Seeking A Clue Of Flu

With a simple color change from blue to red, two materials created by LBL researchers signal the presence of influenza, offering the possibility of a quick nasal or throat swab test for viral infection.

Both materials are based on flu-binding molecules developed by the researchers. In one, the molecules are assembled into a thin film; in the other, they are formed into microscopic spheres known as liposomes.

Materials scientist Deborah Charych developed the technologies with LBL chemist Jon Nagy, U.C. Berkeley graduate student Wayne Spevak, and former LBL scientist Mark Bednarski, who initiated the research. The work is part of an ongoing research program to tailor materials for detecting pathogens, environmental toxins, and other targets of interest.

LBL materials scientists Deborah Charych and chemist Jon Nagy use a new apparatus designed to assemble membrane-like films that detect viruses and other infectious disease agents.

The tests are a significant advance in the field of biosensor research, where scientists have generally relied on elaborate combinations of antibodies, or electronic and optical instrumentation to measure biological substances. "Simple virus detection with the materials requires little or no instrumentation," Charych says. "You just look for a color change from blue to red."

The molecule that is the basis for the materials has a composite structure, where one part of the molecule binds the virus and the other serves as a structural backbone. The virus-binding element is the cell surface sugar, called sialic acid, that serves as an attachment site on human cells for flu viruses. The sialic acid is connected to a diacetylene lipid, a molecule similar to the phospholipids that are the building blocks for cell membranes.

The molecules can be made to assemble into thin films on surfaces or into free liposomes in solution. Exposure to UV light activates a triple bond within the diacetylene lipids, creating stable, blue-tinted films or liposomes which are covered with sialic acid sugars.

Potentially infected samples are dropped onto the surface of the film or into the liposome solution, and virus present binds to the sialic acid sugars. Virus binding changes the structure of the interconnected lipid chains beneath the sugars, and causes the molecules to absorb a different wavelength of light, i.e. change color from blue to red.

The amount of color change depends on how much flu virus is present in a sample; lower concentrations of virus generate only an intermediate purple color. Researchers can estimate the amount of virus in a sample by reading the films or liposomes with a colorimeter.

"We think we can detect the virus at levels lower than what you see in a full-blown flu case," Charych says. "The next step is obtaining throat or nasal swab samples from flu patients to show that these could be easy tests to use in the field or in a doctor's office."

The researchers are also working to understand the molecular mechanisms of the color change, and to apply the sensor technology to other environmental agents.

-- Mike Wooldridge