Illumina faces short-read rivals
In October, Pacific Biosciences — a company best known for its long-read sequencers — launched an ultra-high-quality short-read benchtop instrument. This direct challenge to Illumina, whose technology has long dominated the short-read sequencing world, was only the latest salvo in a larger skirmish.
Certainly, these new platforms are the culmination of years of behind-the-scenes R&D, but they are also abetted by other factors, such as the emerging gaps and cracks in Illumina’s intellectual property fortifications. “Some of the key sequencing-by-synthesis patents that Illumina had are starting to expire,” says Shawn Baker, head of the genomics industry consultancy SanDiegOmics.
Some of the new versions of SBS are similar to Illumina’s while others introduce distinctive twists. For example, Element and PacBio employ ‘sequencing-by-binding’ variants, in which the fluorescently tagged nucleotides are not directly incorporated into the newly synthesized strands on the flow-cell. In Element’s, the DNA clusters on the flow-cell are incubated with ‘avidites’, fluorescently labeled polymeric structures decorated with many copies of the same nucleotide.
Others in the short-read space have chosen to focus on a particular set of consumers for their initial offerings. PacBio, Element and Singular are targeting current users of Illumina’s mid-range NextSeq instruments with their benchtop instruments. Henry says that PacBio chose this route early on, with an initial price-point for Onso of $259,000, based on a decision to focus on clinical applications.
Illumina has built its reputation on gold-standard quality, but several of the newcomers are looking to push the bar even higher. For example, PacBio reports that Onso can produce runs where more than 90% of reads achieve accuracy of 99.99%, whereas current-generation NextSeq instruments achieve a lower threshold of 99.9% in most of their reads.
Element’s AVITI aims to thread the needle of high quality at a lower price tag: CEO He says their SBB chemistry and flow-cell design considerably reduce the cost per run to less than $6 per gigabase with an accuracy that approaches that of the PacBio Onso. This pricing puts the instrument well ahead of the current-generation NextSeq, and since those instruments will not be compatible with the new chemistry until 2024, Element may have a golden opportunity.
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