For over a decade, Illumina has maintained a strong leadership position in the field of Next-Generation Sequencing (NGS). This dominance is largely attributed to its robust Sequencing by Synthesis (SBS) technology, a diverse portfolio of platforms catering to a wide spectrum of research needs, and a comprehensive ecosystem of readily available reagents and user-friendly analysis tools 1. This established presence has resulted in a significant market share, estimated to be around 80% according to some industry reports, and a widespread adoption of Illumina instruments in both academic and clinical research environments 3. The familiarity of researchers with Illumina’s workflows, the extensive library of compatible protocols, and the well-established analysis pipelines create a considerable advantage for the company, making it challenging for new entrants to gain traction.
However, the NGS market is substantial and continues to experience rapid growth, with a valuation exceeding $8 billion in 2023 and projections indicating a rise to tens of billions of dollars by the early 2030s 1. This high growth rate signifies a persistent demand for increased sequencing capacity and reduced costs, creating an opportune environment for the emergence of disruptive technologies. Besides Illumina, other prominent players in the NGS market include Thermo Fisher Scientific, PacBio, Oxford Nanopore Technologies, and BGI, illustrating a competitive landscape where innovation and differentiation are essential for success 1.
In this dynamic market, Ultima Genomics has emerged as a new contender with the aim of disrupting the high-throughput sequencing segment through its innovative UG 100 platform 7. The UG 100 was initially launched commercially in February 2024 and has since been enhanced with the introduction of UG 100 Solaris in February 2025, demonstrating a commitment to continuous development and improvement 7. This platform represents a fundamental shift in NGS technology, employing a “reinvention of NGS chemistry and hardware” by adapting components and methodologies from the semiconductor industry 11. The UG 100 is specifically engineered for ultra-high throughput sequencing and is designed to significantly decrease the cost per base, positioning it as a highly attractive option for large-scale studies and projects where budget limitations are a primary concern 1. Ultima Genomics has set an ambitious goal of enabling the “$100 genome,” a long-anticipated milestone that promises to democratize access to extensive genomic data and potentially revolutionize genomics research 7. This focus on cost reduction could pave the way for new experimental designs and research endeavors that were previously economically prohibitive.
II. UG 100 Technology: A Different Approach
At the core of the Ultima Genomics UG 100 lies a unique “flow-based” Sequencing by Synthesis (SBS) chemistry that distinguishes it from the more traditional approaches utilized by Illumina 7. Understanding these fundamental technological differences is paramount for researchers seeking to evaluate the potential advantages and limitations of the UG 100 for their specific applications.
One of the key distinctions between the UG 100 and Illumina platforms lies in the initial DNA amplification step. While Illumina typically employs bridge amplification directly on the flow cell to generate clusters of identical DNA molecules, the UG 100 utilizes an emulsion-based clonal amplification method 11. This means that the UG 100 sequences native DNA without the need for on-flow cell PCR amplification. Eliminating this on-instrument amplification step could potentially minimize amplification bias, leading to a more accurate representation of the original DNA sample’s composition 11. PCR amplification, while a powerful tool, is known to sometimes introduce errors and skew the relative abundance of certain sequences. By circumventing this process on the flow cell, the UG 100 might offer more reliable quantitative results for certain applications.
Furthermore, the sequencing chemistry itself differs significantly. The UG 100 employs a single nucleotide flow chemistry, where only one type of nucleotide (A, C, G, or T) is introduced during each flow cycle 12. The system then measures how many of that specific nucleotide are incorporated into each growing DNA strand. This contrasts with Illumina’s SBS approach, which adds all four nucleotides simultaneously, utilizing reversible terminators and fluorescent labels to identify the specific base that is incorporated 18. This fundamental difference in chemistry has notable implications for the types of errors that are most likely to occur. Ultima’s flow-based method may result in fewer base substitution errors because the identity of the base being added is known in each step; the primary error type tends to be indels, which are errors in determining the precise number of bases added in homopolymer regions (stretches of the same nucleotide) 7. Conversely, Illumina’s SBS is generally recognized for its lower indel rates but can exhibit higher substitution error rates 14. Additionally, Ultima’s chemistry does not rely on reversible terminators, which are a critical component of Illumina’s SBS technology 14. The absence of reversible terminators can potentially contribute to faster sequencing cycles.
The distinct flow-based chemistry of the UG 100 necessitates a different methodology for base calling. Instead of detecting a specific fluorescent signal associated with each base, the system measures the number of nucleotides incorporated during each flow 12. Accuracy on the UG 100 is typically assessed in “flow space,” which does not directly translate to the traditional “sequence space” (BQ) Phred quality scores commonly used in Illumina data 14. However, Ultima Genomics reports high levels of accuracy, with SNP F1 scores reaching 99.8% and INDEL F1 scores at 99.4% 23. These metrics suggest that the UG 100 can achieve a level of performance comparable to Illumina platforms for many research applications. To further enhance accuracy, particularly in challenging regions or for specific error types, the UG 100 incorporates advanced machine learning algorithms in its base calling and variant calling processes 9. The application of artificial intelligence in NGS data analysis is becoming increasingly prevalent and can be instrumental in overcoming challenges associated with novel sequencing chemistries.
A notable feature of the UG 100 is its “Paired Plus-Minus Sequencing” (ppmSeq) technology, designed to significantly improve accuracy, especially for the detection of rare variants 8. ppmSeq achieves a raw read accuracy of one part per million (Q60) for single nucleotide variants. This technology leverages the initial clonal amplification step to sequence both strands of a DNA molecule and then computationally identify and exclude sequencing errors that might have originated from DNA damage. This unique capability could be particularly advantageous for applications like liquid biopsy and minimal residual disease detection, where the ability to confidently identify very low-frequency variants is crucial.
The physical design of the UG 100 also represents a departure from traditional NGS instruments. Instead of using a conventional flow cell, the UG 100 employs a large, open 200mm silicon wafer, a standard component in the semiconductor industry 7. This unconventional design is a key factor in enabling the UG 100’s high throughput and potentially contributing to lower costs due to the economies of scale in silicon wafer manufacturing. The larger surface area of the wafer allows for a significantly higher density of sequencing reactions to occur simultaneously, resulting in a greater number of reads per run. During operation, sequencing reagents are dispensed onto the rotating wafer via a process called spin-coating, and data acquisition is performed by two fixed high-speed cameras as the wafer spins 11. This “inversion of the standard architecture,” with a moving wafer and fixed cameras, as opposed to a fixed flow cell and moving optics, contributes to the increased speed and overall throughput of the system 12. Furthermore, the UG 100 is designed for continuous 24/7 operation, featuring automated wafer handling and the ability to hot-swap reagents and consumables, further maximizing data generation and minimizing the need for manual intervention 16. This level of automation is essential for achieving the very high throughput capabilities promised by the platform.
III. Key Advantages of the UG 100
The Ultima Genomics UG 100 offers several key advantages that make it a compelling alternative to established Illumina sequencing platforms, particularly for researchers focused on large-scale and cost-sensitive projects.
One of the most significant advantages of the UG 100 is its potential for cost-effectiveness. Ultima Genomics aims to substantially reduce the cost of sequencing, with the ultimate goal of achieving a “$100 genome” in terms of the cost of consumables7. The initial UG 100 was reported to have a cost of $1.00 per gigabase (Gb) or $0.30 per million reads 8, which has been further reduced with the introduction of UG 100 Solaris to $0.80 per Gb or $0.24 per million reads 16. These figures suggest a considerable reduction in sequencing costs compared to traditional Illumina platforms, potentially making large-scale genomic studies more accessible and affordable. For instance, the University of Minnesota Genomics Center has reported that with the new Solaris chemistry, the cost of whole-genome sequencing at 30X coverage for Drosophila is now just a few dollars, making it a routine tool for variant and genome edit characterization 10. This real-world example underscores the potential for the UG 100 to dramatically lower costs for specific organisms and applications. While Illumina has also been actively driving down sequencing costs, with the NovaSeq X series aiming for a $200 genome 30, the UG 100 appears to be pushing the boundaries of affordability even further 21. It is important to note that the UG 100 is offered with reagent kits that support runs of up to 4 wafers, whereas Illumina typically offers single-unit kits 24. Researchers with varying throughput requirements should consider these kit configurations to determine the most cost-effective solution for their specific needs.
The UG 100 is specifically designed for high throughput sequencing. With the Solaris update, the platform can generate 10-12 billion reads per wafer, representing a 50% increase in output compared to the initial UG 100 10. This massive output capacity translates to the potential to sequence more than 30,000 whole human genomes per year on a single UG 100 instrument equipped with Solaris, compared to approximately 20,000 genomes per year with the original configuration 10. This level of throughput makes the UG 100 exceptionally well-suited for large-scale population genomics studies and for sequencing service providers needing to process a high volume of samples. The run times for the UG 100 are reported to be less than 14 hours, with even shorter times (around 12 hours) for applications requiring shorter read lengths 7. The University of Minnesota Genomics Center reports a run time of approximately 20 hours for a run with a median read length of ≥ 300 bases 11. These relatively short run times, combined with the substantial read output, contribute to the overall high throughput of the UG 100. Comparable high-throughput Illumina platforms, such as the NovaSeq X Plus, can generate up to 16 terabases of data per run using dual flow cells and can also process tens of thousands of whole genomes annually, with run times ranging from 17 to 48 hours depending on the specific flow cell and read length configuration 21. The Illumina NovaSeq 6000 offers up to 6 Tb of data in under 2 days 18. The throughput of the UG 100 appears to be on par with Illumina’s top-tier instruments, indicating its capability to handle similarly demanding sequencing projects, with potentially faster run times in some scenarios.
Accuracy is a critical factor in NGS, and Ultima Genomics reports high accuracy for the UG 100, with SNP F1 scores of 99.8% and INDEL F1 scores of 99.4% 23. Furthermore, the UG 100 features its unique ppmSeq mode, which achieves a raw read accuracy for SNVs as low as 1 in a million (Q60) 8. These metrics suggest that the UG 100 can provide highly accurate sequencing data, particularly for single nucleotide variants. The Q60 accuracy achieved in ppmSeq mode is especially significant for applications requiring high confidence in the detection of rare variants. Independent validation from the University of Minnesota Genomics Center, through comparative RNA-Seq experiments, showed equivalent results on the UG 100 compared to their existing Illumina NovaSeq sequencers 11. This provides additional confidence in the data quality produced by the UG 100 for at least one important application. Illumina’s NovaSeq X series also boasts high accuracy, with software updates enabling 80-85% of bases to achieve a quality score of Q40 or higher 35. The NovaSeq 6000 series also reports high quality scores, typically with ≥ 85-90% of bases exceeding Q30 18. While directly comparing Q-scores and F1 scores can be complex due to differences in calculation methods and error profiles, the available data indicates that both the UG 100 and Illumina’s high-end platforms offer excellent accuracy. The flow-based chemistry of the UG 100 might offer a slight advantage in terms of substitution error rates, while Illumina’s terminated chemistry has traditionally been strong in homopolymer regions, although Ultima claims to have made significant improvements in this area 14.
The UG 100 is well-suited for a variety of applications that benefit from its high throughput and cost-effectiveness. These include large-scale population studies and whole-genome sequencing (WGS), where the capacity to sequence tens of thousands of genomes at a lower cost is highly advantageous 7. The University of Minnesota Genomics Center has validated the UG 100 for research-grade WGS 11. RNA-Seq is another application where the UG 100 has demonstrated strong performance, producing high-quality data comparable to Illumina platforms, with the added benefit of long (300bp) contiguous reads that enhance isoform detection 7. While primarily designed for high throughput, the cost-effectiveness of the UG 100 could also be beneficial for large-scale targeted sequencing projects 5. The UG 100 is also compatible with leading single-cell sequencing library preparation workflows, such as those from 10x Genomics and Parse Biosciences, potentially increasing the scale and depth of single-cell experiments due to the lower cost per read 7. The ultra-high throughput capabilities of the UG 100 make it well-suited for deep sequencing in metagenomics and metatranscriptomics studies 11. Furthermore, the platform supports methylation sequencing via WGBS or RRBS 7. The unique ppmSeq technology, offering exceptional accuracy for SNVs, positions the UG 100 as a strong contender for rare variant detection and minimal residual disease (MRD) detection applications 8. Ultima Genomics is also exploring the potential of the UG 100 in proteomics research, leveraging its affordability to enable the generation of population-scale proteomic datasets 27.
In terms of ease of use and workflow, the UG 100 incorporates built-in automation for continuous 24/7 operation, including automated wafer handling and hot-swappable reagents, which minimizes operator intervention 8. This level of automation simplifies the experimental process and enhances efficiency, particularly for laboratories with high throughput demands. The UG 100 utilizes non-kit-based sequencing reagent cartridges, providing a degree of flexibility in experimental design 8. Ultima Genomics also provides pre-configured secondary analysis pipelines that are optimized for their data. These pipelines run on an integrated high-performance compute server without impacting the sequencing run time 16. The system outputs data in standard file formats, such as FASTQ and CRAM, ensuring compatibility with a wide range of third-party analysis software tools 7. Library preparation workflows for the UG 100 are designed for simplicity and flexibility, with compatibility for leading third-party library preparation providers 15. Ultima offers Solaris Free (PCR-free) and Solaris Flex workflows to accommodate different library types and experimental needs 10. This open ecosystem approach provides users with the freedom to choose the tools and workflows that best suit their specific research requirements.
IV. UG 100 vs. Illumina: A Head-to-Head Comparison
To provide a clearer understanding of how the Ultima Genomics UG 100 compares to Illumina’s offerings, a table summarizing the key differences between the UG 100 and comparable Illumina platforms is presented below. The data is based on specifications and information available for the UG 100 and representative high-throughput Illumina instruments, the NovaSeq X Plus and the NovaSeq 6000.
| Feature | Ultima Genomics UG 100 | Illumina NovaSeq X Plus | Illumina NovaSeq 6000 |
| Technology | Flow-based SBS (single nucleotide flows) | SBS (four nucleotides with reversible terminators) | SBS (two-channel or four-channel with reversible terminators) |
| Flow Cell | 200mm open silicon wafer (rotating) | Patterned flow cells (fixed) | Patterned flow cells (fixed) |
| Amplification | Emulsion PCR (off-instrument) | Bridge amplification (on-instrument) | Bridge amplification (on-instrument) |
| Read Length | 225bp to 300bp+ (median ≥ 300bp) 7 | Up to 2 x 150 bp 21 | Up to 2 x 250 bp (SP flow cell) 18 |
| Max Output | 10-12 billion reads/wafer (2.5-3.0 Tb/wafer) 10 | Up to 16 Tb/run (dual flow cell) 21 | Up to 6 Tb/run (dual flow cell) 18 |
| Run Time | 12-20 hours 7 | 17-48 hours 21 | 13-44 hours 18 |
| Cost per Genome | Target $80-$100 (consumables cost) 8 | ~$200 (on 25B flow cell, consumables only) 30 | ~$600 (with v1.5 reagent kit) 33 |
| Accuracy | SNV F1 99.8%, INDEL F1 99.4%, ppmSeq Q60 for SNVs 8 | ≥ 80-85% bases >= Q40 40 | ≥ 85-90% bases >= Q30 18 |
| Primary Error | Indels (in homopolymers) 7 | Substitutions 21 | Substitutions 22 |
| Applications | High-throughput WGS, population studies, RNA-Seq, single-cell, metagenomics, rare variant detection, proteomics 7 | Broad range including WGS, WES, RNA-Seq, single-cell, ctDNA, etc31. | Broad range including WGS, WES, RNA-Seq, single-cell, ctDNA, etc38. |
This comparison highlights several key areas where the UG 100 excels. Primarily, its cost per genome is significantly lower than that of comparable Illumina platforms, making it particularly attractive for projects requiring very large-scale sequencing. The high throughput, measured by the number of reads per wafer and potential genomes sequenced per year, positions the UG 100 as an ideal instrument for studies involving extensive sample cohorts. Additionally, the unique ppmSeq technology offers exceptional accuracy for detecting rare single nucleotide variants, which is a critical advantage for applications such as liquid biopsy and minimal residual disease detection.
Conversely, Illumina platforms maintain certain advantages. The established user base and mature ecosystem surrounding Illumina instruments mean that researchers may find a wider range of validated protocols, analysis pipelines, and readily available support. Illumina’s diverse portfolio of instruments also offers greater flexibility in terms of read length options, which can be important for specific research applications like de novo genome assembly. While the UG 100 has made progress in reducing indel errors, Illumina’s SBS chemistry has traditionally been associated with lower indel rates, which might be a consideration for highly sensitive applications. Furthermore, for laboratories with lower throughput needs or a diverse range of project types, the broader selection of instruments offered by Illumina might provide a more suitable fit.
V. Conclusion: A New Era in Genomic Sequencing?
In conclusion, the Ultima Genomics UG 100 represents a significant challenge to Illumina’s long-standing dominance in the NGS market, particularly for researchers prioritizing high-throughput and cost-sensitive projects. Its innovative flow-based chemistry and open wafer design enable a substantial reduction in sequencing costs and a remarkable increase in throughput, bringing the “$100 genome” closer to reality. While Illumina remains a powerful and well-established platform with its own distinct advantages, the UG 100 offers comparable accuracy for many applications, with a potential edge in substitution error rates and a unique capability for highly accurate rare variant detection through its ppmSeq technology.
The implications of increased affordability and throughput in genomic sequencing are profound. Platforms like the UG 100, by dramatically reducing sequencing costs, pave the way for larger and more statistically robust studies, allowing researchers to investigate complex biological questions with greater confidence. The ability to sequence larger cohorts enables advancements in fields like population genomics and the identification of subtle genetic associations with disease. Lower costs also facilitate deeper sequencing, which is essential for detecting rare variants in critical applications such as cancer diagnostics and monitoring. Moreover, previously cost-prohibitive experiments, like ultra-deep sequencing of complex microbial communities or large-scale single-cell analyses, become more feasible, opening up new avenues of research and discovery. Ultimately, the emergence of highly cost-effective sequencing platforms like the UG 100 has the potential to democratize genomics, making advanced sequencing technologies accessible to a wider range of researchers and institutions, thereby accelerating the pace of discovery across the life sciences.
The Ultima Genomics UG 100 marks a significant step towards achieving truly massive-scale, low-cost genomic sequencing. As this technology continues to mature and gain broader adoption within the research community, it holds the potential to reshape the landscape of life science research, empowering scientists to undertake increasingly ambitious and impactful projects. Researchers should carefully evaluate their specific application requirements, budget constraints, and the evolving performance metrics of both the UG 100 and comparable Illumina platforms to make informed decisions about the most appropriate sequencing solution for their work.
Navigating the UG 100 Landscape with Genohub’s Streamlined Platform
As the Ultima Genomics UG 100 gains traction in the research community, accessing this cutting-edge technology and navigating the nuances of its workflow are key considerations. This is where Genohub, a leading online marketplace connecting researchers with a global network of trusted genomics service providers, offers a powerful solution. Beyond simply connecting researchers with service providers, Genohub provides an easy-to-use and streamlined online project management platform designed to simplify and enhance the entire sequencing experience, particularly for UG 100 projects.
Genohub’s network includes service providers who are early adopters and experts in UG 100 sequencing. Through Genohub’s platform, researchers can effortlessly connect with these specialized labs and manage their projects from initial inquiry to final data delivery, all within a centralized online environment.
The platform facilitates every stage of your NGS project, ensuring transparency and efficient communication:
- Finding the Right Partner: Easily search and compare service providers offering UG 100 sequencing based on their expertise, services, and pricing, all within the Genohub platform.
- Simplified Project Initiation: Initiate your UG 100 sequencing project by submitting clear and concise project details through the platform’s intuitive interface, ensuring all necessary information is captured upfront.
- Centralized Communication: Communicate directly with your chosen service provider through the platform’s messaging system, keeping all project-related discussions organized and easily accessible.
- Quoting and Ordering: Receive and review detailed quotes directly within the platform, making it easy to compare options and finalize your project order.
- Progress Tracking: Stay informed about the status of your UG 100 sequencing project with real-time updates and tracking features available on the platform.
- Secure Data Delivery: Once sequencing and analysis are complete, access your data securely through the Genohub platform.
Genohub’s partners, accessible through the platform, offer comprehensive services encompassing the entire NGS workflow for UG 100 projects, including nucleic acid extraction, library preparation (both PCR-based and PCR-free methods optimized for the UG 100), expert UG 100 sequencing, and comprehensive data analysis pipelines. Furthermore, for researchers with existing Illumina-compatible libraries, some Genohub partners are experienced in the processes for potential conversion and sequencing on the UG 100, offering added flexibility.
By leveraging Genohub’s user-friendly online project management platform, researchers can significantly streamline the process of accessing and managing their UG 100 sequencing projects. This allows you to focus on your research goals, knowing that the logistical aspects of your sequencing are being handled efficiently and transparently through a centralized and intuitive system. Whether you’re embarking on a large-scale genomics initiative or exploring other high-throughput applications on the UG 100, Genohub provides the tools and connections needed for a successful and seamless sequencing experience. You can browse our current NGS services here or just submit a request with some information about your project.
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