Nanobubble formation and pinning on nanoelectrodes significantly hinder the efficiency of gas evolution reactions, limiting the potential of hydrogen production technologies. This work uncovers the pivotal role of nanoelectrode curvature in influencing catalytic performance and nanobubble detachment. Using molecular dynamics simulations supported by experimental evidence, we establish that convex nanoelectrodes, such as those of hemispherical and spherical geometries, sustain higher catalytic performance by maintaining greater reactive surface exposure than flat or concave electrodes. Most importantly, we demonstrate that convex electrodes mitigate bubble pinning by promoting unlimited growth and spontaneous detachment. Surprisingly, our calculations reveal that bubble detachment contributes minimally to the overall current. Our findings provide a mechanistic framework for optimizing electrode geometry to enhance gas evolution efficiency, emphasizing the role of convex nanoparticles in maximizing surface exposure rather than relying primarily on bubble detachment dynamics to improve gas production rates.

Herein, we investigate the origin of selectivity in the alternating current (AC)-enabled partial reduction of (hetero)arenes to cyclic alkenes. Reduction of (hetero)arenes can be considered as a reaction involving two consecutive irreversible electrochemical steps: the first generates the desired cyclic alkene, while the second leads to its undesired overreduction. Conventional constant current or voltage (DC) electrolysis results in poor selectivity toward the partial reduction products, originating from overreduction and base-induced decomposition of the desired product. Fast-scan cyclic voltammetry shows that the rate constant for the first reduction (k1) exceeds that of the second one (k2). Finite element simulations based on this experimental finding semiquantitatively capture the frequency-dependent selectivity observed in AC electrolysis experiments (i.e., increasing the AC frequency enhances selectivity). The results further reveal that AC electrolysis mitigates the low selectivity by only collecting the products at the initial stage of the reduction reaction, which is mostly under a kinetically controlled regime. We then extend the finite element model and introduce ΔEFOW, the foot-of-the-wave potential difference between cyclic voltammograms of substrate and partial reduction product, as an accessible proxy for k2/k1. A ΔEFOW > 80 mV predicts synthetically useful selectivity (>30%) toward the partial reduction product below 100 Hz.

Electroorganic reduction reactions are canonically carried out at a cathode at which a significant negative potential is applied. Specifically, aryl bromides and chlorides undergo heterogeneous reduction in organic solvents at potentials more negative than –2 V vs E0’ for the Fc/Fc+ couple (Fc = ferrocene). To decrease the overpotential for reduction reactions, electrocatalysis strategies are often employed. Here, we present an electrochemical method to reduce aryl bromides and chlorides that is initiated by an oxidation reaction at very mild potentials (~ 0 V vs Fc/Fc+). Specifically, electrochemical oxidation of an outer-sphere redox mediator, 1,1-dimethylferrocene, in dry N,N-dimethylformamide (DMF) containing oxalate (C2O42–), results in the homogeneous one-electron oxidation of C2O42–. The resulting C2O4•– decomposes in ~1 µs to release the carbon dioxide radical anion (CO2•–), a potent reductant that is oxidized to CO2 at –2.68 V vs Fc/Fc+. In this way, an oxidation reaction at very low electrode potentials enables the homogeneous reduction of aryl bromides and chlorides, which are otherwise directly reduced at very negative potentials. Using this method, selective hydrodehalogenations of electron-deficient aryl bromides and chlorides are carried out at a reticulated vitreous carbon anode with up to quantitative conversion yields. Cyclic voltammetry and finite difference simulations are used to characterize the hydrodehalogenation of 4-bromobenzonitrile via C2O42– oxidation. Additionally, we show that the efficiency of hydrodehalogenation can be tuned by deliberate additions of water to the DMF solutions, leading to a substantial improvement in overall conversion yields without interference from water or proton reduction.

Nanobubble formation and binding to nanoelectrodes significantly hinder the efficiency of gas evolution reactions, limiting the potential of hydrogen production technologies. This work uncovers the pivotal role of the nanoelectrode shape in influencing catalytic performance and nanobubble detachment. Using molecular dynamics simulations supported by experimental evidence, we establish that nanoparticle electrodes with convex geometries (e.g., hemispheres, spheres, and cubes) sustain higher catalytic performance by maintaining greater reactive surface exposure than flat or concave electrodes. Most importantly, we demonstrate that convex nanoparticle electrodes mitigate bubble pinning by promoting unlimited growth and spontaneous detachment. We develop a diffusional theory that explains and generalizes our simulations, predicting the onset currents that drive nanobubbles into a nonstationary growth regime. This theory reveals that the transition to continuous bubble growth occurs when the electrochemically generated gas rate surpasses the diffusion-limited escape rate, independent of electrode size and convex shape but sensitive to the electrode support. The theoretical model extends the predictions to other gas-evolving electrochemical processes, highlighting its relevance to diverse catalytic systems. Surprisingly, our calculations reveal that bubble detachment contributes minimally to the total current. Instead, the enhanced catalytic efficiency of convex electrodes stems from their ability to sustain an exposed reactive surface, even during bubble growth. These findings provide a fundamental framework for designing nanoelectrodes that optimize gas evolution by prioritizing surface exposure rather than relying solely on bubble detachment.

This report describes an investigation of the role of H2O and DMF (N,N-dimethylformamide) as solvents on the electrochemical oxidation of oxalate (C2O42–). In H2O/0.1 M Na2SO4, the 2e– oxidation of C2O42– yields two CO2 molecules via a classical ECE mechanism, resulting in a single oxidation wave at 1.2 V vs Ag/AgCl. In contrast, two distinct oxidation waves are observed in DMF/0.1 M TBAP at ~0.1 V and ~0.7 V vs Ag/AgCl. The second wave at more positive potentials in DMF was first assigned by Maran and co-workers to the oxidation of the adduct C2O42–•CO2 formed from generation of CO2 during the first wave. Electronic interaction of C2O42– and CO2 stabilizes C2O42–, making it more difficult to oxidize than free C2O42–. Herein, we present cyclic voltammetry (CV), finite difference (FD) simulations, Raman spectroscopy, and ab initio molecular dynamics (AIMD) simulations to determine the thermodynamics and kinetics of C2O42–•CO2 formation, as well as the adduct structure. FD simulations of the voltammetric data provide approximate thermodynamic and kinetic parameters for C2O42–•CO2 formation in DMF, as well as a new value for the diffusion coefficient of C2O42– in DMF that differs substantially from previously reported values. Raman spectroscopy directly demonstrates C2O42–•CO2 formation in DMF, while AIMD simulations predict that the solvent-dependent thermodynamics and mechanism for C2O42– oxidation can be explained by C2O42––solvent and C2O42––CO2 interactions. A by-product of this investigation is the prediction from AIMD simulations that the C2O42–•CO2 interaction in DMF destabilizes CO2. Consistent with this finding, cyclic voltammetry demonstrates that the thermodynamic potential for CO2 reduction in DMF at a Hg electrode decreases by ~0.3 V upon addition of C2O42– to the solution.

Many technologies involve immobilizing catalysts such as enzymes on surfaces, and the catalytic activities or functional efficiencies of these surface-bound catalysts can vary depending on orientations, localized binding sites, active sites, and intrinsic molecular nature. Accurate and rapid quantification of reaction products from surface-immobilized catalysts is crucial for understanding the selectivity, mechanisms, and reaction dynamics of catalytic systems and for revealing heterogeneous catalytic activities and reaction sites for applications such as biosensors and energy conversion/generation systems. Here, we demonstrate the feasibility of localized enzymatic activity measurements using microscale carbon dioxide (CO2)-sensitive ion-selective electrode (ISE) pipettes (0.5-2.5 μm tip radius) as a probe, with in situ potentiometric scanning electrochemical microscopy (SECM). We develop carbonate (CO32-) ionophore-incorporated ISEs exhibiting a Nernstian response (26.7 mV/decade) with a detection limit of 1.72 μM and explore surface-immobilized formate dehydrogenase (FDH) activity by detecting CO2 generated by the enzymatic reaction via potentiometric measurements. SECM is used for real-time spatial/temporal investigation of FDH immobilized onto the surface at a micrometer-scale resolution. Moreover, unlike voltammetric techniques based on faradaic reactions, the potentiometric measurements using ISEs allow highly sensitive and selective detection of CO32-, rendering efficient quantification of CO2 without interference from solution composition changes arising from faradaic processes. The total amount of CO2 generated at an FDH-immobilized Au ultramicroelectrode is quantified as a function of coenzyme, i.e., NAD+, and substrate, i.e., formate, concentrations both in constant tip-sample distance mode and variable depth mode. Finally, we demonstrate the use of the ISE to quantify CO2 levels in blood serum.

Innovator who pioneered scanning electrochemical microscopy, bioassays and solar fuels. Innovator who pioneered scanning electrochemical microscopy, bioassays and solar fuels.

Simultaneous multipass resistive-pulse sensing and fluorescence imaging have been used to correlate the size and fluorescence intensity of individual E. coli lipid liposomes composed of E. coli polar lipid extract labeled with membrane-bound 3,3-dioctadecyloxacarbocyanine (DiO) fluorescent molecules. Here, a nanopipette serves as a waveguide to direct excitation light to the resistive-pulse sensing zone at the end of the nanopipette tip. Individual DiO-labeled liposomes (>50 nm radius) were multipassed back and forth through the orifices of glass nanopipettes 110-to-150 nm radius via potential switching to obtain sub-nanometer sizing precision, while recording the fluorescence intensity of the membrane-bound DiO molecules. Fluorescence was measured as a function of liposome radius and found to be approximately proportional to the total membrane surface area. The observed relationship between liposome size and fluorescence intensity suggests that multi-vesicle liposomes emit greater fluorescence compared to unilamellar liposomes, consistent with all lipid membranes of the multi-vesicle liposomes containing DiO. Fluorescent and non-fluorescent liposomes are readily distinguished from each other in the same solution using simultaneous multipass resistive-pulse sensing and fluorescence imaging. A fluorescence ‘dead zone’ of ~1 m thickness just outside of the nanopipette orifice was observed during resistive-pulse sensing, resulting in ‘on/off’ fluorescent behavior during liposome multipassing. Our results provide a path forward to simultaneously characterize the size of biologically relevant nanoparticles (e.g., extracellular vesicles) and the presence of fluorescently labeled surface proteins.

Recent studies suggest extracellular vesicles (EVs) of cancerous origin contribute to cancer metastasis, immune suppression, and the emergence of therapy-resistant cancer cells. Distinguishing oncogenic EVs from ‘healthy’ EVs poses a challenge for current technologies, where a range of various analytical techniques is required to assess EVs characteristics (e.g., size, contents). Traditional methods such as Cryogenic TEM are low-throughput, while others such as flow cytometry and nanoparticle tracking lack the size precision to quantify small, <50 nm, EVs. Herein, we introduce simultaneous resistive-pulse sensing and fluorescence imaging on an EV-by-EV basis to comprehensively characterize EV size, surface charge, surface biomarkers, cargo, and concentration. Individual EVs are multipassed through the orifice of a laser-pulled glass nanopipette approximately 100-200 nm in radius, enabling sub-nanometer sizing precision while simultaneously quantifying the fluorescence emission of labeled EV surface markers and internal contents. A fiber optic cable is placed within the interior of the nanopipette, which serves as a waveguide to direct the excitation light to the resistive-pulse sensing zone at the pipette orifice. By characterizing EVs one-at-a-time, accurate statistics of unique EV subpopulations within the population ensemble are obtained. This multipass resistive-pulse sensing approach offers a high-throughput solution for rapidly characterizing heterogeneous EV populations, promising advancements in our understanding of EV-mediated processes in cancer progression and therapy resistance. Figure 1

The elementary steps of the electrocatalytic reduction of S2O82– using the Ru(NH3)63+/2+ redox couple were investigated using scanning electrochemical microscopy (SECM) and steady-state voltammetry (SSV). SECM investigations were carried out in a 0.1 M KCl solution using a 3.5-µm radius carbon ultramicroelectrode (UME) as the SECM tip and a 25-µm radius platinum UME as the substrate electrode. Approach curves were recorded in the positive feedback mode of SECM by reducing Ru(NH3)63+ at the tip electrode and oxidizing Ru(NH3)62+ at the substrate electrode, as a function of the tip-substrate separation and S2O82– concentration. The one-electron reaction between electrogenerated Ru(NH3)62+ and S2O82– yields the unstable S2O83•-, which rapidly dissociates to produce highly oxidizing SO4•–. Because SO4•– is such a strongly oxidizing species, it can be further reduced at both the tip or the substrate, or it can react with Ru(NH3)62+ to regenerate Ru(NH3)63+. SECM approach curves display a complex dependence on the tip-substrate distance, d, due to redox mediation reactions at both the tip and the substrate. Finite element method (FEM) simulations of both SECM approach curves and SSV confirm a previously proposed mechanism for the mediated reduction of S2O82– using Ru(NH3)63+/2+ redox couple. Our results provide a lower limit for dissociation rate constant of S2O83•– (~ 1 × 106 s–1), as well as the rate constants for electron transfer between SO4•– and Ru(NH3)62+ (~ 1 × 109 M–1s–1) and between S2O82– and Ru(NH3)62+ (~7 × 105 M–1s–1).

The self-assembly of graphene oxide (GO) and M13 bacteriophage results in the formation of micro-porous structures, known as GraPhage13 aerogels (GPA). Given the limited applications of aerogels in industry due to their nanomechanical properties, along with the previously observed temperature-dependent characteristics in graphene-based nanocomposites, a thorough exploration of the thermosensitive nanomechanical properties of GPA is essential. Herein, a comprehensive characterisation of the morphology, composition, and spectroscopic analysis of the GPA for a range of temperatures has been conducted and correlated with its nanomechanical properties. Elevated temperatures have been found to lead to gradual removal of oxygen-containing functional groups (OCFGs) from GPA, resulting in increased structural defects and reduced stiffness. Notably, unique nanomechanical behaviours of GPA have been further identified, where the thermal expansion of sp3 bonds exceeds that of a crystalline sp3 structure, while the thermal contraction of sp2 bonds in GPA is found to be between graphite and GO. This underscores the impact of GO functionalisation on the thermal expansion behaviour of GPA. The obtained insights enhance the overall comprehension of the temperature annealing impact on GPA and highlight the tunability of its nanomechanical properties, showcasing a broad potential of this novel nanocomposite across a diverse range of applications.

Graphene oxide (GO) and M13 bacteriophage can self-assemble to form ultra-low density porous structures, known as GraPhage13 aerogels (GPA). Due to the insulating nature of GPA and the challenges in producing highly conductive aerogels, it is paramount to explore ways to enhance the conductivity of GPA. Herein, we have developed a method to enhance the conductivity of GPA, via the integration and optimisation of 5 nm and 20 nm diameter gold nanoparticles (AuNPs) into the aerogel structure and systematically analysed the morphology, composition and spectroscopic properties of the resulting GPA-Au nanocomposite. The fabricated GPA-Au nanocomposites exhibited remarkable increases in conductivity, with the integration of 5 nm AuNPs leading to a 53-fold increase compared to GPA, achieving a performance of up to 360 nS/cm, which is within the range suitable for miniaturised semiconductor devices. The mechanism behind the conductivity enhancement was further investigated and attributed to GO-AuNP interactions increasing the carrier density by introducing new energy levels in the GO band gap or shifting its Fermi level towards the conduction band. These findings demonstrate the potential of functionalised AuNPs to significantly improve the electrical properties of GPA, paving the way for their application in gas sensors for biological and chemical detection and a new range of advanced semiconductor devices.

Proton transfer at solid/liquid interfaces is a fundamental step in many complex biological and electrocatalytic processes. Previous model studies using electrodes modified with self-assembled monolayers (SAMs) of carboxylic acid-terminated alkanethiols have demonstrated that interfacial proton transfer is controlled by the local electrochemical microenvironment. The thermodynamic driving force for electrochemically driven protonation/deprotonation of acid/base SAMs is governed by a combination of the electric potential at the SAM/solvent interface, the pK(a) of the acid group, and the solution pH. Here, we develop a kinetic model to describe electric potential-driven protonation/deprotonation as a two-step process. This comprises a reversible proton transfer step at the SAM/electrolyte interface (i.e., (de)protonation) and a proton transport step describing the motion of protons as they traverse the diffuse electrical double layer to and from the solution bulk. The kinetics of the transport step are investigated using finite element simulations, providing numerical estimates for the transport rate constants under combined diffusional and migrational transport modes. Using the dependence of these rate constants on the electric potential at the SAM/electrolyte interface, we define situations where the overall rate expression is limited by either (de)protonation, proton transport, or a combination of both. From this analysis, we determine a lower limit for the acid group pK(a) of approximate to 3, above which proton transfer at the plane of acid dissociation is generally the rate-determining step. The electric potential-driven proton transfer/transport kinetic model developed herein provides a general approach to treat electric potential-driven coupled ion transfer and transport phenomena, with potential applications including proton-coupled electron transfer processes, ion intercalation in alkali metal batteries, and ion transport across biological membranes.

Innovator who pioneered scanning electrochemical microscopy, bioassays and solar fuels.

Previous reports of the electrocatalytic activity of Ag nanoparticles (AgNPs) toward the reduction of organic halides have been limited to measurements of immobilized nanoparticle ensembles. Here, we have investigated the electrochemical reduction of benzyl bromide (PhCH2Br) occurring at single AgNPs (4.2 to 37 nm radius) in methanol, where the effects of nanoparticle size on catalytic behavior can be more thoroughly examined and rigorously quantified. AgNP collisions at a 6.3 mu m radius Au ultramicroelectrode (UME) result in measurable electrocatalytic amplification currents from the reduction of PhCH2Br, where collision events are indicated by a sudden step increase in the reduction current recorded in the current-time trace. The dependence of the height of these steps on the applied potential allowed for an analysis of reaction kinetics based on the Butler-Volmer model, resulting in an estimation of the standard rate constant (k(0)) as a function of AgNP size. Measured values of k(0) range from 4.0 x 10(-4) to 8.0 x 10(-4) cm/s on AgNPs with radii of 14, 29, and 37 nm, whereas k(0) was found to be 6.2 x 10(-4) cm/s at a 12.3 mu m radius Ag disk UME. The results indicate that the kinetics of PhCH2Br reduction are independent of AgNP size and are similar to the reaction kinetics observed at a Ag UME. The frequency of observed particle collisions was found to be dependent on particle size, where 14 nm radius AgNPs resulted in the highest-frequency collisions. The potential- and size-dependent interactions of AgNPs with the Au UME are discussed in terms of the DLVO theory.

A mechanism for the concerted pathway of coupled electron- and phase-transfer reactions (CEPhT) is proposed. CEPhT at three-phase interfaces formed by a solid electrode, an insulating organic solvent, and an aqueous electrolyte is driven by electric double layer (EDL) spillover, with significant electrostatic potential gradients extending a few nanometers into the insulating phase. This EDL spillover phenomenon is studied using scanning electrochemical cell microscopy to interrogate the oxidation of ferrocene in toluene to ferrocenium in water, (Fc)tol -> (Fc+)aq + e-. Finite element method simulations of the electrostatic potential distribution and species concentration profiles enable the calculation of complete i-E curves that incorporate mass transport, electron transfer, phase transfer, and the EDL structure. Simulated and experimental i-E traces show good agreement in the current magnitude and the effect of the supporting electrolyte, identifying an unexpected dependence of overall reaction kinetics on the concentration of the supporting electrolyte in the aqueous phase due to EDL spillover. An interfacial toluene/water mixing region generates a unique electrochemical microenvironment where concerted electron transfer and solvent shell replacement facilitate CEPhT. Kinetic expressions for concerted and sequential CEPhT mechanisms highlight the role of this interfacial environment in controlling the rate of CEPhT. These combined experimental and simulated results are the first to support a concerted mechanism for CEPhT where (Fc)tol is transported to the interfacial mixing region at the three-phase interface, where it undergoes oxidation and phase transfer. EDL spillover can be leveraged for engineering sample geometries and electrostatic microenvironments to drive electrochemical reactivity in classically forbidden regions, e.g., insulating solvents and gases.

Aqueous solutions containing both the strong oxidant, peroxydisulfate (S2O82‒), and the strong reductant, oxalate (C2O42‒), are thermodynamically unstable due to the highly exothermic homogeneous redox reaction: S2O82‒ + C2O42‒ ® 2 SO42‒ + 2 CO2 (DG0 = −490 kJ/mol). However, at room temperature, this reaction does not occur to a significant extent over the timescale of a day due to its inherently slow kinetics. We demonstrate that the S2O82‒/C2O42‒ redox reaction occurs rapidly, once initiated by the Ru(NH3)62+-mediated 1e– reduction of S2O82‒ to form S2O83•‒ at a glassy carbon electrode. Theoretically, the mediated electrochemical generation of a single molecule of S2O83•‒ is capable of initiating an autocatalytic cycle that consumes both S2O82‒ and C2O42‒ in bulk solution. Several experimental demonstrations of S2O82‒/C2O42‒ autocatalysis are presented. Differential electrochemical mass spectrometry measurements demonstrate that CO2 is generated in solution for at least 10 minutes following a 30-s initiation step during which S2O83•‒ is generated. Quantitative bulk electrolysis of S2O82‒ in solutions containing excess C2O42‒ is initiated by electrogeneration of immeasurably small quantities of S2O83•‒. Capture of CO2 as BaCO3 during electrolysis additionally confirms the autocatalytic generation of CO2. First- principles density functional theory calculations, ab initio molecular dynamics simulations, and finite difference simulations of cyclic voltammetric responses are presented that support and provide additional insights into the initiation and mechanism of the S2O82‒/C2O42‒ autocatalytic reaction. Preliminary evidence indicates that autocatalysis also results in a chemical traveling reaction front that propagates into the solution normal to the planar electrode surface.

Water is the ideal green solvent for organic electrosynthesis. However, a majority of electroorganic processes require potentials that lie beyond the electrochemical window for water. In general, water oxidation and reduction lead to poor synthetic yields and selectivity or altogether prohibit carrying out a desired reaction. Herein, we report several electroorganic reactions in water using synthetic strategies referred to as reductive oxidation and oxidative reduction. Reductive oxidation involves the homogeneous reduction of peroxydisulfate (S2O82-) via electrogenerated Ru(NH3)62+ at potential of -0.2 V vs. Ag/AgCl (3.5 M KCl) to form the highly oxidizing sulfate radical anion (E0' (SO4˙-/SO42-) = 2.21 V vs. Ag/AgCl), which is capable of oxidizing species beyond the water oxidation potential. Electrochemically generated SO4˙- then efficiently abstracts a hydrogen atom from a variety of organic compounds such as benzyl alcohol and toluene to yield product in water. The reverse analogue of reductive oxidation is oxidative reduction. In this case, the homogeneous oxidation of oxalate (C2O42-) by electrochemically generated Ru(bpy)33+ produces the strongly reducing carbon dioxide radical anion (E0' (CO2˙-/CO2) = -2.1 V vs. Ag/AgCl), which can reduce species at potential beyond the water or proton reduction potential. In preliminary studies, the CO2˙- has been used to homogeneously reduce the C-Br moiety belonging to benzyl bromide at an oxidizing potential in aqueous solution.

The electrical double layer (EDL) can lead to unexpectedvoltammetricphenomena. A notable example is the Frumkin effect, observed for thereduction of peroxydisulfate (S2O8 (2-)). In the absence of excess supporting electrolyte, the rate of S2O8 (2-) reduction decreases as thecathodic overpotential is increased, contrary to expectations forfaradaic electron-transfer processes. Here, we report a demonstrationof the Frumkin effect for S2O8 (2-) reduction at Hg ultramicroelectrodes, revealing steady-state voltammetrybehavior consistent with prior observations at rotating disk electrodes.A finite element model is used to simulate the effect of the EDL onS(2)O(8) (2-) reduction in the presenceand absence of excess supporting electrolyte (K2SO4). Semiquantitative agreement between experimental and simulatedvoltammograms is obtained, including capturing the decrease in currentfor S2O8 (2-) reduction withincreasing overpotential. We show that S2O8 (2-) migration within the EDL, at electrode potentialsnegative of the potential of zero charge, is the primary process responsiblefor the observed decrease in current with increasing driving force.These combined experiments and finite element simulations representthe first quantitative description of the Frumkin effect with rigorousinclusion of the EDL, migrational and diffusional mass-transport,and long-range electron transfer kinetics.

A quantitative description of ionophore-mediated ion transport is important in understanding ionophore activity in biological systems and developing ionophore applications. Herein, we describe the direct measurement of the electrical current resulting from K+ transport mediated by individual valinomycin (val) ionophores. Step fluctuations in current measured across a 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) bilayer suspended over a ∼400 nm radius glass nanopore result from dynamic partitioning of val between the bilayer and torus region, effectively increasing or decreasing the total number of val present in the membrane. In our studies, approximately 30 val are present in the membrane on average with a val entering or leaving the bilayer approximately every 50 s, allowing measurement of changes in electrical current associated with individual val. The single-molecule val(K+) transport current at 0.1 V applied potential is (1.3 ± 0.6) × 10-15 A, consistent with estimates of the transport kinetics based on large val ensembles. This methodology for analyzing single ionophore transport is general and can be applied to other carrier-type ionophores.