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St Leonards, Australia

Krishnamurthy V.,University of British Columbia | Cornell B.,Surgical Diagnostics Ltd.
Protoplasma | Year: 2012

This paper presents two important engineering aspects of biological ion channels-how to build sensors out of gramicidin channels and how to construct computational models for ion channel permeation. We describe our recent research in these areas, potential challenges and possible solutions. © 2011 Springer-Verlag.

Krishnamurthy V.,University of British Columbia | Monfared S.M.,University of British Columbia | Cornell B.,Surgical Diagnostics Ltd.
IEEE Transactions on Nanotechnology | Year: 2010

This paper deals with the construction and operation of a novel biosensor that exploits the molecular switching mechanisms of biological ion channels. The biosensor comprises gramicidin A channels embedded in a synthetic tethered lipid bilayer. It provides a highly sensitive and rapid detection method for a wide variety of analytes. In this paper, we outline the fabrication and principle of operation of the ion-channel switch (ICS) biosensor. The results of a clinical study, in which the ion-channel biosensor is used to detect influenza A in untreated clinical samples, is presented to demonstrate the utility of the technology. Fabrication of biochip arrays using silicon chips decorated with ink jet printing is discussed. We also describe how such biochip arrays can be used for multianalyte sensing. Finally, reproducibility/stability issues of the biosensor are addressed. © 2006 IEEE.

Hoiles W.,University of British Columbia | Krishnamurthy V.,University of British Columbia | Cornell B.,Surgical Diagnostics Ltd.
IEEE Transactions on Biomedical Circuits and Systems | Year: 2015

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. © 2014 IEEE.

Moradi-Monfared S.,University of British Columbia | Krishnamurthy V.,University of British Columbia | Cornell B.,Surgical Diagnostics Ltd.
Biosensors and Bioelectronics | Year: 2012

This paper describes the construction, operation and predictive modeling of a molecular machine, functioning as a high sensitivity biosensor. Embedded gramicidin A (gA) ionchannels in a self-assembled tethered lipid bilayer act as biological switches in response to target molecules and provide a signal amplification mechanism that results in high sensitivity molecular detection. The biosensor can be used as a rapid and sensitive point of care diagnostic device in different media such as human serum, plasma and whole blood without the need for pre and post processing steps required in an enzyme-linked immunosorbent assay. The electrical reader of the device provides the added advantage of objective measurement. Novel ideas in the construction of the molecular machine, including fabrication of biochip arrays, and experimental studies of its ability to detect analyte molecules over a wide range of concentrations are presented. Remarkably, despite the complexity of the device, it is shown that the response can be predicted by modeling the analyte fluid flow and surface chemical reactions. The derived predictive models for the sensing dynamics also facilitate determining important variables in the design of a molecular machine such as the ion channel lifetime and diffusion dynamics within the bilayer lipid membrane as well as the bio-molecular interaction rate constants. © 2012 Elsevier B.V.

Abolfath-Beygi M.,University of British Columbia | Krishnamurthy V.,University of British Columbia | Cornell B.,Surgical Diagnostics Ltd.
IEEE Sensors Journal | Year: 2013

This paper addresses the problem of detecting minute concentrations (nano to pico-molar) of analyte in a fluid flow chamber using an array of surface-based sensors. It is shown that in the mass-transport influenced case, when the rate of transport of analyte is comparable to or smaller than the intrinsic reaction rates at the sensor surface, substantial improvements in the response rate can be obtained from an array of spaced small sensor surfaces relative to a single large surface. Advection-diffusion-reaction models are developed to predict the response of such sensor arrays, which are compared to individual sensor surfaces of the same total area. Formulas are derived for quantifying the improvement in performance and optimal size of the sensors in the array. The results of the model are compared with experimental data obtained for an ion-channel switch biosensor and a surface plasmon resonance biosensor. © 2001-2012 IEEE.

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