Electrophysiological assays of ion channels for pharmaceutical discovery and safety screening are problematic to perform in high throughput because the ion channels must be incorporated into a lipid bilayer membrane to enable measurement of their ionic conductance. As a result, there are currently no high quality, high throughput assays for ion channel screening. Recent developments of automated patch clamp instrumentation are still over two orders of magnitude lower throughput than conventional drug screening for soluble proteins and also require expensive instrumentation, specialized cell lines, and consumables. For existing methods of ion channel screening, there is a large gap in information quality, throughput, and cost. Librede Inc. is developing an alternative technology for ion channel measurement in which the ion channels are reconstituted in artificial lipid bilayer membranes. Librede's patent pending formulation of cell-free artificial bilayers has the potential for significantly higher throughput and lower consumable costs, while requiring less expensive equipment and trained personnel. Librede was founded by the UCLA inventors of this technology;we are now working to transfer this technology from the academic laboratory and develop it commercially. In preliminary work, we have developed inexpensive, disposable, shippable bilayer array chips capable of supporting ion channel measurement in 48 sites simultaneously. We have measured bilayers and ion channels in these chips previously using a multiplexed single channel amplifier;in the work proposed here, we aim to demonstrate higher throughput by measuring all sites in the chip simultaneously using a 48 channel patch clamp amplifier. Simultaneous measurement will be a key test of our technology;we will explore the effects of noise, crosstalk, and bilayer size on our ability to measure bilayers and incorporated ion channels over the entire chip at once. The noise and bandwidth achieved with our system using this instrument will determine our signal detection and temporal resolution and determine the feasibility of this platform for high throughput measurement of ion channels as well as paths to improvements in performance. The ability to measure ion channels in bilayer arrays in parallel will be a major milestone in the development of this technology toward commercialization, and is a preliminary step of the full demonstration of our final product. We will use the materials and experience gained in our Phase I research for Phase II development in which we will integrate low cost mass-producible injection molded shippable bilayer chips with automatable instrumentation for fluid handling and parallel ion channel measurement. This will bring us closer to our goal of reducing the cost and expertise required for ion channel screening by eliminating cell culture and cellular manipulation in pharmaceutical screening, thus significantly increasing throughput and decreasing costs, enabling more effective searches for ion channel drugs.
Measurement of ion channel interactions with drugs is a key process in drug discovery and drug safety screening, but due to the difficulty in working with ion channels the existing processes used are slow, laborious, and expensive. Librede has recently developed a platform for ion channel measurement which is much less expensive and much easier to use, based on lipid membranes that can be shipped-a world first. We propose here to develop instrumentation for simultaneously measuring arrays of ion channels contained in these membranes.
