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Amphora Improves Cell-Based Screening of Caliper System; Caliper Purchases Rights

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In a move expected to strengthen its cell-based assay offerings on its LabChip microfluidics system, Caliper Life Sciences, of Hopkinton, Mass., earlier this month agreed to acquire cell culture and other technology developed by Amphora Discovery, of Research Triangle Park, NC.

Caliper said it will now incorporate the technology into a new calcium-flux assay, which will enable users of the LabChip to perform assays against G-protein coupled receptors — one of the more important cellular targets in drug screening.

According to an official statement released May 6, the agreement calls for Amphora to transfer cell-culture techniques, hardware, and software upgrades to Caliper in exchange for cash, Caliper products, and royalties based on future sales of the assays.

Amphora is a pure drug-discovery company that was spun out of Caliper in 2001. Since that time, the companies have shared what Kevin Hrusovsky, Caliper's president and CEO, called in the official statement "a truly symbiotic relationship." Amphora's drug-discovery services are based primarily on the LabChip platform.

"We had limited cell-based assay capabilities prior to this agreement, which is what motivated us to do it," said Michele Boudreau, Caliper's director of corporate communications. "Up until this point, [the LabChip systems] have been capable of doing some cell-based assays, but not as wide a variety as it turns out our customer base would like."

Caliper offers a variety of automated instrumentation, including the LabChip, for both biochemical and cell-based screening and drug discovery. The LabChip system uses a combination of electrokinetic and pressure-driven flow to move molecules or cells from wells in well-plates, into and through microchannels, making it different from many of Caliper's other "macro" sized and static instruments.

Although this combination flow system helps increase throughput and automation, while reducing size and cost, it is not particularly suited to many of the adherent cell lines popular in static cell-based assays. According to Boudreau, several large pharmaceutical companies use the LabChip platform — mostly for biochemical assays — but Caliper realized it had to accommodate the recent push towards cell-based assays, particularly with primary cell lines.

Amphora made the upgrades to the LabChip 250 platform, about 20 of which it uses internally, according to Boudreau. She added that Caliper plans to incorporate the upgrades in its recently launched LabChip 3000, which is the newest in the product line and is slated to eventually replace the 250.

"When Caliper set out to sell this product, it was geared towards enzymatic assays with an eye towards cell-based," said Paul Bernasconi, director of high-throughput biology at Amphora. "We extended the usefulness to cell lines they were not ideal for."

Keeping Cells Happy

The big news, according to Bernasconi, is that customers using the LabChip can now choose cell lines that are popular for cell-based assays but were previously difficult to use in microfluidics-based instruments. One of those cell lines, for instance, is HEK-293 (human embryonic kidney), which Bernasconi characterized as "the workhorses of the cell biology world," adding that "everybody and their brother uses them."

"Some cells, like CHO (Chinese hamster ovary) cells, you can pretty much mistreat," Bernasconi continued. "But HEK cells, being mammalian cells, are at their happiest when they are sticking to something."

So Amphora devised a proprietary culture method to keep the cells in suspension for use in the LabChip, while keeping them alive and well. "Being able to keep the cells as close as possible to their natural state keeps the assays more relevant," Bernasconi said.

In addition, Amphora changed the laser line used in the LabChip to "better match the existing fluorescent dye for calcium imaging," he said. "The trick was to optimize the laser for the cell-based assays, but not penalize the biochemical assay capabilities."

Bernasconi said that the upgrades should make the LabChip system more attractive for cell-based assays because researchers can continue to use the cell lines best-suited for their particular assay. He added that he thought many of the other LabChip features already made it an excellent choice, particularly because researchers can save money by using only a small amount of primary cells in their assays.

"When people do cell-based assays, they usually work with plates," he said. "And they need several hundred or thousand cells per well. Instead of needing this many, we can actually use about 200 cells per well. And it's almost like a cell sorter rather than a plate reader, because you can get information on individual cells."

Boudreau said that there were no advance customers for the platform as of May 5, because news of the upgrade was just released. But Caliper has begun marketing the new capabilities, and hopes that Amphora's continued use of the products in service business convinces Amphora's customers to purchase LabChips for in-house screening.

Perhaps one of those future customers will be Aventis, which on March 30 of this year signed a two-year research agreement with Amphora to screen drugs against kinase and ion channel targets. The deal was the first major pharmaceutical agreement announced by Amphora since its inception.

"Depending on what [a pharma] wants to do, it may have in-house screening capabilities, or maybe they say: 'Hey, we don't want to screen, we just want to be provided leads for this candidate,'" Boudreau said. "There's such a broad array of need out there that we're very happy that Amphora is out there promoting the technology and highlighting it."

— BB

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