Jain Abhishek, Graveline Amanda, Waterhouse Anna, Vernet Andyna, Flaumenhaft Robert, Ingber Donald E
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.
Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
Nat Commun. 2016 Jan 6;7:10176. doi: 10.1038/ncomms10176.
Accurate assessment of blood haemostasis is essential for the management of patients who use extracorporeal devices, receive anticoagulation therapy or experience coagulopathies. However, current monitoring devices do not measure effects of haemodynamic forces that contribute significantly to platelet function and thrombus formation. Here we describe a microfluidic device that mimics a network of stenosed arteriolar vessels, permitting evaluation of blood clotting within small sample volumes under pathophysiological flow. By applying a clotting time analysis based on a phenomenological mathematical model of thrombus formation, coagulation and platelet function can be accurately measured in vitro in patient blood samples. When the device is integrated into an extracorporeal circuit in pig endotoxemia or heparin therapy models, it produces real-time readouts of alterations in coagulation ex vivo that are more reliable than standard clotting assays. Thus, this disposable device may be useful for personalized diagnostics and for real-time surveillance of antithrombotic therapy in clinic.
准确评估血液止血功能对于使用体外设备、接受抗凝治疗或患有凝血病的患者的管理至关重要。然而,目前的监测设备无法测量对血小板功能和血栓形成有显著影响的血流动力学力的作用。在此,我们描述了一种微流控设备,它模拟了狭窄小动脉血管网络,能够在病理生理流动条件下,在小样本体积内评估血液凝固情况。通过基于血栓形成的现象学数学模型进行凝血时间分析,可以在体外对患者血液样本中的凝血和血小板功能进行准确测量。当该设备集成到猪内毒素血症或肝素治疗模型的体外循环中时,它能够在体外实时读出凝血变化情况,比标准凝血检测更可靠。因此,这种一次性设备可能有助于个性化诊断以及临床抗血栓治疗的实时监测。