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Leburton, Timp, and team propose DNA fabrication technique

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By Lauren Eichmann, ECE Illinois
March 10, 2008

  • Prof. Greg Timp and Prof. Jean-Pierre Leburton are studying DNA sequencing using synthetic nanopores.
  • The project is part of an effort to make DNA sequencing faster and more cost effective.
  • Timp and Leburton are also collaborating with professors in the Physics Department and Department of Molecular and Cellular Biology.

Along with ECE Professor Gregory L. Timp, Professor Jean-Pierre Leburton is studying DNA sequencing using a synthetic nanopore. The effort stems from a large goal of the National Human Genome Research Institute, part of the National Institutes of Health (NIH), to make DNA sequencing faster and more cost effective. The current model to establish a human genome involves a process that requires hundreds of thousands of dollars and takes weeks to complete through a biochemical process.

Leburton said the multidisciplinary aspect of the work is essential. Through their research, Timp and Leburton are also collaborating with Professor Klaus Schulten and Assistant Professor Oleksii Aksimentiev with the Physics Department, and Department of Molecular and Cellular Biology Director Stephen Sligar.

Illustration "A" shows a DNA strand enveloped by a cylindrical surface, a phantom pore, initially wide enough to accommodate the strand. Images "B" and "C" show the conformation of a DNA strand in a 1-nm-diam pore. The DNA backbone is stretched, and the DNA bases are tilted toward the end of the strand.
Illustration "A" shows a DNA strand enveloped by a cylindrical surface, a phantom pore, initially wide enough to accommodate the strand. Images "B" and "C" show the conformation of a DNA strand in a 1-nm-diam pore. The DNA backbone is stretched, and the DNA bases are tilted toward the end of the strand.

The initiative began nearly five years ago between Leburton, Timp, and Schulten, and revolves around the idea to use a very small semiconductor membrane as a capacitor made of a silicon dioxide layer with a nanopore. This is used to push a DNA molecule through the nanopore so the charge carried by each base on the DNA strand of the electrode can be read.

"It is a very nice project - aside from the fundamental scientific implications - to show that science today is not really limited to a particular discipline and that if we want to make a new discovery, we have to put complementary expertise in common to achieve our goal," said Leburton.

The project has some extremely important implications, according to Leburton. He said that, once perfected, it would be an extremely fast, cheap, and fully reliable way to sequence DNA. In fact, if their effort is successful, their process using a nanopore could fall within the NIH goal to make fabrication costs total less than $1,000.

Other groups in the U.S and worldwide are also currently researching and proposing different scenarios to cheaply read the human genome. In 2002, the Illinois team received a four-year National Science Foundation grant. Their research is now being funded by the National Institutes of Health.

"It is an extremely difficult project," said Leburton. "It is not obvious that we will be able to achieve our goal (DNA sequencing) because the DNA doesn’t pass through the nanopore rigidly; there is a lot of electrical fluctuation going on."

Leburton said they are currently looking at different methods to suppress or reduce the fluctuations. One potential option involves moving the DNA slowly through the nanopore, thus allowing for a good reading of each charge on the base. Another approach, proposed by Timp, is to record multiple DNA sequence readings and likewise use the averages as it goes back and forth through the nanopore.

The use of electricity to confine the DNA strand in a volume of the nanopore that is even smaller than the nanopore, or implementing the structure so the DNA remains fixed as it goes through the pore, are other proposed areas of research. Such studies will have an "enormous" impact on society once perfected, said Leburton, especially in terms of cancer studies and the detection of biochemical agents.

For more information about the research, or to watch a movie that simulates a DNA molecule moving through a nanopore, visit Timp's Web site at https://netfiles.uiuc.edu/gtimp/www. According to the publisher of Nanotechnology, a paper co-authored by ECE faculty, "Simulation of the electric response of DNA translocation through a semiconductor nanopore capacitor," was among the most highly downloaded articles in Nanotechnology in 2006.

Editor's note: media inquiries should be directed to Brad Petersen, Director of Communications, at bradp@illinois.edu or (217) 244-6376.

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