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Oxford Gene Technology Preparing a New Enterprise in Array Manufacturing

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Oxford Gene Technology, the firm that manages the microarray intellectual property developed by Edwin Southern at Oxford University, is assembling a new enterprise apparently to commercialize an electrochemical technique for manufacturing microarrays.

Oxamer, which was founded in 2002 by Southern and two others, has completed a round of hiring for its core team of scientists and is in a rapid-growth phase, according to its website ([http://www.oxamer.com]).

Any technology emerging under Southern’s aegis should be regarded with interest as Southern and Oxford University own the intellectual property that enables the in situ methods used by Affymetrix and Agilent Technologies to manufacture microarrays at an industrial scale. Both companies have licenses to the OGT technology, which is critical in a market that is 10 years old and nearing an estimated $1 billion a year in revenues.

Alan-Philippe Blanchard, a Seattle-based scientist who helped develop the ink-jet based microarray manufacturing system used by Agilent Technologies and was a co-founder of Rosetta Inpharmatics, said the technology Oxamer is incubating appears to fit into a space unoccupied by Affymetrix or Agilent and might have potential to be marketed as a bench-top platform.

Oxford Gene Technology officials told BioArray News last week that an Oxamer manager would not be available for comment before the deadline for the publication of this article.

The company’s co-founders include John Jarvis, who is managing director for OGT, and Ryan Egeland, who developed the underlying technology as a graduate student in Southern’s lab in the department of biochemistry at Oxford, according to the company website.

The technology is designed for the in situ production of microarrays and relies on an electrochemical process to enable DNA synthesis on glass slides. The method the company is developing uses an electrochemical deblocking step, enabled by an array of microelectrodes, to control the delivery of nucleic acids to specific sites on a surface. So far, according to the company, the technology has enabled the successful synthesis of 17-mer DNA chains and has successfully discriminated single-base-pair mismatched hybrids.

The company also has created software, electronics, and a fluidics chamber to automate synthesis for a process that it said may be applied to other biochemical syntheses. Oxamer is creating second-generation prototypes for large-scale analysis of biological samples.

The company said the system may be applied for the “detection and characterization of human diseases such as cancer and heart disease; evaluation of potential new drugs and their side effects, [as well as] forensics, agriculture, and basic scientific studies.”

According to Blanchard, Oxamer uses a “clever” microelectronic technology to change the pH of minute areas in its microarray manufacturing process.

“They generate a very small acidic patch using [microelectronics],” said Blanchard. “When you electrolyze something, you get a patch of low pH and another patch of high pH. The key is that you want to keep the low pH very localized because that is what deprotects DNA during the standard synthesis cycle. So if you can locally deprotect a growing DNA chain, you can then add whatever base you want there and then locally deprotect a separate area and add a separate base there. You can use these locally generated acidic pH patches generated by these microelectrodes to direct where the next nucleotide is going to attach to a growing DNA chain.”

The features created by this process are 40 microns each, said Blanchard, which “fits nicely between what you can get from an Agilent ink-jet printed array, which is probably around 100 microns, and an Affy chip, which can go down to maybe 10 microns.”

Blanchard, who helped create an ink-jet system for manufacturing microarrays while a graduate student under Lee Hood at Cal Tech, then as a post-graduate under Hood at the University of Washington, said Oxamer’s technology could be adapted for bench-top use.

“I don’t know what their business plan is, but I would assume that you could actually make an instrument that would sit on a desktop that you could put in a researcher’s lab,” he said. “The density is a bit better than an ink-jet printed array, but not an order of magnitude better, so I don’t know how well they could compete with an Agilent, for example, who has spent tens of millions of dollars putting together facilities for making ink-jet arrays.”

Blanchard, who has collaborated with Southern in the past, said he thinks the technology follows Southern’s philosophies about technology.

“Ed likes to get technology out to everyone,” said Blanchard. “Part of his philosophy in licensing his patents is to try and make other people be more flexible in licensing their patents, so that you don’t end up with these monopoly situations like Affymetrix had for years. So, I could imagine the idea of an instrument that goes onto a researchers’ bench being personally appealing to Ed Southern.”

The Team

Egeland, the young scientist at the center of this technology and a director of Oxamer, earned an MBA and a D.Phil in biomolecular engineering from Oxford, where he studied as a Rhodes scholar. He gradu-ated magna cum laude from Colorado College in 1997 with a degree in chemistry, and was an academic All-America football player. He attended the school on a Westinghouse scholarship earned in 1993.

Oxamer said it also has recently hired Wouter Meuleman, Steve Latham, and Matt Moorcroft for electrochemical and microfabrication work.

For OGT, this is not the first venture into creating a manufacturing enterprise. In January 2002, the company sold its DNA microarray business to Arrow Therapeutics of London.

— MOK

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