Profile: Pacific Biosciences of California Inc (PACB.OQ)
20 Jun 2019
Pacific Biosciences of California, Inc., incorporated on July 14, 2000, designs, develops and manufactures sequencing systems to help scientists resolve genetically complex problems. The Company is engaged in the development, manufacturing and marketing of an integrated platform for genetic analysis. The Company's Single Molecule, Real-Time (SMRT) technology enables single molecule, real-time detection of biological processes. The Company offers The SMRT Cell, Phospholinked nucleotides and The PacBio RS II and Sequel instruments. PacBio sequencing systems, including consumables and software, provide an end-to-end workflow for SMRT sequencing.
The Company's SMRT technology enables the observation of DNA synthesis as it occurs in real-time by harnessing the natural process of deoxyribonucleic acid (DNA) replication, which is actuated by the DNA polymerase. The DNA polymerase attaches itself to a strand of DNA to be replicated, examines the individual base at the point it is attached, and then determines which of four building blocks or nucleotides is required to complement that individual base. After determining which nucleotide is required, the polymerase incorporates that nucleotide into the growing strand being produced. After incorporation, the enzyme advances to the next base to be replicated and the process is repeated. DNA sequencing is performed on SMRT Cells, each having an array of zero-mode waveguides (ZMWs). The SMRT Cells for the PacBio RS II System each contain approximately 150,000 ZMWs, whereas the SMRT Cells for the Sequel System each contain approximately one million ZMWs. Each ZMW is capable of containing a DNA polymerase molecule bound to a single DNA template. Its immobilization process distributes polymerases into ZMWs across the SMRT Cell, resulting in approximately one-third of the ZMWs having a single template.
The Company's phospholinked nucleotides have a fluorescent dye attached to the phosphate chain of the nucleotide rather than to the base. As a natural step in the synthesis process, the phosphate chain is cleaved when the nucleotide is incorporated into the DNA strand. Thus, upon incorporation of a phospholinked nucleotide, the DNA polymerase naturally frees the dye molecule from the nucleotide when it cleaves the phosphate chain. Upon cleaving, the label diffuses away, leaving a natural piece of DNA without evidence of labeling. The PacBio RS II and Sequel instruments conduct, monitor and analyze single molecule biochemical reactions in real-time. The PacBio RS II and Sequel instruments are integrated units that include high performance optics, automated liquid handling, a touchscreen control interface and computational hardware and software. Each instrument's high performance optics monitor the ZMWs in a SMRT Cell in real time.
The automated liquid handling system performs reagent mixing and prepares SMRT Cells. Each instrument's touchscreen control interface is the user's primary control center to design and monitor experiments. The computational hardware and software in each instrument is responsible for processing the sequencing data produced by the SMRT Cells. The consumable products include its SMRT Cells and reagent kits. One SMRT Cell is consumed per sequencing reaction, and scientists can choose the number of SMRT Cells they use per experiment. For the PacBio RS II instrument, eight SMRT Cells containing approximately 150,000 ZMWs each are individually and hermetically sealed then packaged together into a streamlined 8Pac format. The instruments use sensitive imaging systems to collect the light pulses emitted by fluorescent reagents allowing the observation of biological processes.
Computer algorithms are used to translate the information that is captured by the optics system. Using the recorded information, light pulses are converted into either an A, C, G or T base call with associated quality metrics. Once sequencing is started, the real-time data is delivered to the system's primary analysis pipeline, which outputs base identity and quality values (QVs). To generate a consensus sequence from the data, an assembly process assembles the different fragments from each ZMW based on common sequences. It offers several reagent kits, each designed to address a specific step in the workflow. A template preparation kit is used to convert DNA into SMRTbell double-stranded DNA library formats and includes typical molecular biology reagents, such as ligase, buffers and exonucleases. Its binding kits include its modified DNA polymerase, and are used to bind SMRTbell libraries to the polymerase in preparation for sequencing. Its sequencing kits contain reagents required for on-instrument, real-time sequencing, including the phospholinked nucleotides.
The Company competes with Illumina, Inc. and Thermo Fisher Scientific Inc.
Pacific Biosciences of California Inc
1305 O'brien Drive
MENLO PARK CA 94025