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.

Pressure-dependent ion current rectification in conical-shaped glass nanopores.

Ion current rectification that occurs in conical-shaped glass nanopores in low ionic strength solutions is shown to be dependent on the rate of pressure-driven electrolyte flow through the nanopore, decreasing with increasing flow rate. The dependence of the i-V response on pressure is due to the disruption of cation and anion distributions at equilibrium within the nanopore. Because the flow rate is proportional to the third power of the nanopore orifice radius, the pressure-driven flow can eliminate rectification in nanopores with radii of ∼200 nm but has a negligible influence on rectification in a smaller nanopore with a radius of ∼30 nm. The experimental results are in qualitative agreement with predictions based on finite-element simulations used to solve simultaneously the Nernst-Planck, Poisson, and Navier-Stokes equations for ion fluxes in a moving electrolyte within a conical nanopore.

Nanoparticle transport in conical-shaped nanopores.

This report presents a fundamental study of nanoparticle transport phenomena in conical-shaped pores contained within glass membranes. The electrophoretic translocation of charged polystyrene (PS) nanoparticles (80- and 160-nm-radius) was investigated using the Coulter counter principle (or "resistive-pulse" method) in which the time-dependent nanopore current is recorded as the nanoparticle is driven across the membrane. Particle translocation through the conical-shaped nanopore results in a direction-dependent and asymmetric triangular-shaped resistive pulse. Because the sensing zone of conical-shaped nanopores is localized at the orifice, the translocation of nanoparticles through this zone is very rapid, resulting in pulse widths of ~200 µs for the nanopores used in this study. A linear dependence between translocation rate and nanoparticle concentration was observed from 10(7) to 10(11) particles/mL for both 80- and 160-nm-radius particles, and the magnitude of the resistive pulse scaled approximately in proportion to the particle volume. A finite-element simulation based on continuum theory to compute ion fluxes was combined with a dynamic electric force-based nanoparticle trajectory calculation to compute the position- and time-dependent nanoparticle velocity as the nanoparticle translocates through the conical-shaped nanopore. The computational results were used to compute the resistive pulse current-time response for conical-shaped pores, allowing comparison between experimental and simulated pulse heights and translocation times. The simulation and experimental results indicate that nanoparticle size can be differentiated based on pulse height, and to a lesser extent based on translocation time.

Negative differential electrolyte resistance in a solid-state nanopore resulting from electroosmotic flow bistability.

A solid-state nanopore separating two aqueous solutions containing different concentrations of KCl is demonstrated to exhibit negative differential resistance (NDR) when a constant pressure is applied across the nanopore. NDR refers to a decrease in electrical current when the voltage applied across the nanopore is increased. NDR results from the interdependence of solution flow (electroosmotic and pressure-engendered) with the distributions of K+ and Cl- within the nanopore. A switch from a high-conductivity state to a low-conductivity state occurs over a very narrow voltage window (<2 mV) that depends on the nanopore geometry, electrolyte concentration, and nanopore surface charge density. Finite element simulations based on a simultaneous solution of the Navier-Stokes, Poisson, and Nernst-Planck equations demonstrate that NDR results from a positive feedback mechanism between the ion distributions and electroosmotic flow, yielding a true bistability in fluid flow and electrical current at a critical applied voltage, i.e., the NDR "switching potential". Solution pH and Ca2+ were separately employed as chemical stimuli to investigate the dependence of the NDR on the surface charge density. The NDR switching potential is remarkably sensitive to the surface charge density, and thus to pH and the presence of Ca2+, suggesting possible applications in chemical sensing.

Resistive-pulse analysis of nanoparticles.

The development of nanopore fabrication methods during the past decade has led to the resurgence of resistive-pulse analysis of nanoparticles. The newly developed resistive-pulse methods enable researchers to simultaneously study properties of a single nanoparticle and statistics of a large ensemble of nanoparticles. This review covers the basic theory and recent advances in applying resistive-pulse analysis and extends to more complex transport motion (e.g., stochastic thermal motion of a single nanoparticle) and unusual electrical responses (e.g., resistive-pulse response sensitive to surface charge), followed by a brief summary of numerical simulations performed in this field. We emphasize the forces within a nanopore governing translocation of low-aspect-ratio, nondeformable particles but conclude by also considering soft materials such as liposomes and microgels.

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.

Resistive Pulse Analysis of Microgel Deformation During Nanopore Translocation.

Deformation of 570-nm radius poly(N-isopropylacrylamide-co-acrylic acid) microgels passing through individual 375- to 915-nm radius nanopores in glass has been investigated by the resistive-pulse method. Particle translocation through nanopores of dimensions smaller than the microgel yields electrical signatures reflecting the dynamics of microgel deformation. Translocation rates, and event duration and peak shape, are functions of the conductivities of microgel and electrolyte. Our results demonstrate that nanopore resistive-pulse methods provide new fundamental insights into microgel permeation through porous membranes.