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DNA Circling the Nanopore Drain May Improve Sequencing Flow

GEN | August 07, 2019

At the nanoscale, a clogged drain wont clear be cleared with a plunger or a snake or Drano, for that matter. But application of an external force can help, provided the nanoscale plumbing has the right surface, an irregular surface, or rather, a surface that is irregular in the right way. Graphene membranes that contain nanopores are being evaluated for use in DNA sorting and sequencing applications. Often, when these membranes are fabricated, they end up with surface-step defects, tiny terraced regions that would require any biomolecules sliding over the surface to occasionally step up, or down, to keep traveling along a given path—which could, for example, lead to a nanopore sensor. Rather than try to eliminate these defects, scientists at the University of Illinois at Urbana-Champaign (UIUC) resolved to find a way to work with them. Using all-atom molecular dynamics, the scientists demonstrated that DNA physisorbed to a graphene surface moved much faster down a step defect than up, and even faster along the defect edge, regardless of whether the motion was produced by a mechanical force or a solvent flow. These findings were surprising, not the least because gravity at the nanoscale is negligible, which means that moving a biomolecule a step up shouldn’t require any more energy than moving the same biomolecule a step down. While puzzling, this difference is interesting. It suggests that architectures are possible that could overcome the strong physisorption of DNA onto graphene, which has so far severely limited the sensing and sequencing applications of graphene nanopores. Initially, the UIUC scientists, physics professor Aleksei Aksimentiev, PhD, and graduate student Manish Shankla, thought they could use concentric defect patterns around the pores to force biomolecules down. The scientists’ simulations, however, showed that biomolecules tended to congregate along the edges of the steps. That was when the scientists had a revelation: A defect with edges spiraling into a pore, combined with an applied directional force, would give a biomolecule no other option than to go into the pore—as though circling down a drain.

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