NIH grant to develop a new method for rapidly screening blood samples for biomarkers

Dr. Jennifer Brodbelt, professor of chemistry and biochemistry at The University of Texas at Austin, has received a $734,068 grant from the National Institutes of Health (NIH) to develop a new method for rapidly screening blood samples for biomarkers.

Biomarkers are small molecules that indicate the presence of a particular physiological condition, typically a disease. The new method, if successful, could prove useful not just for identifying markers of specific diseases such as cancer or heart disease, but for discovering broader metabolic patterns correlated with conditions such as aging or obesity.

"There are technologies right now that are very effective at separating and analyzing the different compounds in a blood sample, but they tend to be relatively slow," says Brodbelt, the principal investigator of the grant. "It makes it very hard to do analyses of lots of samples. What we're developing is a chip-based method, where entire classes of compounds are captured on the chips and then all the compounds are released and analyzed by mass spectrometry in just a few seconds."

Although the technology, if successful, should be useful in searching for biomarkers in all sorts of conditions, Brodbelt and her collaborators from Southwestern University in Georgetown, Texas, Drs. Lynn and Frank Guziec, are focusing on patterns that correlate with aging.

"We're trying to develop maps that can correlate the progression of aging with metabolites that might be circulating in your blood," says Brodbelt. "These could be small molecules that increase in quantity as you age, or actually change in composition as one ages."

The new method, says Brodbelt, involves three basic stages.

The first stage is the coating of different regions of a mesh chip with a variety of "capture agents," which chemically bind to specific compounds in a blood sample. A burst from an ultraviolet light then severs the chemical bonds between the chip and the captured substances. Then an electrospray, which is similar to a solvent aerosol spray, shoots through the mesh chip and transfers the different compounds into the mass spectrometer for analysis.

By analyzing the mass spectrometric data, says Brodbelt, scientists should be able to measure the presence and quantity of different compounds, and to do so on a scale, and with a speed, that wasn't possible before.

"The payoff could be big," she says. "It's a different strategy than what might be pursued by molecular biologists or biochemists. They'll often focus on studying one or two proteins at a time, and develop a really deep understanding of those proteins. We're looking for the more generalized profile, and we may notice some patterns that weren't apparent to them.

"There are so many other areas where you'd want to do profiling. It might involve looking for pesticides as part of an environmental study, or doing protein-related work or drug profiling work. If this approach is successful, I imagine other groups will try to develop these chips as well."

Brodbelt's grant, which is being funded as part of the American Recovery and Reinvestment Act (ARRA) government stimulus package, is a "Challenge Grant," meant to encourage high-risk, high-reward research projects that may produce results quickly.

This is the second NIH grant in two years that Brodbelt and the Guziecs have received. In 2008, the collaborating groups received a four-year, $1,113,615 grant to evaluate an innovative technique that could assess the anti-cancer activity of new compounds.