Oxford Nanopore employs a team of more than 450 people including scientists, engineers, informaticians, manufacturing and commercial specialists. Headquartered in Oxford, UK, the Company has a commercial or scientific presence in all major markets including the US, China, Singapore, France, Germany and Japan. The company sells to nearly 100 countries and is in a period of rapid growth.
From an idea, to fundamental science, to a technology platform and working chemistry, and onward to a working, integrated technology
The concept of nanopore sequencing was first described in publication by Branton, Deamer et al in PNAS in 1996. The group showed translocation of nucleic acids through a nanopore set in a lipid bilayer, and noted that "Channel blockades can therefore be used to measure polynucleotide length. With further improvements, the method could in principle provide direct, high-speed detection of the sequence of bases in single molecules of DNA or RNA". Key patents were filed by the group at Harvard University.
Hear more from Deamer and Branton who spoke at London Calling 2018:
Years later in 2005, Oxford Nanopore was founded as Oxford Nanolabs by Dr Gordon Sanghera, Dr Spike Willcocks and Professor Hagan Bayley (currently Professor of Chemical Biology at the University of Oxford), with seed funding from IP Group plc.
The early years
In the first years of the Company, Professor's Bayley's work to characterise the structure of protein nanopores was combined with expertise and intellectual property from collaborators including Dan Branton, Dave Deamer and Mark Akeson, at global institutions including Harvard, Boston University and the University of California Santa Cruz. Since these foundational years, Oxford Nanopore's internal, multidisciplinary teams of hundreds scientists have continued to innovate in multiple disciplines related to nanopore sensing, in order to bring the only nanopore sequencing technology to market, and continue to improve that technology. Oxford Nanopore's intellectual property portfolio now includes more than 1,000 patents and patent applications, the majority generated by internal R&D, but complemented with key in-licenced IP from collaborators.
Gordon Sanghera has been CEO since the Company's foundation. He brings his experience of combining biological and electronic technologies and working across all disciplines at a senior level in a technology company. He previously delivered blood glucose-sensing products to the market, a technology that has transformed the lives of diabetes patients worldwide. Gordon now leads an experienced management team towards the development and commercialisation of a disruptive technology platform for the analysis of biological molecules.
In 2008, Dr John Milton and Clive G. Brown joined the executive management team, bringing previous experience of having developed DNA sequencing technology at Solexa, which was acquired and commercialised by Illumina.
During these early years the company was focused on researching and developing breakthrough nanopore sequencing chemistry, but was also focused on the development of a new, bespoke electronics platform that could measure picoamp currents, in large-scale arrays for high throughput research of nanopore sensors, and ultimately for the production of commercial nanopore sequencers. Oxford Nanopore first moved from single-channel 'Axopatch' devices to inventing and building small arrays of 4, then 9, then 128 channel sensor chips, then designing and building the larger arrays that feature in todays' products. This was in conjunction with the development of bespoke ASICs that enable the high-frequency, highly sensitive measurement of nanopore signals.
In July 2009, the Company relocated to the Oxford Science Park. Our premises at Edmund Cartwright House were inaugurated by the UK Science and Innovation Minister, Lord Drayson. In 2011, an additional 7,000 square feet on the Oxford Science Park was opened and a new Cambridge office was also opened.
Introducing the MinION
In February 2012 at the AGBT conference, Oxford Nanopore presented the first ever nanopore sequencing data, and provided an overview of the hardware and software behind the GridION and MinION systems. These data included small genomes that had been sequenced using the Company's technology over the sense and antisense strands, showing tens of kilobases in single reads.
In the following months, the company prepared the first system - the handheld MinION device - for launch. Developments in this period included: the invention of a new, robust membrane to replace traditional (and fragile) lipid bilayers so that consumable flow cells could be shipped by standard courier to anywhere in the world; improvement of nanopore and enzyme chemistries; data analysis methods to enable basecalling of the raw nanopore signal, and myriad other innovations.
In spring 2014, the MinION Access Programme (MAP) commenced; early access users were invited to contribute a refundable $1,000 deposit to use the MinION in its earliest stages of release. Over the subsequent months, performance and processes were improved and publications on the technology started to emerge.
In October 2014, at the ASHG conference, the PromethION was presented for the first time. PromethION is a benchtop instrument giving users the choice of the number of samples and the number of nanopores being used for a particular experiment, ranging from individual samples at a time to multiple samples in parallel. in 2019, PromethION is now capable of delivering more than 7Tb of sequence data in a single run equipped across all 48 flow cells.
In May 2015, the first nanopore sensing conference was convened (London Calling) where users of MinION technology gathered to hear from 20 speakers and additional abstracts from numerous other MAP participants across a range of applications. MinION became commercially available at this time and the MinION Access Programme became the Nanopore community.
In November 2015, Professor Hagan Bayley retired from the Board and MinION users gathered at the first Nanopore Community Meeting in New York.
In May 2016, the second London Calling conference was convened. A series of announcements were made including the full availability of the new R9 nanopore with improved performance. The mobile phone compatible, pipeline product SmidgION was announced.
In September 2016, Oxford Nanopore held a technical update, announcing new product upgrades to the MinION.
In October 2016, registration for the VolTRAX Introduction Programme was announced. VolTRAX is a programmable, automated sample preparation device, designed to contribute to the Company's goal of enabling sequencing by anyone, anywhere.
In December 2016, the second Nanopore Community Meeting was held. During this meeting, three groups presented or released the first human genomes to be sequenced on the handheld MinION.
In February 2017, the GridION X5 was announced; a desktop system integrating five MinION Flow Cells with integrated compute function, that can be used to offer nanopore sequencing as a service and is suitable for customers interested in higher-throughput projects such as human or plant genomes, at scale, or on-demand sequencing for multiple projects.
In May 2017, the GridION X5 started shipping and the company introduced 1D squared, a new method of sequencing that gives a boost in accuracy while keeping simple library prep processes.
In June 2017, Oxford Nanopore launched its RNA sequencing solutions. This provides the only direct, real time RNA sequencing technology and additional cDNA analysis.
In October 2018, Oxford Nanopore announced its entry into the Chinese market, having appointed a distributor and established its first sales to customers.
In December 2017-January 2018, the PromethION Early Access Programme started to deliver very high throughput DNA sequencing with nanopore technology
In January 2018, the novel method of direct RNA analysis using nanopores was published in Nature Methods. Direct RNA analysis circumvents reverse transcription or amplification steps, enabling full-length, strand-specific RNA sequences and the direct detection of nucleotide analogues in RNA.
In March 2018, Oxford Nanopore announced that it will be opening a new high tech manufacturing facility to address growing global demand for nanopore technology
In May 2018, the London Calling conference hit nearly 600 attendees. A technical update by CTO Clive Brown outlined multiple improvements to nanopore sequencing, resulting in higher yields of sequence data at higher accuracy, in easier to use formats. PromethION was transitioned from an early access phase into being commercially available.
The same month, the longest ever continuous DNA sequence was generated, 2.3Mb in a single nanopore read. Matt Loose and a team from Nottingham University used special techniques to extract ultra-long fragments of DNA, which were then processed in one read using a MinION. A new version of the device software, MinKNOW, was released in May 2018 - featuring 'progressive unblock', a technique that enabled higher yields from MinION flow cells, and as pricing remained consistent, driving greater value for money.
In the autumn of 2018, as further technology improvements including upgrades in algorithms and chemistries continued to drive performance improvement, the performance of PromethION in customers' hands started to climb, pushing beyond 100Gb per flow cell (PromethION is designed to run up to 48 flow cells on demand), and therefore exceeding the mark of delivering a 30X human genome on one flow cell.
With a continuing push for increasing yields on MinION/GridION as well as PromethION, Oxford Nanopore released 'Rev D' flow cells, which enabled as much as 30Gb of sequence data to be generated on a single MinION flow cell. With the pricing of MinION flow cells remaining unchanged, and available at as little as $500, with no capital charge for a MinION device, this was making sequence data increasingly accessible.
In October 2018, the MinIT was launched. A companion device to the MinION, the MinIT contains GPU technology that can optimise rapid basecalling and data analysis, in place of - or alongside - a laptop. As nanopore uniquely streams data in real-time, the MinIT supports the increasing speed and power of the MinION with enhanced compute power.
In November 2018, the annual Nanopore Community Meeting was held in San Francisco. The largest so far, it included an array of novel and breakthrough science using nanopore technology. During Clive Brown's talk, he outlined that the Company was in advanced development of R10, a new nanopore with a longer barrel that is designed for very high consensus accuracy. A new basecaller, 'flip-flop' was also announced, enabling high accuracy analysis with the current 'R9.4.1' nanopore.
Read '18 highlights of 2018' for more.
2019 has been a year of further innovation and acceleration. In January, the Company introduced the 'Field kit' - a lyophilised sample preparation kit that no longer needs a cold chain. Used by scientists sequencing in remote locations, as well as those in the lab, this was another step towards the anyone/anywhere goal.
Early in the year, PromethION was offered as two new devices: P24 and P48, offering the use of up to 24 and 48 flow cells in each device.
In February, the Company introduced two new kits for the sequencing of cDNA, offering the ability to sequence full length RNA transcripts (via cDNA), at high throughput.
In March, the Company launched Flongle, an adapter for MinION or GridION that enables low-cost, on-demand, smaller sequencing tests.
The same month, the first usage of nanopore sequencing in regulated environments came online. This included food safety testing by Clear Labs, and the use of GridION in infectious disease testing in Switzerland, and Huntingdon's Disease in the UK.
In April, PromethION 48 generated more than 7Tb in a single sequencing run at Oxford Nanopore. This is the highest known single yield from any sequencing device. At this stage, PromethION is now being used in many ultra-high throughput projects including at Grandomics in a 100k genome project focusing on structural variation, and at Decode genetics.
The 2019 London Calling conference featured 71 speakers, in an unprecedented array of application areas. With more than 450 publications using nanopore sequencing, the nanopore community has expanded to all areas of biological research. In an update by Clive Brown and team, the recent increases in performance of nanopore sequencing were outlined, as well as a pathway to reach beyond Q50 consensus accuracy for DNA sequencing, and to deploy multiple methods of achieving high accuracy analysis of single fragments of DNA. Clive also introduced the concept of Plongle - a 'plate flongle' that would allow multiple samples to be sequenced at low cost per sample.
In July 2019, Oxford Nanopore's new manufacturing facility at Harwell, Oxfordshire, came online. With 2-3X growth in sales over recent years reflecting increase in demand for nanopore products, the factory is designed to support rapid expansion of production, including many automation processes to ensure smooth and consistent production.
Nanopore users also started speaking about their 'early access' experiences with the new R10 nanopore, noting for example that it allows accurate analysis of SNVs and SVs.
To follow all our news updates, visit the News page.
Applications and publications
In the early days of MinION usage, many users of the technology were exploring pathogens/small genomes, environmental sequencing and developing tools for nanopore analysis. As the community has grown, the performance of nanopore sequencing has evolved dramatically and with the addition of GridION and PromethION to the instrument portfolio, this has evolved to include a larger number of researchers working in plant genetics, human genetics, clinical research, transcriptomics and other larger scale projects.
Continuous performance improvement
Continuous integration of multiple technology upgrades drives ongoing improvements
MinION was launched into the MinION Access Programme in Spring 2014 and made commercially available in May 2015. Since that time, Oxford Nanopore has delivered continual improvement in performance, usability and other metrics. The format of the hardware, software and chemistry changes on a regular basis (often over weeks rather than months). This iterative improvement process will continue throughout the lifetime of all Oxford Nanopore products.
Updates across different parts of the technology can combine to produce specific, measurable improvements. This has been achieved through a combination of software updates, changes in the library preparation kits and protocols, changes in the flow cell design and changes in the flow cell chemistries.
Examples of developments to date include:
Library preparation kits
- These have been updated several times during the Nanopore Community, and additional kits and protocols have been introduced to enable new applications, for example cDNA sequencing and barcoding of genomic DNA and amplicons. Changes have also contributed towards improving the accuracy of sequence data.
- We have also made several changes to our library preparation kits to improve the user experience. These include reducing the number of steps and consequently the time taken, and improving robustness and performance. The Rapid Sequencing kit prepares a library in five minutes.
- VolTRAX, an automated library preparation device, is designed for ease of use, anywhere, and to make it easier to prepare high quality libraries for the best sequencing results.
MinION flow cells, containing the bespoke nanopore sensor and associated chemistries
- Multiple new versions of these flow cells have been delivered to date that increase yield by delivering more working nanopores per flow cell.
- In the summer of 2016, 'R9' was released to supercede the previous R7. This was designed to improve sequencing accuracy. Running at speeds of 250+ bases per second per nanopore it was designed to increase the speed of data generation and therefore yield of a flow cell.
- In October 2016, new flow cells containing R9.4 were shipped, increasing sequencing speeds to 450 bases per second and enabling 10Gb DNA sequencing data to be obtained from a MinION Flow Cell.
- In May 2017, R9.5 was shipped, to be compatible with the new 1D squared method of sequencing. Oxford Nanopore was at this stage producing more than 20Gb from a single Flow Cell.
- at June 2019, more than 50Gb had been achieved on a single MinION flow cell internally, with many users outside the company generating 30Gb
- in 2019, R10 flow cells were shipped to users in early access. Early results indicate enhanced consensus accuracy and accurate variant calling with this novel nanopore.
- Continuous improvements to all parts of the technology including the software continue to be delivered
- In May 2015 the second version of the device, the MinION MkI was introduced. The MinION MkI was a full production device featuring improvements of performance and ease of use.
- In May 2016, the MinION Mk 1B was introduced. Preparing for future iterations of nanopore chemistry it included improvements such as greater temperature control of the flow cell.
- multiple versions of GridION and PromethION also deliver improved computational power, temperature control and a variety of other performance-enhancing qualities.
Speed of individual nanopore processing
Faster processing speed results in greater yield of data per unit of time. Speed is affected by multiple factors including buffers, temperature and the motor enzyme deployed
- During the first year of the Nanopore Community, Oxford Nanopore recommended a speed of around 30 bases per second per nanopore
- By 2015 users could run at 70bps.
- With the introduction of R9 in the summer of 2016, DNA was passed through the nanopore at 250+bps
- From October 2016, processing speeds have been 450 bases per second
- The electronics of the MinION are designed for as much as 1,000 bases per second, for further capacity for yield improvements
Flow cells: Duration of use
- Nanopore devices do not have a fixed run time; users may run the instrument for as long as it takes to accumulate sufficient data for their needs. The total available life time of a flow cell does not need to be consumed in a single experiment.
- More recent releases of flow cells and software have enabled flow cells to be run for longer (at a constant price), enabling resulting in increased overall yields.
The instrument control software (MinKNOW)
- New versions of MinKNOW have been released to improve MinION performance for all applications. For example, adjusting the frequency of data sampling can improve yield and accuracy.
- Most recently, MinKNOW now allows local basecalling.
- In February 2017, MinKNOW 1.4.2 was released, enabling larger data yields
- Further upgrades have included features such as progressive unblock, allowing enhanced yields by allowing longer run times, and improvement in 'MUX' processes to select the most productive channels early in an experiment.
Based on electronics rather than optics, nanopore technology can scale to any size:
- Following on from the success of the MinION, the GridION X5 was launched in 2017. This can run up to five MinON Flow Cells with onboard compute and has now been upgraded to the GridION Mk1, with enhanced compute power
- The PromethION is now available and offers nearly 300 times the power of a MinION except modular and on-demand. The PromethION is designed to operate up to 48 Flow Cells individually or together
- The Flongle was introduced in 2019, for rapid, smaller tests
- Oxford Nanopore continues to develop SmidgION, a smartphone sequencer
Continuous iteration of basecalling algorithms, device control software and the availability of a broad range of analysis tools from Oxford Nanopore or the community, have contributed to improvements in accuracy of raw and consensus data, and improved variant detection. At June 2019, the current R9.4.1 nanopore can generate more than Q40 accuracy (99.99%) on selected genomes, with further work ongoing to expand the range of genomes and further improve accuracy. R10 has demonstrated >Q50 on similar genomes. Read more here about analysis methods.