A Year-End Flurry of Activity at Ion Torrent

By Bio-IT World Staff 

November 8, 2013 | November and December are shaping up to be big months for Ion Torrent. Like many of its competitors, the next-generation sequencing company has been hard at work assembling an end-to-end sequencing pipeline, adding the Ion Reporter suite of informatics software to its pair of sequencers, the Ion PGM and the high-throughput Ion Proton, in the hopes of keeping customers in the Ion Torrent marketplace from library construction all the way up to genomic analysis. With Illumina doubling down on its BaseSpace cloud informatics environment, and Qiagen preparing to release the GeneReader sequencer coupled with an in-house collection of analysis tools from recent acquisitions Ingenuity Systems and CLC bio, this sort of comprehensive approach may shortly be seen as a necessity for retaining a major share of the sequencing market.

This scaling up of the product line, however, has not distracted Ion Torrent from refining its core catalogue on the sequencing end, and the next several weeks will see the early release of four products to improve the accuracy and ease of use of the company’s sequencers. The combination of these new technologies will give Ion Torrent "the fastest and simplest whole exome workflow capture that there is on the market today, by far,” said Andy Felton, Vice President of Product Marketing, in an interview with Bio-IT World.

Two new products are becoming available this month on a trial basis to members of the new Technology Access Program, an initiative to identify researchers using Ion Torrent sequencers whose work could most benefit from products in the last stages of development. Prospective members can now apply to access the Hi-Q Sequencing Chemistry or the Isothermal Amplification Chemistry, both slated for full release in early 2014.

The Hi-Q Sequencing Chemistry is intended to replace the current sequencing chemistry in the Ion PGM sequencer, introducing a new enzyme said to reduce read errors by 90%. “Today we’re already over 99.1% accurate,” says Felton, but like other next-generation sequencers, the PGM has had limited capacity to capture microinsertions and microdeletions, where a few bases are added or removed from the genome. That’s “really the only error rate our technology has,” adds Felton. To address this constraint on their technology, Ion Torrent took a page from the pharmaceutical industry’s strategy for molecular discovery, starting with a few promising enzymes and synthesizing thousands of random molecular variants in the lab. After testing roughly 10,000 of these artificial enzymes in their sequencers, Ion Torrent discovered one that retained the PGM’s accuracy in reading single-nucleotide variations, but also showed remarkable improvement in calling insertions and deletions.

The Isothermal Amplification Chemistry has previously been reported on under the project code name “Avalanche.” This kit is designed for rapidly preparing library templates, and is compatible with either the Ion PGS or Ion Proton. Unlike the Hi-Q, the Isothermal Amplification Chemistry is not a refinement of existing techniques, but a novel approach to amplification, and its precise mechanism is being kept under wraps for now. “It is a truly isothermal amplification reaction, it is not based on polymerases, and it is a brand new technology to NGS sequencing,” says Felton. Its advantages, however, are being proclaimed very publicly: the chemistry is contained in a single-tube kit, it does not require repeated heating and cooling, and the entire amplification process can be completed in forty minutes, a massive reduction from the five hours or so that are the current industry standard. This time savings is of particular concern for larger labs performing very high-turnover sequencing for counting applications, says Felton. “That run time on our platform [for a counting application] would probably be about an hour on the sequencer. If you’re trying to match a template preparation process on the order of seven to nine or ten hours, they’re not very well impedance-matched.” By bringing template prep in line with the sequencer’s run time, the new amplification chemistry may provide a much more efficient workflow to take full advantage of the speed of next-generation sequencing. The simplicity of a single-tube isothermal reaction could also remove barriers to entry for small labs, who would require much less equipment to start sequencing without the need for a sophisticated thermal cycler.

Another product scheduled for release to a limited slate of first adopters before the end of the year is the Ion Chef. Ion Torrent has been excited about the prospect of automating template prep almost since they first announced their semiconductor chip technology for sequencing. The previous Ion One Touch system broke ground in this area for simpler sequencing tasks, but its limited productivity made the instrument inappropriate for high-throughput sequencing. The Ion Chef is designed to scale up automated template prep for any application of next-generation sequencing on the Ion PGM or Ion Proton, with the instrument doing all the work of loading the sample library onto a chip and preparing it for sequencing.

 

The Ion Chef promises a hands-on time of as little as fifteen minutes to load the enriched sample library, consumables, and empty chips. “You simply load a couple of things into the Chef, you walk away, and you come back to two loaded chips the next day,” says Felton, who sees this ease of use for staff at any experience level as a prominent selling point for the Ion Torrent pipeline. “Because the interplay of the beads and the loading of the beads onto the chip is something that’s very unique, I think it would be very difficult for other companies to try to automate [template prep for large genomes] successfully.” In addition to preparing templates, the Ion Chef barcodes the chips loaded into it for future reference, minimizing potential user error.

A new kit for genotyping a trio on a single chip will also be released commercially in November.

Despite this flurry of year-end activity, the wild card for Ion Torrent remains the PII chip, a new semiconductor chip for the Ion Proton with much higher information density than the current PI. The PII was originally scheduled for release in early 2013, but that date has repeatedly been pushed back as developers ran into challenges associated with shrinking the chip’s microwells to the sub-micron level – “about the size of a very large virus” – and particularly with managing the huge volume of data output involved in reading 660 million beads on a single chip. Felton likens this output to streaming an HD movie every second, but says that Ion Torrent is finally closing in on a reproducible model. “We’re going through the final processes now to bring it into manufacturing,” he says, adding that the current projected date for early access is March of next year. The first batch of chips will be strictly for counting applications, because the DNA fragments supported will be limited to the 100-base pair scale. “And then as we evolve the read lengths going through next year,” adds Felton, “we’ll then move through exome and then to genome.”

If Ion Torrent is able to stick to that schedule, 2014 may be the year the company makes major inroads against Illumina in the highly data-intensive whole-genome sequencing market – one of the few applications for which Illumina’s HiSeq instruments retain a near-monopoly. In the meantime, users of Ion Torrent sequencers for targeted applications will see a range of new options to improve their workflows as the company rounds out 2013. Applications are open to join the Technology Access Program for any researchers using the Ion PGM or Proton.