biological
fire alarm

One research team has demonstrated that a cantilever device can pick up the addition of a single virus's worth of mass.

New York's Penn Station at rush hour is a logistical marvel. But from the point of view of a bioterrorist, it is heaven on earth. Millions of commuters rub shoulders each day in the warren of passageways and platforms. Add one person infected with a virulent strain of plague or smallpox, and the pathogen could be spread up and down the Eastern Seaboard before authorities had the first hints of catastrophe.

What could help avert such a disaster? Perhaps a device that's under development at Purdue University in West Lafayette, Ind. The device would sniff the air, looking for viruses. When it found one, the device could alert health workers immediately. Think of it as a biological fire alarm.

Researchers have worked to develop such devices for more than a decade. In the immediate aftermath of the end of the Cold War, experts feared that the fruits of Soviet biological warfare research could fall into the hands of terrorists, and that the United States and other Western governments were unprepared. Funding for such work was scarce, and the plans for detectors were often rudimentary. Some schemes even relied on using live animals, which were more sensitive to target diseases than are humans—an almost literal application of the "canary in the coal mine" idea.

Shortly after Sept. 11, 2001, when the prospect of bioterrorism became immediately apparent, the National Institutes of Health put out an offer to fund research in developing devices that could detect pathogens in public spaces in real time. "The call itself didn't really mention bioterrorism," said Purdue biomedical engineer Rashid Bashir. "It laid out a technical challenge we thought we could meet."

A vibrating silicon cantilever (above) is sensitive enough to detect a single virus's mass (below).

Together with student Amit Gupta and researcher Demir Akin, Bashir devised a three-part development program. The first was to find a means of detecting the presence of a single virus—a not-quite-alive bit of DNA encased inside a protein sheath with a typical mass measured in femtograms— quadrillionths of a gram. Viruses don't reproduce outside living cells, and they are so small that only powerful optical or electron microscopes can make them out.

The key was to locate a virus-scale device that could react to something so negligible. Bashir's team found it in a slender silicon arm. Such an arm, called a cantilever, juts from a block of silicon and has the natural tendency to vibrate at a specific, regular frequency dependent on its mass and length. Change the mass, and the vibration frequency changes.

If a virus particle landed on a vibrating cantilever, the vibration would change in a way that could be picked up almost immediately. "The system would employ filters that would screen out anything over a half-micron in diameter," Bashir said, including dust, spores, and bacteria. In January, the team was able to demonstrate that such a cantilever device was capable of picking up the addition of a single virus's worth of mass. The cantilever that the team used was only 4 micrometers long and 30 nanometers thick.

Next up is figuring out just what kind of virus the cantilever has detected. Bashir's team has that problem in its sights: It plans to coat a cantilever with antibodies tuned to a specific virus. The antibodies act as a molecular Velcro, glomming on to the right viruses and rejecting all others. A set of cantilevers, each one coated with a different antibody, could scan for a whole suit of potentially deadly biological agents—both naturally occurring and terrorist planted.

Bashir expects to have an antibody coating on a cantilever by the end of the summer. Then comes the hard part: making the whole system work. Antibodies are biological particles that work best in liquids—or, at the very least, extremely humid air. Nano- scale cantilevers, on the other hand, are best suited to vacuums. Integrating those two elements and adding others to deliver a steady airstream remains a challenge.

Once a system is operational, its benefits would extend beyond bioterrorism monitoring, Bashir says. The system could track the spread of pathogens in hospitals or alert authorities to the introduction of epidemic strains of the flu in schools.

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© 2004 by The American Society of Mechanical Engineers