Voltage-Rectified Current and Fluid Flow in Conical Nanopores.

Ion current rectification (ICR) refers to the asymmetric potential-dependent rate of the passage of solution ions through a nanopore, giving rise to electrical current-voltage characteristics that mimic those of a solid-state electrical diode. Since the discovery of ICR in quartz nanopipettes two decades ago, synthetic nanopores and nanochannels of various geometries, fabricated in membranes and on wafers, have been extensively investigated to understand fundamental aspects of ion transport in highly confined geometries. It is now generally accepted that ICR requires an asymmetric electrical double layer within the nanopore, producing an accumulation or depletion of charge-carrying ions at opposite voltage polarities. Our research groups have recently explored how the voltage-dependent ion distributions and ICR within nanopores can induce novel nanoscale flow phenomena that have applications in understanding ionics in porous materials used in energy storage devices, chemical sensing, and low-cost electrical pumping of fluids. In this Account, we review our most recent investigations on this topic, based on experiments using conical nanopores (10-300 nm tip opening) fabricated in thin glass, mica, and polymer membranes. Measurable fluid flow in nanopores can be induced either using external pressure forces, electrically via electroosmotic forces, or by a combination of these two forces. We demonstrate that pressure-driven flow can greatly alter the electrical properties of nanopores and, vice versa, that the nonlinear electrical properties of conical nanopores can impart novel and useful flow phenomena. Electroosmotic flow (EOF), which depends on the magnitude of the ion fluxes within the double layer of the nanopore, is strongly coupled to the accumulation/depletion of ions. Thus, the same underlying cause of ICR also leads to EOF rectification, i.e., unequal flows occurring for the same voltage but opposite polarities. EOF rectification can be used to electrically pump fluids with very precise control across membranes containing conical pores via the application of a symmetric sinusoidal voltage. The combination of pressure and asymmetric EOF can also provide a means to generate new nanopore electrical behaviors, including negative differential resistance (NDR), in which the current through a conical pore decreases with increasing driving force (applied voltage), similar to solid-state tunnel diodes. NDR results from a positive feedback mechanism between the ion distributions and EOF, yielding a true bistability in both fluid flow and electrical current at a critical applied voltage. Nanopore-based NDR is extremely sensitive to the surface charge near the nanopore opening, suggesting possible applications in chemical sensing.

A Paper-Based "Pop-up" Electrochemical Device for Analysis of Beta-Hydroxybutyrate.

This paper describes the design and fabrication of a "pop-up" electrochemical paper-based analytical device (pop-up-EPAD) to measure beta-hydroxybutyrate (BHB)-a biomarker for diabetic ketoacidosis-using a commercial combination BHB/glucometer. Pop-up-EPADs are inspired by pop-up greeting cards and children's books. They are made from a single sheet of paper folded into a three-dimensional (3D) device that changes shape, and fluidic and electrical connectivity, by simply folding and unfolding the structure. The reconfigurable 3D structure makes it possible to change the fluidic path and to control timing; it also provides mechanical support for the folded and unfolded structures that enables good registration and repeatability on folding. A pop-up-EPAD designed to detect BHB shows performance comparable to commercially available plastic test strips over the clinically relevant range of BHB in blood when used with a commercial glucometer that integrates the ability to measure glucose and BHB (combination BHB/glucometer). With simple modifications of the electrode and the design of the fluidic path, the pop-up-EPAD also detects BHB in buffer using a simple glucometer-a device that is more available than the combination BHB/glucometer. Strategies that use a "3D pop-up"-that is, large-scale changes in 3D structure and fluidic paths-by folding/unfolding add functionality to EPADs (e.g., controlled timing, fluidic handling and path programming, control over complex sequences of steps, and alterations in electrical connectivity) and should enable the development of new classes of paper-based diagnostic devices.

Paper-based potentiometric ion sensing.

This paper describes the design and fabrication of ion-sensing electrochemical paper-based analytical devices (EPADs) in which a miniaturized paper reference electrode is integrated with a small ion-selective paper electrode (ISPE) for potentiometric measurements. Ion-sensing EPADs use printed wax barriers to define electrochemical sample and reference zones. Single-layer EPADs for sensing of chloride ions include wax-defined sample and reference zones that each incorporate a Ag/AgCl electrode. In EPADs developed for other electrolytes (potassium, sodium, and calcium ions), a PVC-based ion-selective membrane is added to separate the sample zone from a paper indicator electrode. After the addition of a small volume (less than 10 µL) of sample and reference solutions to different zones, ion-sensing EPADs exhibit a linear response, over 3 orders of magnitude, in ranges of electrolyte concentrations that are relevant to a variety of applications, with a slope close to the theoretical value (59.2/z mV). Ion-selective EPADs provide a portable, inexpensive, and disposable way of measuring concentrations of electrolyte ions in aqueous solutions.

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.

Designed post-self-assembly structural and functional modifications of a truncated tetrahedron.

Post-self-assembly modifications of a discrete metal-organic supramolecular structure have been developed. Such modifications allow the properties of the self-assembled supramolecular species to be changed in a simple and efficient manner (>90% yield). Initiated by the application of chemical stimuli, the post-self-assembly modifications described herein result in three distinct changes to the supramolecular system: an individual building-block component change, an overall structural modification, and a functional evolution of a [6+4] metal-organic supramolecular structure. The three modifications have been carefully examined by a range of characterization methods, including NMR and UV-vis spectroscopy, electrospray ionization mass spectrometry, pulsed field gradient spin echo NMR measurements, electrochemical analysis, and computational simulations.

Post-self-assembly covalent chemistry of discrete multicomponent metallosupramolecular hexagonal prisms.

The multicomponent coordination-driven self-assembly of hexakis[4-(4-pyridyl)phenyl]benzene, cis-(PEt(3))(2)Pt(II)(OTf)(2), and amine- or maleimide-functionalized isophthalate forms discrete hexagonal prisms as single reaction products. The amino or maleimide groups decorating the isophthalate pillars of the prisms provide reactive sites for post-self-asssembly modifications. In this communication, we demonstrate that the hexagonal prisms can be functionalized without disrupting the prismatic cores, enabling the incorporation of new functionalities under mild conditions.

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.

Prognostic value of time to generalization in 71 Chinese patients with sporadic amyotrophic lateral sclerosis.

BACKGROUND: It is important to determine prognostic factors for the outcome of amyotrophic lateral sclerosis (ALS) at an early stage. The time taken for symptoms to spread from spinal or bulbar regions to both (time to generalization; TTG) is considered a strong predictor of survival; however, this has rarely been studied in Asian populations. The aim of this retrospective study was to evaluate potential factors affecting prognosis in Chinese patients with sporadic ALS, with a focus on the association between TTG and overall survival. METHODS: Seventy-one patients with sporadic ALS who were hospitalized at Chinese PLA General Hospital from 2009 to 2016 were followed up until December 2017. Survival analysis was performed using univariate Kaplan-Meier log-rank and multivariate Cox proportional hazards models. The clinical data of the patients were recorded and analyzed. Variables studied were age at symptom onset, sex, site of symptom onset, diagnostic latency, TTG, diagnostic category, ALS Functional Rating Scale-revised score, percent predicted forced vital capacity (FVC%), and disease progression rate (DPR) at diagnosis. RESULTS: The mean age at onset was 54 (SD = 10.2) years, and the median survival time from symptom onset was 41 months (95% confidence interval: 34-47). By univariate analysis, factors independently affecting survival were age at symptom onset (Log rank = 15.652, P < 0.0001), TTG (Log rank = 14.728, P < 0.0001), diagnostic latency (Log rank = 11.997, P = 0.001), and DPR (Log rank = 6.50, P = 0.011). In the Cox multivariate model, TTG had the strongest impact on survival time (hazard ratio = 0.926, P = 0.01). CONCLUSIONS: TTG can be used as an effective indicator of prognosis in patients with sporadic ALS.

Redox preparation of mixed-valence cobalt manganese oxide nanostructured materials: highly efficient noble metal-free electrocatalysts for sensing hydrogen peroxide.

High-performance hydrogen peroxide sensors provide valuable signals of biological interactions, disorders, and developing of diseases. Low-cost metal oxides are promising alternatives but suffer from low conductivity and sensing activity. Multi-component metal oxides are excellent candidates to accomplish these challenges, but the composition inhomogeneity is difficult to manage with conventional material preparation. We demonstrated redox preparation strategies to successfully synthesize highly homogeneous, noble metal-free H2O2 sensors of spinel nanostructured cobalt manganese oxides with enhanced conductivity, multiple mixed-valence features, and efficient H2O2 sensing activities. The designed redox reactions accompanied with material nucleation/formation are the key factors for compositional homogeneity. High conductivity (1.5 × 10(-2) S cm(-1)) and H2O2 sensing activity (12 times higher than commercial Co3O4) were achieved due to the homogeneous multiple mixed-valence systems of Co(ii)/(iii) and Mn(iii)/(iv). A wide linear detection range (from 0.1 to 25 mM) with a detection limit of 15 µM was observed. Manganese species assist the formation of large surface area nanostructures, enhancing the H2O2 reduction activities, and inhibit the sensing interference. The material controls of hierarchical nanostructures, elemental compositions, porosity, and electrochemical performances are highly associated with the reaction temperatures. The temperature-dependent properties and nanostructure formation mechanisms based on a reaction rate competition are proposed.

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.

Hierarchical nanostructures with unique Y-shaped interconnection networks in manganese substituted cobalt oxides: the enhancement effect on electrochemical sensing performance.

A general redox procedure was successfully developed for the controlled synthesis of substituted cobalt oxides with hierarchical flower-like nanostructures comprising unique Y-shaped interconnections. The substitution and nanostructures synergistically enhance the material's electrochemical activities for highly efficient sensing of H2O2.

Rectification of ion current in nanopipettes by external substrates.

We describe ion distribution and the current-voltage (i-V) response of nanopipettes at different probe-to-substrate distances (Dps) as simulated by finite-element methods. Results suggest electrostatic interactions between a charged substrate and the nanopipette dominate electrophoretic ion transport through the nanopipette when Dps is within 1 order of magnitude of the Debye length (∼10 nm for a 1 mM solution as employed in the simulation). Ion current rectification (ICR) and permselectivity associated with a neutral or charged nanopipette can be reversibly enhanced or reduced dependent on Dps, charge polarity, and charge density (σ) of the substrate. Regulation of nanopipette current is a consequence of the enrichment or depletion of ions within the nanopipette interior, which influences conductivity of the nanopipette. When the external substrate is less negatively charged than the nanopipette, the substrate first reduces, and then enhances the ICR as Dps decreases. Surprisingly, both experimental and simulated data show that a neutral substrate was also able to reduce and reverse the ICR of a slightly negatively charged nanopipette. Simulated results ascribe such effects to the elimination of ion depletion within the nanopipette at positive potentials.

Paper-based electroanalytical devices with an integrated, stable reference electrode.

This paper describes the development of a referenced Electrochemical Paper-based Analytical Device (rEPAD) comprising a sample zone, a reference zone, and a connecting microfluidic channel that includes a central contact zone. We demonstrated that the rEPADs provide a simple system for direct and accurate voltammetric measurements that are referenced by an electrode with a constant, well-defined potential. The performance of the rEPADs is comparable to commercial electrochemical cells, and the layout can be easily integrated into systems that permit multiplexed analysis and pipette-free sampling. The cost of this portable device is sufficiently low that it could be for single-use, disposable applications, and its method of fabrication is compatible with that used for other paper-based systems.

Diffusional motion of a particle translocating through a nanopore.

The influence of diffusional motion on the capture and release of individual nanoparticles as they are driven through a conical-shaped glass nanopore membrane (GNM) by pressure-induced flow is reported. In these experiments, one to several hundred particles are driven through the orifice of the nanopore. Following the initial translocation, the pressure is reversed and the particles are driven through the GNM orifice in the reverse direction. The resistive-pulse technique is used to monitor the temporal sequence of particle capture and release translocations. The size of the particles (120-160 nm) and the direction of translocation can be determined from the pulse amplitude and shape. The stochastic influence of diffusion on particle trajectories has been investigated, including instantaneous transfer rate, release probability, and cumulative release success rate. We demonstrate that the sequence of particle translocations in the capture step (a, b, c... where the letters represent different particles) is largely preserved and can be read out by resistive-pulse signature during the release translocations (...c, b, a). The observed stochastic events are in good agreement with a convective diffusion model of particle trajectory within the confined geometry of the nanopore. The pressure-reversal technique opens new avenues for chemical analysis of particles using resistive-pulse methods.

A novel microfluidic approach for monodispersed chitosan microspheres with controllable structures.

A novel and simple approach to prepare monodispersed chitosan microspheres with relative small size and controlled structures was developed by combining the solidification methods of solvent extraction and chemical crosslinking in a capillary-embedded microfluidic decive. The microspheres with different structures are used in the field of protein drug controlled release and immobilization lipases and they show different release profiles and good stability, respectively.

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.

Dispersibility, stabilization, and chemical stability of ultrathin tellurium nanowires in acetone: morphology change, crystallization, and transformation into TeO2 in different solvents.

The dispersibility and stabilization of freshly synthesized ultrathin tellurium nanowires with diameters of 4-9 nm using poly(vinyl pyrrolidone) (PVP) as a capping agent can be well controlled through an easy acetone-addition process. Ultrathin Te nanowires synthesized by a hydrothermal method using PVP as a capping agent will aggregate in a water/acetone system, and their aggregation state strongly relies on the volume of water and acetone in this mixed solution. This phenomenon is due to the different solubility of PVP in water and acetone, which has significant influence on the dispersibility and stabilization of the nanowires. The results also demonstrate that the freshly prepared Te nanowires are not stable after being stored for a prolonged time in contact with air, ethanol, and water. Ultrathin Te nanowires can be oxidized easily with various final morphologies, which are core-shell structures in contact with air, amorphous nanoparticles and nanoplatelets in ethanol, and large square flakes in water. The entire conversion process from crystalline Te nanowires to amorphous TeO2 nanoparticles or single-crystal paratellurite (TeO2) at room temperature was carefully studied, implying that tellurium nanowires synthesized by other chemical methods and other nanomaterials after synthesis could also not be stable, and their storage methods require special attention.