By Kevin Davies
January 28, 2011 | It hardly qualifies as an all-out media blitz, but two years after the publication of a landmark paper that demonstrated the feasibility of protein nanopores for base discrimination in next-generation sequencing applications, Oxford Nanopore Technologies (ONT) has finally sneaked the first details of its playbook, a prototype sequencing system dubbed GridION.
Although the first public details of the GridION system were displayed on the British company’s redesigned web site today, ONT is downplaying the release. The timing, however -- just days before the start of the annual Advances in Genome Biology and Technology (AGBT) conference -- is almost certainly not coincidental. AGBT is typically a prime showcase for new DNA sequencing platforms, but ONT is not breaking its silence on this year’s program. However, scientific founder Hagan Bayley, professor of chemistry at Oxford University, is presenting his own lab’s latest work in the closing session.
The choice of the term “GridION” does not reflect any particular connection with American football. Rather, it refers to the networking and “cross-communication” capacity of the individual instruments, or “nodes” as ONT refers to them, and the fact that nanopore sequencing relies on detecting shifts in electrical (or ionic) current as nucleotides pass through a protein nanopore. (There is also no connection with the Ion Torrent next-gen sequencing platform, which measures hydrogen ion by-products during DNA synthesis.)
In principle, the GridION platform can be applied to several different uses, not merely DNA sequencing. Indeed, ONT would like to be known as more of a platform company than merely a DNA sequencing company. A company spokesperson stresses that ONT’s sales and marketing deal with Illumina is for the exonuclease sequencing approach, in which an enzyme snips individual bases from a single-stranded DNA molecule and drops them into a nanopore. However, ONT is also actively pursuing the sequencing of intact single-stranded DNA molecules and the applicability of the platform for protein detection and eventually other kinds of analytes.
The most immediately noticeable feature of the ONT sequencer is that it looks nothing like a sequencer. The “box” or node resembles a large DVD player, complete with an automatic front-loading cartridge. A single node is the width of a computing blade, and fits into a standard 19” rack. The unit is 3.5” high and 20” deep. Each node weighs less than 22 pounds and rates a power consumption of less than 50 W.
The GridION nodes can be installed on a benchtop or stacked vertically in a computing rack, and plugged into a network. This can produce a scalable electronics platform that ONT says resembles cluster computing more than a traditional high-throughput sequencing instrument. The individual nodes can communicate with each other across a network, whether stacked or remote, becoming a single, higher-power instrument while also providing remote access and instrument control.
The node analyzes a single array of nanopores housed in a lipid membrane. (The number could be in the thousands or tens of thousands, although ONT has not yet divulged its launch specification.) The array is placed inside a single-use cartridge containing the necessary fluidics, which is then loaded into the node as if loading a DVD.
The GridION system performs continuous system monitoring to check for experiment parameters, reagent volume, and so on. It also records and analyzes the sequence data in real time, analyzing data volume and quality, for example. The system also gives the operator the flexibility to design the experiment with a specific goal in mind, running the node(s) until a pre-determined sequence coverage or protein concentration confidence limits have been reached.
ONT is partnering with Accelrys to build a bioinformatics workflow (based on Pipeline Pilot) to handle the sequence data. ONT says that data can be streamed directly from nodes or clusters into such workflows, allowing end-to-end analyses to be executed in real-time. With data records flowing through the workflow in real-time, the computing load for data analysis is spread evenly over the runtime of the system. This, says ONT, should make the computing cheaper and with lower admin overheads. Workflows can be saved, annotated and shared with other users through a simple web-based reuse interface.
Full details of the GridION system can be found at the Oxford Nanopore web site: http://www.nanoporetech.com/.
ONT is not releasing any preliminary sequence data with the unveiling of the node, but while many researchers will find that frustrating, it is not a surprise. Two of ONT’s senior staffers, Clive Brown and John Milton, were key scientific managers at Solexa, the British next-gen sequencing pioneer, which deliberately did not publish details of its technology platform until it had sequenced a complete human genome in 2008. Moreover, the release of any exonuclease sequencing data will only be done with marketing partner Illumina’s consent.
ONT has a little more flexibility in discussing its progress in strand sequencing, for which it has not yet struck a commercialization deal, but that appealing technology, a dream since the mid-90s, still has a long way to go.
Nevertheless, the release of the first details of the GridION platform will only make next-gen sequencing aficionados yearn even more to see if the sequencing system lives up to the growing expectations as ONT inches ever closer to the goal line.