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At ASMS, Mass Spec Debuts Take Back Seat To Consumables, Chromatography

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This story has been updated from a previous version to reflect a more accurate head count of ASMS attendees.

ASMS 2004, held this week in Nashville, Tenn., was not quite the mass spec release party that it has been in previous years. In fact, only Bruker Daltonics and Waters released new mass specs at the 5,300-person event. Instead, consumables and chromatography headed the bill, with life science mass spec vendors scrambling to promote smaller, application-focused releases targeted overwhelmingly at biomarker discovery.

Take the Q-TOF, leave the FT-MS

One year after it began to rebuild its quadrupole-based mass spec portfolio with the release of the Quattro premier triple quad, Waters was at it again this week with its new Q-TOF Premier. The Q-TOF, which uses the same T-wave technology introduced in the Quattro Premier, was released in three forms: as a standalone Q-TOF; linked up with a new version of Waters’ UPLC chromatog-raphy system called nanoAcquity; and packaged with nanoAcquity, custom-designed MassLynx software, a set of columns, and a set of standard operating procedures.

The UPLC system was first released as Pittcon in March (see PM 3-12-04), but at that time it was not capable of handling the low flow rates and high pressure required for most sample-limited proteomics experiments, Tim Riley, vice president for proteomics business development at Waters, said at the time. The nanoAcquity version tweaks the system to address both these problems, according to Riley. “We have a novel flow control system and some parts that weren’t adapted to high pressure [and now are],” he said.

Waters is marketing the nanoAcquity-Q-TOF combination as a sort of FT-MS alternative, ICAT alternative, and biomarker discovery system rolled into one. The system has listed resolution specs of 3 ppm, “but if you have good signals, you can get closer to 1 ppm,” Mark McDowall, marketing director for the Micromass Mass Spectrom-etry Technologies Center in Manchester, UK, told ProteoMonitor. The T-wave technology, which concentrates the signal, as well as the higher separation powers of the UPLC, allows for these capabilities, he said. In addition, due to the accurate mass measurements and a system that does parallel fragmen-tation of peptides for MS/MS, the machine is also able to do label-free relative quantitation between samples to look for up- and down-regulated proteins, as well as identification of proteins with up to 80 percent protein sequence coverage, according to Riley. “You can either identify everything and quantitate everything, or you can find a subset [of peptides] where the quantitation is different, and then only identify those,” Riley said.

McDowall said that for scientists looking to buy an FT-MS for its accurate mass capabilities, the Q-TOF could be an alternative. “If you compare performance statistics, it’s similar to the FT-MS,” he said, noting that while FT-MS can reach an extremely high resolution of about 40,000 for low molecular weight proteins, it can reach only about 10,000 for high molecular weights. The Q-TOF system’s capabilities are flatter, at about 18,000 across the board.

McDowall noted, however, that the system was not designed for top-down approaches — an appli-cation popular among FT-MS users.

Meanwhile, Bruker released a Q-TOF update of its own, called the ultrOTOF, that the company also claims has mass accuracy capabilities rivaling that of FT-MS. The system regularly reaches a resolution of 20,000, but can be switched into a special mode, called MultiPass, that can reach resolutions of 40,000, according to CEO Frank Laukien. The special mode is “not something you’re going to do on the fly for every sample, but when you need it, you can use it,” he said.

Biomarkers Steal the Show

Bruker’s announcment of its new Q-TOF was almost buried in other news of its Bruker’s ClinProt biomarker system, for which the company released a set of new consumables and software. In addition to several new chemistries for its magnetic beads, the company introduced the first product in a new line of magnetic beads to which it will attach various antibodies. The first version, which will attach Protein G, will be available this summer, but it will soon be followed up with other pre-made offerings — perhaps containing cytokines — as well as customizable antibody beads, the company said. “This is just the first proof of prin-ciple for affinity pulldown,” Victor Fursey, director of sales and marketing at Bruker Daltonics, told ProteoMonitor.

While the beads for now will be intended solely for affinity pull-down of biomarkers from serum and other mixtures as a front-end sample prep method, Fursey is not ruling out the eventual adaptation of the technology as a bead-based antibody array for interaction studies. “Maybe in the future, years down the road,” Fursey said. “This could be one step in that direction.” He added that similarly down the road, mass spec could also potentially be hooked up as a read-out tool for such interaction experiments.

Fursey expressed confidence that ClinProt was catching on, although more people “need to publish using the system” before it will really take off, he said. Eventually, he predicted, scientists will be drawn away from alternatives such as SELDI by the economic value of having the biomarker discovery and protein identification functions on one machine. “It’s a lot of value for your money,” he said.

Applied Biosystems Gets on the iTRAQ

Applied Biosystems’ big new release was also consumables and biomarker-oriented: Its iTRAQ reagents — billed as a multiplexed stable isotope labeling of peptides without the cysteine dependence of ICAT (see PM 3-5-04) — are being driven straight at the biomarker market. With iTRAQ, “we can start the validation process with quanti-tation,” Tony Hunt, ABI’s director of systems integration, proteomics, told ProteoMonitor. “That’s going to be our focus over the next year: getting the tagging reagents into biomarker workflows,” he said.

ABI didn’t release any new mass specs at ASMS this year, but Hunt expected iTRAQ to drive sales of existing ABI instruments, since the reagents “work best with the ABI platform,” and, perhaps more importantly, since the software designed to interpret the data acquired using the reagents is adapted only for ABI instruments.

PerkinElmer and Ciphergen both opted to focus only on biomarker applications at their booths and in their press conferences, in place of releasing any new products. Mary Lopez, business leader of analytical proteomics for PerkinElmer, gave a press conference describing a new collaboration she has formed with Emanuel Petricoin and Lance Liotta of the NCI-FDA Clinical Proteomics program for biomarker screening, in which they will use PerkinElmer’s proTOF and a set of affinity capture sample prep chemistries that PerkinElmer obtained from a collaboration with VivaScience (see story p. 1). The collaboration, which is expected to be formalized in a CRADA this summer, will seek to screen serum for biomarkers by capturing and analyzing proteins such as albumin, a “sticky” protein that several NCI-associated researchers believe captures low molecular weight proteins of interest from the serum.

The pattern recognition/global screening approach is new for PerkinElmer, Lopez told ProteoMonitor. “What this essentially means is that [now] PerkinElmer is pursuing two strategies in proteomics: differential protein expression (gel-based proteomics, protein arrays) and Biomarker screening (mass spectrometry-based pattern recognition),” Lopez wrote in an e-mail. Lopez said that the company will release four biomarker pull-down kits based on VivaScience’s membrane chromatography columns, beginning early in the first quarter of 2005.

GE Healthcare Makes its ASMS Debut

Thermo Electron and GE Healthcare (formerly Amersham Biosciences) this week debuted the MDLC-LTQ, their first integrated system to be released since the beginning of the Thermo-Amersham collaboration in February 2003. The system was the only brand new Thermo release at ASMS. It interfaces a new MDLC front-end from GE Healthcare with Thermo’s LTQ.

Veering away from the popular “user-friendly” model that has gained popularity over the last year, the MDLC-LTQ is “more for people who are capable chromatog-raphers,” Ken Miller, product marketing manager for Thermo, told ProteoMonitor. While Thermo provides a variety of column types and an interfaced system that can accommodate up to four dimensions, “the column selection is left to the end-user,” Miller said. “Experienced users know what they want to use.”

Miller also said “the nature of the relationship [between Thermo and the former Amersham] may change” now that Amersham is part of GE, “but I don’t know how or when. If anything, it will be stronger.” He said the collaborators next plan to integrate DIGE-2D gel-based systems from GE with Thermo’s mass specs — although in this case, he said, the main integration step would be just be marketing and sales support that would cover both systems when used together. He also said that Thermo would be interested in combining the protein arrays that GE has said it is developing (see PM 4-16-04) with its instruments. Thermo does not have interest, however, in developing its own front-end products. “You need to know your core competency and not dilute your effort. There are a lot of things we’d like to do that we won’t,” Miller said.

On the instrument side, Miller said to expect new hybrid combinations and “different flavors of the LTQ and LTQ-FT” coming up.

Thermo Enters Biomarker Arena

While front-end tools may be something that Thermo won’t do, the company has not been able to resist the allure of biomarkers. Miller told ProteoMonitor that Thermo is currently in the process of setting up an applied technology lab in the Boston area for a new biomarker initiative that the company is starting. “The objective is the development of technology and systems for biomarker discovery,” Miller said. He said that the lab will develop new instrumentation and software for biomarker applications, and will be set up “very soon.” Around a dozen people will initially work there.

For coverage of previous years’ ASMS conferences, see ProteoMonitor (6-10-02 , 6-13-03).

— KAM

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