A Study on Monitoring Blood Coagulation Reaction by Use of Self-Sensing Piezoresistive Microcantilever and Fast Fourier Transform Analysis System
Date Issued
2015
Date
2015
Author(s)
Lin, Hao-Qin
Abstract
This study has developed a real-time coagulation monitoring sensor by using an externally vibrated, self-sensing piezoresistive microcantilever for disposable point-of-car coagulation device. With the increasing use of oral anti-coagulant drugs and increasing adverse drug events, the need for point-of-care coagulation devices has become necessary. Prothrombin time (PT) is a measure of the extrinsic pathway of blood coagulation, and it is an index for anticoagulant therapy to determine the blood condition in coagulation reaction. In this study, the measurement was performed by vibrating the piezoresistive microcatilever immersed in the sample liquid at a fixed frequency of 10 Hz and fixed amplitude of 40 μm. The acquired signal of resistance change in microcantilever was processed by Fast Fourier Transform algorithm, and the resistance amplitude in 10 Hz indicated the amount of force exerting to the cantilever. In coagulation reaction, the viscosity of samples was sharply changed due to the clot formation, and the increased force can be sensed when the resistance amplitude in 10 Hz rises. Prothrombin time can be obtained by the time needed for fibrin clot formation. The method was initiated by Sonoclot analysis. The amplitude of resistance in the specific frequency was found in a well linear correlation with kinematic viscosity changes of glycerol/water solutions (R2 > 0.99). It was also found that the amplitude-kinematic viscosity curve behave differently in very low kinematic viscosity, probably due to the decrease in viscous drag of low kinematic viscosity fluids. Also, the Reynolds number correlation can be achieved to present the relation of vibrated microcantilevers in sample liquid. Thus, ∆R/R_0 (ppm)=2〖Re〗^(-0.659)(R2 = 0.985) was derived to successfully describe the relation between acquired signals and vibrated Reynolds number. In addition, three types of commercially standard human plasma samples for measurement of coagulation prothrombin time were used for characterizing microcantilever sensors. The measured results of resistance amplitude in specific frequency with specific patterns of signature indicated the viscoelastic changes in blood coagulation reaction process. In coagulation reaction of human plasma control level 1, the PT measured by the microcantilevers was 12.08 sec with std. of 1.53 sec; PT = 27.08 sec with std. of 1.61 sec in human plasma control level 2; and PT = 38.08 sec with std. of 2.75 sec in human plasma control level 3. Compare with commercial coagulation device, the PT showed an excellent agreement between the microcantilever sensor and commercial device in 95% confident range. All results lay in the PT ranges of references. The experiment results demonstrated that the PT can be measured by vibrated microcantilevers accurately and precisely. Thus, this microcantilever sensor has demonstrated the real-time measurement for point-of-care coagulation monitoring, and shown its potential in miniaturization for personal diagnosis.
Subjects
piezoresistance
microcantilever
prothrombin time
viscosity
Type
thesis
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