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Illumina Launches Two New NGS Instruments: Desktop Platform and 'Factory-Scale' System


Illumina said today at the JP Morgan Healthcare conference in San Francisco that it has launched two new sequencing platforms — the NextSeq 500 and the HiSeq X Ten.

The two new platforms incorporate new sequencing technology and will target two different market segments. The NextSeq 500 system is a desktop system that has two different run modes — a mid-output mode that generates up to 40 gigabases per run and a high-output mode that generates up to 120 gigabases per run. Essentially, the NextSeq 500 "puts the rapid run mode [of the HiSeq 2500] into a box roughly the size of a MiSeq," Illumina's CEO Jay Flatley said during a presentation at the conference, which was webcast.

Meantime, the HiSeq X Ten is solely for large-scale whole-genome sequencing. The system is sold in a set of 10 units, each of which can sequence five whole human genomes per day, or generate 1.8 terabases of sequence in under three days.

In addition, Illumina is launching two new reagent kits for the HiSeq in the second quarter of this year. In May, it will begin shipping a kit that can generate 1 terabase of data in six days, giving users the ability to sequence 10 whole human genomes at 30x coverage or 150 human exomes in one run. It also plans to launch a 2x250 bp kit for the HiSeq in rapid mode.

The firm will also launch a new BaseSpace product, called BaseSpace Onsite. The product is essentially a private sequencing cloud with encrypted onsite storage, designed to deliver the functionality of BaseSpace to local appliances where the cloud is not an option.

Illumina also decided to reduce the list price of its MiSeq systems due to increased volume and manufacturing efficiencies. In the fourth quarter of 2013, the firm booked orders for 300 MiSeq systems, Flatley said. As such, the MiSeq will now sell for $99,000, while the MiSeqDx, which was cleared by the US Food and Drug Administration last year, will have a list price of $125,000, Flatley said.

Finally, Flatley said today that Illumina is planning this year to submit for FDA clearance its HiSeq 2500 system along with Verinata Health's Verifi test for fetal aneuploidy.

NextSeq 500

The NextSeq 500 system incorporates both new sequencing-by-synthesis technology as well as improved optics.

The current SBS chemistry in Illumina's sequencers uses four dyes that are detected in four different optical channels. The NextSeq 500 system will be a two-channel version that includes a dark state for the base guanine, single dyes for both adenine and cytosine, and two dyes for the base thymine.

The two-channel version "allows for simpler reagents," Flatley said and "sequencing with half the images."

The system will enable two different flow cell configurations. The mid-output flow cell includes 130 million clusters and will support a 2x75 base kit that will generate 16-19 gigabases of data per 15-hour run, or a 2x150 base kit that will generate 32-39 gigabases of data in a 26-hour run.

The high-output flow cell includes 400 million clusters and will support a 2x150 base kit that will generate 100-120 gigabases of data per 29-hour run, a 2x75 base kit that will generate 50-60 gigabases per 18-hour run, and a 1x75 base kit that will generate 25-30 gigabases per 11-hour run. The last kit is "optimized for NIPT applications," Flatley said, while the 2x150 base kit will support a 30x whole-genome or six to 12 exomes.

The NextSeq system will have a list price of $250,000, with the reagent kits ranging from $1,000 to $4,000. The system is already in full production and available for shipment and Flatley said that the firm has received its first order.

Aside from the two-channel sequencing chemistry, the firm also redesigned its optics. Flatley said the NextSeq 500 includes a new LED camera module based on advances in digital camera technology that is able to "significantly reduce the size, weight, and cost of the optics." The technology combines six cameras into one module giving the system six times the imaging capability of the MiSeq, at one-third the size and cost of the optics in a HiSeq, Flatley said.

The NextSeq 500 also includes around 20 additional innovations. The system will have a new flow cell design with larger random clusters enabling it to work with the lower-resolution optics as well as new surface chemistry to enhance the signal. The new flow cells also have the extra advantage in that they can be shipped dry, Flatley said.

Additionally, the platform includes RFID that communicates with BaseSpace, and an integrated fluidics module that has no tubes and so will be easy to service. It incorporates simultaneous isothermal chemistry and imaging, so there is no need for temperature cycling and the reagents are stable over a full run, eliminating the need for built-in chillers.

The NextSeq 500 will likely compete with Life Technologies' Ion Proton system. The Proton's PI chip generates 10 gigabases of output, and the company has said that its PII chip will initially deliver 20 to 30 gigabases per run, increasing over time.

Joel Fellis, senior manager of product marketing in Illumina's Systems and Genomics Services business unit, told In Sequence in an interview after the presentation that while the NextSeq 500 will compete in the highly competitive desktop market, the firm thinks it will be "well-received." The NextSeq 500 is currently the "only desktop sequencer that can sequence a human genome in a single run," he said.

The system has the same "easy-to-use push button sequencing" features of the MiSeq, he said.

Fellis added that while the NextSeq would enable numerous applications for research and translational applications, one area in particular that has drawn interest has been in the non-invasive prenatal testing market.

That market is essentially split. The existing large providers with high sample volumes have already standardized their workflows on the HiSeq system, but there are other customers and potential customers "that don't have that sample volume," Fellis said.

The system is also positioned for laboratories that want to do whole-genome sequencing but are typically only looking at a single sample at a time.

HiSeq X Ten

While NextSeq was designed to be a "highly flexible desktop platform," Illumina's other new product, the HiSeq X Ten, has one application — whole human genome sequencing, Flatley said.

The system will only be sold in units of 10 for "factory installations," he said. A 10-unit system has a list price of $10 million with each incremental unit costing $1 million.

One unit will be able to generate 600 gigabases of data in one day, enough to sequence five human genomes, or 1.8 terabases of data in under three days.

"The demand for factory-scale sequencing of whole human genomes is about to explode," Flatley said.

The first systems will ship in March, and Illumina has already sold three, to South Korean sequencing service provider Macrogen, the Garvan Institute in Australia, and to the Broad Institute, which purchased a 14-unit system. Flatley added that due to the complexity of the instrument, the firm will supply around five of the 10-unit systems this year.

The HiSeq X Ten incorporates the ordered array technology that Illumina has been developing to increase cluster density and reduce turnaround time. Fellis told IS that the patterned flow cells are the "big breakthrough" in the HiSeq X Ten that enable a "huge increase in data density and output."

On the current HiSeq systems, cluster generation is randomly spaced on the flow cell. But on the HiSeq X Ten, clusters form in nanowells in precise locations on the flow cell. "We can optimally space each cluster because they are in the wells," Fellis said. "We can pack them in, which allows us to get way more data." In addition, the ordered arrays simplify the imaging process because "we know where to look."

The system also includes bi-directional scanning, a six-fold increase in scan speed, new software to support the increase in data, faster paired-end turns, and a new polymerase.

The HiSeq X Ten will enable the "first real $1,000 genome," Flatley said. One reagent kit to enable 16 genomes per run will cost $12,700, or $800 per genome for reagents. Hardware will add an additional $137 per genome, while sample prep will range between $55 and $65 per genome, he said.

In one year, the HiSeq X Ten system will be able to sequence 18,000 whole human genomes at 30x coverage. "Four installations are capable of sequencing more genomes per year than in all of history," Flatley said.

Fellis told IS that there is currently not a lot of competition for the HiSeq X Ten. The projects Illumina is aiming to target with the system are large-scale population-based studies that sequence tens to hundreds of thousands of genomes. For such studies, often nation-wide projects, customers do not want to send samples out of their country, Fellis said, for instance to service providers such as BGI.

Additionally, Fellis anticipated that some service providers would become customers of the HiSeq X Ten.

There's an "emerging need for population-scale sequencing bubbling up," Fellis said.