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Roche NimbleGen to Expand CGH Array Menu, Plans Additional High-Density Chips

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By Justin Petrone

Roche NimbleGen will later this year introduce higher-multiplex, high-density arrays for use in comparative genomic hybridization applications.

The Madison, Wis.-based company also plans to debut arrays in its new, 4.2-million feature format for other applications, such as gene expression.

NimbleGen in January released 4.2-million-feature chips in two formats: a slide containing one array of 4.2 million features and a slide containing three arrays of 1.4-million features. Now it plans to begin offering chips containing six arrays of 630,000 features and 12 arrays of 270,000 arrays, according to company officials.

"This is the most comprehensive, highest-resolution, highest-throughput CNV platform on the market," Kary Staples, director of international marketing, told BioArray News this week.

Staples said the cost of the arrays varies per region. He estimated that the 3x1.4M arrays typically cost $500 per sample, while the 1x4.2M arrays are more expensive. He declined to elaborate.

The new high-density chips could give Roche NimbleGen an advantage in the market for clinical research arrays, such as cytogenetics, where it competes against Affymetrix, Agilent Technologies, and Illumina.

The company maintains the arrays benefit researchers.

"Smaller copy number changes, rare events can still be significant," said Xinmin Zhang, director of international product management in Roche NimbleGen's research division. "Many have reported changes in a single gene or exon where the deletions can lead to a disease. These new arrays allow researchers to go to the single-gene or single-exon level; they enable people to look at smaller or rare events."

Roche NimbleGen builds its arrays using photo-mediated synthesis chemistry with its maskless array synthesizer system. The system relies on a digital micromirror device that uses miniature aluminum mirrors to pattern individual pixels of light on an array surface.

Zhang said that the company has had the ability to make 4.2-million-feature chips since it launched its 2.1-million-feature array platform in 2007, but decided not to as the scanners used at that time could not image such high-density arrays.

"Even with our 2.1-million-feature arrays we had 4.2 million features, but we left every other feature blank [during synthesis] so that the features didn't interfere with each other," Zhang told BioArray News. "Now we are using all the features. Every spot on the mirror is used to generate oligonucleotide probes. That's how we are able to double the density so easily."

The company has also introduced its own scanner, the NimbleGen MS200, which is capable of 2-micron-level resolution and can be used to image the new generation of 4.2-million-feature chips (BAN 4/19/2010). Older generations of scanners on the market at the time the 2.1-million-feature chips were launched enabled 5-micron-level resolution.

"We were able to push technology to the limit, able to push the features to 4.2 million," said Zhang. Staples noted that the company is also planning even higher-density chips. "We are not at the endpoint. We will expand beyond this density as well," he said without elaborating.

Roche NimbleGen isn't the only firm selling a higher-resolution scanner. As Roche NimbleGen and Agilent released higher-density chips — Agilent began offering 1-million-feature arrays in 2009 — companies like Molecular Devices, Tecan, and Innopsys upgraded their scanners that could image the new NimbleGen arrays.

Still, Staples said, there were advantages for researchers to invest in the Roche NimbleGen workflow. The MS200 "goes hand in hand" with the firm's array technology, and "both have been optimized for each other as a complete workflow solution," he said.

Staples added that the company has seen "significant uptake" of its instruments. "We saw a significant number of installs in 2010," he said. "We expect that trend to continue this year."

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Others are less optimistic, though. A recent Leerink Swann research note, for instance, predicted flat demand for arrays compared to last year. It is unclear if that predicted downward trend will also hit Roche NimbleGen (BAN 3/22/2011).

In terms of next-generation sequencing, which some see as a replacement for microarrays, Staples and Zhang said that while the price of the technology continues to drop, other issues should make arrays more desirable for some time.

Arrays benefit from "cost advantages, ease of use, and the back end — the amount of data and how easy it is to interpret that data," said Staples. "It's true that the cost of sequencing is going down rapidly, but in terms of bioinformatics, there still isn't a consensus method to make CNV calls for next-gen sequencing data," Zhang noted.

CGH/SNP

Roche NimbleGen sees an opportunity for its new high-density arrays in other application areas. Zhang said the arrays could be used in high-multiplex gene-expression profiling and made available as soon as next year. However, he cautioned that product plans are not finalized.

"This is something that we are working on to further our portfolio," he said.

A product line with a harder launch date is the NimbleGen CGH/SNP-LOH arrays. The new chips, expected to launch later this year, will be available in "numerous, high-density formats" and could give the firm some advantages in the research market, Staples said. The company disclosed the pending debut in its 2010 annual report, released last month (BAN 2/11/2011).

Though geneticists have increasingly adopted CGH chips to help them identify causes of constitutional abnormalities, the arrays are still unable to detect conditions like uniparental disomy or copy-neutral loss of heterozygosity. SNP chips, on the other hand, can.

This distinction has led some projects to pair SNP arrays sold by Illumina and Affymetrix with CGH arrays sold by Agilent and Roche NimbleGen to identify the root of genomic disorders. For instance, researchers involved in a new UK project plan to use both Agilent CGH and Illumina SNP chips to decipher developmental disorders (see related story, this issue).

By offering both CGH and SNP content on one array, NimbleGen can appeal to researchers interested at looking at both rare copy number variation and detecting copy-neutral LOH. The firm won't be alone, though. Agilent similarly began offering CGH and SNP-LOH content last fall (BAN 9/14/2010).


Have topics you'd like to see covered in BioArray News? Contact the editor at jpetrone [at] genomeweb [.] com.

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