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Oxford Nanopore Technologies

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From Molecupedia, the encyclopedia of very small things
British maker of nanopore DNA and RNA sequencers
Oxford Nanopore Technologies
FormerlyOxford Nanolabs
TypePublic limited company
IndustryBiotechnology, DNA sequencing
Founded2005, Oxford, England
HeadquartersOxford Science Park, Oxford, England
ProductsMinION, GridION, PromethION, Flongle
Websitenanoporetech.com

Oxford Nanopore Technologies is a British company that makes instruments for nanopore sequencing, in which single strands of DNA or RNA are read as they pass through a protein pore and change the electric current flowing through it. It began in 2005 as a spinout from the University of Oxford's Department of Chemistry, built on the nanopore research of the chemist Hagan Bayley, and has been listed on the London Stock Exchange since September 2021.[1][2] Its devices range from the Flongle, a single-use flow cell with 126 sensing channels, to the PromethION, which runs up to 48 flow cells of about 3,000 channels each. The best known is the MinION, a palm-sized sequencer that plugs into a laptop.[3][4][5]

The company's sensors are biological nanopores: engineered proteins set in a thin synthetic polymer membrane, with a motor protein that feeds each strand through the pore at a controlled speed.[6][7] Its MinIONs have read Ebola virus genomes in Guinea, DNA aboard the International Space Station and DNA barcodes in an Ecuadorian rainforest, and its long reads helped close the last gaps in the human genome in 2022.[8][9][10][11]

Oxford Nanopore is the company that Molecular Reality Corporation, a much smaller nanopore company, measures itself against. The smaller company's quiz game calls it a "kin-spirit".[12]

History

Origins

The company's own history begins in 1989, with the idea of a protein channel that could detect individual nucleotides, and records the first experiments in 1993.[2] Bayley's research group had developed "stochastic sensing", the detection of single molecules by the brief changes in current they cause as they bind inside a protein pore; a 1999 paper in Nature used an engineered alpha-hemolysin pore with a molecular adapter to detect small organic molecules this way.[13] The idea that a pore might read DNA had been published in 1996 in PNAS, in work from Harvard, the University of California, Santa Cruz, and the US National Institute of Standards and Technology, and the company's history lists that paper as part of its background.[2][14] Bayley and two former Oxford chemists founded the company in 2005, under the name Oxford Nanolabs, and it moved to the Oxford Science Park in 2009.[2][1]

The approach the company described in a 2009 paper was exonuclease sequencing. An enzyme would clip bases one at a time from the end of a strand, and an engineered alpha-hemolysin pore fitted with a ring-shaped cyclodextrin adapter would identify each loose base by its current.[15] The company later turned to strand sequencing, in which the intact strand is threaded through the pore. Its history records the parts of strand sequencing working together for the first time in 2010 and its first DNA sequencing with a nanopore in March 2011.[2]

MinION and its users

At a genomics meeting in February 2012 Oxford Nanopore presented its first nanopore sequencing data and described two systems, GridION and MinION. Two years later, in the spring of 2014, it began the MinION Access Programme, sending early devices to outside laboratories, and the MinION went on general sale in May 2015, the month of the company's first London Calling conference.[2]

The early users took the device into the field. In April 2015 a team carried a sequencing laboratory to Guinea "in standard airline luggage", under 50 kg of it, and sequenced 142 Ebola virus samples collected between March and October 2015, with results less than 24 hours after receiving a positive sample.[8] In August 2016 the NASA astronaut Kate Rubins used a MinION for the first DNA sequencing in space, aboard the International Space Station.[9] The first human genomes sequenced on MinIONs followed in December 2016.[2] Other groups sequenced DNA in the Antarctic Dry Valleys and identified species in a rainforest in Ecuador from DNA barcodes read on site.[16][10]

When a new coronavirus appeared in January 2020, the ARTIC network, a project for sequencing virus outbreaks, released a protocol for reading its genome on nanopore devices, and the first genome produced with it was posted to the public database GISAID.[17] Laboratories that took up the method typically moved from the MinION to the GridION as their numbers of samples grew.[18] In October 2020 the company's own test for the virus, LamPORE, received CE marking in Europe.[2]

Pores and chemistry

The pore in the company's 2016 chemistry came from a bacterium. In May 2016 the company introduced its R9 pore, developed from CsgG, a protein that Escherichia coli uses to export the curli fibres on its surface.[2][19] The pore's structure had been solved by the lab of Han Remaut at VIB in Belgium and published in 2014, and it is in the Protein Data Bank as entries 4UV2 and 4UV3.[20] A 2020 paper from the same collaboration described a CsgG pore with a second constriction, formed by a fragment of the partner protein CsgF, that improved the reading of runs of identical bases.[21] The company announced the R10 pore in 2018 and moved its flow cells to R10.4.1 with a new chemistry, Kit 14, in 2022.[2] Accuracy rose along the way. In December 2020 the company reported 98.3% accuracy for single reads, and in March 2021 it introduced a kit called Q20+; on the Phred scale used for sequencing quality, Q20 means one error in 100 bases.[2]

Instruments

Five MinION flow cells fit in the GridION X5, which began shipping in May 2017. A high-throughput benchtop instrument, the PromethION, went on sale in May 2018, and in April 2019 a PromethION 48 produced more than 7 terabases in a single run.[2] In March 2019 came the Flongle, an adapter that lets a MinION or GridION use a smaller single-use flow cell, and in October 2022 the company announced the PromethION 2 Solo, which takes two of the large flow cells.[2] The current MinION, the Mk1D, measures 55 by 13 by 125 mm, weighs 130 g and connects to a laptop by USB-C.[5]

Oxford Nanopore flow cells and devices
Device On sale Flow cells per device Channels per flow cell Maximum output per flow cell
Flongle 2019 1 (adapter) 126 2.8 Gb
MinION 2015 1 up to 512 50 Gb
GridION 2017 up to 5 MinION flow cells up to 512 50 Gb
PromethION 2018 2, 24 or 48 up to 3,000 290 Gb

Later years

The company opened a manufacturing site at Harwell in July 2019. In September 2021 it was listed on the London Stock Exchange.[2][1] In 2023 it bought Northern Nanopore Instruments, a 2020 spinout of the University of Ottawa whose instruments make solid-state pores by controlled dielectric breakdown, with the stated aim of scaling that method of fabrication.[22]

Technology

A motor enzyme sitting on the mouth of a funnel-shaped pore in a membrane, with a DNA strand of lettered bases passing through it and four bases at the constriction highlighted, an applied-voltage arrow from minus to plus, and below, a staircase of five current levels lined up with the strand's steps
Strand sequencing as Oxford Nanopore describes it: a motor protein feeds one strand of DNA through a protein pore set in a polymer membrane, and the ionic current through the pore changes as the bases pass. Schematic, not to scale.

In Oxford Nanopore's description, "A protein nanopore is set in an electrically-resistant polymer membrane", and each pore sits in its own channel, measured individually by an application-specific integrated circuit (ASIC).[6] A voltage across the membrane drives an ionic current through the pore. During library preparation a motor protein is attached to each strand, and "the motor protein associates with a nanopore and controls the speed at which the molecule passes through the pore."[7] As the bases pass the narrowest part of the pore, the current changes, and basecalling software turns the trace into a sequence. The company states read lengths "from 20 to 4,000,000 bases".[7]

The instruments are run by the MinKNOW software, and basecalling is done by Dorado, which offers three tiers of model, fast, high accuracy (hac) and super accurate (sup).[23] The names of the models record the chemistry and the speed, as in dna_r10.4.1_e8.2_400bps_hac, a model for the R10.4.1 pore at 400 bases per second.[23] Because the strand is read as it moves, software can also decide what to read: in "Read Until", published in 2016, the computer recognizes an unwanted molecule in real time and reverses the voltage to eject it, freeing the pore for the next one.[24] RNA can be read directly, without first copying it into DNA, a method the company published in 2018.[25] Its quiz-game clue adds that the RNA passes through the pore "3' to 5'", the reverse of the direction in which a cell reads it.[12]

In 2018 a group at the University of Nottingham reported a read of 2,272,580 bases, which the instrument software had "reported in eleven consecutive reads". The paper noted that reads exceeding 1 Mb "have been referred to as 'whales'".[26]

Read length is the method's best-known strength, because long reads span repeated stretches of a genome that short reads cannot place. The Telomere-to-Telomere consortium's complete human genome of 2022, which added nearly 200 million bases missing from the earlier reference, was assembled from Oxford Nanopore ultra-long reads together with HiFi reads from Pacific Biosciences.[11]

Relationship with Molecular Reality

Molecular Reality Corporation makes solid-state pores and describes Oxford Nanopore as the proof that nanopores have a market: in its materials, "Nanopores already sell, in biological form", and Oxford Nanopore "proved demand with biological pores, protein-based and fixed."[27] The smaller company also says its founding team included alumni of Oxford Nanopore.[27] Its field guide, narrated by a puppet, is less respectful of the hardware: "Biological pores are protein channels that bacteria build themselves; the famous MinION sequencer uses those. Protein pores are delicate flowers."[28][a]

Its quiz game, JeoPOREdy!, has several clues about Oxford Nanopore. One describes it as the company Bayley co-founded "to commercialize stochastic sensing", whose "commercial pores are now built from a mutant of the curli transporter CsgG"; the host's commentary begins "ONT is our kin-spirit in many ways, dear nanopioneer".[12] Another asks for the unit in which the 2018 record read was measured; the answer is "What is a megabase?"[12]

In The Hole World, the company's atlas of 2,112 groups and companies that work on molecular sensing, Oxford Nanopore is one of 38 entries marked as flagships. Each entry is drawn with a small picture of its pore; Oxford Nanopore's is labelled "CsgG + motor", an archetype the atlas uses for only two of its entries.[29] The company's essay on its planned nanopore world model proposes testing its machine-learning claims first on public raw data, such as Oxford Nanopore's recordings of lambda phage DNA, because "Terabytes of clean, labeled, public nanopore signal already exist."[30] The same essay warns against forcing the two kinds of data to look alike, because "a solid-state 5 nm pore and a biological ONT pore probe genuinely different physics", which it summarizes as "side-chain interactions vs. pure volume".[30]

See also

Notes

  1. ^ One of the flowers has been to the International Space Station.[9]

References

  1. ^ a b c "Oxford Nanopore Technologies floated on the London Stock Exchange". University of Oxford, Department of Chemistry. 2021.
  2. ^ a b c d e f g h i j k l m n "History". Oxford Nanopore Technologies. Retrieved October 25, 2026.
  3. ^ "Flongle Adapter Technical Specification". Oxford Nanopore Technologies. Retrieved October 25, 2026.
  4. ^ "Oxford Nanopore Store". Oxford Nanopore Technologies. Retrieved October 25, 2026.
  5. ^ a b "MinION". Oxford Nanopore Technologies. Retrieved October 25, 2026.
  6. ^ a b "Flow cells and nanopores". Oxford Nanopore Technologies. Retrieved October 25, 2026.
  7. ^ a b c "Technology". Oxford Nanopore Technologies. Retrieved October 25, 2026.
  8. ^ a b Quick, Joshua et al. (2016). "Real-time, portable genome sequencing for Ebola surveillance". Nature 530: 228-232. doi:10.1038/nature16996.
  9. ^ a b c "Kate Rubins, NASA's DNA sequencing scientist, returning to Earth". The Planetary Society. October 28, 2016.
  10. ^ a b Pomerantz, Aaron et al. (2018). "Real-time DNA barcoding in a rainforest using nanopore sequencing: opportunities for rapid biodiversity assessments and local capacity building". GigaScience 7. doi:10.1093/gigascience/giy033.
  11. ^ a b Nurk, Sergey et al. (2022). "The complete sequence of a human genome". Science 376: 44-53. doi:10.1126/science.abj6987.
  12. ^ a b c d "JeoPOREdy!" EQBio-OS. Molecular Reality Corporation. April 2026.
  13. ^ Gu, Li-Qun et al. (1999). "Stochastic sensing of organic analytes by a pore-forming protein containing a molecular adapter". Nature 398: 686-690. doi:10.1038/19491.
  14. ^ Kasianowicz, John J. et al. (1996). "Characterization of individual polynucleotide molecules using a membrane channel". Proceedings of the National Academy of Sciences 93: 13770-13773. doi:10.1073/pnas.93.24.13770.
  15. ^ Clarke, James et al. (2009). "Continuous base identification for single-molecule nanopore DNA sequencing". Nature Nanotechnology 4: 265-270. doi:10.1038/nnano.2009.12.
  16. ^ Johnson, Sarah S. et al. (2017). "Real-Time DNA Sequencing in the Antarctic Dry Valleys Using the Oxford Nanopore Sequencer". Journal of Biomolecular Techniques 28: 2-7. doi:10.7171/jbt.17-2801-009.
  17. ^ "ARTIC Network provides protocol for rapid, accurate sequencing of novel coronavirus (nCoV-2019): first genomes released". Oxford Nanopore Technologies. January 2020.
  18. ^ "Oxford Nanopore supports COVID-19 pandemic: epidemiology and research". Oxford Nanopore Technologies. 2020.
  19. ^ "New DNA sequencing nanopore: VIB collaborates with Oxford Nanopore Technologies". Bionity. March 10, 2016.
  20. ^ Goyal, Parveen et al. (2014). "Structural and mechanistic insights into the bacterial amyloid secretion channel CsgG". Nature 516: 250-253. doi:10.1038/nature13768.
  21. ^ Van der Verren, Sander E. et al. (2020). "A dual-constriction biological nanopore resolves homonucleotide sequences with high fidelity". Nature Biotechnology 38: 1415-1420. doi:10.1038/s41587-020-0570-8.
  22. ^ "Oxford Nanopore Technologies acquires uOttawa Deep Tech spinout Northern Nanopore Instruments". University of Ottawa, Faculty of Science. November 20, 2023.
  23. ^ a b "Dorado". GitHub. Oxford Nanopore Technologies. Retrieved October 25, 2026.
  24. ^ Loose, Matthew; Malla, Sunir; Stout, Michael (2016). "Real-time selective sequencing using nanopore technology". Nature Methods 13: 751-754. doi:10.1038/nmeth.3930.
  25. ^ Garalde, Daniel R. et al. (2018). "Highly parallel direct RNA sequencing on an array of nanopores". Nature Methods 15: 201-206. doi:10.1038/nmeth.4577.
  26. ^ "BulkVis: a graphical viewer for Oxford nanopore bulk FAST5 files". Bioinformatics 35: 2193-2198. 2019. doi:10.1093/bioinformatics/bty841.
  27. ^ a b "Company records". Molecular Reality Corporation. October 2026.
  28. ^ "Keltar's Field Guide to Molecular Reality". Molecular Reality Corporation. August 2026.
  29. ^ "The Hole World". Molecular Reality Corporation. September 26, 2026.
  30. ^ a b "The Nanopore World Model (Hardened)". Molecular Reality Corporation. 2026.
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