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TECHNIQUE MAKES PROTEIN ARRAYS
Dip-pen nanolithography may lead to useful, miniaturized screening tools
CELIA HENRY
By using the technique known as dip-pen nanolithography, chemists at Northwestern University and the University of Chicago have made protein arrays with feature sizes ranging from 100 to 350 nm. The advance could lead to protein or nucleic acid arrays--useful screening tools--that are 1 million to 10 million times denser than those currently available.
The arrays are made by adsorbing proteins to patterns drawn on a gold surface with 16-mercaptohexadecanoic acid [Science, published Feb. 7, Science Express, http://www.sciencemag.org/feature/express/expresstwise.shl]. The proteins can recognize complementary protein structures or analytes. For example, an array of rabbit immunoglobulin G bound only rabbit anti-IgG. Another array was used to study cell adhesion. The arrays are monitored with atomic force microscopy.
Miniaturization is important for more than just making higher density arrays, says Northwestern chemistry professor Chad A. Mirkin, who led the study: "It allows you to probe recognition on a length scale that matters in biology." The team also includes University of Chicago chemistry professor Milan Mrksich and graduate students Ki-Bum Lee, So-Jung Park, and Jennifer C. Smith.
"We're going to begin using this technique to literally draw receptors on a surface, to understand how structures that we fabricate by dip-pen nanolithography interact in a specific way with biologically important structures," Mirkin says. "We can learn a tremendous amount about recognition, which can be translated into the development of new types of detection systems and a better understanding of biological recognition processes."
The next step is to start working with arrays containing multiple kinds of proteins. Mrksich, who led the cellular component of this work, and Mirkin see no reason why the method can't be general for many proteins. "That's purely a surface chemistry issue," Mirkin says.

NANOGRID Proteins can be adsorbed to a surface in a variety of configurations, including dots and grid lines, as shown in this topographic image of a lysozyme nanoarray. The features' sizes were intentionally
varied, and there is no evidence of nonspecific protein adsorption.
COURTESY OF KI-BUM LEE, SO-JUNG PARK, AND JENNIFER C. SMITH
Chemical & Engineering News
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