GROUNDBREAKING SCIENCE
Imitating Nature

Nanobioscientists like Mike Simpson aim to harness or imitate the complex abilities of bacteria and other single cells to make implantable sensors and actuating devices.

Put a biologist, a physical scientist, and an electrical engineer in the same room, and you have a recipe for an interesting collaboration in nanobioscience. Become a fly on a wall of that room and you might hear statements common to systems biology, invented by physical scientists applying systems analysis tools to biological problems. And you might learn a little about synthetic biology— methods for applying biology's lessons to device design.

(Top): This magnetotactic bacterium exhibits one-dimensional ordering of a nanostructure. (Middle): This diatom is a single-cell eukaryote that exhibits three-dimensional (3D) ordering with a complex but static structure using one material. (Bottom): The sea urchin is a multi-cell organism that has 3D ordering with a complex and dynamic structure that uses many materials. Scientists study these cells because they perform exquisite controlled synthesis and directed assembly of nanoscale materials.

What you might hear in that room: "Living cells work using the information processing of gene circuits and networks." "We need to find out how these circuits and networks are built and interconnected to make cells and organisms function." "Let's put the intelligence in genes on an electronic chip." "Our funding agencies want us to create engineered systems that closely mimic the size and functional complexity of biological systems, such as bacteria and other single cells."

In the mid-1990s, ORNL electrical engineer and nanobioscientist Mike Simpson heard University of Tennessee biologist Gary Sayler give a presentation. Simpson and Sayler then talked, and a collaboration began. The result was a silicon chip harboring bacteria engineered to light up in the presence of their favorite food—a pollutant called toluene. The light from an activated fluorescent protein triggered an electronic response. The "critters on a chip" sensor, formally labeled a bioluminescent bioreporter integrated circuit (BBIC), was licensed to Micro Systems TECH for homeland security uses.

Based on research by Simpson's and Sayler's groups and funded by the National Institutes of Health, ORNL recently patented a method for using an implantable BBIC sensor chip for glucose detection. "Sayler's group engineered human mammalian cells to emit light to the circuitry our group designed for an implanted sensor," Simpson says. "The amount of light is related to the glucose level. We have suggested that incorporating our glucose-sensing capability in a closed feedback loop with an implantable insulin pump could lead to an artificial pancreas."

Simpson is intrigued by the infor-mation-processing capabilities that are packed into single cells. "If you compare the information-processing ability of a piece of silicon the same size as an E. coli bacterium, the bacterial cell wins by a lot," says Simpson, who has a joint appointment at the University of Tennessee and Oak Ridge National Laboratory..

He is fascinated by magnetotactic bacteria, which are found in aquatic environments. These aquatic bacteria gather materials to make nanomagnetic particles, assemble them into a rod that aligns itself with the earth's magnetic field, and then start up a protein motor that enables the bacteria to travel, following the magnetic field's curvature. "These bacteria use the magnetic field to guide them down into water where the dissolved oxygen level is just right," Simpson says.

Another micro-organism of interest is the diatom, which builds an elaborate silicon structure in which it lives until the structure divides into two diatom cells. Each of the daughter cells inherits half the structure and must manufacture the other half.

"I am interested in these cells because they perform exquisite controlled synthesis and directed assembly of nanoscale materials," Simpson says. "Understanding how their genetic and biochemical circuits and networks make possible their complex functionality could teach us how to create engineered systems with similar abilities."

Simpson's group, including Tim McKnight and Anatoli Melechko, is collaborating with Mitch Doktycz's group in biomimetics—mimicking cell structure and function in engineered devices.

They can grow an array of vertically aligned carbon nanofibers in any pattern they choose. Thus, they can imitate a cellular membrane by controlling the spacing between the nanofibers so that small molecules will pass through, while larger molecules are excluded. They demonstrated this capability by transporting fluorescently labeled latex beads of different sizes down a microfluidic channel intersected with a stripe of nanofibers and detecting a buildup of the larger beads at the intersection.

For nanobioscientists, Mother Nature is a role model.

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