Influence of nanopore coating patterns on the translocation dynamics of polyelectrolytes.

Polyelectrolytes can electrophoretically be driven through nanopores in order to be detected. The respective translocation events are often very fast and the process needs to be controlled to promote efficient detection. To this end, we attempt to control the translocation dynamics by coating the inner surface of a nanopore. For this, different charge distributions are chosen that result in substantial variations of the pore-polymer interactions. In addition and in view of the existing detection modalities, experimental settings, and nanopore materials, different types of sensors inside the nanopore have been considered to probe the translocation process and its temporal spread. The respective transport of polyelectrolytes through the coated nanopores is modeled through a multi-physics computational scheme that incorporates a mesoscopic/electrokinetic description for the solvent and particle-based scheme for the polymer. This investigation could underline the interplay between sensing modality, nanopore material, and detection accuracy. The electro-osmotic flow and electrophoretic motion in a pore are analyzed together with the polymeric temporal and spatial fluctuations unraveling their correlations and pathways to optimize the translocation speed and dynamics. Accordingly, this work sketches pathways in order to tune the pore-polymer interactions in order to control the translocation dynamics and, in the long run, errors in their measurements.

Probing the distribution of ionic liquid mixtures at charged and neutral interfaces via simulations and lattice-gas theory.

Room temperature ionic liquid solutions confined between neutral and charged surfaces are investigated by means of atomistic Molecular Dynamics simulations. We study 1-ethyl-3-methylimidazolium dicyanamide ([EMIm]+[DCA]-) in water or dimethylsulfoxide (DMSO) mixtures in confinement between two interfaces. The analysis is based on the comparison of the molecular species involved and the charged state of the surfaces. Focus is given on the influence of different water/DMSO concentrations on the microstructuring and accumulation of each species. Thermodynamic aspects, such as the entropic contributions in the observed trends are obtained from the simulations using a lattice-gas theory. The results clearly underline the differences in these properties for the water and DMSO mixtures and unravel the underlying mechanisms and inherent details. We were able to pinpoint the importance of the size and the relative permittivity of the molecules in guiding their microstructuring in the vicinity of the surfaces, as well as their interactions with the latter, i.e. the solute-surface interactions. The influence of water and DMSO on the overscreening at charged interfaces is also discussed. The analysis on the molecular accumulation at the interfaces allows us to predict whether the accumulation is entropy or enthalpy driven, which has an impact in the removal of the molecular species from the surfaces. We discuss the impact of this work in providing an essential understanding towards a careful design of electrochemical elements.

Deep learning for nanopore ionic current blockades.

DNA molecules can electrophoretically be driven through a nanoscale opening in a material, giving rise to rich and measurable ionic current blockades. In this work, we train machine learning models on experimental ionic blockade data from DNA nucleotide translocation through 2D pores of different diameters. The aim of the resulting classification is to enhance the read-out efficiency of the nucleotide identity providing pathways toward error-free sequencing. We propose a novel method that at the same time reduces the current traces to a few physical descriptors and trains low-complexity models, thus reducing the dimensionality of the data. We describe each translocation event by four features including the height of the ionic current blockade. Training on these lower dimensional data and utilizing deep neural networks and convolutional neural networks, we can reach a high accuracy of up to 94% in average. Compared to more complex baseline models trained on the full ionic current traces, our model outperforms. Our findings clearly reveal that the use of the ionic blockade height as a feature together with a proper combination of neural networks, feature extraction, and representation provides a strong enhancement in the detection. Our work points to a possible step toward guiding the experiments to the number of events necessary for sequencing an unknown biopolymer in view of improving the biosensitivity of novel nanopore sequencers.

Functionalized Nanogap for DNA Read-Out: Nucleotide Rotation and Current-Voltage Curves.

Functionalized nanogaps embedded in nanopores show a strong potential for enhancing the detection of biomolecules, their length, type, and sequence. This detection is strongly dependent on the features of the target biomolecules, as well as the characteristics of the sensing device. In this work, through quantum-mechanical calculations, we elaborate on representative such aspects for the specific case of DNA detection and read-out. These aspects include the influence of single DNA nucleotide rotation within the nanogap and the current-voltage (I-V) characteristics of the nanogap. The results unveil a distinct variation in the electronic current across the functionalized device for the four natural DNA nucleotides with the applied voltage. These also underline the asymmetric response of the rotating nucleotides on this applied voltage and the respective variation in the rectification ratio of the device. The electronic tunneling current across the nanogap can be further enhanced through the proper choice of an applied bias voltage. We were able to correlate the enhancement of this current to the nucleotide rotation dynamics and a shift of the electronic transmission peaks towards the Fermi level. This nucleotide specific shift further reveals the sensitivity of the device in reading-out the identity of the DNA nucleotides for all different configurations in the nanogap. We underline the important information that can be obtained from both the I-V curves and the rectification characteristics of the nanogap device in view of accurately reading-out the DNA information. We show that tuning the applied bias can enhance this detection and discuss the implications in view of novel functionalized nanopore sequencers.

In silico Complexes of Amino Acids and Diamondoids.

We report on the specific interaction of a small diamond-like molecule, known as diamondoid, with single amino-acids forming nano/bio molecular complexes. Using time-dependent density-functional theory calculations we have studied two different relative configurations of three prototypical amino acids, phenylalanine, tyrosine, and tryptophan, with the diamondoid. The optical and charge-transfer properties of these complexes exhibit amino acid and topology specific features which can be directly utilized for in the direction of novel biomolecule detection schemes.

Hybrids made of defective nanodiamonds interacting with DNA nucleobases.

The characteristics of hybrids made of a defective nanodiamond and a biomolecule unit are investigated in this work. Focus is given on the interaction between the nanodiamond and a DNA nucleobase. The latter is placed close to the former in two different arrangements, realizing different bonding types. The nanodiamond includes a negatively charged nitrogen-vacancy center and is hydrogen terminated. Using quantum-mechanical calculations, we could elucidate the structural and electronic properties of such hybrids. Our study clearly identifies the importance of the relative orientation of the two components, the nanodiamond and the nucleobase, in the complex in controlling the electronic properties of the resulting hybrid. The position of the defect at the center or closer to its interface with the nucleobase further controls the electronic orbitals around the defect center, hence its optical activity. In the end, we discuss the relevance of our work in biosensing.

Optical Properties of Single- and Double-Functionalized Small Diamondoids.

The rational control of the electronic and optical properties of small functionalized diamond-like molecules, the diamondoids, is the focus of this work. Specifically, we investigate the single- and double- functionalization of the lower diamondoids, adamantane, diamantane, and triamantane with -NH2 and -SH groups and extend the study to N-heterocyclic carbene (NHC) functionalization. On the basis of electronic structure calculations, we predict a significant change in the optical properties of these functionalized diamondoids. Our computations reveal that -NH2 functionalized diamondoids show UV photoluminescence similar to ideal diamondoids while -SH substituted diamondoids hinder the UV photoluminescence due to the labile nature of the S-H bond in the first excited state. This study also unveils that the UV photoluminescence nature of -NH2 diamondoids is quenched upon additional functionalization with the -SH group. The double-functionalized derivative can, thus, serve as a sensitive probe for biomolecule binding and sensing environmental changes. The preserved intrinsic properties of the NHC and the ideal diamondoid in NHC-functionalized-diamondoids suggests its utilization in diamondoid-based self-assembled monolayers (SAM), whose UV-photoluminescent signal would be determined entirely by the functionalized diamondoids. Our study aims to pave the path for tuning the properties of diamondoids through a selective choice of the type and number of functional groups. This will aid the realization of optoelectronic devices involving, for example, large-area SAM layers or diamondoid-functionalized electrodes.

Electrokinetic Lattice Boltzmann Solver Coupled to Molecular Dynamics: Application to Polymer Translocation.

We have developed a theoretical and computational approach to deal with systems that involve a disparate range of spatiotemporal scales, such as those composed of colloidal particles or polymers moving in a fluidic molecular environment. Our approach is based on a multiscale modeling that combines the slow dynamics of the large particles with the fast dynamics of the solvent into a unique framework. The former is numerically solved via Molecular Dynamics and the latter via a multicomponent Lattice Boltzmann. The two techniques are coupled together to allow for a seamless exchange of information between the descriptions. Being based on a kinetic multicomponent description of the fluid species, the scheme is flexible in modeling charge flow within complex geometries and ranging from large to vanishing salt concentration. The details of the scheme are presented and the method is applied to the problem of translocation of a charged polymer through a nanopores. Lastly, we discuss the advantages and complexities of the approach.

The properties of residual water molecules in ionic liquids: a comparison between direct and inverse Kirkwood-Buff approaches.

We study the properties of residual water molecules at different mole fractions in dialkylimidazolium based ionic liquids (ILs), namely 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM/BF4) and 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM/BF4) by means of atomistic molecular dynamics (MD) simulations. The corresponding Kirkwood-Buff (KB) integrals for the water-ion and ion-ion correlation behavior are calculated by a direct evaluation of the radial distribution functions. The outcomes are compared to the corresponding KB integrals derived by an inverse approach based on experimental data. Our results reveal a quantitative agreement between both approaches, which paves a way towards a more reliable comparison between simulation and experimental results. The simulation outcomes further highlight that water even at intermediate mole fractions has a negligible influence on the ion distribution in the solution. More detailed analysis on the local/bulk partition coefficients and the partial structure factors reveal that water molecules at low mole fractions mainly remain in the monomeric state. A non-linear increase of higher order water clusters can be found at larger water concentrations. For both ILs, a more pronounced water coordination around the cations when compared to the anions can be observed, which points out that the IL cations are mainly responsible for water pairing mechanisms. Our simulations thus provide detailed insights in the properties of dialkylimidazolium based ILs and their effects on water binding.

Diamondoid-based molecular junctions: a computational study.

In this work, we deal with the computational investigation of diamondoid-based molecular conductance junctions and their electronic transport properties. A small diamondoid is placed between the two gold electrodes of the nanogap and is covalently bonded to the gold electrodes through two different molecules, a thiol group and a N-heterocyclic carbene molecule. We have shown that the thiol linker is more efficient as it introduces additional electron paths for transport at lower energies. The influence of doping the diamondoid on the properties of the molecular junctions has been investigated. We find that using a nitrogen atom to dope the diamondoids leads to a considerable increase of the zero bias conductance. For the N-doped system we show an asymmetric feature of the I-V curve of the junctions resulting in rectification within a very small range of bias voltages. The rectifying nature is the result of the characteristic shift in the bias-dependent highest occupied molecular orbital state. In all cases, the efficiency of the device is manifested and is discussed in view of novel nanotechnological applications.

Benchmark investigation of diamondoid-functionalized electrodes for nanopore DNA sequencing.

Small diamond-like particles, diamondoids, have been shown to effectively functionalize gold electrodes in order to sense DNA units passing between the nanopore-embedded electrodes. In this work, we present a comparative study of Au(111) electrodes functionalized with different derivatives of lower diamondoids. Focus is put on the electronic and transport properties of such electrodes for different DNA nucleotides placed within the electrode gap. The functionalization promotes a specific binding to DNA leading to different properties for the system, which provides a tool set to systematically improve the signal-to-noise ratio of the electronic measurements across the electrodes. Using quantum transport calculations, we compare the effectiveness of the different functionalized electrodes in distinguishing the four DNA nucleotides. Our results point to the most effective diamondoid functionalization of gold electrodes in view of biosensing applications.

Towards double-functionalized small diamondoids: selective electronic band-gap tuning.

Diamondoids are nanoscale diamond-like cage structures with hydrogen terminations, which can occur in various sizes and with a diverse type of modifications. In this work, we focus on the structural alterations and the effect of doping and functionalization on the electronic properties of diamondoids, from the smallest adamantane to heptamantane. The results are based on quantum mechanical calculations. We perform a self-consistent study, starting with doping the smallest diamondoid, adamantane. Boron, nitrogen, silicon, oxygen, and phosphorus are chosen as dopants at sites which have been previously optimized and are also consistent with the literature. At a next step, an amine- and a thiol- group are separately used to functionalize the adamantane molecule. We mainly focus on a double functionalization of diamondoids up to heptamantane using both these atomic groups. The effect of isomeration in the case of tetramantane is also studied. We discuss the higher efficiency of a double-functionalization compared to doping or a single-functionalization of diamondoids in tuning the electronic properties, such as the electronic band-gap, of modified small diamondoids in view of their novel nanotechnological applications.

Type-dependent identification of DNA nucleobases by using diamondoids.

The possibility of distinguishing between DNA nucleobases of different sizes is manifested here through quantum-mechanical simulations. By using derivatives of small, modified diamond clusters, known as diamondoids, it is possible to separate the pyrimidines (cytosine and thymine) from the larger purines (adenine and guanine), according to the collective electronic and binding properties of these DNA nucleobases and the diamondoid. The latter acts as a probe with which these properties can be examined in detail. Short single-stranded DNA is built up from single nucleobases to reveal the effect of each DNA unit on the sensing abilities of the diamondoid probe. Several ways of orienting the nucleobases, nucleosides, nucleotides, and short single-stranded DNA are investigated; these lead to quite different electronic properties and may or may not enhance the possibility of separating the DNA nucleobases. For the optimum orientation, that is, one that promotes stronger hydrogen bonding of the diamondoid to the short DNA strand, it is found that the electronic band gaps of a purine strand lie in a completely different range to the band gaps of a pyrimidine strand. This difference can be over 1 eV, which is measurable and shows the potential of using diamondoids and their derivatives in biosensing devices.

Stable boron nitride diamondoids as nanoscale materials.

We predict the stability of diamondoids made up of boron and nitrogen instead of carbon atoms. The results are based on quantum-mechanical calculations within density functional theory (DFT) and show some very distinct features compared to the regular carbon-based diamondoids. These features are evaluated with respect to the energetics and electronic properties of the boron nitride diamondoids as compared to the respective properties of the carbon-based diamondoids. We find that BN-diamondoids are overall more stable than their respective C-diamondoid counterparts. The electronic band-gaps (E(g)) of the former are overall lower than those for the latter nanostructures but do not show a very distinct trend with their size. Contrary to the lower C-diamondoids, the BN-diamondoids are semiconducting and show a depletion of charge on the nitrogen site. Their differences in the distribution of the molecular orbitals, compared to their carbon-based counterparts, offer additional bonding and functionalization possibilities. These tiny BN-based nanostructures could potentially be used as nanobuilding blocks complementing or substituting the C-diamondoids, based on the desired properties. An experimental realization of boron nitride diamondoids remains to show their feasibility.

The role of a diamondoid as a hydrogen donor or acceptor in probing DNA nucleobases.

It has been shown that diamondoids can interact with DNA by forming relatively strong hydrogen bonds to DNA units, such as nucleobases. For this interaction to occur the diamondoids must be chemically modified in order to provide donor/acceptor groups for the hydrogen bond. We show here that the exact arrangement of an amine-modified adamantane with respect to a neighboring nucleobase has a significant influence on the strength of the hydrogen bond. Whether the diamondoid acts as a hydrogen donor or acceptor in the hydrogen binding to the nucleobase affects the electronic structure and thereby the electronic band-gaps of the diamondoid-nucleobase complex. In a donor arrangement of the diamondoid close to a nucleobase, the interaction energies are weak, but the electronic band-gaps differ significantly. Exactly the opposite trend is observed in an acceptor arrangement of the diamondoid. In each of these cases the frontier orbitals of the diamondoid and the nucleobase play a different role in the binding. The results are discussed in view of a diamondoid-based biosensing device.

Force fields for divalent cations based on single-ion and ion-pair properties.

We develop force field parameters for the divalent cations Mg(2+), Ca(2+), Sr(2+), and Ba(2+) for molecular dynamics simulations with the simple point charge-extended (SPC/E) water model. We follow an approach introduced recently for the optimization of monovalent ions, based on the simultaneous optimization of single-ion and ion-pair properties. We consider the solvation free energy of the divalent cations as the relevant single-ion property. As a probe for ion-pair properties we compute the activity derivatives of the salt solutions. The optimization of the ionic force fields is done in two consecutive steps. First, the cation solvation free energy is determined as a function of the Lennard-Jones (LJ) parameters. The peak in the ion-water radial distribution function (RDF) is used as a check of the structural properties of the ions. Second, the activity derivatives of the electrolytes MgY(2), CaY(2), BaY(2), SrY(2) are determined through Kirkwood-Buff solution theory, where Y = Cl(-), Br(-), I(-). The activity derivatives are determined for the restricted set of LJ parameters which reproduce the exact solvation free energy of the divalent cations. The optimal ion parameters are those that match the experimental activity data and therefore simultaneously reproduce single-ion and ion-pair thermodynamic properties. For Ca(2+), Ba(2+), and Sr(2+) such LJ parameters exist. On the other hand, for Mg(2+) the experimental activity derivatives can only be reproduced if we generalize the combination rule for the anion-cation LJ interaction and rescale the effective cation-anion LJ radius, which is a modification that leaves the cation solvation free energy invariant. The divalent cation force fields are transferable within acceptable accuracy, meaning the same cation force field is valid for all halide ions Cl(-), Br(-), I(-) tested in this study.

Functionalized electrodes embedded in nanopores: read-out enhancement?

In this review, functionalized nanogaps embedded in nanopores are discussed in view of their high biosensitivity in detecting biomolecules, their length, type, and sequence. Specific focus is given on nanoelectrodes functionalized with tiny nanometer-sized diamond-like particles offering vast functionalization possibilities for gold junction electrodes. This choice of the functionalization, in turn, offers nucleotide-specific binding possibilities improving the detection signals arising from such functionalized electrodes potentially embedded in a nanopore. The review sheds light onto the use and enhancement of the tunnelling recognition in functionalized nanogaps towards sensing DNA nucleotides and mutation detection, providing important input for a practical realization.

Electronic analysis of hydrogen-bonded molecular complexes: the case of DNA sensed in a functionalized nanogap.

DNA nucleotides can be interrogated by nanomaterials in order to be detected. With the aid of quantum-mechanical simulations, we unravel the intrinsic details of the electronic transport across nanoelectrodes functionalized with tiny modified diamond-like molecules. These electrodes generate a gap in which DNA nucleotides are placed and can be identified. The identification is strongly affected by the hydrogen bonding characteristics of the diamond-like particle and the nucleotides. The results point to the connection of the electronic transmission across the functionalized nanogap and the electronic and bonding characteristics of the molecular complexes within the nanogap. Specifically, our discussion focuses on the influence of the DNA dynamics on the electronic signals across the nanogap. We identify the molecular complex's details that hinder or promote the electronic transport through an analysis that moves from the bonding within the molecular complex up to the electronic current that this can accommodate. Accordingly, our work discusses pathways for analyzing hydrogen-bonded molecular complexes or molecules hydrogen-bonded to a material part having the optimization of the design of biosensing nanogaps and read-out nanopores in mind. The presented approach, though, is applicable to a wide range of applications utilizing exactly the bio/nano interface.

Ionic force field optimization based on single-ion and ion-pair solvation properties: going beyond standard mixing rules.

Using molecular dynamics (MD) simulations in conjunction with the SPC/E water model, we optimize ionic force-field parameters for seven different halide and alkali ions, considering a total of eight ion-pairs. Our strategy is based on simultaneous optimizing single-ion and ion-pair properties, i.e., we first fix ion-water parameters based on single-ion solvation free energies, and in a second step determine the cation-anion interaction parameters (traditionally given by mixing or combination rules) based on the Kirkwood-Buff theory without modification of the ion-water interaction parameters. In doing so, we have introduced scaling factors for the cation-anion Lennard-Jones (LJ) interaction that quantify deviations from the standard mixing rules. For the rather size-symmetric salt solutions involving bromide and chloride ions, the standard mixing rules work fine. On the other hand, for the iodide and fluoride solutions, corresponding to the largest and smallest anion considered in this work, a rescaling of the mixing rules was necessary. For iodide, the experimental activities suggest more tightly bound ion pairing than given by the standard mixing rules, which is achieved in simulations by reducing the scaling factor of the cation-anion LJ energy. For fluoride, the situation is different and the simulations show too large attraction between fluoride and cations when compared with experimental data. For NaF, the situation can be rectified by increasing the cation-anion LJ energy. For KF, it proves necessary to increase the effective cation-anion Lennard-Jones diameter. The optimization strategy outlined in this work can be easily adapted to different kinds of ions.

Ab initio determination of coarse-grained interactions in double-stranded DNA.

We derive the coarse-grained interactions between DNA nucleotides from ab initio total-energy calculations based on density functional theory (DFT). The interactions take into account base and sequence specificity, and are decomposed into physically distinct contributions that include hydrogen bonding, stacking interactions, backbone, and backbone-base interactions. The interaction energies of each contribution are calculated from DFT for a wide range of configurations and are fitted by simple analytical expressions for use in the coarse-grained model, which reduces each nucleotide into two sites. This model is not derived from experimental data, yet it successfully reproduces the stable B-DNA structure and gives good predictions for the persistence length. It may be used to realistically probe dynamics of DNA strands in various environments at the µs time scale and the µm length scale.