Sniffing Out Airborne Diseases
by David Pescovitz
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Albert Pisano explains the big idea behind the biosensor.
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You are on a return flight from your summer vacation and notice that someone seated nearby has quite a cough. You don't think much of it, until later that day when you receive a text message advising you that the plane's microbial monitoring system detected SARS on the aircraft. After reporting to a testing site, you're relieved to find out that you haven't been infected. Meanwhile, the passenger carrying the virus is positively identified and quarantined for treatment.
This is just one scenario envisioned by UC Berkeley mechanical engineers who are developing air-monitoring technology to help stop the spread of airborne diseases. Amazingly, the powerful sensor in their design is a living human cell.
"In the war between humans and diseases, this biosensor could be another weapon in our arsenal," says principal investigator Albert Pisano, chair of the Department of Mechanical Engineering. "You could imagine these mounted in bus stations, trains, or anywhere else you'd like to get a frequent status report on the microbial population in the air. That way diseases can be isolated so they don't infect the population so rapidly."
The system, still under construction, combines several of UC Berkeley's recent advances in nanotechnology, bioengineering, and microfabrication. According to Pisano, it's a quintessential example of use-inspired basic research that will eventually enable their device to work in the real world.
"This isn't about putting a cell on a petri dish where it can sit for a week and die," he says. "We're looking at how you keep a cell alive on a piece of silicon for a long time, unattended, and automatically detect physiological changes."
At the core of the biosensor is a microfluidic chip etched with channels that stream nutrients and refrigeration liquid to the cells and carry off waste. (Peg Skorpinski photo)
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At the center of the shoebox-sized device, dozens of individual cells will float inside tiny wells etched out of a silicon chip. A microfluidic plumbing system will circulate cooled liquid past the wells, deliver food to the cells, and remove waste. Periodically, a single cell will be pumped into a tiny chamber that allows outside air to flow in while still keeping the cell hydrated. It's here that the cell will react to any agents in the surrounding air. After a pre-determined exposure and incubation period, the cell will again be transported into another part of the device for analysis. Simultaneously, a new cell will be loaded into the exposure chamber.
Pisano has collaborated with bioengineering professor Dorian Liepmann on a nanoscale hypodermic needle that can probe the cell for physiological signs of infection. Just 200 nanometers wide (1/500 the diameter of a human hair), the needle is fabricated similarly to the way integrated circuits are manufactured.
"In the biosensor, the needle would stick into the microfluidic system like a harpoon," Pisano says. "The cell would get impaled on it and then analyzed."
As skewering the cell obviously kills it, the researchers are considering several other assays in development at Berkeley that could also be integrated into the biosensing system. For example, professor Bernhard Boser's finger-nail sized biochip uses magnets to detect antigens indicative of a particular disease, while professor Luke Lee has designed nano-microscopes with optical sensors that can automatically identify the smallest biomolecules. Another approach, invented by professor Boris Rubinsky, measures subtle changes in the electrical resistance of a cell membrane caused by exposure to toxins. The various chip-based assays could be combined to increase the accuracy of the biosensor, Pisano explains.
Once the assays are complete, an onboard microprocessor will collect the data and feed it to a wireless transmitter. A central computer can then analyze the information and alert the proper authorities if a pathogen is detected.
Currently, Pisano and his collaborators are fine-tuning the myriad components of the biosensor so that it can be integrated into a single robust unit. Once installed, Pisano says, it should be self-maintaining until the cell supply needs to be replenished, perhaps monthly. The researchers are also launching collaborations with molecular and cell biologists to better understand the biochemistry behind disease detection.
"The goal of this whole thing is to help people avoid becoming a Typhoid Mary for diseases like SARS and tuberculosis," Pisano says. "It's a matter of nipping problems in the bud."
Al Pisano's home page
"Nano-Microscope Spots Single Molecules" by David Pescovitz (Lab Notes, November 2001)
"Diagnosis on a Chip" by David Pescovitz (Lab Notes, October 2003)
"Researchers create potential toxic sensor chip by combining electronics with living cell" by Sarah Yang (Media Relations, 09 June 2003)
"Revolutionizing drug delivery with a tiny syringe" by Melinda Levine (Forefront, Spring 2003)
Dorian Liepmann's home page
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