By Monica Heger
Intelligent Bio-Systems is developing a low-cost sequencing system that it claims is particularly suited for the clinical market and plans to commercially launch the system in 2012.
Steven Gordon, CEO of Waltham, Mass.-based IBS, disclosed the company's plans for the system at this month's X-Gen Congress meeting in San Diego. He said the company plans to line up early-access customers in the third or fourth quarter of this year.
The system, called the PinPoint Mini, will cost $85,000, with sequencing reactions estimated to cost $75 per gigabase, and will have a throughput of up to 80 gigabase pairs, Gordon said. Each cycle of a flow cell takes about half an hour, so one exome could be sequenced to 30-fold coverage in about a day and a half for around $150, he said.
The development of the PinPoint Mini marks a shift in the company's strategy toward a low-cost, customizable system that is suited for clinical applications.
Founded in 2005, the company spent several years developing a higher-priced system called the PinPoint based on four-color reversible terminator chemistry that was developed by Jing Ju at Columbia University and licensed by the company in 2006. The PinPoint was priced at around $250,000 with a throughput of around 8 gigabases per day, 5.5 hour run times, and consumable costs of around $250 per gigabase.
Initially targeting a 2008 launch date for the system, the company later said it planned to begin beta-testing in late 2009 with commercialization to follow, but IBS has not launched that system (IS 3/24/2009). Gordon told In Sequence that the company is still developing it, but would not comment on when it expects to commercially launch it or how far along it is in development.
He said that the company decided to change its strategy because he saw a "hole in the market" for customizable systems suited for clinical applications. The PinPoint Mini is "designed to run smaller runs cost effectively, and the other is a higher-throughput system that would be used for whole-genome sequencing or other kinds of genome center projects," he said.
Other companies are also launching systems that they say will be suited for clinical applications, such as Life Technologies' Ion Torrent PGM and Illumina's MiSeq. IBS's system would likely compete with these other machines, which are priced at around $50,000 and $125,000, respectively.
Additionally, Illumina has said that it will apply for 510(k) approval from the US Food and Drug Administration for its MiSeq instrument (IS 1/18/2011).
Gordon said that the company built the Mini around parameters that it thought would be necessary to bring next-generation sequencing into the clinic, and thus would have an advantage over other research-grade systems that vendors and users are now trying to adapt for clinical uses.
The system holds up to 20 flow cells. Researchers can run one sample in one flow cell, 20 samples in 20 flow cells simultaneously, or start runs in different flow cells at different times, without interrupting the sequencing run, Gordon said.
He added that this feature should make it applicable for clinical purposes because a single patient who needs a diagnosis immediately would not have to wait for the machine to finish a run, nor would there be a need to multiplex samples to keep costs down, since the cost is determined based on the number of flow cells run.
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"One of the main design goals for the machine was to allow users to do smaller runs without paying a penalty because they did not batch samples to construct a very large run. Thus, the cost of a run is approximately proportional to its size," he said.
The Mini can achieve read lengths up to 100 base pairs and is customizable depending on a user's needs, Gordon said. For instance, one exome can be sequenced to 30-fold coverage with 75-base-pair reads in a day and a half, he said. Or, a researcher could cut the sequencing time in half by using two flow cells and reducing the read lengths.
Each flow cell has 20 million reads, so a system loaded to capacity produces 400 million reads and 80 gigabases of paired-end sequence data with read lengths at 100 base pairs.
Sample prep will initially be based on emulsion PCR, the same technology used by the Life Technologies SOLiD and Ion Torrent PGM platforms, which clonally amplifies DNA fragments on beads. The beads are then loaded onto chips with ordered arrays and placed into flow cells for sequencing and imaging. Eventually, sample prep will be based on DNA nanoballs, similar to what is used by Complete Genomics, and be fully automatable, Gordon said.
The Mini is based on the same chemistry as the original Pinpoint, and Gordon said the error rate of the system is about 1 percent.
The reagents are key to the platform's low cost. The dye-labeled nucleotides, which drive the price of sequencing up, are used in low concentration and in conjunction with less expensive unlabeled nucleotides. In the initial extend step, only 10 percent of the nucleotides are fluorescently tagged— "just enough to get a signal," said Gordon. Then, a second extend step using solely unlabeled nucleotides drives it to completion.
Holli Dilks, director of core services at Vanderbilt University Medical Center's division of human genomics, who was also at the San Diego meeting, told In Sequence that, as presented, the system seemed like an "interesting alternative to sequencers on the market."
"It definitely is a niche product that would fill a need many people have right now, not just in diagnostics, but at core facilities" where there are often wait times for sequencers.
She thought the machine's ability to run multiple samples at different start times would be its biggest advantage, but was concerned about the lack of information presented about data output. "There was no information on what the data would look like," she said. "And that's the big question — what to do with the data that comes off the instrument."
Dilks thought that the fact that IBS does not yet have any commercially available products, coupled with its current lack of data, would make it difficult to compete against other well-known companies with proven technology.
While she is not in charge of purchasing sequencing equipment, she said that if she were, she would first want to see data from the machine before deciding whether to purchase one.
IBS currently has one PinPoint Mini in house and is planning to ship to early-access customers before the end of the year. Gordon said that genome centers, translational research centers, and clinical labs have expressed interest in acquiring a system.
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