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Abstract
Nanopore-based sensors are an emerging class of devices capable of detecting individual molecules owing to its operation simplicity. Despite the ability of nanopore-based sensors to detect single analyte molecules traversing through the nanopore in real-time by means of monitoring the magnitude of ionic current flowing across the pore, the performance of nanopore-based sensors is ultimately limited by the diffusion of the analyte molecule in finding the sensing interface, which is the nanopores in this case and hence results in a long response time. This phenomenon is analogous to the “finding a needle in a haystack problem”, which is evident in a large volume of an extremely diluted analyte sample whereby a long period of time is required for enough analyte molecules to be detected in order to obtain a statistically reasonable measurement of analyte concentration in the sample. This thesis describes the development of a prototype nanoparticle-based nanopore that aims to solve the slow response time problem. Antibody-modified magnetic nanoparticles were employed as selective capture vehicles for the analyte, which upon application of a magnetic field, the analyte-bound magnetic nanoparticles can be pre-concentrated into the nanopores. As the surface of the solid- state nanopores was similarly functionalised with antibodies, the analyte-bound magnetic nanoparticles will be immobilised inside the nanopores while the magnetic nanoparticles that did not bind to any analytes can be removed from the nanopores via application of a magnetic field in the opposite direction. As a result, only magnetic nanoparticles that have captured analytes bound on their surface can cause a decrease in the measured ionic current. The hallmark of this concept is that it is possible to “count” the number of nanopores that were blocked by monitoring the changes in ionic current and thus sensitive enough for applications that requires detection of single molecules in a massively paralleled fashion.