用于凝血检测的声波传感器研究及应用进展

Research and Application Progress of Acoustic Sensors for Coagulation Detection

针对大力发展灵敏准确、实时快速及不受场地环境限制的床旁(POC)凝血检测需求,本文基于凝血过程主要物理化学变化及相应参数变化,对声波传感器在凝血检测中的传感分析原理及模型进行了分析总结。凝血过程是内源性或者外源性的激活剂激活凝血因子引发的一系列酶联反应,血液的黏度、剪切阻力、密度等物理参数随之发生变化,声波传感器通过感应凝血过程中这些物理参数的变化,建立待测样本与凝血时间、血凝块的形成动力学及蛋白质分子含量等的关系,以反映患者的凝血状态。本文重点对石英晶体微天平(QCM)、声表面波(SAW)传感器、薄膜体声波谐振器(FBAR)和兰姆(Lamb)波传感器的传感原理及数学模型进行了介绍;从传感器的结构、压电材料、敏感膜、加工等角度出发,对声波传感器的设计思路及研究重点进行了探讨;结合血液样本特色,剖析了声波传感器的检测信号与凝血过程的对应关系,并综述声波传感器在凝血过程中的应用进展;基于声波传感器快速灵敏、体积小、测试所需样品量少等特点,将其集成到微流控芯片中,以控制凝血检测环境、测试条件等,并适应床旁凝血测试应用需求,对集成声波传感器的微流控芯片在凝血检测中的应用进展和研究重点进行了分析,并对声波传感器在凝血检测中面临的挑战及发展趋势进行了讨论和展望。

For the urgent need to develop a point-of-care test(POCT)method for coagulation detection that is rapid,sensitive,accurate,real-time,and environment-independent,the sensing principles and models of acoustic sensors used in coagulation detection were analyzed and summarized following the introduction of the main physical and chemical changes and corresponding parameters in the process of coagulation.The coagulation process consists of a series of enzyme-linked reactions promoted by coagulation factors triggered by endogenous or exogenous activators and the physical parameters such as blood viscosity,shear resistance,and density change accordingly.Acoustic sensors were adopted to detect the physical parameters in the coagulation process.The relationship between the samples and the coagulation time,thrombus dynamics,protein content,and so on was elaborated and provided information for the patient’s clotting state.In this paper,the sensing principle and mathematical model of quartz crystal microbalance(QCM),surface acoustic wave(SAW)sensor,thin-film bulk acoustic resonator(FBAR),and Lamb wave sensor were introduced.The design idea and hot points of the acoustic sensors were discussed in terms of structure,piezoelectric material,sensitive film,and processing technology.Combined with the characteristics of blood samples,the relationship between acoustic signals and the coagulation process was analyzed,and the application of acoustic sensors in coagulation detection was summarized and prospected.In addition,the application and research hotspots of microfluidic chips integrated with acoustic sensors for coagulation detection have been included,because the integration of the acoustic sensors into the microfluidic chip can help to control the environment and operation conditions for coagulation testing,which can better meet the needs of POC coagulation testing.Finally,the challenges and future development for coagulation detection of acoustic sensors were discussed and prospected.