Skip to main content
Premium Trial:

Request an Annual Quote

Pacific Biosciences Updates Sequel, Preps for Wider Rollout; Sees Strong Interest From China


NEW YORK (GenomeWeb) – Pacific Biosciences said this week that it would continue to ramp up shipments of SMRT cells for its Sequel instrument, which it launched on a limited basis last year.

In addition, the company launched several updates to the Sequel system's software, sample prep, and sequencing chemistry to improve performance, company officials said during a conference call discussing the firm's second quarter 2016 performance and in an interview with GenomeWeb.

PacBio's CEO Mike Hunkapiller also said during the call that the firm is seeing a lot of interest in its single-molecule sequencing technology from researchers in China, due to the launch of the country's Precision Medicine Initiative. Illumina, too, recently said that universities and commercial laboratories in China are both increasingly purchasing sequencing instruments in anticipation of grants under the Precision Medicine Initiative.

PacBio first launched the Sequel last year on a limited basis because of manufacturing constraints on the chips, which were being supplied by Belgian-based Imec, which does research and development and early manufacturing but not production-level manufacturing. PacBio is in the midst of transitioning to a high-volume supplier and as more of the SMRT chips are produced by that supplier, it will ramp up the rollout, increasing sales of the Sequel instrument and associated consumables.

Hunkapiller said this week that it will now lift constraints on orders of the SMRT cells for customers who have downloaded the latest software release and sample prep protocols.

Not only has the performance of the chips manufactured by Imec "become more consistent," but also more of the chip production has shifted to the high-volume supplier, a transition that will be completed before the end of the year, Hunkapiller said.

PacBio CSO Jonas Korlach  told GenomeWeb that the new sample prep method would help to filter out the shorter, unwanted DNA fragments as well as any polymerase not used in the sequencing reaction, which  can end up at the bottom of the zero-mode waveguides (ZMWs) and negatively impact performance. The polymerase is not attached to a DNA template, "but can occasionally bind nucleotides for a short period of time and cause a false signal," he said.

The software upgrade will help fix issues customers have been having with data transfer issues and support additional sequencing applications for the Sequel, Hunkapiller said during the call.

The various upgrades will increase the overall performance of the Sequel system. For instance, Korlach said that customers who have been using the new chemistry and software have been seeing throughputs on average of about 5 gigabases per SMRT cell, ranging from around 3 gigabases to as high as 8 gigabases. Average read lengths should increase to between 8 and 12 kilobases he said, and over time would increase to 15 kb.

When PacBio first launched the system, it said that initial throughput would average 7 gigabases per SMRT cell with average read lengths between 8 kb and 12 kb. However, in a recent Piper Jaffray research memo, senior analyst William Quirk wrote that customers the investment bank had spoken with are getting average read lengths of 2 kb to 6 kb and throughput of 3 Gb to 5 Gb. During the call, Hunkapiller said that the issues that customers have been having with Sequel could primarily be attributed to the fact that most of the SMRT cells were produced from the prototype supplier and not the high-volume supplier. But, he said, the company "feels comfortable that the process has ironed itself out" and that future "performance will be substantially improved." 

PacBio is also working on an "active loading" protocol for the RSII with early customers. Currently, DNA molecules and polymerases fill the ZMWs based on random placement, so efficiency is currently limited to 37 percent, according to Poisson distribution statistics.

The goal of the active loading technology is to enable more ZMWs to be loaded with one single molecule of DNA, which will ultimately enable more and longer reads. The company is currently working with one large unnamed customer interested in using the technology for targeted sequencing applications, Hunkapiller said.

PacBio also noted that interest in China for its technology has been growing due to the China Precision Medicine Initiative in which the country plans to invest approximately $10 billion over the next several years.

Hunkapiller pointed to a recent publication in Nature Communications in which researchers from Jinan University in China, the University of Southern California, and elsewhere used PacBio's technology along with BioNano Genomics' mapping technology to de novo assemble a Chinese individual to serve as a Chinese reference. The researchers identified 12.8 megabases of sequence that are not in the human reference GRCh38, including 4.1 megabases of sequence not present in previously sequenced in Asian genomes. In addition, the assembly had a contig N50 of 8.3 megabases, compared to genomes assembled with short-read technology, which typically have contig N50s no longer than 100 kilobases to 200 kilobases, Hunkapiller said.

The paper is an indicator of "the growing interest among scientists worldwide to generate high-quality reference genomes that are specific to particular ethnic populations," Hunkapiller said.