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BioTrove Secures Method Patent for Cell-Based Apps, But Eyes Other Assay Types First

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With a new cell-based assay patent in its arsenal, BioTrove is looking to develop its core nanofluidics platform, OpenArray, into one that can run a wide variety of biological assays.

The platform, which is designed to use low sample volumes in a highly parallel fashion, has other potential applications including SNP analysis, RNA transcript analysis, and protein binding or enzymatic assays, according to the Woburn, Mass.-based biotechnology company.

The cell-based assay-related patent is number 6,716,629, “Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof.” According to Robert Hess, BioTrove’s director of licensing and intellectual property, the patent primarily outlines methods for “preventing evaporation and condensation” on OpenArray, while still allowing gas exchange. Hess added that such a conundrum is faced by any technology with an eye toward miniaturizing cell-based assays.

At the core of the OpenArray platform is technology the company calls “Thru-Holes.” Invented at the Massachusetts Institute of Technology and co-developed by MIT and BioTrove, the term Thru-Holes refers to a grid of 300-micron-deep holes on a standard microtiter plate. Each hole can hold approximately 25 nanoliters of fluid. The current OpenArray plate contains 3,072 holes, BioTrove said, with a future potential of 25,000 or more.

“It’s sort of like doing [assays] within a microtiter or nanotiter plate, but we’ve taken the bottoms out, so you don’t have some of the dead volume problems that you have with traditional … approaches to microfluidics,” said Patrick Carroll, BioTrove’s chief business officer. “We can move liquids in and out of these channels much easier.”

Even with the patent, BioTrove says that cell-based applications for OpenArray still have a ways to go.

“We’ve done some initial work with cells, back when we first started looking at the OpenArray when we brought it over from MIT,” said Patrick Carroll, BioTrove’s chief business officer. “But we’ll probably start focusing more on cell-based products in late 2005, and I wouldn’t expect to see anything there until 2006.”

It doesn’t appear as if the company needs to rush. High-content or high-throughput cell-based assays are definitely becoming more prominent in drug discovery and development, but it seems as if researchers are currently focusing more on grappling with the data generated from such assays. Platforms that potentially allow thousands of cell-based assays to be performed in parallel will still have to face this obstacle.

In terms of competition, Hess said that “with the cell stuff, we’re not even sure what the product is going to look like yet,” but mentioned that there are other products being worked on that might be considered competitive. Specifically, he mentioned Akceli, a biotech startup founded on cell-based chip technology developed at the Whithead Institute. But Akceli has apparently gone belly-up, unable to secure proper financial backing. (For more, see IB’s sister publication, RNAi News, 3/19/2004). Hess also said he believes Cellomics is working on a similar platform.

In addition, Hayward, Calif.-based Biolog is having success with its bacterial and fungal cell phenotyping array, and plans to eventually extend that platform to mammalian cells. (See Inside Bioassays, 5/4/2004).

“But all the approaches to cell-based chips have been planar surfaces with adherent cells,” Hess said. “Ours would be different in that it could either have suspended or adherent cells. We could measure analytes secreted, for instance, by the cells into solution, in isolated containers, and those [that] retain all the characteristics of the cells rather than producing cross-talk.”

In the meantime, however, BioTrove will concentrate its efforts on the biochemical- and proteomics-based platforms. According to Carroll, the first application for the OpenArray is transcriptional analysis, which the company expects to introduce at the Chips-to-Hits conference in September, and to officially launch in December. The company recently secured a patent related to this application as well, acquiring a license to specific methods from Stanford University. (For more on the OpenArray’s genomics applications, see IB’s sister publications, PGx Reporter, 4/1/2004; and BioArray News, 3/31/2004).

The company will use some $18.9 million in funds to help support the OpenArray launch, cash that resulted from a Nov. 2002 $5.2-million funding round and a $13.7-million round that closed this past April.

Following the OpenArray launch, Carroll said, the company will begin working on protein applications, such as protein binding and enzymatic assays. The company’s ultimate goal is to package a platform on which all of these assay types can be performed, so researchers have their choice of ways to explore gene expression and screen drug targets.

“What we’re seeing across the platforms is an advantage over planar arrays,” Carroll said. “With the through holes we can actually do solution-phase PCR, solution-phase antibody reactions, or we can do work with the cells without having to rely on the planar surface — yet we get the throughput advantages of some of the planar arrays. That’s the angle we’re trying to work with all three potential areas.”

—BB

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