Microfluidic platform for bilayer experimentation: from a research tool towards drug screening

Ion channels, which are located in the membranes of cells, are responsible for a number of physiological processes. Mutations in genes encoding ion channels resulting in alteration of their function can be associated with diseases, which makes them attractive targets for drug screening. In this thesis, a microfluidic device for bilayer experimentation has been developed, and its possible utilization for drug screening on ion channels discussed. First, various technical aspects have been considered such as the design and fabrication of the microfluidic platform, a reliable protocol for bilayer formation has been established, and the coupling of the platform to various detection techniques including high resolution confocal imaging and electrophysiological measurements has been achieved. The potential of the platform has been demonstrated through electrophysiological measurements of ion channel models (α-hemolysin and gramicidin) down to the single molecule level, and by proof-of-principle experiments to sense changes in the pore formation of the peptide gramicidin after its exposure to external soluble factors (ethanol & acetylsalicylic acid). The combination of optical and high resolution confocal imaging with electrophysiological measurements has particularly been applied to study the impact of cholesterol on the bilayer properties (thickness and fluidity) and their effect on the ion channel function. Finally, the multiplexing of the device has been demonstrated. While most of these developments have been driven by the motivation to develop a drug-screening platform, a technology assessment exercise has been conducted to identify alternative applications and to foresee possible hurdles that could be encountered during technology transfer and product development.