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Hi-res Reigns as ASMS 2014 Sees a Number of New QTOF, Q-Orbitrap Instrument Launches

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BALTIMORE (GenomeWeb News) – While triple quads predominated at last year's American Society for Mass Spectrometry annual meeting, high-resolution instruments were the focus of this year's gathering with several vendors launching new high-end QTOF or Q-Orbitrap machines.

With these releases, the meeting, held this week here, saw a renewed emphasis on data-independent acquisition mass spec workflows, as vendors touted the capabilities of their new instruments to simultaneously collect qualitative and quantitative data on a proteome-wide scale.

Among those launching a new high-resolution platform this week was AB Sciex, which introduced its TripleTOF 6600, an upgrade over the TripleTOF 5600 that it launched at the 2010 ASMS meeting.

The new instrument features a new TOF detection system that gives it an additional order of dynamic range compared to the 5600, taking it over five orders of dynamic range, Mark Cafazzo, AB Sciex's global market manager for proteomics, told ProteoMonitor this week. It also offers 35,000 resolution in MS mode, 30,000 resolution in high-resolution MS/MS mode, 20,000 resolution in high-sensitivity MS/MS mode, and a speed of up to 100 MS/MS per second.

The company also modified the instrument's upfront quadrupole to extend its mass selection range, Cafazzo said, noting that while the 5600's quadrupole could only select ions up to 1250 m/z, the 6600's quadrupole will select ions up to 2250 m/z.

This change came in response to "some pushback we got from some of our customers who want to do modified peptides like glycopeptides," he said. Because such modifications add mass (m) without adding charge (z), they sometimes pushed the m/z of target ions above the 5600's range.

With the new m/z range, "that's not a problem anymore," Cafazzo said.

With the launch of the 6600, AB Sciex also launched Swath 2.0, an updated version of its DIA workflow. During the company's press conference, Anne-Claude Gingras a researcher at Mount Sinai Hospital, Toronto, and an early access user of both the 6600 and Swath 2.0, said that using the new workflow she and her colleagues had seen a roughly 50 percent increase in protein IDs compared to the original Swath product.

Waters and Bruker likewise launched new flagship QTOF instruments this week.

Waters introduced its Xevo G2-XS mass spec, which, the company said, offers 40,000 resolution and features its new XS Collision Cell. The new cell improves performance by "taking the ion beam and sharply focusing its intensity and orientation, thereby getting a higher percentage of the ions into the time-of-flight [analyzer] at a higher resolution," said Brian Smith, Waters' vice president of mass spectrometry operations.

The instrument also features Waters' Tof-MRM technology – a high-resolution approach to targeted quantitation similar to the parallel-reaction monitoring method developed on Thermo Fisher Scientific's Q Exactive machine. According to the company, when run in Tof-MRM mode, the G2-XS offers a 10-fold improvement in signal-to-noise compared to full scan mode.

While such high-resolution approaches provide potential advantages in terms of selectivity and assay development, they typically haven't offered the sensitivity of conventional triple quad-based targeted quantitation assays. However, in its internal work the company has found that Tof-MRM sensitivity "is getting very close" to competing with conventional targeted assays, said James Langridge, director of discovery, pharmaceutical, and life sciences at Waters.

Bruker this week launched its impact II QTOF, which, according to the company, offers 50,000 resolution along with five orders of dynamic range.

The instrument features a DC gradient in its collision cell that allows it to move ions more quickly through the cell, increasing scan speeds and ion transmission, Ole Vorm, Bruker's vice president for life sciences research and proteomics, told ProteoMonitor.

Thermo Fisher doesn't sell QTOF technology, but this week it launched a new version of its Q Exactive instrument, a quadrupole-Orbitrap machine aimed at the QTOF market. The new system, the Q Exactive HF, features a high field Orbitrap that offers 240,000 resolution and a scan speed of 18Hz, both double that of the original Q Exactive.

The company also introduced four different types of DIA methodologies for use on its Q Exactive, Q Exactive HF, and Orbitrap Fusion instruments, and indicated that it is taking aim at the growing market for DIA analysis that has been fostered in large part by AB Sciex's launch of Swath in 2011.

DIA "is compelling in principle because there is [little] method development, and it gives you large coverage as well as quantitative measurement of your samples," Ken Miller, Thermo Fisher's vice president of marketing for life sciences mass spectrometry, told ProteoMonitor.

Additionally, "you are creating a permanent digital archive of your sample – you have MS/MS on all the species in your sample – and you can go back and retrospectively search it as you become interested in other markers or compound classes," he said.

Data demands

Of course, all this data calls out for software to help researchers manage it, and, with this in mind, a number of vendors introduced new informatics packages, as well.

Waters introduced its Progenesis QI for proteomics 2.0, a package for quantification and identification of differentially changing proteins between samples. The software includes pathway analysis tools for understanding biology based on MS data, and pre-processing functions to help exclude poor quality data from analysis.

Several vendors also touted integration of their platforms with the University of Washington's Skyline software, the leading open access software package for quantitative proteomics including MRM, PRM, and DIA workflows. Shimadzu, for instance, announced that it was collaborating with the Skyline team to integrate the software with its LC-MS/MS instruments. Thermo Fisher likewise said that it was working with Skyline to implement its new DIA workflows.

Thermo Fisher is also working on DIA workflows using its internal Pinpoint software, a package aimed at targeted quantitation. It is collaborating as well with Swiss targeted proteomics firm Biognosys, a spinout of the lab of Swiss Federal Institute of Technology Zurich researcher Ruedi Aebersold, developer of the original Swath method.

Clinical questions

Clinical mass spec received somewhat less attention than in the past, though there were some developments on this front, as well.

Most notably, Agilent this week introduced its 6495 triple quadrupole, which, the company said, offers a five-fold increase in sensitivity over its 6490 instrument, considered by many researchers to be one of the leading systems in the field.

While the 6495 is not explicitly aimed at clinical proteomics, the instrument launch has potential implications for this area given the significant work Agilent has done building clinical workflows for its triple quad systems. Indeed, last year Integrated Diagnostics launched on the 6490 its Xpresys lung test, the first multiplexed proteomic test to go to market using MRM-MS on a triple quadrupole instrument.

Shimadzu highlighted its clinical mass spec ambitions with a partnership with Indigo Biosystems, developer of the Ascent clinical analysis software package. Under the partnership, the two firms will combine Shimadzu's mass spec instruments with Ascent, which aids in the interpretation of mass spec data and automated review of that data for problematic results.

Thermo Fisher this week announced that it has registered its San Jose, Calif. facility with the US Food and Drug Administration as a medical device establishment, part of its ongoing initiative to develop Class I mass spec devices for the clinical market.

At the 2013 ASMS meeting, Ian Jardine, CTO of life sciences mass spectrometry at Thermo Fisher, told ProteoMonitor that the company planned that year to register some of its mass specs as Class I devices, however it has not yet done so. Miller this week reiterated the company's plans to register its instruments in the near future.

AB Sciex last year launched its 3200MD and 3200MD QTRAP instruments as Class I medical devices. However, speaking this week, President Rainer Blair said that despite the progress mass spec-based clinical proteomics has made in recent years, he thought the wider introduction of multiplexed biomarker panels on mass spec was still three to five years off.

"We've been targeting the clinical research as well was the clinical diagnostics space," he said. "We're pretty excited about the progress we're making there and you're going to continue to hear from us there this year, as well."

However, he added, as protein biomarker firms are "starting to enter the clinic [as laboratory-developed tests], they are running into the issue that they need to get over the regulatory hurdle in order to scale their business model."

He said he thought that to overcome this hurdle, test developers and vendors would need to demonstrate significant clinical benefit of mass spec-based tests.

"I think that when the treatment benefit is indisputably positive, then we're going to see an acceleration of FDA approval times," he said.

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