Development of raman spectroscopic point of care diagnostics for the detection of key targets of disease

Buchan, Emma L (2024). Development of raman spectroscopic point of care diagnostics for the detection of key targets of disease. University of Birmingham. Ph.D.

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Abstract

Inflammatory bowel disease (IBD) and cardiovascular disease (CVD) represent two distinct yet urgent healthcare concerns. IBD, characterised by chronic inflammation of the gastrointestinal tract, poses a significant burden on the affected individuals. Both conditions require early and accurate diagnostic methods to optimise patient care and treatment outcomes. Conversely, CVD continues to be a leading global cause of morbidity and mortality, necessitating innovative approaches to diagnosis and monitoring. Here, we explore the transformative potential of Raman spectroscopy (RS) as a rapid and non-invasive diagnostic tool in the assessment of saliva and blood plasma. The multidimensional approach combining RS with multivariate analysis unveils distinct molecular profiles thus enabling early and accurate disease diagnosis. Classification accuracies of >88 % are demonstrated between three sample types applied to healthy, CVD and follow-up blood plasma. Similarly, in IBD, classification yields accuracies >90 % over four sample types applied to saliva and tissue. This further extends into biomarker discovery, unveiling novel CVD- and IBD-indicative molecular signatures. Feature extraction, inherently connected to classification results, indicates an increase in circulating cytokines, a hallmark of inflammation in both CVD and IBD. Extracellular vesicles (EVs), as biomarkers serve as key carriers of disease-specific biomolecules, therefore, rendering them invaluable in diagnostics and personalised treatment. Conventional EV isolation methods suffer from several limitations such as, low throughput, sample loss, limited scalability and EV damage thus this has led to the exploration of alternative EV isolation techniques. The developed methodologies harness the power of RS to redefine the paradigm of disease diagnosis and risk stratification and as a means of increasing diagnostic accuracy, bridging the translational gap, and facilitating the clinical integration of RS-based diagnostics via a novel lab-on-a-chip (LoC) platform for the isolation and separation of disease-indicative EVs from biofluids. The developed platform marks a significant advance in utilising the diagnostic potential of EVs, offering a streamlined and efficient approach to their isolation and analysis.

Type of Work:	Thesis (Doctorates > Ph.D.)
Award Type:	Doctorates > Ph.D.
Supervisor(s):	Supervisor(s) Email ORCID Goldberg Oppenheimer, Pola UNSPECIFIED UNSPECIFIED Thomas, Mark UNSPECIFIED UNSPECIFIED Harrison, Paul UNSPECIFIED UNSPECIFIED Lord, Janet UNSPECIFIED UNSPECIFIED Thomas, Michael UNSPECIFIED UNSPECIFIED
Licence:	All rights reserved
College/Faculty:	Colleges > College of Engineering & Physical Sciences
School or Department:	School of Chemical Engineering
Funders:	Engineering and Physical Sciences Research Council
Subjects:	Q Science > Q Science (General) Q Science > QD Chemistry R Medicine > RZ Other systems of medicine
URI:	http://etheses.bham.ac.uk/id/eprint/14941

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