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GEN Exclusives: January 10, 2018

Seeking New Users for iSeq

The Changing Sequencing Landscape

<p> How does Illumina’s new tool differ from its prior technologies, and who is poised to benefit most from the new offering? </p>

  • Inside every one of the Illumina DNA sequencers—which dominate the industry—is a high-powered fluorescence microscope. This type of technology enables the imaging of the series of single base additions that generate genome sequencing data. While the core technology is over a decade old, over the years, Illumina has rolled out for some newer instruments that incorporate small changes to how the DNA clusters are constructed, or tweaks such as going from four distinct fluorophores on the reversible terminators to a binary labeling scheme. But the basic nature of the instrument as a photomicroscope has remained constant. Around this technology has grown a fleet of instruments covering a wide range of market opportunities, now ranging from the small capacity MiniSeq through the MiSeq (and its clinical cousin MiSeq DX) through the NextSeq and various HiSeqs and finally the tremendous throughput of the NovaSeq. Pricing for these instruments also spanned a wide range, with the MiniSeq at $50K and MiSeq at $100K, providing relatively low-capital options.

    Two years ago, Illumina announced Project Firefly, with a goal of an instrument that could sequence without relying squarely on optics, enabling an even more compact and rugged instrument with a substantially lower price point. At this week’s J.P. Morgan Conference, Illumina CEO Francis deSouza introduced the iSeq instrument, the $19.5K device that was the focus of Project Firefly.

    A key feature of the new instrument is a cartridge-based operation that requires less than 5 minutes to transition from prepared libraries to a running sequencer. A flow cell is snapped into the cartridge and the library pipetted in, and then the machine is set to run. With about the footprint of a notebook computer, the iSeq requires little bench space. Interaction is via the built-in touchscreen, with data offloaded to Illumina’s BaseSpace for further analysis.

    The single-use cartridge contains all the wet elements of the system, as well as the complementary metal–oxide–semiconductor (CMOS) imaging electronics. A patterned flow cell uses Illumina’s ExAmp technology to build DNA clusters immediately over imaging elements. The CMOS sensors can’t distinguish colors, so Illumina uses a two-pass imaging scheme. The A and T terminators are initially labeled and that pattern is imaged, and then a chemistry step both removes the labels from A terminators and adds them to C terminators. So, clusters lit in both rounds are T, in the first round only are A, in the second round only are C, and in none are G. Hence the chemistry of the new tool sticks to the proven Illumina method of presenting all four terminating nucleotide types simultaneously.

    Illumina is supporting several running modes, with a 2x150 paired-end format, yielding around 1 gigabase and costing $625 for the cartridge plus flow cell, according to a phone conversation with Illumina's Kevin Meldrum. It runs for 17.5 hours. CEO deSouza characterized iSeq as a platform with significant future growth, with plans to increase sensor density to enable yields of up to 10 gigabases. deSouza also claimed that Illumina believes that running times can be decreased as much as 50%.

  • New Users

    deSouza also announced at the conference a partnership with Thermo Fisher to bring the AmpliSeq multiplex PCR technology into the Illumina fold. So, what does the market look like for Illumina’s new instrument, and who may now begin using Illumina sequencers as a result of the recent partnership? The coupling of the two companies may mean running small targeted panels with AmpliSeq may be one new market. Another would be for investigators seeking to verify synthetic biology constructs, an area in which even a gigabase of data may be far more than needed. deSouza also suggested areas such as infectious disease monitoring.