Krampa, F.D2020-11-232020-11-232019-07http://ugspace.ug.edu.gh/handle/123456789/35889PhD. Molecular Cell Biology of Infectious DiseasesIn the field of biomedical diagnostics, rapid and effective monitoring of important analytes is an essential goal, and for this reason, significant progress has been made towards developing high performing analytical tools. Despite these advancements, the majority of the techniques are not suitable for routine uptake in resource-limited regions due to technical and infrastructural challenges. Clinical diagnostics is particularly affected since it is not always available at the point-of-need, notably for infectious diseases which is the key concern to public health in these regions. It is therefore necessary to explore efficient and robust analytical techniques that address the deficiencies of traditional diagnostic methods in preparedness for outbreaks and fieldreadiness. Electrochemical biosensors provide an attractive means to analyze the content of a biological sample due to the direct conversion of a biological event to an electronic signal. The thesis aimed at applying advances in electrochemical biosensor technologies in the development of diagnostic devices for point-of-care testing of infectious diseases. Given that the transducer is of uttermost importance in electrochemical sensors, the suitability of screen-printed electrodes was assessed for use as base transducers. Following this step, nanocomposites made from conductive polymers; poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS), 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]), nafion (Naf) and graphene nanoplatelets (GNPs) were used to modify the electrode surfaces in order to enhance their electrochemical performance. Characterization of screen-printed carbon electrodes (SPCE) modified with IL/PEDOT:PSS and GNPs/Naf showed nano-porous surfaces with enhanced electrocatalytic properties of up to 40-fold compared to the bare unmodified electrodes. The modified surfaces were applied to detect trace levels of electroactive analytes in environmental and biological samples. The PEDOT:PSS/IL was utilised in conjunction with amperometry towards sensitive detection of catechol and differential pulse voltammetry applied at the GNPs/Naf for simultaneous analysis of dopamine (DA) and N-acetyl-p-aminophenol (APAP) in their binary mixtures. The sensors showed excellent selectivity and sensitivity toward the target analytes, with limit of detection of 23.7 μM for catechol and 0.13 μM and 0.25 μM for DA and APAP, respectively. Subsequently, three strategies for immobilizing antibodies (physisorption, covalent binding and polydopamine assisted binding) on screen-printed micro gold electrode surfaces were evaluated for the development of a malaria immunosensor. A sensitive and efficient biosensor was achieved for Plasmodium falciparum histidinerich protein-II (PfHRP-II), aided by the robust covalent coupling between anti-PfHRPII antibodies and an amine layer glutaraldehyde crosslinking on a screen-printed gold microelectrode. The sensor which was built on a label-free impedimetric format was highly reproducible with a low detection limit of 38.0 pg/mL. Based on the efficiency of the covalent immobilisation, the method was repurposed to detect surface antigens of hepatitis B virus. The sensor possessed sufficient sensitivity and selectivity for hepatitis B surface antigens in buffer with a low detection limit of 0.7 ng/mL. These findings demonstrate that the novel nanocomposite-modified sensing platforms could be effective conductive supports in enhancing electroanalysis. The impedimetric immunosensors are a promising inexpensive alternative for label-free analyte detection. Together, these strategies could be integrated into high performing portable selfcontained instruments for point-of-care diagnostic application in resource-limited settings.enElectrochemical BiosensorsClinical DiagnosisInfectious DiseasesThesis