Single-entity Electrochemistry Research Articles

Single entity electrochemistry and the electron transfer kinetics of hydrazine oxidation

The mechanism and kinetics of the electro-catalytic oxidation of hydrazine by graphene oxide platelets randomly decorated with palladium nanoparticles are deduced using single particle impact electrochemical measurements in buffered aqueous solutions across the pH range 2–11. Both hydrazine, N2H4, and protonated hydrazine N2H5+ are shown to be electroactive following Butler-Volmer kinetics, of which the relative contribution is strongly pH-dependent. The negligible interconversion between N2H4 and N2H5+ due to the sufficiently short timescale of the impact voltammetry, allows the analysis of the two electron transfer rates from impact signals thus reflecting the composition of the bulk solution at the pH in question. In this way the rate determining step in the oxidation of each specie is deduced to be a one electron step in which no protons are released and so likely corresponds to the initial formation of a very short-lived radical cation either in solution or adsorbed on the platelet. Overall the work establishes a generic method for the elucidation of the rate determining electron transfer in a multistep process free from any complexity imposed by preceding or following chemical reactions which occur on the timescale of conventional voltammetry.

Correlated Optical-Electrochemical Measurements Reveal Bidirectional Current Steps for Graphene Nanoplatelet Collisions at Ultramicroelectrodes.

Single-entity electrochemistry has emerged as a powerful tool to study the adsorption behavior of single nanoscale entities one-at-a-time on an ultramicroelectrode surface. Classical single-entity collision studies have focused on the behavior of spherical nanoparticles or entities where the orientation of the colliding entity does not impact the electrochemical response. Here, we report a detailed study of the collision of asymmetric single graphene nanoplatelets onto ultramicroelectrodes. The collision of conductive graphene nanoplatelets on biased ultramicroelectrode surfaces can be observed in an amperometric i-t trace, revealing a variety of current transients (both positive and negative steps). To elucidate the dynamics of nanoplatelet adsorption processes and probe response heterogeneity, we correlated the collision events with optical microscopy. We show that positive steps are due to nanoplatelets coming into contact with the ultramicroelectrode, making an electrical connection, and adsorbing partly on the glass surrounding the ultramicroelectrode. Negative steps occur when nanoplatelets adsorb onto the glass without an electrical connection, effectively blocking flux of ferrocenemethanol to the ultramicroelectrode surface. These measurements allow rigorous quantification of current transients and detailed insights into the adsorption dynamics of asymmetric objects at the nanoscale.

Nanoconfined Electrochemical Sensing of Single Silver Nanoparticles with a Wireless Nanopore Electrode.

Single entity electrochemistry (SEE) has emerged as a promising method for precise measurement and fundamental understanding of the heterogeneity of single entities. Herein, we propose the dual responsive SEE sensing of the silver nanoparticles (AgNPs) collisions through a wireless nanopore electrode (WNE). Given the high temporal resolution and low background noise features, the Faradaic and capacitive currents provide the AgNPs' collision response. The electron transfer between the AgNPs and the electrode surface is identified under a bipolar electrochemical mechanism. Compared to the ultramicroelectrode, multistep oxidation of 30 nm AgNPs is observed due to the decreased interaction of the nanoparticles to the electrode. Moreover, the nanoconfinement of WNE plays a vital role in the repeated capturing of nanoparticles from the nontunneling region into the tunneling region until a complete oxidation. As a comparison, the collision of 5 nm AgNPs with higher interaction at the electrode surface shows great decrease in the multistep events. Thus, we propose a nanoconfined interaction based SEE method which could be used for simultaneously capturing the Faradaic and capacitive response. The nanoconfined interaction based SEE method holds great promise in the better understanding of heterogeneity of single particles.

Revealing Dynamic Rotation of Single Graphene Nanoplatelets on Electrified Microinterfaces.

Nanoparticles interact with a variety of interfaces, from cell walls for medicinal applications to conductive interfaces for energy storage and conversion applications. Unfortunately, quantifying dynamic changes of nanoparticles near interfaces is difficult. While optical techniques exist to study nanoparticle dynamics, motions smaller than the diffraction limit are difficult to quantify. Single-entity electrochemistry has high sensitivity, but the technique suffers from ambiguity in the entity's size, morphology, and collision location. Here, we combine optical microscopy, single-entity electrochemistry, and numerical simulations to elucidate the dynamic motion of graphene nanoplatelets at a gold ultramicroelectrode (radius ∼5 μm). The approach of conductive graphene nanoplatelets, suspended in 10 μM NaOH, to an ultramicroelectrode surface was tracked optically during the continuous oxidation of ferrocenemethanol. Optical microscopy confirmed the nanoplatelet size, morphology, and collision location on the ultramicroelectrode. Nanoplatelets collided on the ultramicroelectrode at an angle, θ, enhancing the electroactive area, resulting in a sharp increase in current. After the collision, the nanoplatelets reoriented to lay flat on the electrode surface, which manifested as a return to the baseline current in the amperometric current-time response. Through correlated finite element simulations, we extracted single nanoplatelet angular velocities on the order of 0.5-2°/ms. These results are a necessary step forward in understanding nanoparticle dynamics at the nanoscale.

In Situ Measuring Partition Coefficient at Intact Nanoemulsions: A New Application of Single-Entity Electrochemistry.

We report a new application of the single-entity electrochemistry (SEE) to in situ measure a partition coefficient at intact nanoemulsions (NEs). The partition coefficient at intact NEs is the most crucial physicochemical property to determine the uptake of delivery molecules inside NEs. It, however, has not been unequivocally elucidated by currently existing techniques based on ex situ measurements. Herein, we apply the single-entity electrochemistry (SEE) to directly and quantitatively measure the partition coefficient at NEs in situ. In this work, we use NEs featured with amphiphilic triblock copolymer (Pluronic F-127) as a model system to extract/preconcentrate 2-aminobiphenyl (2-ABP) dissolved in the water and demonstrate a new application of SEE to in situ quantitatively estimate the amounts of 2-ABP distributed into each intact NE. Our SEE measurements reveal that the partitioning is governed by extraction of 2-ABP inside NEs rather than its adsorption on the NE surface, and this extraction is remarkably efficient with up to ∼8 orders of magnitude of the preconcentration factor, thus leading to the unprecedentedly large partition coefficient of 1.9 (±1.4) × 1010. This result implies that not only the thermodynamic distribution but also the intermolecular interaction of extracted compounds inside NEs could play a significant role in the apparent partition coefficient (P = 1.9 (±1.4) × 1010). The experimentally determined partition coefficient was validated by molecular dynamics (MD) simulations with showing a stabilizing role of intermolecular interaction in the partitioned system. We further verified our methodology with other compounds exhibiting aromatic properties, e.g., ferrocenemethanol. Significantly, our new approach can be readily applicable to investigate practical NEs commercially marketed for drug, food, and cosmetics.

Impact experiments at the Interface between Two Immiscible Electrolyte Solutions (ITIES)

Within the field of single-entity electrochemistry through so-called impact experiments, the use of soft interfaces can be a valuable and advantageous complement to conventional solid microelectrodes, as recently demonstrated for both hard and soft micro- and nanoparticles. Additionally, this approach can offer a new platform for fundamental studies of key aspects of electronic and ionic transfers across liquid–liquid interfaces, with applications in relevant biological, technological and industrial systems. Experimental results with Interfaces between Two Immiscible Electrolyte Solutions (ITIES) are reviewed and discussed under the light of theoretical treatments are here revisited or developed. • The use of ITIES in impact experiments extends the capabilities of this methodology. • Ion and electron transfer-based spikes enable detection of soft and hard particles. • Capacitive and open circuit potential events have also been reported. • Mass transport conditions strongly affect the magnitude and duration of the events. • Challenges and new methodologies are envisaged.

Electrochemical Detection Method Using Serotonin Oxidation inside a Single Human Platelet

An early diagnosis of platelet-related diseases is important for maintaining a healthy human life for blood clotting disorders caused by internal and/or external stimuli. Various technologies based on physics and chemistry have been developed for the detection of platelets. These methods are mainly set up in clinical laboratory and hospitals, cannot be portable, and require both complex pretreatment procedure and expensive detectors for platelet detection. Platelets are one of the human blood compositions and an important role in blood coagulation. Therefore, it is necessary to develop a method that can be adopted as a medical device capable of diagnosis in everyday life. We proposed an electrochemical collision method for direct detection of serotonin in a single platelet from human blood. This method is based on collisions of platelets with an ultramicroelectrode (UME) and observed the oxidation signal of serotonin without any modification of electrode through single-entity electrochemistry (SEE). When a platelet collides with the UME, secreted serotonin from the platelet gets oxidized at the electrode surface generating anodic currents. In our methods, the current for effective detection of platelets is very sensitive because there is no redox species. Studies on biomolecule detection through SEE can be useful for measuring the number of blood cells in our blood. Observing changes in the current that occur when platelets selectively collide with the UME, is medically useful information obtained cheaply and easily. The SEE method applied to blood analysis will be a new way to overcome the limitations of the existing sampling process, analysis time and environment. It is also expected to contribute to the development of high-performance sensors based on point-of-care-testing (POCT) devices capable of on-site and real-time diagnosis.

Electrochemical Detection of Individual Catalytic and Redox-Inactive Materials

Using low noise electronics and micro-electrodes we can now detect single analytes in solution, one at a time.1,2 In this talk, we will briefly cover recent discoveries in the field of single entity electrochemistry and show that both electroactive and electro-inactive materials can be detected using complementary approaches.3,4 However, some strong limitations in this field persist. In the case of electroactive entities, in order to detect the single entity above the electrochemical noise level, a careful choice of the analyte that differs in its physical properties from the electrode is needed. Here, we show that an active particle-active electrode composed of the same material can provide mechanistic insight into electrochemical reactions.5 Current transients obtained during hydrogen evolution allow simultaneous measurement of the Pt catalyst over different length scales, size dependency suggests H atom intercalation as a catalytic deactivation mechanism.In the case of redox-inactive materials, a different analytical problem exists. The location of the adsorbed individual material at the electrode surface influences the magnitude of the electrochemical signal being blocked during a steady-state flux of a redox probe towards the electrode.6,7 Our recent discovery shows that coupling the electrochemical reaction to a homogeneous rate-limiting chemical reaction offers a platform for high precision measurements. Using both finite element simulations and experimental statistical analysis we provide guiding rules for sizing redox-inactive materials with high analytical precision under various conditions such as analyte and electrode size and analyte concentration.

In Situ Monitoring of Collision and Recollision Events of Single Attoliter Droplets via Single-Entity Electrochemistry.

We describe a simple method for real-time observation of collision and recollision behavior of a single aqueous attoliter droplet in an organic solvent through single-entity electrochemistry. The dynamics and morphology of the droplet after the collision event at the Au ultramicroelectrode (Au-UME) were monitored by consecutive cyclic voltammetry and amperometric current-time measurements. By sequentially applying oxidative potential and reductive potential at the Au-UME in the presence of attoliter droplets containing reversible redox species (e.g., ferrocyanide), we successfully detected the oxidative collision spike and its reductive recollision spike successively owing to the reversible redox reactions inside the droplet. Because the redox species was dissolved in a reduced form, the reductive collision spikes observed are the direct evidence that the water droplets colliding at the electrode surface are detached after the oxidation reaction. The collided droplet properties, such as size change and contact area, are also investigated and discussed.

The role of macromolecular crowding in single-entity electrochemistry: Friend or foe?

The recent development of nanoscale probes has enabled the study of single molecules and single cells with unprecedented resolution and the expansion of the field of single-entity electrochemistry. There is a growing evidence suggesting that highly crowded intracellular environment facilitate nanoelectrochemical measurements in cells by improving the signal-to-noise ratio. In this opinion piece, we discuss the concept of macromolecular crowding and its implications in single-entity electrochemistry. • The macromolecular crowding of the intracellular environment plays a crucial role in regulating cellular physiology. • Single-entity electrochemistry is enabling high-resolution intracellular measurements. • In vitro macromolecular crowding enhances the detection of single entities.

Towards ultralow detection limits of aromatic toxicants in water using pluronic nanoemulsions and single-entity electrochemistry

We demonstrate a new electroanalytical technique using nanoemulsions (NEs) as a nanoextractor combined with single entity electrochemistry (SEE) to separate, preconcentrate analytes from bulk media, and even detect them in situ, enabling ultratrace level analysis. This approach is based on our hypothesis that the custom-designed NEs would enable to effectively scavenge compounds from bulk media. Herein, we use Pluronic F-127 functionalized NEs to extract, preconcentrate target analytes e.g., ferrocene derivatives as a model aromatic toxicant dissolved in the water, and employ SEE to in situ detect and quantitatively estimate analytes extracted in individual NEs. Extraction was markedly efficient to reach ∼8 orders of magnitude of preconcentration factor under the true equilibrium, thereby enabling ultratrace level analysis with a detection limit of ∼0.2 ppb. The key step to attain high sensitivity in our measurements was to modulate the total amount of added NEs respect to the total volume of bulk solution, thereby controlling the extracted amount of analytes in each NE. Our approach is readily applicable to investigate other aromatic toxicants dissolved in the water, thus detecting hazardous carcinogen, 2-aminobiphenyl in the water up to ∼0.1 ppb level. Given the excellent detection performance as well as the broad applicability for ubiquitous aromatic contaminants, the combination of NEs with SEE offers great prospects as a sensor for environmental applications.

Electrodeposition in aqueous nanoreactors

One frontier of measurement science is pushing the limit of what is measurable. Nanoelectrochemistry has transformed what is measurable at the nanoscale, elucidating reactivity of single atoms, molecules, and nanoparticles, one by one. The ability to interrogate physicochemical properties of single entities has elucidated new truths of nature that are otherwise averaged out during measurements over many entities (ensemble experiments). Single-entity experiments also give access to the ultimate sensitivity in measurement science: the specific detection of one single entity (not nanomolar quantities, not picomolar quantities—one single unit). One exciting subset of single-entity electrochemistry, and the topic of this review, is the study of reactions in nanoreactors of subfemtoliter (10−15 L) volumes with a particular focus on nanoparticle synthesis.

Stochasticity in Single-Entity Electrochemistry.

Most electrochemical processes are stochastic and discrete in nature. Yet experimental observables, e.g., i vs E, are typically smooth and deterministic, due to many events/processes, e.g., electron transfers, being averaged together. However, when the number of entities measured approaches a few or even one, stochasticity frequently emerges. Yet all is not lost! Probabilistic and statistical interpretation can generate insights matching or superseding those from macroscale/ensemble measurements, revealing phenomena that were hitherto averaged over. Herein, we review recent literature examples of stochastic processes in single-entity electrochemistry, highlighting strategies for interpreting stochasticity, contrasting them with macroscale measurements, and describing the insights generated.

Detection of individual insulating entities by electrochemical blocking

Electrochemical blocking is a type of single-entity electrochemical measurement particularly well adapted to the detection of insulating particles. The digital detection of ultralow concentrations of artificial entities such as polymer particles or biotargets such as proteins and bacteria represents an exceptional opportunity for sensing applications. In this review, we explore the latest development in the field of electrochemical blocking and propose some perspectives. • Electrochemical blocking is sensitive enough to sense individual proteins. • Single-entity electrochemistry may be used to detect subattomolar concentrations of particles. • The size of spherical particles can be estimated within about 10% of error by electrochemical blocking.

Determination of Serotonin Concentration in Single Human Platelets through Single-Entity Electrochemistry.

This research introduces a method to directly detect serotonin in a single platelet through single-entity electrochemistry. Platelets isolated from human blood were analyzed by cyclic voltammetry and current-time measurements. When a single platelet collides with an ultramicroelectrode, serotonin inside the platelet is oxidized at the electrode surface, and an anodic current peak is consequently observed during measurement. The concentration of serotonin can be determined by integrating this peak current. In addition, this method can be used to determine the platelet concentration. Analysis of the collision frequency of platelets can provide information about the platelet concentration in the blood. As a result, platelet levels and serotonin concentrations in single platelets can be measured quickly and easily.

Scanning electrochemical cell microscopy: A natural technique for single entity electrochemistry

Scanning electrochemical cell microscopy (SECCM) is a robust and versatile scanning electrochemical probe microscopy technique that allows direct correlation of structure–activity at the nanoscale. SECCM uses a mobile droplet cell to investigate and visualize electrochemical activity at interfaces with high spatiotemporal resolution, while also providing topographical information. This article highlights diverse contemporary challenges in the field of single entity electrochemistry tackled by the increasing uptake of SECCM globally. Various applications of SECCM in single entity electrochemistry are featured herein, including electrocatalysis, electrodeposition, corrosion science and materials science, with electrode materials spanning particles, polymers, two-dimensional materials and complex polycrystalline substrates. The use of SECCM for patterning structures is also highlighted.

Exploring dynamic interactions of single nanoparticles at interfaces for surface-confined electrochemical behavior and size measurement

With the development of new instruments and methodologies, the highly dynamic behaviors of nanoparticle at the liquid-solid interface have been studied. However, the dynamic nature of the electrochemical behavior of individual nanoparticles on the electrode interface is still poorly understood. Here, we generalize scaling relations to predict nanoparticle-electrode interactions by examining the adsorption energy of nanoparticles at an ultramicroelectrode interface. Based on the theoretical predictions, we investigate the interaction-modulated dynamic electrochemical behaviors for the oxidation of individual Ag nanoparticles. Typically, significantly distinct current traces are observed owing to the adsorption-mediated motion of Ag nanoparticles. Inspired by restraining the stochastic paths of particles in the vicinity of the electrode interface to produce surface-confined current traces, we successfully realize high-resolution size measurements of Ag nanoparticles in mixed-sample systems. This work offers a better understanding of dynamic interactions of nanoparticles at the electrochemical interface and displays highly valuable applications of single-entity electrochemistry.

Nitrogen Bubbles at Pt Nanoelectrodes in a Nonaqueous Medium: Oscillating Behavior and Geometry of Critical Nuclei.

Gas bubble evolution is present in many electrochemical and photoelectrochemical processes. We previously reported the formation of individual H2, N2, and O2 nanobubbles generated from electrocatalytic reduction of H+ and oxidation of N2H4 and H2O2, respectively, at Pt nanodisk electrodes in an aqueous solution. All the nanobubbles formed display a dynamic stationary state of a three-phase boundary with an invariant residual current. Here, we test the hypothesis that gas nanobubbles can also be electrogenerated in a nonaqueous medium. Interestingly, we found oscillating bubble behavior corresponding to nucleation, growth, and dissolution in dimethyl sulfoxide and methanol. One possible explanation of the oscillation mechanism is provided by the instable dynamic equilibrium between the gas influx due to supersaturation and outflux due to Laplace pressure. Furthermore, the critical gas concentrations for N2 nanobubble nucleation are estimated to be 148, 386, 200, and 16 times supersaturation and the contact angles of the critical nuclei to be 164°, 151°, 160°, and 174° in water, dimethyl sulfoxide, ethylene glycol, and methanol, respectively. This is the first report on electrochemical nucleation of gas bubbles in nonaqueous solvents. Our electrochemical gas bubble study based on a nanoelectrode platform has proven to be a prototypical example of single-entity electrochemistry.

Single-entity electrochemistry at confined sensing interfaces

Measurements at the single-entity level provide more precise diagnosis and understanding of basic biological and chemical processes. Recent advances in the chemical measurement provide a means for ultra-sensitive analysis. Confining the single analyte and electrons near the sensing interface can greatly enhance the sensitivity and selectivity. In this review, we summarize the recent progress in single-entity electrochemistry of single molecules, single particles, single cells and even brain analysis. The benefits of confining these entities to a compatible size sensing interface are exemplified. Finally, the opportunities and challenges of single entity electrochemistry are addressed.

One-to-Many Single Entity Electrochemistry Biosensing for Ultrasensitive Detection of microRNA.

Single-entity electrochemistry (SEEC), a promising method for biosensing, has an intrinsic limitation on sensitivity since at most one colliding entity can be successfully triggered by one target. Here, we take advantage of one-to-many (1:n) signal amplification to develop a new single-entity electrochemistry biosensing (SEECBS), integrating satellite magnetic nanoparticle (MN)-DNA-Pt nanoparticle (NP) conjugates, duplex-specific nuclease (DSN) assisted Pt NPs releasing with stabilization, and effective collision of small sized and nearly naked Pt NPs. Compared with conventional SEECBS, the 1:n SEECBS can successfully enrich ∼2 nM Pt NPs by adding 50 aM microRNA (miRNA), in other words, ∼4 × 107 Pt NPs can be triggered by one target. The proposed SEECBS allows the detection of 47 aM miRNA-21, nearly 6 orders of magnitude lower than the previous work, and discrimination of nontarget miRNAs containing even single-nucleotide mismatch. Besides, this method has also been successfully demonstrated for quantification of miRNA in different cell lines. Therefore, the proposed method holds great potential for the application of SEECBS in early diagnosis and prognosis monitoring of cancer.