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After Working with MDS, Thermo Opts To Commercialize Hybrid Trap-FT/MS

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To proteomics researchers, Thermo Finnigan might be best known for its robust and relatively inexpensive ion trap mass spectrometers. But now the San Jose, Calif.-based manufacturer has decided to use the ion trap as a stepping stone to the next level of competition in the booming market for mass spectrometers in proteomics. Last week, Thermo announced that it would commercialize a hybrid ion trap/Fourier transform mass spectrometer that it has helped MDS Proteomics install and develop at its headquarters in Toronto.

As ProteoMonitor reported in March, Thermo has had designs on a hybrid ion trap instrument, but at the time Thermo Finnigan President Ian Jardine did not clarify whether this hybrid would include a time-of-flight (TOF) or FT/MS mass analyzer. But given Thermo’s long-standing relationship with Don Hunt, a protein mass spectrometrist at the University of Virginia and a consultant to both Thermo and MDS, it follows that FT/MS would be the logical choice.

While Thermo isn’t planning to launch the new hybrid instrument — at a cost of about $650,000 — until the second half of 2003, it has the potential to vie for market share with both the FT/MS instruments currently on the market from Bruker Daltonics and IonSpec, and the high-end MALDI-TOF/TOF instruments that have become available in the last six months from Applied Biosystems and Bruker. The reason lies in the ability of the ion trap to synchronize the flow of peptides streaming from an electrospray ionization source at flow rates compatible with liquid chromatography, with a low vacuum, collision-induced fragmentation procedure for MS/MS analysis easily integrated into the highly sensitive Fourier transform ion cyclotron resonance (FTICR) mass analyzer.

“You can do everything [with the hybrid instrument] that you can do on an ion trap, but you can do it at, conservatively, 1,000 times higher sensitivity, at a resolution as high as 50,000, and at a dynamic range of at least 10,000,” said Hunt, whose hybrid ion trap/FTICR at U. Va. was used by MDS and Thermo as a model.

MDS, for its part, is hoping that its acquisition of the technology from Hunt two years ago, along with its alliance with Thermo, will give it a head start on others wishing to develop similar technology, as well as early access to Thermo’s expertise in software and instrumentation development. Although the ion trap/FTICR instrument currently installed at MDS already contains significant improvements in software and instrument control over the mass spectrometer in Hunt’s lab, the company will also have rights to use the beta versions of the instrument as they become available from Thermo, said Mike Moran, MDS’ chief scientific officer.

Within MDS, Moran said the exquisite sensitivity of the instrument, which a colleague termed “obscene,” will allow the company to perform comparative analyses of minute amounts of clinical material, and to recognize changes in cells and tissue caused by therapeutics, including the ability to recognize the potential side effects of the drugs.

But not everyone is convinced that on-line chromatography coupled with even such a sensitive mass spectrometer as a hybrid ion trap/FTICR is the ultimate answer to the problem of analyzing complex protein samples. ABI touts the advantages in sample throughput of its MALDI-TOF/TOF instrument. And at a more fundamental level, some scientists see front-end protein separation methods as an acceptable alternative to relying on mass spectrometry instrumentation and software as means of unraveling the components of complex mixtures.

“The world is preoccupied with dealing with complexity rather than fractionation,” said Al Burlingame, whose mass spectrometry lab at the University of California, San Francisco, holds an ABI MALDI-TOF/TOF.

“It’s not clear to me that dealing with complexity in a brute force manner is going to be the final game plan. I think people would be better off doing some intelligent sample handling on the front-end.”

Not surprisingly, MDS’ Moran sees the hybrid ion trap FTICR as a shortcut. “Where this new instrument is really efficient is in its ability to handle these really complex mixtures, so you save a considerable amount of effort on the upfront separation and fractionation that one would otherwise have to do with other technologies.”

It’s unlikely that this argument will resolve itself anytime soon. In the meantime, more mass spectrometry manufacturers are developing hybrid ion trap mass spectrometers: MDS Sciex, a sister to MDS Proteomics, is developing its own hybrid ion trap/triple-quadrupole mass spectrometer that the company will allow customers to preview in the coming months. And Kratos Analytical, a subsidiary of Shimadzu Biotech, is developing its own MALDI ion trap-TOF.

[Although Hunt is a consultant for MDS Proteomics, his affiliation with Thermo prevented him from knowing what instruments Sciex and MDS Proteomics were jointly developing. “I couldn’t know what Sciex was doing to continue consulting for Thermo,” Hunt said.]

Burlingame points out that comparing mass spectrometers on the basis of their hardware potential, and without data, is ultimately a tough row to hoe. “It’s very difficult to do comparisons between different systems from the point of view of the reliability of data that comes out the other end,” he said.

“You have algorithms involved in massaging the raw data, you’ve got algorithms involved in database interrogation, and you’ve got scoring systems that are poorly understood, [before] you come out with answers at the other end. Where all this distills down and how you compare one to another is not so easy to do, actually.”

— JSM