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UBC Theses and Dissertations

Modeling the bioelectronic interface in engineered tethered membranes : biosensing and the electrophysiological response Hoiles, William August


The unifying theme of this thesis is the construction and predictive models of four novel tethered membrane measurement platforms: (i) the Ion Channel Switch (ICS) biosensor for detecting the presence of analyte molecules in a fluid chamber, (ii) a Pore Formation Measurement Platform (PFMP) for detecting the presence of pore forming proteins and peptides, (iii) a Controlled Electroporation Measurement Device (CED) that provides reliable measurements of the electroporation phenomenon, and (iv) an Electrophysiological Response Platform (ERP) to measure the response of ion channels and cells to an electrical stimulus. Common to all four measurement platforms is that they are comprised of an engineered tethered membrane that is formed via a rapid solvent exchange technique developed by Dr. Bruce Cornell allowing the platform to have a lifetime of several months. The membrane is tethered to a gold electrode bioelectronic interface that includes an ionic reservoir separating the membrane and gold surface, allowing the membrane to mimic the physiological response of natural cell membranes. The electrical response of the ICS, PFMP, CED, and ERP are predicted using coarse-grained molecular dynamics, continuum theories for electrodiffusive flow, and macroscopic fractional order models. Experimental measurements are used to validate the predictive accuracy of the dynamic models. These include using the PFMP for measuring the pore formation dynamics of the antimicrobial peptide PGLa and the protein toxin α-Hemolysin; the ICS biosensor for measuring nano-molar concentrations of streptavidin, ferritin, thyroid stimulating hormone (TSH), and human chorionic gonadotropin (pregnancy hormone hCG); the CED for measuring electroporation of membranes with different tethering densities, and membrane compositions; and the ERP for measuring the response of the voltage-gated NaChBac ion channel, and the response of skeletal myoblasts which are attractive donor cells for cardiomyoplasty. We envisage the tethered membrane and atomistic-to-observable dynamic models presented in this thesis to be invaluable for the future development of membrane based biosensors.

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Attribution-NonCommercial-NoDerivs 2.5 Canada