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Nascent Swedish Biotech SymCel Looks to Bring Calorimetry to Cell-Based Screening Market


Swedish biotech SymCel has signed on a new beta-tester at an undisclosed company for its calorimetry-based live-cell screening device, its third overall beta placement and first at a commercial entity, the company's CEO told CBA News last week.

A parallel development to the increasing interest in high-content cellular-imaging has been a decidedly simpler approach to live-cell screening using label-free technology, most of which measures physical cellular characteristics to determine general cell health, and in some cases, specific compound effects.

One of the earliest examples of this is Molecular Devices' now-discontinued Cytosensor, which measured changes in extracellular ion levels using a potentiometric microchip.

The latest example is technology based on electrical impedance measurements, which companies such as MDS Sciex, Acea Biosciences, and Applied Biophysics are attempting to market.

Now SymCel is hoping to sell an instrument based on calorimetry, or measuring thermal power from cells as a way to assess their total metabolic rate.

Calorimetry is not a new concept, but using it to conduct a screen on more than one cell at a time is. And, like many drug-discovery technologies, it was spawned from a scientist — SymCel CEO Dan Hallén — who saw shortcomings in an otherwise solid assay concept.

"I had been working in drug discovery for more than 10 years, and I experienced in so many projects that the toughest part is normally the cellular assays."

Prior to SymCel's founding late last year, Hallén was working for Swedish biotech BioVitrum, which, according to Hallén, was an early research site for Pharmacia.

"In the beginning we did this as an academic project, and I had the blessing from the company, as well," Hallén said. "I had been working in drug discovery for more than 10 years, and I experienced in so many projects that the toughest part is normally the cellular assays.

"The assay development takes a lot of time and you don't really know whether, or when something has gone wrong, if it's because of the cell, because of the assay, or anything else," he added. "Also, it takes a long time to get data."

Hallén said that he flirted with the idea of using calorimetry as a quick and painless method for screening general cellular states such as necrosis, apoptosis, metabolic inhibition, mitosis, and infection, using existing calorimetry instruments.

"But this failed in principle because of two things," he said. "One, you can only do one experiment at a time, and two, it's a very complicated experiment. You need to be very skilled to do this experiment."

So Hallén and colleague Ingemar Wadso, a professor of thermochemistry at Sweden's Lund University, set about trying to apply the calorimetry concept in relatively high-throughput — at least compared to single-cell measurements.

What they came up with is a device they dubbed CalScreener, which can measure thermal power output from 48 wells containing cells in parallel. Each well is equipped with a separate thermopile with associated electronics, which also remain separate. The entire instrument, which is about the size of a large breadbox, connects to a computer terminal for data readout.

Characteristic thermal outputs have been published for a number of popular cell lines used in screening experiments, so the concept is as simple as watching for changes in thermal output to determine if the cell is doing anything unusual.

One of the major benefits of CalScreener, Hallén said, is that there is next to no assay development needed.

"Each experiment, in whatever therapeutic area, whatever target you're working on, the experiments would look exactly the same," he said. "One of the problems with doing cellular assay development is choosing the right cells in the first place. So you can actually do screening for the optimal cell line to use in further assays. And you can assay for cells as well as for compounds."

Another side benefit of using CalScreener might be discovering off-target toxicity effects, "even though that may not be what you are looking for exactly," Hallén said.

SymCel is attempting to market CalScreener as a "first filter" method, before researchers move on to more specific assays that are also more expensive. Hallén thinks the instrument can fit along side other label-free technologies, such as those based on electrical impedance, but admits there is some direct competition.

"To some extent yes, they are competitive, because they are all general methods and they measure something that has to do with metabolic activity," he said. "But they are also complementary methods."

In order to successfully market a product to such a niche, the price must be right if instrument vendors are expecting laboratories to buy several products using different means to achieve the same end. Hallén said CalScreener will retail in the $100,000 range when it hits the market — though the company is unsure when this will be.

SymCel had its coming-out party at the Society for Biomolecular Sciences conference held in Geneva in September, and recently signed on a first commercial beta-tester for its product. This undisclosed partner joins current beta-testers Karolinska Institutet and the University of Stockholm, both in Sweden.

Moving forward, the company said it will remain very small and eschew investment capital as "long as possible," Hallén said. It recently was awarded an 18-month, approximately $150,000 contract from Stockholm Innovation & Growth, a Swedish government-funded technology incubator group. Hallén said that money will go toward moving CalScreener to market, helping with networking and legal issues, and eventually developing a 96-well version of CalScreener.

— Ben Butkus ([email protected])

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