Towards minimally invasive respiratory diagnosis: functional biomaterials for biomarker extraction from the nasal passage
File(s)
Author(s)
Jones, Paul
Type
Thesis
Abstract
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.
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.
Version
Open Access
Date Issued
2018-05
Date Awarded
2018-12
Copyright Statement
Creative Commons Attribution NonCommercial NoDerivatives Licence
Advisor
Jones, Julian
Hansel, Trevor
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)