Early in the recent war with Iraq, sandstorms buffeted U.S. troops, choking lungs, guns, and tanks. But it was the potential presence of invisible threats in the air–sandstorm or not–that was most worrisome. At any time or place, it seemed, nerve gas could be lurking. Or anthrax. Or maybe some brand new chemical or biological weapon. Such concerns go beyond the battlefield. Back home, while on “orange alert” during the combat phase of the Iraq war, subway riders wondered how safe, exactly, was the air underground.SENSITIVE DETECTION. A capillary tip emits ions during mass spectrometry. Researchers use this method to identify proteins, including those that might serve as markers of disease. Eventually, this technology may detect early signs of infection in troops. H. Schulman/SurroMed SMART SENSOR. Illustration depicts how silicon smart dust could detect airborne chemicals. The porous nanostructure is chemically modified so that its optical code (lower right) changes in a predictable fashion when it’s exposed to selected molecules (inset). In this example, the smart dust would detect certain types of nerve-targeted warfare agents, such as sarin. Sailor, UCSD DETECTION BY DUST. A microscope image (background) shows particles of porous silicon smart dust, each grain about the width of a human hair. The colorful dust is visible to the naked eye in a vial of liquid (foreground). F. Cunin, UCSD
While the tanks waited in the sand this March, scientists at a national meeting of the American Chemical Society in New Orleans paused in front of convention-hall monitors tuned to CNN. They had a special interest in the situation’s complications. “There is this clear and present danger that only analytical chemistry will be able to do something about,” said Anthony Czarnik, a researcher at the Germantown, Md., company Sensors for Medicine and Science.
In the fictional universe of Star Trek, a device called a tricorder spits out a complete list of chemical and biological contaminants. Unfortunately, there’s no real-world instrument that can instantly sift through the messy brew in the air of the Iraqi desert or the New York subway.
Instead, there’s a host of limited analytical techniques for scrutinizing the air, soil, and water on the battlefield and at home. Some analytical chemists now aim to step up those systems to make them better matched to the tasks at hand. Meanwhile, other chemists are developing novel technologies intended to be more sensitive and more portable than existing methods. Some of the new approaches incorporate ideas from many disciplines, ranging from microengineering to biomedical science.
On the battlefield–and to a lesser extent at home–an array of devices detects chemical and biological weapons and sends out a warning. The instruments range from low-tech, chemically sensitive paper to leading-edge laboratory equipment.
There is no tricorder, says Barbara Seiders of the Pacific Northwest National Laboratory in Richland, Wash., and it’s unlikely there ever will be a detector that can work in all situations.
Today’s detectors must be tuned for certain chemical or biological threats and suit specified environmental conditions.
Two of the simplest tools used by the military are an indicator paper called M-8 and a tape called M-9. Troops can place these on their uniforms or vehicles to detect nerve gas or blister-causing compounds. Coated with chemical-sensitive dyes, the paper changes color when at least one of these agents is present. But simplicity comes with drawbacks. The paper isn’t very sensitive, working well only when it’s in a location that’s “dripping” with the chemical, says Seiders. It’s also not very selective about which chemicals cause its color to change, so harmless compounds sometimes trigger a response.
On the battlefield, small handheld detectors employing ion-mobility spectrometry are more sensitive and selective than indicator paper. This technology, sometimes called the poor-man’s mass spectrometry, is also used in airports. These systems break up a substance into electrically charged pieces and then interpret how the molecular fragments move. The pattern in which the pieces arrive at a charge-sensitive element constitutes a signature for the original molecule.
Ion-mobility spectrometers can detect a variety of molecules but can’t necessarily tell the difference between chemically similar molecules, such as certain pesticides and nerve agents.
The military also has reconnaissance vehicles with larger instruments, including mass spectrometers. Although more effective than current handheld devices, they’re less powerful and sensitive than laboratory-scale machines, says Seiders.
For detecting agents at a distance, there are systems that include lasers that the military can aim, for example, at a cloud that’s suspected of harboring dangerous chemical or biological agents. These instruments can give troops an idea of the chemical composition of a cloud or indicate whether the cloud contains small aerosol particles that are the size of biological agents that they suspect the enemy possesses.
“Then, the idea is, you could go the other way,” says Seiders. “Or tell your guys to suit up.”
None of these systems, or other currently used methods of detection, provides results as conclusive as rigorous sample testing in a state-of-the-art laboratory facility. So, military troops usually ship potentially hazardous materials to a lab, says Seiders.
However, by asking thoughtful questions, analytical chemists can help the military make the current field methods more valuable, Seiders says. They must consider how detectors will work in different settings: Can the device work fast enough? Is it sensitive enough? Is it giving too many false alarms? Is it displaying enough information to guide decisions?
While there’s already a wide range of instrumentation available for detecting chemical and biological agents, many researchers are heading off in new directions. In some cases, they’re applying ideas from microengineering and biomedical science.
Ideally, a threat would be detected long before it comes close enough to harm anyone. That’s the aim of the “smart dust” being developed by chemist Michael Sailor of the University of California, San Diego, who reported his work at the American Chemical Society meeting.
These tiny sensors, built of a porous form of silicon, just look like sparkly specks of dust, but each one is designed to change color in a characteristic way when a particular organic material alights upon it.
Sailor plans for his sensors to be as small as a grain of dust but capable of reliably detecting a particular biological or chemical agent. Hundreds of thousands of these dust grains, tuned to detect many dangerous substances, could be dropped on a battlefield, stuck to vehicles and buildings, or placed in a small box inside a subway air vent.
Next, a laser–say, on an airplane flying over a desert sandstorm–would read the spectrographic signature of the smart dust to see what agents the particles had encountered.
Currently, Sailor can read a signature from the dust at 25 meters, and he’s aiming for 1 kilometer. In a system for use in subway vents, sensors monitored by a laser hooked to a computer might trigger filters to switch on when they detect a potential threat, such as a nerve agent.
This could save money on a filtration system that’s too expensive to run continuously, says Sailor, who’s working with a company to devise such a system.
One of the biggest challenges in chemical and biological weapons detection is how to identify a harmful agent that’s never before been seen. “You don’t necessarily know what organisms you’re going to come across,” says Pacific Northwest National Laboratory’s Karen Wahl.
This spring, Seiders notes, the world was blindsided by one of Mother Nature’s own creations, a virus that causes severe acute respiratory syndrome, or SARS. What if a terrorist were to engineer a new pathogen?
For several years, Wahl has led a team using a system known as MALDI-MS, or matrix-assisted laser desorption/ionization mass spectrometry. Researchers have used this process for a couple of decades. It turns large molecules such as proteins into gaseous ions and then, on the basis of their charge and mass, separates the ions to determine the makeup of the original sample.
Wahl and her team used this technology to analyze proteins from some 20 organisms, including strains of Escherichia coli, Bacillus, and Pseudomonas bacteria. From their experiments, they’ve developed a library of data that enables them to classify or identify related pathogens. In the Dec. 15, 2002 Analytical Chemistry, the researchers reported a particular strength of their technique: It can identify individual bacteria in a mixture.
Sensitive mass spectrometers, including MALDI-MS systems, are generally too large to carry into the field, however. Wahl’s group at PNNL is collaborating with Johns Hopkins University’s Applied Physics Laboratory (APL) in Laurel, Md., where researchers are developing portable MALDI-MS systems that could take advantage of its bacterial library. Ideally, says Wahl, systems such as these could eventually monitor for bioweapons in the air on a battlefield, in a subway, in an office building, or at a variety of other locations.
Biological warfare may result in a mix of pathogens at very low concentrations. For those reasons, APL’s miniaturization work is accompanied by research that aims to discover the best ways for their systems to collect aerosols for analysis.
Indeed, miniaturization is a big area of development in chemical- and biological-agent detection, and the topic was a focus of the analytical chemistry sessions in New Orleans last month. For example, many researchers are now working to miniaturize mass spectrometry. It’s the ideal technique for analyzing the proteins of microorganisms, says Robert Cotter of Johns Hopkins University in Baltimore, who is also collaborating with APL scientists on the miniaturization of mass spectrometers. This miniaturization is “not just an engineering problem,” he comments, “because you don’t just shrink it and get the same results. You actually have to redesign.”
Portable mass spectrometry devices could open novel approaches to detecting a bioattack. Cotter’s team is one of several looking into a means to detect, within hours of exposure, whether a bacterial or viral agent has infected a person. This technique was developed for medical use, but Cotter says it could have important military applications.
With mass spectrometry, Cotter and his colleagues search for telltale, chemical markers of an immune response in pigs before symptoms appear. They do this by examining the proteins in the animals’ expired breath. Such information could enable the military to be better prepared for combat, says Cotter.
For example, a soldier infected with a contagious agent–whether it’s a deadly terrorist bioagent or a common cold virus–could be quarantined before he infects the rest of his team, says Michael Natan of Nanoplex Technologies in Mountain View, Calif.
Nanoplex’s parent company, SurroMed, uses mass spectrometry and several other technologies to monitor the first signs that a person will develop particular diseases, such as arthritis or Alzheimer’s. To do this, SurroMed scientists track thousands of proteins and watch how cells behave.
SurroMed plans to translate its work on biomarkers into military technology. The company’s goal, Natan says, is to discover the first responses that may be shared by infections, whether they’re minor or serious, bacterial or viral. For example, there may be five particular molecules in the blood that increase during the first hour after exposure. Even if the cause of this signal in a particular soldier is nothing more than a common cold virus, military commanders still may want to pull him from the front line, says Natan.
Czarnik works along these avenues, too. He’s developed a small glucose sensor for eventual use by diabetic people. He proposes that it might be transformed into a system for detecting other substances, such as warfare agents, in the blood.
The Tic-Tac-size sensor, which Czarnik described at the American Chemical Society meeting in March, would be implanted just under the skin of the wrist. It would monitor glucose concentrations in the blood 24 hours a day and wirelessly relay this information to a small display on a watch that could be worn just over the implant. So far, he’s tested the system successfully in rabbits, and he plans to try it in monkeys later this year.
One potential pitfall acknowledged by scientists who strive to improve detectors is that the devices are not regulated. Czarnik points out that the Food and Drug Administration regulates glucose sensors for medical use, which forces him to include important safeguards, such as a way to tell the user when the system is failing so that the patient doesn’t believe false readings.
There is no agency that says whether an instrument is qualified to detect a biowarfare agent, says Seiders.
Developing standards for these detectors is a high priority for the Department of Homeland Security, says Seiders. In the meantime, she says, the analytical chemistry community needs to make sure that any new device does the things that its developers claim. The life of a soldier or commuter could depend upon it.
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