Nanopores Make Big Waves
The latest potential product entrant to win the appellation, according to company CEO Gordon Sanghera, is Oxford Nanopore Technologies’ MinION, set to go on sale in the second half of 2012. The company says the machine will cost less than $900. Way smaller than a bread basket, the MinION is about the size of a USB thumb drive.
The company described the device as well as its bigger sibling, the GridION system, on February 17 at the Advances in Genome Biology & Technology (AGBT) conference, which has emerged as the industry’s best-publicized hush-hush meeting at which to announce breakthroughs.
The MinION can be plugged into a laptop’s USB port. The GridION, a larger version of the machine, can be stacked to increase processing power. The sequencers are based on the company’s nanopore “strand sequencing” technology combined with the two electronic devices, GridION and MinION. The MinION, said to deliver 150 megabases of DNA sequences per hour, is intended for one-time use only and will sequence up to a million bases. According to some reports including a story in The New York Times, executives said that the GridION could cost about $30,000. However, an Oxford Nanopore spokesperson noted that this is incorrect as there is no fixed price for a single instrument. The systems will reportedly be priced in packages that include instruments and consumables.
Oxford describes its technology as a method of DNA “strand sequencing” that uses an array of protein nanopores embedded in a polymer membrane. Each nanopore sequences multiple strands of DNA from solution in succession, as individual strands are passed through the nanopore by a proprietary “processive” enzyme. Base identification is accomplished by identifying characteristic electronic signals.
These signals are created by unique combinations of DNA bases as they pass through a specially engineered region inside the nanopore. DNA and enzyme are mixed in solution, engage with the nanopore for sequencing, and once the strand has been completed, a new strand is loaded into the nanopore for sequencing. The technology does not require sample amplification; the company says that any user-derived sample preparation that yields dsDNA will work with the system.
“If it does work, it will be a game-changer,” said Elaine Mardis, co-director of The Genome Institute at Washington University in St. Louis. Chad Nusbaum of the Broad Institute called it “impressive, credible, possibly amazing,” according to an article in The New York Times.
But does it work? Life Technologies’ Ion Torrent division head, Jonathan Rothberg, and inventor of the ion torrent technology behind that company’s Personal Genome Machine, said in an e-mail interview with Forbes’ Matthew Harper, “I don’t believe it.” If it is real, Rothberg said, it has to scale a million-fold, from 5,000 bases to six billion. “How are they going to do that all this year? How are they going to manufacture the parts?”
Rothberg noted that Life Technologies showed three human genomes completed with the Ion Proton instrument last month at AGBT. More importantly, he added, they had the machine—not a mock-up or a design—on the stage. “That’s where you need to be to ship mid-year.”
Rotherberg’s technology combines fluidics, micromachining, and semiconductor technology, allowing direct translation of DNA into DNA sequence. The technology works by generating sequencing data by directly sensing hydrogen ions produced by template-directed DNA synthesis.
In less than a year since the semi-conductor-based instrument was launched, it became the best-selling next-generation sequencing machine in the world. The technology provides low cost and scalable sequencing on a massively parallel ion chip. Reactions are performed using natural nucleotides, and the individual ion-sensitive chips are disposable and inexpensive.