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Thermo Fisher Launches Two New Mass Specs at HUPO, Including Updated Version of Q Exactive

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Thermo Fisher Scientific will launch two new mass spectrometers next week at the Human Proteome Organization's 12th annual meeting in Yokohama, Japan, including an updated version of its popular Q Exactive system.

This instrument, the Q Exactive Plus, features enhancements to its ion transmission that will enable more sensitive peptide and protein quantitation as well as improved data independent acquisition-based workflows, Andreas Huhmer, proteomics marketing director at Thermo Fisher, told ProteoMonitor.

The second release is the company's Exactive Plus EMR, which offers an extended mass range of up to 20,000 m/z and is aimed at the biopharma market, Huhmer said.

The two instruments mark the fourth and fifth new mass spec releases from Thermo Fisher in the last four months, following on the company's launch of its Orbitrap Fusion, TSQ Endura, and TSQ Quantiva instruments at this year's American Society of Mass Spectrometry annual meeting in June (PM 6/14/2013).

Introduced at the 2011 ASMS meeting, the original Q Exactive was the first of the company's instruments to combine a quadrupole for precursor selection with an Orbitrap analyzer (PM 6/10/2011). Designed to help Thermo Fisher compete in the roughly $250 million Q-TOF market, the system has proved a hit. During a presentation this week at the Morgan Stanley Healthcare Conference in New York, President and CEO Marc Casper called the machine a "blockbuster," noting that since it began shipping at the end of 2011 it has "far eclipsed" $100 million in sales.

The Q Exactive Plus, Huhmer said, builds on the original machine by incorporating improved technologies for improving quadrupole precursor selection and managing transmission of ions through the instrument.

"The request that we got from customers is that they were sensitivity limited," he said. "A lot more people are using the Q Exactive for [protein] quantitation, and one of the benefits of the Orbitrap technology is that you can accumulate ions of interest even if they are very low abundance. So what [customers] would really like to do is collect more of those low abundance proteins for quantitation."

The enhanced ion transmission should also improve the Q Exactive Plus' utility in data independent acquisition workflows, Huhmer said, noting that "if you have better transmission and very uniform transmission across the mass range [you are examining], data independent acquisition methods will benefit tremendously."

Indeed, in past interviews, researchers including the University of Washington's Michael MacCoss and the Buck Institute's Brad Gibson have suggested to ProteoMonitor that one significant reason for the success of AB Sciex's TripleTOF 5600+-based Swath DIA methodology is the uniformity of that system's ion transmission (PM 6/8/2012).

According to Thermo Fisher, the Q Exactive Plus will also need less frequent maintenance than the original version of the instrument due to its Advanced Active Beam Guide feature. While this, Huhmer said, is something of a minor enhancement compared to the ion transmission improvements, reduced maintenance would likely prove a boon for many customers, as, despite the Q Exactive's popularity, it has drawn criticism for the amount of cleaning its quadrupole requires.

The new Exactive Plus EMR (extended mass range) instrument also targets the Q-TOF market, albeit a different segment. Intended for analysis of native proteins and protein complexes, the instrument could prove useful for the characterization of biotherapeutics, a space that Q-TOFs have traditionally dominated.

Thermo Fisher developed the instrument via a collaboration with Utrecht University research Albert Heck who, Huhmer said, was interested in using Orbitrap-based instruments for studying protein complexes "and how they potentially interact with other proteins in a native state."

In a 2012 Nature Methods paper, Heck and Thermo Fisher researchers demonstrated the use of a modified Exactive instrument to analyze a range of targets including native IgG antibodies, bacteriophage HK97 capsid pentamers and hexamers, yeast 2OS proteasome, and Escherichia coli GroEL (PM 10/19/2012).

At the time, Heck suggested to ProteoMonitor that, given the potential of the modified Exactive for biopharmaceutical research and characterization, Thermo Fisher might look to offer the modified version of the instrument as a discrete product aimed at "the analysis of intact proteins and glycoproteins and other heavily post-translationally modified proteins."

One year later, his hunch appears to have been borne out.

"If you think about the development of biopharma, for the last 10 to 12 years they've kept telling us: 'Peptide mapping is ok. We use your instrument. But really we don't want to touch those [biopharma] products, because every time we touch them – say in a trypsin digestion – we know we are introducing artifacts," Huhmer said.

"They were very interested in characterizing these products, typically antibodies, in their intact states," he added. "And we have made a lot of progress in the last few years enabling this. But then, of course, if you want to study the more modern drugs, which are typically antibody-drug conjugates, then for that actually you have to study the complex in its native state, and that is a different challenge. And that is why we developed the [Exactive Plus] technology."

When proteins are introduced into a mass spectrometer at neutral pH in a native state they don't retain as many charges, meaning that they often move in m/z ranges higher than can be measured with a conventional Orbitrap, Huhmer said. To account for this, the company optimized the instrument's ion optics to extend its mass range, allowing for analysis of molecules ranging from 350 to 20,000 m/z.

In addition to biopharma, the instrument has also received interest from academics looking to study large protein complexes that are difficult to characterize via X-ray crystallography or NMR, he said.

Thermo Fisher declined to disclose pricing for the new systems. The original Q Exactive sells for around $400,000.

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