The Sequel nucleic acid sequencing platform by Pacific Biosciences.

Pacific Biosciences of California Inc, Menlo Park, Calif, has launched a new nucleic acid sequencing platform called Sequel. The new system got its public debut earlier this month in Baltimore, at the annual meeting of the American Society of Human Genetics.

Compared to the company’s previous sequencer, the PacBio RS II system, the Sequel system provides higher throughput, more scalability, a reduced footprint, and lower sequencing project costs—all while maintaining the existing benefits of the company’s single molecule, real-time (SMRT) technology.

The core advancement embodied in the Sequel system resides in the capacity of its redesigned SMRT cells. At launch, Sequel’s SMRT cells each contain one million zero-mode waveguides (ZMWs)—a significant increase over the cells of the PacBio RS II, which contained 150,000 ZMWs. Immobilized within the ZMWs are active individual polymerases, providing windows to observe and record DNA sequencing in real time. The Sequel system is able to perform about seven times as many reads per SMRT cell as the PacBio RS II was able to perform. According to the company, customers should be able to realize lower costs and shorter timelines for sequencing projects, with approximately half the upfront capital investment compared to the previous technology. The US list price for the Sequel system is $350,000.

Pacific Biosciences’ products enable scientists to perform a number of operations essential for resolving genetically complex problems:

  • De novo genome assembly, finishing genomes in order to more fully identify, annotate, and decipher genomic structures.
  • Full-length transcript analysis, to improve annotations in reference genomes, characterize alternatively spliced isoforms in important gene families, and find novel genes.
  • Targeted sequencing to more comprehensively characterize genetic variations.
  • DNA base modification identification to help characterize epigenetic regulation and DNA damage.

According to Pacific Biosciences, the company’s SMRT technology provides industry’s highest consensus accuracy over the longest read-lengths, in combination with the ability to detect real-time kinetic information. The Sequel system, including consumables and software, provides a simple, fast, end-to-end workflow for SMRT sequencing.

Although the Sequel system occupies a smaller footprint and is less than one-third the size and weight of its predecessor, it offers access to the key attributes associated with SMRT sequencing, including long reads, high consensus accuracy, uniform coverage, and integrated methylation information. Since the new system is built on the company’s established SMRT technology, most aspects of the sequencing workflow are unchanged.


Michael Hunkapiller, PhD, Pacific Biosciences.

“The system’s lower price and smaller footprint represent our continued commitment to leveraging the scalability of our technology and the unique characteristics of SMRT sequencing,” says Michael Hunkapiller, PhD, CEO of Pacific Biosciences. “Moreover, with its lower cost of goods (approximately a quarter of that of the PacBio RS II) we expect to be able to achieve substantial gross margin improvement and move more quickly toward profitability.”

“We will continue to support our PacBio RS II customers, and we expect to introduce improvements in sample prep, sequencing chemistry, and software that will extend the performance of that system,” says Hunkapiller. “We expect to make similar, substantial performance improvements each year for the Sequel system. In addition, the Sequel architecture provides the ability to scale throughput by substantially varying the number of ZMWs on future SMRT cells, thereby optimizing throughput and operating costs for specific applications.”

The Sequel system is designed for projects such as rapidly and cost-effectively generating high-quality, whole-genome de novo assemblies. It can characterize a wide variety of genomic variation types, including those in complex regions not accessible with short-read or synthetic long-range sequencing technologies, while simultaneously revealing epigenetic information. Using the company’s Iso-Seq protocol, the system can also be used to generate data for full-length transcriptomes and targeted transcripts.

“We are excited to support the human genetics community as they pursue the generation of higher quality whole human genomes, and move beyond SNPs to sequence the full size-spectrum of human genetic variation,” says Jonas Korlach, chief scientific officer at Pacific Biosciences. “With the introduction of our Sequel platform, SMRT sequencing will be available to more scientists seeking to find the underlying heritability of genetic diseases.”

According to the company, the Sequel system’s increased throughput should also facilitate applications of SMRT technology in metagenomics and targeted gene applications, for which interrogation of larger numbers of individual DNA molecules is important.

The Sequel system was developed as part of the company’s collaboration with F. Hoffman-La Roche Ltd, Basel, Switzerland, which is ultimately aimed at providing a nucleic acid sequencing system for use in human in vitro diagnostics. Under that agreement, Roche agreed to pay Pacific Biosciences $40 million in milestone payments related to the development of the Sequel system. The company previously reported that it has earned $20 million to date, and now expects to earn the remaining $20 million during the fourth quarter of 2015.


Dan Zabrowski, Roche.

“This new sequencing platform has significant advantages over existing commercial platforms, and will be used as the basis for the Roche sequencing instrument being developed initially for clinical research, followed later by an IVD instrument launch,” says Dan Zabrowski, head of Roche sequencing and tissue diagnostics. “We anticipate the initial launch in the second half of 2016.”

Pacific Biosciences expects to begin limited US shipments of the Sequel system during the fourth quarter of 2015, and will begin scaling the manufacturing process for Sequel systems and new SMRT cells during early 2016. Shipments outside the United States are expected to commence thereafter. A portion of the initial group of Sequel instruments will be delivered to Roche to expand its internal assay development program.

For further information, visit Pacific Biosciences of California Inc.