Using an atomic force microscope tip as a pen and different single-stranded DNA as inks, scientists at Northwestern University have demonstrated a technique that could lead to the ultimate high-density gene chip because it takes gene chips to the limit of miniaturization – down to the scale of the DNA molecules themselves.

This development, which uses the same tool to write patterns and read the results on the nanometer scale, could have an enormous impact on genomics and proteomics research.

Results of the DNA patterning on both gold and silicon oxide, which is important for electronic and optical materials applications, will be published in the June 7 issue of the journal Science.

“With this new tool, we can take a normal chip that’s made and sold today for studying a problem in genomics and miniaturize it to 1/100,000th of its size,” said Chad A. Mirkin, director of Northwestern’s Institute for Nanotechnology, who led the research team. “In a normal chip with 100,000 different spots of DNA, each spot is 20 to 40 micrometers in diameter. Using state-of-the-art dip-pen nanolithography we can prepare 100,000 DNA spots in the area occupied by a single spot in a conventional gene chip.”

This technology, which can produce spots of DNA down to 50 nanometers in diameter, may make it possible to one day have a gene chip with an array of 100,000 different diagnostic é™Fs in an area the size of the tip of a needle. In the future, it may take only a few seconds to make a gene chip, said Mirkin. And by putting in more information per unit area, smaller sample sizes would be required, reducing cost and time.

“Our direct-write patterning of multiple DNA strands also opens up new possibilities for building and studying nanoscale architectures,” said Mirkin, also George B. Rathmann Professor of Chemistry. “By taking advantage of DNA as a type of biochemical Velcro, we should be able to build a circuit, a catalyst, a sensor or a transistor from the bottom up, instead of the top down.

“We want to build materials in a fundamentally new way, by taking advantage of the ability of DNA to self-assemble into a pre-programmable structure. If one uses the analogy of building a house, the deposited DNA is not only an architectural blueprint for a structure but also the construction worker which directs where each brick goes. Because single-stranded DNA molecules have a natural pre-programmed chemical match and attract complementary molecules, we can use them to control material and device fabrication.”

The ability to use different strands of DNA adds to the chemical complexity of the structure, and researchers now can vary the size, shape and distance between DNA “spots.” The features of size and shape can be controlled by a simple change in humidity and by controlling the path of the microscope’s tip.

The method of dip-pen nanolithography, invented and developed at Northwestern, allowed the researchers to use an atomic force microscope (AFM) tip as a nano-pen to write out a checkerboard pattern of spots of two different DNA strands on an oxidized silicon substrate. The surface between the spots was processed to prevent it from absorbing target DNA and disturbing the readings. When the array was exposed to a solution containing DNA complementary to the two types of spots (one complement attached to large gold nanoparticles and the other to small gold nanoparticles), the DNA selectively assembled on the correct spots. The researchers used the same AFM tip to image the results, which appeared as nanoscopic boulders of different heights.


Other authors on the paper are Linette Demers and David Ginger (lead authors), So-Jung Park, Zhi Li and Sung-Wook Chung, all at Northwestern. The research was supported by the Air Force Office of Scientific Research, the Defense Advanced Research Projects Agency and the National Science Foundation.