Biodetectors aim to broaden search for anthrax bacteria
By Charles J. Murray
EE Times
(10/15/01, 10:25 a.m. EST)
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PARK RIDGE, Ill. — While medical experts ponder the anthrax medical mystery in Florida, scientists and engineers around the country continue work to develop devices that could detect deadly contaminants in military and civilian settings.
The devices range from large, desktop biodetectors that could find lethal pathogens in the air, water or soil to handheld units that could quickly detect such contaminants in blood or saliva. While desktop detectors could be only a year from production, handheld versions may still be three to five years away, researchers said.
The work, which has been under way for more than two years, has taken on new urgency since the Sept. 11 terrorist attacks. Scientists said this past week that the focus of the work has shifted since that time from military to civilian applications, especially after the recent death of a Florida man who had been exposed to anthrax bacteria.
"We're getting a lot more calls from private companies," said Harvey Drucker, associate director of Argonne National Laboratory (Argonne, Ill.). "Since Sept. 11, there's been a sense that we need to protect subway stations, airports and other public places."
"Unfortunately, we now know that terrorists don't care if a target is military or civilian," added Joseph Firca, chief scientific officer for Nanosphere Inc., which develops biodetection systems for medical and military applications. "It's scary, because we don't have enough vaccines to go around for the military, let alone the civilian population."
Stepped-up development
Researchers thus hope to build military and medical detectors whose usage might trickle down to the consumer market.
Because of market pressures, scientists and engineers have stepped up their development efforts. Teams of researchers are working on the technology at Argonne National Laboratory, Russia's Englehardt Institute of Molecular Biology, Pacific Northwest National Laboratory and Northwestern University, as well as at Nanosphere, Motorola Life Sciences and other companies.
Systems being developed today employ a combination of chemical and electronic techniques to identify strands of DNA from such pathogens as anthrax, smallpox, tuberculosis and the HIV virus.
Nanosphere (Northbrook, Ill.) uses an electrical technique to measure bonding between DNA strands in, for example, a blood sample. DNA strands in the sample are combined with similar strands in a silicon substrate and in gold nanoparticles, each measuring about 15 nm wide. To check for bonding, researchers measure the electrical resistance across two gold electrodes, located microns from one another.
When no bonding is present, resistance is high, and electricity barely conducts across the gap. But by laying a "capture strand" of anthrax DNA in the gap and then applying a blood sample, along with gold nanoparticles also containing an anthrax DNA strand, researchers can create an electrical bridge. If the blood sample contains anthrax or another target bacteria, the DNA on the gold nanoparticles bonds with DNA in the sample, and both of those attach to the capture strand in the gap.
The electrical bridge allows current to flow from one electrode to the other. Researchers strengthen the electrical connection by adding a silver "hydroquinone" solution.
The resulting change in electrical conduction is easily recognized. "If you start out with megohms of resistance across the gap and you apply the target and the resistance suddenly drops to 1 ohm, then you know your [pathogen] is present," said William Cork, chief technical officer of Nanosphere.
Cork said that when targets such as anthrax, smallpox or tuberculosis are in the sample, electrical resistance across the gap typically drops by a factor of about 1 million, thus providing a definitive sign of their presence.
The company is building prototype detectors using single-board computers for processing needs. If prototype detectors are designed to look for only one target, such as anthrax, then those processing needs are not critical, Cork said. Software algorithms, too, can be relatively simple.
"The software doesn't need to be sophisticated," Cork said. "You have to establish that the target is present. You also need to look at changes in resistance, and you need to recognize background noise."
Nanosphere engineers said that the key to the company's technology lies in its ability to attach DNA sequences to gold nanoparticles in a stable manner. "People have been able to attach DNA to nanoparticles for some time, but usually their stability is measured in days or weeks," Cork said. "We've developed a chemical means for attachment that is stable for years."
DNA bonds examined
Scientists at Argonne National Laboratory have teamed with counterparts from Englehardt Institute of Molecular Biology in Russia to create a biodetection system that also looks at DNA bonds. The system differs from other techniques, however, in its use of fluorescence to locate those bonds. By using a reader to shine a predetermined wavelength of light on tiny gel pads, the system recognizes the "light fingerprint" of DNA bonds. The results are then fed to a computer that analyzes the data and determines whether dangerous bacteria are present.
Argonne researchers are also teaming with scientists from Pacific Northwest National Laboratory to combine a commercial air collector with the light-fingerprint technology, in a bid to produce a biodetector that could examine samples from the air, water or soil. The detector would be a desktop unit, measuring about 2 feet x 2 feet by 6 inches deep.
Researchers are confident that the system could be ready as soon as a year from now. "We know our biochip works, and we know how to read it," said Lawrence Hill, special assistant to the associate director at Argonne National Laboratory. "Once we get it going, we don't envision a limit to the kinds of 'bugs' we can collect and detect."
Other teams are also working on biodetection technology. Motorola Life Sciences, for example, is developing a detector that's capable of simultaneously identifying 36 DNA targets. The company, formerly known as Clinical Microsensors, was acquired by Motorola in June 2000. A spokeswoman for the company would say only that its technology could be used for detection of deadly bacteria such as anthrax.
Despite all the efforts, scientists and engineers are not sure they can make smaller, handheld instruments that could detect airborne bacteria. Such instruments would need to be capable of detecting very low levels of the bacteria, because it takes only a few spores to cause disease in a human, they said.
"It's one thing to detect it in a blood or sputum sample," Cork said. "It's another to detect it when it's airborne. How do you pull volumes of air through a small instrument, grab a piece of DNA and detect it?"
For those reasons, airborne-pathogen monitors are expected to be larger, tabletop instruments for the foreseeable future.
Cost questions
Researchers are also uncertain about whether they can build biodetectors at the low costs and high volumes needed by the consumer market. The military, they said, has traditionally been willing to pay large sums for ultrareliable instruments. The medical industry is similarly willing to pay for new technology.
But before consumers consider buying such detectors and placing them in apartment buildings or workplaces, costs would need to drop significantly, possibly to the levels of smoke detectors. Engineers from companies such as Nanosphere predict that costs of less than $500 are possible in a few years, but no one is betting on $30 price tags.
"It's difficult to make a device that has the right economics and the right size," said Drucker of Argonne. "Even with a lot of money and a lot of sincere effort, it's going to take a while. This is not trivial."
Versatility may thus be the key to success for biodetectors, many engineers believe. Because the technology can be used to determine the presence of disease, it could be pushed forward by the needs of the medical community as well as the military.
"There are a lot of diseases that require faster identification and faster treatment," Cork said. "That's why it would be good for society to have systems like these for a lot of reasons, not just for biological warfare."
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