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Agilent to Debut 244K ArrayCGH Chips by June; Leukemia Emerges as Area of Diagnostic Interest


Delivering on a promise to quadruple the density of its microarray platform by the second quarter of this year, Agilent will launch 244K chips in June — meeting the deadline it set when it first announced its density upgrade last November, according to a company scientist (see BAN 10/12/2005).

Michael Barrett, a scientist in Agilent Laboratories' Molecular Research Lab, told attendees of the World Microarray Congress in Vancouver last month that the company was on schedule to complete the density upgrade by the end of June.

In a follow-up interview with Agilent, the company disclosed for the first time that it has plans to introduce arrays with 500,000 and, later, 1.2 million features. The company did not offer specific timelines.

The density upgrade will affect all of Agilent's microarray products, Barrett said last month, including its chips for array comparative genomic hybridization — the subject of his talk in Vancouver. Separately, Barrett said that though Agilent has no direct interest in diagnostics, it has determined that its array CGH product is indeed suitable for diagnostic assays, particularly in leukemia.

"Agilent believes that this technology combined with the right expertise could translate very quickly to very robust diagnostic assays," Barrett said.

"Agilent believes that this technology combined with the right expertise could translate very quickly to very robust diagnostic assays."

Explaining why Agilent thinks leukemia may be the gateway to clinical applicability for its array CGH product, Barrett said that "existing DNA-based tests such as [fluorescent in situ hybridization] and cytogenetic assays are available on the market, and array CGH has the potential to do these assays at a much higher definition."

"Leukemias are an attractive model for the application of array CGH [because] they are cancers of blood cells, frequently present in the clinic as homogeneous cell populations, and existing technologies are available to purify leukemic cells from a patient sample," he wrote in an e-mail to BioArray News.

"That ability to purify tumor cells allows more accurate molecular assays such as array CGH than with non-purified samples," Barrett added.

Barrett explained that the "purity of a cancer biopsy is particularly relevant to array CGH measurements because unlike gene expression, where all cells present in a biopsy may contribute to the signature, genomic alterations are specific to the cancer cells."

He wrote that "some of the challenges for studying solid tumors are that tissues are typically mixtures of different cell types and can be harder to locate, biopsy, and purify than in leukemia."

In the e-mail Barrett also stressed that Agilent is not interested in grooming its array CGH product for diagnostics. However, he did not rule out its use in future clinical applications. "If an organization [has] the necessary expertise in tissue acquisition and processing, it [could] probably be possible for it to develop robust CGH-based assays," he wrote.

Agilent declined to disclose to BioArray News which researchers are currently using their array CGH product for leukemia work. But Jeremy Squire, a senior scientist at the Ontario Cancer Institute in Toronto, supported Barrett's statement that its array CGH technology is less clinically relevant for solid tumor cancers.

Squire told BioArray News last week that his lab at OCI has been using array CGH for its work in cytogenetics and cancer. "We have projects where we are integrating multi-colored cytogenetic approaches and then adding arrays to that analysis," he said.

"By looking at chromosomes using traditional cytogenetic methods like FISH, and comparing the findings from these chromosome painting techniques to the Agilent array CGH, it is possible to compare the pattern of imbalance in DNA copy number change to the actual rearrangements that take place within the cancer cells," he said.

"The cancer genome is remarkably unstable, so you have to use more than one technique to figure out what's going on," he added. Because OCI is attached to Princess Margaret Hospital in Toronto, Squire said that his lab is "very much a translational lab so [it tries] to do bench to bedside stuff."

"Anything that we are doing, we are thinking of having tests down the road that are going to be more clinically applicable," he said. Still, he said he had no plans to introduce tests using Agilent's CGH product, and instead likened it to a "fishing net."

"At the moment I don't see arrays being used much clinically," Squire said. "I think what happens is that the arrays are used to identify regions of the genome that can be then be used as individual tests, like PCR or a conventional Enzyme-Linked Immunosorbent Assay test," he said. "I think arrays tend to act sort of as a fishing net," Squire said.

Casting a Wider Net

Though it is unlikely that Agilent's array CGH product will be used bedside at Princess Margaret Hospital in the future, Squire said that the advantage of array CGH was that it afforded researchers a high definition look at the human cancer genome.

Building on that perceived strength, Agilent's next generation array CGH chips will offer researchers like Squire access to a higher-density technology.

As Scott Cole, Agilent's microarray marketing director, told BioArray News in October, that feedback from researchers is pushing the company to offer higher-density chips.

"In the world of CGH, in the scanning level, people want higher density. And that's one of the drivers from a technical standpoint in that space," Cole said at that time.

According to Sameer Rohatgi, Agilent's director of strategic marketing for integrated biology solutions, the company currently offers "catalog and custom microarrays with 44,000 probes, and [is] in an Early Access Program for arrays at 185,000."

"In the June/July timeframe, [Agilent] will commercially release microarrays for several applications including CGH, which offer 244,000 features on the industry standard 1 x 3 inch glass slide," Rohatgi wrote BioArray News in an e-mail this week.

Agilent will not cut down on the size of its features in order to make room for all those probes. The company said that it will continue to offer 60-mer oligos on all of its arrays. However, the space between probes will decrease, according to the company, moving from 50 to 60 microns between features on a 244K array to 35 microns on a planned 500K array, and on to 20-25 microns between features on a planned 1.2-million probe array.

Still, according to Rohatgi, the company only has exact numbers for the 244K microarrays, and beyond that it is "still in the development phase and can only provide estimates."

In addition to the release of the 244K chips, Rohatgi said the company will also release a new version of its Feature Extraction software in June or July. He said that Feature Extraction Software version 9.1 will make it easier for users to process the 244k arrays regardless of application via faster processing time and data compression capability.

— Justin Petrone ([email protected])

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