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Development of coagulation monitoring devices

Dudek, Magdalena M. (2010) Development of coagulation monitoring devices. PhD thesis, Dublin City University.

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This thesis describes several aspects of the development of point-of-care, blood coagulation monitoring assay devices including, the design and modification of the underlying substrate platform, development and optimisation of the active assay reagent formulations required for particular assays, the investigation of novel coagulation detection approaches, and analysis of resulting clinical data to establish the usefulness of such assays in point-of-care diagnostic applications. The work resulted in the demonstration of two types of point-of-care coagulation assays; one for measuring fibrinogen levels and the other for the performance of clotting time tests such as an activated partial thromboplastin time. Chapter 1 is an introductory chapter describing the normal process of haemostasis and mechanisms of thrombosis. Various classes of anticoagulant drugs and mechanisms by which they exert their activity were explained. A number of substances used to induce clotting and their application in coagulation monitoring assay devices were discussed, as were issues relating to substrate materials and their surface modification for the purposes of assay device development. Chapter 2 outlines the materials and methods used in this study. Chapter 3 investigates the use of a novel micropatterned polymer substrate material for the development of coagulation assays and the modifications these required to make this feasible. It provides an in-depth characterisation of the modification of the micro-patterned substrate with various surface layers such as oxygen plasma treatment, poly (acrylic acid), polyelectrolyte, SiOx and dextran to produce surfaces which were hydrophilic and biocompatible with blood. A broad range of modified surfaces were investigated and documented. A detailed physical and biological characterisation was performed of the best performing surface. Chapter 4 demonstrates the development of a lateral flow clotting assay device based on the platform investigated in Chapter 3. A fibrinogen content assay device was successfully developed based on the established principle. This rapid, simple and reliable device was shown to be a viable assay for point-of-care determination of clinically relevant concentrations of fibrinogen. The device was capable of measuring plasma and whole blood fibrinogen. Assay precision and accuracy were evaluated by correlating against the “gold standard” hospital method and the assay was validated with patient samples. Chapter 5 focuses on the characterisation of a range of commercially available aPTT reagents and their performance in dried format to assess their suitability for incorporation into the aPTT assay developed in the subsequent chapter (Chapter 6). A comparison of ten reagents in terms of their ability to rapidly and reliably activate coagulation was performed. Their response to heparin dosage was also comprehensively investigated. Chapter 6 describes the development of an assay for the accurate determination of clotting times and their modification by anticoagulant drugs. This device was again based on the platform studied in Chapter 3 and the reagents screened in Chapter 5. The assay was based on the detection of clot formation in a lateral flow device by using a fluorescently-labelled fibrinogen reagent. The overall outcome was a reproducible, single-step, fluorescence-based assay capable of a wide heparin dosage range assessment, 0 – 2 U/mL in both plasma and whole blood samples. The assay was validated using both heparin-spiked control plasma and samples from patients subject to anticoagulant therapy. The results correlated well with two independent methods routinely used in hospital practice for aPTT determination. Chapter 7 briefly summarises the overall conclusions of the thesis and suggests further potential work relating to these assay devices.

Item Type:Thesis (PhD)
Date of Award:June 2010
Supervisor(s):Killard, Anthony J.
Uncontrolled Keywords:Biomedical diagnostics
Subjects:Physical Sciences > Analytical chemistry
Biological Sciences > Microfluidics
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Chemical Sciences
Research Initiatives and Centres > Biomedical Diagnostics Institute (BDI)
Research Initiatives and Centres > National Centre for Sensor Research (NCSR)
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 License. View License
Funders:Science Foundation Ireland
ID Code:15719
Deposited On:04 Apr 2011 15:22 by Tony Killard. Last Modified 01 May 2012 16:17

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