Illumina Launches Push-Button Sequencing With New Low-Throughput MiSeq i100 Line | GenomeWeb

Illumina's MiSeq i100 instrument

NEW YORK – On the second floor of Illumina's "Building Four," home to its R&D team, sits a machine that offers to produce, with almost no hands-on time and automated fluidics, many a scientist's great desire. With touch-screen simplicity, scientists and engineers can select one of several preprogrammed workflows and a short while later get what they need: the perfect cup of coffee, or a cappuccino, or maybe a cafe latte. And just down the hall, there's a room full of similar, more expensive machines that have taken cues from their caffeinating cousin.

"It's an espresso [machine] for sequencing," quipped Emmanuel Naouri, a product manager who oversaw the three-year development of Illumina's new MiSeq i100 instrument line, announced Wednesday.

This is the future of benchtop, low-throughput sequencing for Illumina. "Our customers told us they need a faster, smaller, and easy-to-use instrument, and that's what we're delivering," said CEO Jacob Thaysen. "Whether you are an established next-generation sequencing lab or looking to start sequencing for the first time, our latest benchtop instrument adds the plug-and-play flexibility that today's labs are seeking."

Like the coffee maker, the MiSeq i100 offers a touch screen with up to 18 preprogrammed workflows. Sample loading is simple: just pipette it into a hole on a plastic cartridge the size of a VHS tape and slide it into the front-facing elevator-style loading door. Inserting the reagent pack is just as easy. With X-Leap SBS sequencing chemistry trickling down from higher-throughput models, runs take only hours instead of days. And, like coffee grounds, reagents should be stored at room temperature — a first for Illumina (other new NGS reagents can be shipped ambiently but must be stored in a freezer).

In addition to ease of use, Illumina is touting better costs per Gb and low cost per run. Moreover, the instrument introduces the new concept of index-first sequencing, the default mode for the MiSeq i100, which the firm said will lead to faster library QC for large runs compared to the original MiSeq.

"It looks very appealing, spec-wise," said Lutz Froenicke, manager of the University of California, Davis DNA Technologies and Expression Analysis Core lab. The speed, simplicity, and room-temperature reagent storage were also appealing, he added. His lab has three MiSeqs; however, only one is operational "because they have been quite outdated for a while," he said. But before purchasing a new instrument, "we would need to know more about the reagent costs," he said.

The MiSeq i100 is a long-awaited refresh for Illumina's low-throughput offerings. The original MiSeq was launched in 2011, and the last addition, the iSeq, came in 2018.

Recently, Illumina has focused investments on the high- and mid-throughput segments, with the NovaSeq X series launched in 2022, with XLeap chemistry trickling down to the midsized NextSeq 1000 and 2000. But the low-throughput market has continued to drive placements. In 2022, Illumina shipped about 1,670 low-throughput instruments with nearly 700 going to new customers. In the same year, Illumina shipped 1,215 mid-throughput instruments.

"Low-throughput instruments and consumables accounts for approximately 15 percent of Illumina's total sequencing revenues and is not enough of a needle mover," Evercore ISI analyst Vijay Kumar wrote in a note to investors, adding that the instrument was likely not what investors had hoped the company would announce. "Investors had hypothesized whether the new system could be a multiomics box, which could do proteomics and potentially enable singe-cell sequencing," he wrote.

Recently, competitors in the mid-throughput segment, including from Element Biosciences, Singular Genomics, and Complete Genomics, have begun to offer kits that dipped down into the range that the MiSeq i100 Plus will address, around 30 Gb and 50 to 100 million reads.

The MiSeq i100 Plus, available now for $109,900, can sequence between 5 million and 100 million reads, or 3 Gb to 30 Gb total output. At the highest throughput levels, it costs about $48 per Gb, including onboard secondary data analysis, with a minimum cost to turn it on of $400 for lower-output runs. The i100, available next year, will have a max output of 15 Gb or 25 million reads.

A minimum cost per run of about $400 is "about what they did before," Froenicke said. "That is nice, but not as nice as it could be."

Illumina officials said there would be promotions for existing customers, but they declined to say more about terms. They noted that they're considering a diagnostics-focused version of the instrument to refresh the MiSeqDx but were not ready to commit to a release timeline.

The new instrument takes only an hour to set up, Illumina said, but the real time savings will come from shorter runs. "We can start two runs on the same day and thereby increase our sample flow massively," Tim Roloff, a microbiologist and diagnostics developer at the University of Zurich, said in a statement. "And given that the reagents are shipped at room temperature, we don't need to wait for the cartridges to thaw. We can just launch a run whenever we're ready with a new pool, and there is no planning needed upfront. This gives us great flexibility, and this can provide new possibilities to develop new tests."

Microbe-focused researchers like Roloff may appreciate the menu of automated infectious disease workflows, including 16S metagenomics, CovidSeq, and the Illumina Respiratory Pathogen ID panel, among others.

Several oncology panels will also be preprogrammed into the instrument, including the Illumina TruSight Hereditary Panel and four panels from Pillar Biosciences: the Multi-Cancer CNV plus RNA Fusion Panel, and the OncoReveal Myeloid, Essential MPN, and BRCA1 and BRCA2 plus CNV panels.

Immune repertoire analysis is a new application that couldn't have been done before on a MiSeq, Illumina officials said.

The MiSeq i100 enjoys some trickle-down tech, namely from Illumina's new chemistry. "The data quality improvements are outstanding compared to the original MiSeq," said Joel Fellis, Illumina's VP of product management. "In a 2x300 [bp] run, the data quality error by cycle is flat," an improvement of more than eightfold compared to the same kit on the old machine. Illumina Chief Technology Officer Steve Barnard noted that the unbinned Q scores are "pushing towards Q40."

Some of the improvements may even trickle up to other sequencers, namely the ability to store reagents at room temperature, though that's not the case just yet. Shelf life for room temperature storage is 12 months, and reagents will carry a three-month guarantee. "Continued development is expected to increase the shelf life of reagents," Illumina said.

At launch, Illumina will offer a 5 million read and 3 Gb kit as well as a 25 million read and 15 Gb kit. In 2025, the firm will add 50 million and 100 million read 30 Gb kits.

The instrument run modes will be 1x100 bp, 2x150 bp, and 2x300 bp. "Read-first sequencing can still be performed on the MiSeq i100 Series through custom recipes; however, index-first sequencing is the default sequencing method," Illumina said. This means that the indices are sequenced before the DNA insert. This enables "early demultiplexing" approximately 2.5 hours into the run and provides users faster access to QC results such as index assignments and the percent of each sample in a pooled run.

Illumina has an installed base of over 10,000 MiSeqs, and Thaysen said he expects Illumina to replace every one of them with an i100 series instrument "over time." He also expects the instrument to be "a gateway into Illumina" and help new customers "get comfortable with our instruments."

The firm will continue to support existing low-throughput instruments, "but all of our active investment is going to be on the new MiSeq i100 series," Barnard said.