While it’s a fairly widely held assumption that a protein analysis and identification facility should include a range of both high- and low-end mass spectrometers, the constantly shifting seas of mass spectrometry technology can sometimes create quandaries for proteomics researchers seeking to find the right balance between price, reliability, and optimal performance.
These days, scientists in the field speak with anticipation of the days when high-end instruments such as the MALDI-TOF/TOF will one day prove themselves cost-effective. But beneath that swell of expectation lies an undercurrent: for proteomics experiments involving the analysis of complex mixtures of peptides, has the cost of Q-TOF technology dipped to the point where ion traps are no longer necessary?
A preliminary view of the data might make one think so. Looking back to November 2000, Caprion Pharmaceuticals opted to ally itself with Micromass, partly to access its Q-TOF technology. In recent months both GeneProt and Beyond Genomics chose to invest heavily in Q-TOFs for LC/MS applications that ion traps could also have served. Purely on a cost comparison, Micromass’ Q-TOF micro costs around $300,000, compared to $180,000 for a Bruker Daltonics Esquire 3000 ion trap.
Certainly, Micromass is eager to point to its improvements over the last few years in software, thermal stability, and reductions in laboratory footprint — not to mention price and superior performance — as reasons why researchers in proteomics labs would lean towards its Q-TOF technology. “What is changing now is that Q-TOFs are getting smaller, the software that’s going on to them is making them far more usable by non-mass spectrometrists, if you like, and the price dynamic has changed,” said Mark McDowall, marketing manager for Micromass.
And many scientists would agree that today’s Q-TOFs exceed the ion traps on the market in terms of resolution. Despite the incentive from Micromass in the form of a $7.5 million equity investment, Caprion chose Micromass’ Q-TOF technology because “we just wanted the best performing instrument that will deliver the information on a regular basis,” said Pierre Thibault, director of protein analysis at Caprion. “The choice we clearly made from the outset was not to compromise the type of information that we’d be generating because of the instrument capability.”
Even staunch supporters of ion trap technology admit that it has certain advantages. The improved resolution on a Q-TOF means researchers are able to differentiate between different peptides that might seem to have the same mass on another instrument, said Don Hunt, a protein mass spectrometrist at the University of Virginia with ties to MDS Proteomics. “And if you know the mass of your peptide accurate to three decimal places, the number of things you have to search [in a database] is less than if you know your mass only to point five, which is what the ion traps do,” he said. “So you would shorten your search time.” This improved mass accuracy is important, other researchers said, because it makes searching poorly annotated databases more efficient.
But these advantages don’t necessarily mean the ion trap will fade away. Nor in the cases of GeneProt’s and Beyond Genomics’ acquisitions of Q-TOF technology is the situation as clear cut as that of Caprion. GeneProt’s deal with Micromass’ parent Waters to purchase $20 million in HPLC and Q-TOF technology was accompanied by a $10 million equity investment in GeneProt, and the company’s purchase of MALDI-TOF/TOF technology from Bruker Daltonics last November may have reduced the number of samples necessary to analyze with LC/MS/MS, said John Wronka, vice president for Bruker Daltonics. Nevertheless, in an interview last fall, GeneProt chief scientific officer said the company chose Q-TOFs to take advantage of new technology with improved capabilities.
In the case of Beyond Genomics, the company’s purchase of Q-TOF technology from Micromass also came hand-in-hand with a “non-trivial” equity investment in Beyond Genomics, according to McDowall of Micromass. Steve Naylor, chief technology officer for Beyond Genomics, said he saw no evidence of a general trend away from ion traps in most proteomics labs, but he admitted that given an unlimited budget for mass spectrometry equipment, there would be no reason not to purchase Q-TOF technology over ion traps.
But diehard ion trap users such as U.Va.’s Hunt claim the technology won’t be going anywhere, particularly with new ion trap technology that vendors may introduce to the market within 12 to 18 months. Although Hunt declined to go into specifics, he said “I know for a fact that what’s coming down the pike are [ion trap-like instruments] that are superior to the Q-TOFs.” Furthermore, Hunt believes the ion trap mass spectrometers currently on the market have “much more sophisticated” software than the Q-TOFs.
But there’s little doubt that the argument is relevant. For academic users, the lower price tag attached to an ion trap may always be the deciding factor, but for high-end industrial users, such as Jay Boniface, senior director of protein science and proteomics at Myriad Proteomics, who is weighing his options before making a major equipment purchase, the choice between the two technologies is real.
“For GeneProt to industrialize the Q-TOF is interesting,” he said. “One of the reasons we’ve delayed the development of our [LC/MS platform] is because we wanted to wait to do a little bit more thorough job of distinguishing between a Q-TOF style instrument and an ion trap.”