Biosensor Research Group, Institute of Clinical and Experimental Transfusion Medicine, University Hospital of Tübingen, Germany.
Anal Chem. 2010 Jan 15;82(2):658-63. doi: 10.1021/ac9021117.
Monitoring of blood coagulation and fibrinolysis is an important issue in treatment of patients with cardiovascular problems and in surgery when blood gets into contact with artificial surfaces. In this work a new method for measuring the coagulation time (prothrombin time, PT) of human whole-blood samples based on a quartz crystal microbalance (QCM) biosensor is presented. The 10 MHz sensors used in this work respond with a frequency shift to changes in viscosity during blood clot formation. For driving and for readout of the quartz, both a network analyzer and an oscillator circuit were utilized. The sensor surfaces were specifically coated with a thin polyethylene layer. We found that both frequency analysis methods are suitable to measure exact prothrombin times in a very good conformity with a mechanical coagulometer as a reference. The anticoagulant effect of heparin on the prothrombin time was exemplarily shown as well as the reverse effect of the heparin antagonist polybrene. The change of the viscoelastic properties during blood coagulation, reflected by the ratio of frequency and dissipation shifts, is discussed for different dilutions of the whole-blood samples. In conclusion, QCM is a distinguished biosensor technique to determine prothrombin time and to monitor heparin therapy in whole-blood samples. Due to the excellent potential of miniaturization and the availability of direct digital signals, the method is predestinated for incorporation and integration into other devices and is thus opening the field of application for inline coagulation diagnostic in extracorporeal blood circuits.
监测血液凝固和纤维蛋白溶解是治疗心血管问题患者和手术中血液与人工表面接触时的一个重要问题。在这项工作中，提出了一种基于石英晶体微天平（QCM）生物传感器测量人全血样本凝血时间（凝血酶原时间，PT）的新方法。在这项工作中使用的 10MHz 传感器对血液形成过程中粘度变化的响应是频率偏移。为了驱动和读取石英，同时使用了网络分析仪和振荡器电路。传感器表面专门涂有一层薄的聚乙烯层。我们发现，这两种频率分析方法都适用于测量非常精确的凝血酶原时间，与机械凝血计作为参考具有很好的一致性。肝素对凝血酶原时间的抗凝作用以及肝素拮抗剂聚多卡醇的反作用也得到了很好的证明。通过测量全血样本不同稀释度时的频率和耗散偏移比来反映血液凝固过程中粘弹性的变化。总之，QCM 是一种用于确定凝血酶原时间和监测全血样本中肝素治疗的杰出生物传感器技术。由于其出色的小型化潜力和直接数字信号的可用性，该方法非常适合集成到其他设备中，从而为体外血液回路中的在线凝血诊断开辟了应用领域。
