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Oxford Nanopore Technologies: super-fast desktop sequencing

Copyright: nanoporetech.com

A new wave of electronic chemical sensing devices based around bacterial nanopores – tiny holes in the membranes of microbes – can change the way DNA sequencing is performed, opening it up to people in new environments and for new applications. Led by Oxford Nanopore Technologies (ONT), a spin-out company based on BBSRC-funded research at the University of Oxford, it is ushering while-you-wait DNA analyses, replacing the ‘sample now, results later’ regimen widely used today. Further down the line, it could even lead to more ‘personalised medicine’ using mobile phone-based 'self quantification', which could measure biomarkers and track changes in your daily health.

The arrival of DNA sequencing in the late 1980s ushered in a new era of genomics. The problem was that it was so slow and expensive. It took nearly a decade and $2.7Bn (at 1991 rates) to sequence one human genome. Researchers around the world raced to make it faster with the next-generation Solexa Sequencing, also developed using BBSRC funding, improving DNA sequencing rates by ten thousand times.

Data breakout

30-70 Number of DNA base pairs per second that can be read by the nanopore technology (500 is said to be imminent)
10s-100,000s Possible number of DNA bases that can be sequenced in one continuous read (traditional instruments: hundreds)
$1000 Access fee to start using the MinION device, compared to capital costs of $100,000-$millions for traditional machines

Oxford Nanopore takes a different approach by using direct electronic sensing made possible by biological pores rather than sequencing chemistry, and could be a game changer in the field. The company was founded by Professor Hagan Bayley at the University of Oxford in 2005. In the foundation years, they utilised BBSRC-funded training grants to make early, critical discoveries, such as demonstrating that biological nanopores from the bacteria Staphylococcus aureus could differentiate between the individual bases of the genetic code. “Quite critical to this was involvement of graduate students who were sponsored by these [BBSRC] training grants,” says Bayley.

As the DNA bases pass through the channel-like pore, an electrical signal can be measured that is unique to each molecule. Computational methods then help to understand the order of DNA bases that have passed through the pore. This all happens at speeds far in excess of previous methods.

The result is smaller, faster and portable sequencers such as the MinION, which at just 87g (other instruments are around 50kg) can plug into a computer’s USB port. This allows much faster and easier analysis – ideal for use by field researchers tracking down anything from food poisoning outbreaks to Ebola virus strains and counterfeit timber. It takes 15-20 minutes to see the first data streaming, whereas traditional instruments can take at least a day or more.

And it’s not all about DNA. Bayley says Oxford Nanopore was founded as a company interested in developing single molecule sensing technology for metabolites, sugars and other compounds of biochemical interest. "We saw it as a platform technology. But quite soon it became obvious that its application in third-generation DNA sequencing was an area with enormous potential."