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  Single Virus Detector Invented  
by: Francis C. Assisi

West Lafayette, 08 Feb 2004 -- Researchers at Purdue University reported Feb 4th that they have developed a miniature device sensitive enough to detect a single virus particle. The advancement could have many applications, including better disease detection, environment monitoring and bioterrorism defense.

The research was conducted by Indian American doctoral candidate Amit Gupta, under the supervision of Pakistani American Associate Professor Dr. Rashid Bashir at the Laboratory of Integrated Biomedical Micro/Nanotechnology and Applications at the Birck Nanotechnology Center.

Although the idea still must clear some major hurdles, Bashir says the scientists involved hope it might be commercialized in the next five to eight years. The ability to detect airborne viruses with a small, easy to use device in real time would be a major advantage in the confinement and management of viral epidemics, he says

The device is a tiny "cantilever," a diving board-like beam of silicon that naturally vibrates at a specific frequency. When a virus particle weighing about one-trillionth as much as a grain of rice lands on the cantilever, it vibrates at a different frequency, which was measured by the Purdue researchers.

"Because this cantilever is very small, it is extremely sensitive to added mass, such as the addition of even a single virus particle," said Rashid Bashir, an associate professor of electrical and computer engineering and biomedical engineering.

Findings are detailed in a paper to appear March 8th in Applied Physics Letters, a journal published by the American Institute of Physics.

The work, funded by the National Institutes of Health, is aimed at developing advanced sensors capable of detecting airborne viruses, bacteria and other contaminants. Such sensors will have applications in areas including environmental-health monitoring in hospitals and homeland security.

Disease Detector

"This work is particularly important because it demonstrates the sensitivity to detect a single virus particle," Gupta said. "Also, the device can allow us to detect whole, intact virus particles in real time. Currently available biosensing systems for deadly agents require that the DNA first be extracted from the agents, and then it is the DNA that is detected."

As part of the grant, the researchers intended to demonstrate three things: that the sensors have the sensitivity needed to detect a single virus particle; that the sensors can detect the viruses selectively without becoming clogged with other particles; and that it’s possible to concentrate enough particles near the sensors to detect airborne viruses.

So far, Bashir says, they have demonstrated the first of these: that the sensors have the sensitivity to detect a single virus particle. “The challenges will be active concentration of the particles, and removal of the non-specifically bound particles -- different viruses we’re not looking for that could give a false positive.”

The scientists now hope to be awarded funding for three more years, Bashir says, adding that the grant then would total $2.1 million. If they are awarded the three-year extension, they will attempt to construct devices that can look for different virus particles simultaneously, and they also may begin seeking additional funding for their project, he says.

At the end of the five years, Bashir says, the researchers might be in a position to start a company in an effort to commercialize the technology, which has other possible applications as well. For example, viruses are between 50 and 200 nm in size, Bashir says. Meanwhile, bacteria and spores range between 1 and 2 micrometers. “If we can detect the smaller particles, then the same technology is extendable to spores and bacteria,” he says.

The researchers have filed a patent application on their technology, Bashir says.

The next step for the scientists will be to coat a cantilever with the antibodies for a specific virus, meaning only those virus particles would stick to the device. Coating the cantilevers with antibodies that attract certain viruses could make it possible to create detectors sensitive to specific pathogens.

"The long-term goal is to make a device that measures the capture of particles in real time as air flows over a detector," Bashir said.

Earlier, Bashir and colleagues, including Arun Bhunia an Associate Professor of Food Science, created the first protein "biochips," mating silicon computer chips with biological proteins that could quickly and cheaply detect specific microbes, disease cells and harmful or therapeutic chemicals. It would save lives detecting toxins in food immediately. The chip could speed diagnosis, test in real-time for poisoning (as opposed to the days currently required for food samples to be cultured) and even prevent tainted foods from ever being shipped.

Bashir and his group are striving to create "lab-on-a-chip" technologies in which miniature sensors perform essentially the same functions now requiring bulky laboratory equipment, saving time, energy and materials. Thousands of the cantilevers can be fabricated on a 1-square-centimeter chip.

The Purdue researchers used the device to detect a particle of the vaccinia virus, which is a member of the Poxviridae family and forms the basis for the smallpox vaccine.

The cantilever is about one micron wide - or about one-hundredth the width of a human hair - 4 microns long and 30 nanometers thick. A nanometer is a billionth of a meter, or roughly the length of 10 hydrogen atoms strung together.

"This cantilever mechanically resonates at a natural frequency, just like anything that vibrates has a natural frequency," Bashir said. "What we do is measure the natural frequency of the cantilever, which is a function of its mass. As you increase the mass, the frequency decreases. And the way to increase the sensitivity is to make that starting mass very, very small."

A single vaccinia virus particle weighs about 9 femtograms, or quadrillionths of a gram. "So, if a grain of rice weighs a couple of milligrams, one of these virus particles weighs about one-trillionth as much," Bashir said.

MEM devices

Because the cantilevers are mechanical parts measured primarily on the scale of microns, or millionths of a meter, they are called "micromechanical devices."

The cantilever measures just about one micron wide, four microns long and 30 nanometers thick. A human hair, for comparison, measures about 100 microns wide. There are major challenges to the development of MEM devices. At the scale they work, the physical forces of importance are not those of our world. Gravity, for example, becomes less important than atomic forces.

But the benefits of MEM have attracted much attention. For starters, thousands of MEM machines can be cheaply manufactured from a small piece of silicon.

Much research is focused on using MEM for sensors and the construction of a "lab-on-a-chip." Miniaturization allows for extremely sensitive sensors that can detect single molecules, and a lab-on-a-chip would take advantage of such sensitivity to perform rapid, cheap and portable diagnostic tests.

There is much overlap between MEM and nanotechnology, which is concerned with nanometer-scale objects. A MEM device shrunk to the nanoscale could enable molecular nanotechnology, the theorized ability to manipulate molecules using nanoscale "machines."

Science researchers interested in profiling their work in this column are encouraged to submit their biodata and relevant publications to INDOlink at: editor@indolink.com