Limited access to high-quality genomic sequencing can hold back small research labs and start-ups.Credit: Kiyoshi Takahase Segundo/Alamy
After developing world-class genomic institutes at Vanderbilt University and HudsonAlpha Institute for Biotechnology, Shawn Levy has more insight than most into the transformative potential of single-cell genomics. But when he joined Element Biosciences in 2022, he had long been arguing that for sequencing to provide the most value to science, costs need to come down. At Element, a sequencing company where Levy is now chief scientific officer, he saw an opportunity to address the field‘s access problem with innovative technology.
“Element had a unique perspective,” says Levy, who has hands-on experience with nearly every commercial sequencing system. “They saw all the lessons in the field — about surface chemistry, instrument design, sequencing chemistry — and really took a departure from what’s common for sequencing by synthesis. That's what made it exciting.”
This unconventional thinking is behind the company’s AVITI benchtop sequencer, which offers a throughput-based model with costs ranking among the lowest in the sequencing market — $200 for a genome, and single-cell sequencing approaching $0.60 per million reads.
Element Biosciences co-founder Matthew Kellinger (left), chief scientific officer Shawn Levy (centre) and co-founder Michael Previte with the Element AVITI System.Credit: Element Biosciences
Affinity for avidity
At the heart of AVITI are dye-labelled polymers, dubbed ‘avidites’, which bear multiple copies of identical nucleotides on octopus-like arms. One avidite can bind to multiple polymerase-DNA complexes within a polony on a flow cell, setting off strong fluorescence signals.
“Initially we could generate signals, but they wouldn't stick around,” recalls Matthew Kellinger, a co-founder of Element who now heads its biochemistry division. “Then we thought about Velcro: the more hooks you have, the better the attachment. That led us to enzymology, where antibody avidity can give incredible binding power.”
The synergistic effects of avidites boost signal-to-noise levels and allow the AVITI platform to use nanomolar concentrations of dye-labelled reagents, dropping average consumable costs more than three-fold compared to other sequencers. Data quality tests show more than 90% of the sequencing has 1-in-1000 error rates and continue to push into the 1-in-10,000 range.
High quality, low cost
With two flow cells, users can run multiple sequencing experiments independently with tuneable throughput up to two billion reads. Typical read lengths are 2x150 bases, though the company also offers 10-kb reads through its LoopSeq interface and plans to enter the 2x300 space this year.
Kellinger notes that AVITI can plug into existing library preparations or bioinformatic tools, saving users time and simplifying the switch from other instruments.
“In the genomic single-cell market, you always want more information, but the real hurdle is cost,” says Kellinger. “We wanted to bring a benchtop system to the market that has an incredible amount of throughput, and a price attractive to people who have traditionally outsourced.”
While the $200 genome model‘s lowest prices require significant throughput, Levy emphasizes that the economics of AVITI make it possible for labs large and small to build efficiency and flexibility into their output. Labs with lower throughput can buy only the instruments they need, accruing significant savings — Element estimates a per-genome price of $256 in cases of moderate use — while building toward the most economical model as they grow.
“As an industry, we need to break the model that you need ever-increasing machine costs and run sizes to progress,” Levy says. “We enable people to take chances, to have that flexible output.”