for screening ion-channel drugs
Yale licensed to Axon Instruments, Inc., a revolutionary technology for screening new drugs that act on cell-membrane ion channels and transporters.
Ion channel activity is important for studying many medical disorders, among them migraine headaches, epilepsy, irregular heartbeat and cystic fibrosis.
Axon is a developer of instrumentation and software for genomics and high throughput screening. The company plans to use the technology as the core component in a "Patch-Clamp-on-a-Chip" device. Patch clamp is a technique in which an electrode is held against a cell's plasma membrane to form an electrically-tight seal, enabling current flowing through individual ion channels to be measured.
The inventors of the new technology are Kathryn Klemic, a postdoctoral associate in physiology at the School of Medicine; Frederick Sigworth, a physiology professor; James Klemic, a postdoctoral associate in electrical engineering and applied physics; and Mark Reed, the Harold Hodgkinson Professor of Engineering and Applied Science and chair of the Department of Electrical Engineering.
The researchers developed a new fabrication method for electrodes used in patch clamp recording of ionic currents. Based on this advance, inexpensive integrated planar electrode and amplifier arrays can be microfabricated for use in highly parallel electrical assays, or analyses, of cells. Microfluidic channels can be incorporated on-chip to permit fast solution exchange on both sides of the membrane. The electrode arrays can be used to record from standard cultured mammalian cell lines.
"A highly-parallel electrode array makes possible multiple, simultaneous, single-cell electrical recordings," Sigworth says. "Both single-channel and whole-cell currents can be measured with high fidelity. The high parallelism increases the throughput of patch-clamp screening by several orders of magnitude, enabling industrial-scale screening of pharmaceutical agents."
"We are extremely enthusiastic about developing an automated, high-throughput patch clamp device," says Chris Mathes, Axon's manager of high throughput electrophysiology screening. "Currently, pharmaceutical screening of important ion-channel drugs is inefficient because the assays are indirect. Because the Yale technology replaces unwieldy conventional patch clamp electrodes, we now have the potential to record ionic currents from a thousand mammalian cells in parallel. This 'Patch-Clamp-on-a-Chip' device can resolve a major bottleneck in the drug discovery process and reduce the total drug discovery timetable."
Andy Blatz, Axon's vice president of screening technology, added, "Axon Instruments is uniquely placed to bring this technology to market. We can leverage our existing expertise in patch clamp hardware and software development to produce an instrument that we believe has the potential to provide more and better information to the pharmaceutical companies than existing patch clamp approaches."
Axon Instruments is located in Foster City, California, and was founded in 1984. It produces a broad spectrum of instrumentation and software for genomics and high throughput screening.
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