用于aPTT测量的Parylene-C增强型石英晶体微天平耗散检测系统
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摘要
房颤、血栓等患者抗凝药物日常口服等场景迫切需要凝血参数快速检测,本文设计和制作了一种Parylene-C增强型石英晶体微天平(QCM)传感器及其耗散因子检测系统用于凝血测量。首先使用Parylene-C有效增加石英晶体微天平传感器的峰峰值和有效使用次数,基于传感器耗散因子对血液凝固过程血液粘弹性变化敏感,设计电导谱分析法的压电传感器耗散因子快速测量系统,对血浆部分凝血活酶时间(aPTT)进行测量。并用SYSMEX CS 5100光学凝血仪、Lambda 950分光光度计验证系统测量结果。实验表明,Parylene-C增强型QCM传感器信号峰峰值增加8±1%,传感器aPTT实验有效重复使用次数为30次,系统30℃温差最大耗散偏移2.09×10-6。aPTT耗散曲线与光学法(lambda950)吸光度曲线变化趋势一致。与SYSMEX CS 5100临床结果线性拟合决定系数R2为0.99。同样本10次重复实验结果变异系数为1.48%。Parylene-C增强型QCM传感器与耗散分析法的联合应用具备多场景下凝血参数快速检测的能力,系统温度稳定性好,具有满足即时检测应用的潜力。
To address the need to rapidly detect blood coagulation in daily administration ofanticoagulant for atrial fibrillation and thrombus patients and others,a Parylene-C enhanced quartz crystal microbalance(QCM)sensor and a dissipation detection system were designed and manufactured for the measurement of coagulation parameters.Parylene-C was used to enhance the peak-to-peak value and reusability of the QCM sensor.A dissipation detection system for piezoelectric sensors was designed using the principle of conductance spectrum analysis to measure the activated partial thromboplastin time(aPTT)based on the sensitivity of the sensor's dissipation to the change of blood viscoelasticity in the coagulation process.The SYSMEX CS 5100 optical coagulometer system and Lambda 950 spectrophotometer were used to evaluate the system.The results indicate that Parylene-C increases the sensor's peak-to-peak value by 8±1% and it can be reused 30 times.The system has a maximum dissipation excursion of 2.09×10-6 with a temperature difference of 30 ℃.The dissipation and absorbance curves of optical detection(Lambda 950)have the same variation trend.The adjusted R-square value of the linear fitting with SYSMEX CS 5100 is 0.99.The results of the experiment,repeated 10 times with the same sample,have a variable coefficient of 1.48%.The combination of the Parylene-C enhanced QCM and dissipation detection system is highly temperaturestable,can rapidly detect blood coagulation in different scenarios,and has the potential for point-ofcare testing.
To address the need to rapidly detect blood coagulation in daily administration ofanticoagulant for atrial fibrillation and thrombus patients and others,a Parylene-C enhanced quartz crystal microbalance(QCM)sensor and a dissipation detection system were designed and manufactured for the measurement of coagulation parameters.Parylene-C was used to enhance the peak-to-peak value and reusability of the QCM sensor.A dissipation detection system for piezoelectric sensors was designed using the principle of conductance spectrum analysis to measure the activated partial thromboplastin time(aPTT)based on the sensitivity of the sensor's dissipation to the change of blood viscoelasticity in the coagulation process.The SYSMEX CS 5100 optical coagulometer system and Lambda 950 spectrophotometer were used to evaluate the system.The results indicate that Parylene-C increases the sensor's peak-to-peak value by 8±1% and it can be reused 30 times.The system has a maximum dissipation excursion of 2.09×10-6 with a temperature difference of 30 ℃.The dissipation and absorbance curves of optical detection(Lambda 950)have the same variation trend.The adjusted R-square value of the linear fitting with SYSMEX CS 5100 is 0.99.The results of the experiment,repeated 10 times with the same sample,have a variable coefficient of 1.48%.The combination of the Parylene-C enhanced QCM and dissipation detection system is highly temperaturestable,can rapidly detect blood coagulation in different scenarios,and has the potential for point-ofcare testing.
引文
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[16]李敬,潘海曦,郭振,等.Parylene增强型声表面波传感器及其温度响应[J].光学精密工程,2017,25(12):3048-3055.LI J,PAN H X,GUO ZH,et al..Parylene-enhanced SAW sensor and its temperature response[J].Opt.Precision Eng.,2017,25(12):3048-3055.(in Chinese)
[17]YANG Y,WEI Z,ZHEN G,et al..Stability Enhanced,Repeatability Improved Parylene-C Passivated on QCM Sensor for aPTT Measurement[J].Biosensors and Bioelectronics,2017,98:41-46.
[18]LAKSHMANAN R S,EFREMOV V,CULLEN S M,et al..Measurement of the evolution of rigid and viscoelastic mass contributions from fibrin network formation during plasma coagulation using quartz crystal microbalance[J].Sensors and Actuators B:Chemical,2014,192(3):23-28.
[19]黄佳.高频小型石英晶体微天平的研究[D].东南大学,2015.HUANG J.Study on miniaturized high-frequency quzrtz crystal microbalance[D].Southeast University,2015.(in Chinese)
[20]SINAURIDZE E I,VUIMO T A,TARANDOVSKIY I D,et al..Thrombodynamics,a new global coagulation test:Measurement of heparin efficiency[J].Talanta,2017,180:282-291.
[2]HARRIS L F,CASTRO L V,KILLARD A J.Coagulation monitoring devices:Past,present,and future at the point of care[J].Trends in Analytical Chemistry,2013,50:85-95.
[3]HARRIS L,LAKSHMANAN R S,EFREMOV V,et al..Point of care(POC)blood coagulation monitoring technologies[M].Medical Biosensors for Point of Care(POC)Applications.2017.
[4]HUSSAIN M,WENDEL H P,SCHMIDT K,et al..QCM-D surpassing clinical standard for the dose administration of new oral anticoagulant in the patient of coagulation disorders[J].Biosensors&Bioelectronics,2017,104:15.
[5]WITT V,PICHLER H,BEIGLBOECK E,et al..Changes in hemostasis caused by different replacement fluids and outcome in therapeutic plasma exchange in pediatric patients in a retrospective single center study[J].Transfusion&Apheresis Science Official Journal of the World Apheresis Association Official Journal of the European Society for Haemapheresis,2017,56(1):59.
[6]HUSSAIN M.QCM-D for Haemostasis Assays:Current Status and Future:A Review[J].UK Journal of Pharmaceutical and Biosciences,2016,4(1):121-132.
[7]LEI K F,CHEN K H,TSUI P H,et al..Realtime electrical impedimetric monitoring of blood coagulation process under temperature and hematocrit variations conducted in a microfluidic chip[J].Plos One,2013,8(10):e76243.
[8]CHEN D,SONG S,MA J,et al..Micro-electromechanical film bulk acoustic sensor for plasma and whole blood coagulation monitoring[J].Biosensors&Bioelectronics,2016,91:465.
[9]YANG C L,HUANG S J,CHOU C W,et al..Design and evaluation of a portable optical-based biosensor for testing whole blood prothrombin time[J].Talanta,2013,116(22):704-711.
[10]薛严冰,李亚,于婧怡.基于PANI/SnO2符合材料的QCM水果气体传感器[J].光学精密工程,2015,24(10):0511-0519.XUE Y B,LI Y,YU J Y.QCM fruit gas sensor based on PANI/SnO2composite materials[J].Opt.Precision Eng.,2015,24(10):0511-0519.(in Chinese)
[11]张冬至.静电诱导自组装碳纳米管薄膜的结构表征与电学性能[J].光学精密工程,2014,22(6):1562-1570.ZHANG D ZH.Structure characterization and electric properties of electrostatic-induced self-assembly carbon nanotube films[J].Opt.Precision Eng.,2014,22(6):1562-1570.(in Chinese)
[12]HUSSAIN M,NORTHOFF H,GEHRING F K.QCM-D providing new horizon in the domain of sensitivity range and information for haemostasis of human plasma[J].Biosensors and Bioelectronics,2015,66:579-584.
[13]JIN J,JIANG W,YIN J,et al..Stagnaro P.Plasma Proteins Adsorption Mechanism on Polyethylene-Grafted Poly(ethylene glycol)Surface by Quartz Crystal Microbalance with Dissipation[J].Langmuir.,2013,29(22):6624-6633.
[14]EFREMOV V,KILLARD A J,BYRNE B,et al..The modelling of blood coagulation using the quartz crystal microbalance[J].Journal of Biomechanics,2013,46(3):437.
[15]MULLER L,SINN S,DRECHSEL H,et al..Investigation of prothrombin time in human wholeblood samples with a quartz crystal biosensor[J].Analytical Chemistry,2010,82(2):658.
[16]李敬,潘海曦,郭振,等.Parylene增强型声表面波传感器及其温度响应[J].光学精密工程,2017,25(12):3048-3055.LI J,PAN H X,GUO ZH,et al..Parylene-enhanced SAW sensor and its temperature response[J].Opt.Precision Eng.,2017,25(12):3048-3055.(in Chinese)
[17]YANG Y,WEI Z,ZHEN G,et al..Stability Enhanced,Repeatability Improved Parylene-C Passivated on QCM Sensor for aPTT Measurement[J].Biosensors and Bioelectronics,2017,98:41-46.
[18]LAKSHMANAN R S,EFREMOV V,CULLEN S M,et al..Measurement of the evolution of rigid and viscoelastic mass contributions from fibrin network formation during plasma coagulation using quartz crystal microbalance[J].Sensors and Actuators B:Chemical,2014,192(3):23-28.
[19]黄佳.高频小型石英晶体微天平的研究[D].东南大学,2015.HUANG J.Study on miniaturized high-frequency quzrtz crystal microbalance[D].Southeast University,2015.(in Chinese)
[20]SINAURIDZE E I,VUIMO T A,TARANDOVSKIY I D,et al..Thrombodynamics,a new global coagulation test:Measurement of heparin efficiency[J].Talanta,2017,180:282-291.