Nanotechnology is a buzzword that often brings to mind images of microscopic gears and springs etched into silicon wafers.

	Tony Tye, Post-Gazette Christian Schafmeister of the University of Pittsburgh has developed a system for building nanodevices using molecular building blocks. Click photo for larger image. Related coverage Graphic: The nanoscale building blocks A twist on the double helix

But if you really want to build nanomachines, ones measured in billionths of meters, or nanometers, it makes sense to consider the nanomachines of nature -- proteins.

That's what Christian Schafmeister did.

"We've got 40,000 of these machines in our bodies that make us what we are," explained the University of Pittsburgh chemist. Proteins digest our food, move our arms and transport materials. And the beauty of it is that all are made from about 20 different types of building blocks, called amino acids.

Taking this cue from nature, Dr. Schafmeister and his students have spent the last five years concocting their own set of 14 building blocks -- the molecular equivalent of Lego pieces.

By his estimation, that's enough to make roughly 140 trillion structures. So creating different shapes is no longer the challenge; rather, "it's finding those sequences that do interesting things," he said.

New types of pharmaceuticals, chemical catalysts and sensors are all among the possibilities.

"We haven't made a big splash with this yet," acknowledged Dr. Schafmeister, an assistant professor of chemistry and a researcher at Pitt's Institute of NanoScience and Engineering. But that should change once applications are identified, something he hopes will occur within the next year.

Even so, the work already has drawn attention within the nanotech community. Last month, the Foresight Nanotech Institute, a nanotechnology think tank, awarded its Feynman Prize for experimental work to Dr. Schafmeister and its Distinguished Student Award to one of his graduate students, Christopher Levins, who developed one of the building blocks.

"It's the most impressive work we've seen on the pathway to building useful three-dimensional structures with atomic precision," said Christine Peterson, Foresight's founder and vice president for public policy. "The biggest payoffs across the board in nanotechnology . . . are from reaching the ultimate goal of atomic precision."

Controlling the position of each atom within a molecule would be difficult to achieve simply by trying to build molecules out of the same amino acids used so skillfully by nature.

Trouble is, as good as humans may be with their hands, they still lack the intellectual dexterity needed to build machines with amino acids. Arrange a set of amino acids one way and you've made an enzyme; rearrange the same amino acids and you've got a muscle component.

The reason for these dramatically different functions lies in what's called the protein folding problem. Proteins are more than just long, floppy chains of amino acids; their function depends in large part on their shape, how they fold themselves up. And the rules that govern that folding procedure are only dimly understood.

During four years of graduate school at the University of California, San Francisco, Dr. Schafmeister designed his own protein, called 4HB1, with 180 amino acids. "It's a molecular doorstop," he said wistfully, gazing at its structure on his computer monitor. "It doesn't do anything. But it is well-folded."

So he reasoned that to control the shape of his molecules -- and thus increase the chances of designing a molecule that does something -- he would need to eliminate the folding problem. And that meant developing molecular building blocks with rigid connections between them.

Rigid connections

Amino acids connect to each other with single bonds, creating chains with all of the rigidity of a string of plastic beads. He and his students devised blocks with a pair of bonds, creating rigid connections between the molecules much like those between Lego blocks.

Most of the blocks have been processed from 4-hydroxyproline, a form of the amino acid proline obtained commercially from chicken feathers; two are processed from the amino acid tyrosine. Making the building blocks "is boring chemistry, pedestrian chemistry," he said, and intentionally so. Though he and his students now make their own building blocks, he hopes that someday they will be churned out in large quantities by industry.

The building blocks each have a different shape, though they are not as simple as pieces of an Erector set -- no straight sections, or right angles. All twist a bit in three dimensions, but can be assembled to form a number of shapes.

Simply repeating the same building block will form something roughly rod-shaped. Alternating a block with a mirror-image block will form a horseshoe- or ring-shaped molecule. Dr. Schafmeister has devised a software program that can show a designer the options available for shaping a molecule with each of the available building blocks.

"You can sculpt almost anything," said William A. Goddard III, director of the Materials and Process Simulation Center at the California Institute of Technology. "Proteins are like a piece of string, but his structure is like having a wide ribbon" that can be used to build all sorts of three-dimensional objects.

This "bottom-up" approach to building nanotech devices still must be further developed, but eventually will be essentially for building nanomachines, he suggested.

The "top-down" approach, particularly that used by the semiconductor industry, may soon reach its limits, Dr. Goddard explained. Computer chip makers, who etch transistors and wires into silicon wafers, now are preparing to build devices measuring 130 nanometers and have begun to struggle with 90 nanometer devices.

Increasingly smaller component sizes have been the key to "Moore's Law," the concept that chip capabilities roughly double every year or so. On the horizon are 45- and 32-nanometer components. But within 10 years, he said, continued progress may depend on switching over from a top-down to a bottom-up strategy.

"There's a good chance that by 2015, this might be the only solution to maintaining Moore's Law," he added.

Dr. Schafmeister envisions using his building blocks, each measuring about half a nanometer, to build little boxes with lids that could serve as sensors; when a molecule of interest enters the box, the lid would shut and send a signal. The blocks might also be used as scaffolding to construct customized catalysts, which promote certain chemical reactions, or to build artificial antibodies.

He also is exploring the use of his building blocks for devising multivalent drugs -- drugs that bind to multiple receptors on the surface of cells, thus blocking toxins, such as cholera. Unlike the floppy molecules that now carry sugars designed to bind with these receptors, Dr. Schafmeister's rigid molecules could hold the sugars at the same precise distance as the spacing of the receptors on the cell.

"I have so many applications I want to try," he said. Though it's not clear which one is likely to prove itself first, he has encountered few limitations to the underlying building blocks themselves.

"If there are walls," he said, "we haven't hit them yet."