The success of graphene for nanopore DNA sequencing has shown that it is possible to explore other potential single- and few-atom thick layers of 2D materials beyond graphene, and also that these materials can exhibit fascinating and technologically useful properties for DNA base detection that are superior to those of graphene. In this article, we review the state-of-the art of DNA base detection using 2D materials beyond graphene. Initially, we present an overview of nanopore-based DNA sequencing methods using biological and solid-state nanopores, and discuss several challenges that limit their use for single-base resolution. Then we outline the progress, challenges, and opportunities using graphene. Additionally, we discuss several potential 2D materials beyond graphene such as hexagonal boron nitride, elemental 2D materials beyond graphene, and 2D transition metal dichalcogenides. Finally, we highlight the potential of using van der Waals materials for advanced DNA base detection technologies.
Despite many studies on how geometry can be used to control the electronic properties of graphene, certain limitations to fabrication of designed graphene nanostructures exist. Here, we demonstrate controlled topographical replication of graphene by artificial deoxyribonucleic acid (DNA) nanostructures. Owing to the high degree of geometrical freedom of DNA nanostructures, we controlled the nanoscale topography of graphene. The topography of graphene replicated from DNA nanostructures showed enhanced thermal stability and revealed an interesting negative temperature coefficient of sheet resist…
The success of graphene for nanopore DNA sequencing has shown that it is possible to explore other potential single-atom and few-atom thick layers of elemental 2D materials beyond graphene (e.g., phosphorene and silicene). Using density functional theory, we studied the interaction of DNA bases with nanopores created in finite-size nanoribbons from graphene, phosphorene, and silicene. We observe that binding energies of DNA bases using nanopores from phosphorene and silicene are generally smaller compared to graphene. The band gaps of phosphorene and silicene are significantly altered due to i…
In this study, structural stability, electronic, optical and vibrational properties of DNA nucleobase adsorbed Graphene Quantum Dot (GQD) has been investigated using density functional theory. Based on state-of-art electronic structure calculations, we predict order of GQD sensitivity for DNA nucleobase as Thymine > Cytosine > Guanine > Adenine. An interaction of GQD with DNA nucleobase leads to modulation in electronic energy gap. Our calculated UV/vis and IR vibrational spectra show unique spectral band that can be used fingerprints in next generation DNA sequencing diagnostics.
A graphene channel field-effect biosensor is demonstrated for detecting the binding of double-stranded DNA and poly-l-lysine. Sensors consist of CVD graphene transferred using a clean, etchant-free transfer method. The presence of DNA and poly-l-lysine are detected by the conductance change of the graphene transistor. A readily measured shift in the Dirac Voltage (the voltage at which the graphenes resistance peaks) is observed after the graphene channel is exposed to solutions containing DNA or poly-l-lysine. The Dirac voltage shift is attributed to the binding/unbinding of charged molecules …
The ability to detect and discriminate DNA bases by reading it directly using simple and cost-effective methods is an important problem whose solution can produce significant value for areas such as cancer and human genetic disorders. Two-dimensional (2D) materials have emerged as revolutionary materials for electronic DNA sequencing with strong potentials for fast, single-nucleotide direct-read DNA sequencing with a minimum amount of consumables. Among 2D materials, graphene is the most explored for DNA sequencing. This is due to its commercial availability. The major hindrance of graphene is…
We study how double-stranded DNA translocates through graphene nanogaps. Nanogaps are fabricated with a novel capillary-force induced graphene nanogap formation technique. DNA translocation signatures for nanogaps are qualitatively different from those obtained with circular nanopores, owing to the distinct shape of the gaps discussed here. Translocation time and conductance values vary by $\sim 100$%, which we suggest are caused by local gap width variations. We also observe exponentially relaxing current traces. We suggest that slow relaxation of the graphene membrane following DNA transloca…
Electronic DNA sequencing using two-dimensional (2D) materials such as graphene has recently emerged as the next-generation of DNA sequencing technology. Owing to its commercial availability and remarkable physical and conductive properties, graphene has been widely investigated for DNA sequencing by several theoretical and experimental groups. Despite this progress, sequencing using graphene remains a major challenge. This is due to the hydrophobic nature of graphene, which causes DNA bases to stick to its surface via strong π-π interactions, reducing translocation speed and increasing error …
We present a tight-binding model study of a two-terminal graphene nanopore device for sequential determination of DNA bases. Using Green's function technique we investigate the changes in electronic transport properties of the device due to insertion of different nucleotides into the nanopore created within a zigzag graphene nanoribbon. First we try to characterise the device in static condition and then go for sequencing application by setting the bias across it to a specific voltage and then recording the characteristic current signals corresponding to each nucleotides of a translocating DNA…
We demonstrate that biological molecules such as Watson-Crick DNA base pairs can behave as biological Aviram-Ratner electrical rectifiers because of the spatial separation and weak hydrogen bonding between the nucleobases. We have performed a parallel computational implementation of the ab-initio non-equilibrium Green's function (NEGF) theory to determine the electrical response of graphene---base-pair---graphene junctions. The results show an asymmetric (rectifying) current-voltage response for the Cytosine-Guanine base pair adsorbed on a graphene nanogap. In sharp contrast we find a symmetri…
We present an unique way to detect basepair mismatches in DNA leading to different epigenetic disorder by the method of nanopore sequencing. Based on a tight-binding formulation of graphene nanopore based device, using Greens function approach we measure the changes in the electronic transport properties of the device as we translocate a double-stranded DNA through the nanopore embeded in a zigzag graphene nanoribbon. In the present work we not only successfully detect the usual AT and GC pairs, but also a set of possible mismatches in the complementary base-pairing without any ambiguity. Our …
We propose a water-immersed nucleobase-functionalized suspended graphene nanoribbon as an intrinsically selective device for nucleotide detection. The proposed sensing method combines Watson-Crick selective base pairing with graphene's capacity for converting anisotropic lattice strain to changes in an electrical current at the nanoscale. Using detailed atomistic molecular dynamics simulations, we study sensor operation at ambient conditions. We combine simulated data with theoretical arguments to estimate the levels of measurable electrical signal variation in response to strains and determin…
In this work we numerically calculate the electric current through three kinds of DNA sequences (telomeric, λ-DNA, and p53-DNA) described by different heuristic models. A bias voltage is applied between two zig-zag edged graphene contacts attached to the DNA segments, while a gate terminal modulates the conductance of the molecule. The calculation of current is performed by integrating the transmission function (calculated using the lattice Green's function) over the range of energies allowed by the chemical potentials. We show that a telomeric DNA sequence, when treated as a quantum wire in t…
A theoretical understanding of the experimental electronic transport phenomena in gas sensors based on DNA functionalized graphene is presented by quantitatively investigating the time-dependent electronic transport in these devices using the nonequilibrium Green's function (NEGF) formalism and tight-binding approximation. The time-dependent zeroth and first order contributions to the current are calculated with derivations of the equation of motion and Dyson equation. The zeroth order contribution is identified as the time-dependent Landauer formula in terms of the slow time variable and the …
Topological line defects in graphene represent an ideal way to produce highly controlled structures with reduced dimensionality that can be used in electronic devices. In this work we propose using extended line defects in graphene to improve nucleobase selectivity in nanopore-based DNA sequencing devices. We use a combination of QM/MM and non-equilibrium Green's functions methods to investigate the conductance modulation, fully accounting for solvent effects. By sampling over a large number of different orientations generated from molecular dynamics simulations, we theoretically demonstrate t…
Nanopores -- nanosized holes that can transport ions and molecules -- are very promising devices for genomic screening, in particular DNA sequencing. Both solid-state and biological pores suffer from the drawback, however, that the channel constituting the pore is long, viz. 10-100 times the distance between two bases in a DNA molecule (0.5 nm for single-stranded DNA). Here, we demonstrate that it is possible to realize and use ultrathin nanopores fabricated in graphene monolayers for single-molecule DNA translocation. The pores are obtained by placing a graphene flake over a microsize hole in…
Translocation of DNA through a nanopore with embedded electrodes is at the centre of new rapid inexpensive sequencing methods which allow distinguishing the four nucleobases by their different electronic structure. However, the subnanometer separation between nucleotides in DNA requires ultra-sharp probes. Here, we propose a device architecture consisting of a nanopore formed in bilayer graphene, with the two layers acting as separate electrical contacts. The 0.34 nm interlayer distance of graphene is ideally suited for electrical coupling to a single nucleobase, avoiding the difficulty of fab…
Graphene is a true two dimensional material with exceptional electronic properties and enormous potential for practical applications. Graphene's promise as a chemical sensor material has been noted but there has been relatively little work on practical chemical sensing using graphene, and in particular how chemical functionalization may be used to sensitize graphene to chemical vapors. Here we show one route towards improving the ability of graphene to work as a chemical sensor by using single stranded DNA as a sensitizing agent. The resulting broad response devices show fast response times, c…
DNA methylation plays a pivotal role in the genetic evolution of both embryonic and adult cells. For adult somatic cells, location and dynamics of methylation has been very precisely pinned down with the 5-cytosine markers on cytosinephosphate- guanine (CpG) units. Unusual methylation on CpG islands are identified as one of the prime causes for silencing the tumor suppressant genes. Early detection of such methylation can diagnose the potentially harmful oncogenic evolution of cells, and provide a promising guideline for cancer prevention. With this motivation, we propose a cytosine methylatio…
Based on a model of the optical biosensors (Science 311, 508 (2006)) by wrapping a piece of double-stranded DNA around the surface of single-walled carbon nanotubes (SWCNT), we propose a new design model of this sensor, in which the SWCNT is replaced by a semiconductor graphene ribbon (SGR). Using a simple theory of exciton in SGRs, we investigated transition of DNA secondary structure from the native, right-handed B form to the alternate, left-handed Z form. This structural phase transition of DNA is the working principle of this optical biosensor at the sub cellular level from DNA and semico…
Graphene nanogaps and nanopores show potential for the purpose of electrical DNA sequencing, in particular because single-base resolution appears to be readily achievable. Here, we evaluated from first principles the advantages of a nanogap setup with functionalized graphene edges. To this end, we employed density functional theory and the non-equilibrium Green's function method to investigate the transverse conductance properties of the four nucleotides occurring in DNA when located between the opposing functionalized graphene electrodes. In particular, we determined the electrical tunneling …
Innovative methodologies for reliably and inexpensively sequencing DNA can lead to a new era of personalized medicine. In this work, we performed a theoretical investigation of a nanogap-based all electronic DNA sequencing device. To do so, we used a nitrogen-terminated nanogap on a graphene sheet with the environment fully taken into account. Our investigation is performed using a hybrid methodology combining quantum and classical mechanics coupled to non-equilibrium Green's functions for solving the electron transport across the device. The obtained results show that the DNA nucleotides can …
We propose using graphene electrodes with hydrogenated edges for solid-state nanopore-based DNA sequencing, and perform molecular dynamics simulations in conjunction with electronic transport calculations to explore the potential merits of this idea. The results of our investigation show that, compared to the unhydrogenated system, edge-hydrogenated graphene electrodes facilitate the temporary formation of H-bonds with suitable atomic sites in the translocating DNA molecule. As a consequence, the average conductivity is drastically raised by about 3 orders of magnitude while exhibiting signifi…
The fabrication of nanopores in atomically-thin graphene has recently been achieved and translocation of DNA has been demonstrated. Taken together with an earlier proposal to use graphene nanogaps for the purpose of DNA sequencing, this approach can resolve the technical problem of achieving single-base resolution in electronic nucleobase detection. We have theoretically evaluated the performance of a graphene nanogap setup for the purpose of whole-genome sequencing, by employing density functional theory and the non-equilibrium Green's function method to investigate the transverse conductance…
We propose two-terminal devices for DNA sequencing which consist of a metallic graphene nanoribbon with zigzag edges (ZGNR) and a nanopore in its interior through which the DNA molecule is translocated. Using the nonequilibrium Green functions combined with density functional theory, we demonstrate that each of the four DNA nucleotides inserted into the nanopore, whose edge carbon atoms are passivated by either hydrogen or nitrogen, will lead to a unique change in the device conductance. Unlike other recent biosensors based on transverse electronic transport through DNA nucleotides, which util…
Nanopore based sequencing has demonstrated significant potential for the development of fast, accurate, and cost-efficient fingerprinting techniques for next generation molecular detection and sequencing. We propose a specific multi-layered graphene-based nanopore device architecture for the recognition of single DNA bases. Molecular detection and analysis can be accomplished through the detection of transverse currents as the molecule or DNA base translocates through the nanopore. To increase the overall signal-to-noise ratio and the accuracy, we implement a new "multi-point cross-correlation…
We present a comparative study of DNA nucleobases [guanine (G), adenine (A), thymine (T), and cytosine (C)] adsorbed on hexagonal boron nitride (\textit{h}-BN) sheet and graphene, using local, semilocal, and van der Waals (vdW) energy-corrected density-functional theory (DFT) calculations. Intriguingly, despite the very different electronic properties of BN sheet and graphene, we find rather similar binding energies for the various nucleobase molecules when adsorbed on the two types of sheets. The calculated binding energies of the four nucleobases using the local, semilocal, and DFT+vdW schem…
Based on combined density functional theory and nonequilibrium Greens function quantum transport studies, we have demonstrated quantum interference effects on the transverse conductance of Hachimoji synthetic nucleic acids placed between the oxygen-terminated zigzag graphene nanoribbon nanoelectrodes. We theorize that the QI effect could be well preserved in pi-pi coupling between a nucleobase molecule and the carbon-based nanoelectrode. Our study indicates that QI effects such as anti-resonance or Fano-resonance that affect the variation of transverse conductance depending on the nucleobase c…
In this study, we examine the mechanism of nanopore-based DNA sequencing using a voltage bias across a graphene nanoribbon. Using density functional theory and a non-equilibrium Green's function approach, we determine the transmission spectra and current profile for adenine, guanine, cytosine, thymine, and uracil as a function of bias voltage in an energy minimized configuration. Utilizing the transmission current, we provide a general methodology for the development of a three nanopore graphene-based device that can be used to distinguish between the various nucleobases for DNA/RNA sequencing…
Using first-principles quantum transport simulations, based on the nonequilibrium Green function formalism combined with density functional theory (NEGF+DFT), we examine changes in the total and local electronic currents within the plane of graphene nanoribbon with zigzag edges (ZGNR) hosting a nanopore which are induced by inserting a DNA nucleobase into the pore. We find a sizable change of the zero-bias conductance of two-terminal ZGNR + nanopore device after the nucleobase is placed into the most probable position (according to molecular dynamics trajectories) inside the nanopore of a smal…
Single-molecule biosensing, with a promise of being applied in protein and DNA sequencing, could be achieved using tunneling current approach. Electrode-molecule-electrode tunneling current critically depends on whether molecular levels contribute to electronic transport or not. Here we found employing DFT and Non-Equilibrium Green's Function formalism that energies of benzene molecular levels placed between graphene electrodes are strongly influenced by electrode termination. Termination-dependent dipoles formed at the electrode ends induce in-gap field effect that is responsible for shifting…
This paper presents an electrolytically gated broadband microwave sensor where atomically-thin graphene layers are integrated into coplanar waveguides and coupled with microfluidic channels. The interaction between a solution under test and the graphene surface causes material and concentration-specific modifications of graphene's DC and AC conductivity. Moreover, wave propagation in the waveguide is modified by the dielectric properties of materials in its close proximity via the fringe field, resulting in a combined sensing mechanism leading to an enhanced S-parameter response compared to me…
The atomically-precise controlled synthesis of graphene stripes embedded in hexagonal boron nitride opens up new possibilities for the construction of nanodevices with applications in sensing. Here, we explore properties related to electronic structure and quantum transport of a graphene nanoroad embedded in hexagonal boron nitride, using a combination of density functional theory and the non-equilibrium Green's functions method to calculate the electric conductance. We find that the graphene nanoribbon signature is preserved in the transmission spectra and that the local current is mainly con…
Single-molecule sensing is at the core of modern biophysics and nanoscale science, from revolutionizing healthcare through rapid, low-cost sequencing to understanding various physical, chemical, and biological processes at their most basic level. However, important processes at the molecular scale are often too fast for the detection bandwidth or otherwise outside the detection sensitivity. Moreover, most envisioned biophysical applications are at room temperature, which further limits detection due to significant thermal noise. Here, we theoretically demonstrate reliable transduction of force…
Heterostructures composed of dissimilar two-dimensional nanomaterials can have nontrivial physical and mechanical properties promising for many applications. Interestingly, in some cases, it is possible to create heterostructures composed of weakly and strongly stretched domains with the same chemical composition, as it has been demonstrated for some polymer chains, DNA, and intermetallic nanowires supporting this effect of two-phase stretching. These materials at relatively strong tension forces split into domains with smaller and larger tensile strain. Within this region, average strain incr…
We offer new high-performance label-free electrochemical impedimetric DNA sensors of non-faradaic type. The DNA sensors based on a platform of crystalline carbon nanotube (CNT) arrays are fabricated by the Langmuir--Blodgett (LB) deposition technique. The CNT arrays are suspended on a nanoporous anodic alumina (aluminium oxide, AOA) support. Single-stranded (ss) 19- and 20-base oligonucleotides and double-stranded (ds) nucleotide sequences were used as probes for chosen molecular target -- human KRAS (Kirsten Rat Sarcoma viral oncogene homolog) gene. Genomic deoxyribonucleic acids (DNAs) were …
Fabrication of DNA nanostructures primarily follows two fundamental rules. First, DNA oligonucleotides mutually combine by Watson-Crick base pairing rules between complementary base sequences. Second, the geometrical compatibility of the DNA oligonucleotide must match for lattices to form. Here we present a fabrication scheme of DNA nanostructures with non-complementary and/or geometrically incompatible DNA oligonucleotides, which contradicts conventional DNA structure creation rules. Quantitative analyses of DNA lattice sizes were carried out to verify the unfavorable binding occurrences whic…
Surface-enhanced Raman spectroscopy (SERS) sensing of DNA sequences by plasmonic nanopores could pave a way to new generation single-molecule sequencing platforms. The SERS discrimination of single DNA bases depends critically on the time that a DNA strand resides within the plasmonic hot spot. However, DNA molecules flow through the nanopores so rapidly that the SERS signals collected are not sufficient for single-molecule analysis. In this work, we report an approach to control the time that molecules reside in the hot spot by physically adsorbing them onto a gold nanoparticle and then trapp…
