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Nano-Bio Interface

Theory & Computation
Selected Publications

K. K. Saha, M. Drndic, and B. K. Nikolic, DNA base-specific modulation of microampere transverse edge currents through a metallic graphene nanoribbon with a nanopore, Nano Lett. 12, 50 (2012).

The successful realization of fast and low-cost methods for reading the sequence of DNA bases is envisaged to lead to personalized medicine and applications in various subfields of genetics. A variety of tools borrowed from condensed matter physics, such as solid-state nanopores or nanogaps between two metallic electrodes,  have recently emerged as one of the pillars of the so-called third generation DNA sequencing. The key issue in these approaches revolve around how to slow down the translocation speed of the DNA molecule and how to achieve single-base resolution.

The very recent fabrication of graphene nanopores and successful detection of DNA translocation through has opened new avenues for the nanopore-based sequencing. Graphene, as a two-dimensional crystal of carbon atoms densely packed into a honeycomb lattice, brings its unique electronic and mechanical properties into the search for an optimal biosensor. Since single layer graphene is only one-atom-thick, the entire thickness of the nanopore through which DNA is threaded is comparable to the dimensions of DNA nucleotides. Therefore, there is only one recognition point rather than multiple contacts with DNA in the nanopore. Also, since graphene is mechanically strong, it can be used as both the nanopore and the electrode material, thereby making it easier to build sequencing devices.

At the same time, there have been great theoretical strides to further advance the understanding and design of nanopore- and nanogap-based devices in the transverse current measuring geometry [8-10]. For example, a number of devices have been theoretically considered where DNA molecules translocate through a nanogap between two metallic electrodes [8,11,12] (including graphene nanoribbons [13,14] and carbon nanotubes [15]). The first-principles analysis of such biosensors suggests that the passage of DNA nucleotides can modulates the transverse tunneling current. The promise of such devices has also been demonstrated in the very recent experiments utilizing bare [16] or functionalized [17] gold electrodes. While these experiments still have to integrate nanopores [9], they present a proof-of-principle demonstration that DNA bases can be distinguished based on the measurement of transverse currents.

Nevertheless, many challenges remain for these approaches to make them practical and far-reaching, including efficient control of the DNA translocation rate, suppressing stochastic nucleotide motions, and resolving the signal overlap between different nucleotides. For example, the recent experiments [4-6] on nanopores within single or multilayer large-area graphene, which have measured fluctuations in the vertical ionic current [18] flowing while DNA passes through the pore, have not reached sufficient resolution to detect and identify individual bases [19].

On the other hand, small transverse current (typically of the order of pA) remains a fundamental issue with any DNA sequencing approach based on tunneling across a nanogap because of poor signal-to-noise ratio. That is, transverse tunneling current is extremely sensitive to changes in the atomic and molecular positions caused by thermal fluctuation, as well as to changes in the electrodes themselves due to strong electric field in the nanojunction which can cause contamination of the electrodes with counterions, electromigration of surface atoms and local heating. In addition, for typically off-resonant tunneling, when molecular eigenleves are far away from the Fermi energy of the electrodes, the device does not have intrinsic chemical selectivity. Thus, the recent experiments have observed broad current distributions for each nucleotide between bare gold electrodes. The current distributions can be narrowed by using functionalized gold electrodes, but in that case one still findssome overlap of the distributions corresponding to different nucleotides.

Thus, new and improved designs should be explored to resolve these issues and guide future experiments and possible fabrication of commercially viable nanoelectronic biosensors. On this quest, computational techniques, such as density functional theory coupled with nonequilibrium Green functions (NEGF-DFT) or molecular dynamics and multiscale techniques, could play an essential role.

On the experimental side, UD researchers focused on magnetism and spintronics are developing devices which exploit interaction between functionalized magnetic nanoparticles and biological molecules and systems for their detection via, e.g., magnetic tunnel junctions with greatly reduced noise.