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Nano-probes for point of care diagnostics
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Baker, Alexander Neil (2021) Nano-probes for point of care diagnostics. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3817482
Abstract
The COVID-19 pandemic has exposed deep health inequalities between more economically developed and less economically developed countries: both in terms of diagnostics and vaccinations. Robust and low-cost point of care devices are needed to ease these diagnostic inequalities. Current point of care lateral flow immunoassays, utilise proteins, such as antibodies, to sense for analytes. This is epitomised by the malaria rapid diagnostic test and archetypal home pregnancy test. Glycans are emerging as alternative detection units due to their fundamental role in biological signalling and recognition events. Furthermore, the increased robustness, low-cost and synthetic possibilities offered by glycan-based systems, especially glycosylated polymers, make them a promising alternative to antibody-based biosensing and diagnostic systems.
Chapter 1 discusses the current use of protein-based lateral flow and flow-through devices; their advantages and disadvantages versus non-point of care techniques, and the potential of glycan-based lateral flow devices. The concepts introduced in Chapter 1 are then applied in Chapters 2 through 5. Chapter 2 demonstrates the use of glycosylated polymer-coated nanoparticles, produced by controlled radical polymerisation techniques for the sensitive, label-free detection of lectins in lateral flow and flow-through. The systems produced use only glycans, not antibodies, to provide recognition – a “lateral flow glyco-assay.” The lessons learned in Chapter 2 are applied in Chapter 3 to probe the glycan-binding of the SARS-COV-2 spike protein in a “flow-through glyco-assay” and target a pseudovirus mimic of the target coronavirus in a lateral flow glyco-assay. Chapter 4 builds on Chapters 2 and 3, applying the fledgling glyco-assay technology to the “real-world” by sensing for the SARS-COV-2 virus in patient samples, alongside exploring the robustness of the devices themselves. Having explored the concept of glycosylated polymer-coated nanoparticles in lateral flow and flow-through setups; Chapter 5 changes focus and explores the use of polymeric anchors for the design of all-polymer (“vegan”) lateral flow and flow-through devices. This work completely removes proteins as either detecting units or anchors from lateral flow for the first time. Chapters 6 and 7 explore more fundamental Chemistry than the previous chapters. Chapter 6 considers the use of the Mannich reaction to produce monosaccharides with amine functionality at C2, ideal for polymer conjugation, while maintaining hydroxyl functionality at C2. Although unsuccessful with the reagents used, the chapter highlights a potential avenue of future chemical exploration in novel glycan synthesis. Chapter 7 pulls together the x-ray photoelectron analysis data and spectra collected across a range of studies, including data collected in previous chapters, and considers if x-ray photoelectron spectroscopy can be used to determine relative grafting density in glycosylated polymer-coated nanoparticle systems.
In summary, the key components of the emerging technology of lateral flow glycoassays are introduced, interrogated and investigated. The prototype devices tested against model proteins, viral proteins and patient samples, are found to show specificities and sensitivities that rival lateral flow immunoassay systems. The understanding developed in this thesis could pave the way to the first generation of lateral flow glyco-assays that are low-cost, stable in a wide range of conditions, and able to target a wide range of analytes and diseases.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QD Chemistry Q Science > QP Physiology Q Science > QR Microbiology R Medicine > R Medicine (General) R Medicine > RB Pathology R Medicine > RC Internal medicine |
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Library of Congress Subject Headings (LCSH): | Immunoassay, Nanoparticles -- Diagnostic use, Point-of-care testing, Glycoproteins, Clinical chemistry, Biosensors | ||||
Official Date: | December 2021 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Department of Chemistry | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Gibson, Matthew I. | ||||
Sponsors: | Midlands Integrative Biosciences Training Partnership ; Biotechnology and Biological Sciences Research Council (Great Britain) ; Iceni Diagnostics | ||||
Format of File: | |||||
Extent: | 2 volumes (multiples leaves) : illustrations, charts | ||||
Language: | eng |
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