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Title: Towards minimally invasive respiratory diagnosis : functional biomaterials for biomarker extraction from the nasal passage
Author: Jones, Paul
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Delay of diagnosis is a significant bottleneck in current healthcare practice, reducing the efficacy of administered treatments. Biomolecular identification and profiling of mucosal fluids constitutes a promising means of minimally invasive and effective diagnosis. This thesis develops a silica-based biomaterial prototype device formulated around the hypothesis of improved respiratory diagnosis through selective marker extraction and separation from nasal fluid. Polydimethylsiloxane rods were successfully functionalised with octadecyl silica (ODS) via surface-initiated atom transfer radical polymerisation (ATRP). Analysis under desorption electrospray ionisation mass spectrometry yielded significant improvements in lipid marker detection compared to currently used cotton swabs. Silica-based scaffolds were then synthesised into xerogels, with their porous and increased surface area properties benefitting diagnostic potential. Surface grafting of ODS onto such xerogels again increased detection of various lipid species via liquid chromatography mass spectrometry detection. Whilst the xerogels’ polydimethylsiloxane-like network allowed for a direct transfer of ATRP functionalisation, the stringent reaction environment conditions of ATRP favoured the use of facile thiol-ene surface grafting methods as a more efficient means of surface modification – and did not affect the inherent beneficial properties of xerogels. The ease and flexibility of xerogel surface modification through thiol-ene methods was then expanded to broaden the range of surface-graftable groups and thus extraction capabilities of the proposed xerogel platform. Allyl methacrylate block copolymers with precise architectures synthesised in solution ex-situ were successfully grafted onto xerogels without any detrimental effect on the xerogels’ inherent physical properties. Shifting focus towards specific marker extraction, grafted mannose glycomonomers allowed dendritic cell extraction from model solutions. Finally, the successful surface-functionalisation of capture antibodies onto xerogels allowed the extraction of specific proteins and their in-situ detection, constituting a firm basis for a point-of-care diagnostic device. Thus, the aim of developing a prototype medical device platform for improved diagnosis through the selective extraction of biomarkers was fulfilled.
Supervisor: Jones, Julian ; Hansel, Trevor Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral