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Febit to Debut HybSelector Instrument, Disease-Specific Sequence Capture Arrays in 2010

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By Justin Petrone

Febit next year plans to expand its menu of products for customers that use its sequence-capture arrays with second-generation sequencers.

Chief Scientific Officer Peer Stähler told BioArray News this week that the Heidelberg, Germany-based firm will launch a new instrument called HybSelector designed specifically for processing the firm's HybSelect sequence-capture arrays.

Additionally, Febit is planning to launch higher-density versions of its Geniom biochips over the next year, and will begin rolling out disease-themed HybSelect arrays, with an emphasis on oncology and neurodegenerative diseases.

According to Stähler, the new products are being introduced to strengthen Febit's offering to researchers who use second-generation sequencers. Febit debuted HybSelect earlier this year, and the company, which also maintains an office in Lexington, Mass., has made sequence capture one of its primary applications, along with microRNA expression profiling (see BAN 2/17/2009).

HybSelect, which uses Febit's Geniom instrument, synthesizes defined oligonucleotides within the eight channels of a Geniom biochip and uses them as capture probes for the targeted genomic DNA loci within a sample, according to the firm. Fragmented genomic DNA is then hybridized to the biochip, washed, and eluted. After elution, the selected DNA can be used for sequencing.

Since HybSelect was launched, users have been running it on Febit's RT-Analyzer instrument, which also supports miRNA-expression profiling and other applications. However, some HybSelect users do not require the imaging capabilities of the RT-Analyzer, which has led Febit to design HybSelector, an instrument designed solely for sequence capture, Stähler said.

"The HybSelector instrument will more or less be a stripped-down version of the Geniom RT-Analyzer," Stähler said. "It will contain all the fluidics components [of the RT-Analyzer], everything we need to exploit the biochips, but it will not contain the CCD camera and all the components you need for fluorescent imaging," he said.

By removing the CCD camera and imaging components, Febit will be able to shave half the cost of manufacturing the instrument, and reduce its footprint by a third, allowing the firm to offer it for "below $90,000," Stähler said. The RT-Analyzer costs over $100,000, he said.

"We have customers that will focus completely on HybSelect ,and they have given us a strong case to have a dedicated HybSelect instrument that does not perform imaging," said Stähler. "HybSelector users don’t want to have an instrument with applications they will never use," he said. Sequence capture will be "all this instrument will do," he added. "It will perform HybSelect, HybSelect, and HybSelect."

HybSelector will be initially optimized for use with the Applied Biosystems' SOLiD platform. Febit and Life Technologies unit ABI began cooperating earlier this year, and Febit has installed several SOLiDs in house, to which it offers access via its services arm (see BAN 9/29/2009).

Febit plans to provide more details about HybSelector at the Advances in Genome Biology and Technology conference in February. The instrument is scheduled to launch in the second quarter of 2010. Later in the second quarter, Febit will provide protocols to support other sequencing platforms, Stähler said.

While Febit puts the finishing touches on its new instrument, the company is also in the middle of a biochip density upgrade. Febit's current generation of Geniom Biochips carry a total of 120,000 probes in eight separate channels. Next month, the firm will launch a new chip that will carry 240,000 features. By the middle of 2010, Febit hopes to have 1.5-million feature arrays in beta testing.

"That will be a major new level for us," said Stähler. "You can do a lot with 1.5 million features and it is obviously very interesting for the target-enrichment product line," he said. According to Stähler, the new arrays will be available in the same Geniom biochip format, and users will not require any upgrade to use them.

Febit is also developing a menu of theme arrays for HybSelect customers. The first, a human cancer biochip covering 115 genes, was launched in June (see BAN 7/14/2009). Stähler said that Febit has seen "quite some interest" in the chip, but that the majority of customers preferred to build custom arrays based on Febit's design. A more uniform second version of the chip, including additional genes, should launch next quarter.

More than half of Febit's HybSelect customers are working in oncology and Febit plans additional disease-focused arrays, including a breast cancer panel, next year, followed by other panels for neurodegenerative diseases. The third largest group of customers is those involved in plant biotechnology, Stähler said. Ultimately, the company "plans to have a whole portfolio of optimized disease arrays" for sequence capture, he said.

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'Explosion in Slow Motion'

Febit's flurry of planned product launches shows that the company is interested in capturing a chunk of the market for target enrichment technologies. Over the past year and a half a number of firms big and small have also debuted applications for targeted resequencing, including Roche NimbleGen, Agilent Technologies, RainDance Technologies, LC Sciences, and Fluidigm.

Stähler said that the interest in sequence capture is warranted, but added that the sequencing market is taking longer than expected to develop, partially because of the time constraints inherent in current sequencing technology.

"The market has unfolded slower than we thought it would," Stähler said. "One run on a sequencer takes seven days. Then you have a real challenge in bioinformatics. It might take two weeks to a month to get a clue out of a run," he said. "So a lot of sequencing instruments have been acquired and installed but we are still waiting for papers to come out. It's like an explosion in slow motion."

For Febit, sequence capture has been "taking off quite nicely," Stähler said. The firm's services arm is booked for the first quarter of 2010, and he described Febit's sales force as "busy." According to Stähler, many researchers are interested in using sequence capture, but relatively few have used it in their own projects.

"I expect in 2010 and 2011 things will really take off," Stähler said. "The economics make a lot of sense and I expect pharmaceutical and biotechnology companies will be a significant part of the market in next year and 2011," he said. "With targeted next-generation sequencing, it makes so much sense for them to include it in some of their programs."

One aspect of Febit's offering that it hopes will set it apart from some competitors is its ability to barcode samples so that users can process multiple samples per run on a sequencer. Stähler said that Febit can currently barcode up to 20 different samples in house, but that the firm will launch a protocol for barcoding four samples for sequence capture next quarter, with a 16-plex protocol to be made available sometime next year.

Both Illumina and Life Tech have developed protocols allowing their platforms to process up to 16 samples at a time. Stähler said that, using Febit's application, users could run many more.

"Look at the SOLiD instrument — it has 16 entities on two slides," said Stähler. "Physically you can separate 16 samples on the SOLiD. If you apply our technology, you do, say, 10 barcoded samples, pool them, and enrich them, then you could process 160 samples in one run on a SOLiD instrument," he said. "Then next-gen sequencing would finally be high throughput in terms of the number of samples."

When it comes to barcoding, one rival is South San Francisco, Calif.-based Fluidigm. The firm's Access Array integrated fluidic circuit, which enables sample capture and target enrichment, sample barcoding for multiplexed sequencing, and sequencing library preparation using amplicon tagging, became available earlier this year.

Stähler said that it is likely that most vendors will eventually offer barcoding as part of their sequence capture offerings. "I think barcoding gives the user such an incredible advantage that everyone in the space will work hard to include it in some way," he said. "Every competitor will work hard to make it happen on its platform," he said." It makes sense both in economics and in terms of throughput."

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