Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium.
Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium.
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DOI：
10.1007/s10544-016-0095-6
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发表时间：
2016-08
影响因子：
2.8
通讯作者：
Ingber DE
中科院分区：
文献类型：
--
作者：
Jain A;van der Meer AD;Papa AL;Barrile R;Lai A;Schlechter BL;Otieno MA;Louden CS;Hamilton GA;Michelson AD;Frelinger AL 3rd;Ingber DE
血管内皮和剪切应力是体内生理止血和血小板功能的关键决定因素，但当前的诊断和监测设备在评估中并未完全纳入血流下的内皮功能，因此可能不可靠且不准确。由于活细胞培养物不够稳健，因此将内皮纳入临床实验室或护理点环境的检测中具有挑战性。在这里，我们描述了一种微流体装置，其内衬有化学固定的人内皮，但即使在储存几天后，仍然保留其在体外连续流动下调节止血的能力。该装置内衬固定内皮，在生理剪切力存在的情况下支持富含血小板的血栓形成，类似于活动脉血管。我们通过使用从接受抗血小板药物的受试者中采集的少量（0.5 mL）全血，可以在几分钟内测量血栓形成和血小板功能，从而证明了该设备的潜在临床价值。包含固定的内皮微血管将产生可用于诊断和护理点应用的仿生分析装置。本文的在线版本 (doi:10.1007/s10544-016-0095-6) 包含补充材料，可供授权用户使用。
The vascular endothelium and shear stress are critical determinants of physiological hemostasis and platelet function in vivo, yet current diagnostic and monitoring devices do not fully incorporate endothelial function under flow in their assessment and, therefore, they can be unreliable and inaccurate. It is challenging to include the endothelium in assays for clinical laboratories or point-of-care settings because living cell cultures are not sufficiently robust. Here, we describe a microfluidic device that is lined by a human endothelium that is chemically fixed, but still retains its ability to modulate hemostasis under continuous flow in vitro even after few days of storage. This device lined with a fixed endothelium supports formation of platelet-rich thrombi in the presence of physiological shear, similar to a living arterial vessel. We demonstrate the potential clinical value of this device by showing that thrombus formation and platelet function can be measured within minutes using a small volume (0.5 mL) of whole blood taken from subjects receiving antiplatelet medications. The inclusion of a fixed endothelial microvessel will lead to biomimetic analytical devices that can potentially be used for diagnostics and point-of-care applications. The online version of this article (doi:10.1007/s10544-016-0095-6) contains supplementary material, which is available to authorized users.