Searching for a Secure Channel

The building looks innocent enough. But this is a war zone, and members of the patrol have to stay alert, especially inside buildings.

As the soldier on point enters the first room, an alarm goes off. From a pocket on his combat vest he pulls out a sensor about the size of a deck of cards. The device can identify a dozen different agents commonly used in biological warfare. The biosensor is part of his standard issue gear.

The sensor has detected a single molecule of anthrax in the room. The soldier alerts the rest of his patrol to evacuate the building.

Science fiction? For now, yes. But maybe not for much longer.

A portable sensor with this degree of sensitivity does not yet exist. But a team of researchers at Arizona State University is working to make it a reality.

“The state-of-the art-biosensor is pretty poor,” says Stephen Goodnick, an ASU professor of electrical engineering. “You don’t want to empty the New York City subway system based on a biosensor that’s only 30 percent accurate. You have to distinguish between something innocuous and the real thing.”

A very good system for detecting biological agents already exists and has been used by scientists for decades. The technique is called gas chromatography. It can achieve 99 percent accuracy. But gas chromatography is expensive and must be performed in a lab.

At the other extreme, portable and cheap bioagent sensors also exist. However, they can give high numbers of false positives and sound the alarm in response to non-dangerous substances. The goal of Goodnick’s project is to create a cheap, portable sensor that has a very, very low false positive rate.

“Sensor technology is a suite of different tools that do different things depending on the technology and what you have to evacuate,” explains Trevor Thornton, professor of electrical engineering and director of ASU’s Center for Solid State Electronics Research. “Our sensors have the best false positive rates because they’re based on biology and a very specific type of binding.”

ASU researchers are developing a biosensor in conjunction with scientists working at Rush Medical College in Chicago and six other partner universities. The sensor is a biomolecular hybrid nanodevice. More simply, it combines a tiny silicon chip with a cell membrane.

A membrane made of lipid, or fat, molecules forms the boundary of all cells. The cell membrane acts like the walls of a house. It keeps some stuff inside and other things outside. Getting into the house requires a door. Cars enter through the garage door, people walk in through the front door, and pets enter through a doggie door. Similarly, proteins in the cell membrane act like doors. These proteins only allow certain materials to enter and exit.

One type of membrane protein is an ion channel. Ions are molecules or atoms that are positively or negatively charged. Ion channels create pores across the membrane. These pores only allow specific ions to pass through. Researchers can measure an electric current through single channels of proteins in the membrane. Molecules in the solution around ion channels can influence this current even if they do not pass through the channel. The ASU researchers have exploited this characteristic in designing their sensor.

“Nature spent a long time designing ion channels to be specific to molecules. We can build on that; we don’t need to create a whole new system,” Thornton says.

The heart of the sensor is a silicon chip similar to those found in computers and other electronic devices. In the chip is a tiny hole with a diameter of 100 microns, the width of a human hair. The chip is also coated with a very thin layer of Teflon, a plastic often used in nonstick coatings for kitchen equipment.

Across the hole stretches a membrane. Some of the experimental membranes use the same lipids as those found in cells, but others have been specially engineered. Cell membranes contain many different ion channels and other proteins, but the membranes in the sensor include many copies of just one ion channel.

A solution of water and salts surrounds the chip. Electrodes on the silicon measure the electric current passing through the ion channels. The current is very small, so the electrodes and electronics must be extremely sensitive. When a single molecule of a bioagent enters the solution surrounding the chip, the current across the ion channel changes. The electrodes detect this change and sound the alarm.

“It’s amazing that we are able to measure a single protein. The dimensions are so small, and the current is so small,” says Seth Wilk, a postdoctoral research associate. “I like being able to see a device actually do what we planned for it to do.”

The researchers have finished the first phase of their work, which was simply to determine if a sensor based on this technology is realistic to build. The answer was a resounding yes. Phase two involves building a prototype that satisfies criteria set forth by the Defense Advanced Research Projects Agency (DARPA), which funds the project.

For example, the entire sensor package should be something that every soldier could carry in a pocket. The eventual device will consist of an array of silicon chips with membranes. Each membrane will contain a different ion channel that is tailored to detect a particular bioagent, such as anthrax, nerve gas, and blister agents.

Putting a dozen detection elements on one device means that each element must be very tiny. For example, the researchers want to make the hole in the chip—currently the width of a human hair—more than a hundred times smaller. The military also wants the sensor to be stable for at least 90 days. The current chips work for about 24 hours. The sensor must also be self-contained. Researchers currently drip in solutions with a pipette. The final prototype will eventually include a microfluidic system to transport tiny quantities of liquid within the sensor.

“It’s remarkably difficult to scale working device features below 100 nanometers,” says graduate student Leo Petrossian.

The researchers will test their system against chemicals that are similar in structure to bioagents, but not as dangerous. They will also make sure that the sensor doesn’t react when it isn’t supposed to.

For example, lots of gas fumes circulate in a war zone. The sensor must be immune to these and only be triggered by actual biological agents.

ASU scientists say that this technology also has applications in areas other than security. Ion channels are crucial to many biological processes, including the transmission of signals in the nervous system and proper beating of the heart.

Technology similar to that used in these sensors is employed by the pharmaceutical industry in its search for new drugs that affect ion channels. The silicon-membrane hybrids being developed at ASU could speed drug discovery and have other medical uses.

“We’re excited. Whatever happens with DARPA, this technology has promise in other areas, such as nanomedicine and bioengineering,” Thornton adds. “This project is really a stepping stone.”—Linley Erin Hall