Modelling the Bioelectronic Interface in Engineered Tethered Membranes: From Biosensing to Electroporation

Abstract

This paper studies the construction and predictive models of three novel measurement platforms: (i) a Pore Formation Measurement Platform (PFMP) for detecting the presence of pore forming proteins and peptides, (ii) the Ion Channel Switch (ICS) biosensor for detecting the presence of analyte molecules in a fluid chamber, and (iii) an Electroporation Measurement Platform (EMP) that provides reliable measurements of the electroporation phenomenon. Common to all three measurement platforms is that they are comprised of an engineered tethered membrane that is formed via a rapid solvent exchange technique 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 PFMP, ICS, and EMP are predicted using continuum theories for electrodiffusive flow coupled with boundary conditions for modelling chemical reactions and electrical double layers present at the bioelectronic interface. 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 Staphylococcal α-Hemolysin; the ICS biosensor for measuring nano-molar concentrations of streptavidin, ferritin, thyroid stimulating hormone (TSH), and human chorionic gonadotropin (pregnancy hormone hCG); and the EMP for measuring electroporation of membranes with different tethering densities, and membrane compositions.

Understanding electrochemical properties of supported lipid bilayers interfaced with organic electronic devices

“…As SLBs have both resistive and capacitive properties, and these properties have unique frequency-dependent behaviours, the evolution of the net impedance with frequency provides information on the time constants of the physical processes within the system. 18,24 EIS has been extensively used for the characterization of SLBs including those formed on PEDOT:PSS electrodes. 19 Such studies have primarily focused on understanding the electrochemical properties of SLBs and their interactions with the external environment using experimental data.…”

“…This practice allows for greater interpretability of the sensor output (and thus fluctuations in the nature of the SLB) and improved accuracy in estimating SLB state quantities. Hoiles et al 18 and Valincius et al 19,20 for example, examine the impact of changes in tethered lipid bilayer state and defect formation on sensor output, respectively. Such models have been underutilized, however, in synthesizing sensor output as a function of variations in device-related parameters, such as geometry and material properties.…”