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Thermo Releases New Fusion Mass Spec, Combining Quadrupole, Ion Trap, and Orbitrap in One Instrument

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This story has been updated to include comments from an early access user.

Minneapolis -- Thermo Fisher Scientific has introduced a new mass spectrometer that combines in one device a quadrupole for precursor selection with both an Orbitrap and ion trap mass analyzer.

Named the Orbitrap Fusion Tribrid, the instrument, which the company launched this week here at the American Society of Mass Spectrometry annual meeting, is the first to feature such a configuration of components and, according to one leading researcher, could enable significant improvements in the depth and speed of proteomics experiments.

Calling the release the biggest advance in Thermo Fisher's mass spec offerings since the company launched its original Orbitrap device in 2005, University of Wisconsin-Madison researcher Joshua Coon – an early-access user of the new machine and a frequent Thermo Fisher collaborator – told ProteoMonitor that he expects that within months of its launch the proteomics community would "see people detecting and quantifying more proteins than anyone has ever done before."

Coon said that in his time with the Fusion, his lab had been able to identify two to three times more peptides than they could using Thermo Fisher's previous top-of-the-line instrument, the Orbitrap Elite.

The improved performance, Coon said, stems from a combination of factors including increases in speed and resolution as well as the multiple-analyzer configuration. That configuration, according to Ken Miller, Thermo Fisher's vice president of marketing, life sciences mass spectrometry, is designed to allow various aspects of the mass spec proteomics workflow to proceed in parallel.

"The operation of the system is highly parallelized, so that you don't pay a real-time penalty for taking advantage of [the system's multiple components]," Miller told ProteoMonitor. "For instance, you can be isolating ions with the quadrupole and sending them to the ion trap, and while that is taking place you can isolate, fragment, and be scanning with the Orbitrap."

"We put it together in a way that allows you to use all of these aspects of the system very efficiently, so you can do experiments you have never been able to do before because you have access to all these elements and [can use them] in a way that is very efficient."

The system's quadrupole allows for precursor selection at isolation widths down to 0.4 amu. Its dual-pressure linear ion trap, which is preceded by an ion routing multipole, enables CID and ETD fragmentation and scan rates of up to 20 Hz. The Orbitrap analyzer, meanwhile, offers resolution in excess of 450,000 and scan rates up to 15 Hz. This almost doubles the resolution of the Orbitrap Elite, which maxes out at 240,000.

"You can imagine doing in half a second a 240,000 [resolution] precursor scan in the Orbitrap, and while that is going on at the same time doing 10 data-dependent MS/MS experiments [in the ion trap]," Miller said. "So that means that in one second you could do two 240,000 precursor scans and 20 data-dependent MS/MS [scans] – so many more rich, productive, sequencing attempts than were previously possible."

He cited as an example of research enabled by the technology early-access work by Harvard University researcher Steven Gygi using the Fusion for MS3 quantitation using isobaric tags.

Isobaric labeling uses stable isotope tags attached to peptides of interest to enable relative or absolute quantitation of proteins via tandem mass spectrometry. Digested peptides are labeled with tags that fragment during MS2 to produce signals corresponding to the amount of peptide present in a sample.

However, precursor interference problems can lower the accuracy and precision of the quantitative data obtained through isobaric tagging, a drawback that has hampered the technology's adoption (PM 10/14/2011).

Gygi has attacked this problem by adding a third stage of mass spectrometry to the process, selecting a target ion produced in MS2 for a further round of isolation and fragmentation to produce an MS3 spectra, essentially adding an extra layer of purification before analyzing the target ions.

The method has proven successful in reducing precursor interference, but the extra scan time required by the MS3 analysis significantly reduces the number of peptides the mass spec is able to measure.

According to Gygi, the increased speed and capabilities of the Fusion will help mitigate this problem.

"With the new instrument configuration of the Orbitrap Fusion, the duty cycle is greatly improved," he told ProteoMonitor. "Because the instrument carefully balances ion injection time with ion analysis, the vast majority of the ion beam is utilized in the scan cycle. This translates into improved sampling speed and depth."

"The architecture of the Fusion allows the events of ion accumulation and analysis to run in parallel," Gygi said, noting that because of this "the large time penalties associated with this [MS3]method are largely negated."

He added that beyond aiding his lab's MS3 approach to isobaric tagging, the Fusion would prove particularly useful for analysis of low abundant proteins.

"Ion transmission and manipulation efficiency are greatly improved with this instrument," he said. "Coupled with the more efficient use of the ion beam, we expect [it] will push the lower limits of detection. As such, we think it will be a superb platform for analyzing low abundance ions."

Coon said he thought that the release of the Fusion would render a number of his lab's instruments "obsolete."

"I think what we saw when we tested [the Fusion] was that it was so much better than what we currently have that I immediately recognized that we have to come up with the resources to figure out how to switch over our [current mass spec] technologies," he said.

Coon added that he anticipates interest in the machine would extend beyond expert mass spec labs like his to a wide swath of users including novice users and applied researchers.

"It's my expectation that interest in this system won't be limited to expert labs that want to be on the cutting edge," he said. "I think it has broad appeal because it is just such a step ahead – any experiment you want to do I think it is just going to do it better. The only limit to placement in labs will be can people come up with the resources to buy them?"

Thermo Fisher declined to say what the new instrument would cost. Miller did note that with the release of the Fusion, the Orbitrap Elite would likely see a price cut.

The company plans to begin shipping the Fusion by the end of June.

Thermo Fisher also introduced two new triple quadrupole instruments at this week's ASMS meeting. The two systems, the Thermo Scientific TSQ Quantiva and the Thermo Scientific TSQ Endura, represent the company's first foray into this space since the release of its TSQ Vantage machine in 2008.

The higher-end model of the pair, the Quantiva features an ion funnel as well as Thermo Fisher's active ion management system and, according to the company, can perform as many as 500 selected-reaction monitoring experiments per second. The Quantiva shares common source housings and software with the Orbitrap Fusion with the instruments designed for plug-and-play exchange and automatic transfer of methods between the two.

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