluxion Biosciences, Inc., South San Francisco, CA 94080, USA.

出版信息

J Lab Autom. 2011 Apr;16(2):148-52. doi: 10.1016/j.jala.2010.10.005.

DOI:10.1016/j.jala.2010.10.005
PMID:21609696
Abstract

Shear stress plays a critical role in regulating platelet adhesion and thrombus formation at the site of vascular injury. As such, platelets are often examined in vitro under controlled shear flow conditions for their hemostatic and thrombotic functions. Common shear-based platelet analyses include the evaluation of genetic mutants, inhibitory or experimental compounds, matrix substrates, and the effects of different physiological and pathological shear forces. There are several laboratory instruments widely used for studying shear flow, including cone and plate viscometers and parallel plate perfusion chambers. These technologies vary widely in the types of samples, substrates, blood volumes, and throughput that are involved. Here, we describe a microfluidic system for platelet analysis under shear flow. We used the devices to study thrombus formation on collagen I and von Willebrand factor. The system was also used to investigate dose response to the antiplatelet compound, Abciximab, under shear flow conditions with an emphasis on maximizing the number of data points per single patient sample. The presented method confers multiple advantages over conventional approaches. These include the ability to assess up to 24 conditions simultaneously in real time, maintain identical physical conditions across experiments, and use extremely low donor volumes.

摘要

剪切应力在调节血管损伤部位的血小板黏附和血栓形成过程中起着关键作用。因此,血小板通常在体外可控的剪切流条件下进行止血和血栓形成功能的检测。常见的基于剪切的血小板分析包括对基因突变体、抑制性或实验性化合物、基质底物以及不同生理和病理剪切力影响的评估。有几种实验室仪器广泛用于研究剪切流,包括锥板粘度计和平行板灌注室。这些技术在涉及的样品类型、底物、血量和通量方面差异很大。在此,我们描述一种用于在剪切流下分析血小板的微流控系统。我们使用该装置研究I型胶原蛋白和血管性血友病因子上的血栓形成。该系统还用于在剪切流条件下研究抗血小板化合物阿昔单抗的剂量反应,重点是使每个患者样品的数据点数量最大化。所提出的方法相对于传统方法具有多个优点。这些优点包括能够实时同时评估多达24种条件、在实验过程中保持相同的物理条件以及使用极低的供体血量。

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