In an effort to increase the resolution and mass accuracy of its ion trap mass spectrometers, Thermo Finnigan is developing hybrid ion trap instruments with time-of-flight or Fourier transform mass analyzers connected to the back end of an ion trap, Thermo Finnigan President Ian Jardine told ProteoMonitor last week.
While Jardine staunchly defended the capabilities of ion trap mass spectrometers against the suggestion that Q-TOF instruments are better suited to the analysis of complex mixtures of peptides, he said that Thermo hoped to narrow the lead that Q-TOFs currently have over ion traps in their ability to distinguish between peptides of similar mass. The new instrument is at least 12 to 18 months from reaching the market, Jardine said.
“We’re looking at making alternative arrangements of these technologies to perhaps even further advance the analytical capabilities [of ion traps],” he said. “One of the combinations that one can imagine is that you could add another mass spectrometer type on to the back end of an ion trap, and that would certainly improve the size, cost, and complexity, but it could also add potential capability. TOF and FT/MS are the most obvious ones.”
But Jardine said that the incremental advantages in performance that such a hybrid would provide would have to be carefully weighed against the concomitant increase in cost. “That’s one of the things we’re considering quite carefully if we’re going to build a hybrid type machine and put one of these additional analyzers on it,” he said. “We would want to make sure that the incremental advantage analytically is well worth [the higher price]. We think it would be.”
Thus far, Thermo’s attempts to serve the proteomics market have most prominently taken the form of adding software and front-end separations packages to appeal to researchers who prefer integrated systems for separating digested proteins and identifying their masses and amino acid sequences. Indeed, rather than compete with Bruker Daltonics and Applied Biosystems to build high-end MALDI-TOF/TOF systems, the San Jose, Calif.-based subsidiary of Thermo Electron has recently released packages such as a combined LC/MS ion trap system, called ProteomeX, that utilizes the MudPIT technology and other algorithms for identifying proteins and matching their sequences to databases.
And Thermo is busy adding additional such separations and software capabilities to its mass spectrometers. Jardine said the company has developed software compatible with the ICAT reagent technology, as well as newer methods for quantifying the differential expression of proteins, such as a method called AQUA, developed by Steven Gygi, an assistant professor in the department of cell biology at Harvard Medical School.
Unlike the ICAT technology, which can measure changes in protein expression relative to another sample, the AQUA experiment, short for “absolute quantitation,” relies on internal standards to allow more accurate measurement of protein expression levels. Gygi and his colleagues have yet to publish on the details of the method, but used the technique in experiments published in the journal Cell in December to measure the amount of phosphorylated and nonphosphorylated separase protein during the HeLa cell cycle. Gygi and his colleagues have filed a patent on the AQUA technique.
Thermo Finnigan is also planning to use Thermo Electron’s recent acquisition of CRS Robotics to enhance its front-end offerings for mass spectrometers targeted at proteomics. One such system launched last week at Pittcon, the MALDI-ion trap mass spectrometer, could potentially benefit from closer collaborations with the robotics company, said Bill Hancock, a vice president and general manager for proteomics at Thermo Finnigan. “That plays very nicely into robotics, but it’ll take a little time to develop a product,” he said.