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Waters, University of Warwick Collaborate to Build Out Applications for Synapt Platform


This story originally ran on April 22.

Waters and the University of Warwick in the UK last week announced a collaboration aimed at expanding applications for the company's Synapt HDMS platform and other Waters mass specs.

As part of the partnership, the two along with regional government are creating the Waters Centre for BioMedical Mass Spectrometry at the university, which will serve as a center of excellence in state-of-the-art mass spectrometry.

The center is expected to become operational within the next year and will be outfitted with a full portfolio of Waters instruments, including at least 10 mass specs, James Scrivens, a professor in biological sciences at the school who will lead the new center, told ProteoMonitor this week. The university has one Synapt and has ordered a second one. Triple-quadrupole instruments and MALDIs will also be included as will Waters' Xevo TQ mass spec, launched at last year's American Society for Mass Spectrometry conference, and the company's 1D and 2D nanoAcquity UPLC systems,

In addition to the current 12 researchers in his group who will eventually move over to the center, other positions will be filled during the next year to round out staff who will be dedicated to the center.

Both parties declined to disclose the center's price tag.

Not a Proteomics Service Center

The center will not function as a mass spec or proteomics core facility, and though Scrivens' group has several projects ongoing with other researchers, the role of the center will not be to provide services to other scientists, but rather will serve to explore new capabilities of the Synapt platform.

Mark McDowall, Waters' strategic development manager for mass spectrometry, added that the firm would not be interested in collaborating with a "generic service lab" as that would have "no strategic value for us."

Beyond classic biomarker work, Scrivens has been researching "shape-specific separation," which Waters has been working on as well and which could benefit the company, McDowall, said.

Scrivens' lab "brings a wealth of experience of most of the ion ability technique [and] its concepts, but uniquely they can see where that will bring advantages to biological research, and where it's probably a waste of time. That is something that helps us drive our technology to the marketplace," McDowall said.

Part of the center's role, Scrivens said, is to serve as a kind of technology distributor.

"We tend to develop the technologies and when they become established within a research platform, the scientists involved would go out and purchase their own equipment which would then be dedicated to their own project," he said. "So if you like, we're sort of a hothouse of development and establishing technologies which can then be incorporated in other parts of the university."

Its partnership with Waters, he added "is focused on exciting new technologies but in recognizing that [they will be implemented] in important and far-reaching biological applications," Scrivens said.

One area Scrivens' group is researching is phosphorylation in enzymes — how phosphorylation changes the shape of the enzyme and then how the newly shaped molecule converts other ligands into their biological processes.

"The ability of the Synapt to have the sensitivity and the speed and the information content to study these things in real time gives what we believe is a unique insight into real occurring biological processes," Scrivens said.

Another area he is exploring is the use of ion mobility as "an alternative dimension." Experiments in the ion mobility technology occur in the millisecond time scale, while time-of-flight works on a microsecond time scale and separation occurs in the second time scale.

"And the ability to put all those things together to give us an extra dimension to extraordinarily complex datasets is in its infancy, and I believe will grow very quickly in the next few years," Scrivens said.

According to McDowall, because the Synapt has been around only since 2006, applications for the platform are only in the budding stage. While protein-folding analysis was a first application for the Synapt technology and many of the subsequent uses of the platform have been for protein analysis, researchers are beginning to see that it has use in other areas, for example, small-molecule work, he said.

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Drawing on the history of quadrupole time-of-flight technology — which Waters invented — as a comparison, McDowall said that when that technology first appeared in the mid-90s, it was used almost exclusively for protein work. Today, 60 to 70 percent of sales of Q-TOFs are sold for small-molecule analysis, such as drug discovery.

"And I would imagine you would likely see a similar expansion into small molecules with the Synapt-type technology," he said.

While Scrivens' work is mainly focused on proteins, his group also uses the Synapt coupled with ambient ionization for the identification of counterfeit drugs. They also are using the platform to examine synthetic macromolecules "where we look at complex macromolecules and find end groups and try to correlate that with performance," and use the Synapt to research how protein shapes change as a result of metal binding to them, he said.

One new area he is "very excited about" is use of the platform as a compound-class analyzer. Recently, his group published a study showing the potential of the Synapt to differentiate phosphopeptides.

In addition to developing new research technology, Scrivens is doing biomarker work and developing mass spec-based diagnostics for blood-borne diseases.

His group is also conducting biomarker discovery work in diseases of pregnancy with a particular focus on preeclampsia and Down syndrome. The identification of putative biomarkers for those diseases is underway and the next step will be to validate candidate biomarkers using triple-quadrupole based technology, Scrivens said.

He also has done extensive research into prion disease using the Synapt technology that separates ions based on their shape as well as mass-to-charge ratios.

Familiar Face

McDowall said the collaboration with Warwick is the first of its kind into which Waters has ever entered. Scrivens first approached the company about the creation of the center and a collaboration.

Key to the firm's decision to do so was the long history it has had with Scrivens dating back to the days when the mass-spec business was called Micromass before it was purchased by Waters, and Scrivens was at Imperial Chemical Industries before moving on to the university three years ago.

According to Scrivens, he and Waters have published 25 peer-reviewed papers together and been involved in more than 100 jointly authored presentations at conferences. He also purchased the first commercially available Synapt.

McDowall credits Scrivens with fast-forwarding the commercial launch of the Synapt: Scrivens bought the platform "essentially from the drawings" even before an actual product had been built. "We had the idea, but it was Professor Scrivens who looked at the concept and said, 'Yes, make me one.'"

That first Synapt was used to study prion disease.

While Waters is interested in establishing formal relationships with research groups and academia, ultimately the decision to do such a collaboration is "driven by the application … by the quality of the resource and the people, and the quality of the relationship," McDowall said.

From a proteomics perspective, he added, the appetite of funding agencies such as the National Institutes of Health for traditional biomarker-based research is waning and shifting, instead, to work directed at structure and function relationships.

"Of course, our bread-and-butter proteomics income is very much related to biomarker discovery today [and] probably will continue outside of the public sector significantly, but … accelerating the development of technology that can do more than just biomarker discovery … gives our academic customers tools to help them go and get the funding that they need," McDowall added. "But obviously, it's important from a business point of view for us."