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Genome on a Stick

Tanya Lewis

Oxford Nanopore introduces a method to read DNA strands through nanopores and debuts a disposable sequencer that fits in the palm of a hand.

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Last week, Oxford Nanopore Technologies unveiled two new DNA sequencing systems, the high-throughput GridION unit and the portable MinION unit the size of a USB stick.

At the Advances in Genome Biology and Technology meeting in Marco Island, Florida, the company announced that both products will be available later this year. The systems rely on nanopore sequencing, a method for reading long, unbroken strands of DNA and RNA. A proprietary enzyme pulls the strands through specially engineered nanopores in a polymer membrane. Meanwhile, an electronic chip senses disruptions in electrical current as uniquely identifiable combinations of nucleotide bases pass through each nanopore. At the meeting, company representatives presented data that demonstrated that the 48-kilobase genome of the lambda bacteriophage could be sequenced as a complete fragment.

Oxford Nanopore shows off the new MinION nanopore sequencer, which is slated to cost less than $900. Source: Oxford Nanopore

Nanopore sequencing involves threading strands of DNA or RNA through a membrane pore using an enzyme, and measuring resultant changes in electrical current as nucleotide bases pass through it. Source: Oxford Nanopore

The nanopore chips process DNA at a rate of 20-400 bases per second per pore, which is significantly quicker than current sequencing systems. However, the systems have a high error rate of 4%. Before the products are officially launched, the company aims to trim the error down to 0.1-2% by developing better nanopores.

The GridION nodes contain a consumable cartridge with 2000 nanopores, capable of processing tens of gigabytes of sequence data in a 24-hour period. Multiple nodes can be linked together for greater computing power. The portable and disposable MinION will feature 500 nanopores and cost less than $900. While the company has not priced the GridION yet, it expects to charge a cost per gigabase competitive with other systems.

Such an affordable technology could transform diagnostic medicine. “We could scan patients and see what viruses or bacteria they have,” said David Deamer, a professor of biomolecular engineering at the University of California, Santa Cruz, who developed the original idea for nanopore sequencing more than 20 years ago. He filed a joint patent application with Daniel Branton, a professor of biology at Harvard, and geneticist George Church, also of Harvard.

Soon after, Deamer went on to collaborate with physical scientist John Kasianowicz of the National Institute of Standards and Technology and chemical biologist Hagan Bayley who were studying a pore called alpha-hemolysin. In a paper published in the Proceedings of the National Academy of Sciences in 1996, the group described the nanopore sequencing technique. In 2005, Bayley joined technologist Gordon Sanghera to found the company that would become Oxford Nanopore Technologies.

"We have designed the MinION and GridION systems to offer a range of new properties,” wrote Sanghera, now CEO of Oxford Nanopore, in an email. “Nanopores are very well suited to simple sample prep and a new type of informatics workflow where the system is programmed to run the experiment until sufficient data has been gathered to conclude the experiment.”

By 2013, Oxford Nanopore hopes to sequence an entire human genome in just 15 minutes. This will require 20 GridION nodes equipped with 8,000 nanopores each. “I think it’ll be possible from what I’ve seen,” said Deamer, who is on the company’s advisory board. “They wouldn’t give these promises unless they were pretty confident.”

Keywords:  sequencing