NovaSeq X: Meet the Sequencer that Will Change Everything

By Alex Aravanis, M.D., Ph.D. Chief Technology Officer, Senior Vice President, and Head of Research and Product Development at Illumina. This article was originally published here.

The world’s scientists still have hundreds of millions of genomes to sequence. To explore new dimensions of biology such as epigenetics and proteomics, to accelerate our understanding of the causes of disease and find new ways to diagnose and cure them—we knew the problems left to solve required something more powerful. No Illumina technology could sequence that many genomes and achieve our vision of accessible and affordable precision health care…until now.

At our inaugural Illumina Genomics Forum, we proudly introduced the NovaSeq X and NovaSeq X Plus Sequencing Systems. Both platforms provide tremendous flexibility and efficiency—three different flow cell types, up to eight individually addressable lanes per flow cell, up to 16 addressable lanes per run, and automated, integrated secondary analysis—removing the bioinformatics bottlenecks. NovaSeq X Plus is capable of fully independent dual flow cell processing, delivering up to 16 terabases of output. It can generate more than 20,000 whole genomes per year—it redefines what you can do with a sequencer.

To create this product, we had to reinvent everything that goes into it—including our new XLEAP-SBS chemistry, the result of the largest development project in the history of genomics technology. We now have novel polymerases and fully functional nucleotides that are twice as fast as existing SBS, enabling single-day runs. The chemical bonds in XLEAP-SBS nucleotides are 50 times more stable, making it our most accurate SBS ever, with lower percent phasing and raw error rate.

We created 15 new reagents to enable ambient shipment without dry ice, including our first lyophilized reagents. We eliminated the need for cold chain logistics. Compared to NovaSeq 6000, we reduced plastic mass by over 50 percent, cartridge volume by 50 percent, and overall packaging weight and waste by 90 percent. We created an imaging system that boasts four times more pixels, twice the data rate, and scans the length of a flow cell in a second while maintaining nanometer-scale focus. That’s like throwing a baseball from San Diego to London and being off by only the thickness of a human hair!

NovaSeq X scans so quickly that we can image from top to bottom of a lane in less than one second and repeat that process thousands of times in a run. Because of this massive increase in data, we added DRAGEN on board, which can process 128 genomes all the way to variant calls in a single run.

And with Illumina Complete Long Reads, we increase accuracy even further in the FDA-defined benchmark regions. It’s a complete and accurate representation of the genome at the single-molecule level, providing contiguous long reads. By the end of next year, we will launch a complete long-read enrichment product on NovaSeq X.

The NovaSeq X is our most sustainable, most powerful sequencer ever. My hope is that you see the breakthroughs and the lives that will change with this platform. Together with our partners, we’re going to unleash the power and potential to transform genomics and human health.