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Intelligent Bio-Systems Plans to Debut Its Sequencing-by-Synthesis Tool Next Year

Almost a year after revealing its licensing agreement with Columbia University, Intelligent Bio-Systems plans to launch its sequencing-by-synthesis platform sometime next year, according to a company official.
IBS, which uses a four-color reversible terminator SBS chemistry developed by Jingyue Ju at Columbia University’s Genome Center (see GenomeWeb Daily News 12/12/2006), has placed one prototype instrument in an undisclosed genome center and is currently looking for other early-access customers, IBS President and CEO Steven Gordon told In Sequence at a conference last week.
Although late to the game, the company wants to carve its niche by focusing on the clinical sequencing market, at least in the long run. Its platform, called the Pinpoint Sequencer, is designed to be “useful for the research market” but also to be able to “cross over [into the clinical market] when the time comes,” Gordon said during a presentation at Cambridge Healthtech Institute’s Exploring Next Generation Sequencing: Applications and Case Studies conference in Providence, RI, last week.
IBS said it will price the instrument under $300,000, or about $140,000 below Illumina’s list price for its Genome Analyzer, which also uses a four-color SBS chemistry and reversible terminators, and cluster station.
Consumables will cost about $1,500 per gigabase of sequence, or about half of what Applied Biosystems’ and Illumina’s  instruments consume in reagent costs per gigabase (see In Sequence 5/29/2007).
Amortized over several years, the instrument cost will add about $45 per gigabase sequenced, Gordon estimated, which he claimed is less than other systems.
The company’s plan to eventually target the tool for the clinical sequencing market guided some of the choices for its design, according to Gordon. For instance, in order to be useful in the clinic, the cost per run per test, rather than cost per base, has to be low. Also, the run time has to measure in hours rather than days.
Accuracy and sensitivity will also be crucial - “it has to be a fail-safe system,” according to Gordon - and the acquisition cost must be low because the clinical market “is probably more cost-sensitive on the capital equipment” than the research market, he said.
The first Pinpoint Sequencer model aims to meet these criteria. Notably, each run will only take 4.5 hours. By comparison, 454’s Genome Sequencer currently has 7.5-hour runs, and Illumina’s and ABI’s next-gen sequencers each have run times of several days.
In addition, each run on the Pinpoint Sequencer generates 60 million reads on two chips that run in parallel, one synthesizing DNA while the other one is imaged, similar to the dual chips used by ABI’s SOLiD instrument and Helicos’ HeliScope. Each chip is divided into 30 panels that each contain 1 million spots By comparison, 454’s GS FLX currently yields about 400,000 reads while Illumina’s Genome Analyzer and ABI’s SOLiD platform each produce at least 40 million reads.
IBS has not yet determined the initial read length for its platform but hinted that it will be “closer to ABI and Solexa than it is to 454.” These systems currently offer reads ranging from 25 bases to 36 bases, with plans to increase them to 50 bases.
He added that the system is expected to yield 5 gigabases of data per day, but did not say over how many runs.

The tool will cost less than $300,000, or about $140,000 below Illumina’s list price for its Genome Analyzer and cluster station, while consumables will cost about $1,500 per gigabase of sequence, or about half of what Applied Biosystems’ and Illumina’s instruments consume in reagent costs per gigabase.

In order to keep the run time short, IBS minimized the image-acquisition time by packing the DNA targets tightly on the chips: Samples are deposited in an ordered array using a “proprietary method,” according to Gordon.
Also, the time it takes to run each chemistry synthesis cycle is “approximately matched” with the image acquisition time, so one chip never waits for the other to finish.
The system will sequence clonally amplified DNA, rather than single DNA molecules, but Gordon did not give details on the nature of the sample prep, citing pending patents. The firm also has a paired-end method available, he said.
He pointed out that the first three PCR cycles are critical in keeping errors in the amplified material low, though it is impossible to make these early cycles completely error-free. In order to keep amplification errors low, the system is using off-the-shelf polymerases with very high accuracy.
At present, IBS is looking for additional early-access customers who “really understand sequencing and can help us debug the system and find ways of improving it,” Gordon told In Sequence last week.
The company, which has a headcount of about 20, still has to decide how to market and distribute the system, he said.
IBS has been funded through private investments and several NIH grants and closed a multimillion dollar Series A funding round from angel investors earlier this year. Last month, it won a one-year, $154,000 grant from the National Cancer Institute to develop a sample-prep method for measuring digital gene expression in cancer.
Earlier this year, IBS received a two-year, $600,000 phase I SBIR grant from the National Institute of Allergy and Infectious Disease to apply its next-generation sequencing platform to HIV resistance testing (see In Sequence 6/19/2007).

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