Tiny heaters may pave way for easier tissue engineering, medical sensors

Tiny microheaters that can prompt chemical changes in surrounding material may provide the means to more easily grow replacement tissue for injured patients and form the basis for medical sensors that could quickly detect pathogens, according to researchers at the University of Washington who are the first to demonstrate the process.

The key to the technique, according to Associate Professor Karl Böhringer in the UW’s Department of Electrical Engineering, lies in temperature-driven changes in the material with which the less-than-one-millimeter-wide electric heaters are coated. Proteins stick to the material as its temperature rises, and release when it goes back down. That, according to Böhringer, opens the door to a wide array of possibilities.

“The proteins stick locally to the areas we heat, and we can stick cells to the proteins,” he said. “This provides a relatively simple, low cost way of creating cell chips to run experiments and to create other useful devices.”

Böhringer and colleague Buddy Ratner, director of the UW Engineered Biomaterials program, presented the research recently at the 12th International Conference on Solid-State Sensors, Actuators and Microsystems in Boston, and a patent is pending for the process.

To make the chips, researchers started with a thin slide of glass, on which they built arrays of microheaters using lithographic techniques. They then deposited poly-N-isopropylacrylamide (pNIPAM), a temperature sensitive polymer, onto the microheater arrays.

At temperatures below about 90 degrees Fahrenheit in a liquid environment, the polymer exists in a water-saturated, gel-like state. But when the temperature exceeds that threshold, the polymer’s chemical properties change. It becomes water-repellant and allows proteins to stick to it.

“When you go above this low critical solution temperature, there is a transition from the gel-like wet state to a dry, more dense state, but there also is a conformational, or shape, change in the molecules,” Böhringer explained. “There are some end groups in the molecule that flip around and essentially show another end of the molecule to the surface, and the proteins like to stick to that end.”

By turning on different portions of the heating array while the chip is exposed to different solutions, the researchers found that they could selectively attach different proteins in pre-determined patterns. And, since certain cells attach to certain proteins, researchers could use the method to layer proteins and cells, custom-designing chips that feature different cells grouped in whatever patterns the scientists need.

At the research level, Böhringer said, this could help make efficient use of time and funding.

“You could create a chip that runs a number of different experiments at the same time,” he said.

There are also powerful applications outside the research lab, he added. The technique could be used to fashion biosensors or diagnostic devices.

“We could have arrays of proteins or cells with specific functions – they may be sensitive to a pathogen, for example,” he said. “You could watch the array as it’s exposed to some unknown sample and see how it reacts.”

Medical applications are another promising area. Since the arrays can be positioned however one wants, they could be used to grow tissue in specific shapes.

“We can basically create shapes of cell cultures,” Böhringer said. “Then if you switch off the heater, the attachment ends and the whole cell culture lifts off. So it may be a way of making, for example, a replacement skin graft. You grow it on the surface, prompt it to lift off, and you could transplant it. That could directly follow from this.”

Other contributors to the project include Denice D. Denton, Ashutosh Shastry, Yael Hanein, Xuanhong Cheng and Yanbing Wang, all with the UW. Funding for the research came from the UWEB Research Center, the UW’s NIH Microscale Life Sciences Center and the National Science Foundation.

For more information, contact Böhringer at 206-221-5177 or karl@ee.washington.edu. A paper detailing the process is available on the Web at: http://www.ee.washington.edu/research/mems/publications/2003/conferences/transducers-ywang-03.pdf