RESEARCHERS CREATE TINY HOLES TO EXAMINE DNA MOLECULES

FAYETTEVILLE, Ark. - Researchers have created a nanoscale hole that can detect individual DNA molecules, a significant step on the path to simple sequencing methods for biologically and medically important molecules.

Jiali Li, assistant professor of physics at the University of Arkansas, Jene Golovchenko, professor of physics and applied physics at Harvard University, staff scientist Eric Brandin and Harvard graduate students Derek Stein and Marc Gershow reported their findings in the journal Nature Materials.

"These tiny holes can see DNA molecules pass one by one," said Li. "They can see the details of the molecules."

One long-term goal of this research is to eventually simplify DNA sequencing, making it a matter of reading the sequence of a single DNA molecule instead of marching through today’s difficult, time-consuming DNA sequencing technologies, which first must amplify the sample for detection, leaving ample room for error.

Li and her colleagues created the molecular microscopes using silicon nitride to build a membrane-like surface that mimics ion channels in biological membranes. Biological membranes allow individual molecules to pass through, but prove delicate and difficult to control and not suitable for developing and integrated single molecular sensor. However, with the synthetic surface, researchers can build the silicon nitride channels and can control their size using an ion beam to change the diameter of the opening in the pore.

The nanopore chip is placed in a solution with ions in it. A voltage applied to the system causes the ions to flow through the nanopore opening. When the DNA molecule is introduced to this system, it blocks the hole as it moves through, causing the ionic current to decrease. The ionic current changes in proportion to the molecule’s diameter, and the length of time the molecule blocks the hole is proportional to the length of the molecule.

"You can measure length, diameter and other information," Li said.

The nanopore microscope also gives information on the folding of the molecule, an important component as structure determines function in the molecular world. Changes in structure can enhance or inhibit molecular properties, which can have consequences in genetic susceptibility to disease and biomedical research into new drugs, among other things.

Li plans to expand on the DNA detection work, which she and her colleagues developed when she was a postdoctoral fellow at Harvard, by using similar concepts to look at proteins here at the University of Arkansas.

"Protein sequences are very complicated," Li said. DNA consists of pairs of four bases of uniform charge, whereas proteins are formed from 20 amino acids with widely varying shapes and properties.

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