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At Pittcon, FTMS Enters Proteomics: Thermo, Bruker Launch Instruments

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Proteomics grabbed the spotlight on the vast stage at the Pittcon conference in Orlando, Fla., last week. Not only did the 23,000-plus attendees have a chance to listen to plenary and special lectures by pioneers of protein mass spectrometry techniques — Nobel Laureate John Fenn and Fourier Transform mass spectrometry guru Fred McLafferty — but a number of companies chose the 15-football field-wide exhibition space at the Orange County Convention Center to be the launch pad for their proteomics products.

Indeed, Fourier Transform mass spec probably made the biggest splash among the products launched for proteomics at the conference, with Thermo Electron and Bruker Daltonics each introducing a hybrid Fourier Transform mass spectrometer. Both instruments promise unprecedented resolution and mass accur- acy, paving the way for better shotgun proteomics as well as top-down analysis of intact proteins, although they also have applications in small molecule and metabolite analysis. However, the new capabilities come at a steep price.

Bruker rolled out a Rolls Royce version of a mass spectrometer: its Apex-Q couples a Q-q quadrupole front end with a Fourier Transform analyzer on the back end, offering either a 9.4 -Tesla or a 12-Tesla shielded high-field magnet. It sells for between $1.2 million and $2 million, depending on the magnet, and is equipped with an ESI source, with a MALDI source as an option. Bruker’s computer-switchable combi-source will be available for this instrument by early fall.

According to the company, the Apex-Q offers a resolution in excess of 100,000 with routine ESI and MALDI use, and of 30,000 in fast LC-MS mode, as well as sub-ppm mass accuracy with internal standards and low femtomolar sensitivity under typical nanoflow LC conditions. It also promises a high dynamic range due to the ability of the Q-q to filter selected ions into the FT analyzer. Moreover, it incorporates electron capture dissociation (ECD) and infrared multi photon dissociation (IRMPD) for the top-down analysis of intact proteins.

In proteomics, the new instrument will complement rather than replace other types of mass specs for high-end applications, said Bruker CEO and president, Frank Laukien. For example, the instrument’s high resolution will help save time in shotgun proteomics by allowing users to get away with one-dimensional liquid chromatography, the company said. “You don’t separate everything; you accept that at the end, your mass spectrometer turns this jungle [of peaks] into separated peaks,” Laukien said.

Bruker’s instrument is the result of a collaboration with Richard Smith at Pacific Northwest National Laboratory, who developed it especially for shotgun proteomics applications. Further input for top-down protein analysis applications came from Fred McLafferty’s group at Cornell and a number of scientists coming out of his group.

Two Apex-Q’s, which Bruker has been demonstrating to users for the last six months, will have been installed at customer sites by the end of the month, one of them — with a 12-Tesla magnet — at the Mayo Clinic, the other one, equipped with a 9.4-Tesla magnet, at Sanofi-Synthélabo in France, Laukien said.

Laukien hopes that the majority of the new instruments will be sold for proteomics applications — both to the pharmaceutical industry, which has traditionally been using FTMS for small molecules analysis, and to academic and government users. He believes that funding even for academic centers will become available in the future, just as NMR researchers have been able to obtain grants for million-dollar equipment in the past.

Thermo Shoots For User-Friendly Angle

Thermo stressed not only the high-end capabilities but also the user-friendliness of its new FTMS hybrid instrument, called Finnigan LTQ FT. It couples a new linear ion-trap front end with a Fourier Transform analyzer, based on a 7-Tesla superconductive magnet. Priced at $750,000, it can be used for small- molecule and metabolite analysis — its main anticipated application in the pharmaceutical industry — as well as for protein analysis, according to Ian Jardine, chief technology officer for Thermo’s life and laboratory sciences sector. The idea was “to try and make people forget that it’s an FTMS, and to look at it as simply being an automated ion trap mass spectrometer,” he said.

The instrument, which currently comes with an electrospray source and is set to ship by September, reaches a resolution of 100,000 at m/z 400, a mass accuracy of 1 ppm, and attomolar sensitivity when spectra are acquired over one second in LC-MS-mode, according to Jardine. In June, Thermo is planning to introduce an automated AP-MALDI source for it as well. The main reason why Thermo chose an ion trap as the front end, rather than a quadrupole, is the trap’s ability to do MSn analyses, Jardine said. Also, Thermo’s ion traps have a good reputation for being rugged and robust, he added.

Like Bruker’s machine, the LTQ-FT promises to discriminate between overlapping peaks in shotgun sequencing experiments of complex protein mixtures. “It will be the technique of choice — the only restriction will be the price,” Jardine said.

The first commercial instrument will go to Don Hunt at the University of Virginia, who has been a long-standing collaborator of Thermo in developing the machine. MDS Proteomics helped define its performance characteristics, Jardine said, and has a prototype of the LTQ-FT installed.

The new linear ion trap that is part of the instrument has a 100-fold higher ion storage capacity than Thermo’s three-dimensional ion traps, Jardine said. This increases the instrument’s sensitivity and, as a consequence, the number of protein identifications and protein sequence coverage in MudPit-type experiments. This summer, Thermo is planning to launch the new linear ion trap, called LTQ, without the FT analyzer. It will be priced at $300,000, and the AP-MALDI source will be available for it.

Jardine estimates that about half the instruments will be sold for proteomics applications, primarily to academic laboratories, while the other half will be for small-molecule and metabolite analysis. He does not believe the market for top-down protein analysis applications is large at the moment. “It doesn’t mean that it won’t be a big application in some years to come,” he added.

Will Thermo’s LTQ-FT directly compete with Bruker’s Apex-Q? Jardine thinks it will, though Laukien said the two instruments will mainly come face to face in the market for small molecule applications. The price will obviously play a role : Bruker also offers a 7-Tesla version of the Apex-Q for about $850,000, Laukien said.

Waiting in the wings?

Bruker and Thermo’s entry into the hybrid-FTMS stage may not be unchallenged: Waters has an ongoing research collaboration with IonSpec to develop a hybrid-FTMS with a quadrupole-based front end, but a product is at least a year away, according to Lance Nicolaysen, Waters’ director of sales for mass spectrometry. Applied Biosystems did not reveal whether it is working on its own version of an FTMS hybrid instrument.

— JK

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