Capture and Detection of Aerosolized Fentanyl in a Suspended Electrochemical Cell.

Fentanyl is an extremely potent opioid that is commonly laced into other drugs. Fentanyl poses a danger to users but also to responders or bystanders who may unknowingly ingest a lethal dose (∼2 mg) of fentanyl from aerosolized powder or vapor. Electrochemistry offers a small, simple, and affordable platform for the direct detection of illicit substances; however, it is largely limited to solution-phase measurements. Here, we demonstrate the hands-free capture and electroanalyzation of aerosols containing fentanyl. A novel electrochemical cell is constructed by a microwire (cylindrical working electrode) traversing an ionic liquid film that is suspended within a conductive loop (reference/counter electrode). We provide a quantitative finite element simulation of the resulting electrochemical system. The suspended film maintains a high-surface area:volume, allowing the electrochemical cell to act as an effective aerosol collector. The low vapor pressure (negligible evaporation) of ionic liquid makes it a robust candidate for in-field applications, and the use of a hydrophobic ionic liquid allows for the extraction of fentanyl from solids and sprayed aqueous aerosols.

An Electrochemical Perspective on Reaction Acceleration in Droplets.

Analytical techniques operating at the nanoscale introduce confinement as a tool at our disposal. This review delves into the phenomenon of accelerated reactivity within micro- and nanodroplets. A decade of accelerated reactivity observations was succeeded by several years of fundamental studies aimed at mechanistic enlightenment. Herein, we provide a brief historical context for rate enhancement in micro- and nanodroplets and summarize the mechanisms that have been proposed to contribute to such extraordinary reactivity. We highlight recent electrochemical reports that make use of restricted mass transfer to enhance electrochemical reactions and/or quantitatively measure reaction rates within droplet-confined electrochemical cells. A comprehensive approach to nanodroplet reactivity is paramount to understanding how nature takes advantage of these systems to provide life on Earth and, in turn, how to harness the full potential of such systems.

Single Liquid Aerosol Microparticle Electrochemistry on a Suspended Ionic Liquid Film.

Liquid aerosols are ubiquitous in nature, and several tools exist to quantify their physicochemical properties. As a measurement science technique, electrochemistry has not played a large role in aerosol analysis because electrochemistry in air is rather difficult. Here, a remarkably simple method is demonstrated to capture and electroanalyze single liquid aerosol particles with radii on the order of single micrometers. An electrochemical cell is constructed by a microwire (cylindrical working electrode) traversing a film of ionic liquid (1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide) that is suspended within a wire loop (reference/counter electrode). An ionic liquid is chosen because the low vapor pressure preserves the film over weeks, vastly improving suspended film electroanalysis. The resultant high surface area allows the suspended ionic liquid cell to act as an aerosol net. Given the hydrophobic nature of the ionic liquid, aqueous aerosol particles do not coalesce into the film. When the liquid aerosols collide with the sufficiently biased microwire (creating a complex boundary: aerosol|wire|ionic liquid|air), the electrochemistry within a single liquid aerosol particle can be interrogated in real-time. The ability to achieve liquid aerosol size distributions for aerosols over 1 µm in radius is demonstrated.

Femtoliter oil droplets act as CO2 micropumps for uninterrupted electrochemiluminescence at the water|oil interface.

Interfacial effects are well-known to significantly alter chemical reactivity, especially in confined environments, where the surface to volume ratio increases. Here, we observed an inhomogeneity in the electrogenerated chemiluminescence (ECL) intensity decrease over time in a multiphasic system composed of femtoliter water droplets entrapping femtoliter volumes of the 1,2-dichloroethane (DCE) continuous phase. In usual electrochemiluminescence (ECL) reactions involving an ECL chromophore and oxalate ([C2O4]2-), the build-up of CO2 diminishes the ECL signal with time because of bubble formation. We hypothesised that relative solubilities of chemical species in these environments play a dramatic role in interfacial reactivity. Water droplets, loaded with the ECL luminophore [Ru(bpy)3]2+ and the coreactant [C2O4]2- were allowed to stochastically collide and adsorb at the surface of a glassy carbon macroelectrode. When water droplets coalesce on the surface, they leave behind femtoliter droplets of the DCE phase (inclusions). We report the surprising finding that the addition of multiple interfaces, due to the presence of continuous phase's femtoliter inclusions, allows sustained ECL over time after successive potential applications at the triple-phase boundary between water droplet|electrode|DCE inclusion. When femtoliter droplets of DCE form on the electrode surface, bright rings of ECL are observed during the simultaneous oxidation of [Ru(bpy)3]2+ and [C2O4]2-. Control experiments and finite element modelling allowed us to propose that these rings arise because CO2 that is generated near the 1,2-dichloroethane droplet partitions in due to relative solubility of CO2 in 1,2-dichloroethane and builds up and/or is expelled at the top of the droplet. The small droplets of the DCE phase act as micropumps, pumping away carbon dioxide from the interface. These results highlight the unexpected point that confined microenvironments and their geometry can tune chemical reactions of industrial importance and fundamental interest.

Multiphase Chemistry under Nanoconfinement: An Electrochemical Perspective.

Most relevant systems of interest to modern chemists rarely consist of a single phase. Real-world problems that require a rigorous understanding of chemical reactivity in multiple phases include the development of wearable and implantable biosensors, efficient fuel cells, single cell metabolic characterization techniques, and solar energy conversion devices. Within all of these systems, confinement effects at the nanoscale influence the chemical reaction coordinate. Thus, a fundamental understanding of the nanoconfinement effects of chemistry in multiphase environments is paramount. Electrochemistry is inherently a multiphase measurement tool reporting on a charged species traversing a phase boundary. Over the past 50 years, electrochemistry has witnessed astounding growth. Subpicoampere current measurements are routine, as is the study of single molecules and nanoparticles. This Perspective focuses on three nanoelectrochemical techniques to study multiphase chemistry under nanoconfinement: stochastic collision electrochemistry, single nanodroplet electrochemistry, and nanopore electrochemistry.

The Microelectrode Insulator Influences Water Nanodroplet Collisions.

Studying chemical reactions in very small (attoliter to picoliter) volumes is important in understanding how chemistry proceeds at all relevant scales. Stochastic electrochemistry is a powerful tool to study the dynamics of single nanodroplets, one at a time. Perhaps the most conceptually simple experiment is that of the current blockade, where the collision of an insulating particle is observed electrochemically as a stepwise decrease in current. Here, we demonstrate that nanodroplet collisions on microelectrodes are not as simple as water droplets adsorbing to the electrode to block current and that the environment immediately around the microelectrode (glass insulator) plays a pivotal role in the electrochemical collision response. We use correlated opto-electrochemical measurements to understand a variety of electrochemical responses when water nanodroplets collide with a microelectrode during the heterogeneous oxidation of decamethylferrocene in oil. The amperometric current reports not only on current blockades but also on nanodroplet coalescence events and preferential wetting to the glass around the microelectrode. Treating the glass with dichlorodimethylsilane creates a hydrophobic environment around the working electrode, and the simple current blockade response expected from the absorption of insolating nanoparticles is observed. These results highlight the importance of the environment around the working electrode for nanodroplet collision studies.

Reagentless Voltammetric Identification of Cocaine from Complex Powders.

Cocaine is one of the most commonly trafficked and abused drugs in the United States, and deployable field tests are important for rapid identification in nonlaboratory settings. At present, colorimetric tests exist for in-field determination, but these fundamentally suffer from interferent effects. Cocaine is an organic salt that is readily water soluble as a cation and almost insoluble in the deprotonated neutral form. Here, we take advantage of the electrochemical window of water to increase the pH at the electrode surface by driving water reduction, effectively electroprecipitating the cocaine base. The precipitate on the electrode surface is then electrochemically oxidized by a voltammetric sweep through sufficiently positive potentials. We demonstrate excellent selectivity to cocaine compared to common adulterants, such as procaine, lidocaine, benzocaine, caffeine, and levamisole. Finally, we detect cocaine on a carbon fiber microelectrode, demonstrating miniaturizability and allowing access to low-resistance media (e.g., tap water).

Oxidation of Cysteine by Electrogenerated Hexacyanoferrate(III) in Microliter Droplets.

Chemical reactivity in droplets is often assumed to mimic reactivity in bulk, continuous water. Here, we study the catalytic oxidation of cysteine by electrogenerated hexacyanoferrate(III) in microliter droplets. These droplets are adsorbed onto glassy carbon macroelectrodes and placed into an immiscible 1,2-dichloroethane phase. We combined cyclic voltammetry, optical microscopy, and finite element simulations to quantify the apparent bimolecular rate constant, kc,app, in microdroplets and bulk water. Statistical analyses reveal that the apparent bimolecular rate constant (kc,app) values formicrodroplets are larger than those in the continuous phase. Reactant adsorption to the droplet boundary has previously been implicated as the cause of such rate accelerations. Finite element modeling of this system suggests that molecular adsorption to the liquid|liquid interface cannot alone account for our observations, implicating kinetics of the bimolecular reaction either at the boundary or throughout the microliter volume. Our results indicate that cysteine oxidation by electrogenerated hexacyanoferrate(III) can be accelerated within a microenvironment, which may have profound implications on understanding biological processes within a cell.

Detecting Methamphetamine in Aerosols by Electroanalysis in a Soap Bubble Wall.

We present a facile method to detect methamphetamine in aerosols by trapping aerosols in a soap bubble wall for electroanalysis. A microwire was placed through a soap bubble wall as a sensing electrode along with a 1 mm diameter platinum wire as the counter/reference electrode. The resulting electrochemical cell and electrode geometry are unique and allow for reproducible electrochemistry between bubble walls. We first provide a thorough investigation of the cell and electrode geometry and an electrochemical characterization of ferrocene methanol in a soap bubble wall composed of 0.1 M KCl and 0.1% Triton X-100 (v/v). To visualize the boundary where the bubble wets the microwire (the effective electrode area) with tens of nanometer resolution, we electrodeposited platinum on carbon microwire. Scanning electron microscopy and energy dispersive X-ray spectroscopy revealed the bubble contact (i.e., cylindrical electrode height) is 157 ± 30 µm. Correlated digital microscopy suggests that the wetting reaches r ∼ 125 µm along the bubble wall laterally from the microwire. Beyond the wetting region, the bubble thickness is 18 ± 1 µm, as indicated by ultraviolet-visible spectroscopy experiments probing dissolved bis(bipyridine)ruthenium(II) chloride. We illustrate that the voltammetric character in this system is highly dependent on the bubble wetting parameters, which are tuned by changing the microwire material. We then applied this system to the collection and electrochemical detection of methamphetamine in liquid aerosols, where the bubble wall acts as a low volume collector.

Electrochemical quantification of accelerated FADGDH rates in aqueous nanodroplets.

Enzymes are molecules that catalyze reactions critical to life. These catalysts are often studied in bulk water, where the influence of water volume on reactivity is neglected. Here, we demonstrate rate enhancement of up to two orders of magnitude for enzymes trapped in submicrometer water nanodroplets suspended in 1,2-dichloroethane. When single nanodroplets irreversibly adsorb onto an ultramicroelectrode surface, enzymatic activity is apparent in the amperometric current-time trace if the ultramicroelectrode generates the enzyme cofactor. Nanodroplet volume is easily accessible by integrating the current-time response and using Faraday's Law. The single nanodroplet technique allows us to plot the enzyme's activity as a function of nanodroplet size, revealing a strong inverse relationship. Finite element simulations confirm our experimental results and offer insights into parameters influencing single nanodroplet enzymology. These results provide a framework to profoundly influence the understanding of chemical reactivity at the nanoscale.

Single enzyme electroanalysis.

Traditional studies of enzymatic activity rely on the combined kinetics of millions of enzyme molecules to produce a product, an experimental approach that may wash out heterogeneities that exist between individual enzymes. Evaluating these properties on an enzyme-by-enzyme basis represents an unambiguous means of elucidating heterogeneities; however, the quantification of enzymatic activity at the single-enzyme level is fundamentally limited by the maximum catalytic rate, kcat, inherent to a given enzyme. For electrochemical methods measuring current, single enzymes must turn over greater than 107 molecules per second to produce a measurable signal on the order of 10-12 A. Enzymes with this capability are extremely rare in nature, with typical kcat values for biologically relevant enzymes falling between 1 and 10 000 s-1. Thus, clever amplification strategies are necessary to electrochemically detect the vast majority of enzymes. This review details the progress toward the electroanalytical detection and evaluation of single enzyme kinetics largely focused on the nanoimpact method, a chronoamperometric detection strategy that monitors the change in the current-time profile associated with stochastic collisions of freely diffusing entities (e.g., enzymes) onto a microelectrode or nanoelectrode surface. We discuss the experimental setups and methods developed in the last decade toward the quantification of single molecule enzymatic rates. Special emphasis is given to the limitations of measurement science in the observation of single enzyme activity and feasible methods of signal amplification with reasonable bandwidth.

Enzyme Kinetics via Open Circuit Potentiometry.

We demonstrate the application of open circuit potentiometry (OCP) to measure enzyme turnover kinetics, kturn. The electrode surface will become poised by the addition of a well-behaved redox pair, such as ferrocenemethanol/ferrocenium methanol (FcMeOH/FcMeOH+), which acts as the cosubstrate for the enzymatic process. A measurable change in potential results when an enzyme consumes the one-electron transfer mediator. Glucose oxidase was studied as a test-case, but the method is generalizable across oxidoreductase enzymes that rely on electron transfer mediators. In the presence of glucose and FcMeOH+, glucose oxidase delivers electrons to FcMeOH+, and the potential changes with respect to the Nernst equation. A theoretical model incorporating enzymatic rate expressions into the Nernst equation was derived to explain the observed potential transients, and experimental data fit theory well. A similar experiment was performed using amperometry on ultramicroelectrodes (UMEs). Here, the same enzymatic rate expression may be incorporated into the equation for steady-state flux to an UME to obtain kturn. While similar kinetic information was obtained from the potentiometric and amperometric responses, potentiometry is independent of electrode size and mass transfer effects. Finally, we show how kturn changes as a function of one-electron mediator. Our results may eventually find applications to biosensors, where electrode fouling plagues long-term sensor performance.