Nanopore-based single-molecule detection and analysis have been pursued intensively over the past decade. One of the most promising applications in this regard is DNA sequencing achieved through DNA translocation-induced blockades in ionic current. Recently, nanopores fabricated in graphene sheets were used to detect double-stranded DNA. Due to its sub-nanometer thickness, graphene nanopores show great potential to realize DNA sequencing at single-base resolution. Resolving at the atomic level electric field-driven DNA translocation through graphene nanopores is crucial to guide the design of graphene-based sequencing devices. Molecular dynamics simulations, in principle, can achieve such resolution and are employed here to investigate the effects of applied voltage, DNA conformation and sequence as well as pore charge on the translocation characteristics of DNA. We demonstrate that such simulations yield current characteristics consistent with recent measurements and suggest that under suitable bias conditions A-T and G-C base pairs can be discriminated using graphene nanopores.

Epigenetic modifications in eukaryotic genomes occur primarily in the form of 5-methylcytosine (5 mC). These modifications are heavily involved in transcriptional repression, gene regulation, development and the progression of diseases including cancer. We report a new single-molecule assay for the detection of DNA methylation using solid-state nanopores. Methylation is detected by selectively labeling methylation sites with MBD1 (MBD-1x) proteins, the complex inducing a 3 fold increase in ionic blockage current relative to unmethylated DNA. Furthermore, the discrimination of methylated and unmethylated DNA is demonstrated in the presence of only a single bound protein, thereby giving a resolution of a single methylated CpG dinucleotide. The extent of methylation of a target molecule could also be coarsely quantified using this novel approach. This nanopore-based methylation sensitive assay circumvents the need for bisulfite conversion, fluorescent labeling, and PCR and could therefore prove very useful in studying the role of epigenetics in human disease.

By using the nonequilibrium Green's function technique, we show that the shape of the edge, the carrier concentration, and the position and size of a nanopore in graphene nanoribbons can strongly affect its electronic conductance as well as its sensitivity to external charges. This technique, combined with a self-consistent Poisson-Boltzmann formalism to account for ion charge screening in solution, is able to detect the rotational and positional conformation of a DNA strand inside the nanopore. In particular, we show that a graphene membrane with quantum point contact geometry exhibits greater electrical sensitivity than a uniform armchair geometry provided that the carrier concentration is tuned to enhance charge detection. We propose a membrane design that contains an electrical gate in a configuration similar to a field-effect transistor for a graphene-based DNA sensing device.O ver the past few years the need has grown for low-cost, highspeed, and accurate biomolecule sensing, propelling the socalled third generation of genome sequencing devices (1-4). Many associated technologies have been developed, but recent advances in the fabrication of solid-state nanopores have shown that the translocation of biomolecules such as DNA through such pores is a promising alternative to traditional sensing methods (5-9). Some of these methods include measuring (i) ionic blockade current fluctuations through nanopores in the presence of nucleotides (10), (ii) tunneling currents across nanopores containing biomolecules (11), and (iii) direct transversecurrent measurements (12). Graphene is a prime candidate for such measurements. Theoretical studies suggest that functionalized graphene nanopores can be used to differentiate passing ions, demonstrating the potential use of graphene membranes in nanofluidics and molecular sensing (13). In addition, its atomicscale thickness allows a molecule passing through it to be scanned at the highest possible resolution, and the feasibility of using graphene nanopores for DNA detection has been demonstrated experimentally (14-17). Lastly, electrically active graphene can, in principle, both control and probe translocating molecules, acting as a gate as well as a charge sensor, which passive, oxide-based nanopore devices are incapable of doing.Molecular dynamics studies describing the electrophoresis of DNA translocation through graphene nanopores demonstrated that DNA sequencing by measuring ionic current blockades is possible in principle (18,19). Additionally, several groups have reported first-principles-based studies to identify base pairs using tunneling currents or transverse conductance-based approaches (12,20,21). Saha et al. reported transverse edge current variations of the order of 1 μA through graphene nanoribbons (GNRs) caused by the presence of isolated nucleotides in a nanopore, and reported base pair specific edge currents (12). These studies, however, do not account for solvent or screening effects; the latter effects are due to the presence of ions in the solution and ...

A graphene membrane conductor containing a nanopore in a quantum point contact (QPC) geometry is a promising candidate to sense, and potentially sequence, DNA molecules translocating through the nanopore. Within this geometry, the shape, size, and position of the nanopore as well as the edge configuration influences the membrane conductance caused by the electrostatic interaction between the DNA nucleotides and the nanopore edge. It is shown that the graphene conductance variations resulting from DNA translocation can be enhanced by choosing a particular geometry as well as by modulating the graphene Fermi energy, which demonstrates the ability to detect conformational transformations of a double-stranded DNA, as well as the passage of individual base pairs of a single-stranded DNA molecule through the nanopore.

In this paper, we present a computational model to describe the electrical response of a constricted graphene nanoribbon (GNR) to biomolecules translocating through a nanopore. For this purpose, we use a self-consistent 3D Poisson equation solver coupled with an accurate three-orbital tight-binding model to assess the ability for a gate electrode to modulate both the carrier concentration as well as the conductance in the GNR. We also investigate the role of electrolytic screening on the sensitivity of the conductance to external charges and find that the gate electrode can either suppress or enhance the screening of biomolecular charges in the nanopore depending on the value of its potential. Translocating a double-stranded DNA molecule along the pore axis imparted a large change in the conductance at particular gate voltages, suggesting that such a device can be used to sense translocating biomolecules and can be actively tuned to maximize its sensitivity.