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Posted: Feb 17, 2012
Oxford Nanopore introduces DNA 'strand sequencing' on the high-throughput GridION platform and presents MinION
(Nanowerk News) Oxford Nanopore Technologies Ltd. today presented for the first time DNA sequence data using its novel nanopore 'strand sequencing' technique and proprietary high performance electronic devices GridION and MinION. These data were presented by Clive G Brown, Chief Technology Officer, who outlined the Company's pathway to a commercial product with highly disruptive features including ultra long read lengths, high throughput on electronic systems and real-time sequencing results. Oxford Nanopore intends to commercialise GridION and MinION directly to customers within 2012.
Oxford Nanopore's GridION system consists of scalable instruments (nodes) used with consumable cartridges that contain proprietary array chips for multi-nanopore sensing. Each GridION node and cartridge is initially designed to deliver tens of Gb of sequence data per 24 hour period, with the user choosing whether to run for minutes or days according to the experiment.
Oxford Nanopore will introduce a new model of versatile pricing schemes designed to deliver a price per base that is as competitive as other leading systems at launch. Further substantial pricing improvements are expected with future development to the technology, in particular with increases in nanopore processing speed and higher density electronic sensor chips.
Oxford Nanopore has also miniaturised these devices to develop the MinION; a disposable DNA sequencing device the size of a USB memory stick whose low cost, portability and ease of use are designed to make DNA sequencing universally accessible. A single MinION is expected to retail at less than $900.
"The exquisite science behind nanopore sensing has taken nearly two decades to reach this point; a truly disruptive single molecule analysis technique, designed alongside new electronics to be a universal sequencing system. GridION and MinION are poised to deliver a completely new range of benefits to researchers and clinicians," said Dr Gordon Sanghera, CEO of Oxford Nanopore. "Oxford Nanopore is as much an electronics company as a biotechnology company, and the development of a high-throughput electronics platform has been essential for us to design and screen a large number of new candidate nanopores and enzymes. Our toolbox is customer-ready and we will continue to develop improved nanopore devices over many years, including ongoing work in solid state devices."
Summary of presentation
At the Advances in Genome Biology and Technology conference (AGBT), FL, US, Oxford Nanopore presented:
A novel method of DNA 'strand sequencing' that uses an array of proprietary protein nanopores embedded in a robust 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 calling is performed by identifying characteristic electronic signals (disruptions in current through the nanopore), 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.
Genomes that have been sequenced as contiguous reads comprising both complementary strands of the entire genome. An example was shown of lamda, a 48kb genome, sequenced as complete fragments, whose sense and antisense strand total ~ 100 kilobases. Read lengths mirror fragment sizes in the sample with no exponential loss of processivity.
Accuracy levels competitive with existing market-leading systems were shown. No deterioration of accuracy is seen throughout the sequencing of individual strands. A development pathway was presented that is expected to achieve accuracy exceeding current market-leading platforms through further design iteration of Oxford Nanopore's custom-made nanopores.
Oxford Nanopore's GridION platform was presented, consisting of a scalable network device - a node - designed for use with a consumable cartridge. Each cartridge is initially designed for real-time sequencing by 2,000 individual nanopores at any one time. Alternative configurations with more processing cores will become available in early 2013 containing over 8,000 nanopores.
Nodes may be clustered in a similar way to computing devices, allowing users to increase the number of nanopore experiments being conducted at any one time if a faster time-to-result is required. For example, a 20-node installation using an 8,000 nanopore configuration would be expected to deliver a complete human genome in 15 minutes.
A variety of sample preparation options were presented. No sample amplification is required and any user-derived sample preparation resulting in double stranded DNA (dsDNA) in solution is compatible with the system. With nanopores embedded in robust polymer membranes, dsDNA can be sensed directly from blood and in some cases with no sample preparation.
Oxford Nanopore's disruptive "Run Until..." informatics workflow: Nanopores allow the analysis of data in real time, as the experiment happens. Each GridION node contains all the computing hardware and control software required for primary analysis of data as it is streamed from each nanopore, resulting in full length real-time delivery of complete reads so that the user can perform secondary analyses as the experiment progresses. This allows the user to pre-determine an experimental question and continue the sequencing experiment until sufficient data have been accumulated to answer the question and move on to the next experiment.
Oxford Nanopore intends to introduce a new pricing model for its GridION sequencing system, which moves away from the traditional instrument price and consumable price. This is designed as a series of packages that allow the user to tailor a scheme to their budget structure, whether more flexible with capital or consumable expenditure. Transparent pricing schemes are designed for online ordering and fulfilment, with discounts applying to larger packages. Overall the schemes are designed to deliver a competitive 'price per base' compared to other systems on the market based on like-for-like user settings.
Further information is available at the Company's website www.nanoporetech.com. While orders are not yet being taken for the GridION and MinION systems, interested users may register their interest at the website.
About Oxford Nanopore
Oxford Nanopore Technologies Ltd is developing a novel technology for direct, electronic detection and analysis of single molecules using nanopores. The modular, scalable GridION technology platform is designed to offer substantial benefits in a variety of applications. The miniaturised MinION device is the size of a USB memory stick, designed for portable analysis of single molecules. Oxford Nanopore intends to commercialise GridION and MinION directly to customers for DNA 'strand sequencing' in 2012.
In addition to DNA sequencing, the system is also compatible with the direct analysis of RNA. Oxford Nanopore is also developing a Protein Analysis technology that combines target proteins with ligands for direct, electronic analysis using protein nanopores. These nanopore sensing techniques are combined with the Company's proprietary array chip within the GridION system and MinION.
The Company is also developing the subsequent generation of nanopore sensing devices based on solid-state nanopores.
Oxford Nanopore has licensed or owns more than 300 patents and patent applications that relate to many aspects of nanopore sensing including fundamental nanopore sensing patents, analysis using protein nanopores or solid state nanopores and for the analysis of DNA, proteins and other molecules, including the analysis of probe molecules on DNA. The Company has collaborations and exclusive licensing deals with leading institutions including the University of Oxford, Harvard and UCSC. Oxford Nanopore has funding programmes in these laboratories to support the science of nanopore sensing. This includes the use of functionalised solid-state nanopores for molecular characterisation, methods of fabricating solid-state nanopores and modifications of solid-state nanopores to adjust sensitivity or other parameters.