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Agilent May Quadruple Array Density by Q2 06 As Expression Plateaus and CGH Expands

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Spurred on by demand for its new array-based applications and what it calls a "transition phase" in the marketplace for gene expression, Agilent is preparing to make higher-density arrays available for customers as soon as the second quarter of 2006.

According to Scott Cole, Agilent's marketing director of microarrays, the company will quadruple the amount of features printed on its standard 3' X 1' slides, from the current limit of 44,000 features per chip to 185,000 features per array, by early next year.

Driven by demand for higher density by users of Agilent's newer applications like array comparative genomic hybridization, the high-density arrays will reach customers first through Agilent's custom array service. Taking advantage of the new density capabilities, Agilent may add gene expression arrays that have several sub-arrays printed on them to their portfolio in the future.

The decision is significant. The last time Agilent upgraded density, in 2004, it doubled it — from 22,000 to 44,000 features per chip with the launch of its whole human genome array. The plan to quadruple the number of features this time around shows that the Palo Alto, Calif.-based firm is shifting its business towards emerging array-based applications that demand much higher density.



"What we are seeing now is a transition from just a gene expression world with some SNP analysis to what we see as a multi-application microarray world."

Cole said that the company had initially planned to make 95K arrays available first, followed by 185K arrays, but may just go straight to 185K arrays if feedback from early-access customers continues to be positive.

"This first jump has taken us to 95K and also to 185K and our original idea was to take those two steps. The jury is still out — we may just go straight to 185K. We need to get some results back, but everything is looking extremely positive, better than what we expected," Cole said.

"We already have beta customers using the 95K arrays. We'll have customers using 185K arrays next month and the idea is that they'll be integrated into our entire portfolio, both our catalog arrays in gene expression but also our catalog arrays in some of our new application areas, and then our custom arrays for all of our applications, in Q2 of next year," Cole explained. Agilent's Q2 ends April 30.

Cole said that there were two key factors in Agilent's decision to go to higher density: a noticeable plateau in the market for gene expression arrays, and the profitability of Agilent's newer array-based applications, like array comparative genome hybridization, which demand higher-density chips.

"The way we see it, the microarray market is very much at an inflection point, a transition phase. The past several years have been really dominated by gene expression. But what we are seeing now is a transition from just a gene expression world with some SNP analysis to what we see as a multi-application microarray world," Cole said.

Agilent isn't the only company to recognize the market is changing. In an interview with BioArray News last month, Charles Ma, chief scientist at Phalanx Biotech, said that "initially, growth [has been] exponential, but we are starting to hit a phase where it is going up, but not at the explosive rate you had before."

"Basically that means that we are slowing down and at some point, if that does not change, we are going to hit a wall. Because somewhere along the line growth is going to really slow down," he warned (see BAN 9/21/2005).

And Agilent is also not the only company to recognize that density sells. Madison, Wisc.-based NimbleGen, which also is playing in the nascent array CGH market, has claimed that its arrays offer the highest density in the market.

"We are the only company that can offer high-density — up to 390,000 features with long oligos up to 100 nucleotides — arrays," Dan Clutter, NimbleGen's vice president of sales, told BioArray News about its CGH offering last February (see BAN 2/23/2005).

"[With] our large number of features combined with the length of oligonucleotide probes we use, we can cover a lot of genomic territory on a single array," he said.

And then there's Affymetrix, which just launched its GeneChip Mapping 500K Set, composed of two 250K SNP arrays each capable of genotyping on average 250,000 SNPs for whole-genome associational studies as well as its Human Exon Array, reducing the distance between probes to 5 microns with the new products (see BAN 10/05/2005).

In Agilent's new assessment of the array world, "density is an important component. And 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," according to Cole.

Cole also said that applications that use Agilent's arrays for chromatin immunoprecipitation (ChIP)-on-chip, splice variant analysis, and microRNA research would benefit from higher-density arrays. It is in these key growth areas that Agilent sees the greatest potential for its customers and its next-generation chips.

Agilent recently began distributing splice-variant arrays for Exonhit Therapeutics, and its arrays are used as the platform for Jivan Biologics, which sells splice-variant arrays as well. Cole said that the company is also catering to the marketplace for microRNA arrays.

"Think about microRNAs. People are discovering new microRNAs every week. To keep up with the technology in that field, you need a platform that can go into a new application for the next several years that will be critical [to] deliver a complete product," Cole said.

Agilent's the new arrays will benefit its gene-expression business as well by enabling the company to provide more than one array per slide.

"[Right now], you can put one array per slide or per chip — we have formats that customers are using [in early access] that we will be promoting more in the future that have multiple arrays per slide," Cole explained.

"There are both throughput advantages and cost advantages to going to multi-array slides. [For] standard gene expression analysis, the way we would handle extra density is to put two genomes on a slide," Cole said. He said that the scientific benefit wouldn't be as great with the whole-genome content Agilent has been providing as it would be with array CGH, which needs higher density for more comprehensive analysis, but that there would be more of a cost benefit for gene expression.

With relation to cost, Agilent is not planning on charging per feature, Cole said.

"There's not going to be a large cost or price differential between the high density arrays and our current arrays. Small if any," said Cole.

In fact, the company believes that price will be a selling point for the higher-density arrays. "There are both throughput advantages and cost advantages to going to multi-array slides," Cole said. Cole was not more specific on pricing.

Agilent will eventually retire its standard 44K arrays, but Cole declined to comment on the company's timeline for phasing them out. In the meantime, they will be available to customers that prefer the 44K chips.

"In the gene-expression area, customers build up databases and they don't always think more and better is in fact better," Cole said. "In some cases they want to stick with what they are using just so they'll have comparable data."

Printing Technology & Informatics

Cole said that Agilent has optimized its proprietary inkjet printing method to meet demands for printing the higher-density arrays.

"What we are doing is going from a standard inkjet cartridge that may have been used in a standard inkjet printer to a much more sophisticated commercial-grade print head. That's part of the equation," Cole said.

What that means in terms of printing technology is "improved spot placement accuracy" as well as "further optimized synthesis uniformity," the company said in a statement provided to BioArray News.

"This enables features to be synthesized closer together than on the previous generations of microarrays with minimal impact on feature size. Therefore, the new microarrays are compatible with existing experimental protocols without the need for further capital investment in a new scanner," the company said.

In addition to upgrading its printing technology to meet market demand, Agilent is also preparing a suite of data analysis products for launch next year, based on the GeneSpring software that Agilent acquired when it bought Silicon Genetics in 2004 (see BAN 9/1/2004).

According to Cole, "next year GeneSpring is going to be called GeneSpring GX, for gene expression." The company will also launch GeneSpring CGH, for array CGH, GeneSpring LA for location analysis, and it is "building out a GeneSpring MS, for mass spectrometry data."

"SG isn't just here to create next-generation gene-expression software," Cole said. "They are creating a completely integrated informatics package that will deliver multi-application integrated microarray analysis going forward."

Agilent also said in the statement that it plans to continue packing more features on its chips, stating that it expects to increase feature density by "potentially 10-fold in 2007."

-- Justin Petrone ([email protected])

 

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