View source for Pacific Biosciences

{{Short description|American maker of single-molecule real-time DNA sequencers}}
{{Infobox company
| name = Pacific Biosciences of California, Inc.
| former_name = Nanofluidics, Inc.
| type = Public (Nasdaq: PACB)
| industry = DNA sequencing
| founded = Incorporated in Delaware in 2000
| hq_location = Menlo Park, California, United States
| products = Revio, Vega, Sequel II and IIe, SMRT Cells
| website = [https://www.pacb.com pacb.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.<ref name="k10" /> 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.<ref name="k19" /><ref name="t2t" />

== Technology ==
[[File:Zero-mode_waveguide_SMRT.svg|thumb|right|upright=1.5|alt=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.<ref name="k10" /> The principle was published in ''Science'' in 2003, and real-time sequencing from single polymerase molecules in 2009.<ref name="levene" /><ref name="eid" /> The core patents were licensed to the company exclusively by the Cornell Research Foundation.<ref name="k10" />

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.<ref name="k25" /><ref name="wenger" /> Because the polymerase's pace changes with chemical modifications of the bases, the same data can also report epigenetic marks.<ref name="k25" />

== History ==
Pacific Biosciences of California, formerly Nanofluidics, was incorporated in Delaware in 2000.<ref name="k19" /> 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.<ref name="k10" /> On November 1, 2010 the company sold 12.5 million shares to the public at $16.00, for gross proceeds of $200 million.<ref name="k10" /> 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.<ref name="k10" />

{| class="wikitable"
|+ PacBio sequencers
! Instrument !! Introduced !! Notes
|-
| PacBio RS || Commercial launch planned for the second quarter of 2011 || About 75,000 ZMWs watched at once<ref name="k10" />
|-
| Sequel || September 2015 || Production of the RS II was phased out<ref name="k21" />
|-
| Sequel II || April 2019 || SMRT Cell 8M, about 8 million molecules at once<ref name="k19" /><ref name="k21" />
|-
| Sequel IIe || October 2020 || Added computing capacity<ref name="k21" />
|-
| Revio || Announced in the fourth quarter of 2022 || Runs up to four SMRT Cells at once<ref name="k22" /><ref name="k25" />
|-
| Onso || Shipments began in 2023 || Short reads; assets sold January 2026<ref name="k25" />
|-
| Vega || 2024 || Benchtop; up to 60 gigabases of long reads per run<ref name="k24" />
|}

== 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.<ref name="k19" /> In September 2021 PacBio bought Omniome, a San Diego company with a short-read sequencing platform, which became the Onso.<ref name="k22" /> 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.<ref name="k25" />

== 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.<ref name="t2t" /> A paper of 2019 had shown circular consensus reads improving both the detection of variants and the assembly of a human genome.<ref name="wenger" />

== 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".<ref name="holeworld" /> 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 ==
* [[Illumina]]
* [[List of nanopore companies]]
* [[Single-molecule biophysics]]

== References ==
{{Reflist|refs=
<ref name="k10">{{cite web |url=https://www.sec.gov/Archives/edgar/data/1299130/000119312511075269/d10k.htm |title=Form 10-K for fiscal year 2010 |publisher=Pacific Biosciences of California, Inc., filed with the US Securities and Exchange Commission |date=2011-03-23}}</ref>
<ref name="k19">{{cite web |url=https://www.sec.gov/Archives/edgar/data/1299130/000129913020000008/pacb-20191231x10k.htm |title=Form 10-K for fiscal year 2019 |publisher=Pacific Biosciences of California, Inc., filed with the US Securities and Exchange Commission |date=2020-02-28}}</ref>
<ref name="k21">{{cite web |url=https://www.sec.gov/Archives/edgar/data/1299130/000129913022000030/pacb-20211231x10k.htm |title=Form 10-K for fiscal year 2021 |publisher=Pacific Biosciences of California, Inc., filed with the US Securities and Exchange Commission |date=2022-02-28}}</ref>
<ref name="k22">{{cite web |url=https://www.sec.gov/Archives/edgar/data/1299130/000129913023000032/pacb-20221231x10k.htm |title=Form 10-K for fiscal year 2022 |publisher=Pacific Biosciences of California, Inc., filed with the US Securities and Exchange Commission |date=2023-02-28}}</ref>
<ref name="k24">{{cite web |url=https://www.sec.gov/Archives/edgar/data/1299130/000129913025000061/pacb-20241231.htm |title=Form 10-K for fiscal year 2024 |publisher=Pacific Biosciences of California, Inc., filed with the US Securities and Exchange Commission |date=2025-03-17}}</ref>
<ref name="k25">{{cite web |url=https://www.sec.gov/Archives/edgar/data/1299130/000129913026000034/pacb-20251231.htm |title=Form 10-K for fiscal year 2025 |publisher=Pacific Biosciences of California, Inc., filed with the US Securities and Exchange Commission |date=2026-02-25}}</ref>
<ref name="levene">{{cite journal |last1=Levene |first1=M. J. |display-authors=etal |title=Zero-mode waveguides for single-molecule analysis at high concentrations |journal=Science |volume=299 |issue=5607 |pages=682-686 |year=2003 |doi=10.1126/science.1079700}}</ref>
<ref name="eid">{{cite journal |last1=Eid |first1=John |display-authors=etal |title=Real-time DNA sequencing from single polymerase molecules |journal=Science |volume=323 |issue=5910 |pages=133-138 |year=2009 |doi=10.1126/science.1162986}}</ref>
<ref name="wenger">{{cite journal |last1=Wenger |first1=Aaron M. |display-authors=etal |title=Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome |journal=Nature Biotechnology |volume=37 |issue=10 |pages=1155-1162 |year=2019 |doi=10.1038/s41587-019-0217-9}}</ref>
<ref name="t2t">{{cite journal |last1=Nurk |first1=Sergey |display-authors=etal |title=The complete sequence of a human genome |journal=Science |volume=376 |issue=6588 |pages=44-53 |year=2022 |doi=10.1126/science.abj6987}}</ref>
<ref name="holeworld">{{cite web |url=https://molecularreality.com/the_hole_world |title=The Hole World |publisher=Molecular Reality Corporation |date=2026-09-26}}</ref>
}}

{{Nanopore companies}}

[[Category:DNA sequencing]]
[[Category:Companies based in Menlo Park, California]]
[[Category:Biotechnology companies of the United States]]
[[Category:Single-molecule biophysics]]
[[Category:Companies listed on the Nasdaq]]