Javascript is currently disabled in your web browser. For full site functionality, it is necessary to enable Javascript. In order to enable it, please see these instructions. May 20, 2013 by Evan Lerner This is an illustration of a single-stranded DNA homopolymer translocating through a silicon nitride nanopore. The thickness of the membrane tapers within the nanopore, enhancing its sensitivity. Credit: University of Pennsylvania

(Phys.org) The allure of personalized medicine has made new, more efficient ways of sequencing genes a top research priority. One promising technique involves reading DNA bases using changes in electrical current as they are threaded through a nanoscopic hole.

Now, a team led by University of Pennsylvania physicists has used solid-state nanopores to differentiate single-stranded DNA molecules containing sequences of a single repeating base.

The study was led by Marija Drndi, an associate professor in the Department of Physics and Astronomy in the School of Arts and Sciences, along with graduate students Kimberly Venta and Matthew Puster and post-doctoral researchers Gabriel Shemer, Julio A. Rodriguez-Manzo and Adrian Balan. They collaborated with assistant professor Jacob K. Rosenstein of Brown University and professor Kenneth L. Shepard of Columbia University.

Their results were published in the journal ACS Nano.

In this technique, known as DNA translocation measurements, strands of DNA in a salt solution are driven through an opening in a membrane by an applied electric field. As each base of the strand passes through the pore, it blocks some ions from passing through at the same time; amplifiers attached to the nanopore chip can register the resulting drop in electrical current. Because each base has a different size, researchers hope to use this data to infer the order of the bases as the strand passes through. The differences in base sizes are so small, however, that the proportions of both the nanopores and membranes need to be close those of the DNA strands themselvesa major challenge.

The nanopore devices closest to being a commercially viable option for sequencing are made out of protein pores and lipid bilayers. Such protein pores have desirable proportions, but the lipid bilayer membranes in which they are inserted are akin to a film of soap, which leaves much to be desired in terms of durability and robustness.

Solid-state nanopore devices, which are made of thin solid-state membranes, offer advantages over their biological counterpartsthey can be more easily shipped and integrated with other electronicsbut the basic demonstrations of proof-of-principle sensitivity to different DNA bases have been slower.

"While biological nanopores have shown the ability to resolve single nucleotides, solid-state alternatives have lagged due to two challenges of actually manufacturing the right-sized pores and achieving high-signal, low-noise and high-bandwidth measurements," Drndi said. "We're attacking those two challenges here."

Because the mechanism by which the nanopore differentiate between one type of base and another is by the amount of the pore's aperture that is blocked, the smaller a pore's diameter, the more accurate it is. For the nanopore to be effective at determining a sequence of bases, its diameter must approach the diameter of the DNA and its thickness must approach that of the space between one base and the next, or about 0.3 nanometers.

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Advance in nanotech gene sequencing technique

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