Meeting mass spec challenges head-on

Samuel Lunenfeld Research Institute advances protein research with help from new AB SCIEX technology

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TORONTO—While scientists around the world continue to adopt mass spectrometry to solve biomedical problems, with this powerful technology come significant challenges. Mass spectrometry is viewed as both a blessing and a curse, as new instruments can produce more accurate data than ever before, but analyzing large volumes of data poses can be a daunting task. In their use of mass spectrometry technology to apply protein research to enhance the field of cell biology, researchers at the Samuel Lunenfeld Research Institute (SLRI) of Mount Sinai Hospital have turned to AB SCIEX, a developer of life science analytical technologies, to ease this analysis burden.

Both parties last month took the wraps off an ongoing academic-industry collaboration in which SLRI researchers are using the AB SCIEX TripleTOF 5600 System, a new accurate-mass technology that AB SCIEX will unveil to the market in June. The technology is hailed as the first mass spectrometry system that combines on a single platform the quantitative capabilities typically associated with triple quadrupoles and the qualitative capabilities of a high-resolution, accurate-mass system.

The TripleTOF 5600 System delivers a series of new innovations, including SmartSpeed 100Hz Acquisition at least five times higher speed than any other high-resolution mass spectrometry system; Accelerator TOF Analyzer for high resolution data at high-speed with the industry's highest sensitivity; and EasyMass Accuracy to achieve stable ~1ppm mass accuracy without continuous user calibration.

The result, AB SCIEX says, is a system that provides life scientists access to powerful new workflows for comprehensive exploration, rapid profiling and high-resolution quantitation of complex samples that are not possible with any other mass spectrometer.

Considered to be at the forefront of using mass spectrometry technology to apply protein research to enhance the field of cell biology and provide new insights into human diseases, the SLRI team is focusing its biomedical studies on analyzing complex protein interactions and modifications in the pathways and processes of communication between cells. Leading researcher Dr. Tony Pawson, a Kyoto Prize-winning scientist, and his team say AB SCIEX's TripleTOF 5600 System is a significant leap forward in mass spectrometry tools for biomedical analysis, primarily because the technology will improve the quality of information they generate.

"Mass spectrometry carries a lot of challenges, such as figuring out false positives, and the biggest challenge of all, bioinformatic analysis, especially with large data sets," Pawson says. "We're particularly interested in scaffolding proteins and their interactions with various signaling proteins. There is an increasing call for understanding the cell at a quantitative level. At the end of the day, mass spectrometry is just a tool, but nothing is as quantitative. The new mass spec technology that AB SCIEX is unveiling will be critical in our efforts to model cell networks because that is dependent on the quantitative data we obtain."

Andrew James, a mass spectrometry specialist at SLRI, notes that the new AB SCIEX technology marries quantitative and qualitative analysis.

"It does a lot to address both of those workflows on one instrument platform," James says. "That makes the technology particularly attractive because you don't have to switch information around between platforms. That results in significant time savings in how our experiments are run."

The SLRI team will continue to use the new technology for the next few years, and it will likely become "a cornerstone of their analytical arsenal," says Dr. Dominick Gostick, director of AB SCIEX's biomarker, mass spectrometry, pharmaceutical and proteomics businesses.

"One of the things that has been critical for groups like SLRI is making sense of the biology behind what they are doing," Gostick says. "They serve a fairly large group of biologists who look at how proteins interact, and how modifications of proteins change over time and under certain conditions. Their challenge has been how to get good quantitative information as well as this sort of qualitative information. They have traditionally used techniques like Western Blots, but those have been limited in the sense that you have to have a certain antibody or particular protein. What mass spectrometry instruments like ours allow them to do is to identify a protein of interest, develop an assay and do a quantitative assessment of that to monitor any changes and figure out how it relates back to biology."

Pawson's team has collaborated with AB SCIEX on changes to the new technology, which has allowed AB SCIEX to "tweak" it before moving from beta testing to full product launch, Gostick says.

"We develop powerful instrumentation, but it's only through collaborations with groups like this that we can make the technology more accessible for other groups," he says. "The valuable feedback we gain from these sorts of collaborations means we are developing next-generation software. We're constantly innovating and breaking through in terms of the core elements of mass spectrometry, but these collaborations give us insight into what biologists need and brings the power of mass spectrometry to a level where the biologists can access the information they need from the instruments they have used to acquire it."

"For us, it has been a fruitful collaboration," Pawson agrees, "and a good example of how industry-academic collaborations can work. We go back and forth, and on occasion, we have been able to point out problems and issues to them and let them know how biologists think—and at the same time, they have been able to give us the benefit of access to new technologies."

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