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Waters Hopes to Lure Structural Biologists With New Mass Spec; Thermo Launches Improved LTQ

Last week at the American Society for Mass Spectrometry conference in Seattle, Waters unveiled a new category of mass spectrometers that differentiates ions by size and shape, as well as mass. The firm is initially targeting structural biologists, but company officials believe uses for the new technology will ultimately be determined by researchers employing it in a variety of applications.

Waters was just one of several mass spectrometry vendors at the conference trying to woo customers with new or updated instruments. Rivals, including Thermo Electron, Agilent, and Shimadzu, also launched new mass specs in an effort to reel in customers at both the low and high end of the market.

Waters Launches a New Kind of Mass Spec

At the conference, Waters introduced its new Synapt High Definition Mass Spectrometry, or HDMS, system incorporating the company's Triwave technology. The technology features an ion trap; ion mobility-based separation within an electric field that separates ions based on their shape and size; and mass quadrupole time-of-flight mass spectrometry that performs traditional mass and charge analysis, said Mary Ellen Goffredo, director of product marketing at Waters, during a company presentation.

Initial applications for the HDMS system are in structural biology "where it really is the three-dimensional shape of a molecule that's important and its reactivity within a biological system. Historically, mass spectrometry has not been a technique that has been able to afford those researchers with discrimination based on the shape of the molecule."

"That's what makes this system quite a bit different," said Gene Cassis, director of investor relations at Waters, in an interview this week.

Pricing the Synapt HDMS instrument at around $650,000, Waters is targeting the high end of the mass spec market. According to Cassis, the firm doesn't have an estimate of the market size for the new system, because "it's not clear to us that mass spectrometrists are going to be the only people interested in this."

He told BioCommerce Week that the initial applications for the HDMS system are in structural biology, "where it really is the three-dimensional shape of a molecule that's important and its reactivity within a biological system. Historically, mass spectrometry has not been a technique that has been able to afford those researchers with discrimination based on the shape of the molecule," he said.

One of the first research groups to test the Synapt technology was a structural biology team at the University of Cambridge led by Carol Robinson, said Goffredo. The group used the new technology to help demonstrate that the gas phase structures of intact, multi-protein complexes, though devoid of bulk content, are essentially equivalent to native solvated structures.

There are other instruments that can be used to look at the shape of a molecule, such as nuclear magnetic resonance or X-ray crystallography, but "each of those techniques has some limitations," said Cassis. "I think the sensitivity, the speed of analysis of mass spectrometry, really does open up some new areas of research."

Cassis said that although structural biology is the first target market for the HDMS technology, "we can envision a future where we take this technology and embed it in different devices that are maybe more application-specific."

Although he was reluctant to say what specific applications, other than proteomics and metabonomics, may benefit from the technology in the future, Cassis cited "complete analysis of a biological fluid" as a natural fit for HDMS. "At this point, you don't want to narrow it down too much, but I think in general, people who are going to find utility with this technology will be people who are looking at complicated samples and trying to see changes either from living system to living system or within the same living system over time," which was not possible with previous MS technology.

"How this tool ends up benefiting researchers is going to be really determined by the researchers," he said. "This is not … a turn-key, full system solution targeted at a specific market. Rather, what we're doing is providing a tool, and we expect that maybe some application-defined market will evolve as researchers begin to use this tool."

Although other mass spec vendors may eventually develop their own HDMS, or similar, instruments, Cassis said Waters' head start might be an advantage. "It does create a benchmark in the marketplace for others to begin to look at and see how they could deliver similar information," Cassis said. "In the meantime, we're confident that researchers out there will want to start using the new capabilities, and we certainly have a window."

Agilent, Shimadzu Launch New MS Instruments

Targeting the lower end of the mass spec market, Agilent launched a family of four new single quadrupole mass spectrometers at ASMS that range in price from $85,000 to a little over $100,000 — discounted from its predecessor single quads.

As reported in BioCommerce Week last week, the firm has said that it hopes to double its share in the estimated $1.3-billion mass spectrometry market by 2008, and it has been aggressive over the past couple of years in developing and launching new mass specs (see BioCommerce Week 5/31/2006).

The launch of the 6100 Series single quads were only part of Agilent's new offerings at ASMS. The firm also unveiled its 6510 Q-TOF LC/MS, which it claims offers a 10-fold sensitivity advantage over other instruments in its class.

Shimadzu, which is not part of the BCW Index but is a major mass spec player, launched the vertical-standing Axima-TOF2 at the conference. Company officials said the advantage of the new instrument is its improved curved field reflectron technology, which allows very high energy collision-induced dissociation without the loss of ions on the ion path.

The new instrument costs about $250,000. It is currently available for order, and the time from order to delivery is about 60 days, according to company officials.

— EW, TL

Waters currently is able to demonstrate the technology and take orders, said Cassis, but the firm doesn't expect to begin shipping the instrument until at least the third quarter — and it's likely that production of the instruments in that quarter "will be used to populate our demonstration laboratories."

He said the firm expects "to see some level of customer shipments that could potentially influence our company's performance" in the fourth quarter.

Thermo Introduces ETD Capabilities

Also at ASMS, Thermo showed off updates to its LTQ and LTQ FT ion trap mass spectrometers.

The main improvement of the new LTQ XL over its predecessor is that the LTQ XL can perform electron transfer dissociation and pulsed-Q dissociation, in addition to traditional collision-induced dissociation, said Ken Miller, proteomics product marketing manager at Thermo, during a company presentation at ASMS.

"When you combine CID with ETD, you get better information than before," said Miller. "The two [dissociation] methods are complementary — they break apart the peptide backbones at a different place."

Using Thermo's new instrument, researchers can do "middle-down sequencing," said Miller. First, they use CID to break the peptide into big "chunks." Then they do ETD on the big segment of interest.

"It's too complicated with just ETD; there [are] too many fragments, and you won't figure out the fragments," said Miller. "If you first fragment using CID and then do ETD on the big chunk, that works well. We've tried this stuff out."

Miller maintained that ETD implemented on an LTQ XL offers a great sensitivity advantage over competitors' ETD-capable instruments, such as Bruker's HCTultra.

"The LTQ can store a huge number of charges — 15 times what competitors' so-called 'high-capacity' traps can store," said Miller. "We're firmly convinced that the 2D implementation of ETD is vastly superior to any implementation on a 3D trap."

In addition to performing ETD, the LTQ XL also has the ability to perform proton transfer reactions — another type of fragmentation technique that reduces all charge states of fragments to just one charge state.

Thermo also launched the LTQ FT Ultra at ASMS. The new instrument has parts-per-billion mass accuracy, compared to a mass accuracy of about two parts per million for the original LTQ FT. The new instrument has also more than doubled its dynamic range to between 4,000 and 5,000, compared with about 2,000 for the LTQ FT.

"The key is inside the ICR cell of the magnet," said Miller. "The new grid cell has a much larger volume that it can fill with ions, resulting in increased sensitivity and dynamic range. In addition, with the new cell, the ions are traveling closer to the electrodes, which results in a bigger current, which results in increased sensitivity."

According to Miller, though the LTQ FT Ultra contains a seven-Tesla magnet, it has the sensitivity and mass accuracy of a 12T instrument.

Miller declined to give prices on the LTQ XL and the LTQ FT Ultra but said that they cost around the same as their predecessors.

— Edward Winnick ([email protected])
and Tien-Shun Lee ([email protected])

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