Biothreat analysis: While you wait

Oct. 15, 2013

In the 1968 Michael Crichton book “Andromeda Strain”, scientists working in the highest underground biosafety levels took days using the most sophisticated equipment available at the time to identify an alien pathogen.

In the 45 years since, the equipment and protocols have improved, but it can still take weeks or even months to identify some terrestrial toxins.

Now, a faster survey method has emerged.

A scientist at the Texas Biomedical Research Institute has developed a way of detecting bioterror threats in about an hour. The new process, called Rapid Antibody Pairing, is not only faster but cheaper, which may accelerate bioterror countermeasures.

Normally, this type of resource-intensive biochemical screening requires costly chromatography systems to purify and analyze protein molecules that can number in the hundreds and takes months to complete.

“I figured out a very simple and reliable way to bypass the need for purifying these proteins and scaling everything down such that a target capture assay can be developed in hours rather than weeks,” says Texas virologist Andrew Hayhurst.

Improvements in biothreat detection are welcome, not only to meet mandates of the Public Health Security and Bioterrorism Preparedness and Response Act of 2002, but to help protect police and other first responders at the scene of a suspected biochemical incident. According to the National Institute of Standards and Technology, suspicious packages and powders have triggered more than 30,000 responses by domestic police agencies since 2001—or about eight every day. These responses are expensive, time-consuming, and potentially dangerous.

Hayhurst’s streamlined process performs at any biosafety level, with minimal equipment. “The system works at enhanced biosafety level 2 using botulinum neurotoxins—the world’s most poisonous poisons, and at biosafety level 4 using Ebolavirus Zaire, a hemorrhagic fever virus with 95 percent fatality rate,” he says. Botulinum neurotoxins and Ebolavirus are among the biothreats categorized as Tier 1 agents by the departments of Agriculture, and Health and Human Services. Tier 1 agents present the most significant potential for mass casualties. The list also includes anthrax, Marburg virus, and plague.

Hayhurst says his methods are so straightforward that most laboratories are probably already familiar with the nuts and bolts of his new process, so it would be easy to adapt existing processes to take advantage of the benefits of the new system.

"Being able to respond quickly to known biological threats will better prepare us for combating emerging and engineered threats," Hayhurst says.

Better biochemical detectors

Hayhurst’s biothreat analysis work is not the only research effort attempting to harden the country against chemical-based terror attack. At the University of Maryland, scientists are working on a better way to detect biochemical weapons with a faster, more sensitive photodetector.

Researchers at the UM Center for Nanophysics and Advanced Materials have come up with a superconducting bolometer technology that can be used in everything from airport body scanners to standoff detection of chemical and biochemical weapons. A bolometer is a device for measuring electromagnetic radiation.

The UM bolometer uses two atom-thin sheets of graphene, whose unique properties make it sensitive to a broad range of light energies, from terahertz frequencies or submillimeter waves through infrared to visible light.

“The terahertz frequency range is an area of the electronic spectrum which is particularly difficult to detect, but is important for security applications, such as standoff detection of explosives or chemical weapons materials, and scanning of opaque objects such as structures or clothed people,” says UM physics professor Michael Fuhrer.

While chemical and biological weapons are considered weapons of mass destruction (U.N. Resolution 687) and their use banned by international law (Chemical Weapons Convention, 1993), they are nevertheless a present threat. A United Nations report released September 16 confirmed that rockets loaded with sarin gas were used in the Syrian civil war August 21 against civilians in the Damascus suburb of Ghouta. The U.N. called the attack a war crime, but stopped short of saying who was responsible. The United States, however, places blame on forces loyal to the ruling regime of President Bashar al-Assad. Over 1,400 civilians died in the attack, including over 400 children.

An attack by terrorists using chemical agents is generally considered to have a low-probability, due to the difficulty of manufacturing, storing, and delivering the agents. According to the Stimson Center's Chemical and Biological Weapons Nonproliferation Project, it would take 18 years for a basement-sized operation to produce the more than two tons of sarin gas that the Pentagon estimates would be necessary to kill 10,000 people, assuming the sarin was even manufactured correctly.

Still, prudence demands readiness. The potential consequences of a biochemical attack are sufficient to justify appropriate first responder preparation and response protocols, particularly since there is concern that terrorists could just steal an existing stockpile and avoid the bother of making it themselves. It is feared that al-Qaeda groups fighting in Syria, for instance, could exploit Syrian government instability and seize the Syrian chemical agent stockpile.

It is therefore important that readiness includes making the latest chemical weapon detection technologies available to domestic law enforcement agencies. Law enforcement personnel will likely be on the scene of any reported chemical weapon incident, performing everything from initial investigation and evidence collection to perimeter control and site access.

Fuhrer's technology may eventually be among those in the hands of law enforcement. He claims it is highly efficient, with a sensitivity superior to the best existing detectors. Plus, he says, it operates up to 1,000 times faster.

One problem he admits is, superconducting detectors must currently operate at low temperature. While the UM superconducting detector can operate at somewhat higher temperatures (about -420 F) than existing superconducting detectors (about -460 F), it is still a low-temperature device that requires a cooling system that currently precludes widespread first responder or homeland security use.

However, Fuhrer says the UM team is currently working on a new graphene detector scheme designed to operate at room temperature and be significantly more sensitive than state of the art detectors.

Foam sweet foam

Better explosive detection is also exploiting the special properties of graphene. New research shows that graphene foam out-performs existing gas sensors in detecting the chemicals used in making explosives.

The discovery, at Rensselaer Polytechnic Institute, may open the door for a new generation of sensors that can be used by airport screeners, police bomb squads, and defense organizations. The RPI graphene sensor has demonstrated proficiency at detecting trace amounts of explosive chemicals such as ammonia and nitrogen dioxide. So far, the sensor has shown to be significantly more sensitive at detecting these chemicals at room temperature than currently available commercial gas detectors. Ammonium nitrate mixtures are favorite ingredients of car and truck bombers. Also, a nitrogen-based fertilizer known as anhydrous ammonia was responsible for the April fertilizer plant explosion in West, Texas.

Explosive detection is currently commonly used in airport, port and border control settings.

“Our sensor can detect ammonia and nitrogen dioxide at the parts per million level at room temperature,” says RPI engineering professor Nikhil Koratkar.

Koratkar says he believes the foam may prove to be more sensitive compared to conventional gas sensors. Koratkar found when graphene foam is exposed to air containing ammonia or nitrogen dioxide molecules, the gas particles adhere to the foam’s surface, changing its surface chemistry. This change affects the electrical resistance of the graphene. When measured, this change in resistance is the mechanism by which the sensor indicates the presence of different gases.

Many police agencies use specially trained dogs to detect explosives. The dogs have been trained to use their sensitive noses to locate scents of explosive ingredients. This method is effective until the dog tires or gets bored.

Security agencies at airports, ports, and borders generally use one of several types of machines to detect trace amounts of explosive materials, the most common of which is ion mobility spectrometry, or IMS. Gas chromatography (GC) is often coupled with IMS to improve performance. The down side is GC typically requires bottled gas, which makes the systems more difficult to use.

Koratkar sees his technology as the first practical nanostructure-based gas detector that's viable for commercialization.

"Our results show the graphene foam is able to detect ammonia and nitrogen dioxide at concentrations an order of magnitude lower than commercial gas detectors on the market today," he says.

Sweating the small stuff

On another front, university researchers have found a way to address deficiencies in common scintillation radiation detection technology. Scintillations are minute flashes of light that are produced by certain materials when exposed to radiation.

A team at Georgia Tech Research Institute is utilizing novel materials and nanotechnology techniques to improve sensitivity, accuracy, and robustness of radiation detection.

Standard scintillation detection technology is proficient at detecting gamma rays and subatomic particles emitted by nuclear material, but it requires large difficult-to-produce crystals grown from sodium iodide or other materials. These crystals are fragile, bulky, and vulnerable to humidity.

The Georgia Tech approach uses a nanopowder glass material composed of rare-earth elements halides and oxides.

“Our glass detector has the advantage of simple preparation, stability, and does not need to be enclosed or otherwise protected,” says Bernd Kahn, of Georgia Tech’s Electro-Optical Systems Lab. Kahn says the Georgia Tech detector can be used by law enforcement as a hand-carried or vehicle-carried radiation monitor to survey areas and people, or as a fixed monitor to scan passing vehicles or foot traffic.

Radiation detection is a growing requirement in law enforcement and public safety agencies. The state of Illinois, for instance, has deployed 6,200 radiation detectors in police and fire vehicles across the state. Radiation detectors have been in the hands of some local police departments, as well as the state police, in New York since 2008. There are some 4,000 pager-sized radiation detectors on the belts of first responders in 150 New York area agencies.

The Department of Homeland Security is behind the push to get radiation detection capability on America's streets as it expands its nuclear security program to meet the threat of a terrorist nuclear, or dirty bomb, device.

Kahn's work involves improving the crystals. Regular scintillator crystals must be transparent to light, which provides its ability to detect radiation. A perfect crystal uniformly converts incoming energy from gamma rays to flashes of light. A device called a photo-multiplier then amplifies these light flashes so they can be accurately measured to provide information about radioactivity.

However, Kahn says, results on conventional devices are unreliable because some crystals scatter the luminescence created by incoming gamma rays. That scattered light can’t be photo-multiplied in a uniform manner, badly skewing the readings, which are manifested as false positives.

To overcome this issue, Kahn reduced the particles to the nanoscale. When a nanopowder reaches particle sizes of 20 nanometers or less, scattering effects fade because the particles are now smaller than the wavelength of incoming gamma rays.

All of these emerging technologies indicate an evolving role of law enforcement in terror threat detection—which puts law enforcement in a preventative, rather than a response, role. These technologies may ultimately find their way into new police and lab protocols designed to either prevent terror attacks or accelerate response measures.

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