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Triple Quads Take the Stage at ASMS 2013 as Vendors Continue Piecing Together Clinical MS Platforms

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Minneapolis – Thermo Fisher Scientific made a splash at this week's American Society of Mass Spectrometry annual meeting with the launch of its hi-res Fusion instrument (see story this issue), but that aside, much of the vendor action was focused on the low-res triple quadrupole end of the market.

Most notably, Bruker and Thermo Fisher released new triple quadrupole machines, with Bruker launching its EVOQ Elite ER triple quad and Thermo Fisher its TSQ Endura and TSQ Quantiva machines.

The EVOQ Elite ER is an expansion of Bruker's EVOQ triple quad line, which the company launched at the 2012 Japan Analytical Scientific Instruments Show in September (PM 9/7/2012). That launch marked Bruker's entry into the LC triple quad market. The EVOQ ER instrument expands the line's mass range up to 2,000 m/z, making it suitable for applications including peptide quantitation.

Thermo Fisher's TSQ Endura and Quantiva instruments, meanwhile, represent the company's first new triple quad offerings since the release of its TSQ Vantage machine in 2008. The Endura is intended as a workhorse instrument, providing equivalent sensitivity to the company's existing Vantage model. The Quantiva is a higher-end offering, featuring Thermo Fisher's new active ion management system, which, the company said, enables it to achieve roughly 10 times the sensitivity of the Vantage. Both instruments can perform up to 500 selected-reaction monitoring assays per second.

The new triple quads are aimed at helping both companies compete in the applied markets business, one of the fastest growing segments in mass spec. During AB Sciex's press event this week, Rainer Blair, the company's president, noted that the applied space currently makes up roughly one third of the LC-MS market and is growing annually at double-digit rates.

Applied markets typically include areas like food safety and pesticide and toxicology screening as well as clinical diagnostics, including protein and proteomic diagnostics. The clinical component, Blair said, still has a number of hurdles to overcome, such as securing necessary approvals from regulatory bodies like the US Food & Drug Administration and driving clinician adoption. Ultimately, however, this space has the highest growth potential of all the applied markets, he said, noting that "in terms of the adjacencies with the greatest potential over time, [the clinical market] is the one that certainly, we're focused on."

Indeed, AB Sciex was one of several vendors presenting additions or enhancements to their clinical mass spec workflows. The firm this week formally announced a collaboration with its Danaher stable mate Beckman Coulter developing that company's Biomek lab automation platform for use in sample prep for clinical mass spec assays.

The Biomek platform is well-suited "for preparing samples for the proteomics space," said Dave Hicks, vice president and general manager of AB Sciex's pharma and academic business, adding that it could enable the sort of high-throughput mass spec workflows required for verification, validation, and, ultimately, clinical implementation of protein biomarkers.

With the integration of the Biomek platform, AB Sciex feels it now has all the components required for a clinical proteomics workflow, Hicks told ProteoMonitor. "We have Class I medical device registration [on the company's 3200MD and 3200MD QTRAP instruments], automation on the front end, the appropriate LC on the front end, [and] software," he said. "We believe that we're as well positioned as anyone."

Arguably, Agilent has been the leader in terms of putting together a complete workflow for clinical proteomics, collaborating with protein diagnostic firms like Integrated Diagnostics, Applied Proteomics, and Sera Prognostics on developing mass spec platforms on which they can bring their tests to market.

The company was relatively quiet in terms of new releases this week, but it did present several smaller offerings that could prove of use in its clinical proteomics platform. Specifically, it introduced its StreamSelect LC/MS system consisting of two 1200 Series LCs coupled to a 6400 triple quad – a configuration that could enable improved throughput in protein quantitation assays where LC separation is required.

Agilent also launched a new version of its RapidFire system, the RapidFire 365 mass spec system, which, the company said, can run unattended for up 60 hours, enabling more than 20,000 injections. A high-throughput chromatography system that enables processing and injection of samples into mass spectrometers at rates as fast as one per every seven seconds, the RapidFire is a key component of Agilent's clinical mass spec platform.

Like Agilent and AB Sciex, Thermo Fisher has been piecing together workflows for mass spec-based clinical proteomics, with much of its effort revolving around its mass spec immunoassay, or MSIA, technology. However, as Ian Jardine, Thermo Fisher's vice president of global R&D, told ProteoMonitor this week, the company's lack of a top-of-the-line triple quad has been a frustration for its efforts in this area.

"What we would find was that we would be selling Orbitraps [for discovery work] into labs, especially proteomics labs, and then they would want to transition their discovery into high-throughput quantitation and they would go buy a triple quad from somebody else," he said. "So we needed a better triple to ensure that they stayed with us across that entire discovery-applied [proteomics] cycle."

According to Jardine, Thermo Fisher plans this year to register the Endura as a Class I medical device, clearing its way for use in clinical markets. "There's tremendous interest in mass spectrometry moving into clinical applications," he noted.

And while the bulk of that interest has revolved around triple quad-based SRM assays, Jardine suggested that high-resolution machines like Thermo Fisher's Orbitraps and other vendors' QTOFs could make their way into the clinic for protein assays, as well.

"I think in the clinic for small molecules, triple quads will be the way to go, and for peptides and proteins it will be a mix of triples and high-resolution accurate mass systems," he said. He added that, given this, the company would likely in the future register some of its Orbitrap instruments as Class I medical devices, noting that the Q Exactive and Exactive machines were the likeliest candidates.

With regard to Thermo Fisher's renewed efforts in the triple quad space, Jardine said the company hoped to use the popularity of its Orbitrap instruments to drive sales of its triple quads. In particular, he noted, it has taken care in its software development for the new systems to ensure easy method transfer from Orbitraps to the triple quads.

AB Sciex leads in triple quad market share with Agilent second and Waters third. Between them, these three companies own roughly 90 percent of the triple quad market, presenting a challenge for Bruker and Thermo Fisher and their new pushes into this space.

"We'll pick our spots and try to leverage our discovery platform" to gain market share, Jardine said. "We're certainly not going to go into a pharma bioanalysis lab that has 10 [AB] Sciex [instruments] and say, 'Hey, we've got a better triple quad for that application.' Because they're just going to tell us to go away."

Rohan Thakur, vice president of Bruker's quadrupole MS business, told ProteoMonitor that he believes his company's software offerings would help set its EVOQ instruments apart, citing, in particular, its Pacer quantitative analysis software.

Jardine noted, as well, the potential opportunity for gaining share in geographies and applications where the major triple quad players are less entrenched. Mass spec-based clinical diagnostics – still being very much in a nascent phase – would be one such area. "I think you'll see from us in the near future some very nice developments in the clinical area," Jardine said.

Beyond the triple quads and clinical talk, ion mobility technology also made a significant showing, with Agilent, AB Sciex, and Waters all touting additions in this area.

Agilent introduced a new drift ion mobility system for use with its iFunnel QTOF system. AB Sciex, meanwhile, expanded its Selexion ion mobility technology – which it first introduced in 2011 as part of its 5500 series instruments – to its TripleTOF 5600+ instrument. And Waters released its Synapt G2-Si mass spec, which, the company said, adds another parameter for ion identification by integrating collision cross-section information determined via the company's T-wave ion mobility separations.

The ASMS meeting also saw the release of a new high-resolution machine from Bruker, the Impact HD QTOF, an instrument the company said is aimed at the proteomics and protein biomarker market. Featuring Bruker's Captivespray Nanobooster ionization system for noise reduction, the system offers five orders of dynamic range and in an analysis of HeLa cells performed by the company identified roughly 8,500 proteins at a false discovery rate of less than 1 percent.