This story originally ran on June 6.
DENVER — With the release of its new Q Exactive mass spec instrument at this week's American Society of Mass Spectrometry annual meeting here, Thermo Fisher Scientific is "going directly after the Q-TOF market," Ian Jardine, the company's vice president of global R&D, told ProteoMonitor.
The instrument, which combines a quadrupole for precursor selection with an Orbitrap mass analyzer, represents Thermo Fisher's first entry into the $250 million Q-TOF market.
While not a traditional Q-TOF in that it uses an Orbitrap instead of a time-of-flight device for mass analysis, the Q Exactive is "fundamentally conceptually equivalent to a Q-TOF," Jardine said, noting that the company plans to market the device to proteomics researchers for applications like peptide sequencing commonly done on Q-TOF machines.
"People buy Q-TOFs for both small-molecule work like drug metabolism as well as for peptide and protein work, so we're targeting both of those [applications]," he said. He added that "the price on the instrument will be extremely competitive compared to Q-TOFs."
The Q Exactive is essentially a modified version of Thermo Fisher's Exactive benchtop Orbitrap instrument but with a quadrupole up front for MS/MS workflows. The machine "is going to be a pretty tough comparison for Q-TOFs," Jardine predicted, citing in particular its resolution, which, at 140,000 FWHM in full-scan mode and maximum scan speed, is roughly three times higher than that of the typical Q-TOF, he said. It's also a jump from the original Exactive, which offers resolution of 100,000 FWHM.
The Q Exactive improves over the Exactive in terms of speed, as well, offering double its scan speed. It also allows for up to ten precursor ions to be collected and stored for simultaneous detection in the Orbitrap, which will also increase the machine's throughput, Jardine noted.
Additionally, the instrument offers high collision dissociation, or HCD, fragmentation, which, he said, will be useful for multiplexed experiments using isobaric tags like the Tandem Mass Tag reagents the company offers through its license with proteomics firm Proteome Sciences.
Going after the Q-TOF market "has always been [Thermo Fisher's] intention," Jardine said. "It's just taken us this amount of time to get this particular Q-Orbitrap out there."
The company also released this week a new faster, more sensitive ion trap machine, the Thermo Scientific Velos Pro, and a new Orbitrap hybrid, the Orbitrap Elite.
The Velos Pro offers scan speeds of up to 66,000 Da/sec – roughly double that of the current LTQ Velos machine – as well as linear quantitation of up to six orders of magnitude, which will help prevent the instrument from becoming saturated during peptide quantitation work, Jardine said. Like the Q Exactive, the Velos Pro also features HCD fragmentation capability, which will similarly improve its utility for isobaric tagging experiments.
The Orbitrap Elite, which combines the Velos Pro ion trap with a new high-field Orbitrap, represents a roughly four-fold improvement in resolution compared to previous Orbitrap hybrid machines, featuring a maximum resolving power at 1 Hz of 240,000 FWHM – a level that previously has been obtainable only with Fourier transform ion cyclotron resonance instruments, Jardine said.
The machine also offers a four-fold improvement in scan speed compared to previous Orbitraps, a factor that's particularly significant given that Orbitraps have long been thought at a disadvantage to TOF machines when it comes to speed.
While asserting that TOF's perceived advantage in this regard is "a little bit smoke and mirrors," Jardine noted that this jump should help the company make the argument for the Orbitrap from a speed perspective.
"We would argue that in fact we've now gone way ahead of what time-of-flights do," he said. "If you ran the Orbitrap [Elite] at the same resolution – let's say you dropped the Orbitrap [Elite] resolution down to 30,000 [FWHM], which is a normal resolution for a time-of-flight, then we would [scan] roughly 8 to 10 spectra per second, which is actually quite a bit faster than most time-of-flights."
The Orbitrap Elite is aimed primarily at high-end proteomics researchers, Jardine said. "These are really proteomics advances. The increase in resolution and the increase in scan speed basically mean that if you want to use, for example, the collision cell before the Orbitrap to fragment and record the fragments at high resolution and accurate mass, then it means that that experiment – which of course gives you much more accurate product ion spectra – you can do at either much higher resolution and mass accuracy or you can do much faster, which means many more peptides analyzed per unit time."
In addition to peptide-based experiments, the Elite is also particularly well-suited to top-down proteomics work analyzing intact proteins, Jardine said. FT-ICR machines have been widely used for this sort of research because of their high resolution. At 240,000 FWHM, the Elite offers similar capabilities while retaining the Orbitrap's relative simplicity of operation.
"As you go through larger and larger proteins and you fragment many complex molecules that have many charges on them from electrospray, the resulting product ions are extremely complex," he said. "So the more resolution you have in the product ion spectrum, the easier [it is] to interpret those complex spectra in terms of the fragmentation of the intact proteins."
"If you're at all interested in looking at much bigger peptides or protein fragmentation by top-down [proteomics], then you would want to get this instrument," he added.
All three machines, the Q Exactive, Velos Pro, and Orbitrap Elite are currently shipping, Jardine said. The company did not disclose pricing for the new instruments.
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