NEW YORK – For the proteomics market, 2024 was more a year of incremental progress than dramatic developments as the field continued to incorporate the advances of recent years.
The year saw several new mass spectrometry releases, but none as significant as the launch the year before of Thermo Fisher Scientific's Orbitrap Astral and Bruker's TimsTOF Ultra, both of which marked leaps forward for instrument performance.
Meanwhile, next-generation proteomics firms continued to struggle as Quantum-Si missed sales targets for its Platinum sequencer and Nautilus Biotechnology again pushed back the timeline for releasing its planned proteomics platform.
At the same time, a number of firms teased new developments that could prove meaningful in coming years. Ion mobility outfit Mobilion, for instance, introduced a new technology that could reshape certain commonly used mass spec proteomics workflows, while Alzheimer's diagnostics company C2N announced plans to develop a fully automated mass spec system that would be a first for clinical proteomics.
One of the biggest stories of 2023 was the launch of new instruments, the aforementioned Orbitrap Astral and TimsTOF Ultra in particular, that substantially increased the throughput and depth of coverage of proteomics experiments — especially in plasma. The field continued to make gains in this area in 2024 as competition grew among vendors of plasma proteome enrichment systems, which, along with improving mass spec technology, have been key to enabling deeper, faster proteomic experiments in plasma.
Proteomics firm Seer pioneered the plasma enrichment space with its Proteograph Product Suite, which uses nanoparticles to enrich proteins within a sample prior to mass spec analysis. At the American Society for Mass Spectrometry (ASMS) annual meeting in June, diagnostics firm PrognomiQ, in which Seer has a roughly 19 percent ownership stake, presented data from a 2,840-subject cancer biomarker study in which, using Seer's Proteograph platform, it detected an average of 8,200 proteins per sample and a total of more than 13,000 proteins. This marked an increase over data Seer released the year before showing that its system could measure around 6,000 to 7,000 proteins per sample when coupled to top-of-the-line instruments like Thermo Fisher's Orbitrap Astral.
Other companies also launched new products in the space. At the ASMS meeting, Biognosys introduced its P2 Plasma Enrichment offering, which the company said allows for the measurement of up to 7,000 proteins in plasma, while PreOmics introduced its Enrichplus kits, which the company said enable up to sevenfold increased protein identifications compared to neat plasma and with which company researchers identified a total of 5,800 proteins across 12 different patient samples.
Bruker owns a majority stake in both firms. According to Biognosys CEO Oliver Rinner, using the P2 approach on Bruker's TimsTOF HT running a 17-minute LC gradient, the company was able to detect around 6,000 proteins per sample and a total of around 7,000 proteins across a small cancer cohort.
While Seer continues to lead the field in depth of coverage, the relatively high price of the company's products (around $600 per sample, according to quotes provided to some researchers) has created an opening for products at lower price points that firms like Biognosys and PreOmics are looking to fill. To that end, proteomics separations firm Evosep presented this year a fully automated version of the Mag-Net plasma enrichment assay developed by Michael MacCoss, professor of genome sciences at the University of Washington, that uses magnetic microparticles from South Africa-based ReSyn Biosciences and costs around $5 per sample.
The affinity angle
Affinity-based platforms from companies including Olink and Standard BioTools also continued to make inroads, though the latter firm saw delays in contracts for its SomaScan services negatively impact revenues.
Standard BioTools' then-CFO Jeffrey Black said during a conference call following the company's Q2 2024 results that it was exploring new sales models, including offering lower plexes of its SomaScan tool as well as single Somamer reagents, to help expand and diversify its customer base. In October the company officially announced that it will make each of the roughly 11,000 Somamer affinity agents used in the SomaScan platform available for individual purchase. Standard BioTools acquired the SomaScan technology via its merger with SomaLogic in January.
Standard BioTools is also preparing for the launch of the Illumina Protein Prep assay, which will make the SomaScan assay available on an automated system composed of a Tecan Fluent 780 liquid handler and an Illumina NovaSeq sequencer. The assay is slated to launch in the first quarter of 2025 and will measure between 9,000 and 10,000 protein targets. At a workshop at the American Society of Human Genetics annual meeting in November, Illumina said the workflow will have a turnaround time of 2.5 days and offer femtomolar sensitivity as well as a 10-log dynamic range. SomaLogic, and now Standard BioTools, have viewed moving SomaScan to an NGS-based kit product as opposed to a service offering as key to driving uptake of the assay.
Olink's Explore HT platform, which measures more than 5,300 proteins, also uses Illumina NGS systems as a readout option. In July, Thermo Fisher completed its $3.1 billion acquisition of Olink following delays for reviews by the Swedish Inspectorate of Strategic Products and the UK's Competition and Markets Authority.
Meanwhile, a more recent entry to the affinity proteomics space, Alamar Biosciences, continued to build its business in 2024. While the company offers much smaller assay multiplexes than Olink (which is currently suing Alamar for patent infringement) or SomaLogic, its platform's sensitivity and high level of automation has attracted customers. It has drawn particularly strong interest from neurology researchers as it allows them to measure in blood large panels of proteins linked to neurological diseases like Alzheimer's. In March, Alamar launched its NULISAseq CNS Disease Panel 120 for analysis of 120 proteins implicated in major neurological disorders and its NULISAqpcr pTau-217 Assay for focused measurement of the Alzheimer's biomarker phosphorylated-tau 217. In August, proteomics firm Biognosys began offering Alamar's assays under a strategic partnership announced last year.
Next-gen approaches
Next-generation protein analysis methods progressed, as well, though in some cases more slowly than hoped. Nautilus once again pushed back the projected launch of its proteomics platform, and in October the company noted that it has experienced higher-than-expected failure rates for the affinity agents it is developing for the platform.
Quantum-Si, meanwhile, has struggled to drive sales of its Platinum protein sequencer and in November announced that it is laying off roughly a quarter of its 187-person workforce.
Both companies, however, drew interest for targeted uses of their technologies. At the ASMS annual meeting, University of Virginia researcher Gloria Sheynkman presented on her lab's use of the Platinum system to detect variant peptides difficult to measure via mass spectrometry. At the recent HUPO annual meeting, Nautilus detailed a targeted assay on its platform capable of measuring hundreds to thousands of proteoforms of the protein tau. Sally Temple, scientific director of the Neural Stem Cell Institute in Rensselaer, New York, said that her lab has been using the system to measure tau proteoforms in organoid brain models it has developed.
Nanopore-based protein analysis technologies also continued to advance, with some researchers suggesting that such measurements are approaching feasibility.
Most immediate on the horizon is nanopore-based protein fingerprinting, in which nanopores are used not to read an amino acid sequence but to generate a "fingerprint" signal that is characteristic of a protein. Researchers can use this fingerprint to identify the protein as well as use deviations from the expected signal to identify potential variations in its sequence or posttranslational modifications.
Andrew Heron, cofounder and CEO of nanopore firm Portal Biotech, said his company has been generating experimental nanopore data on proteins and using it to train machine-learning algorithms to predict nanopore signals from protein sequences with the goal of producing databases of simulated signals that can be used to make identifications. He said the company is now at the point where it is capable of producing such simulated databases and identifying individual proteins out of thousands of potential candidates with accuracies above 90 percent, though it has not yet published peer-reviewed research detailing this work.
Looking ahead
2024 also saw the announcement of several new proteomic technologies and platforms that, while not currently available, could have major impacts in coming years.
During its recent investor day, Quantum-Si said that it is developing a platform called Proteus that could ultimately enable proteome-scale protein sequencing. The company plans to launch an initial version of the system in 2026 that will be capable of analyzing around 50 million peptides per experiment. Longer term, though, the firm believes it can scale the system to sequence billions of peptides per experiment, allowing for analysis of complex samples on a scale comparable to that of shotgun mass spec proteomic experiments, said Quantum-Si Chief Technology Officer Todd Rearick.
In a move that could reshape mass spec proteomic workflows, sample separation firm Mobilion Systems announced plans to apply its SLIM (structures for lossless ion manipulation) ion mobility technology to proteomics.
Developed by researchers at Pacific Northwest National Laboratory (PNNL) and licensed by Mobilion, SLIM ion mobility extends ion mobility path lengths beyond that allowed by conventional IMS systems, enabling much more extensive separations. To date, the company has largely focused on targeted applications, but it now plans to position SLIM technology as a tool that will eliminate the need for quadrupole filtering of precursor ions. Such an approach could significantly boost the percentage of sample ions analyzed in mass spec experiments, providing increases in speed and sensitivity.
Diagnostics firm C2N, meanwhile, announced that it is developing a fully automated, high-resolution mass spec platform for running its protein tests for Alzheimer's. If the company is successful, this would be the first sample-to-answer clinical mass spec system intended for protein-based testing to come to market and would mark a significant milestone for clinical proteomics.
CEO Joel Braunstein said the system will be a C2N-branded instrument produced by a third-party original equipment manufacturer, and that the company expects to have a first-generation system in hand in the first half of 2025.