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See Inside May 2007

Structured Settings

Novel techniques expand the nanotech tool kit
FAST DIAGNOSES



MARK REED Yale University
Nanoparticles are tantalizing construction blocks for researchers, capable of displaying properties of both tiny atoms and far bulkier conventional materials. They generally behave only like balls, however, which makes it hard to assemble them into solid structures other than those resembling displays of oranges in a grocery store. Now researchers have taken big steps in creating and using nanostructures that have eluded manipulation in the past.

In the January 19 Science, materials scientist Francesco Stellacci of the Massachusetts Institute of Technology and his colleagues revealed a way to make nanoparticles act like links in a chain, capable of hooking together into strings of beads. The strategy was to take advantage of the so-called hairy ball theorem, which states that if a sphere is covered in hair, attempts to brush those strands to make them all lie flat will always leave behind two hairs standing up straight, each at opposite poles. (Imagine flattening hair on a globe just along the latitude lines; in the end, the hair on the poles will stick out.)

The investigators covered gold nanoparticles with a mix of two kinds of sulfurous molecular hairs. The points where hairs were supposed to stand up essentially became unstable defects on the nanoparticles' surfaces, making it easy to replace those hairs. Stellacci and his colleagues substituted these standouts with chemicals that behaved as handles, enabling the nanoparticles to hold onto one another.

"This really makes nanoparticles analogous to atoms--specifically, divalent atoms that have two chemical bonds. You can now form really interesting structures with them, just like you can make molecules from atoms," says Stanford University materials scientist Yi Cui. Stellacci mentions that his group is now pursuing ways for nanoparticles to each have four bonds.

These nanostructures could be connected together with nanowires to help form advanced electronics. Researchers can make nanowires either by growing them from the bottom up or by etching them from the top down, akin to whittling toothpicks from a log. Bottom-up approaches face the challenge of integrating each tiny, floppy and often randomly dispersed strand into devices, whereas top-down methods, encompassing more traditional industrial techniques, "are like hacksaws," explains Yale University biomedical engineer Eric Stern. They leave behind rough-edged nanowires with poor electrical properties.

In the February 1 Nature, Yale researchers revealed an etching method that creates high-quality, smooth-walled nanowires. The trick was using the ammonium salt TMAH. It can etch silicon more slowly and more smoothly than other solvents used thus far. Yale biomedical engineer Tarek Fahmy adds that the technique is readily compatible with standard industrial semiconductor processes, which would help integrate nanowires into electronics.

These nanowires proved extraordinarily sensitive to their environment, changing in voltage on contact with molecules. They can detect the activation of a T cell immune response to a foreign compound within roughly 10 seconds by sensing the acid released by the cells. Detecting such activation usually takes several minutes, if not hours, to complete via conventional diagnostic assays using tagged antibodies. The investigators also show that nanowires bound with antibodies could detect as few as 60 cancer-linked molecules per cubic millimeter, as good as any current state-of-the-art sensor.

"You can imagine diagnosing patients right at the point of care with devices based off these nanowires, at the ER, the office or the battlefield," says Jonathan Schneck, an immunologist at Johns Hopkins University. "This represents a much more powerful tool than anything I've seen coming down the road in terms of speed of response."

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