Monitoring crystallization in real time at the nanoscale can provide valuable new insights into the nucleation process. Herein, the application of nanopipettes as nanoreactors to study the nucleation of organic materials (pharmaceutical crystals) is demonstrated, using bicalutamide (BIC), an active pharmaceutical ingredient of the prostate cancer drug CASODEX, as a model. Crystallization is achieved using a nanoscale antisolvent system, whereby a nanopipette containing an aqueous inert salt solution is brought into contact with a dimethyl sulfoxide (DSMO) solution containing soluble BIC and the same inert salt (at the same concentration). Crystallization is driven and controlled by a combination of the applied bias between an electrode in the nanopipette and one in the bulk DMSO phase and mixing of the two solvents in the mouth of the nanopipette. Crystallization at the tip of the nanopipette causes transient blockages, as BIC particles form and translocate at the end of the nanopipette opening. At low inert electrolyte concentration, the current–time signature is highly stochastic and comprises a sequence of pulses, which could either indicate nucleation–dissolution during phase transformation, and/or be due to the particles formed being charged. Particles produced in this way can be used as seeds for crystal growth, and Raman spectroscopy analysis of the crystals produced indicates rather rare Form II BIC which is rarely formed. Thus, in addition to monitoring nucleation, nanopipettes can serve as reactors to synthesize organic crystals with polymorphs that are not typically found. Finite element method modeling provides valuable insight into the solvent mixing process and effect of applied bias, and helps to explain some of the observations.

Scanning electrochemical microscopy (SECM) operating as a variable gap ultra-thin layer twin-working electrode cell, has long been recognised as a powerful technique for investigating fast kinetics (heterogeneous electron transfer and homogeneous reactions coupled to electron transfer) as a consequence of high mass transport rates between the working electrodes when biased to promote redox shuttling. Recently, SECM has advanced technically and nanogap cells with dimensions on the 10s of nm scale have been reported. In this paper, we consider double layer effects on voltammetric measurements in this configuration, outlining a comprehensive model that solves the Nernst-Planck equation and Poisson equation with charged interfaces. For supporting electrolyte concentrations that have been used for such measurements (50 mM and 100 mM), it is shown that for typical electrode charges and charge on the glass insulator that encases the ultramicroelectrode (UME) tip used in SECM, there are profound effects on the voltammetric wave-shapes for redox reactions of charged redox couples, in the common modes used to study electron transfer kinetics, namely the tip-voltammetry (feedback) mode and substrate-voltammetry (substrate-generation/tip-collection and competition) modes. Using the reduction and oxidation of a singly charged redox species to a neutral and doubly charged species, respectively, as exemplar systems, it is shown that the charge on the electrodes can greatly distort the voltammetric wave-shape, while charge on the glass that surrounds the UME tip can affect the limiting current. Analysis of SECM voltammograms using methods that do not account for double layer effects will thus result in significant error in the kinetic values derived and tip-substrate distances that have to be estimated from limiting currents in SECM. The model herein provides a framework that could be developed for further studies with nanogap-SECM (e.g. consideration of alternative models for the electrical double layer, other supporting electrolyte concentrations, potential of zero charge on the electrodes and charges on the redox couples). The model results presented are shown to qualitatively match to SECM voltammetric features from experimental data in the literature, and are further supported by experimental data for redox processes of tetrathiafulvalene (TTF), namely the TTF/TTF ⁺

and TTF ⁺

/TTF²⁺ redox couples. This serves to demonstrate the immediate practical application of some of the ideas presented herein. For future applications of SECM, the use of different supporting electrolyte concentrations and a range of tip-substrate separations may allow the determination of both electron transfer kinetics and double layer properties.

A comparison of the electrochemical performance of noble metal, sp²- and sp³-carbon electrodes towards the reduction of concentrated hypochlorite (ClO⁻; 0.02 M–1.88 M), an alkaline (pH ~ 13) and chemically oxidising solution, is presented. Boron-doped diamond (BDD) gave no discernible electrochemical response whilst all other electrodes showed an electrochemically irreversible cathodic response in the following order (most facile electron transfer): Pt > Au > edge plane pyrolytic carbon (EPPG) ≈ sp²-containing BDD > basal plane (BP) sp² carbon > glassy carbon ≈ highly ordered pyrolytic graphite. Reduction at sp²-BDD occurred at a similar potential to EPPG, but with much lower currents, suggesting edge-plane-like sites are the active sp² sites in this sp²-BDD, but at much lower surface coverage than in EPPG. Finally, both EPPG and sp²-BDD showed linear current versus [ClO⁻] responses over the concentration range 0.02 M–1.41 M (R² > 0.995).

Electrochemical interfaces used for sensing, (electro)catalysis, and energy storage are usually nanostructured to expose particular surface sites, but probing the intrinsic activity of these sites is often beyond current experimental capability. Herein, it is demonstrated how a simple meniscus imaging probe of just 30 nm in size can be deployed for direct electrochemical and topographical imaging of electrocatalytic materials at the nanoscale. Spatially resolved topographical and electrochemical data are collected synchronously to create topographical images in which step-height features as small as 2 nm are easily resolved and potential-resolved electrochemical activity movies composed of hundreds of images are obtained in a matter of minutes. The technique has been benchmarked by investigating the hydrogen evolution reaction on molybdenum disulfide, where it is shown that the basal plane possesses uniform activity, while surface defects (i.e., few to multilayer step edges) give rise to a morphology-dependent (i.e., height-dependent) enhancement in catalytic activity. The technique was then used to investigate the electro-oxidation of hydrazine at the surface of electrodeposited Au nanoparticles (AuNPs) supported on glassy carbon, where subnanoentity (i.e., sub-AuNP) reactivity mapping has been demonstrated. We show, for the first time, that electrochemical reaction rates vary significantly across an individual AuNP surface and that these single entities cannot be considered as uniformly active. The work herein provides a road map for future studies in electrochemical science, in which the activity of nanostructured materials can be viewed as quantitative movies, readily obtained, to reveal active sites directly and unambiguously.

Calcium carbonate crystallisation on surfaces has been studied extensively due to its prominence in biomineralisation, but the role of surface charge in nucleation and growth is not well understood. We have employed potential-controlled Highly Oriented Pyrolytic Graphite (HOPG) surfaces to demonstrate the significant impact of surface charge on calcium carbonate crystallisation: at negatively charged HOPG surfaces, calcite, aragonite and vaterite all nucleate from high energy positively-charged crystal faces, contrasting with the stable (104) calcite planes nucleated at positively charged surfaces. These observations are explained and rationalised.

Scanning ion conductance microscopy (SICM) is a nanopipette-based scanning probe microscopy technique that utilizes the ionic current flowing between an electrode inserted inside a nanopipette probe containing electrolyte solution and a second electrode placed in a bulk electrolyte bath, to provide information on a substrate of interest. For most applications to date, the composition and concentration of the electrolyte inside and outside the nanopipette is identical, but it is shown herein that it can be very beneficial to lift this restriction. In particular, an ionic concentration gradient at the end of the nanopipette, generates an ionic current with a greatly reduced electric field strength, with particular benefits for live cell imaging. This differential concentration mode of SICM (ΔC-SICM) also enhances surface charge measurements and provides a new way to carry out reaction mapping measurements at surfaces using the tip for simultaneous delivery and sensing of the reaction rate. Comprehensive finite element method (FEM) modeling has been undertaken to enhance understanding of SICM as an electrochemical cell and to enable the interpretation and optimization of experiments. It is shown that electroosmotic flow (EOF) has much more influence on the nanopipette response in the ΔC-SICM configuration compared to standard SICM modes. The general model presented advances previous treatments, and it provides a framework for quantitative SICM studies.