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Base4, Hitachi Aim to Develop Solid-State Nanopore Sequencer with Optical Detection

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Last week, Base4 Innovation said it plans to collaborate with Hitachi to develop a solid-state nanopore sequencer.

The sequencer will be based on technology being developed at Cambridge, UK-based Base4 and will incorporate a solid-state nanopore with optical detection using gold nanostructures and lasers, CEO Cameron Frayling told In Sequence.

Base4 was founded in 2007 and has raised £6 million ($9 million) from investors and grant funding. It has around 25 people on staff and ongoing collaborations with the University of Cambridge Nanophotonics Group, the Wellcome Trust Sanger Institute, and the University of Cambridge Veterinary School. It was previously a contestant in the Archon Genomics X-Prize contest, but has since decided not to participate.

Frayling said that development of the nanopore system would take place over the next three years, adding that the company will collaborate with early access users to publish data as it becomes available. He declined to speculate on a commercial launch time frame, cost, or specifications of an eventual instrument.

Frayling told IS that what distinguishes the company's technology from other nanopore sequencing technology is that it does not rely on electrical detection. Most other nanopore sequencing systems that are being developed rely on current blockage to read DNA bases as they translocate through the pore. Each base elicits a slightly different blockage signature when it is trapped in the pore.

By contrast, the system being developed by Base4 incorporates gold nanostructures, which sit at the pore and "act as antennae," Frayling explained. "They collect laser light and condense it into a tiny space, a hot spot," and bases are read using optical detection.

"It's a nanopore-based technology, but not reliant on electrical detection," said Frayling. "So we have more flexibility in how we manipulate the molecule."

For instance, nanopore systems that rely on current blockage and electrical detection need pores with diameters around the size of a single DNA base itself, so that current blockage is generated from one base, as opposed to a combination of several bases, and also so that there is enough blockage to generate a distinct signal.

But, Frayling said that because Base4 will use optical detection, the nanopore does not have to be as small. Instead, the nanopore's main function is to simply hold the DNA in the hot spot. "The nanopore is there to orient the molecule," he said.

Controlling the translocation of DNA through the nanopore has been another major challenge in the field. Frayling declined to specify how the company planned to do this, but said that it is working on a number of different strategies for controlling translocation, one that would be commercialized with a first version of the system, and a separate translocation strategy with a second version of the instrument.

Unlike the systems being developed by Oxford Nanopore and Genia, which combine protein nanopores with solid-state electronics, Base4's system will be entirely solid-state, which Frayling said will give the company an advantage in terms of being able to mass produce systems and in the longevity of the system.

Protein nanopores have so far led the field, however. Last year for instance, researchers from the University of Washington showed that the bacterial nanopore MspA can read DNA with single-base resolution (IS 3/27/2012).

But researchers working on solid-state nanopores have also made advances. Earlier this year, a group from the University of Pennsylvania demonstrated a solid-state nanopore that could distinguish between short DNA homopolymers (IS 5/14/2013).

As it moves toward commercialization, Base4 will likely face steep competition. Genia has said that it will have a beta instrument in the hands of early access customers this year with a commercial product in 2014 (IS 10/2/2012). And, although Oxford Nanopore's original 2012 timeline for having a system available has come and gone, it maintains that it is still developing its GridIon and MinIon systems (IS 2/26/2013).

Additionally, Base4 will have to compete with already established next-gen sequencing systems from Illumina and Life Technologies.

Frayling said that the company plans to look for additional partners to further develop the system and intends to raise additional funds.

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