Dataset Information

ZnO Film Bulk Acoustic Resonator for the Kinetics Study of Human Blood Coagulation.

ABSTRACT: Miniaturized and rapid blood coagulation assay technologies are critical in many clinical settings. In this paper, we present a ZnO film bulk acoustic resonator for the kinetic analysis of human blood coagulation. The resonator operated in thickness shear resonance mode at 1.4 GHz. When the resonator contacted the liquid environment, the viscous loading effect was considered as the additional resistance and inductance in the equivalent circuits, resulting in a linear relationship with a slope of approximately -217 kHz/cP between the liquid viscosity and the frequency of the resonator. The downshift of the resonant frequency and the viscosity change during the blood coagulation were correlated to monitor the coagulation process. The sigmoidal trend was observed in the frequency response for the blood samples activated by thromboplastin and calcium ions. The coagulation kinetics involving sequential phases of steady reaction, growth and saturation were revealed through the time-dependent frequency profiles. The enzymatic cascade time, the coagulation rate, the coagulation time and the clot degree were provided by fitting the time-frequency curves. The prothrombin times were compared with the results measured by a standard coagulometer and show a good correlation. Thanks to the excellent potential of integration, miniaturization and the availability of direct digital signals, the film bulk acoustic resonator has promising application for both clinical and personal use coagulation testing technologies.

SUBMITTER: Chen D

PROVIDER: S-EPMC5469538 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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ZnO Film Bulk Acoustic Resonator for the Kinetics Study of Human Blood Coagulation.

Chen Da D Zhang Zhen Z Ma Jilong J Wang Wei W

Sensors (Basel, Switzerland) 20170503 5

Miniaturized and rapid blood coagulation assay technologies are critical in many clinical settings. In this paper, we present a ZnO film bulk acoustic resonator for the kinetic analysis of human blood coagulation. The resonator operated in thickness shear resonance mode at 1.4 GHz. When the resonator contacted the liquid environment, the viscous loading effect was considered as the additional resistance and inductance in the equivalent circuits, resulting in a linear relationship with a slope of ...[more]

PMID: 28467374

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Project description:Blood function defines bleeding and clotting risks and dictates approaches for clinical intervention. Independent of adding exogenous tissue factor (TF), human blood treated in vitro with corn trypsin inhibitor (CTI, to block Factor XIIa) will generate thrombin after an initiation time (T(i)) of 1 to 2 hours (depending on donor), while activation of platelets with the GPVI-activator convulxin reduces T(i) to ∼20 minutes. Since current kinetic models fail to generate thrombin in the absence of added TF, we implemented a Platelet-Plasma ODE model accounting for: the Hockin-Mann protease reaction network, thrombin-dependent display of platelet phosphatidylserine, VIIa function on activated platelets, XIIa and XIa generation and function, competitive thrombin substrates (fluorogenic detector and fibrinogen), and thrombin consumption during fibrin polymerization. The kinetic model consisting of 76 ordinary differential equations (76 species, 57 reactions, 105 kinetic parameters) predicted the clotting of resting and convulxin-activated human blood as well as predicted T(i) of human blood under 50 different initial conditions that titrated increasing levels of TF, Xa, Va, XIa, IXa, and VIIa. Experiments with combined anti-XI and anti-XII antibodies prevented thrombin production, demonstrating that a leak of XIIa past saturating amounts of CTI (and not "blood-borne TF" alone) was responsible for in vitro initiation without added TF. Clotting was not blocked by antibodies used individually against TF, VII/VIIa, P-selectin, GPIb, protein disulfide isomerase, cathepsin G, nor blocked by the ribosome inhibitor puromycin, the Clk1 kinase inhibitor Tg003, or inhibited VIIa (VIIai). This is the first model to predict the observed behavior of CTI-treated human blood, either resting or stimulated with platelet activators. CTI-treated human blood will clot in vitro due to the combined activity of XIIa and XIa, a process enhanced by platelet activators and which proceeds in the absence of any evidence for kinetically significant blood borne tissue factor.

Dataset Information

ZnO Film Bulk Acoustic Resonator for the Kinetics Study of Human Blood Coagulation.

Publications

ZnO Film Bulk Acoustic Resonator for the Kinetics Study of Human Blood Coagulation.

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