Special Report: Benchtop Genomics Accelerating Research and Discovery

Ever since the structure of DNA was discovered by James Watson and Francis Crick in 1954, life sciences have been dominated by the genomics revolution. Advancements in the understanding of the genome were given a significant boost in 1987 with the first automated sequencing machine, the Applied Biosystems AB1370, which ultimately led to today’s next generation (NGS) benchtop sequencers that have made genomic research possible and affordable for scientists around the world.

From its inception to today, sequencing output has grown over a thousand-fold. Experiments that once required complex workflows now use simple push-button sequencing.

The NGS market also reflects the expanding power of the technology. Currently, the NGS market is valued at $6.3 billion and is expected to grow at a 16% rate over the next five years, fueled by rapid developments in sequencing platforms, increasing applications of NGS services, development of more advanced bioinformatics tools, investments in R&D and increasing rates of cancer and infections disease, according to a May 2022 report by research firm Medi-Tech Insights.

The rapid NGS market growth coincides with the growth of the overall genomics industry, which is expected to reach $54.4 billion globally by 2025, according to an August 2022 report by MarketsandMarkets Research.

Leader of the Pack

Leading the pack of NGS players, according to the MarketsandMarkets report, is San Diego-based Illumina, Inc., which has been a dominant player in the market since at least 2014 when the company released its HiSeq X Ten sequencer which lowered the cost of sequencing a genome to around $1,000 from a cost upward of $1 million just a few years before.

Today, Illumina’s NGS platform portfolio includes six sequencers that offer high data quality and performance, flexible throughput and streamlined workflows for every kind of researcher and every scale of study.

“Over the past two decades Illumina has pioneered major advances in sequencing simplicity, flexibility, platform performance and has played a leading role in driving down the cost of sequencing,” said Brooke Murphy, director of Product Marketing at Illumina. “And today, Illumina platforms are the leading generators of genomic data.”

Worldwide, Illumina has installed more than 20,000 of its NGS benchtop systems and offers customers access and engagement with a large ecosystem of applications, protocols, library prep, analysis options and technology to propel genomic research.

“The scale and breadth of Illumina’s global commercial organization ensures that our customers receive best in class commercial support, including sales, scientific and applications support, as well as field service and technical support,” Murphy said.

New Players

San Diego is not only home to the largest NGS company, but also two of the newest with both Singular Genomics and Element Biosciences releasing their first NGS benchtops to the market within the last 12 months.

Singular launched its G4 sequencer in December 2021 – a machine that is “significantly more powerful, faster, and more flexible  than any other,” said Singular CEO Drew Spaventa. “We believe the G4 is in a class of its own when it comes to benchtop NGS offerings.”

Among the G4’s attributes, Spaventa cites a two to three times more powerful data output rate; run times in the range of six to 19 hours compared to the 20 to 48 hours offered by competing sequencers; and an accuracy “gold standard with Q30 scores of 80-90% on average.”

The G4 also has four flow cells and 16 independent lanes.

“Other benchtop instruments have one or two flow cells and no lane-to-lane flexibility,” Spaventa said.

Singular designed its G4 after extensive research into the needs of various labs in academic, clinical, industrial and hospital settings to understand where improvements could be made regarding their sequencing needs.

“Our goals were simple, to improve on the state of the art in sequencing.  This started with understanding the voice of the customer,” Spaventa said. “We then created a product profile based on the commonalities and most common feature requests.”

For Element Biosciences, the goal behind creating the AVITI benchtop sequencer was to “remove the roadblocks in genomic sequencing and democratize genomics,” said Element CEO and co-founder Molly He.

Element launched AVITI in March of this year with a price point of $289,000 for all customers. The sequencer offers Q30 data scores and two independent flow cells that can run different sample types simultaneously.

“Using AVITI, a researcher can achieve $5-7 gigabases, which is unheard of for a benchtop sequencer,” He said. “Simply put, we believe customers are getting a lot more bang-for-the-buck with our instrument when compared to any competing option.”

Element also recently announced it will not raise prices on its reagents for all current and future customers for the life of the instrument – part of its mission to empower more researchers with access to genomics.

“By offering higher quality data, at a lower cost, and with faster turnaround times, our goal is to learn more about the building blocks of biology and support potentially life changing breakthroughs for society,” He said. “The current standard operating procedure for many researchers and clinicians is to outsource their sequencing, resulting in potentially weeks-long delay in results. AVITI is entering the market with an offering and at a price point that will empower these same scientists to receive results in a matter of hours, not weeks.”

Space in the Market

Element and Singular are the latest companies to launch benchtops into a steadily growing market of choices that include instruments from Pacific Biosciences, Roche, Thermo Fisher Scientific, Oxford Nanopore and more.

Despite the growing number of options for machines, companies still see a lot of space in the market for growth.

“It is still very early in the evolution of NGS as a tool in life sciences and medicine,” Spaventa said, adding that he sees  future opportunities in the context of specific applications or understanding specific areas of biology or medicine such as immunology and oncology.

“Sequencing is the underlying tool that has helped drive our understanding in these areas thus far, however applications and content specific kits and technologies will improve our understanding further,” he said.  “In addition, clinical sequencing is still in the very early days, so there will be a large opportunity for companies with sequencing technology to understand and develop solutions for clinical applications.  There will be many opportunities to develop unique solutions in a nascent space with the bulk of growth still ahead of us in terms of clinical adoption of NGS.”

Spaventa described competition in the market as “healthy and overall positive” because it accelerates science and medicine and creates a market where customers win.

“It forces companies to do the best they can, and raises the bar for everyone,” he added.

Illumina also sees competition as a benefit as it offers choices in platforms to customers that suit their needs and keeps companies committed to driving down costs in sequencing while increasing the capabilities of their products.

“The ways in which genomics will be used to understand and improve human health will only continue to expand in the years to come,” Murphy said. “We welcome the additional players and investment to help propel this industry forward to realize the promise of genomics across the many markets and applications.”

He said that competition in the market is “imperative” in order to continue performance and decrease costs.

“We are still only in the early innings of what some would call the ‘genomics revolution,’” she said. “For too long, customers did not have much choice in this market, but now that is changing”

Another way the market is changing, He said, is the growing range of applications for NGS. Cancer, pediatric rare disease, virology, agriculture, food safety, forensics and more have opened the door for smaller genomics companies to pursue niche or specialized markets.

“This will only increase as the field continues to mature and find new applications to further elucidate the many areas of biology we still do not fully understand today,” He said.

Spaventa agrees that the specialization in NGS has already begun.

“A good example is long read offerings,” he said.  “[Companies] have found niche applications and built businesses around them.  NGS is a big enough space that there will be many ways to win, and some companies will likely need to turn to specific applications or niches in order to win.”

‘Downstream from NGS’

In addition to developing a niche specialty in NGS, the ‘genomics revolution’ has also opened the door to a completely new kind of benchtop machine – DNA printers.

“If you look at the genomics revolution as a read revolution, we’re really about the write part of it,” said Jyotsna Venugopal, director of product marketing at Codex DNA, a San Diego-based company specializing in biological synthesis of DNA and mRNA in a wide range of applications.

Codex DNA launched its first BioXP printers in 2015 based on an assembly method to stitch together short pieces of DNA to create longer sequences that can be used in testing. The process in now known as the Gibson Method, named for Codex DNA founder and current CTO Dan Gibson.

“Dan is the pioneer of that method and it’s widely used across the industry,” Venugopal said. “The technology that’s on the instrument that’s based on Gibson assembly can now be something that people can use on their benchtop.”

Venugopal is quick to point out that Codex DNA is not an NGS company, explaining that DNA printing in “downstream from NGS” because creating and printing wanted DNA or RNA follows its discovery using NGS. Where the two are similar is that the advanced benchtop instruments in both fields offer researchers a way to accelerate testing and discovery of potential therapies and vaccines. In Codex’s case, by allowing them to print DNA or RNA overnight with the convenience of full automation.

“Someone can just submit a sequence, get a kit, load it on the instrument, press start and then you just know when the whole process is ready and the material is ready to retrieve,” Venugopal said. “It’s a really simple process.”

Until recently, researchers would outsource DNA synthesis to a larger lab, slowing down the process of testing desired DNA or RNA for therapies or vaccines.

“That’s just how it was done, it just wasn’t possible to do it in your own lab,” Venugopal said. “Our goal with the BioXP system and CodexDNA and the vision of Dan and the other founding team members was really to empower scientists, researchers to do that themselves.”

Codex is the pioneer in the field of benchtop DNA printing with only a handful of companies – including DNA Script and Molecular Assembly – starting to get into the market using a newer enzymatic DNA synthesis approach. Codex is also working on its own enzymatic platform called Sola for its next-generation printers, Venugopal said.

“We’re already in a position to do that so hopefully that’s what is going to keep us ahead of the curve because we sort of know what to do next already,” she said.

Looking Ahead

For NGS companies like Illumina, Element and Singular, staying ahead of the curve means continuing to make improvements to the functionality of their benchtops and developing kits for new applications.

“We are also highly focused on where NGS is going, and what it will take to accelerate the clinical adoption of sequencing,” Spaventa said.

For Element, He said the mission for the company is to “speed the global scientific race to find the most critical answers to improve human health.”

“So we will stay true to this and continue our innovation with our future products,” she added.

In late September, Illumina plans to share its “Innovation Roadmap” at the company’s inaugural Illumina Genomics Forum (IGF), where it will share announcements about a new chemistry named “Chemistry X,” Murphy said.
“Also at IGF we’ll discuss new patented technologies for a highly accurate and cost-effective long read workflow, codenamed Infinity which will deliver contiguous data up to 10Kb in length to address the final edge cases of the genome,” she said, adding that Infinity enables ten times greater throughput with 90% less DNA input than legacy long reads, can be fully automated and is seamlessly compatible with sequencing by synthesis chemistry, enabling it to be rapidly applied across Illumina’s installed base.

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