Tuesday, May 26, 2009



The Xevo TQ MS system.


Mass (Spec) Appeal

Sensitivity, simplicity highlight new systems

If there'S one word that has been the promotional hallmark of mass spectrometry (MS) systems, it'S sensitivity. Everyone wants to know how much more sensitive a new system is and how well it achieves that sensitivity without increasing chemical noise. At the American Society for Mass Spectrometry (ASMS) conference in June, sensitivity definitely held its place in the spotlight, with several newly unveiled systems boasting improvements. But another watchword also took its turn onstage: simplicity.

With its new Xevo TQ (tan quadrupole) MS, the Waters Corporation (Milford, Mass.) rethinks high-performance MS with a focus on mass appeal. The company has taken the technology out of the domain of the mass spec gurus and made it operational for labs where the scientists and technicians may not be MS specialists.

"Quadrupole and tandem-quadrupole instruments are now going into labs where non-MS specialists-specialists in clinical areas, pharmaceutical chemistry, food production, and food safety-need this equipment in order to get their data, usually quantitative, as quickly as possible," says David Little, Waters' senior product manager for quadrupole MS. "The Xevo tan-quadrupole system is designed with ease of use as its primary underlying philosophy." In other words, "We've tried to make it idiot-proof."

What'S so easy about the Xevo? Little offers one example. "The handle to get into the ion source chamber looks like a door handle for a car," he says. "If you open it up, it automatically turns off all the voltages that are running the system. You can get to the components you need to clean off the instruments that have been contaminated with materials from the matrix without disrupting the vacuum. The last thing you want to do is open a valve somewhere and the whole thing vents to the atmosphere."

This isn't Waters' first venture into easy-to-use MS. The Acquity TQD tandem UPLC/MS/MS system, sister product to the SQD system, offers IntelliStart technology that automatically tunes and calibrates the system. But that was a baby step. "We didn't initially take that step with the high-performing product; with the lower-performing product, the requirements were less," says Little.

Learning from the launch of the TQD, Waters applied the technology to a much higher-performing platform in the Xevo. "There'S a factor of about five or six differential between this and the lower performing product," says Little, cautioning that it'S difficult to be precise about the difference in performance because the system'S redesigned ion generation is compound-dependent in its efficiency.

The Xevo also uses the IntelliStart system, with a revamped design that adapts the easy interface. "It does things like pumping in reference compounds for you automatically when it'S doing certain operations," says Little.

Little compares IntelliStart to the computerized self-check systems in high-end cars. "I have an Audi, and when you turn the ignition on, it goes through a sequence of checks and then tells you everything'S okay-except, of course, if it'S not," he explains. The Xevo does something similar: it can identify instruments that are not operating correctly or calibrated properly, for example. Its additional features include pumping in reference compounds automatically, as the software requires, when performing certain operations.

Designed primarily for the quantitative measurement market, the Xevo'S IntelliStart system also allows the user to load a standardized compound reference file into the fluidics area and use it to calibrate sample concentration against a certain response. "It'S much more approachable instrumentation," says Little. "You load the reference, enter the compound name and molecular weight, and it develops a method for you."

Still Sensitive

This new focus on simplicity doesn't mean that sensitivity wasn't still high on the agenda for the Xevo or, for that matter, for any other new product.

The TSQ Vantage triple quadrupole MS system.

The S-Lens in the TSQ Vantage helps conserve the signal.


The Xevo boosts sensitivity with a new ionization source that Little touts as "much more efficient than previous designs we've had," one that allows for increased sample throughput and improved detection, with a flow rate between 0.6 and 1 mL per minute.

Agilent, which entered the field two years ago with triple quadrupole and q-top mass spectrometry, says it has greatly lowered sensitivity limits with its new 6460 triple quadrupole LC/MS, which lowers detection limits five-fold compared to previous instruments, breaking through the femtogram level for many compounds.

"We believe we have unsurpassed sensitivity in the triple quad arena with this product," says John Fjeldsted, PhD, Agilent'S director of research and development. "We think it'S important to put a big stake in the ground here. This system shows results at 500 atograms, which takes it to the ultimate in sensitivity. Our samples show signal improvements that typically are five, six, and seven-fold on things like pesticides as well as new compounds in the pharma area."

But maximizing signal-to-noise isn't Agilent'S only goal with the 6460, which is aimed at the target quantification and target compound analysis markets. "We also want to operate quantitatively at a very low range," Dr. Fjeldsted says. "We're focusing on the limits of quantification and the impact of relative standard deviations on people'S analyses by making sure that there'S lots of signal there to be quantified."

That, of course, gets back to ion generation. The 6460 uses Agilent'S Jet Stream technology to improve nebulization and sampling. "It provides a columnated and focusing desolvation process that increases ion production," Dr. Fjeldsted says. "It has to do with a concentrated sheath gas that goes around the nebulizer flow, [one] that'S able to run at a very high temperature."

Dr. Fjeldsted notes that Agilent'S signature orthogonal configuration is also a hallmark of the 6460. "The pool of liquid flow is directed not straight at the sampling optics, but perpendicular," he says. "It doesn't ionize residual contamination. The potentials on the surface draw ions in, losing nothing in sensitivity, but things that don't 'play well' just pass by."

To date, Agilent'S triple-quadrupole system has had its strongest penetration in the applied market, in areas such as food safety. But Dr. Fjeldsted predicts that the 6460'S performance will make strong inroads in the pharmaceutical industry. "We've had parity with other systems in the past, and pharma has said to us, 'When you get something that dominates, please get back to us.' This opens that door," he says. "I'm convinced that our uptake in the pharmaceutical industry will be quite substantial, particularly with the additional software packages we've put in place that round out pharma work flow."

We're focusing on the limits of quantification and the impact of relative standard deviations on people'S analyses by making sure that there'S lots of signal there to be quantified.

-John Fjeldsted, PhD, director of research and development, Agilent

Thermo Fisher, meanwhile, lays claim to a 10-fold increase in sensitivity for its TSQ Vantage triple quadrupole MS system, thanks to an innovation called the S-Lens, which cleans up the signal. The "S" stands for stacked ring, the key to its ability to capture ion-rich gas flow.

"While we focus the ions into a tight beam for transfer into the next vacuum chamber, the extraneous solvent-laden gas is actually pumped out between the stacked ring elements before it has a chance to enter the multipole," says Rohan Thakur, PhD, director of small molecule solutions marketing. "Most technology has a skimmer-based design that transfers a lot of the extraneous solvent-laden gas into the next chamber, but the stacked-ring design lets us efficiently pump out the solvent-laden gas and conserve the signal."

Maximizing return on investment is another key focus for customers, says Waters' Little. "We're blurring the edge a little now, because customers want to do more with an instrument they've spent a lot of money on than just purely quantitative work," he says. "They may have a small percentage of work that'S qualitative and would rather not spend money on an entirely different system."

But while tandem quadrupole systems are efficient for quantitative analysis, they're much less so for full scan mode qualitative analysis. That'S where new ion source collision cell technology from Waters-what Little calls "intelli-gent ion selection"-comes in. "This cell can accumulate ions and mass-selectively eject them at the right time for us to get the most efficient duty cycle in full scan mode."

Dr. Thakur predicts the sensitivity of quadrupole MS systems can be taken even further. "I think it'S going to be a race to preserve and improve sensitivity and further reduce the chemical noise," he says. "I think there'S probably another order of magnitude'S worth of improvement somewhere in the system.

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