At the nanoscale, a clogged drain won’t 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.

The scientists summarized their findings in an article (“Step-defect guided delivery of DNA to a graphene nanopore”) that appeared August 5 in the journal Nature Nanotechnology. The article reveals how the scientists stopped fighting physisorption, and instead embraced it by exploiting the direction dependence of forced displacement over a defect.

“We utilized this direction dependency to demonstrate a mechanical analogue of an electric diode and a system for delivering DNA molecules to a nanopore,” the article’s authors wrote. “The defect-guided delivery principle can be used for the separation, concentration, and storage of scarce biomolecular species, on-demand chemical reactions, and nanopore sensing.”

In 2014, Aksimentiev and Shankla demonstrated that a graphene membrane that controlled a biomolecule’s movement through a nanopore by means of electrical charge. They discovered that once the molecules are on the surface of the membrane, it is very difficult to get them to shuffle into the membrane’s pores because molecules like to stick to the surface.

While on sabbatical at Delft University of Technology in the Netherlands, Aksimentiev found that DNA tends to accumulate and stick along the edges of fabrication-formed defects that occur as linear steps spanning across the membrane’s surface.

In the current work, the scientists sought to use these flaws to direct the stuck molecules into a graphene surface’s nanopores. The scientists tested their ideas by using the Blue Waters supercomputer at the National Center for Supercomputing Applications at Illinois and the XSEDE supercomputer to model the system and molecule movement scenarios at the atomic level.

“Molecular dynamics simulations let us watch what is happening while simultaneously measuring how much force is required to get the molecule to clear a step,” Aksimentiev explained. The simulations also revealed that it would be possible to drop molecules anywhere on the membrane covered with spiraling step-defect structures, whereupon the molecules would be pulled into a pore.

The researchers have not yet produced a membrane with spiral defects in the laboratory, but that task may be easier than trying to rid a graphene membrane of the current molecule-immobilizing step defects.

“When manufactured at scale, defect-guided capture may increase the DNA capture throughput by several orders of magnitude, compared with current technology,” Shankla suggested. Going forward, Aksimentiev and Shankla hope to see their defect-guided delivery used in a variety of other materials and applications such as delivery of individual molecules to reaction chambers for experiments.

“Defect-guided transport of biomolecules can be of use in a diverse range of technological processes, from lab-on-chip sorting and synthesis of biomolecules to single-molecule nanopore sequencing,” the scientists concluded. “Importantly, the deliberate patterning of two-dimensional materials with step defects is well within reach of modern nanofabrication technology.”

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