Exploiting novel antibodies for the early detection of cardiac disease
Conroy, Paul John (2011) Exploiting novel antibodies for the early detection of cardiac disease. PhD thesis, Dublin City University.
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Cardiovascular disease, the single greatest killer in the western world, is credited with causing 48% of all deaths worldwide and is of huge economic importance in healthcare provision. The cardiac troponins are definitive indicators of cardiovascular disease and elevated levels of cardiac troponin I (cTnI) are highly-specific for cardiovascular damage.
Using a specific targeting strategy, a panel of novel antibodies were successfully generated against key epitopes in cTnI that are of paramount importance for specific cardiovascular disease detection. Panels of both monoclonal and recombinant antibodies were generated and fully characterised. This approach required a combination of high-throughput assay screening with „state-of-the-art‟ multiplexed surface-plasmon resonance-based instrumentation. The selected antibodies were demonstrated to outperform current commercially available reagents.
In addition, inherent difficulties associated with the use and expression of cardiac troponin I, the key target analyte, were investigated in detail and alternative recombinant constructs developed and evaluated.
The antibodies ultimately selected were chosen for their applicability for integration on to a point-of-care risk-chip for cardiovascular disease determination due to their specificity, high affinity and genetic tailoring for deployment on a microfluidic device. This stage involved close collaboration with clinical and industrial partners and the commercial feasibility and performance of the antibodies are now under evaluation.
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