Investigation of Prothrombin Time in Human Whole-Blood Samples with a Quartz Crystal Biosensor

Abstract

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.

Adenosine diphosphate-decorated chitosan nanoparticles shorten blood clotting times, influencing the structures and varying the mechanical properties of the clots

“…This phenomenon provides a sensitive and convenient method for measuring the Tc values of clots. 17,19 Figure 4 plots a typical response curve of the ∆F 2 measured by the QCM during clot formation, which is similar to curves presented elsewhere. 17,21 Briefly, recalcified blood samples containing the various NPs were loaded onto a QCM sensor, which rapidly reduced its frequency, by approximately 4KHz, within approximately 30 seconds.…”

“…28 Interestingly, the ∆F 2 values obtained in this study were similar to those revealed by the oscillatory circuit in the QCM with dissipation monitoring (QCM-D) technique, which is used to detect mass deposition or changes in the viscosity of adjacent liquids or blood clots on quartz sensors. 17,19 Although the energy dissipation attributable to the differences in viscosity and density among the clot/PBS and others could not be evaluated by this QCM system, the SEM morphologies of the clots analyzed herein indicated the variation in ∆F 2 values among clots. The SEM morphologies in Figure 3 Figure 4D), according to the equation of Kanazawa and Gordon.…”

“…The QCM has demonstrated high sensitivity to small changes in mass, such as changes caused by the absorption of a protein on a surface or blood coagulation/clot formation, to which the oscillation frequency of the quartz in the device responds. [17][18][19][20][21] The oscillation frequency shifts (∆F 2 ) associated with the propagation of the fibrin network during the formation of clots were analyzed to determine how ANPs or FNPs affect blood clot structure. Compressional flow properties, including clot hardness and compressibility, were determined by texture profile analysis [22][23][24] using a micromechanical test system.…”

A cartridge based sensor array platform for multiple coagulation measurements from plasma

“…Detailed information can be obtained from our previous studies on blood plasma viscosity 21,22 . During blood coagulation, a sudden change in the blood plasma viscosity occurs due to fibrin generation 13 . This kind of viscosity change creates an increase in the hydrodynamic loading of the vibrating structures in viscous liquids according to Sader's theory 27 .…”

LoC sensor array platform for real-time coagulation measurements

“…The researchers utilized microfluidic platforms [3], Quartz Crystal Microbalance (QCM) [4,5] Film Bulk Acoustic Resonator (FBAR) [6] based techniques for clot-time measurements. But they are limited to single tests and not multiplexed.…”