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Intelligent Bio Says PinPoint Platform Could Lower Consumables Cost to $2 Per Gigabase


Sequencing technology startup Intelligent Bio-Systems expects that its first commercial sequencing platform — the PinPoint I sequencer — will allow users to generate gigabases of sequence data within hours for hundreds of dollars, according to company officials.

According to Jerzy Olejnik, who gave an update on the company's technology during a talk at Cambridge Healthtech Institute's Next-Generation Sequencing meeting in San Diego last week, the instrument will be priced at around $250,000 and will be able to generate several gigabases of data per 5.5-hour run, with consumables costs of $250 per gigabase.

The platform is scheduled to enter beta-testing later this year, and will launch commercially "shortly after," he said. However, the company already projects that later versions will drive consumables costs per gigabase down to as little as $2.

The Waltham, Mass.-based firm is building its PinPoint sequencer on four-color reversible terminator chemistry invented by Jing Ju at Columbia University. Columbia licensed Ju's sequencing chemistry exclusively to IBS in 2006 (see In Sequence's sister publication GenomeWeb Daily News 12/12/2006).

By the fall of 2007, IBS had developed a prototype instrument and was looking for early-access partners to test it (see In Sequence 10/23/2007).

Earlier this year, the firm raised an undisclosed amount of funding led by Norwich Ventures of Waltham (see In Sequence 2/24/2009) that will enable it "to advance our prototype sequencer and allow the company to deliver working instruments to the laboratories of early-access customers during the coming year," IBS CEO Steven Gordon said in a company statement.

The technology will be "affordable for smaller labs" and be "the fastest and most cost-effective method for sequencing DNA on the market," according to Gordon.

Last week, Olejnik said during his talk that the company is building three beta-prototype instruments. He also provided an update on the technical specs of various parts of the system.

The platform uses emulsion PCR to clonally amplify DNA fragments on beads, similar to how the Applied Biosystems SOLiD and 454 Life Sciences platforms prepare DNA for sequencing. What is different about IBS's approach is that the steps in the sample-prep process are "optimized for automation," and that the company is "working on trying to automate the entire sample-preparation workflow for unattended overnight processing," Olejnik said.

At launch, IBS said it expects to have sample-prep kits for single-end as well as paired-end sequencing available, and to launch a digital gene expression-profiling kit "shortly after that," he added.

After amplification, the DNA beads are loaded onto disposable chips with ordered arrays, filling the arrays — which have 40 million spots, each 5 micrometers in diameter — almost completely. Once filled, the arrays are quite stable: the company has found that 99 percent of the beads are retained in the wells after 35 sequencing cycles. The arrays are then loaded onto flow cells for sequencing and imaging.

Olejnik stressed that IBS "recognized the importance of having ordered array features from the very beginning" to decrease the imaging time, and second-generation chips will have 650 million features 1 micrometer in size. In fact, both Illumina and ABI recently said they are working on ordered, or "semi-ordered," arrays for their second-generation sequencing systems, which have so far been using unordered arrays (see In Sequence 2/10/2009).

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For its sequencing chemistry, IBS now uses — in addition to the fluorescently labeled reversible terminators, which are used at a low concentration — eight unlabeled nucleotide analogs to drive the extension reactions to completion.

"We found that this particular trick improved the performance of the chemistry in a very significant way," Olejnik said. In addition, the system employs a thermophilic DNA polymerase, so the flow cells are heated.

The read length currently stands at 30 to 35 bases, with an error rate of 0.5 percent, but that is not the limit, he said, adding that the company recently received data from Ju's lab showing a read length of about 50 bases "using improved chemistry and protocols."

Two flow cells are processed in parallel in each run, one performing the sequencing reaction while the other one is being imaged — a feature similar to the ABI SOLiD and Helicos sequencers. The platform uses a 16-megapixel "low-cost, ultra-high resolution" cold CCD camera, and image processing includes a data rephrasing step that computationally accounts for strands that are leading or lagging in the number of bases they have incorporated.

IBS is currently building three beta-prototype instruments that "are going to have all the features of the commercial system," according to Olejnik, after having worked with two alpha-prototypes with smaller chips and cameras for over a year. The systems will "enter beta-testing later this year," he said, with a commercial launch planned "shortly after."

Using the beta-prototypes, the company is optimizing its protocols, continuing to improve the speed of the chemistry and camera, and sequencing model organisms, he said.

PinPoint I, the first instrument generation, will cost approximately $250,000 and have consumable costs of about $250 per raw gigabase. The instrument has a projected throughput of 8 gigabases per day, based on a 5.5-hour run time.

In parallel, the company is already designing future generations of its instrument. PinPoint II is expected to cost $300,000 and generate 12 gigabases of data per day at a projected consumables cost of $10 per gigabase. Its run time will be about 1.5 days.

PinPoint III would be priced similarly as PinPoint II but would generate 20 gigabases per day, with a six-day run. A gigabase of data would cost as little as $2, the company projects. Olejnik did not say when IBS plans to commercialize PinPoint II and III.