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Better than Gold? GWC Receives $100K ARRA Grant to Develop New Substrate for Protein Arrays


This story originally ran on July 6.

By Tony Fong

GWC Technologies is taking advantage of Washington's stimulus efforts to develop a new protein array technology.

Last week, the Madison, Wis.-based protein array firm announced it had been awarded a six-month Phase I $100,000 Small Business Innovation Research grant by the National Science Foundation to accelerate development of its proprietary "carbon-on-metal" technology for protein arrays.

The award was granted under the American Recovery and Reinvestment Act of 2009, more commonly known as the stimulus bill signed by President Obama in February.

The technology, developed in collaboration by GWC and the laboratory of Lloyd Smith, a professor of chemistry at the University of Wisconsin, was originally applied to DNA arrays, but according to Tim Burland, president and CEO of GWC, it has several potentially important benefits for proteomics and protein researchers.

GWC, which is licensing the technology from the university, was especially interested in its application for protein arrays where label-free methods can more accurately reflect how proteins behave in real life. "Any small chemical changes to a protein might radically alter its function," Burland told ProteoMonitor last week. "If you're looking at protein function rather than just trying to detect them, label-free is very beneficial," and the CoM method could make label-free protein array analysis "much more robust and versatile" than is currently available with conventional arrays, he said.

GWC's surface plasmon resonance detection systems analyze protein arrays made on biochips made of gold, which enables label-free analysis. While gold is an ideal material in some respects "because you need a novel metal to get the surface plasmons excited … [it] compromises some assays," Burland said. For example, because of gold's fragility, it is not suitable for array technologies based on harsh chemical methods.

But GWC's CoM technology makes the array substrate more robust, and in an article describing the technology, Smith showed it could be used to build arrays with amine-modified oligonucleotides on aldehyde-terminated surfaces prepared on amorphous carbon and gold self-assembled monolayers. The carbon substrates, Smith and his colleagues wrote, "offer inherently lower background fluorescence intensity and a greater number of hybridization-accessible sites."

The NSF grant announced last week is aimed at investigating whether the CoM technology can be applied to protein arrays. Voula Kodoyianni, GWC's chief scientific officer, is the principal investigator on the project.

Smith's lab "already showed all the robustness features of it by using it for DNA arrays. Now we're going to try it for protein arrays," Burland said, who added that the technology is expected to have "some hidden benefits."

In addition its fragile nature, gold has other issues that have prevented its use in the building of protein arrays, which the project also seeks to address.

When gold is exposed to the atmosphere, organic materials are attracted to and adhere to the gold, Burland said. While that causes proteins to stick to it — a good thing as far as building a protein array is concerned — that same property makes it difficult to keep clean. But carbon's lower surface activity is expected to result in less non-specific binding, which the project will be testing.

Another aim is to test whether the carbon surface can decrease gold's tendency to denature proteins. "One of the challenges of doing label-free detection of proteins is that it's always done on a surface, so when you immobilize proteins on a surface, there's a danger that the immobilization will destroy the activity," he said, adding that that's often the case with gold.

GWC will test whether and how the lower surface activity of the carbon affects the immobilization of specific proteins, Burland said.

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Finally, the company will investigate whether the CoM technology can improve the reusability of protein arrays. Smith has already shown that DNA arrays manufactured with the technology can be reused more frequently than arrays built by conventional methods.

When protein arrays are manufactured, the molecules on the array, including the probe molecules, aren't "very permanently attached" and can fall off, Burland said. This is true for arrays manufactured on glass surfaces, as well, he added.

The carbon surface, however, allows carbon chemistry to be used, "so the fundamental bond linking a probe to the surface is now a carbon-carbon bond, which is a strong covalent bond and is going to give a permanent attachment of your probes to the surface," he said. "So they're much more likely to be reusable and experimentally more robust," he said.

Despite the precious nature of gold, Burland said that he doesn't expect it to dramatically increase the cost of the arrays, though it could significantly lower the cost per sample if the technology improves reusability.

In the grant's abstract, the researchers said that "the broader impacts of this research are to reduce costs, and improve the speed of analysis in proteomics research, clinical diagnostics, and the development of therapeutic antibodies. …Established markets for this platform include basic research, lab-on-a-chip diagnostics, drug discovery, forensics, detection of bioterror agents, and food and crop testing."

While other researchers have explored the use of carbon as a surface for array development, the potential advantage of the CoM method is the combination of the carbon surface with a label-free detection system, according to Burland. Putting biomaterial on gold tends to "damp the SPR response," Burland said, so getting "good label-free detection with this carbon surface [is] really the trick here."

Translating the technology from DNA to protein arrays, he added, is expected to depend mostly on the attachment chemistry for the proteins, which is part of the project. So far, there appears to be nothing inherent about proteins that would make them especially unsuitable for the CoM technology, he said.

In addition to the use of gold, GWC is exploring other metals for the technology, including silver, which allows for greater sensitivity than gold. Because silver oxidizes, it normally cannot be used as substrate material, but the CoM method may protect silver from oxidation, Burland said, and GWC plans to test that theory for its next project.

For now though, GWC is already seeking corporate partners to commercialize the technology, with an eye toward licensing the technology to firms that provide SPR detection.

"We can't make substrates in everybody's format," he said. The company is early in that process and given the economic climate, Burland acknowledged that it could be a challenge finding a partner willing to make the necessary investments.