Pacific Biosciences of California, Inc. (aka PacBio) is an American biotechnology company founded in 2004 that develops and manufactures systems for gene sequencing and some novel real time biological observation.  PacBio has two principal sequencing platforms: single-molecule real-time sequencing (SMRT), based on the properties of zero-mode waveguides and sequencing by binding (SBB) chemistry, which uses native nucleotides and scarless incorporation for DNA binding and extension.

History
The company was founded based on research done at Cornell University that combined semiconductor processing and photonics with biotechnology research. Three graduate students in the lab of Professors Watt W. Webb — Jonas Korlach — and Harold Craighead — Steve Turner and Mathieu Foquet — became the first employees.

It began under the name Nanofluidics, Inc.  The company raised nearly  in six rounds of primarily venture capital financing, making it one of the most capitalized startups in 2010 leading up to their public offering in October of that year.  Key investors included Mohr Davidow Ventures, Kleiner, Perkins, Caufield & Byers, Alloy Ventures, and Wellcome Trust.

The company's first commercial product, the PacBio RS, was sold to a limited set of customers in 2010 and was commercially released in early 2011.  A subsequent version of the sequencer called the PacBio RS II was released in April 2013.

Leadership 
In 2004, Kleiner Perkins entrepreneur-in-residence Hugh Martin became CEO. On 6 January 2012 board member Michael Hunkapiller, PhD assumed the role of CEO. Hunkapiller retired in September 2020, and was replaced by chairman of the board Christian Henry. Henry was a former executive VP and chief commercial officer of Illumina before joining the board at PacBio in July 2018.

Illumina: attempted acquisition
On 1 November 2018, Illumina, Inc. agreed to purchase PacBio for US$1.2 billion in cash. The deal was expected to close in the fourth quarter of 2019. In December 2019, the Federal Trade Commission sued to block the acquisition. The deal was abandoned with an announcement on 2 January 2020. Illumina further agreed to pay Pacific Biosciences a $98 million US termination fee plus previously agreed upon deal extension payments of $22 million US in February and $6 million US in March 2020.

Recent acquisitions 
On 3 August 2021, Circulomics Inc. was acquired by PacBio to expand offerings in high-molecular weight DNA extraction sample preparation. The acquisition led to the development of the high throughput Nanobind DNA extraction kits which were later introduced in April, 2023. Omniome, Inc. was acquired by PacBio on 20 September, 2021 to develop a short-read sequencing instrument using sequencing by binding (SBB) chemistry which led to the development of the Onso sequencing system. On 2 August 2023, PacBio acquired Apton Biosystems to develop a high throughput short-read sequencer using optics and image processing.

Sequencing technology

Sequencing instruments 

The company's first scientific instrument, called the PacBio RS, was released to a limited set of customers in late 2010, with full commercial release in early 2011. Sequencing provider GATC Biotech was selected by Pacific Biosciences as its first European service provider in late 2010. A new version of the sequencer was released in April 2013. It produced longer sequence reads and higher throughput than the original RS instrument. The RS instrument will officially be supported until the end of 2021. In September 2015, the company released a new sequencing instrument, the Sequel System, with increased sequencing capacity at a smaller size and lower price compared to the PacBio RS II. In October 2020, PacBio announced the Sequel IIe system that featured an advanced on-instrument data processing and cloud enablement allowing for 70% reduction in overall secondary analysis time for certain applications and 90% reduction in file transfer and storage data.

Subsequently, in October 2022, PacBio launched a new sequencing system, which can sequence 1,300 human genomes per year as compared to 86 per year of the previous PacBio sequencing machines. . Also in October 2022, PacBio announced the beta testing of a short-read desktop sequencer, Onso, which is available as of 2023.

Reagents and SMRT Cells 

To use either instrument, customers must also purchase reagent packs for DNA preparation and sequencing and small consumables called "SMRT Cells." Cells for early forms of the sequencer are slightly less than one-centimeter square and contains tens of thousands of zero-mode waveguides, whereas newer systems have a higher density of cells and contain 25 million zero-mode waveguides (ZMWGs), allowing for faster DNA sequencing.

Software and applications 
Their secondary analysis bioinformatics product for the RS, called “SMRT Analysis”, was open source.  For the Sequel system the secondary analysis software was reorganized as the "SMRT Link" application. In 2013, the company released new bioinformatics tools for automated genome assembly (HGAP) and finishing (Quiver).

External links
 Company web site
 Wall Street Journal profile

References

Companies listed on the Nasdaq
Companies based in Menlo Park, California
Technology companies based in the San Francisco Bay Area
Biotechnology companies of the United States
Biotechnology companies established in 2004
American companies established in 2004
Genomics companies
Research support companies
Health care companies based in California
2004 establishments in California
2010 initial public offerings