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Mass Spec Vendors Highlight New Qual-Quan Technology at ASMS

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This story originally ran on May 27

By Adam Bonislawski

Qual-quan was the catchphrase this week at the American Society for Mass Spectrometry annual conference as AB Sciex and Waters both introduced new time-of-flight mass spectrometers that the companies said combine the qualitative abilities of a high-resolution, accurate-mass system with the quantitative sensitivity of a triple-quadrupole machine.

AB Sciex's new TripleTOF 5600 and Waters' new Xevo G2 QTof will enable researchers to run qualitative and quantitative workflows simultaneously, the companies said, allowing for full scans of complex samples that can then be interrogated in a more targeted fashion — enabling, for instance, the collection of high-resolution full mass spectra data on a protein sample while at the same time running multiple-reaction monitoring assays.

"It takes two workflows and allows [users] to do it on one workflow," AB Sciex chief operating officer Andy Boorn said to ProteoMonitor about the TripleTOF 5600 in an interview before the ASMS conference, which was held in Salt Lake City this week (see related story this issue).

Neither Agilent nor Thermo Fisher introduced new qual-quan platforms at the conference, but in meetings at the conference both companies underscored the qual-quan capabilities of existing machines in their portfolios.

"We deliver simultaneous qual-quan measurements on all of our instruments all of the time, and we have been for two years," said Thermo Fisher's vice president of global R&D Ian Jardine, referring to products like the TSQ Vantage and some of its mass specs based on the Orbitrap technology.

Thermo Fisher also highlighted a pair of studies — one published in the February 2009 edition of Rapid Communications in Mass Spectrometry and one published online in March 2009 in the Journal of the American Society for Mass Spectrometry — that explored the qual-quan abilities of its LTQ Orbitrap and Exactive Orbitrap machines.

Gus Salem, vice president and general manager of Agilent's Life Sciences and Chemical Analysis Group's LC/MS division, pointed out the qual-quan capabilities of the company's 6540 UHD Q-TOF mass spectrometer, which was released in June of last year.

"As the performance of the Q-TOF instruments has gotten so much better, it's encouraged people to want to do quantitative on TOF," he told ProteoMonitor. "The methods development is easier. There's a huge improvement in time."

He dismissed, though, the notion, that the development of qual-quan machines would cut into the market for traditional quantitative instruments like triple-quads. At the conference Agilent introduced its newest triple-quad model — the 6490 Triple Quadrupole LC/MS System, which it said features 10 times the sensitivity of the company's previous triple-quad instruments, allowing for detection at the zeptomole level.

"Fundamentally we believe that this is an additive capability. I don't anticipate that we'll see a replacement of triple-quad business in routine use applications," Salem said. "You may do that qual-quan experiment up front because you now have that capability, but if you were going to develop a truly quantitative protein assay, and you had done all of the right work to define all the appropriate peptides, their transitions, programmed in the correct MRM information and set the instrument to go, you'd probably end up executing that on a routine basis on a triple quad."

Lorne Taylor, director of the Ontario Proteomics Methods Centre at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, who has been using the AB Sciex TripleTOF 5600 in advance of its release, agreed, telling ProteoMonitor that although he was impressed by the 5600's quantitative abilities, his lab will continue to use triple-quads for high-sensitivity work.

Richard LeLacheur, vice president of Princeton, NJ-based biotechnology firm Taylor Technology, suggested, however, that the qual-quan buzz indicates a shift of interest back to high-resolution mass spec after years of focus on triple-quad platforms.

"With this enormous triple-quad infrastructure that's out in the world there's going to be a lot of push to harness it for problems like peptides and proteins," he told ProteoMonitor, "but the simple reality is that it won't be the best tool for everything. There will be times when a high-resolution mass spec will beat a triple-quad for both the specificity of the answer and the sensitivity of the answer, so you really need to get good at knowing how to harness both tools. That's going to be new for a lot of the quantitation people."

Bruker focused on its high-resolution offerings, particularly its new maXis ETD system, which, the company said, allows for routine ETD-based tandem mass spectrometry on proteins above 60 kDa. Yuri Tsybin of the Swiss Federal Institute of Technology Lausanne presented the results of a study using maXis ETD to analyze intact proteins like serotransferrin of up to 150 kDa.

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Software is 'Key'

One potential issue with the emergence of qual-quan systems is the need for software capable of keeping up with the large amounts of data such systems will generate, Iain Mylchreest, vice president and general manager of Life Sciences Mass Spectrometry at Thermo Fisher, told ProteoMonitor.

"Software is absolutely key," he said. "The amount of information you're acquiring now is significantly higher. It's not just a mass spectrum anymore or a chromatogram. You're trying to see what's going on inside a cell — is a pathway being turned on or is a protein being expressed? So, the whole software infrastructure has got to change and evolve with the instrumentation."

Mylchreest cited Thermo Fisher's Pinpoint software — designed to aid in the quantitative verification of putative biomarkers — and its Proteome Discoverer software — a platform for analyzing quantitative and qualitative proteomics data — as products facilitating the new qual-quan technology.

AB Sciex released a new suite of application software to accompany the launch of the TripleTOF 5600, including new PeakView software for processing and visualizing large amounts of mass spec data and ProteinPilot for proteomics applications.

David Chiang, CEO of bioinformatics firm Sage-N Research, told ProteoMonitor that he thinks the new platforms will require more robust software than is presently supplied in-house by most mass spec vendors, however.

"Most of the mass spec vendors are really primarily developing PC software. It's kind of like entry-level stuff," he said. "I don't know that anyone fully realizes how much data they're dealing with."

Researchers, LeLacheur said, are just beginning to learn about the capabilities and challenges that the new qual-quan platforms will provide.

"This is the first generation of qual-quan," he said. "This lets you do it. Now people are going to go out and find all the problems trying to do it. There's just not that much of a publication and knowledge base for it yet. The papers are no more than a few years old. Almost everyone is in their infancy for doing this kind of work."

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