Oxford Nanopore was founded in 2005 to develop a disruptive, electronic, single-molecule sensing system based on nanopore science. The first product, MinION, was introduced into early access in 2014 and made commercially available in 2015. The scaled-up GridION was commercially launched in 2017 and PromethION in 2018, with the largest device, the PromethION 48, first shipped in 2019. Flongle, the adapter for MinION/GridION for rapid, cheaper, smaller tests was launched in 2019. The Company has a rich development pipeline that includes solutions to enable any user, anywhere, including the mobile-phone-compatible SmidgION and low cost, portable sample prep Ubik.
The rich history of research and development that has resulted in nanopore sequencing is outlined below. The Company now has more than 1,400 patents and patent applications across 200 patent families, with hundreds generated by internal R&D, and complemented with key in-licenced IP from collaborators. Find out more about the intellectual property portfolio here.
From an idea, to fundamental science, to a technology platform and working chemistry, and onward to a working, integrated technology
In June 1989, Professor David Deamer - at the time at UC Davis - was driving when it occurred to him that a protein channel might be incorporated into the membrane of a liposome, and that the resulting channel might accommodate individual nucleotides - the small components of DNA. Professor Deamer thought that each nucleotide could potentially produce a specific blockade of ionic current as it passed through the channel, a concept that was later shown by Professor Hagan Bayley. For two years, this idea lay undiscussed - and in Professor Deamer's notebook - until a discussion in 1991 with Professor Dan Branton, visiting from Harvard University.
In 1991, Professor Dan Branton visited UCDavis and a decision was made to pursue research into the concept of nanopore sensing, and in 1992 it was agreed that Harvard would be the lead institution for intellectual property. The broad research team now included Church and Balderelli.
In 1993, First experiments were performed with Kasianowicz at NIST, and from 1994-5 with support from NSF SGER grant, research continued at UC Santa Cruz, NIH and Harvard.
The concept of nanopore sequencing was then 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".
In 1997, Professor Mark Akeson joined the project. Key patents were soon filed by the group at Harvard University; in 1998 US Patent 5,795,782, "Characterization of Individual Polymer Molecules Based on Monomer-Interface Interactions" was granted.
In 2001, Professor Hagan Bayley's lab in Oxford described a working nanopore sensor in the journal Nature Nanotechnology: "The binding of single-stranded DNA (ssDNA) molecules to the tethered DNA strand causes changes in the ionic current flowing through a nanopore. On the basis of DNA duplex lifetimes, the DNA-nanopores are able to discriminate between individual DNA strands up to 30 nucleotides in length differing by a single base substitution."
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 Professors 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 of 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.
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.
Around 2010, Oxford Nanopore started bringing together some of the innovations around Strand Sequencing from the academic groups it funded. Key elements were a mutated nanopore with the ability to discriminated nucleotides (Bayley lab), and a enzyme motor capable of controlling DNA movement through the nanopore (Akeson lab). These two elements were brought together for the first time in the summer of 2010. By March 2011, the chemistry had been developed and coupled to a basecalling algorithm, producing the first example of DNA sequencing with a nanopore.
Introducing the technology
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.
Building a Community
In October 2014, at the ASHG conference, the design of 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 2020, 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 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 building a new high tech manufacturing facility to address growing global demand for nanopore technology
Driving technology improvements
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.
Towards anyone, anywhere
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 was 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.
In late 2019, the first use of Oxford Nanopore at ultra-high scale in a population-scale sequencing project was announced by the Department of Health in Abu Dhabi, using PromethION 48.
Read: 19 highlights of 2019.
Innovating to respond to a pandemic whilst optimising on accuracy and yield
In early 2020, Oxford Nanopore's technology was put to use in the surveillance of the coronavirus outbreak. As adoption spread around the world, the tech was being used by researchers in more than 70 countries by the end of the year. See COVID-19 timeline for more information about the use of nanopore technology during the pandemic.
In February 2020, researchers showcased the potential of adaptive sampling. With Oxford Nanopore's unique ability to stream data in real time, new dynamic workflows are possible. Researchers showed that nanopore sequencing can actively select - in real-time, on the device - certain areas of interest, for example cancer genes or exomes in a whole genome sample.
The next generation of the portable MinION device became available in March 2020. MinION Mk1C combines sequencing and analysis with a screen to provide an all-in-one portable and handheld sequencing device.
In June 2020 first Q-line products were announced — a new line of products to support users who wish to develop tests based on nanopore sequencing, for deployment in their own environments The ISO9001-qualified Q Line sequencing portfolio from Oxford Nanopore delivers all the benefits of real-time, on-demand sequencing in a locked-down, standardised format — enabling the implementation of routine, long-term workflows for in-house validated assays.
The LamPORE COVID-19 test became Oxford Nanopore’s first diagnostic, receiving CE marking for in vitro diagnostic use in October 2020. In a study carried out by teams across the UK on more than 23,000 samples, LamPORE was shown to be highly accurate for the detection of SARS-CoV-2. The study demonstrated >99.5% sensitivity and specificity, in both swab and saliva samples, making LamPORE highly effect for testing symptomatic and asymptomatic individuals.
In December 2020, Oxford Nanopore demonstrated 98.3% single read accuracy and generated 10Tb of sequence data from a single PromethION run, utilising all 48 flow cells.
The introduction of a Q20+ kit in March 2021, saw single-molecule, single-pass sequencing reads above a modal 99% accuracy, or Q20+ in external users’ hands, as well as internally.
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