Conical Nanopores Research Articles

Conical nanopores fabricated via a pressure-biased chemical etch

Controlling the size and shape of nanopores in polymer membranes can significantly impact transport of molecular or ionic species through these membranes. Here we describe a facile method to controllably form conical nanopores in ion-tracked polycarbonate membranes. Commercial polycarbonate ion-tracked membranes were placed between a concentrated alkaline solution and an acidic solution. By varying the height of the acidic solution, the hydrostatic pressure was controlled, regulating the acid flux through the nanopores. The resulting asymmetric etching of the membrane produced conical pores with controllable aspect ratios. Scanning electron microscopy of both the pores and nickel nanostructures electrolessly templated in the pores confirms their conical shape. This safe, straightforward approach obviates the need to use large voltages, currents, and/or plasma etching equipment traditionally employed to create conical nanopores.

Physical origin of dynamic ion transport features through single conical nanopores at different bias frequencies

Ionic transport through nanometer scale channels or interfaces is the physical origin of the detection signals in stochastic single molecular sensing, DNA sequencing and nano-structured electrodes. Dynamic transport regulated by systematically varying the bias frequency has not been explored. In this report, ion transport through single conical nanopore platforms is studied by applying an alternating electrical field at a wide range of scan rates. Rich frequency-dependent features of the measured transport current are discovered. The complete transition of characteristic transport features from low to high scan rates or bias frequencies is demonstrated experimentally. Key dynamic features include: multiple hysteresis loops separated by one or two non-zero cross points in the I–V curves, shifts in cross point potentials at different scan rates, and growth and diminishment in the hysteresis loops with normal and negative phase shifts. Combined theoretical and experimental studies reveal different processes contributing to and dominating the total current responses on different time scales. The respective contributions of each type of transport process to the overall measured current signals are quantitatively separated based on the fundamental insights gained. Although these exciting experimental observations are successfully simulated using an optimized model by solving PNP equations, the experimental studies at this nanoscale dimension suggest substantial deviations from a continuum regime. Inputs from molecular theory are needed to further validate the proposed physical mechanism.

Sugar-stimulated robust nanodevice: 4-Carboxyphenylboronic acid modified single glass conical nanopores

In this work, we demonstrate a smart robust nanodevice that rectifies the ion current in response to sugar stimulation. The response is achieved by immobilizing 4-carboxyphenylboronic acid to the wall of a single glass conical nanopore. This smart robust nanodevice shows excellent sugar responsive capacity with the switch between the non-rectifying and rectifying states of the ion transport properties. The ion current rectification ratio increases linearly with increasing concentration of glucose and correlates to the concentration of the target by a simple linear regression equation, which makes quantitative nanosensing easily accessible for application in biomedical fields.

Coupled chemical reactions in dynamic nanometric confinement: Ag2O membrane formation during ion track etching

In this study, continuous swift heavy ion tracks in thin polymer foils were etched from both sides to create two conical nanopores opposing each other. Shortly before both cones merged, one of the nanopores was filled with a silver salt solution, whereas etching of the other cone continued. At the moment of track breakthrough, the etchant reacted with the silver salt solution by forming an impermeable and insulating membrane. Continued etching around the thus-created obstacle led to repetitive {etchant – silver salt solution} interactions. The coupling of the two chemical reactions, {etchant – polymer} and {etchant – silver salt solution}, within the confinement of etched tracks, with continuously changing shapes, showed a highly dynamic nature as recorded by measuring both the electrical current and the optical transmission across the foils. At low etching speeds, a central membrane that grew in radius and thickness with time until, at a critical thickness, the membrane became rather impermeable was formed. However, at high etching speeds, the emerging reaction products exhibited a sponge-like consistency, which allowed for their infinite growth. This precipitation was accompanied by a pronounced current spike formation. A simple theoretical model explains, at a minimum, the basic features.

Numerical study of ionic current rectification through non-uniformly charged micro/nanochannel systems

Ionic transport through cylindrical nanochannels with linearly varied surface charge density was numerically investigated. The ends of the nanochannel were connected to microchannels regarded as reservoirs. The walls at the micro/nanochannel junction were referred to as sidewalls that can be electrically neutral or charged. The results showed that the charged sidewalls could enhance the concentration polarization compared to neutral sidewalls. For neutral sidewall, a limiting current similar to charged permselective membranes and a maximum current rectification ratio at certain bulk concentration similar to charged conical nanopores can be found. For the charged sidewall case, no limiting current regime can be observed and the current varied linearly with the applied voltage with a larger slope compared to the Ohmic relation regime. Moreover, no maximum current rectification ratio can be found and the current rectification ratio increased with the decrease in bulk concentration and increases in surface charge density and sidewall length.

Quantification of Steady-State Ion Transport through Single Conical Nanopores and a Nonuniform Distribution of Surface Charges

Electrostatic interactions of mobile charges in solution with the fixed surface charges are known to strongly affect stochastic sensing and electrochemical energy conversion processes at nanodevices or devices with nanostructured interfaces. The key parameter to describe this interaction, surface charge density (SCD), is not directly accessible at nanometer scale and often extrapolated from ensemble values. In this report, the steady-state current-voltage (i-V) curves measured using single conical glass nanopores in different electrolyte solutions are fitted by solving Poisson and Nernst-Planck equations through finite element approach. Both high and low conductivity state currents of the rectified i-V curve are quantitatively fitted in simulation at less than 5% error. The overestimation of low conductivity state current using existing models is overcome by the introduction of an exponential SCD distribution inside the conical nanopore. A maximum SCD value at the pore orifice is determined from the fitting of the high conductivity state current, while the distribution length of the exponential SCD gradient is determined by fitting the low conductivity state current. Quantitative fitting of the rectified i-V responses and the efficacy of the proposed model are further validated by the comparison of electrolytes with different types of cations (K(+) and Li(+)). The gradient distribution of surface charges is proposed to be dependent on the local electric field distribution inside the conical nanopore.

Fabrication and electrolytic conduction of single conical nanopores

Single conical nanopores were fabricated by etching single-ion-irradiated polymer (ethylene terephthalate) (PET) films. The etching process was monitored by measuring the transmembrane current. A series of conical nanopores with different tip sizes were obtained at different maximum etching currents, "Imax". Results showed that it was possible to control the tip diameter by terminating etching at a certain Imax. The current-voltage characteristic of the nanopores in KCl solution was investigated. Results showed also that the ionic conduction was asymmetrical, this phenomenon is called rectification. The current rectification coefficient, was influenced by the tip size and electrolyte concentration.

Tuning nanopore surface polarity and rectification properties through enzymatic hydrolysis inside nanoconfined geometries

Enzyme-catalyzed reactions inside nanoconfined geometries promote sensitive changes in the surface charge polarity and the concomitant permselective transport properties of the single conical nanopores.

Silicatein conjugation inside nanoconfined geometries through immobilized NTA–Ni(ii) chelates

The chemical modification and bioconjugation processes inside confined geometries by His-tagged silicatein promote sensitive changes in the polarity and surface charge density that mainly contribute to the ionic current rectification properties of the single conical nanopores.

Controlling Nanoparticle Dynamics in Conical Nanopores

Conical nanopores are a powerful tool for characterizing nanoscale particles and even small molecules. Although the technique provides a wealth of information, such pores are limited in their ability to investigate particle dynamics due to high particle velocities through a very short sensing zone. In this report, we demonstrate the use of applied pressure to balance electrokinetic forces acting on 8 nm diameter Au nanoparticles as they translocate through a ∼10 nm diameter orifice. This force balance provides a means to vary nanoparticle velocity by 3 orders of magnitude, allowing for their detection and characterization on time scales as long as 100 ms. We studied nanoparticles having different zeta potentials by varying salt concentration, applied pressure, and voltage to reveal the point at which forces are balanced and the particle velocities approach zero. Variation of the voltage around this force balance point provides a means to precisely control the magnitude and direction of the particle translocation velocity. Nanoparticle velocities computed from finite-element simulations as a function of applied pressure and voltage yield predictions in semiquantitative agreement with the experimental results. Optimizing the conditions of these techniques will allow the characterization of particles and their dynamics down to the smallest end of the nanoscale range.

Voltage-Driven Translocation of DNA through a High Throughput Conical Solid-State Nanopore

Nanopores have become an important tool for molecule detection at single molecular level. With the development of fabrication technology, synthesized solid-state membranes are promising candidate substrates in respect of their exceptional robustness and controllable size and shape. Here, a 30–60 (tip-base) nm conical nanopore fabricated in 100 nm thick silicon nitride (Si3N4) membrane by focused ion beam (FIB) has been employed for the analysis of λ-DNA translocations at different voltage biases from 200 to 450 mV. The distributions of translocation time and current blockage, as well as the events frequencies as a function of voltage are investigated. Similar to previously published work, the presence and configurations of λ-DNA molecules are characterized, also, we find that greater applied voltages markedly increase the events rate, and stretch the coiled λ-DNA molecules into linear form. However, compared to 6–30 nm ultrathin solid-state nanopores, a threshold voltage of 181 mV is found to be necessary to drive DNA molecules through the nanopore due to conical shape and length of the pore. The speed is slowed down ∼5 times, while the capture radius is ∼2 fold larger. The results show that the large nanopore in thick membrane with an improved stability and throughput also has the ability to detect the molecules at a single molecular level, as well as slows down the velocity of molecules passing through the pore. This work will provide more motivations for the development of nanopores as a Multi-functional sensor for a wide range of biopolymers and nano materials.

Calcium Binding and Ionic Conduction in Single Conical Nanopores with Polyacid Chains: Model and Experiments

Calcium binding to fixed charge groups confined over nanoscale regions is relevant to ion equilibrium and transport in the ionic channels of the cell membranes and artificial nanopores. We present an experimental and theoretical description of the dissociation equilibrium and transport in a single conical nanopore functionalized with pH-sensitive carboxylic acid groups and phosphonic acid chains. Different phenomena are simultaneously present in this basic problem of physical and biophysical chemistry: (i) the divalent nature of the phosphonic acid groups fixed to the pore walls and the influence of the pH and calcium on the reversible dissociation equilibrium of these groups; (ii) the asymmetry of the fixed charge density; and (iii) the effects of the applied potential difference and calcium concentration on the observed ionic currents. The significant difference between the carboxylate and phosphonate groups with respect to the calcium binding is clearly observed in the corresponding current-voltage (I-V) curves and can be rationalized by using a simple molecular model based on the grand partition function formalism of statistical thermodynamics. The I-V curves of the asymmetric nanopore can be described by the Poisson and Nernst-Planck equations. The results should be of interest for the basic understanding of divalent ion binding and transport in biological ion channels, desalination membranes, and controlled drug release devices.

Noninvasive Surface Coverage Determination of Chemically Modified Conical Nanopores that Rectify Ion Transport

Surface modification will change the surface charge density (SCD) at the signal-limiting region of nanochannel devices. By fitting the measured i-V curves in simulation via solving the Poisson and Nernst-Planck equations, the SCD and therefore the surface coverage can be noninvasively quantified. Amine terminated organosilanes are employed to chemically modify single conical nanopores. Determined by the protonation-deprotonation of the functional groups, the density and polarity of surface charges are adjusted by solution pH. The rectified current at high conductivity states is found to be proportional to the SCD near the nanopore orifice. This correlation allows the noninvasive determination of SCD and surface coverage of individual conical nanopores.

Voltage-Gated Ion Transport through Semiconducting Conical Nanopores Formed by Metal Nanoparticle-Assisted Plasma Etching

Nanopores with conical geometries have been found to rectify ionic current in electrolytes. While nanopores in semiconducting membranes are known to modulate ionic transport through gated modification of pore surface charge, the fabrication of conical nanopores in silicon (Si) has proven challenging. Here, we report the discovery that gold (Au) nanoparticle (NP)-assisted plasma etching results in the formation of conical etch profiles in Si. These conical profiles result due to enhanced Si etch rates in the vicinity of the Au NPs. We show that this process provides a convenient and versatile means to fabricate conical nanopores in Si membranes and crystals with variable pore-diameters and cone-angles. We investigated ionic transport through these pores and observed that rectification ratios could be enhanced by a factor of over 100 by voltage gating alone, and that these pores could function as ionic switches with high on-off ratios of approximately 260. Further, we demonstrate voltage gated control over protein transport, which is of importance in lab-on-a-chip devices and biomolecular separations.

Tunable Negative Differential Electrolyte Resistance in a Conical Nanopore in Glass

Liquid-phase negative differential resistance (NDR) is observed in the i-V behavior of a conical nanopore (~300 nm orifice radius) in a glass membrane that separates an external low-conductivity 5 mM KCl solution of dimethylsulfoxide (DMSO)/water (v/v 3:1) from an internal high-conductivity 5 mM KCl aqueous solution. NDR appears in the i-V curve of the negatively charged nanopore as the voltage-dependent electro-osmotic force opposes an externally applied pressure force, continuously moving the location of the interfacial zone between the two miscible solutions to a position just inside the nanopore orifice. An ~80% decrease in the ionic current occurs over less that a ~10 mV increase in applied voltage. The NDR turn-on voltage was found to be tunable over a ~1 V window by adjusting the applied external pressure from 0 to 50 mmHg. Finite-element simulations based on solution of Navier-Stokes, Poisson, and convective Nernst-Planck equations for mixed solvent electrolytes within a negatively charged nanopore yield predictions of the NDR behavior that are in qualitative agreement with the experimental observations. Applications in chemical sensing of a tunable, solution-based electrical switch based on the NDR effect are discussed.

Thermally controlled permeation of ionic molecules through synthetic nanopores functionalized with amine-terminated polymer brushes

We present temperature-dependent ionic transport through an array of nanopores (cylindrical and conical) and a single conical nanopore functionalized with amine-terminated poly(N-isopropylacrylamide) [PNIPAAM-NH2] brushes. For this purpose, nanopores are fabricated in heavy ion irradiated polyethylene terephthlate (PET) membranes by a controlled chemical track-etching technique, which leads to the generation of carboxyl (COOH) groups on the pore surface. End-functionalized polymer chains are immobilized onto the inner pore walls via a ‘grafting-to’ approach through the covalent linkage of surface COOH moieties with the terminal amine groups of the PNIPAAM molecules by using carbodiimide coupling chemistry. The success of the chemical modification reaction is corroborated by measuring the permeation flux of charged analytes across the multipore membranes in an aqueous solution, and for the case of single conical pore by measuring the current–voltage (I–V) characteristics, which are dictated by the electrostatic interaction of the charged pore surface with the mobile ions in an electrolyte solution. The effective nanopore diameter is tuned by manipulating the environmental temperature due to the swelling/shrinking behaviour of polymer brushes attached to the inner nanopore walls, leading to a decrease/increase in the ionic transport across the membrane. This process should permit the thermal gating and controlled release of ionic drug molecules through the nanopores modified with thermoresponsive polymer chains across the membrane.

Resistive-Pulse Detection of Multilamellar Liposomes

The resistive-pulse method was used to monitor the pressure-driven translocation of multilamellar liposomes with radii between 190 and 450 nm through a single conical nanopore embedded in a glass membrane. Liposomes (0% and 5% 1,2-dioleoyl-sn-glycero-3-phospho-l-serine (sodium salt) in 1,2-dilauroyl-sn-glycero-3-phosphocholine or 0%, 5%, and 9% 1,2-dipalmitoyl-sn-glycero-3-phospho(1'-rac-glycerol) (sodium salt) in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine) were prepared by extrusion through a polycarbonate membrane. Liposome translocation through a glass nanopore was studied as a function of nanopore size and the temperature relative to the lipid bilayer transition temperature, T(c). All translocation events through pores larger than the liposome, regardless of temperature, show translocation times between 30 and 300 μs and current pulse heights between 0.2% and 15% from the open pore baseline. However, liposomes at temperatures below the T(c) were captured at the pore orifice when translocation was attempted through pores of smaller dimensions, but squeezed through the same pores when the temperature was raised above T(c). The results provide insights into the deformation and translocation of individual liposomes through a porous material.

Transmembrane Potential across Single Conical Nanopores and Resulting Memristive and Memcapacitive Ion Transport

Memristive and memcapacitive behaviors are observed from ion transport through single conical nanopores in SiO(2) substrate. In i-V measurements, current is found to depend on not just the applied bias potential but also previous conditions in the transport-limiting region inside the nanopore (history-dependent, or memory effect). At different scan rates, a constant cross-point potential separates normal and negative hysteresis loops at low and high conductivity states, respectively. Memory effects are attributed to the finite mobility of ions as they redistribute within the negatively charged nanopore under applied potentials. A quantative correlation between the cross-point potential and electrolyte concentration is established.

Electrical, Optical, and Docking Properties of Conical Nanopores

The diffusion-influenced translocation behavior of individual nanoparticles upon passage through a conical nanopore has been elucidated by using a pressure-reversal, resistive-pulse technique, as reported by Lan and White in this issue of ACS Nano. We outline here some recent progress in conical nanopore analysis, and we present some prospects for future developments. Compared to cylindrical nanopores, the geometric change brought about by tapered nanopores causes a dramatic difference in electrical and optical properties. Such conical nanopores may also be integrated into microfluidic chips to capture cells or nanoparticles, one per nanopore, and then to release them. These advances hold the promise of making conical nanopores useful as highly efficient actuators and sensors.

Microfluidic capture and release of bacteria in a conical nanopore array

We present a simple and inexpensive method for the capture and release of bacteria contained in an array of conical nanopores on a membrane inside a microfluidic device. As an example, we demonstrate that cyanobacteria can be captured, one bacterium per pore, in a defined orientation with over 500 bacteria per membrane with viabilities as high as 100%. The device can also specifically capture cyanobacteria from a mixed suspension of cyanobacteria and chlamydomonas with a selectivity as high as 90%.