Blood Rheology and Microfluidics

Lead Research Organisation: Swansea University
Department Name: College of Engineering

Abstract

Researchers at Swansea have developed blood characterisation techniques stimulated by an unmet clinical need for improved monitoring and prediction of abnormal clotting responses to therapy or disease. Thromboembolic disease and associated blood clotting abnormalities cause significant morbidity and mortality in Western society, with stroke being the third-leading cause of death in the UK. Clotting abnormalities are responsible for thousands of preventable deaths annually inside UK hospitals and increasing numbers of NHS outpatients require monitoring of oral anticoagulant therapy (e.g. warfarin). But correlation of standard clotting tests to clinical outcome has been unsatisfactory, with uncertain healthcare benefits and limited clinical utility in terms of informing responses to ongoing treatment or disease progression. This PhD will address some of these shortcomings by exploiting our advances in nanotechnology, microfluidics and clot detection. They provide the basis of a new way of monitoring, assessing and predicting the key microstructural and mechanical properties of fully-formed clots, based on information acquired within a few minutes in near-patient tests on small samples of blood - This is in the research area of `Complex Fluids & Rheology`

"The key objective of this PhD project is to exploit recent advances in the areas of nanotechnology, microfluidics and clot detection technologies to develop novel blood coagulation monitoring tools. These tools will provide a new way of monitoring, assessing and predicting the key microstructural and mechanical properties of fully-formed blood clots, based on information acquired within a few minutes in near-patient tests on small samples of blood.

The project is aligned to the `Complex Fluids & Rheology` research area. "

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509553/1 01/10/2016 30/06/2022
1816900 Studentship EP/N509553/1 01/10/2016 30/09/2020 Laura O'Dea
 
Description In a sample undergoing gelation, the gel point (GP) marks the transition between a viscoelastic liquid and a viscoelastic solid which occurs upon establishment of a sample spanning network. The rheological properties of the critical gel (i.e. the transient network that exists at the instant of the GP) is characterized by frequency independence of the loss tangent, tand = G''/G'. Studies of the impact of gel composition/gelation kinetics on the GP have typically employed small amplitude oscillatory shear rheometry (SAOS). Such techniques are however limited to:
i. relatively slow gelation processes for which the samples' rheological properties can be considered quasi-stable throughout data acquisition,
ii. samples for which the mechanical perturbation can be maintained within the linear viscoelastic range throughout gelation, making highly strain-sensitive materials difficult to study, and
iii. perturbation frequencies less than a few Hertz, operating at higher frequencies resulting in artefacts associated with sample/instrument inertia.

Diffusing wave spectroscopy (DWS) is a passive micro-rheological technique which derives the linear rheological properties of strongly optically scattering samples from the mean square displacement (MSD) of embedded scattering particles. DWS has previously been used to monitor the MSD of particles in a sample undergoing gelation and to track changes in optical properties such as the photon transport mean free path, and autocorrelation function intercept throughout gelation. However, attempts to extract rheological parameters such as G*(?) have been limited by the unknown evolution of sample conditions such as temperature or aggregating particle radius. Whilst DWS requires strongly scattering media, Dynamic Light Scattering (DLS) requires that photons undergo a single scattering event before being detected. Between these scattering regimes, it has recently been suggested that the rheological properties of a sample may be determined using Laser speckle rheology (LSR). Several studies have attempted to employ this technique in a variety of model and biological samples but have been limited to extracting pseudo-rheometric parameters.

This work attempts to develop an algorithm for GP determination from MSD measurements acquired using DWS on gelatin (a model, well characterised gelling sample) doped with titanium dioxide (TiO2) scattering particles. LSR techniques are used in the analysis of TiO2 doped gelatin samples at TiO2 concentrations below the DWS limit in order to determine the minimum scattering particle concentration required to obtain an accurate GP estimation. Results are compared with GP data acquired by conventional SAOS techniques.
Exploitation Route The results will form the basis of an application for responsive mode funding targeting widely deployable technologies for the characterisation of complex fluids undergoing sol-gel transitions
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology