Dynamic Response of Ionic Current in Conical Nanopores.

Ionic current rectification (ICR) of charged conical nanopores has various applications in fields including nanofluidics, biosensing, and energy conversion, whose function is closely related to the dynamic response of nanopores. The occurrence of ICR originates from the ion enrichment and depletion in conical pores, whose formation is found to be affected by the scanning rate of voltages. Here, through time-dependent simulations, we investigate the variation of ion current under electric fields and the dynamic formation of ion enrichment and depletion, which can reflect the response time of conical nanopores. The response time of nanopores when ion enrichment forms, i.e., at the "on" state is significantly longer than that with the formation of ion depletion, i.e., at the "off" state. Our simulation results reveal the regulation of response time by different nanopore parameters including the surface charge density, pore length, tip, and base radius, as well as the applied conditions such as the voltage and bulk concentration. The response time of nanopores is closely related to the surface charge density, pore length, voltage, and bulk concentration. Our uncovered dynamic response mechanism of the ionic current can guide the design of nanofluidic devices with conical nanopores, including memristors, ionic switches, and rectifiers.

Electro-osmotic Flow Generation via a Sticky Ion Action.

Selective transport of ions through nanometer-sized pores is fundamental to cell biology and central to many technological processes such as water desalination and electrical energy storage. Conventional methods for generating ion selectivity include placement of fixed electrical charges at the inner surface of a nanopore through either point mutations in a protein pore or chemical treatment of a solid-state nanopore surface, with each nanopore type requiring a custom approach. Here, we describe a general method for transforming a nanoscale pore into a highly selective, anion-conducting channel capable of generating a giant electro-osmotic effect. Our molecular dynamics simulations and reverse potential measurements show that exposure of a biological nanopore to high concentrations of guanidinium chloride renders the nanopore surface positively charged due to transient binding of guanidinium cations to the protein surface. A comparison of four biological nanopores reveals the relationship between ion selectivity, nanopore shape, composition of the nanopore surface, and electro-osmotic flow. Guanidinium ions are also found to produce anion selectivity and a giant electro-osmotic flow in solid-state nanopores via the same mechanism. Our sticky-ion approach to generate electro-osmotic flow can have numerous applications in controlling molecular transport at the nanoscale and for detection, identification, and sequencing of individual proteins.

Beyond the electrical double layer model: ion-dependent effects in nanoscale solvent organization.

The nanoscale organization of electrolyte solutions at interfaces is often described well by the electrical double-layer model. However, a recent study has shown that this model breaks down in solutions of LiClO4 in acetonitrile at a silica interface, because the interface imposes a strong structuring in the solvent that in turn determines the preferred locations of cations and anions. As a surprising consequence of this organisation, the effective surface potential changes from negative at low electrolyte concentration to positive at high electrolyte concentration. Here we combine previous ion-current measurements with vibrational sum-frequency-generation spectroscopy experiments and molecular dynamics simulations to explore how the localization of ions at the acetonitrile-silica interface depends on the sizes of the anions and cations. We observe a strong, synergistic effect of the cation and anion identities that can prompt a large difference in the ability of ions to partition to the silica surface, and thereby influence the effective surface potential. Our results have implications for a wide range of applications that involve electrolyte solutions in polar aprotic solvents at nanoscale interfaces.

Modulation mechanism of ionic transport through short nanopores by charged exterior surfaces.

Short nanopores have various applications in biosensing, desalination, and energy conversion. Here, the modulation of ionic transport by charged exterior surfaces is investigated through simulations with sub-200 nm long nanopores under applied voltages. Detailed analysis of the ionic current, electric field strength, and fluid flow inside and outside nanopores reveals that charged exterior surfaces can increase ionic conductance by increasing both the concentration and migration speed of charge carriers. The electric double layers near charged exterior surfaces provide an ion pool and an additional passageway for counterions, which lead to enhanced exterior surface conductance and ionic concentrations at pore entrances and inside the nanopores. We also report that charges on the membrane surfaces increase the electric field strength inside nanopores. The effective width of a ring with surface charges placed at pore entrances (Lcs) is considered as well by studying the dependence of the current on Lcs. We find a linear relationship between the effective Lcs and the surface charge density and voltage, and an inverse relationship between the geometrical pore length and salt concentration. Our results elucidate the modulation mechanism of ionic transport through short nanopores by charged exterior surfaces, which is important for the design and fabrication of porous membranes.

Gating ion and fluid transport with chiral solvent.

The development of modern membranes for ionic separations and energy-storage devices such as supercapacitors depends on the description of ions at solid interfaces, as is often provided by the electrical double layer (EDL) model. The classical EDL model ignores, however, important factors such as possible spatial organization of solvent at the interface and the influence of the solvent on the spatial dependence of the electrochemical potential; these effects in turn govern electrokinetic phenomena. Here we provide a molecular-level understanding of how solvent structure can dictate ionic distributions at interfaces using a model system of a polar, aprotic solvent, propylene carbonate, in its enantiomerically pure and racemic forms, at a silica interface. We link the interfacial structure to the tuning of ionic and fluid transport by the chirality of the solvent and the salt concentration. The results of nonlinear spectroscopic experiments and electrochemical measurements suggest that the solvent exhibits lipid-bilayer-like interfacial organization, with a structure that is dependent on the solvent chirality. The racemic form creates highly ordered layered structure that dictates local ionic concentrations, such that the effective surface potential becomes positive in a wide range of electrolyte concentrations. The enantiomerically pure form exhibits weaker ordering at the silica surface, which leads to a lower effective surface charge induced by ions partitioning into the layered structure. The surface charge in silicon nitride and polymer pores is probed through the direction of electroosmosis that the surface charges induce. Our findings add a new dimension to the nascent field of chiral electrochemistry, and emphasize the importance of including solvent molecules in descriptions of solid-liquid interfaces.

Cation pumping against a concentration gradient in conical nanopores characterized by load capacitors.

We study the cation transport against an external concentration gradient (cation pumping) that occurs in conical nanopores when zero-average oscillatory and white noise potentials are externally applied. This pumping, based on the electrically asymmetric nanostructure, is characterized here by a load capacitor arrangement. In the case of white noise signals, the conical nanopore acts as an electrical valve that allows extraction of order from chaos. No molecular carriers, specific ion pumps, and competitive ion-binding phenomena are required. The nanopore conductance on/off states mimic those of the voltage-gated ion channels in the cell membrane. These channels allow modulating membrane potentials and ionic concentration gradients along oscillatory pulses in circadian rhythms and the cell cycle. We show that the combination of asymmetric nanostructures with load capacitors can be useful for the understanding of nanofluidic processes based on bioelectrochemical gradients.

Nanopores: synergy from DNA sequencing to industrial filtration - small holes with big impact.

Nanopores in thin membranes play important roles in science and industry. Single nanopores have provided a step-change in portable DNA sequencing and understanding nanoscale transport while multipore membranes facilitate food processing and purification of water and medicine. Despite the unifying use of nanopores, the fields of single nanopores and multipore membranes differ - to varying degrees - in terms of materials, fabrication, analysis, and applications. Such a partial disconnect hinders scientific progress as important challenges are best resolved together. This Viewpoint suggests how synergistic crosstalk between the two fields can provide considerable mutual benefits in fundamental understanding and the development of advanced membranes. We first describe the main differences including the atomistic definition of single pores compared to the less defined conduits in multipore membranes. We then outline steps to improve communication between the two fields such as harmonizing measurements and modelling of transport and selectivity. The resulting insight is expected to improve the rational design of porous membranes. The Viewpoint concludes with an outlook of other developments that can be best achieved by collaboration across the two fields to advance the understanding of transport in nanopores and create next-generation porous membranes tailored for sensing, filtration, and other applications.

Scanning Ion Conductance Microscopy of Nafion-Modified Nanopores.

Single nanopores in silicon nitride membranes are asymmetrically modified with Nafion and investigated with scanning ion conductance microscopy, where Nafion alters local ion concentrations at the nanopore. Effects of applied transmembrane potentials on local ion concentrations are examined, with the Nafion film providing a reservoir of cations in close proximity to the nanopore. Fluidic diodes based on ion concentration polarization are observed in the current-voltage response of the nanopore and in approach curves of SICM nanopipette in the vicinity of the nanopore. Experimental results are supported with finite element method simulations that detail ion depletion and enrichment of the nanopore/Nafion/nanopipette environment.

Gating with Charge Inversion to Control Ionic Transport in Nanopores.

Multivalent ions modify the properties of the solid/liquid interfaces, and in some cases, they can even invert the polarity of surface charge, having large consequences for separation processes based on charge. The so-called charge inversion is observed as a switch from negative surface charge in monovalent salts, e.g., KCl, to effective positive surface charge in multivalent salts that is possible through a strong accumulation and correlation of the multivalent ions at the surface. It is not known yet, however, whether the density of the positive charge induced by charge inversion depends on the pore opening diameter, especially in extreme nanoconfinement. Here, we probe how the effective surface charge induced by charge inversion is influenced by the pore opening diameter using a series of nanopores with an opening between 4 and 25 nm placed in contact with trivalent chromium ions in tris(ethylenediamine)chromium(III) sulfate at different concentrations. Our results suggest that the effective positive charge density can indeed be modified by nanoconfinement to the extent that is dependent on the pore diameter, salt concentration, and applied voltage. In addition, the correlated ions can increase the transmembrane current in nanopores with an opening diameter down to 10 nm and cause a significant blockage of the current for narrower pores. The results provide guidelines to control ionic transport at the nanoscale with multivalent ions and demonstrate that in the same experimental conditions, differently sized pores in the same porous material can feature different surface charge density and possibly ion selectivity.

Rectified and Salt Concentration Dependent Wetting of Hydrophobic Nanopores.

Nanopores lined with hydrophobic groups function as switches for water and all dissolved species, such that transport is allowed only when applying a sufficiently high transmembrane pressure difference or voltage. Here we show a hydrophobic nanopore system whose wetting and ability to transport water and ions is rectified and can be controlled with salt concentration. The nanopore we study contains a junction between a hydrophobic zone and a positively charged hydrophilic zone. The nanopore is closed for transport at low salt concentrations and exhibits finite current only when the concentration reaches a threshold value that is dependent on the pore opening diameter, voltage polarity and magnitude, and type of electrolyte. The smallest nanopore studied here had a 4 nm diameter and did not open for transport in any concentration of KCl or KI examined. A 12 nm nanopore was closed for all KCl solutions but conducted current in KI at concentrations above 100 mM for negative voltages and opened for both voltage polarities at 500 mM KI. Nanopores with a hydrophobic/hydrophilic junction can thus function as diodes, such that one can identify a range of salt concentrations where the pores transport water and ions for only one voltage polarity. Molecular dynamics simulations together with continuum models provided a multiscale explanation of the observed phenomena and linked the salt concentration dependence of wetting with an electrowetting model. Results presented are crucial for designing next-generation chemical and ionic separation devices as well as understanding fundamental properties of hydrophobic interfaces under nanoconfinement.

Principles of Small-Molecule Transport through Synthetic Nanopores.

Synthetic nanopores made from DNA replicate the key biological processes of transporting molecular cargo across lipid bilayers. Understanding transport across the confined lumen of the nanopores is of fundamental interest and of relevance to their rational design for biotechnological applications. Here we reveal the transport principles of organic molecules through DNA nanopores by synergistically combining experiments and computer simulations. Using a highly parallel nanostructured platform, we synchronously measure the kinetic flux across hundreds of individual pores to obtain rate constants. The single-channel transport kinetics are close to the theoretical maximum, while selectivity is determined by the interplay of cargo charge and size, the pores' sterics and electrostatics, and the composition of the surrounding lipid bilayer. The narrow distribution of transport rates implies a high structural homogeneity of DNA nanopores. The molecular passageway through the nanopore is elucidated via coarse-grained constant-velocity steered molecular dynamics simulations. The ensemble simulations pinpoint with high resolution and statistical validity the selectivity filter within the channel lumen and determine the energetic factors governing transport. Our findings on these synthetic pores' structure-function relationship will serve to guide their rational engineering to tailor transport selectivity for cell biological research, sensing, and drug delivery.

Tunable Nanopore Arrays as the Basis for Ionic Circuits.

There has been considerable interest in preparing ionic circuits capable of manipulating ionic and molecular transport in a solution. This direction of research is inspired by biological systems where multiple pores with different functionalities embedded in a cell membrane transmit external signals and underlie all physiological processes. In this manuscript, we describe the modeling of ion transport through small arrays of nanopores consisting of 3, 6, and 9 nanopores and an integrated gate electrode placed on the membrane surface next to one pore opening. We show that by tuning the gate voltage and strategically placing nanopores with nonlinear current-voltage characteristics, the local signal at the gate affects ionic transport through all nanopores in the array. Conditions were identified when the same gate voltage induced opposite rectification properties of neighboring nanopores. We also demonstrate that an ionic diode embedded in a nanopore array can modulate transport properties of neighboring pores even without a gate voltage. The results are explained by the role of concentration polarization and overlapping depletion zones on one side of the membrane. The modeling presented here is intended to become an inspiration to future experiments to create nanopore arrays that can transduce signals in space and time.

Modulation of Ionic Current Rectification in Ultrashort Conical Nanopores.

Nanopores that exhibit ionic current rectification (ICR) behave like diodes such that they transport ions more efficiently in one direction than in the other. Conical nanopores have been shown to rectify ionic current, but only those with at least 500 nm in length exhibit significant ICR. Here, through the finite element method, we show how ICR of conical nanopores with lengths below 200 nm can be tuned by controlling individual charged surfaces, that is, the inner pore surface (surfaceinner) and exterior pore surfaces on the tip and base side (surfacetip and surfacebase). The charged surfaceinner and surfacetip can induce obvious ICR individually, while the effects of the charged surfacebase on ICR can be ignored. The fully charged surfaceinner alone could render the nanopore counterion-selective and induces significant ion concentration polarization in the tip region, which causes reverse ICR compared to nanopores with all surfaces charged. In addition, the direction and degree of rectification can be further tuned by the depth of the charged surfaceinner. When considering the exterior membrane surface only, the charged surfacetip causes intrapore ionic enrichment and depletion under opposite biases, which results in significant ICR. Its effective region is within ∼40 nm beyond the tip orifice. We also found that individual charged parts of the pore system contributed to ICR in an additive way because of the additive effect on the ion concentration regulation along the pore axis. With various combinations of fully/partially charged surfaceinner and surfacetip, diverse ICR ratios from ∼2 to ∼170 can be achieved. Our findings shed light on the mechanism of ICR in ultrashort conical nanopores and provide a useful guide to the design and modification of ultrashort conical nanopores in ionic circuits and nanofluidic sensors.

Ionic amplifying circuits inspired by electronics and biology.

Integrated circuits are present in all electronic devices, and enable signal amplification, modulation, and relay. Nature uses another type of circuits composed of channels in a cell membrane, which regulate and amplify transport of ions, not electrons and holes as is done in electronic systems. Here we show an abiotic ionic circuit that is inspired by concepts from electronics and biology. The circuit amplifies small ionic signals into ionic outputs, and its operation mimics the electronic Darlington amplifier composed of transistors. The individual transistors are pores equipped with three terminals including a gate that is able to enrich or deplete ions in the pore. The circuits we report function at gate voltages < 1 V, respond to sub-nA gate currents, and offer ion current amplification with a gain up to ~300. Ionic amplifiers are a logical step toward improving chemical and biochemical sensing, separations and amplification, among others.

Gating of Hydrophobic Nanopores with Large Anions.

Understanding ion transport in nanoporous materials is critical to a wide variety of energy and environmental technologies, ranging from ion-selective membranes, drug delivery, and biosensing, to ion batteries and supercapacitors. While nanoscale transport is often described by continuum models that rely on a point charge description for ions and a homogeneous dielectric medium for the solvent, here, we show that transport of aqueous solutions at a hydrophobic interface can be highly dependent on the size and hydration strength of the solvated ions. Specifically, measurements of ion current through single silicon nitride nanopores that contain a hydrophobic-hydrophilic junction show that transport properties are dependent not only on applied voltage but also on the type of anion. We find that in Cl--containing solutions the nanopores only conducted ionic current above a negative voltage threshold. On the other hand, introduction of large polarizable anions, such as Br- and I-, facilitated the pore wetting, making the pore conductive at all examined voltages. Molecular dynamics simulations revealed that the large anions, Br- and I-, have a weaker solvation shell compared to that of Cl- and consequently were prone to migrate from the aqueous solution to the hydrophobic surface, leading to the anion accumulation responsible for pore wetting. The results are essential for designing nanoporous systems that are selective to ions of the same charge, for realization of ion-induced wetting in hydrophobic pores, as well as for a fundamental understanding on the role of ion hydration shell on the properties of solid/liquid interfaces.

Charge Inversion and Calcium Gating in Mixtures of Ions in Nanopores.

Calcium ions play important roles in many physiological processes, yet their concentration is much lower than the concentrations of potassium and sodium ions. The selectivity of calcium channels is often probed in mixtures of calcium and a monovalent salt, e.g., KCl or NaCl, prepared such that the concentration of cations is kept constant with the mole fraction of calcium varying from 0 and 1. In biological channels, even sub-mM concentration of calcium can modulate the channels' transport characteristics; this effect is often explained via the existence of high affinity Ca2+ binding sites on the channel walls. Inspired by properties of biological calcium-selective channels, we prepared a set of nanopores with tunable opening diameters that exhibited a similar response to the presence of calcium ions as biochannels. Nanopores in 15 nm thick silicon nitride films were drilled using focused ion beam and e-beam in a transmission electron microscope and subsequently rendered negatively charged through silanization. We found that nanopores with diameters smaller than 20 nm were blocked by calcium ions such that the ion currents in mixtures of KCl and CaCl2 and in CaCl2 were even ten times smaller than the ion currents in KCl solution. The ion current blockage was explained by the effect of local charge inversion where accumulated calcium ions switch the effective surface charge from negative to positive. The modulation of surface charge with calcium leads to concentration and voltage dependent local charge density and ion current. The combined experimental and modeling results provide a link between calcium ion-induced changes in surface charge properties and resulting ionic transport.