Single molecule electrochemical detection (SMED) is an extremely challenging aspect of electroanalytical chemistry, requiring unconventional electrochemical cells and measurements. Here, SMED is reported using a “quad-probe” (four-channel probe) pipet cell, fabricated by depositing carbon pyrolytically into two diagonally opposite barrels of a laser-pulled quartz quadruple-barreled pipet and filling the open channels with electrolyte solution, and quasi-reference counter electrodes. A meniscus forms at the end of the probe covering the two working electrodes and is brought into contact with a substrate working electrode surface. In this way, a nanogap cell is produced whereby the two carbon electrodes in the pipet can be used to promote redox cycling of an individual molecule with the substrate. Anticorrelated currents generated at the substrate and tip electrodes, at particular distances (typically tens of nanometers), are consistent with the detection of single molecules. The low background noise realized in this droplet format opens up new opportunities in single molecule electrochemistry, including the use of ionic liquids, as well as aqueous solution, and the quantitative assessment and analysis of factors influencing redox cycling currents, due to a precisely known gap size.

Heterogeneous electron transfer rate constants (k₀ values) at a boron-doped diamond (BDD) electrode (10^–2 cm s^–1 range) that are more than an order of magnitude smaller than found at metal or glassy carbon (GC) electrodes (≥2.0 cm s^–1) are reported for the outer-sphere [Ru(NH₃)₆]^3+/2+, [α-SiW₁₂O₄₀]^4–/5–, and [α-SiW₁₂O₄₀]^5–/6– redox couples in aqueous electrolyte media. The k₀ values and other parameters relevant to electrode kinetics were derived from analysis of the higher-order harmonic components available in Fourier transformed large amplitude alternating current voltammetry at BDD, GC, and platinum (Pt) or gold (Au) electrodes for the reduction of highly positively charged [Ru(NH₃)₆]³⁺ and highly negatively charged Keggin-type silicon tungstate ([α-SiW₁₂O₄₀]^4– and [α-SiW₁₂O₄₀]^5–). The slower electron transfer kinetics at the BDD electrode, relative to the other electrode materials, are discussed in terms of the double layer, density of states, and other factors.

Voltammetric studies of dopamine (DA) oxidation on pristine and acid-treated single-walled carbon nanotube (SWNT) network electrodes were undertaken in order to investigate both the effect of network density and acid treatment times on the voltammetric characteristics for DA oxidation and the susceptibility of the electrodes to fouling. Through careful control of catalysed chemical vapour deposition growth parameters, multiply interconnected and randomly oriented SWNT networks of two significantly different densities were grown (high density, HD, coverage >>10 μm length of SWNT per μm-2 and low density, LD, coverage = 5 (±1) μm SWNT μm-2). Acid treatment was performed to provide materials with different electrochemical properties and SWNT coverage, as determined by field emission-scanning electron microscopy, atomic force microscopy and micro-Raman spectroscopy. A high concentration of DA (100 µM) was deliberately employed to accelerate the fouling phenomenon associated with DA oxidation in order to evaluate the lifetime of the electrodes. HD pristine SWNT networks were found to promote more facile electron transfer (ET) and were less susceptible to blocking, compared to LD pristine SWNT networks. Acid treatment resulted in both a further enhancement of the ET rate and a reduction in susceptibility towards electrode fouling. However, lengthy acid treatment detrimentally affected ET, due to a decrease in network density and significant damage to the SWNT network structure. These studies highlight the subtle interplay between SWNT coverage and degree of acid functionalisation when seeking to achieve the optimal SWNT electrode for the voltammetric detection of DA.

The quantification of genotoxic impurities (GI) such as hydrazine (HZ) is of critical importance in the pharmaceutical industry in order to uphold drug safety. HZ is a particularly intractable GI and its detection represents a significant technical challenge. Here we present for the first time, the use of electrochemical analysis to achieve the required detection limits by the pharmaceutical industry for the detection of HZ in the presence of a large excess of a common active pharmaceutical ingredient (API); acetaminophen (ACM) which itself is redox active, typical of many APIs. A flow injection analysis approach with electrochemical detection (FIA-EC) is utilized, in conjunction with a co-planar boron doped diamond (BDD) microband electrode, insulated in an insulating diamond platform for durability and integrated into a two piece flow cell. In order to separate the electrochemical signature for HZ such that it is not obscured by that of the ACM (present in excess), the BDD electrode is functionalized with Pt nanoparticles (NPs) to significantly shift the half wave potential for HZ oxidation to less positive potentials. Microstereolithography was used to fabricate flow cells with defined hydrodynamics which minimize dispersion of the analyte and optimize detection sensitivity. Importantly, the Pt NPs were shown to be stable under flow and a limit of detection of 64.5 nM or 0.274 parts per million for HZ with respect to the ACM, present in excess, was achieved. This represents the first electrochemical approach which surpasses the required detection limits set by the pharmaceutical industry for HZ detection in the presence of an API and paves the wave for on-line analysis and application to other GI and API systems.

A miniaturised electrochemical cell design for Electron Paramagnetic Resonance (EPR) studies is reported. The cell incorporates a Loop Gap Resonator (LGR) for EPR investigation of electrochemically generated radicals in aqueous (and other large dielectric loss) samples and achieves accurate potential control for electrochemistry by using micro-wires as working electrodes. The electrochemical behaviour of the cell is analysed with COMSOL finite element models and the EPR sensitivity compared to a commercial TE011 cavity resonator using 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL) as a reference. The electrochemical EPR performance is demonstrated using the reduction of methyl viologen as a redox probe in both water and acetonitrile. The data reported herein suggest that sub-micromolar concentrations of radical species can be detected in aqueous samples with accurate potential control, and that subtle solution processes coupled to electron transfer, such as comproportionation reactions, can be studied quantitatively using EPR.

The design, development and application of high-speed scanning electrochemical probe microscopy is reported. The approach allows the acquisition of a series of high-resolution images (typically 1000 pixels µm-2) at rates approaching 4 s per frame, while collecting up to 8000 image pixels per second, about 1000 times faster than typical imaging speeds used up to now. The focus is on scanning electrochemical cell microscopy (SECCM), but the principles and practicalities are applicable to many electrochemical imaging methods. The versatility of the high-speed scan concept is demonstrated at a variety of substrates, including imaging the electroactivity of a patterned self-assembled monolayer on gold, visualization of chemical reactions occurring at single wall carbon nanotubes and probing nanoscale electrocatalysts for water splitting. These studies provide movies of spatial variations of electrochemical fluxes as a function of potential and a platform for the further development of high speed scanning with other electrochemical imaging techniques.