Advancement of Next-Generation DNA Sequencing through Ionic Blockade and Transverse Tunneling Current Methods.

DNA sequencing is transforming the field of medical diagnostics and personalized medicine development by providing a pool of genetic information. Recent advancements have propelled solid-state material-based sequencing into the forefront as a promising next-generation sequencing (NGS) technology, offering amplification-free, cost-effective, and high-throughput DNA analysis. Consequently, a comprehensive framework for diverse sequencing methodologies and a cross-sectional understanding with meticulous documentation of the latest advancements is of timely need. This review explores a broad spectrum of progress and accomplishments in the field of DNA sequencing, focusing mainly on electrical detection methods. The review delves deep into both the theoretical and experimental demonstrations of the ionic blockade and transverse tunneling current methods across a broad range of device architectures, nanopore, nanogap, nanochannel, and hybrid/heterostructures. Additionally, various aspects of each architecture are explored along with their strengths and weaknesses, scrutinizing their potential applications for ultrafast DNA sequencing. Finally, an overview of existing challenges and future directions is provided to expedite the emergence of high-precision and ultrafast DNA sequencing with ionic and transverse current approaches.

Enhancing Spin-Transport Characteristics, Spin-Filtering Efficiency, and Negative Differential Resistance in Exchange-Coupled Dinuclear Co(II) Complexes for Molecular Spintronics Applications.

Single-molecule spintronics, where electron transport occurs via a paramagnetic molecule, has gained wide attention due to its potential applications in the area of memory devices to switches. While numerous organic and some inorganic complexes have been employed over the years, there are only a few attempts to employ exchange coupled dinuclear complexes at the interface, and the advantage of fabricating such a molecular spintronics device in the observation of switchable Kondo resonance was demonstrated recently in the dinuclear [Co2(L)(hfac)4] (1) complex (Wagner et al., Nat. Nanotechnol. 2013, 8, 575-579). In this work, employing an array of theoretical tools such as density functional theory (DFT), the ab initio CASSCF/NEVPT2 method, and DFT combined with nonequilibrium Green Function (NEGF) formalism, we studied in detail the role of magnetic coupling, ligand field, and magnetic anisotropy in the transport characteristics of complex 1. Particularly, our calculations not only reproduce the current-voltage (I-V) characteristics observed in experiments but also unequivocally establish that these arise from an exchange-coupled singlet state that arises due to antiferromagnetic coupling between two high-spin Co(II) centers. Further, the estimated spin Hamiltonian parameters such as J, g values, and D and E/D values are only marginally altered for the molecule at the interface. Further, the exchange-coupled state was found to have very similar transport responses, despite possessing significantly different geometries. Our transport calculations unveil a new feature of the negative differential resistance (NDR) effect on 1 at the bias voltage of 0.9 V, which agrees with the experimental I-V characteristics reported. The spin-filtering efficiency (SFE) computed for the spin-coupled states was found to be only marginal (∼25%); however, if the ligand field is fine-tuned to obtain a low-spin Co(II) center, a substantial SFE of 44% was noted. This spin-coupled state also yields a very strong NDR with a peak-to-valley ratio (PVR) of ∼56 - a record number that has not been witnessed so far in this class of compounds. Additionally, we have established further magnetostructural-transport correlations, providing valuable insights into how microscopic spin Hamiltonian parameters can be associated with SFE. Several design clues to improve the spin-transport characteristics, SFE and NDR in this class of molecule, are offered.

High-Order Quantum-Mechanical Analysis of Hydrogen Bonding in Hachimoji and Natural DNA Base Pairs.

High-order quantum chemistry is applied to hydrogen-bonded natural DNA nucleobase pairs [adenine:thymine (A:T) and guanine:cytosine (G:C)] and non-natural Hachimoji nucleobase pairs [isoguanine:1-methylcytosine (B:S) and 2-aminoimidazo[1,2a][1,3,5]triazin-4(1H)-one:6-amino-5-nitropyridin-2-one (P:Z)] to see how the intermolecular interaction energies and their energetic components (electrostatics, exchange-repulsion, induction/polarization, and London dispersion interactions) vary among the base pairs. We examined the Hoogsteen (HG) geometries in addition to the traditional Watson-Crick (WC) geometries. Coupled-cluster theory through perturbative triples [CCSD(T)] extrapolated to the complete basis set (CBS) limit and high-order symmetry-adapted perturbation theory (SAPT) at the SAPT2+(3)(CCD)δMP2/aug-cc-pVTZ level are used to estimate highly accurate noncovalent interaction energies. Electrostatic interactions are the most attractive component of the interaction energies, but the sum of induction/polarization and London dispersion is nearly as large, for all base pairs and geometries considered. Interestingly, the non-natural Hachimoji base pairs interact more strongly than the corresponding natural base pairs, by -21.8 (B:S) and -0.3 (P:Z) kcal mol-1 in the WC geometries, according to CCSD(T)/CBS. This is consistent with the H-bond distances being generally shorter in the non-natural base pairs. The natural base pairs are energetically more stabilized in their Hoogsteen geometries than in their WC geometries. The Hoogsteen geometry makes the A:T base pair slightly more stable, by -0.8 kcal mol-1, and it greatly stabilizes the G:C+ base pair, by -15.3 kcal mol-1. The G:C+ stabilization is mainly due to the fact that C has typically added a proton when found in Hoogsteen geometries. By contrast, Hoogsteen geometries are substantially less favorable than WC geometries for non-natural Hachimoji base pairs, by 17.3 (B:S) and 13.8 (P:Z) kcal mol-1.

Conductance and tunnelling current characteristics for individual identification of synthetic nucleic acids with a graphene device.

Based on combined density functional theory and non-equilibrium Green's function quantum transport studies, in the present work we have demonstrated the quantum interference (QI) effect on the transverse conductance of Hachimoji (synthetic) nucleic acids when placed between the oxygen-terminated zigzag graphene nanoribbon (O-ZGNR) nanoelectrodes. We theorize that the QI effect could be well preserved in π-π coupling between a target nucleobase molecule and the carbon-based nanoelectrodes. Our study indicates that the QI effect, such as anti-resonance or Fano-resonance, affects the variation of transverse conductance depending on the nucleobase conformation. Furthermore, a variation of up to 2-5 orders of magnitude is observed in the conductance upon rotation for all the nucleobases. The current-voltage (I-V) characteristics results suggest a distinct variation in the electronic tunnelling current across the proposed nanogap device for all five nucleobases with the applied bias voltage ranges from 0.1-1.0 V. The different rotation angles keep the distinct feature of the nucleobases in both transverse conductance and tunnelling current features. Both features could be utilized in an accurate synthetic DNA sequencing device.

Identifying Single-Stranded DNA by Tuning the Graphene Nanogap Size: An Ionic Current Approach.

Solid nanopore-based deoxyribonucleic acid (DNA) sequencing has led to low-cost, fast, reliable, controlled, and amplified or label-free and high-resolution recognition and identification of DNA nucleotides. Solid-state materials and biological nanopores have a low signal-to-noise ratio (SNR) and generally are too thick to read at single-nucleotide resolution. The issue with solid-state nanopores is that the DNA strands stick to the nanopore sides and on the surface during the translocation process. The coexistence of DNA nucleotides on the surface and the nanopore sides will complicate the ionic current signals, making nucleotide detection difficult. Therefore, different sized nanogaps can be promising to overcome some of these issues. Using all-atom molecular dynamics (MD) simulations, we have studied the translocation of single-stranded (ss) DNA through solid-state nanogaps embedded in a graphene membrane device. A nucleotide-specific DNA sequencing technique is proposed based on unique differences in the ionic current responses for all the four ssDNA nucleotides (dAMP16, dGMP16, dTMP16, and dCMP16). As the individual homogeneous ssDNA translocate through the nanogaps, characteristic changes are observed in the ionic current. Our results show that ssDNA nucleotides can translocate through the proposed graphene nanogap devices by applying an external electric field. In addition, the sticking issue can be resolved using graphene nanogaps during the ssDNA translocation processes. Therefore, the significant difference in ionic current sensitivity and the translocation event/time yielded by the graphene nanogap-based devices reveal possibilities for utilizing it for ultrafast nanogap-based DNA sequencing.

Identifying DNA Nucleotides via Transverse Electronic Transport in Atomically Thin Topologically Defected Graphene Electrodes.

Extended line defects in graphene (ELDG) sheets have been found to be promising for biomolecule sensing applications. By means of the consistent-exchange van der Waals density-functional (vdW-DF-cx) method, the electronic, structural, and quantum transport properties of the ELDG nanogap setup has been studied when a DNA nucleotide molecule is positioned inside the nanogap electrodes. The interaction energy (Ei) values indicate charge transfer interaction between the nucleotide molecule and electrode edges. The charge density difference plots reveal that charge fluctuates around the ELDG nanogap edges adjacent to the nucleotides. This charge redistribution grounds the modulation of electronic charge transport in the ELDG nanogap device. Further, we study the electronic transverse-conductance and tunnelling current-voltage (I-V) characteristics across two closely spaced ELDG nanogap electrodes using the density functional theory and the nonequilibrium Green's function methods when a DNA nucleotide is translocated through the nanogap. Our outcomes indicate that the ELDG nano gap device could allow sequencing of DNA nucleotides with a robust and consistent yield, giving the tunneling electric current signals that vary by more than 1 order of magnitude electric current (I) for the different DNA nucleotides. So, we predict that the ELDG nanogap-based tunneling device can be suitable for sequencing DNA nucleobases.

Porphyrin nanoribbon-based spin filtering devices.

Advancement in molecular electronics opens up another new domain with a new possibility of realizing its spin-polarized version, which is called molecular spintronics. This novel domain has a range of applications such as high-capacity storage devices and quantum computers. Several contemporary researchers have considered porphyrin molecules and their derivatives as potential candidates for molecular devices. Herein, using the first-principles calculations, we propose a porphyrin nanoribbon-based system for spin-filtering applications. Such a system shows robust half-metallicity and also exhibits itinerant magnetism. Our calculated spin transport properties exhibit that our device can give 100% spin-polarizing efficiency, which is very promising for next-generation spin-filtering applications.

Functionalized carbon nanotube electrodes for controlled DNA sequencing.

In the last decade, solid-state nanopores/nanogaps have attracted significant attention in the rapid detection of DNA nucleotides. However, reducing the noise through controlled translocation of the DNA nucleobases is a central issue for the development of nanogap/nanopore-based DNA sequencing to achieve single-nucleobase resolution. Furthermore, the high reactivity of the graphene pores/gaps causes clogging of the pore/gap, leading to the blockage of the pores/gaps, sticking, and irreversible pore closure. To address the prospective of functionalization of the carbon nanostructure and for accomplishing this objective, herein, we have studied the performance of functionalized closed-end cap armchair carbon nanotube (CNT) nanogap-embedded electrodes, which can improve the coupling through non-bonding electrons and may provide the possibility of N/O-H⋯π interactions with the nucleotides, as single-stranded DNA is transmigrated across the electrode. We have investigated the effect of functionalizing the closed-end cap CNT (6,6) electrodes with purine (adenine, guanine) and pyrimidine (thymine, cytosine) molecules. Weak hydrogen bonds formed between the probe molecule and the target DNA nucleobase enhance the electronic coupling and temporarily stabilize the translocating nucleobase against the orientational fluctuations, which may reduce noise in the current signal during experimental measurements. The findings of our density functional theory and non-equilibrium Green's function-based study indicate that this modeled setup could allow DNA nucleotide sequencing with a better and reliable yield, giving current traces that differ by at least 1 order of current magnitude for all the four target nucleotides. Thus, we feel that the functionalized armchair CNT (6,6) nanogap-embedded electrodes may be utilized for controlled DNA sequencing.

Electronic Transport through DNA Nucleotides in Atomically Thin Phosphorene Electrodes for Rapid DNA Sequencing.

Rapid progresses in developing the fast, low-cost, and reliable methods for DNA sequencing are envisaged for development of personalized medicine. In this respect, nanotechnology has paved the role for the development of advanced DNA sequencing techniques including sequencing with solid-state nanopores or nanogaps. Herein, we have explored the application of a black phosphorene based nanogap-device for DNA sequencing. Using density-functional-theory based non-equilibrium Green's function approach, we have computed transverse transmission and current-voltage ( I- V) characteristics of all the four DNA nucleotides (deoxy adenosine monophosphate, deoxy guanidine monophosphate, deoxy thymidine monophosphate, and deoxy cytosine monophosphate) as functions of applied bias voltages. We deduce that it is in principle; possible to differentiate between all the four nucleotides by three sequencing runs at distinct applied bias voltages, i.e., at 0.2, 1.4, and 1.6 V, where individual identification of all the four nucleotides may be possible. Hence, we believe our study might be helpful for experimentalist towards the development of a phosphorene based nanodevice for DNA sequencing to diagnose critical diseases.

Environmentally Benign Metal-Free Reduction of GO Using Molecular Hydrogen: A Mechanistic Insight.

A simple yet effective methodology to obtain high-quality reduced graphene oxide (RGO) using a tetrahydrofuran suspension of GO under hydrogen at moderate pressure has been demonstrated. The extent of reduction as a function of the pressure of hydrogen gas, temperature, and time was studied, where the abstraction of oxygen is achievable with least mutilation of C-sp2 bonds, hence upholding the integrity of the graphene sheet. Herein, the formation of a short-lived species is proposed, which is possibly responsible for such reduction. A detailed theoretical calculation along with in situ UV-visible experiments reveals the existence of a transient solvated electron species in the reaction medium. The hydrogen RGO (HRGO) achieved a C/O atomic ratio of 11.3. The conductivity measurements show that HRGO reached as high as 934 S/m, which indicates a high quality of RGO. The process is hassle-free, environmentally benign, and can be scaled up effortlessly without compromising the quality of the material.