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Title: Development of nanoparticle-based biosensing for molecular diagnostics
Author: Brangel, Polina
ISNI:       0000 0004 7657 1619
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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Ebola virus disease causes widespread and highly fatal epidemics in human populations. During the latest outbreak in West Africa only 60% of the affected people underwent diagnosis, emphasising the unmet need for suitable diagnostics tools. This thesis harnesses the intrinsic optical properties of nanoparticles for the development of two nanoparticles-based biosensing systems for the detection of Ebola virus. The first system is a serological point-of-care test for humoral immune response to Ebola virus. This test combines in-house made capture ligands, lateral flow technology with a custom smartphone application. The final format of the test replicates all mechanical, optical and electronic functions of a laboratory-based enzyme-linked immunosobent assay in a single and multiple analytes formats. This assay was evaluated validated in Uganda using sera from nearly 130 Sudan Ebola Virus survivors and controls, demonstrating 96% sensitivity and 100% specificity. In addition to the single analyte format, two configurations of the multiple analyte formats were constructed. The first configuration simultaneously detected the immune response to three viral antigens. In the second configuration, the point-of-care test was translated for Bundibugyo Ebola Virus species and used for the identification of immune cross reactivity between viral species. The second system was targeted for earlier stage viral detection via direct detection of fragments of viral nucleic acids. This assay comprised spherical nucleic acids nanoparticles as the biosensing interface and Exonuclease III for target recycling amplification. Although the system is operated in a laboratory, it was addressed to function with the simplest form of laborious equipment to enable its used in resource-limited facilities. These complementary systems have to potential to be utilised for patient management, surveillance during and post outbreaks and vaccine and therapeutic evaluation.
Supervisor: Stevens, Molly Sponsor: Kryszek/Staislawa Scholarship
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral