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Why Millennium Decided Take-Out Affy Tasted Better than Homemade Array Recipe

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Within the next year to 18 months, Millennium Pharmaceuticals will switch over to the Affymetrix platform for most of the 4,000 to 5,000 arrays it uses each month, Craig Muir, vice president of platform technology for Millennium said during a keynote address to the Chips to Hits conference in San Diego this week.

The reasons for this switch, which both companies announced last week, are both economic and technological, according to Muir.

“We had developed quite an infrastructure for manufacturing arrays on nylon substrate,” Muir explained. “We will continue to utilize it for a year or so. There are certain cases where it makes a lot of sense.” But, he said, “we weren’t addressing the issues of manufacturing cDNA clones by PCR.”

Using PCR clones required the company to expend valuable time and money validating these clones, and it soon became clear that oligos would be a better option. The company considered synthesizing oligos, “but it got to the point where the economics were just as good to go with Affymetrix,” said Muir.

Did Millennium consider any rival platforms? Yes. And Agilent’s inkjet-based platform was among them.

The company ideally wanted longer oligos than Affymetrix’s, and would like to have a custom platform that can turn around custom arrays within a week, Muir said. But given that Affymetrix can outpace the others in probe density, the advantages of having longer probes were outweighed by the GeneChip platform’s ability to stick more probes on each chip, according to Muir.

The company will continue to use its nylon membrane arrays in limited instances, such as when it wants to make “mini-arrays” with about 300 to 500 genes per array, and use these to screen thousands or tens of thousands of samples, Muir said.

The company will meanwhile custom-fit its existing laboratory information management system (LIMS) platform with Affymetrix’s LIMS software, in order to integrate GeneChip data and nylon array data.

Affymetrix would like to develop custom chips with Millennium, as well as any other chips that could help move the company’s platform from research into the “high-throughput applications in downstream drug development,” said Anne Bowdidge, director of investor relations at Affymetrix.

Muir did not rule out Millennium’s use of Affymetrix’s CustomExpress program or a special custom program to design lower-density arrays for high-throughput screening. But for Millennium, this might not be the cheapest option. “We will have to be sensitive to the economics of both spotted and prefabricated arrays,” Muir said.

Meanwhile, the company will continue to keep its eyes open for other promising biochip technologies.

Of particular interest, said Muir, are chips like those being marketed by CombiMatrix. This company, a subsidiary of Squolamie, Wash.-based Acacia Research, uses complementary metal oxide semiconductor technology to create chips with 1,024 test sites, or what the company calls “virtual flasks.” The sites are covered with a thick porous layer of material, in which the test sample is contained, and each site is attached to an electode. A fluidics unit delivers the test sample to each virtual flask.

For Millennium, which has proprietary gene sequences in addition to the publicly available data, such a format could provide for custom chips that could be manufactured on-site rather than ordered out. Additionally, this chip platform could provide an entry into the protein chip realm.

Millennium is also looking into microfluidics chip options other than its current partner, Caliper Technologies. Companies that spin out samples on compact disc microfluidics devices, such as Sweden’s Gyros AB, are of particular interest, said Muir.

“I believe Millennium will embrace overlapping strategies to make microfluidics,” Muir said.

— MMJ

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