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At ASMS 2017, Vendors Focus on Software, Applications

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INDIANAPOLIS (GenomeWeb) – The American Society for Mass Spectrometry annual meeting held here this week was relatively subdued from a vendor point of view, with most mass spec firms focusing more on their software and applications offerings and foregoing major instrument releases.

Thermo Fisher Scientific was the exception to this trend, as the company launched three new mass spectrometers along with a series of enhancements to its Orbitrap Fusion Lumos Tribrid system.

Perhaps most significant for proteomics researchers was the release of the company's Q Exactive HF-X mass spec, the latest upgrade to its Q Exactive line of instruments, which combines an upfront quadrupole with an Orbitrap analyzer and has allowed Thermo Fisher in recent years to win significant share within the QTOF market.

According to the company, the new instrument provides between a two- and three-fold improvement in sensitivity compared to previous Q Exactive models and can make the same number of protein identifications in half the time. During a presentation at Thermo Fisher's ASMS user meeting, Jesper Olsen, associate professor at the University of Copenhagen's Center for Protein Research noted that he and his colleagues were able to identify 1,100 unique peptides per minute using the new platform.

The platform supports a new label-free quantitation workflow the company is calling DDA-plus, which tackles the "missing values" problem that has traditionally presented challenges for DDA-based label-free quantitation, according to Ken Miller, Thermo Fisher's vice president, omics marketing, chromatography, and mass spectrometry.

In DDA workflows, the mass spectrometer selects precursor ions for fragmentation and collects quantitative data on these fragmented ions. However, because instruments are not fast enough to select and fragment all the ions, quantitative data is not generated for all peptides in all runs. This creates challenges for experiments where researchers want to compare protein levels across many samples because data for some proteins will be missing in some samples, leading to poor reproducibility.

Miller said that the high speed of the Q Exactive HF-X along with more robust microflow liquid chromatography and the company's new Proteome Discoverer 2.2 software package had allowed it to make progress in addressing the issue of missing values.

Thermo Fisher also released two new triple quadrupole instruments, its TSQ Altis, which is intended for high-performance targeted assays including targeted protein quantitation, and its TSQ Quantis, which is aimed more toward routine and applied use.

Additionally, the company announced the availability of new enhancements to its Fusion Lumos Tribrid instrument. The system now includes ultraviolet photodissociation (UVPD) capabilities, which brings an additional mode of fragmentation that can improve sequence coverage in, for instance, experiments looking at protein and small molecule structural information.

The instrument is also now capable of 1 million FWHM resolution for distinguishing between closely related structures.

Thermo Fisher also incorporated into the system its advanced peak determination algorithm, which Miller said will improve peptide and protein identification by enabling the mass spec to more efficiently select precursors for fragmentation.

The APD algorithm "does a much better job of assigning the charge state and the isotopic distribution so that you're always choosing novel species for fragmentation," he said. "So it does a much better job, I think, of making sure that you're not replicating the same analysis all the time, but that you're constantly looking for new precursors to fragment. And in that way it does a much better job of covering the sample in a way that I think is representative of what's there. So you don't spend all your time analyzing the [most abundant] proteins."

Bruker's presentation at the conference focused largely on its MALDI imaging capabilities including the potential of its MALDI instruments to make inroads into the pathology space. The company introduced its Scils Cloud software, which features a series of web-based tools for handling and sharing MALDI imaging data, and its and Scils Lab software, which provides MALDI imaging data analysis and visualization capabilities. Bruker acquired Bremen, Germany-based Scils in January.

Shannon Cornett, mass spectrometry applications development manager at Bruker, noted that while a move into actual clinical pathology is likely still years away, the company and collaborating commercial and academic pathologists have identified several assays for which MALDI imaging could prove clinically and commercially attractive.

"We are at the stage where those initial assays have been identified, and labs are under contractual agreement to work on those assays," Cornett said, noting that much of this work at present is focused on curating libraries of samples that can be used to develop the assays they are interested in.

Bruker also introduced software for top-down proteomics called ProteoForm Profiling 1.0, as well as a new nanoflow UHPLC system, its nanoElute.

Clinical Considerations

Sciex had little in the way of new proteomics releases, but it highlighted its new Topaz mass spec system and Vitamin D assay kit, which could prove a notable milestone for clinical mass spectrometry and have potential implications for the progress of mass spec-based protein assays towards the clinic.

The vitamin D assay received de novo clearance from the US Food and Drug Administration, making it the first LC-MS vitamin D assay to receive FDA clearance and providing Sciex with a foothold in the clinical diagnostics market.

The company provided little detail on the Topaz system, which it plans to launch formally at the American Association for Clinical Chemistry annual meeting this summer. Aaron Hudson, senior director and GM of Sciex Diagnostics said, though, that the instrument is designed so that it can be locked down for running FDA-cleared assays like the vitamin D test but can also be used for development and running of facilities' own laboratory-developed tests.

By bringing the instrument to market with the FDA-cleared Vitamin D test in place, Sciex hopes to incentivize potential customers like hospital labs to begin using mass spec, with the hope that this use will broaden down the road.

"One of the obstacles to adoption of mass spec in a traditional clinical chemistry lab in a hospital is the fact that they need to be productive right away with reimbursable tests, and they don't really have time to start from scratch and build an LDT and then get going," said Mark Cafazzo, director of global academic and applied markets at Sciex. "The work that we've done to get FDA-cleared on the vitamin D test is a strategy to enable labs to immediately get up and running doing the vitamin D test. They'll be able to run that full locked down in compliant mode and get reimbursed for their test."

Announcement of the Topaz and Vitamin D assay comes shortly after Thermo Fisher announced plans at its investor day to launch a "walkaway" mass spec-based clinical analyzer next year, suggesting that activity is heating up within the clinical mass spec space.

A Dash of DIA

There was some minor activity around data-independent acquisition mass spec methods at the meeting, as well, as Thermo Fisher and DIA software firm Biognosys signed a comarketing agreement this week covering Thermo Fisher's Orbitrap instruments and Biognosys' Spectronaut Pulsar software under which they will develop and optimize DIA workflows.

Waters, meanwhile, highlighted the ongoing development of its SONAR DIA mass spec method, which it initially released last September at the Human Proteome Organization's annual meeting. The method, which runs on its Xevo G2-XS QTOF, uses the quadrupole to actively scan the large m/z windows used in DIA techniques, which adds additional separation of precursors and improves assay performance.

Speaking at ASMS this week, Gary Harland, Waters' senior director of product management for mass spectrometry said that company researchers had found they were able to identify more than 35 percent more protein groups using the SONAR method compared to a traditional Swath approach, though he did not provide specifics regarding the setups of the experiments.