Part one of a two-part series.
Of the three major groups of industry drug targets — G-protein coupled receptors, kinases and phosphatases, and ion channels — some industry insiders have speculated that ion channels represent the fastest growing area, as researchers continue to elucidate the role they play in neurological disease, pain, psychiatric disorders, and addiction.
And when it comes to ion-channel screening, good old-fashioned patch clamping is still the way to go — at least according to a recent market report on ion channel trends by market research firm HTStec.
The report, released in September, is based on a survey of 88 scientists from 66 companies or universities. It claims that automated patch clamping is currently the "main" technology currently used for ion-channel studies in hERG liability testing, secondary screening, and hit-to-lead, with 55 labs identified as using automated patch-clamp systems.
Furthermore, the report claims that the worldwide pharma and biotech markets for automated patch-clamp instruments is around $32 million in 2005, and that sales are expected to peak in 2006 with more than 200 units placed globally.
With the iron hot, two young companies are hoping to strike. Danish firm Sophion Biosciences and German biotech Flyion have developed variations on traditional patch clamp technology, and are attempting to market them to the safety testing, secondary screening, and lead-optimization niches within the drug-discovery industry.
When it comes to ion-channel screening, good old-fashioned patch clamping is still the way to go — at least according to a recent market report on ion channel trends by market research firm HTStec.
Undoubtedly the biggest hurdle for both companies is drug-discovery instrument giant Molecular Devices, which, between its two product lines for automated patch clamping, is widely recognized as the market leader for patch-clamp-based ion-channel screening. It is unclear exactly how big Molecular Devices' market share is, as the company doesn't disclose such information, but the HTStec report identified its PatchXpress 7000A and IonWorks HT as the most widely purchased instruments worldwide to date.
But with Molecular Devices focusing heavily on the high-throughput drug-discovery market with one product, it may have left open a window of opportunity for other companies to snare market share from its other traditional patch-clamp technology. But do these two relatively nascent companies have the chops to make a move?
Sophion, based in Ballerup, Denmark, has a flagship product called QPatch 16, which, as the name implies, is a 16-channel automated system using planar patch-clamp technology, Chris Mathes, Sophion's recently hired vice president and general manager of US operations, told CBA News last week.
Mathes, who previously worked at Molecular Devices and Axon Instruments and was part of the PatchXpress development team, said the QPatch 16 has some similarities to PatchXpress in that they are both 16-channel instruments and both achieve gigaseals, which are important for high-quality ion channel recordings.
Sophion's instrument is different from PatchXpress on several other fronts however. For instance, Mathes said, QPatch has four pipette tips for liquid handling while PatchXpress only has one, making QPatch the "only instrument on the market that has an on-board cell-preparation station," Mathes said.
In addition, the QPatch planar electrode consumable has glass-coated microfluidic channels as opposed to plastic channels in PatchXpress. Mathes claims that there is evidence that plastic compound plates can lead to right-shifted IC50 values, while glass may be less absorptive of compounds and therefore produce more accurate IC50 values.
Finally, Mathes said that QPatch has "100-percent series resistant compensation," which the company has exclusively licensed from Alembic Instruments. "This is important for very accurate measurements without voltage error artifacts," Mathes said. "If you have these artifacts, it can appear as a hit during an experiment when it's really an artifact due to the recording.
"I'm trying to move Sophion in the direction of 'maintain higher quality, but do higher throughput'," Mathes added.
As such, the company currently has a 48-channel version of QPatch in the works, which Mathes said "should be the first 48-channel gigaseal system on the market, and it will be upgradeable from the 16-channel system."
Sophion currently concentrates its sales efforts on pharma and biotech with minor efforts on the academic market, but the firm might also eventually target the academic market more strongly. "I would love to be able to do a QPatch junior in the future, but the trick there is going to be coming up with a very low-cost electrode," Mathes said. "Academics are used to spending twenty cents per pipette."
Flyion, established in 2001, is a spin-out of the Institute of Physiology at the University of T bingen in Germany. Its technology, the Flyscreen 8500, uses a standard patch-clamp pipetting technique, but "reverses the principal of the gigaseal approach," Michael Fejtl, the company's chief scientific officer, told CBA News.
"I'm trying to move Sophion in the direction of 'maintain higher quality, but do higher throughput'"
"Rather than approaching the patch pipette toward the cell, Flyscreen is using what is called the 'Flip the Tip' principle," Fejtl said. "This means that you actually drop cells from behind into a patch-clamp pipette, and the cells fall down toward the end of the tip. With mild suction, the same gigaseal forms inside the patch pipette. So it is similar suction to when you use standard patch clamp."
Flyscreen comes in a three-channel and six-channel version, which results in throughput that Fejtl concedes can't compete with Molecular Devices or Sophion. But, he said, his company has noticed that scientists conducting hERG channel testing and lead optimization, for which the product is primarily designed, are more concerned with data quality than throughput.
"It's [by] no means like IonWorks, where you have a loose patch recording with a low seal." Fejtl said. "Our focus is to maintain high-quality patch-clamp recordings by establishing a gigaseal … with very low excess resistance of between 3 and 5 megaohms, and stability for 15 to 20 minutes, or sometimes longer. It's an intermediate screening device intended for secondary screening, lead optimization, and safety pharmacology.
"We can study voltage activity channels at high time resolution, and it's important to have very low excess resistance," he added. "If this is too high, you have a very large voltage error, and the time to peak activation would be false. So having a tight seal and a lower excess resistance is a prerequisite to screen a very fast voltage-activated ion channel."
As such, Fejtl said, he sees Flyscreen as more of an add-on to something like IonWorks, but still a direct competitor to PatchXpress and QPatch. Even then, he thinks the latter two instruments are more directly competitive, and believes Flyion can convince companies to invest in Flyscreen as an add-on to those, as well.
— Ben Butkus ([email protected])
Part two, which will appear next week, will cover Molecular Devices' offerings for automated patch-clamp and why Sophion and Flyion think there is an opportunity to steal its market share of traditional patch-clamp technologies.