Saturday, August 21, 2010

Sensing Danger: Researchers Develop New Sensing Technologies to Improve Response to Chemical and Biological Attacks

Should terrorists ever use chemical or biological weapons , new sensing technologies being developed at the Georgia Institute of Technology could help public safety officials respond more rapidly and effectively to the threats.

A type of highly fluorescent polymers called PPEs could be the basis for a chemical sensing system that would detect pathogens and toxins that might be used in a bioterrorism attack. The system is under development in the laboratory of Uwe Bunz, professor of chemistry and biochemistry. PIc:Georgia Tech Photo: Gary Meek

For example, chemical sensors in building ventilation systems could detect a release of gas intended to harm the occupants. The detection might then trigger a shut down of the ventilation system, says optical sensor developer Dan Campbell, a senior research scientist at the Georgia Tech Research Institute (GTRI). He recently presented an American Chemical Society invited lecture on using sensor technologies to counter terrorism.

Chemical sensors could also be mounted on an unmanned aerial vehicle (UAV) to track a chemical plume, giving emergency managers insight on evacuation plans, Campbell suggests. And rapid biological sensors could be incorporated into handheld devices for first responders investigating a suspicious package.

“Many sensor technologies under development are becoming reliable, versatile, inexpensive and presumptive – they can help first responders make a reasonable assessment,” Campbell notes.

At Georgia Tech, work has been under way on sensing technologies that could not only improve homeland security, but also enhance response to industrial accidents, environmental pollution and food-borne pathogens.

Multi-Purpose Optical Sensor

Campbell and his GTRI colleagues have been developing an integrated-optics sensor that can detect the presence of biological agents in minutes and chemical agents in seconds. They are tuning the sensor for detection of industrial pollutants, food-borne pathogens and, most recently, agents associated with terrorist attacks. The U.S. Marine Corps Warfighting Laboratory and Marine Corps Systems Command supported the latter research.

The sensor, which may cost significantly less than current devices, consists of a laser light source, a planar waveguide (essentially a small piece of glass through which the light travels) and a detector for monitoring light output.

Pic:Researcher Dan Campbell and his colleagues are testing the operation of GTRI's chemical sensor mounted in the nose cone of the U.S. Department of Defense's Dragon Eye mini-UAV (unmanned aerial vehicle)

Reactions on the waveguide surface alter the speed of light through the waveguide. This change is monitored with an interferometer by comparing a reference beam with another beam traveling under the sensing chemistry. Signal processing software interprets the sensor’s results and delivers information on the agents’ identity and quantity.

The waveguide chip is small enough that it can accommodate several sensing channels designed to detect a wide variety of chemical and biological agents.

“We’ve built one platform for all possible uses, both in the air and in the water,” Campbell explains. “You don’t change out the laser or detector. You just plug in the chip you need and you’re ready to go.”

Georgia Tech Research Institute researchers have successfully and rapidly detected numerous agents, including anthrax, in laboratory tests. In this confocal microscope image of anthrax, cell walls appear in green, while the spores are red.
Photo: Centers for Disease Control and Prevention

Researchers have successfully and rapidly detected numerous agents – including Salmonella and Campylobacter bacteria, anthrax, ricin, chlorine and ammonia – in laboratory tests, as well as groundwater contaminants such as chlorinated hydrocarbons in field tests.

Recently, they have improved the sensor’s reliability and sought new applications for the technology. To sense biological agents, the device takes rapid, direct measurements of the binding of an antigen to a chemical receptor on the waveguide surface. Researchers previously used antibodies as receptors. But they are more expensive and less reliable than aptamers, the synthetic, nucleic-acid-based receptors used in the sensor now, Campbell says. GTRI research scientist Jie Xu has been assisting Campbell with the aptamer work.

Aptamers have been available for more than a decade, but haven’t been used much until recently. “The aptamers are rock stable,” Campbell says. “They work the same way every time. And they are reusable and basically cheaper to make than antibodies.”

GTRI is exploring several opportunities for its sensor. The U.S. Naval Research Laboratory and the Marine Corps Warfighting Laboratory are seeking applications for their Dragon Eye mini-UAV (unmanned aerial vehicle). The reconnaissance device, which can be launched by hand or with a bungee cord, can fly one-hour missions within a 6-mile radius of the launch site. So GTRI researchers are testing the operation of the chemical sensor mounted in the UAV’s nose cone.

Researcher Dan Campbell and his colleagues are testing the operation of GTRI's chemical sensor mounted in the nose cone of the U.S. Department of Defense's Dragon Eye mini-UAV (unmanned aerial vehicle)..
Georgia Tech Photo: Gary Meek

Campbell successfully demonstrated the idea at a recent defense technologies conference. But he wants to shrink the sensor from its current one-half-pound size to about one ounce. Then he plans to mount a sensor on each of the Dragon Eye’s wings to get a more precise reading on the source of a chemical plume, he explains. The same concept could then apply to a remotely operated roving vehicle or one that could swim, Campbell adds.

Meanwhile, Campbell has just begun work for AIMSI, an Oak Ridge, Tenn., company that wants to use GTRI’s sensing technology in a handheld device for first responders and a groundwater monitoring device for environmental professionals.

Also, Campbell’s GTRI colleague David Gottfried is collaborating with the University of Georgia’s Center for Food Safety to develop the sensing chemistry to detect infectious disease agents, including potential bioweapons, in water, fruit juice, milk, food and the environment.

Fully Integrated Sensing Systems

Researchers test an optical chemical sensor with this experimental set-up in the laboratory of Associate Professor of Electrical Engineering Stephen Ralph (right). Associate Professor of Chemical Engineering Cliff Henderson (left) is among those contributing to the project's development of integrated micro-optical sensors for chemical and biological testing.
Georgia Tech Photo: Gary Meek

“The advantages of this system will be better performance, a smaller size that uses less power, full integration and a low cost of only a few dollars per chip,” explains Stephen Ralph, the Georgia Tech School of Electrical and Computer Engineering associate professor who is leading a $1.5 million part of the research effort. “This is our vision. We still have a lot of science and engineering to do to merge these technologies into a fully integrated system.”

The optical sensing technology works like this: A source emits light that passes into a piece of silicon nitride, which serves as a waveguide. This silicon nitride is also an interferometer, which divides the light into two separate paths. On one path, a polymer absorbs the agent being investigated, and on the other path, a reference, no agent is absorbed.

After passing through these two paths, light is recombined by the interferometer. This separation and recombination of light detects relative changes in the optical refractive index caused by the absorbed agent. The recombined signal is optimized with signal processing software to enhance sensitivity. The result is an interference pattern that changes when an agent contacts the sensor.

Now in its fourth year, this proof-of-concept stage of the research – which is funded by the Defense Advanced Research Projects Agency (DARPA) through the University of Illinois – will conclude in December 2004, but researchers are seeking support for continued study.

“The remarkable advantage of a fully integrated system is the ability to apply dynamic signal enhancement strategies to improve sensitivity and selectivity while reducing the likelihood of false positives,” Ralph says. “We have fabricated a fully integrated system, although challenges remain in the integration of the optical sources in an efficient manner with the rest of the chip.”

Researchers have not yet tested the sensor with any agents of concern, but have experimented with compounds having similar properties and demonstrated sensitivities in the hundreds of parts-per-billion range using their signal enhancement strategies. Additional funding will enable tests of “mock” agents that have similar chemical composition to the substances terrorists might use. Then, they hope to make the device more sensitive and address fabrication issues that will affect manufacturing yield and cost, Ralph adds.

The Georgia Tech-based research team involves Ralph and Associate Professor of Chemical Engineering Cliff Henderson and their graduate students. Working with them are former Georgia Tech Professor Nan Jokerst and Associate Professor Martin Brooke, now at Duke University.

Meanwhile, their collaborators at Colorado State University and the University of Michigan are working on microfluidic sensors with a fully integrated design. These devices will detect agents in liquid form as they flow through micro channels created by integrated circuits technology. When light passes through or near these channels, a change in a fluid’s optical properties would indicate the presence of a particular agent of concern.

Also, researchers at the University of Illinois, which is administering the overall project for DARPA, are working on optical sensors that detect agents in the far infrared part of the spectrum.

“Some of these technologies under development will prove to be more effective with certain agents than others, while some will be more integrated than others,” Ralph says in explaining the multi-university, multiple technologies approach. “There will be a tradeoff between selectivity, sensitivity and cost. So there’s not just one solution, but many depending on the application.”

Detecting Changes in Fluorescence in Polymers

Polymers called PPEs are typically not soluble in water, but for use as sensors, they must be. So researchers added very polar, water-like extensions to the lipophilic, or butter-line, substituent chemical side chains that extend from the local chemical backbones that form PPEs.
Georgia Tech Photo: Gary Meek

“Fluorescence is very sensitive to the chemical environment,” says Uwe Bunz, a Georgia Tech professor of chemistry and biochemistry. “So it’s a very good tool to report changes.”

With a one-year, proof-of-concept grant from the National Institutes of Health, Bunz is exploring the feasibility of detecting changes in the fluorescence or color of PPEs when they interact with a pathogen or toxin. But the goal has presented some technical challenges.

PPEs are typically not soluble in water, but for use as sensors, they must be, Bunz says. So researchers added very polar, water-like extensions to the lipophilic, or butter-like, substituent chemical side chains that extend from the long chemical backbones that form PPEs.

“This achievement was very important because we live in a water-based world,” Bunz notes. “Everything with biological importance has to be looked for in water.”

Researchers must also make PPEs mimic the sensing functions of human cells in a primitive way, Bunz explains. On the surface of pathogens and some toxins are proteins called lectins that bind with sugar molecules on the surface of human cells to attack them. Similarly, Bunz wants to add sugar molecules to the chemical side chains that extend from PPEs. Then he will see if these sugars bind with lectins.

Polymers called PPEs could be the basis for a chemical sensing system that would detect pathogens, such as cholera (shown here), and toxins that might be used in a bioterrorism attack. Cholera is a major epidemic disease that has killed millions of people.
Photo: Centers for Disease Control and Prevention

Researchers have been synthesizing a library of PPEs and other polymers with sugars attached, and they have begun early-stage testing of these materials.

“We don’t want to work with something like anthrax right now, so we’re testing these polymers with free lectins to see if we can detect lectin binding with the polymer,” Bunz explains. “We’re looking for a change in the amount of fluorescence or a change in the color of fluorescence.

“We’ve done a little of this lectin sensing, but to do this better, we need to use longer extendable linkers for the sugars attached to our polymers,” Bunz says. “It’s a major challenge to do this.”

But Bunz is hopeful that his research team can overcome the technical obstacles they face and eventually find military, homeland security and medical applications for this technology, he says.

One scenario he envisions would be a field test kit that first responders could use if they found a suspicious package. Hazardous materials personnel could dissolve some of the package’s content in water, add Bunz’ polymer solution and then use a black light to quickly determine a change in the polymer’s fluorescence or color.

If the concept proves feasible, Bunz will seek additional funding and collaborate with a biosafety laboratory that can work with the pathogen anthrax and/or the toxin ricin.

“If we can make the links longer and then detect a change in fluorescence with the addition of 1,000 or even 10,000 lectin molecules, then we’ll know we have something really good,” Bunz adds.


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