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PacBio Launches Higher-Throughput, Lower-Cost Single-Molecule Sequencing System


This article has been modified to clarify a quote. 

NEW YORK (GenomeWeb) – Pacific Biosciences has launched a new single-molecule sequencing system that offers higher throughput and costs about half the price of its RS II system, the company said.

PacBio developed the Sequel as part of its collaboration with Roche to develop a clinical-grade sequencing system for diagnostic purposes. That collaboration is ongoing, and the launch of Sequel marks another step toward the final goal.

Dan Zabrowski, head of Roche Sequencing Unit and Tissue Diagnostics, said in a statement that the Sequel would form the "basis for the Roche sequencing instrument," which is expected to launch in the second half of 2016 for clinical research and later as an in vitro diagnostics instrument.

The Sequel relies on redesigned SMRT cells, which each now contain 1 million zero-mode waveguides, as opposed to 150,000 ZMWs in the RS II. Within ZMWs, active individual polymerases are immobilized so that DNA sequencing can be observed and recorded in real time.

The increased ZMWs per SMRT cell enable an approximately seven-fold improvement in throughput. Per SMRT cell, total throughput will initially range between 5 gb and 10 gb and the system will have initial average read lengths between 8 kb and 12 kb. Both throughput and average read length will increase next year and in following years, the company said.

PacBio also improved the optics and installed a computer architecture that is able to process more data, PacBio CEO Mike Hunkapiller said during a conference call discussing the Sequel. The underlying chemistry is still the same as in the RS II.

The Sequel has a list price of $350,000 — about half the cost of the $695,000 RS II — and a physical footprint about one-third that of the RS II.

Hunkapiller said during a conference call discussing the new instrument that the company would continue to support RS II customers and make improvements to that system for several more years. The firm expects to roll out improvements to "sample prep, sequencing chemistry, and software," as previously planned — improvements that will also be applied to the Sequel system.

He said that PacBio would begin shipping systems in the fourth quarter on a limited basis, expecting to ship about 10 systems. In 2016, it will ramp up manufacturing of the Sequel system for shipments to US customers, followed by international shipments.

Some of those 10 systems it will sell to Roche, which will use the instruments for assay development. PacBio also expects to receive a final development milestone payment of $20 million from Roche in the fourth quarter, for a total of $40 million.

"We worked closely with Roche on the development of Sequel, and it is the core technology we've developed for Roche for clinical research and IVD," Hunkapiller said.

In addition, Hunkapiller said that the launch of the Sequel would help PacBio "penetrate a larger portion of the broader sequencing market," with a lower instrument cost and higher throughput that should result in overall lower operating prices.

Consumables cost per SMRT cell will increase on the Sequel to around $700 from about $250 on the RS II, but customers will also get a seven-fold improvement in throughput. As such, assuming 7 gb of data per SMRT cell, PacBio officials said that the cost of sequencing a human genome at 10x coverage — deep enough to do structural variant analysis — would cost around $3,000. A 30x human genome would cost around $10,000, and a 50x human genome would cost roughly $15,000.

By contrast, assuming a throughput of 1 gb per SMRT cell on the RS II, a 30x human genome would cost around $22,500, while a 50x genome would cost $37,500.

The Sequel will support all of the applications that the RS II currently supports including Iso-Seq for transcript analysis, as well as base modification analysis.

Consensus accuracy of the Sequel will stay the same as the RS II, since the chemistry is the same. Accuracy is a "function of the biochemistry," Hunkapiller said.

Like the RS II, the Sequel can run between 1 and 16 SMRT cells per run. Sample prep will essentially be the same on both instruments, taking around six hours to prepare a library. On the backend, the newest analysis tools will be incorporated into the system's software, and Hunkapiller said that additional upgrades that speed up the analysis would be added in about a month or so.

"We've incorporated our newer assembly algorithms to handle more data and get assembly done on smaller compute frames in shorter times," he said.

Initially, PacBio hopes to appeal to a broader set of the same types of customers it currently targets with the RS II. Those doing de novo assembly, particularly of plant genomes, or those looking at hard-to-sequence regions of the human genome. "It's probably fair to say, the bigger the projects people have in mind, the more quickly they'll take up the new technology," Hunkapiller said. In 2016, when the firm launches its diagnostic instrument as a result of the Roche collaboration, it will begin tapping the clinical market.

In a blog post commenting on the launch, Mick Watson, director of ARK-Genomics at the Roslin Institute, noted that the price to sequence a human genome on the Sequel was still expensive when compared to sequencing on Illumina, but was a huge improvement over the RSII. In addition, he noted that Sequel could challenge Illumina because "in an era of cheap, long read sequencing, Illumina becomes a genotyping platform, not a sequencing platform."

William Quirk, senior research analyst with Piper Jaffray, wrote in a note that the investment bank is "initially encouraged with Sequel as the system touches on some of the most frequent customer complaints including instrument size, throughput, and cost."

Following the conference call, Piper Jaffray said it anticipated PacBio would install 81 Sequel instruments in 2016, an increase from its estimate of 56 RS II systems. But, due to its lower cost, the firm lowered its 2016 estimated instrument revenue for PacBio to $31.3 million from $32.8 million.

Meanwhile, investor reaction to the announcement was overwhelmingly positive with PacBio shares trading up 46 percent at $5.34 in Thursday afternoon trade on the Nasdaq.