Abstract
Despite the significant advancement in Human Immunodeficiency Virus (HIV) diagnosis and treatment, many HIV+ patients live with the unsuppressed virus, at risk of developing Acquired Immunodeficiency Syndrome. Widely available point-of-care HIV tests provide only a qualitative result, negative or positive, insufficient to propose appropriate treatment. Additional examinations are necessary. The infection stage allows choosing of the optimal set of medications and their doses, whereas the patient’s kidney function minimises the risk of the treatment’s side effects, which often include compromised kidney function.Current laboratory-based methods are laborious, have long result waiting times and require frequent hospital visits, which discourage patients living in low-resource settings with poor access to health clinics. To address the problem of low treatment coverage, there is a need to develop a point-of-care HIV management device. As part of this thesis, electrochemical CD4+ cell and creatinine sensors were developed for the infection stage and the patient’s kidney function evaluation, respectively.
Using copper as an alternative to enzymes was assessed for creatinine sensor development, showing a clinically relevant dynamic range (127 µM – 1332 µM), a limit of detection of 91 µM, and no interference from most of the biomolecules present in the blood. CD4+ cell detection was achieved using an antibody-modified electrode. Polydimethylsiloxane-based microfluidic channels were designed and integrated with the sensor to allow for on-chip electrode functionalisation and cell detection. The linear response from 0.125 × 106 to 2 × 106 cells/mL and the limit of detection 1.41 × 105 cells/mL are relevant to the clinical ranges for healthy and unhealthy patients. The sensor was proven to be selective and showed no response to monocytes/neutrophils and bovine serum albumin. Finally, a microfluidic cell separation chip developed by Hou and his research group at Nanyang Technological University in Singapore was tested confirming its suitability to integrate with the cell and creatinine sensors. This research provides substantial foundations for the development of a fully integrated point of-care HIV management device for multiplexed testing.
| Date of Award | 21 Feb 2024 |
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| Original language | English |
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| Supervisor | Pedro Estrela (Supervisor), Despina Moschou (Supervisor) & Mark Lindsay (Supervisor) |