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Moving Beyond Mass Spec, MDS Sciex Previews Screening Tech Based on Electrical Impedance


BOSTON — MDS Sciex, the Ontario-based biotech that has built its business primarily on mass spectrometry platforms, is diversifying its product offerings to include cellular analysis.

The company, the analytical instruments division of publicly traded biotech firm MDS, was previewing its newest product, CellKey, at IBC's Drug Discovery Technology conference, held here last week.

According to Anne Ferguson, a product manager for MDS Sciex, the company plans to officially launch the product next month at the Society for Biomolecular Screening conference in Geneva; however, it wanted to first expose CellKey to a US audience with a pre-launch at DDT.

CellKey is a label-free cellular analysis platform based on cellular dielectric spectroscopy. In this technique, cells are grown on electrodes embedded in microwell plates, and a constant low-level voltage is applied. A detection instrument senses changes in electrical impedance that result from changes in cell morphology, confluence, adherence, and interactions.

MDS officials also believe the technique could be compatible with and complementary to its mass spec products.

Ferguson told CBA News that the product was born from an alliance started with Signature Biosciences begun several years ago in which the companies developed an instrument based on a similar concept to detect protein-protein interactions in biochemical assays.

"I think the prohibitive thing [for academia] is the cost. If you have somebody with good funding, it might be realistic. But we're not targeting academia now because it's likely cost-prohibitive."

However, Ferguson said, this instrument ended up "not being realistic to commercialize," and the companies began focusing on a side project that was in the works for label-free cell detection.

"At some point in that strategic alliance, where the companies were developing it together, Signature Biosciences went out of business, and that was a prime opportunity for MDS Sciex to acquire that specific technology," Ferguson said. "They believed in it, they had seen some of the initial results, and they took a subset of that team that they needed to further complete the development of that product."

To be sure, using electrical impedance techniques to detect changes in cells is not new, and a few companies have recently attempted to introduce the method as an alternative to image-based cellular screening because of its advantages as a label-free, non-invasive, and relatively long-term kinetic assay.

These companies have their own monikers for the technique: San Diego-based Acea Biosciences, which started marketing a product in the middle of last year, calls it "cell electronic sensing" (see CBA News, 1/18/2005); and Applied Biophysics, which says it invented the technique but is just now starting to market it for drug-discovery purposes, (see related story, this issue), calls it "electric cell-substrate impedance sensing."

But whereas Acea has said that its platform may be more appropriate for "back-end research work" rather than primary or secondary screening, MDS Sciex will initially market CellKey to the secondary screening market based on its belief that the instrument can detect the activation of specific GPCRs and tyrosine kinase receptors, according to Ferguson.

"A significant amount of literature from academia shows that when you activate different GPCRs and tyrosine kinase receptors — and even downstream when you hit the nucleus — one common downstream event is a change in the actin cytoskeleton," Ferguson said. "Literally, when you activate a Gs-GPCR, for instance, you're going to cause the cells to round up a little bit, and come off of the microplate well substrate, which will cause a decrease in impedance.

"It just depends on what cell context you're measuring in, and what the receptor is," she added. "So if you activate a Gs-GPCR, you get a certain change in impedance, and with a Gi-GPCR, you might get something completely opposite. That's pretty black and white. There's a little more subtlety with the Gq-GPCRs … but these are all obviously distinguishable between each other."

In fact, David Mark, global head of HTS at Roche and an advance user of CellKey, presented data here Wednesday that showed how CellKey could be used to detect the activity of a specific receptor that signals through a complex Gi- and Gq-protein coupling mechanism.

MDS Sciex said the CellKey is priced for the pharmaceutical market. Ferguson said the company is planning on a price range of $350,000 to $400,000, which may make it prohibitively expensive for most academic labs. In comparison, Acea sells its systems for about $65,000; and Applied Biophysics is eyeing the $45,000 range. MDS Sciex, therefore, hopes that pharmaceutical customers are willing to pay more for what they believe are more specific assay capabilities.

"I think ideally, to get this into the hands of people in academia, we could get so much interesting information about how GPCRs work," Ferguson said. "I think the prohibitive thing is the cost. If you have somebody with good funding, it might be realistic. But we're not targeting academia now because it's likely cost-prohibitive."

So far, Ferguson said, MDS Sciex has been collaborating on feasibility studies with various pharmaceutical companies, which have been using CellKey prototypes. These collaborators include Roche, Amgen, Johnson & Johnson, AstraZeneca, and four additional undisclosed pharmas.

It is not immediately obvious why MDS Sciex is attempting to bolster its mass spec chops with cellular analysis, outside of the fact that it simply already had a semi-developed instrument in its stable. Ferguson suggested that the technique is compatible with and complementary to its mass spec products, but added that the company hasn't yet explored the possibility of co-marketing CellKey with mass spec instruments.

One way CellKey might come in handy is for parent company MDS, which also runs a pharmaceutical services business. This unit, Ferguson said, already incorporates MDS Sciex mass spec products, so folding cellular analysis products into the mix would add to its capabilities.

"There are so many interactions that could happen, and we have to take a look at the big picture," she said. "But right now, until we get a launch, we'll see what customers and our sister companies give us feedback on."

— Ben Butkus ([email protected])

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