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Cellectricon Expands Flagship Chip Tech to Compete in Growing hERG Screening Market

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Swedish biotech Cellectricon said last week that it has released a new version of its flagship chip-based electrophysiology system to enable users to conduct safety pharmacology and hERG studies

Cellectricon also revealed the identity of the system's first beta-tester, Swiss CRO bSys, which has produced data showing that IC50 values obtained with Cellectricon's platform correlate to known values obtained with conventional manual patch clamping techniques.

The new product could open up the rapidly expanding and potentially lucrative hERG screening market to Cellectricon, and, according to Cellectricon vice president of R&D Mattias Karlsson, rounds out the company's product line so customers can now essentially "screen any type of ion channel" with DynaFlow.

It is unclear exactly what the overall size of the hERG screening market is, but there is little doubt of the importance of hERG screening in drug discovery. Several industry sources estimate that 25 to 40 percent of all lead compounds show some activity toward the hERG ion channel.

Add to that the well-documented recalls of pain-relieving drugs in the early 90's due to hERG-related toxicity effects, and pharmaceutical companies have been clamoring for newer, better, and faster ways to screen for hERG-related toxicity early in the drug-discovery process.


It is unclear exactly what the overall size of the hERG screening market is, but there is little doubt of the importance of hERG screening in drug discovery. Several industry sources estimate that 25 to 40 percent of all lead compounds show some activity toward the hERG ion channel.

The original DynaFlow system consists of a microfluidics-based chip and analysis software, and is intended to be used with traditional manual patch-clamp systems, such as those sold by Molecular Devices or German firm Heka. Essentially, researchers can move patch-clamped single cells across a number of the chip's microfluidic channels, each of which can deliver compounds or buffers in varying solutions.

Dynaflow had seen early success as a way to conduct ion channel screens in the lead optimization phase of drug discovery, but its capabilities were still limited, according to Karlsson.

"We've kind of expanded the system a little bit," he said. "Essentially we've designed a new chip family that is tailor-made for hERG screening … or cumulative dose-response work.

"The chips have much longer run times; larger channels so you can work with myocytes and larger cell lines in general; and greatly reduced compound absorption, so you can work with the really sticky stuff that tends to be a problem with hERG screens," Karlsson said. In addition, he said the software has been updated to function with the new chips, and Cellectricon said that the system is GLP-compliant.

The longer run time — about double that of the older chips — is particularly important for hERG screening, Karlsson said.

"It is the effective experimental time you can use the chip," he said. "With hERG screens, you need quite long exposure times … before you get a stable response. For a lot of substances you need a longer run time, because the cell will spend up to 15 minutes in every concentration. So with the old chips you could test many compounds and concentrations before the chip was empty; but with the new chips you can squeeze more data from the cells, essentially."

Cellectricon has spent most of the last year developing the hERG screening-enabled version of DynaFlow, which is called the DF-8 Pro II Chip. The "8" refers to the number of channels in the new version; Karlsson said that a 16-channel version will also be available. The original DynaFlow platform comes in 8-, 16-, and 48-channel versions.

The company anticipates that some customers will prefer the slightly higher throughput of the 16-channel chip for hERG screening, but "it's not as specific as the eight-channel chip," Karlsson said. "In general you don't need more than eight channels to do a hERG screen, because you're doing cumulative dose responses."

Cellectricon's first beta tester, Swiss CRO bSys, has been assessing the data quality of the new chip against known IC50 values for various compounds obtained with traditional manual patch clamping. Cellectricon has published the data on its website, but Karlsson said he was unsure whether bSys was planning to submit its findings for publication in a peer-reviewed journal.

"We have incorporated the DynaFlow system and the new DF-8 Pro II Chip into our cardiac safety assessment services," Daniel Konrad, bSys' CEO, said in a statement. "The system enabled us to perform standardized and reproducible GLP hERG studies of ion channels with outstanding data quality."

"There has been a lot of talk recently about the automated patch clamp systems and data quality — about how your IC50 values from the automated patch clamp systems correlate to conventional patch-clamp data," Karlsson said. "It turns out there are rather large deviations in some of these systems. So bSys showed us that with the new DynaFlow system and chips that you actually get data as good as you get with standard patch clamp systems."

Cellectricon has also placed a few more of the new systems with various biotech and pharma customers, Karlsson said, but has not yet received feedback from them.

Next up for Cellectricon is the release of its platform for high-throughput single-cell transfection using electroporation, which has been in development for almost two years. Early access pharmaceutical partners have been beta-testing the product, called CellAxess, since last year, and Cellectricon had previously targeted the product for release in the first half of 2005.

However, in July, Cellectricon CEO Ulf Jönsson told CBA News that the release of the product had been delayed from its original schedule, and would likely be released in the fourth quarter.

Karlsson confirmed last week that Cellectricon will be launching CellAxess at the upcoming American Society for Cell Biology meeting, to be held Dec. 10-14 in San Francisco.

— Ben Butkus ([email protected])

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