By Julia Karow
This article was originally published December 10
German microarray company Febit plans to launch a dedicated instrument next year for targeted enrichment of DNA for sequencing, In Sequence has learned.
The new platform, called HybSelector, will be a stripped-down version of the firm's Geniom RT Analyzer, lacking a camera, and will use Febit's microfluidic chips and HybSelect sequence capture protocols. Initially optimized for use with the Applied Biosystems SOLiD platform, the instrument is scheduled to launch in the second quarter of 2010 and will cost under $100,000.
Later in the second quarter, Febit will provide protocols to support other sequencing platforms as well.
Febit plans to provide more details about HybSelector at the Advances in Genome Biology and Technology conference in February.
HybSelector will process Febit's Geniom Biochips, which currently carry a total of 120,000 probes in eight separate channels. The company launched its HybSelect DNA capture method earlier this year, offering it both as a service and for users of its Geniom RT Analyzer (see In Sequence 3/17/2009). Febit is working on several higher-density versions of the chips, to be launched over the course of next year, that will allow users to target up to tenfold more DNA per sample.
Febit vice president of marketing and CSO Peer Stähler told In Sequence last week that HybSelect distinguishes itself from other microarray DNA capture products, including Agilent Technologies and Roche NimbleGen, by focusing on smaller targets and providing multiplexed processing of barcoded samples. At the moment, "we are the only platform to do barcoding," he said, while competitors process each sample on a separate array.
Multiplexing is possible, he said, because Febit's platform is an automated microfluidics system that requires no assembly and enables "very precise processing" of the samples, thus preventing bias.
By the middle of next year, Febit plans to be able to process at least 100 samples per week, and eventually up to 1,000 samples per week, in one or two runs on the HybSelector.
At the moment, Febit's capture chips target smaller regions of DNA than, for example, Roche NimbleGen, which offers a human exome array that covers more than 30 megabases. But the firm is working on increasing the density of its chips next year.
Febit's current chips have 120,000 probes in a total of eight channels, and customers typically target 1 megabase of DNA for sequence capture. Targets up to 10 megabases in length are possible, though that is "stretching it a little," Stähler said.
In the first quarter of 2010, Febit plans to launch a new chip version that is going to double the number of probes. By the middle of next year, the company expects to start early-access testing for an even higher-density chip, with 1.5 million probes, which it plans to launch widely by the end of next year or in early 2011. That chip, Stähler said, will enable users to target approximately 50 to 60 megabases of DNA.
In addition to providing custom chips, the company plans to launch new catalog sequence-capture chips next year, focusing initially on cancer research applications, followed by neurodegenerative diseases. In June, it released its first human cancer biochip for HybSelect, covering 115 genes.
The firm also plans to launch an all-exome chip next year.
Targeted Sequencing Services
In the meantime, Febit, which is based in Heidelberg and has a US location in Lexington, Mass., has ramped up its targeted sequencing services, which it has been offering since earlier this year.
Initially, HybSelect protocols were optimized for use with Illumina's Genome Analyzer, and until recently, Febit outsourced the sequencing part of its service to partners, primarily Prognosys Biosciences in San Diego.
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But as part of a non-exclusive co-marketing agreement Febit struck with Life Technologies in September, Febit recently installed two ABI SOLiD instruments at its Heidelberg location (see In Sequence 9/29/2009), which serves as a demo lab to showcase the workflow of Febit's DNA capture method in conjunction with ABI's sequencing platform.
Having its own sequencers has already allowed the company to cut down the turnaround time for its service from four to six weeks to about 10 days, Stähler said.
While the company is still working with its partners for Illumina GA sequencing services, it is now "leaning towards SOLiD." Stähler said the instrument has "caught up" with the GA in terms of automating and optimizing workflows and providing bioinformatics-analysis tools, and that it works well in conjunction with Febit’s capture platform.
Febit might also offer excess capacity on its SOLiD instruments to customers for non-targeted sequencing projects, for example for whole-genome cancer sequencing.
Customers of Febit's complete targeted sequencing service receive lists of variants from the company. Stähler said that, in general, the bioinformatics and data analysis involved even for a targeted next-gen sequencing experiment is still a "huge issue" that has required the company to upgrade its computing hardware.
So far, about 40 to 50 customers have used its sequence-capture services, and the company is already fully booked through the first quarter of 2010, he said.
The vast majority of customer projects are in cancer research and range from analyses of a couple of genes to 100 genes, Stähler said. Other studies focus on, for example, neurodegenerative diseases, ultradeep sequencing of selected cDNAs to find rare splice variants, or characterizing virus insertion sites. None of these studies have been published in peer-reviewed journals yet, but Stähler said he expects several of its customers to publish their results next year.
Febit is currently involved in four large-scale targeted sequencing studies, each involving 100 samples or more, providing capture as well as sequencing services for three of these. Stähler said that early results from some of these studies are likely going to be presented at scientific conferences early next year.
Febit's alliance with Life Technologies is also paying off in other ways, he said. For example, the firms have already provided each other with sales leads. As a small company — it employs around 100 people, three quarters of whom work in Heidelberg and the remainder in Lexington — Febit is also benefiting from Life Tech's large marketing and sales team, he said.
Stähler said he expects targeted sequencing to remain cost-competitive with whole-genome sequencing for a long time to come. Over the next two years, he predicts that a lot of clinical sequencing — currently largely based on Sanger technology — will move over to targeted next-gen sequencing. For applications that require small regions of DNA to be analyzed in lots of samples, "the economics will always be in favor of enrichment," he said.