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Pacific Biosciences

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From Molecupedia, the encyclopedia of very small things
American maker of single-molecule real-time DNA sequencers
Pacific Biosciences of California, Inc.
FormerlyNanofluidics, Inc.
TypePublic (Nasdaq: PACB)
IndustryDNA sequencing
FoundedIncorporated in Delaware in 2000
HeadquartersMenlo Park, California, United States
ProductsRevio, Vega, Sequel II and IIe, SMRT Cells
Websitepacb.com

Pacific Biosciences of California, Inc., known as PacBio, is a company in Menlo Park, California, that makes DNA sequencers based on single-molecule real-time (SMRT) sequencing. Each instrument watches a single DNA polymerase copy a strand of DNA at the bottom of a hole a few tens of nanometers across, and reads the sequence from the colored flashes that mark each base as it is added.[1] The company, which was incorporated in 2000 as Nanofluidics, Inc., went public in 2010. Its long, accurate "HiFi" reads, together with the ultra-long reads of Oxford Nanopore Technologies, were used to assemble the first complete human genome in 2022.[2][3]

Technology

Cross-section of a hole in a metal film over glass with a polymerase at its bottom, and a trace of colored fluorescence pulses
A zero-mode waveguide in cross-section, with the pulses it produces. The hole is narrower than the wavelength of the laser, so only its bottom 30 nm is lit. Schematic, not to scale.

The sequencing takes place in a zero-mode waveguide (ZMW), a hole in a metal film on a glass base. The hole is narrower than the wavelength of the laser, about 600 nm, so the light cannot pass through it and decays instead; only the bottom 30 nm of the hole is lit. A single polymerase is anchored there. Nucleotides, each type labeled with a different fluorescent dye, are flooded above the array. Those floating above the hole stay dark, and only a labeled nucleotide held by the polymerase for the milliseconds that incorporation takes shines long enough to be seen against the ones diffusing past in microseconds.[1] The principle was published in Science in 2003, and real-time sequencing from single polymerase molecules in 2009.[4][5] The core patents were licensed to the company exclusively by the Cornell Research Foundation.[1]

The ZMW is a hole of a different kind from those in nanopore sequencing. Glass closes its bottom, it passes no ions and it measures no current.

Accuracy comes from reading each molecule many times. The DNA is closed into a circle called a SMRTbell template, so that the polymerase goes around it repeatedly, both strands included, and the readings are combined into a consensus. The company's 2025 annual report states that these HiFi reads reach median accuracies above Q30, about one error in 1,000 bases, at average lengths of 15 to 20 kilobases.[6][7] Because the polymerase's pace changes with chemical modifications of the bases, the same data can also report epigenetic marks.[6]

History

Pacific Biosciences of California, formerly Nanofluidics, was incorporated in Delaware in 2000.[2] Its first annual report as a public company, for 2010, calls the PacBio RS a third-generation sequencing platform and notes that the patents on the SMRT methods and ZMW arrays are licensed from Cornell.[1] On November 1, 2010 the company sold 12.5 million shares to the public at $16.00, for gross proceeds of $200 million.[1] When the report was filed in March 2011 it had not yet earned revenue from its products and planned to launch the RS in the second quarter. A SMRT Cell then held about 150,000 ZMWs, of which the system could watch 75,000 at a time.[1]

PacBio sequencers
Instrument Introduced Notes
PacBio RS Commercial launch planned for the second quarter of 2011 About 75,000 ZMWs watched at once[1]
Sequel September 2015 Production of the RS II was phased out[8]
Sequel II April 2019 SMRT Cell 8M, about 8 million molecules at once[2][8]
Sequel IIe October 2020 Added computing capacity[8]
Revio Announced in the fourth quarter of 2022 Runs up to four SMRT Cells at once[9][6]
Onso Shipments began in 2023 Short reads; assets sold January 2026[6]
Vega 2024 Benchtop; up to 60 gigabases of long reads per run[10]

Illumina

On November 1, 2018 PacBio agreed to merge with Illumina. The United States Federal Trade Commission announced on December 17, 2019 that it had authorized legal action to block the deal, and on January 2, 2020 the companies ended the agreement, with Illumina paying PacBio a termination fee of $98.0 million.[2] In September 2021 PacBio bought Omniome, a San Diego company with a short-read sequencing platform, which became the Onso.[9] On January 30, 2026 it sold the intellectual property and other assets of its short-read technology to Illumina Cambridge Limited for $50.0 million in cash.[6]

Use

The first complete human genome, published in 2022 by the Telomere-to-Telomere consortium, added nearly 200 million bases to the previous reference. It was assembled from HiFi reads together with nanopore ultra-long reads.[3] A paper of 2019 had shown circular consensus reads improving both the detection of variants and the assembly of a human genome.[7]

At Molecular Reality

PacBio appears in The Hole World, Molecular Reality's atlas of molecular sensing, as an instrument maker in Menlo Park and one of the atlas's flagship entries, drawn with a pore labelled "Zero-mode waveguides" and noted as "Single-molecule real-time optical sensing".[11] Both companies read one molecule at a time, PacBio with light and Molecular Reality with current. The zero-mode waveguide is entered in List of holes.

See also

References

  1. ^ a b c d e f g "Form 10-K for fiscal year 2010". Pacific Biosciences of California, Inc., filed with the US Securities and Exchange Commission. March 23, 2011.
  2. ^ a b c d "Form 10-K for fiscal year 2019". Pacific Biosciences of California, Inc., filed with the US Securities and Exchange Commission. February 28, 2020.
  3. ^ a b Nurk, Sergey et al. (2022). "The complete sequence of a human genome". Science 376 (6588): 44-53. doi:10.1126/science.abj6987.
  4. ^ Levene, M. J. et al. (2003). "Zero-mode waveguides for single-molecule analysis at high concentrations". Science 299 (5607): 682-686. doi:10.1126/science.1079700.
  5. ^ Eid, John et al. (2009). "Real-time DNA sequencing from single polymerase molecules". Science 323 (5910): 133-138. doi:10.1126/science.1162986.
  6. ^ a b c d e "Form 10-K for fiscal year 2025". Pacific Biosciences of California, Inc., filed with the US Securities and Exchange Commission. February 25, 2026.
  7. ^ a b Wenger, Aaron M. et al. (2019). "Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome". Nature Biotechnology 37 (10): 1155-1162. doi:10.1038/s41587-019-0217-9.
  8. ^ a b c "Form 10-K for fiscal year 2021". Pacific Biosciences of California, Inc., filed with the US Securities and Exchange Commission. February 28, 2022.
  9. ^ a b "Form 10-K for fiscal year 2022". Pacific Biosciences of California, Inc., filed with the US Securities and Exchange Commission. February 28, 2023.
  10. ^ "Form 10-K for fiscal year 2024". Pacific Biosciences of California, Inc., filed with the US Securities and Exchange Commission. March 17, 2025.
  11. ^ "The Hole World". Molecular Reality Corporation. September 26, 2026.
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