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Hopkins' APL inventors pitch in to improve bio-security

If an envelope arrives in your office stuffed with a mysterious white powder, your chances for survival could be slipping away with each tick of the clock.

If that powder proves to be anthrax, for example, and you don't get an effective antibiotic within the first 24 hours, "the chances of survival are slim," said Plamen Demirev, a senior scientist at the Johns Hopkins University's Applied Physics Lab.

But it can take that long just to grow and identify any pathogens in the envelope, he said. And you still might not know which antibiotic would save you, and which the microbe may have been engineered to resist.

"It's critical to be able to answer questions about drug susceptibility or resistance quicker," Demirev said.

Demirev and a team of scientists at the laboratory near Laurel believe they have developed a system to identify unknown pathogens, and any drug resistance they might have, in as little as six hours.

The invention is a potential new application for a system now being tested with real pathogens at a Centers for Disease Control and Prevention biodefense lab in Texas. (The work at APL used harmless stand-ins.)

The technology has been selected from among 118 other innovations as APL's "2009 Invention of the Year." The award recognizes new technology for its potential benefit to society, advances over existing technology, and commercial promise.

APL Director Richard Roca called the entries "perfect examples of how APL's best scientists and engineers apply their skills with innovation, imagination and creativity."

Demirev, who led the group, shared the honors with team members Miquel Antoine, Andrew Feldman, Nathan Hagan and Jeffrey Lin. "All of us are pretty proud of it," Feldman said.

A quicker means to identify deadly pathogens and the right drugs to combat them might have saved lives during the 2001 anthrax attacks.

Spores mailed to several news media and congressional offices eventually killed five people and infected 17 more. In 2008, the FBI identified Bruce Edwards Ivins, a biodefense lab scientist at Fort Detrick in Frederick, as the culprit. Ivins committed suicide shortly after the investigation began to focus on him.

Cryptically named "IsoMS-DrugArray," the technology is an outgrowth of 13 years of APL work on bio-detection, spurred more recently by $500,000 in funding from the Department of Homeland Security's Science and Technology Directorate.

The device uses mass spectrometry to identify the pathogens. An off-the-shelf mass spectrometer bombards the pathogens with laser light in a vacuum, and in a process called "laser desorption," knocks ionized (electrically charged) particles from the pathogen's protein molecules. These ions are then measured, sorted and displayed in graphical form on a computer screen, like a signature.

"We and others have shown that, in the case of microorganisms, we see a pattern of peaks which represent ions and molecules unique to each microorganism" and its DNA, Demirev said.

The DNA genomes of many pathogens are already well-known, he said. But the APL technology can also spot likely new ones.

"There are cases where you may not be able to see an organism beforehand, one that's been only in the hands of terrorists, or may be bioengineered," he said. "Use prior knowledge from DNA sequencing of similar organisms, and you can … recreate the pattern you expect to see, using computer algorithms."

"Even if we have never seen [it] … we could predict its spectrum," he said.

The APL system can simultaneously reveal drug resistance. Organisms are placed in a variety of nutrient cultures that have been laced with different antibiotics and tagged by stable isotopes as "markers."

If the mass spectrometer spots the nutrient markers coming off the organism, the operator knows the bug is metabolizing the food. So it's thriving, apparently resistant to whatever antibiotic is present. If there are no markers, the bug has likely succumbed to the drug.

"You need a half-hour to prepare the sample … five hours to grow .. and a minute to analyze and get an answer for 30 samples," Demirev said. "It's a big improvement from the classical technology."

The current method requires that the organisms be grown for 24 hours in lab dishes filled with a culture of sheep's blood, and then identified under a microscope.

Feldman, another senior scientist on the APL team and a specialist in bio-informatics, said there were scientists, even within APL, who questioned whether the new technology would be able to discriminate among different pathogens. But, despite some difficulties along the way, it did.

"It took a while," Feldman said. But "we opened a few eyes."

If the $150,000 system receives independent verification from the CDC, it could become commercially available soon, combining available mass spectrometry hardware with APL's software and algorithms and user-friendly controls.

It would be made commercially available to Homeland Security and to state public health laboratories and hospitals across the country.

"We've already met with some folks about licensing what we've developed here," Feldman said. "Our goal is to get it used and have it make a difference."

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