Skip to main content
Premium Trial:

Request an Annual Quote

Plasma Proteome Enrichment Attracts New Players, Approaches


NEW YORK – Competition is heating up in the plasma proteome enrichment space as a number of firms are developing sample prep reagents and workflows to help researchers achieve deeper and broader proteomic coverage.

In recent months, companies including Biognosys, Evosep, and ReSyn Biosciences have either released new plasma proteome enrichment products or detailed development work in this area. At the same time, proteomics firm Seer, which sparked the resurgence of this market with the 2022 launch of its Proteograph Product Suite, continues its efforts to drive uptake of its enrichment tools.

Until recently, mass spec-based experiments could typically measure on the order of several hundred proteins in plasma. While it was possible through extensive fractionation to achieve a depth of several thousand proteins, such experiments were extremely time-intensive and did not offer the throughput necessary for large-scale studies.

Seer's technology was the first to enable mass spec-based plasma proteomic experiments capable of measuring thousands of proteins at levels of throughput sufficient to analyze hundreds of samples. In a 2020 paper, company employees and affiliated researchers used the platform to analyze 141 plasma samples from non-small cell lung cancer patients and healthy controls, identifying an average of 1,664 proteins per subject and more than 2,000 proteins across all subjects combined. More recently, the company has shown that its second-generation Proteograph XT Assay Kit can measure around 6,000 to 7,000 proteins per sample when coupled to newer top-of-the-line instruments like Thermo Fisher Scientific's Orbitrap Astral.

Seer's technology uses nanoparticles to enrich proteins in samples like plasma. The approach is based on the observation that when incubated in a biological sample, nanoparticles collect proteins, which form a "corona." Given this, nanoparticles can serve as an enrichment tool, allowing researchers to pull proteins out of a sample, which they can then identify and quantify using technologies like mass spec. Because nanoparticles collect proteins across a large portion of the dynamic range present in plasma, they allow researchers to detect low-abundance proteins without using time-consuming steps like protein depletion and sample fractionation.

Researchers had previously explored the use of nanoparticles for plasma proteome enrichment, but Seer was the first to turn this idea into an effective commercial product. Since then, several other companies have entered the plasma protein enrichment space, perhaps in part due to Seer's success.

Often "it takes an extra bit of effort to make [a method] robust and reliable," said Michael MacCoss, professor of genome sciences at the University of Washington. "And I think we are getting to that [with plasma protein enrichment], and people have recognized now that these [approaches] are working well enough that it is worth the extra time to improve upon them a little bit."

MacCoss and his UW colleague Christine Wu have developed a plasma proteome enrichment technique that uses magnetic microparticles from South Africa-based ReSyn Biosciences to improve depth of coverage by binding membrane-bound vesicles in plasma and analyzing the associated proteins.

According to the researchers, the method, called Mag-Net, can consistently quantify around 4,800 proteins in plasma using a 30-minute liquid chromatography gradient on an Orbitrap Astral, allowing for throughput of around 40 samples per day. It enables measurement of between 5,000 and 6,000 proteins using a one-hour LC gradient.

Swiss proteomics firm Biognosys also entered the proteome enrichment market recently, offering a particle-based enrichment approach as part of its TrueDiscovery services that, according to the company, can measure around 4,500 proteins in plasma at high throughput (roughly 40 samples per day) and around 7,000 at lower throughput.

In April, Chinese firm Nanomics Biotechnology published a BioRxiv preprint detailing its Proteonano plasma enrichment technology, which, like Seer's Proteograph, uses nanoparticles to capture proteins across a wide dynamic range. The company withdrew the preprint several days later, however, due to "incomplete data analysis." It is, nonetheless, an indication of the growing interest in the space.

Seer Chair and CEO Omid Farokhzad indicated that he does not currently view any of these alternative approaches as serious competitors to his firm's technology, saying that "if anything," the activity in the space "signifies the effectiveness and success of [Seer's] platform."

He cited Seer's record of publications detailing the performance of the Proteograph system, as well as the high levels of product development and automation embedded in that system, as key differentiators. Farokhzad also noted what he called Seer's "world class" understanding of the "nano-bio interface and the chemistry, the data science, the manufacturing that goes with making a particle have a particular profile" in terms of capturing biomolecules.

Seer's system has drawn praise from some users for its performance and ease of use. Joshua Coon, professor of biomolecular chemistry and chemistry at the University of Wisconsin-Madison, told GenomeWeb last year that his first- and second-year graduate students had experienced "really good success" with the system, adding that the level of automation "has been really handy."

The system's high price, however, has proved a barrier for some scientists, particularly in the proteomics field where researchers are accustomed to large capital spending on mass spectrometers but less so to high per-sample reagent costs. Karl Mechtler, proteomics head at Vienna's Research Institute of Molecular Pathology, said last year that in his discussions with Seer, the quoted cost per sample was around $600.

"If I have 100 samples, that is a lot of money for a proteomics lab," he said, noting that for a typical proteomics lab, an affordable price point would be around $25 to $50 per sample.

This issue of cost could provide an opening for competitors.

Biognosys CEO Oliver Rinner did not provide pricing for the company's TrueDiscovery service, but he indicated that it is targeting customers at a lower price point than Seer.

Seer "is more really [for getting] maximum depth for people who are willing to pay the price," Rinner suggested, whereas Biognosys aims to provide "plasma protein profiling across large cohorts at an economy that works in the field and that people are willing to pay."

The UW Mag-Net method, meanwhile, costs less than $5 per sample.

Farokhzad suggested, though, that the Mag-Net workflow is more of an academic effort, without the robustness and ease of use of Seer's system.

"The manufacturability and reproducibility [is not] anywhere near on par with a product like Seer," he said.

There are indications, however, that ReSyn Biosciences, possibly in collaboration with other vendors, is working to develop a commercialized version of the Mag-Net workflow. Asked about its ambitions in this regard, the company referred GenomeWeb to UW's MacCoss for comment. He said that ReSyn "is planning on making a kit" to make the workflow more robust and easily accessible to a wide range of researchers.

MacCoss added that he and his UW colleagues plan in the next several months to begin offering the workflow as a service to outside researchers.

ReSyn has also been working with Danish proteomics separations company Evosep on streamlining and automating the workflow. Last year, the companies announced a collaboration focused on integrating their technologies to develop more automated and higher-throughput proteomic workflows. As part of the collaboration, Stoyan Stoychev, head of proteomics at ReSyn, joined Evosep as a senior scientist.

In April, Evosep produced a webinar in which Stoychev presented a fully automated version of the Mag-Net assay, combining ReSyn's magnetic beads with Evosep's Evotip sample prep product and its Evosep One liquid chromatography system.

Nicolai Bache, VP of proteomics research at Evosep, said that while his firm does not necessarily plan to lead the effort to standardize, automate, and commercialize the Mag-Net workflow, it plans to support this effort and, if necessary, take it on itself.

"We need to ensure that there is a fully commercially available end-to-end solution," he said. "We are thinking about how this is best done. We don't have a need to be the ones 'kit-ifying' [the workflow], but obviously we are entertaining and supporting that idea."

"We don't have anything like this coming, but we could very quickly make the decision to do it because it is needed, and if nobody else is going to do it, then we may actually go ahead and make the decision to do it," Bache said.

Like others in the proteomics space, Bache cited the high price of Seer's product and suggested that this left an opening for lower-cost alternatives, even if they don't fully match the performance of Seer's technology.

He said that a major part of the promise of plasma protein enrichment technologies is the ability to collect deep proteomic data across large numbers of samples. But, he noted, "running a lot of Seer experiments is going to cost a fortune."

"The fact of the matter is, we are seeing now quite a few different and similar technologies giving at least useful [plasma] proteome coverage," Bache said.

Seer, meanwhile, does not plan to lower its prices, Farokhzad reiterated, saying that he "is not going to discount" the company's products.

He said that Seer believes demonstrating the biological insights its platform can provide — largely via experimental data and publications produced by its users — will be key to gaining traction in the market.

Such data and publications "will show the differentiated value [of Seer's technology], and I can charge what I charge for my product," Farokhzad said. "I have a value proposition that is so much greater [than alternative technologies]. The thing that is missing is external validation for that value proposition."

This tracks recent statements from the company that it expects relatively modest near-term growth, as it is focused on building out the body of evidence supporting its technology's utility.

While Farokhzad insisted that Seer will hold firm on pricing, he did indicate the company is looking into ways to serve customers at the lower end of the market who might be considering cheaper alternatives for plasma proteome enrichment. He cited the example of Illumina and how it offered different price points for different depths of sequencing, creating a "price ladder."

"The question we have is, should we have a price ladder, and if so, how?" Farokhzad said. "The lower your price, the more of the market segment you grab. There is a sweet spot where if I go too low, I will actually lose on my top line, but if I am too high, I might leave a bunch of folks behind who I actually want to use my product."

"We started off in having differential pricing between academic and commercial [customers]. That gap may need to be larger," he said. "I'm not committing to anything. We are thinking about a price ladder and whether we need to have a lower-priced product, as well."