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Established in 1998, Illumina began its journey into the field of genomics with the launch of its BeadArray technology for high-throughput genotyping of single nucleotide polymorphisms (SNPs). Through the key acquisition of sequencing company Solexa and the persistent development of their instruments, Illumina transformed itself into an international leader in sequencing technologies.
Illumina currently maintains a large majority of the sequencing market, but the emergence of numerous new sequencing companies in recent years has intensified the competition. With the sudden rise in options, one begins to wonder what sets Illumina apart from the rest. “Illumina offers so much more than a sequencer—we have a unique combination of workflow, accuracy, and throughput,” explained David Silva, Staff Product Marketing Manager at Illumina. “There are hundreds of thousands of publications and tens of thousands of instruments in the field, and [our value] has really been demonstrated by our customers.”
There are now more than 20,000 Illumina instruments installed across the globe1, and the company boasts one of the largest sequencer assortments from any provider. “We have a very strong customer base with a lot of experience demonstrating the accuracy and the performance of our technology.”
Illumina’s expansive customer base and a large array of devices have opened the door for many routine sequencing applications and supported Illumina’s initiatives in clinical genomics. According to Brooke Murphy, Senior Director of Global Product Marketing at Illumina, the company’s value extends far beyond the breadth of instruments and the low cost per Gb (gigabase) of their sequencing.
“Whether it's the breadth of the portfolio or instrument performance we are enabling applications, experiments, and projects that otherwise would not be possible.” Murphy also highlighted Illumina’s around-the-clock tech support and highly experienced Field Application Scientists. “It's a major value that goes beyond any sort of sequencing metric, or cost unit,” added Silva.
Available sequencing technologies
Owing to their longevity and innovation, Illumina has a wide range of available sequencing instruments. “We really have a lot of strength in the depth of our portfolio,” said Silva. “We have enormous scalability from smaller sequencers that a customer can install on their own all the way up to our flagship high-throughput instrument, the NovaSeq X.” The newest generation of their powerhouse sequencer, the NovaSeq X and X Plus, are the latest releases from Illumina. Shipments began earlier this year and there has already been a strong demand for the new devices.
The current lineup of Illumina sequencers includes small benchtop devices like the iSeq 100 and workhorse devices such as the long-running MiSeq. From smallest throughput to largest, the available sequencing technologies for Illumina include:
- iSeq 100
- MiniSeq
- MiSeq and MiSeqDx
- NextSeq 550 and NextSeq 550Dx
- NextSeq 1000/2000
- NovaSeq 6000 and NovaSeq 6000Dx
- NovaSeq X and X Plus
Illumina’s sequencers utilize a well-known process called sequencing by synthesis (SBS). Prior to sequencing the DNA or RNA of interest, the samples must first be converted into sequencing-ready libraries through processes like fragmentation or conversion to cDNA for RNA samples, and attachment of specific sequencing adapters. The samples are then loaded onto the appropriate instrument.
After loading, the libraries are - immobilized onto the surface of a flow cell, and then clonal copies are formed from individual libraries to produce a cluster. The SBS process officially begins with the addition of primers that bind specific sequences in the adapters. As DNA synthesis begins, fluorescently labeled nucleotides are added to the complementary template DNA. Once a base has been added, the slide is imaged and the amplified fluorescence from each cluster is associated with the corresponding base. During this time, the sequencer processes the raw image data and translates the signals into base calls. The resulting reads are formatted into files, which are analyzed using either onboard platforms or placed into a corresponding bioinformatics pipeline.
Figure 1. SBS involves the addition of complementary bases, which are fluorescently labeled allowing for their detection (Image courtesy of Illumina)
Common applications
When asked about the most common applications for Illumina instruments, Silva explained that it’s difficult to pick a single one. “Illumina sequencers have enabled a huge breadth of applications, we believe more than all other NGS platforms, and we are continuously innovating, ensuring our customers are at the forefront of genomics. In addition to application breadth, we ensure customers have flexibility and scale that fits their needs and experiment.”
“Single-cell sequencing has ramped up these last couple of years, and the scalability and the cost-effectiveness of our sequencing, along with the ability to generate billions of reads from a sequencing run, pairs nicely with the desire of single-cell methods that really benefit from truly deep sequencing,” explained Silva. He also described the importance of applications involving cell-free DNA and circulating tumor DNA with their instruments. “Anything that requires super deep sequencing and high accuracy really fits nicely with the Illumina portfolio.”
“Multiomics is more accessible than ever,” stated Murphy. “The throughput, scale, flexible and comprehensive data analysis are enabling customers to do more.” Illumina is also supporting multiomics applications through strong partnerships with spatial and proteomic technology providers like NanoString, 10x Genomics, and SomaLogic.
Advances and the future
The most notable introduction to Illumina’s portfolio is the NovaSeq X and X Plus. In addition to the massive increase in scalability, these devices come with the DRAGEN Bio-IT Platform onboard allowing users to directly and immediately process their sequencing data. Additionally, the original chemistry has been completely revamped to produce the new XLEAP-SBS, which has faster, more accurate, and thermostable enzymes. Other important advancements include the reduction of plastic weight and waste, ambient shipment, and enhanced data compression capabilities. “The NovaSeq X is empowering customers; the decreased operating costs and increased throughput are driving bigger and deeper sequencing projects in both research and clinical markets,” explained Murphy. “NovaSeq X will accelerate multiomics and the clinical adoption of WGS and comprehensive genomic profiling.
Announced at the same time as the NovaSeq X, Illumina released its Illumina Complete Long Reads (ICLR) technology. Acknowledging the utility of long reads, ICLR was created to obtain long-read information on existing Illumina instruments. Using tagmentation to normalize and “landmark” long fragments, this technology produces highly accurate sequencing data to process long stretches of DNA. The current system is designed for human whole-genome sequencing with more options, including an enrichment kit, coming later this year.
Another more recent addition to the Illumina instrument line-up is the NextSeq 1000/2000. It comes with many of the same perks as the NovaSeq X, including the DRAGEN onboard analysis options, and soon, utilization of the XLEAP-SBS chemistry. Updates to the sequencer have allowed for sequencing longer read lengths and increased options for reagent kits and flow cells.
Despite several road bumps during its acquisition of GRAIL and recent changes to leadership, Illumina isn’t deterred from its mission of improving human health. As made clear by the newly departed CEO in his farewell letter, “Today, we are the world’s leading clinical genomics company, with about half our revenues coming from clinical markets like non-invasive prenatal testing, cancer therapy selection, and genetic disease testing.” Although the future may seem unclear, one thing is certain—between their new instruments, constant innovations, and expansion into clinical genomics products, Illumina remains at the forefront of advancing human health.
References:
- Illumina, Inc. (2023). At a Glance Fact Sheet. https://www.illumina.com/content/dam...t-a-glance.pdf