Towards the development of a point-of-care detection system for acute respiratory infections

Karagianni, Kyriaki 2024. Towards the development of a point-of-care detection system for acute respiratory infections. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Pneumonia, a severe lower respiratory tract infection, is one of the leading causes of child mortality, especially in lower-middle income countries. In England, 56,210 emergency admissions occurred between 2018-2019, with 3% of cases progressing to complicated pneumonia and secondary sepsis. As pneumonia is the most common cause of paediatric sepsis, early diagnosis and treatment of the underlying infection is crucial to prevent disease progression. The overarching aim of this project is to develop biosensors for the early and accurate diagnosis of pneumonia to ultimately provide guidance on patient treatment, and the risk of developing sepsis. To realise this aim, three different biomarkers implicated in complicated pneumonia have been selected as targets for biosensor development, namely interleukin-6, endotoxin and beta-globin cell free DNA. Utilising electrochemical approaches coupled with recognition elements such as aptamers, antibodies, and molecularly imprinted polymers (MIP), biosensors capable of detecting these markers in citrated plasma have been developed. Endotoxin is a notoriously difficult marker to detect in clinical samples, due to the presence of many interfering components that render the gold standard LAL assay unusable. The development of an aptamer-MIP hybrid sensor coupled with a thorough sample pre-treatment protocol enabled the successful detection of endotoxin from citrated plasma down to concentrations of 10 fg/mL. Utilising aptamer and a capture DNA sequence modified electrodes, detection of IL-6 and beta-globin DNA from citrated plasma has shown to be possible. The use of chemical sensitisers has increased both the sensitivity and dynamic range of these detection systems. The positive results obtained throughout this project provide a platform for further development and integration of the biosensors into a miniaturised format suitable for deployment at point-of-care as a rapid, cost-effective diagnostic. Final testing of the system utilising clinical samples from paediatric pneumonia patients would provide validation of its utility in the clinical space.

Item Type:	Thesis (PhD)
Date Type:	Submission
Status:	Unpublished
Schools:	Schools > Pharmacy
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	5 March 2025
Last Modified:	05 Mar 2025 09:39
URI:	https://orca.cardiff.ac.uk/id/eprint/176618

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