Vitaly Efremov

Measurement of the viscoelastic properties of blood plasma clot formation in response to tissue factor concentration-dependent activation

The coagulation of blood plasma in response to activation with a range of tissue factor (TF) concentrations was studied with a quartz crystal microbalance (QCM), where frequency and half width at half maximum (bandwidth) values measured from the conductance spectrum near resonant frequency were used. Continuous measurement of bandwidth along with the frequency allows for an understanding of the dissipative nature of the forming viscoelastic clot, thus providing information on the complex kinetics of the viscoelastic changes occurring during the clot formation process. Using a mathematical model, these changes in frequency and bandwidth have been used to derive novel QCM parameters of effective elasticity, effective mass density and rigidity factor of the viscoelastic layer. The responses of QCM were compared with those from thromboelastography (TEG) under identical conditions. It was demonstrated that the nature of the clot formed, as determined from the QCM parameters, was highly dependent on the rate of clot formation resulting from the TF concentration used for activation. These parameters could also be related to physical clot characteristics such as fibrin fibre diameter and fibre density, as determined by scanning electron microscopic image analysis. The maximum amplitude (MA) as measured by TEG, which purports to relate to clot strength, was unable to detect these differences.

The modelling of blood coagulation using the quartz crystal microbalance

Blood is a clinically-important analytical matrix that is routinely selected for disease monitoring. Having a clear understanding of the mechanisms involved in blood coagulation is a key consideration in haemostasis, with modern clinical practices requiring rapid, miniaturised and informative diagnostic platforms to reliably study changes in viscoelasticity (VE). Oscillatory transducers such as the Quartz Crystal Microbalance (QCM) have considerable potential in this area, provided that they present simple, linear rheometric readings which can be adequately analysed and interpreted. Hence, integrating QCM data obtained in the laboratory with mathematical modelling of acoustic interactions between quartz crystal surfaces and coagulating blood is an important consideration for modelling thrombus formation. Here, we provide a comprehensive overview of experimental and theoretical applications currently being employed to monitor and model the VE properties of coagulating blood when applied to a QCM resonator, with key emphasis on data modelling and interpretation.

Monitoring the effects of fibrinogen concentration on blood coagulation using quartz crystal microbalance (QCM) and its comparison with thromboelastography

Fibrinogen has been identified as a major risk factor in cardiovascular disorders. Fibrinogen (340 kDa) is a soluble dimeric glycoprotein found in plasma and is a major component of the coagulation cascade. It has been identified as a major risk factor in cardiovascular disorders. The time taken for its conversion to fibrin is usually used as an “endpoint” in most clot-based assays, without any information on dynamic changes in physical properties or kinetics of a forming clot. A global coagulation profile as measured by Thromboelastography® (TEG®) provides information on both the time and kinetics of changes in physical property of the forming clot. In this work, Quartz crystal microbalance (QCM), which is a piezoelectric resonator has been used to study coagulation of plasma and compared with TEG. The changes in resonant frequency (Δf) and half width at half maximum (HWHM or ΔΓ) were used to evaluate effect of fibrinogen concentration. It has been shown that TEG is less sensitive to low concentrations of fibrinogen and dilution while QCM is able to monitor clot formation in both the circumstances.

Lab-on-a disc platform for particle focusing induced by inertial forces

Dean forces have been consistently used in microfluidic mixing units and recently also have been utilized to separate particles in inertial force driven systems by secondary flows. Microfluidic separation systems using inertial forces created by curved asymmetric channels have already been established in the literature. In the present work, we propose a centrifugal lab-on-a-disc platform, which can provide focusing of particles of 21μm diameter size and high separation of two different density types of particles (polystyrene and silica) using of both the inertial focusing forces and sedimentation forces. This comprises the primary advantage of the proposed platform compared to a pump-driven system. This platform can be utilized for the separation of different types of cells bound to specifically-functionalized particles of different densities.

Point of care (POC) blood coagulation monitoring technologies

Abstract The monitoring of bleeding and clotting risk is a critical component of patient care, as either excessive bleeding or abnormal clotting can have obvious and serious consequences for health and well-being and is related to many other co-morbidities. Classical hemostasis management has been around the monitoring of the time it takes activated blood samples to clot. Such techniques have moved from central laboratory tests to point-of-care technologies, allowing more effective management and treatment. However, such techniques are limited in the information they provide on clotting or bleeding status. There is a big move toward novel approaches which purport to be more representative of an individuals clotting and bleeding risk. These techniques are already being used in, and developed for, point-of-care applications.