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By Lindsay Hock

Monday, December 21, 2009


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Thermo Exactive

Thermo Fisher Scientific, Inc.'s Thermo Scientific Exactive LC/MS system.

Small, fast, and cost effective–those are the three words that most scientific laboratories look for in their analytical equipment. However, full-size laboratory equipment may seem like the only option for laboratories looking for highly accurate and high resolution analytical tools. Although bulky and energy consuming, full-size analytical instruments used to be the answer for all mass calculations and chromatography readings. This era has now come to an end thanks to benchtop analytical equipment that meets the condition of the three sought-after features.

One such instrument making a significant impact on laboratories is the Thermo Scientific Exactive LC/MS system from Thermo Fisher Scientific, Inc., San Jose, Calif. This product holds the title of being the first benchtop mass spectrometer based on Orbitrap ion trapping technology, and, according to Ian Jardine, vice president of global R&D at Thermo Fisher, “is specifically designed as a benchtop detector for liquid chromatography.” Being used in applications such as environmental analysis, pharmaceutical drug metabolism, and food safety, the high resolving power, mass accuracy, and dynamic range of the Orbitrap technology “allows users to screen complex mixtures coming from liquid chromatography separations, and perform comprehensive identification and quantification of multiple components in the mixtures,” states Iain Mylchreest, vice president and general manager of life sciences mass spectrometry at Thermo Fisher.

While being the first benchtop Orbitrap mass spectrometer, the instrument also has high resolution capability. “The resolution of our product is 100,000,” claims Jardine. “That is by far the highest ever seen for a benchtop mass spec product.”

Along with the high resolution, the product also claims to measure masses to ppm accuracies. The Exactive is “also compatible with UHPLC units and fast chromatography,” says Mylchreest, so it fits into all lab separation strategies for rapid analysis and high throughput.

While the Exactive was developed primarily with lab space issues in mind, the perception issue of the product also stood out during its developmental stages. “We wanted to create a product that anybody could use to deliver highly accurate mass measurements at a very high resolution,” says Mylchreest. Now, with the Exactive, chemists can walk up to the product and use it with virtually no training. And, although people tend to equate floor standing instruments with high-end research devices, the Exactive rivals floor-standing instruments with its resolution and mass measurements.

The Exactive was virtually created out of “a blueprint of desire,” states Jardine. The engineers behind the product had to look at “how the footprint architecture as far as the electronics fit together, and how the mechanical parts fit together, while also seeing how the product relates to an UHPLC,” continues Jardine. The floor-standing Orbitrap mass spectrometers had to stay the size they were because other instruments were attached to the front end of the product; by removing the front of the floor standing instrument, but keeping all the functionality of the floor standing instrument, the benchtop instrument was created.

Agilent QTOF Benchtop

The 6530 (bottom) and 6540 (top) Ultra- High-Definition (UHD) Accurate-Mass Quadrupole Time-of-Flight (Q-TOF) liquid chromatography/mass spectrometry (LC/MS) systems.

Agilent Technologies, Santa Clara, Calif., has developed a benchtop LC/MS system based off their Quadrople Time-of-Flight (QTOF) hybrid technology. Used to figure out what a substance is, or if a substance or something is present in a sample, Agilent’s 6538 and 6540 instruments “stand about four feet wide and about five feet tall,” says Ken Miller, Global Senior Marketing Manager for LC/MS Business at Agilent. Found in laboratories that deal mainly with pharmaceuticals, proteomic and metabolomic analysis, and food safety, Agilent wanted to enhance performance of floor standing instruments in a benchtop form.

“A lot of [Agilent's] competitors, in order to achieve performance gains, have really had to abandon the benchtop format for their instruments,” says Miller. Agilent created a benchtop instrument that is sensitive and accurate, that “allows for the conservation of lab space,” states Miller. With each laboratory receiving a large number of samples a day, analytical instruments are expected to process samples quickly and accurately. Miller states that since the QTOF instruments needed to fit into the lab with a lot of other instruments, and needed to become part of a standard, custom work flow, the benefits a benchtop QTOF system would have for laboratories became apparent.

With the 6538 and 6540 instruments, Agilent was able to make the instruments' resolution greater than 40,000, where previous models of the instrument had resolutions around 18,000 and 20,000. This, according to Miller, made the project a major investment.

“Had we been willing to accept 30,000 resolution, or 35,000 resolution, I think the project would have been a good deal easier,” states Miller. Agilent was also able to improve the mass accuracy to less than one ppm. And, according to Miller, “the instrument was created based on what users sought after and without compromising the other aspects of the QTOF’s performance.” The decision was made early to make the instruments in benchtop form. In order to do this, Agilent had to extend the flight tube on the system by a half-meter, change the mirror in the TOF flight tube, improve the detector quality by engineering a new detector, and introduce a new technology called the ion beam compressor.

“What this new technology does is take the beam, that is the ion beam, coming through the instrument and it squeezes it down so that all the ions have all the same energy,” says Miller. This technology achieves high resolution and allows a user to take a complex mixture and pull apart the individual components that are present within the mixture to analyze them independently.

The common thread between both products is that they were both customer driven. With customers looking for significant performance improvements within their LC/MS equipment, they were given the performance of floor-standing instruments in a small, compact size with the ability to analyze substances more accurately. So what is to come for these instruments? “The biggest hurdle now that customers face in terms of arriving at an answer in their experiments is the software,” claims Miller. Now that these benchtop instruments are performing well, the next hurdle customers face is that they have these accurate and beautiful data sets, but they need improved data processing capabilities. “We are working significantly to improve our data processing capabilities to meet our customers’ demands,” says Miller.

Published in R & D magazine: Vol. 51, No. 7, December, 2009, p.24.

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