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Researchers Create High-Density Chip With Nanolithography

NEW YORK, June 7 - Researchers have developed a technology that could be used to create oligonucleotide arrays up to 100,000 times as dense as the current industry standard.


A team from Northwestern University's Institute for Nanotechnology used a technique it calls "direct-write dip-pen nanolithography." Specifically, the researchers use an atomic force microscope to directly transfer oligonucleotides onto both gold and silicon oxide surfaces.


By coating the microscope tip with a solution to make it positively charged and hydrophilic, they were able to have precise control over the flow of oligonucleotides.


The technique allowed the team to create truly tiny spots--roughly 50 nm--of DNA. Spotting at this resolution could permit as many as 100,000 oligo spots to fit on a chip as small as 100 ųm by 100 ųm, the researchers said.


"Effectively we can take a normal spot within an Affymetrix-type chip and put an entire gene chip within the area occupied by one of those spots,"  said Chad Mirkin, who directs Northwestern's nanotechnology institute. "There are a variety of benefits--you'd be working with smaller sample sizes, volumes, and smaller absolute amounts of targets."


With this technique, the atomic force microscope is also used to read signals. "When you make spots so small, it turns out that when those spots react with targets all the physical parameters of the spot change--the height, the stickiness, the shape," said Mirkin. "It can be read out fairly quickly with ordinary scanning probe microscope."


The research is described in the June 7 issue of Science.


Mirkin hopes that the technology can be further adapted to probe other biological questions, especially surface interactions.


"The old way was to grab natural receptors for targets and slap them down," he said. "What we're proposing is to take advantage of a tool that allows you to draw patterns on the lengthscale of biology, and look systematically at how pattern recognition takes place."


NanoInk, a Northwestern spinoff that Mirkin founded earlier this spring, is commercializing the technology. The company plans to introduce software that will allow users to adapt atomic force microscopes to make their own arrays.

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