Biochip technology reveals “fingerprints” of biochemical threatsBy Jared Sagoff • March 23, 2009
Argonne biochemist Daniel Schabacker could be considered a Sherlock Holmes of bioterrorism. Although he doesn’t carry around a pipe and magnifying glass as he attempts to nab the culprit, he has a far more powerful deductive tool: the biochip.
The biochip offers Schabacker and his colleagues at Loyola University (Ill.) a chance to determine the “signatures” of biological agents that can be used for bioterrorism, most notably the bacterium that causes anthrax, Bacillus anthracis. While some scientists have used DNA analysis to identify particular strains of the anthrax bacterium, the biochips help scientists and government officials to learn how anthrax bacteria are grown, narrowing the pool of potential suspects. This project, started only within the past couple of years, exemplifies the burgeoning field of microbial forensics.
"Microbial forensics is one of the biggest topics in counterterrorism today, and one of the biggest challenges in dealing with bioterrorism,” Schabacker said. "The proteomic analysis that we’re able to perform with our biochips provides a new and different set of information about biological agents than we’d been able to see before; it can provide us with a complete fingerprint of the organism that we can then use to more precisely identify its origin.”
According to Schabacker, most efforts in microbial forensics today rely on DNA analysis for their findings. But on its own, Schabacker said, DNA analysis may not be sufficient to give investigators all the information they need about a particular bioagent. “The problem with only using conventional DNA analysis is that it only tells you what strain you are dealing with, and strains used by the good guys can be obtained by our enemies. There can be dozens of labs that all share the same strain,” he said. “Our approach attacks the problem in a completely different way. We take advantage of the fact that unlike cellular DNA, bacterial proteins change dramatically when the growth or preparation of the bacterial culture is altered — and that information is incredibly important.”
Because the anthrax bacterium’s proteins hold a unique and detailed record of how the cells were generated and handled, Schabacker believes that pursuing DNA and protein analyses in concert could yield a comprehensive database that identifies the conditions used to prepare almost any B. anthracis culture.
“The ultimate goal of this project is to build a library of ‘signatures’ of B. anthracis grown and prepared under various conditions, which can be used to identify an unknown sample from a possible terrorist attack,” Schabacker said. “This will be a major help to investigators who seek to attribute the agent to a particular perpetrator.”
Schabacker plans to leverage basic studies on the anthrax bacterium from the laboratory of Loyola professor Adam Driks to make biochips into a powerful tool for investigators and other scientists.
Developed in the early part of the decade originally as a diagnostic tool, a biochip consists of a one-centimeter by one-centimeter array that contains anywhere between several dozen and several hundred "dots," or small drops. Each of these drops contains a unique protein, antibody or nucleic acid that will attach to a particular reagent.
Scientists obtain the anthrax proteins to create the biochip through a process called fractionation. Essentially, the scientists use chemicals to break open the anthrax bacterium and collect its cellular proteins. They then use another process to separate the individual proteins by their physiochemical properties.
This process creates hundreds of separate protein fractions, which are then deposited onto a single biochip. Scientists then use different chemicals, or reagents, to characterize the resulting biochips just as a detective would dust for fingerprints. Just like a police interview with a suspect, this chemical process is known as “interrogation.” When a reagent interacts with a particular protein fraction, that spot will “light up,” creating part of the protein signature.
Although the biochip technology has the potential to develop protein signatures of just about any biological agent, Schabacker and Driks have devoted their initial focus initially to B. anthracis. The spores produced by this bacterium, which cause anthrax, are relatively easily manufactured and dispersed, making the anthrax bacterium a relatively easily produced biological weapon.
“B. anthracis is a pretty forgiving species – it will grow in a bunch of different conditions,” Schabacker said. “It’s probably the single most attractive pathogen of choice to terrorists who don’t have a lot of really expensive equipment or expertise, and the spores are the perfect package for dispersion.”
An expert on anthrax, Driks and his laboratory pioneered the forensic analysis of the spore coat of the bacterium. Schabacker combined the biochip technology with fractionation technology developed by Eprogen, Inc., providing a nexus that connects government research, academia and industry.
Helping scientists track down terrorists isn’t the biochip’s only use. Biochips have already shown promise in diagnostic medicine. After developing the biochip technology, Schabacker licensed it to several companies, including Safeguard Biosciences in Toronto, Canada and Akonni Biosystems in Frederick, Maryland.
Instead of looking at anthrax, Eprogen has put biochips to use to look for common cancer biomarkers. That research could open the door for doctors to create “antibody profiles” that could help them design individualized drugs or treatment programs for patients.
The work Akonni has done focuses on identifying other pathogens – those not normally associated with terrorist activity. Soon, biochips may begin showing up in greater numbers in doctor’s offices around the country, as they provide accurate and speedy diagnoses of a wide variety of infections, such as those caused by Multidrug-Resistant Tuberculosis (MDR-TB) and the often deadly Methicillin-resistant Staphylococcus aureus (MRSA).