VANCOUVER, BC – "Evolutionary" – as opposed to "revolutionary" – was the buzzword at the American Society for Mass Spectrometry's 2012 meeting held here this week, as mass spec vendors offered little in the way of blockbuster new releases but focused instead on incremental improvements to existing platforms along with expanded applications and additions to separations and informatics portfolios.
"It's like everything: you sort of peak, plateau, peak again, and I think we're just on one of those plateau phases," Ian Pike, chief operational officer of proteomics firm Proteome Sciences, told ProteoMonitor this week.
"If you look at the changes that have happened over the last five years in the performance of mass spec and the mass spec geometries that are available, it's just been crazy," he said, suggesting that the industry is currently taking something of a breather after this rapid run of innovation. "It takes a while for people to assimilate that, and it takes a while for vendors to actually get people to buy [the new instruments.]"
Among the major mass spec firms, AB Sciex led the way in terms of new instruments, launching its new TripleQuad 6500 and QTRAP 6500 machines, both of which, the company said, offer up to 10 times the sensitivity of its 5000 TripleQuad and QTRAP instruments.
AB Sciex also released the TripleTOF 5600+, an upgraded version of its original TripleTOF instrument that incorporates the company's Swath data-independent acquisition technique (PM 6/10/2011).
Shimadzu likewise launched new triple quadrupole instruments this week, releasing its mid-range LCMS-8040 and high-end LCMS-8080 triple quads, which the company said offer, respectively, up to five and 30 times the sensitivity of its existing LCMS-8030 machine.
New MALDI instruments also made a showing, with Bruker releasing an updated version of its ultrafleXtreme MALDI-TOF/TOF instrument, which, the company said, brings the speed of the platform up to a two kHz repetition rate.
Mass spec startup Simultof Systems announced the launch of three new MALDI mass specs, as well – the SimulTOF 100 Linear system, the two-stage reflector SimulTOF 200 system, and the TOF-TOF SimulTOF 300 Tandem system. The releases, which sell for $175,000, $280,000, and $425,000, respectively, are the company's first commercial products.
According to Marvin Vestal, Simultof's founder and chief science officer, the instruments represent an advance in MALDI mass spec technology in that they provide simultaneous space and velocity focusing to reduce the effects of ions' initial position and velocity, enhancing resolution and sensitivity. He told ProteoMonitor that the company will initially target primarily high-level researchers with an aim toward applications such as pathogen detection and imaging mass spectrometry.
Rounding out the week's instrument releases, Waters and Thermo Fisher Scientific each launched modest additions to existing lines. Waters introduced its new Xevo G2-S QTof and Xevo G2-S TOF machines, a pair of benchtop devices incorporating the company's StepWave ion optics technology; while Thermo Fisher released its new Exactive Plus system, an expanded version of the company's Exactive instrument that can be upgraded to its Q Exactive machine.
Perhaps more than new instruments, though, vendors focused on new mass spec informatics tools and, in particular, on tools to enable researchers to pull together data and develop experiments across a variety of -omics platforms.
Agilent, for instance, cited its recently released GeneSpring 12.0 software, with Gustavo Salem, vice president and general manager of the company's Biological Systems Division, highlighting the product's ability to do "multi-omics" analysis.
He noted a recent collaboration between Agilent and University of Washington researcher Mike MacCoss that combined GeneSpring with MacCoss's Skyline SRM-MS software to allow researchers to automatically generate SRM assays for target proteins identified via other -omics studies.
For instance, Salem said, a researcher might identify via genomics and metabolomics that a process of interest is linked to the Erk signaling pathway. The researcher could then, via GeneSpring, have "that pathway imported into Skyline, have Skyline then tell you what proteins are known to interact with your pathway, and then have it actually give you back the specific conditions to run the targeted proteomics experiment."
Waters likewise focused on multi-omics tools, announcing the release of its new TransOmics Informatics software, which it developed in collaboration with UK bioinformatics firm Nonlinear Dynamics. The software, which was developed for use with Waters' Acquity UPLC I-Class or nanoAcquity UPLC chromatography systems and its Synapt mass spec instruments, is intended to integrate proteomic, metabolomic, and lipidomic data, facilitating work in "the pharmaceutical and life sciences research industry as well as academia" and "in research areas such as biomarker discovery and validation," said Brian Smith, Waters' vice president of mass spectrometry operations.
Thermo Fisher also introduced a variety of new bioinformatics packages, including an expanded suite of software for use with the company's Q Exactive instrument.
The emphasis on software, suggested Proteome Sciences' Pike, whose company has a licensing deal with Thermo Fisher for its Tandem Mass Tag reagents, stems from a growing understanding that the ability to integrate and interpret mass spec data is perhaps lagging behind the field's ability to generate it.
"Really the bioinformatics stuff is going to be the next frontier we have to get through," he said. "We're generating all this really complex sophisticated data on what's changing on proteins. But building that information on a single peptide, on a post-translational modification, into a network, into a pathway, into biological relevance, is the real stuff we're going to struggle with."
Keeping an Eye on the Clinic
Of course, the point of this emphasis on biological relevance is, in large part, to move proteomics into the clinic. And while the week saw some pessimism regarding proteomics' clinical potential (see story this issue), several of the big vendors asserted their ongoing commitment to clinical mass spec.
Agilent "absolutely sees a huge market opportunity for mass spec in the clinic," Salem said during the company's media presentation. He noted that while Agilent's impending acquisition of cancer diagnostics firm Dako (GWDN 5/17/2012) does not necessarily offer a new channel for the company to move its mass spectrometers into the clinic, Dako does offer valuable "regulatory capability and leverage" that will aid the company's move toward clinical mass spec.
Rohit Khanna, Waters' vice president of worldwide marketing, cited his company's commitment to clinical mass spec, noting that it had registered with the US Food & Drug Administration as Class I exempt medical devices its Acquity UPLC, Acquity TQD, Xevo TQ, and Xevo TQ-S instruments.
And, AB Sciex president Rainer Blair reiterated the company's intentions to obtain European and US regulatory clearance for certain of its mass spec instruments (PM 3/16/2012).
"We haven't announced which platform we're going with yet, but as per our announcement, we're on time," he said. "We'll be entering the European market first with a CE IVD mark, and that will likely happen in the first quarter of 2013. Subsequent to that we will be working on the necessary 510(k) approvals for the entry into the US market."
Bruker continues to pursue clinical ambitions, as well, most notably with regard to its MALDI Biotyper device for pathogen detection. The company has thus far placed roughly 500 of the instruments globally and hopes to obtain 510(k) approval for the device by the end of this year.
Bruker is also working to push MALDI into the clinic as a platform for protein biomarker detection, a purpose for which MALDI has drawn increasing interest in recent years (PM 1/20/2012). The company sees the platform's high throughput as a potentially key advantage in the clinical space, said Detlev Suckau, Bruker's head of proteomics R&D.
To validate [biomarkers] you need really big numbers, he told ProteoMonitor. "So I think MALDI immunoassays provide access to those big numbers to be processed in a reasonable time."
Imaging Mass Spec Gains Ground
MALDI is also a key platform for mass spec imaging – another area of emphasis for vendors at ASMS this week. MALDI imaging – which allows researchers to map and identify proteins and metabolites in tissues – remains beset by various technical issues, particularly in terms of informatics. However, a number of firms highlighted the technique, suggesting its growing practicability.
"I think the imaging application is one that is really developing very fast," Vestal said, adding that he expects SimulTof's new machines to be particularly well-suited to the task due to their high speed and sensitivity. The company has been working with Vanderbilt researcher Richard Caprioli, a leader in imaging mass spec, who, Vestal said, has two of its machines in his lab.
According to Frank Laukien, Bruker's CEO, increased interest in imaging mass spec "is driving a resurgence of MALDI for both MALDI FT-MS and MALDI TOF and MALDI TOF-TOF."
"Spatial proteomics – retaining biological information in tissues and cells – which is incredibly important, is driving MALDI," he said.
Data processing remains a challenge for MALDI imaging, Suckau told ProteoMonitor, noting that "the data sets are huge, so if you get into clinical discovery work where you need to work with sample cohorts you are easily talking about [hundreds of gigabytes]."
"But," he added, "[Bruker] is trying to address that by simplifying the data structure, reducing the size of the datasets without reducing the content of the data."
Bruker this week introduced its new ImageID workflow for identifying peptides via mass spec imaging, including in formalin-fixed tissue. Waters also released imaging mass spec software – its High Definition Imaging product, which the company said is designed for use with its Synapt G2-S instrument and offers a fully integrated suite for MALDI imaging research.