We've come a long way since the work of Watson, Crick, and Franklin revealed the structure of DNA.

With the steady evolution of DNA sequencing technology, the cost of the machines as well as the cost of running them continues to drop. Due to their revolutionary technology, one of the biggest players in the field recently has been Ion Torrent (acquired by life sciences giant Life Technologies in 2010). And I don’t use the word “revolutionary” lightly here. Their technology is a game-changer and we previously described how it would lead to a democratization of genomics, making it more accessible to researchers on a small budget. But now, a company called Oxford Nanopore Technologies has barged right into their party, with its own impressive approach to DNA sequencing.

Today’s standard sequencing method uses an indirect approach to DNA sequencing based on fluorescently-tagged nucleotides, the building blocks of DNA. However, Ion Torrent has developed a simple, yet ingenious way to detect the sequence of nucleotides in a sample of DNA. Exploiting the fact that a hydrogen ion is released whenever a nucleotide attaches to a strand of DNA, sensors in Ion Torrent’s microchip have been designed to detect this chemical signature. Simple and straightforward, right? (See the video below for a closer look at the technology.) The company estimates that their new Ion Proton Sequencer (at a cost of $150,000) can sequence a human genome in a few hours for about $1,000. That is really impressive!

Now comes Oxford Nanopore Technologies with its own clever method for sequencing. On their microchip, they’ve embedded a protein pore into a synthetic polymer membrane. The strand of DNA being sequenced is then passed through the pore and as each nucleotide goes through, it registers as a different electrical signal detected by Oxford’s machine. (Check out the video below for a visual explanation.) That’s it – as simple as it can get.

A big advantage of this technology is that it can very easily be scaled up or down. The standard platform is called the GridION and it features a consumable cartridge inside of the sensing instrument or node. The data generated in this node can be accessed via a local network and can be scaled up to be used in conjunction with many other nodes, which then resemble large server towers and allow many sequencing reactions to occur simultaneously. According to the company, a setup with a minimum of 20 nodes is able to sequence an entire person’s genome within about 20 minutes! Speculations are that the cost of the GridION system is in the $30-40K range with the cost of sequencing at about $1,500. With these prices, Oxford Nanopore will really give Ion Torrent some stiff competition.

Oxford Nanopore's MinION sequencer

The scaled down version of Oxford’s technology, called the MinIon is even more impressive. It allows the sequencing reaction to occur on a chip with the size and connectivity of a USB  thumb drive. This way, it can be connected directly to a laptop (or desktop) so you can literally sequence DNA anywhere you can plug a laptop in. The MinIon will supposedly cost approximately $900, though it is unclear what it’s capacity will be. It’s likely that it will only sequence small amounts of DNA, not an entire human genome. But this is great for identifying a virus sequence, for example, at a remote clinic or from a sick passenger at a busy airport. What’s more, both the GridION and MinION can be adapted for many other uses. They can identify proteins from a patient’s sample. They can identify small molecules like drugs (pharmaceutical or illegal) and toxins. Even biologically inactive compounds like explosives or chemicals! We won’t know how well Oxford’s technology works until it is released and scientists put it to the test. But it has the potential to be a real breakthrough.

Both of the technologies developed by Ion Torrent and Oxford Nanopore are impressive, but they are still relatively untested. This is especially the case for Oxford Nanopore. The accuracy, reliability, and functionality of these technologies will take some time to be fully tested and here is where Complete Genomics comes into the picture. They have carved a niche for themselves in sequencing human DNA quickly and accurately. Does a lab interested in doing some sequencing fork over $40-$150K for one of Ion Torrent’s or Oxford’s machines or do they simply outsource it to a proven company? Complete Genomics expects to churn out the complete sequences of 100,000 to 1 million genomes in the near future as they ramp up operations! That sort of infrastructure and experience will be hard to beat.

It’s obvious that we are glimpsing the future here. While the speed and accuracy of sequencing reactions are increasing greatly, costs keep dropping. As companies like Ion Torrent and Oxford Nanopore continue developing these technologies and competing with each other, scientists and patients will reap the benefits. Further, companies like Complete Genomics continue to centralize the process of producing the data that next generation sequencers are designed for. In an ideal world, we would test and decide which approach to DNA sequencing is the best in terms of accuracy and cost, and then have a commercial laboratory like Complete Genomics make it accessible to everyone from top researchers and universities to eventually, the average Joe and his doctor. However this plays out, we are fast approaching a new world in medicine.

Sources: Ion Torrent, Oxford Nanopore Technologies, Wikipedia, Complete Genomics
[Image credits: Oxford Nanopore Technologies]
[Video credits: Ion Torrent, Oxford Nanopore Technologies]