Mutant Bacteria Become Microscopic Motors

"It is hard to move fluid on a micro scale because it takes a lot of pressure," explained Tung, associate professor of mechanical engineering. "Current systems are expensive and inefficient, requiring high voltage or very good seals."

Tung is working with Ajay Malshe, associate professor of mechanical engineering; Jin-Woo Kim, assistant professor of biological and agricultural engineering; and graduate students Ryan Pooran and Chuen Cheak Lee to produce bioMEMS, which use tethered bacteria to pump fluids through the microscopic channels in MEMS devices. The three-year project is sponsored by the National Science Foundation.

MEMS devices are machines so small they cannot be seen by the unaided human eye. With gears no bigger than a grain of pollen, they range in size from micrometers to a millimeter. MEMS combine electrical and mechanical components into an integrated micro device or systems that can function individually or in groups to sense, control and actuate larger devices.

The tiny devices have a big impact on both the consumer and defense industries. Current applications include accelerometers for systems like automobile air bags; pressure, chemical and flow sensors; optical scanners and fluid pumps. The market for MEMS devices was estimated at more than $8 billion in 2001, and it is growing rapidly.

BioMEMS use a specific type of bacteria, which has a tendency to attach itself to a surface by one of its many flagella, the long filaments that protrude from its surface. Bacteria use the whip-like motion of their flagella to move about. While each flagellum normally turns counter-clockwise about 80 percent of the time, it is possible to introduce a mutation that will lock the motors in one direction of rotation, either clockwise or counterclockwise, according to Tung.

"When its flagellum is attached to a surface, the bacterium moves in a circular fashion, and always in the same direction," explained Tung. "A single bacterium can become a flagellar motor or pump, but a number of bacteria, all rotating in the same direction, could become a conveyor belt."

The researchers are using a strain of non-pathogenic bacteria that is harmless and requires no special handling. Although the bacteria will be completely sealed inside the bioMEMS device, these benign characteristics make manufacturing the bioMEMS devices less expensive.

"Our first challenge was to produce bacteria of uniform size with only one, short flagellar filament positioned so the cell will generate maximum flow as they rotate when tethered in the microchannel," Tung said. "Then we had to determine how to cause the filament to attach to a non-toxic material that we could use to line the wall of the microchannel."

"Because they are living creatures, the bacteria must be fed, but their nutritional needs are simple and well understood. If they are fed and securely tethered to prevent them from leaving, they may persist in turning indefinitely," Tung explained. "The tethered cells will continue to spin for many hours, even days, after removal of external nutrient sources. They use energy from stored glycogen or other reserves to maintain rotation, but we do not know yet what will be the limiting factor on how long the cells will be able to spin."

The next hurdle facing the researchers is how to seal the bacteria into the bioMEMS devices without killing them. Traditional fabrication methods use high heat or chemicals that could be fatal to the bacteria.

Although it is very difficult, controlling fluids at the micro level is important because it has the potential to improve analytical techniques. According to Tung, "The performance of present biochemical analysis can be dramatically improved by drastically reducing the amount of fluids and reagents used during the tests. In some processes a 10-fold reduction in the flow-channel size can result in a 100-fold enhancement in analytical performance without any increase in voltage requirements."

While several MEMS-based pumps have been developed, non-mechanical designs have limited applications because they rely on the electrical properties of the fluids. Mechanical micro pumps require a very large pressure drop, which severely limits their performance.

"This project is an important step towards the convergence of cell biology and MEMS," said Tung. "Successful integration of the cell motors and microfluidics channels can potentially revolutionize the design of future microfluidics systems for drug delivery and DNA sequencing."