Molecular wire based bio-electrochemical sensing systems

Partington, Lee Ian

Medicine
June 2016

Thesis or dissertation


Rights
© 2016 Lee Ian Partington. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.
Abstract

This thesis aims to develop rapid, quantitative point of care sensing systems that exploit molecular wire platforms to enable the electrochemical detection of multiple target biomarkers, thereby empowering new technologies for the diagnosis of various medical conditions. Accordingly, the first chapter provides an overview of clinically important biomarkers for pregnancy and cardiovascular disease. The second chapter of this thesis details the electrochemical concepts underpinning subsequent chapters, with the third chapter providing an experimental overview.

The first two research chapters develop a nano-structured, molecular wire platform based on diazonium salt electrochemistry coupled with immobilisation of antibodies conjugated to a suitable electroactive label. Here, the abundance of amine functionalities present at the antibody paratope enable the statistically large number of redox tags to be present at the antibody-antigen binding site, empowering the exquisitely selective and strong affinity of the antibody for a suitable antigen to be monitored quantitatively, through assessing the extent with which the redox labels are partially blocked in the presence of the antigen. In Chapter 4, experiments are contrasted with bespoke theory developed in order to unravel the thermodynamic and kinetic factors that empower this methodology to be singularly sensitive for the pregnancy biomarker human chorionic gonadotropin (hCG). It is demonstrated that quantitative analysis of hCG detection in artificial urine does not suffer interference. Chapter 5 adapts this approach to survey other biomarkers including β-hCG and brain natriuretic peptide. Combinatorial immunoassays are also investigated through the use of two types of antibodies, each tagged with a different redox label.

Chapter 6 exploits the electroactive spin-trapping molecule TEMPO for the detection of biomolecules that have been damaged through oxidative stress.

Last, Chapter 7 presents an overall conclusion to the work presented in this thesis.

Publisher
Hull York Medical School, The University of Hull and University of York
Sponsor (Organisation)
Biotechnology and Biological Sciences Research Council (Great Britain); Boots Company; University of Hull
Qualification level
Doctoral
Qualification name
PhD
Language
English
Extent
10 MB
Identifier
hull:15133
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