Chemical sensors must meet specific criteria, Rotello says. “You don’t want any test results that are false negatives – that is, the test indicating that a harmful chemical is not present, when in fact, it is present. You also want to minimize the number of false positives, or you’ll create panic at every turn.” The project may be ready for commercialization in three to five years’ time, he says. Faculty members collaborating on extending this project include Susan Cumberledge of biochemistry and molecular biology; Joseph Jerry of animal and veterinary sciences; and Craig Martin of chemistry.
The science community already has a firm grasp on detecting small molecules, Rotello says. Essentially, researchers build chemical structures that link onto the surface of the molecule, the way a key fits into a lock. But larger molecules, or macromolecules, such as those on the surface of a virus or bacterium, present a greater challenge. This is because the shape and topography of the large molecule are much more complex.
“These molecules are often so big that chemists can’t build something that fits around them effectively,” Rotello says. “Bacteria come in all different sizes and slightly different shapes, so a custom-designed ‘key’ that fits snugly against or around the molecule just isn’t a viable option.” Adding to the challenge, Rotello says, the chemical “key” can’t be too flexible or too rigid. He uses the analogy of Silly Putty: “If it’s too flexible, it won’t take the imprint from the newspaper page. And if it’s too rigid, it can’t be controlled reliably enough in order to do the job.”
The UMass team is aiming to address the problem by combining biology and materials science. The team is essentially trying to connect smaller, very specific “keys” into “locks” located along the surface of a macromolecule. The difficulty lies in connecting the “key” to the correct “lock” in exactly the right position. “It’s an extremely complex problem, and few good tools exist for dealing with it,” Rotello said. “You just can’t engineer a solution on an atom-by-atom basis.”
The UMass team has turned to assembling tiny scaffold-like structures in an effort to solve the problem. In this case, the tiny structures, called nanoparticles, are made of gold. The nanoparticles provide building blocks on which to construct the chemical “keys.” Researchers turned to gold because it is easy to attach chemical groups to gold surfaces. Once in place, the chemical groups can move, allowing them to selectively bind to the large molecules in exactly the right places – serving as “keys.”
A parallel project, underway with Jacques Penelle of the polymer science and engineering department, focuses on quartz crystals, similar to those used in everyday wristwatches. “The wristwatch works because the quartz crystal vibrates at very specific frequency, moving the clock mechanism,” explained Rotello. Using the same concept, researchers are hoping to identify chemical agents by relying on quartz. “A quartz chip weighs more with the agent on it,” said Rotello. “The chemical actually slows down the crystal, changing its frequency. If you look at the rate of vibration, you can determine whether a given chemical is present.” That project has already been developed for use in environmental pollutants, such as finding PCBs in wells. The project was funded with a total of $75,000 in grants by the National Institutes of Health, the National Science Foundation, and the University’s Materials Research Science and Engineering Center. Rotello’s research has brought $2,450,000 to the University in grant money during the past three years.
Note: Vincent Rotello can be reached at 413/545-2058 or rotello@cisco.chem.umass.edu