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Illumina Targets Single-Cell, Oncology Applications With New NextSeq Platform

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NEW YORK – Illumina's new NextSeq 2000 and NextSeq 1000 benchtop sequencing instruments, announced Monday at the JP Morgan Healthcare Conference, could slash sequencing run costs compared to the current model by up to 50 percent, according to the company, enabling customers to run larger projects or do deeper analyses.

"With two-and-a-half times the output of the NextSeq 550, the new NextSeq 2000 will allow customers to sequence more deeply and analyze more samples in a single run at half the cost," Illumina CEO Francis deSouza said during his presentation.

The NextSeq 2000, which Illumina said is available for order now and will ship in the first quarter, carries a list price of $335,000 and has a maximum data output of 300 gigabases, compared to up to 120 gigabases for the NextSeq 550. However, it will initially launch with a 120-gigabase P2 flow cell. The NextSeq 1000, which is unavailable until the fourth quarter, has a list price of $210,000 and a maximum output of 120 gigabases. While the NextSeq 1000 will only work with the P2 flow cells, the NextSeq 2000 will also be able to run 300-gigabase P3 flow cells once Illumina releases those chips later this year. There will not be an early access program for either instrument, Illumina said.

Cost savings come primarily from reduced reagent volumes, enabled by new technologies that increased flow cell density by a factor of 30. "We have about a tenfold reduction in the volume of reagents being used," Jasmine Pritchard, senior director of product marketing at Illumina, said in an email. "That translates into lower costs for Illumina and, ultimately, the customer."

"NextSeq customers were asking for enhanced output, lower operating costs, and increased ease of use," she added. "As sequencing becomes more deeply embedded in research and clinical settings, customers of all scales have a clear desire to sequence more samples more deeply, often through new and emerging applications. Just as the NextSeq 500 and 550 allowed our benchtop customers to take on larger studies and higher output methods, the NextSeq 1000 and NextSeq 2000 provide access to a flexible platform that enables higher intensity applications which, until now, have been largely limited to the high-throughput systems."

Some applications that Illumina hopes will drive customers to the platform include single-cell sequencing, whole-genome sequencing, liquid biopsy, and comprehensive cancer panels.

Addressing the needs of the so-called "mid-throughput" segment of the sequencing market, required "a ground-up redesign of the [NextSeq] platform," Pritchard said. As part of that effort, Illumina has filed more than 60 patents associated with more than 75 innovations. "This has been our largest development program to date," she said. "It's been years in the making."

Illumina introduced the NextSeq line six years ago at the JP Morgan Healthcare Conference with the launch of the NextSeq 500, an instrument that former CEO Jay Flatley said "puts the rapid run mode [of the HiSeq 2500] into a box roughly the size of a MiSeq." It boasted a new two-color SBS chemistry and improved optics, with the ability to generate up to 120 gigabases of data in a 29-hour run. A year later, Illumina introduced the NextSeq 550, which incorporated array scanning.

The newest NextSeq instruments will not include array scanning capability. They will be compatible with existing Illumina and third-party library preparation kits.

The redesigned NextSeq platform has incorporated several design elements: the need for higher density, a smaller flow cell, simplified cartridges, and faster chemistry.

Pritchard said Illumina focused on data density to achieve its goals on throughput, and therefore cost. "As we push density to the nanometer scale, the fundamental challenge has been accurately resolving DNA clusters when adjacent clusters are only a few hundred nanometers away," she said. Two new technologies — a blue-green chemistry and super-resolution optics (a first for sequencing technology, according to Illumina) — led to a 30-fold increase in data density, versus the NextSeq 550.

The new technology helps lower costs in two ways, Pritchard said. The smaller flow cells reduce reagent "footprint," storage, and usage and allows the P2 (120 gigabase) flow cell to deliver the same output per run as the high-output flow cell of the NextSeq 550, but at a lower price per run and therefore lower price per gigabase. The P3 (300 gigabase) flow cell due later this year will generate even more data. "Customers will be able to use this higher output to sequence more samples in a single run, or more depth per sample — further reducing price per gigabase," Pritchard said.

According to an Illumina spec sheet, NextSeq 2000 with the P2 120 gigabase flow cell will be able to sequence 30 genomes of 130 megabases each at 30x coverage in approximately 29 hours; conduct whole-exome sequencing with 50x mean coverage of 16 human samples in about 21 hours; and perform single-cell RNA-sequencing of two samples of 4,000 cells, with 50,000 reads per cell, in about 13 hours.

In another first, Illumina integrated Dragen Bio-IT technology into the platform, a consequence of the firm's 2018 purchase of Edico Genome. Benefits of the integration include improved efficiency and turnaround time of secondary analysis, Pritchard said, with "a [threefold] reduction in data touchpoints and six times faster secondary analysis."

Whether the NextSeq 2000 will cannibalize the market for the 550 is unclear. Illumina is offering a trade-in promotion for existing NextSeq 550 owners; whether the offer will include NextSeq 500 owners is unclear. On Monday, deSouza said he expected the platform to attract new and existing Illumina customers. Illumina added that it will fill orders with preference given to early orders and multi-unit shipments.

In China and Japan, the NextSeq 2000 may compete with MGI's DNBSEQ-G400 FAST, a new version of the G400 instrument released in those markets. the G500 also known as the MGISEQ-2000 in China and some other markets. The G400 FAST has a maximum output of 330 gigabases per run, maximum read length of PE150, and run times between 12 and 37 hours, according to MGI's website.

Illumina is not working on a diagnostic version of the new platform yet, leaving the NextSeq 550Dx and MiSeqDx as its only benchtop instruments for clinical sequencing. "However, like many recent Illumina systems, the NextSeq 1000 and NextSeq 2000 sequencing systems have been developed with all our learnings from the MiSeqDx and NextSeq 550Dx platforms," Pritchard said.

So far, no users outside the company have had access to the NextSeq 2000 or 1000 but an Illumina spokesperson said that they company is "excited to start to get the platforms in customer hands this quarter," adding that Illumina has completed hundreds of runs internally across applications that span from single-cell sequencing to exome sequencing to RNA-seq. "All showed extremely high correlation and concordance to our on-market NextSeq 550 platform," according to the spokesperson.

Illumina also plans to present more detailed information about the NextSeq 2000 at the Advances in Genome Biology and Technology meeting next month.

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