Probing Ion Channel Function

Courtesy of Cellectricon The beating of a heart, the ability to learn and remember, and the movement of a sperm cell's tail all have at least one thing in common: They depend on the function of ion channels, the membrane proteins that control the flow of ions between cells. Currently the only method for measuring ion channel activity is the patch-clamp method, in which a cell's membrane is pierced by the tip of an electrode-containing micropipette. The electrode detects electrical current passing through the membrane, thereby measuring the number of ion channels that are open in the cell. Pharmaceutical companies often use patch-clamp technology to determine if a drug candidate affects the functioning of ion channels, but the method has been a bottleneck, as it is done primarily manually or semimanually and requires a high level of skill to perform correctly. Swedish company Cellectricon hopes to change this with a novel combination of conventional patch-clamp technology, robotics, and microfluidics. The company's first product release, the Dynaflow™ system, consists of disposable microfluidic chips containing up to 16 microchannels (chips with larger arrays will soon be available) leading to an open reservoir. Drugs passing through the channels and into the reservoir maintain laminar flow and behave as if they are still confined in the channels. A patch-clamped cell located in the open space of the chip can then be exposed to each drug candidate sequentially using a robotic device and controller. Cellectricon's chief science officer, Owe Orwar (coinventor of the Dynaflow chip along with Daniel Chiu of the University of Washington and Cellectricon employees) says that while current state-of-the-art methods based on traditional patch-clamp can measure up to 20 data points per day, the Dynaflow system can measure thousands. "The increase in throughput is orders of magnitude higher than the best current technology can do," says Orwar. He adds that the system is designed to be easily scaled-up and that the quality of data obtainable by this method is much higher than that from current technology, as the cell is exposed to different drugs in a stepwise function rather than in a concentration gradient. "You don't go through any concentration landscape," Orwar explains. "You go from one well-defined concentration of drug A, to another well-defined concentration for drug B, and so forth, in milliseconds." Jakob Lindberg, Cellectricon CEO, says that since the product's launch last spring sales have been higher than expected, owing in part to an increased number of potential ion-channel applications for the technology. "We have started to realize that this basic technology can be used also for a lot of other target systems, like standard G-protein receptors and other kinds of surface-based molecules. So, not only has the technology been very well received so far, but also the potential application area has grown over the last six months," says Lindberg. Three of the largest pharmaceutical companies already have Dynaflow systems in place. Ingemar Jacobson, associate principal scientist at AstraZeneca R&D, Mölndal, Sweden, uses the Dynaflow chip system to study ion channels in heart muscle. Jacobson, whose lab has purchased two systems, says the Dynaflow chips are more robust and stable than conventional patch-clamp perfusion systems and that overall he is pleased with the technology. "It works beautifully. It has made life easier when it comes to our type of patch-clamp experiments," says Jacobson. Cellectricon has two more products in its pipeline, a glass capillary-based high-throughput electroporation instrument called Electroflow™, and an electrophysiology system called Nanoflow™. This latter system, which takes ion channel measurements for multiple cells in parallel, is meant for very high-throughput primary screening of drug candidates. Lindberg says competing manufacturers have attempted to develop parallel instruments but that the resulting products have been too costly to run for primary screening. "If you want to run 400,000 compounds through the system for a screening campaign, there is no way you're going to pay more than 50 cents per data point," he says, adding that Cellectricon's goal is to drive prices down to below this level. The company's competitors, he claims, "are up at roughly $10 a data point," or about 20 times higher than the industry can accept, "which is, of course, a big problem for them." --Aileen Constans function sendData() { document.frm.pathName.value = location.pathname; result = false if (document.frm.score[0].checked) result = true; if (document.frm.score[1].checked) result = true; if (document.frm.score[2].checked) result = true; if (document.frm.score[3].checked) result = true; if (document.frm.score[4].checked) result = true; if (!result) alert("Please select") return result; } .myradio{background-color : #94bee5} Please indicate on a 1 - 5 scale how strongly you would recommend this article to your colleagues? Not recommended 1 2 3 4 5 Highly recommended Please register your vote

Probing Ion Channel Function

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