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多参数微流控血栓形成分析在生理温度下显示出对收缩和抗血小板药物更高的敏感性。

Multiparameter microfluidics assay of thrombus formation reveals increased sensitivity to contraction and antiplatelet agents at physiological temperature.

机构信息

FlowChamber B.V., Oxfordlaan 70, Maastricht, the Netherlands.

Dept. of Biochemistry, CARIM, P.O. Box 616, 6200 MD, Maastricht University, Maastricht, the Netherlands.

出版信息

Thromb Res. 2021 Jul;203:46-56. doi: 10.1016/j.thromres.2021.04.014. Epub 2021 Apr 19.

DOI:10.1016/j.thromres.2021.04.014
PMID:33934017
Abstract

INTRODUCTION

Current developments to assess qualitative and quantitative platelet traits in flowed whole-blood are based on microfluidic devices that mostly operate at room temperature. However, operation at physiological temperature (37 °C) may increase the assay's sensitivity, and facilitates the comparison to other platelet function tests of the diagnostic laboratory.

MATERIALS AND METHODS

We adapted the conventional microspot-based microfluidic device with a simple thermo-coupled pre-heating module. Automated analysis of microscopic images assisted in obtaining five time-dependent parameters of thrombus formation over collagen microspots (shear rate 1000 s). These modifications allowed rapid testing of control and patient blood samples at physiological temperature.

RESULTS AND CONCLUSION

The higher temperature enhanced platelet adhesion and aggregation as well as late thrombus characteristics such as size and contraction, when compared to room temperature. Moreover, assessment at 37 °C indicated a time-dependent impairment of the thrombus parameters in blood from patients taking common antiplatelet medication, i.e. aspirin and/or clopidogrel. This pointed to increased contribution of the autocrine platelet agonists thromboxane A and ADP in the buildup of contracted thrombi under flow. Overall, this study underlined the advantage of multiparameter assessment of microfluidic thrombus formation in detecting an acquired platelet dysfunction, when operating at physiological temperature. This work may bring microfluidics tests closer to the diagnostic laboratory.

摘要

简介

目前在全血流中评估血小板定性和定量特征的方法主要基于在室温下运行的微流控装置。然而,在生理温度(37°C)下运行可能会提高检测的灵敏度,并便于与诊断实验室的其他血小板功能检测进行比较。

材料与方法

我们对传统的基于微点的微流控装置进行了改进,增加了一个简单的热耦预热模块。自动分析显微图像有助于获得胶原微点上血栓形成的五个时间依赖性参数(剪切率 1000 s)。这些改进允许在生理温度下快速测试对照和患者的血液样本。

结果与结论

与室温相比,较高的温度增强了血小板的黏附和聚集,以及血栓后期的特征,如大小和收缩。此外,在 37°C 下评估表明,服用常见抗血小板药物(如阿司匹林和/或氯吡格雷)的患者血液中的血栓参数存在时间依赖性损伤。这表明在流动条件下,血栓收缩时,自分泌血小板激动剂血栓烷 A 和 ADP 的作用增加。总体而言,这项研究强调了在生理温度下进行多参数微流控血栓形成评估检测获得性血小板功能障碍的优势。这项工作可能使微流控检测更接近诊断实验室。

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