Review—Electrochemistry's Potential to Reach the Ultimate Sensitivity in Measurement Science

Abstract

A holy grail in analytical chemistry is the specific quantification of a single entity, be that entity an atom, a molecule, a nanoparticle, a virus, or a circulating tumor cell. Analytical chemistry is entering an era where this sensitivity can be achieved. In these experiments, the limit of detection is 1, and the limit of quantitation is not only measured in units of concentration but units of time: the waiting time before positively identifying a single entity. Electrochemistry is front and center in single entity experiments with hundreds of publications per year detailing observations of various entities colliding with micro-and nano-electrodes. These types of experiments are referred to as 'stochastic electrochemistry' due to the stochastic nature of the collision of an entity with an electrode surface. If methods of detection can be made specific, simple, inexpensive, and robust, the techniques hold the promise of transforming diagnostics (i.e., the specific detection of a single cancerous cell in blood). This review will critically analyze the stochastic electrochemistry literature and focus on reports detailing methods to ensure the response at the electrode surface is specific to the colliding entity. The topic of specificity, and strategies to achieve it, are highlighted.

Detection of individual insulating entities by electrochemical blocking

“…A large variety of "target" has been observed by single entity electrochemistry like polystyrene microbeads, metal nanoparticles, semiconducting nanoparticles, carbon nanotubes, graphene nanoplatelets and also bio-objects like vesicles, bacteria, virus, DNA and proteins. The size of these objects spans between few nm to several microns and their electronic structure covers the entire spectrum from insulator to metallic behavior [6]. Depending on the nature of the particle and the information sought, several strategies of detection (and their combination) may be used.…”

Real‐time Conversion of Electrochemical Currents into Fluorescence Signals Using 8‐Hydroxypyrene‐1,3,6‐trisulfonic Acid (HPTS) and Amplex Red as Fluorogenic Reporters

“…Such an "optical" amplification mechanism, is in principle amenable to quantitative and time-resolved electron-to-photon transduction, and as such is worthy of interest for e. g. "nano-impact" electrochemistry. [14][15][16][17] In this modern field of research, random collisions of electroactive entities with an ultramicroelectrode surface provoke a sequence of discrete, short (sub msec), and low magnitude (10 pA-10 nA) faradaic pulses, which are typically measured by transimpedance potentiostats. [18,19] However, it is likely that such a direct electrical readout may become impossible for studying much lower intensity pulses or for resolving short-lasting collision events, by lack of sensitivity and/or bandwidth of available current measurers.…”

“…Beyond mere imaging, transduction of electron transfer events into fluorescence also constitutes a very powerful amplification mechanism, since a single‐electron transfer event can result in the emission of thousands of photons by the reporting fluorogenic species. Such an “optical” amplification mechanism, is in principle amenable to quantitative and time‐resolved electron‐to‐photon transduction, and as such is worthy of interest for e. g. “nano‐impact” electrochemistry [14–17] . In this modern field of research, random collisions of electroactive entities with an ultramicroelectrode surface provoke a sequence of discrete, short (sub msec), and low magnitude (10 pA–10 nA) faradaic pulses, which are typically measured by transimpedance potentiostats [18,19] .…”

Nanoimpacts at Active and Partially Active Electrodes: Insights and Limitations

“…New methods are therefore needed to analyze these materials. The electrochemical nanoimpact technique has recently emerged as a means of measuring the properties of individual entities rather than ensembles . This method has recently been used to study particle size, porosity, and heterogenous catalytic rates on a single‐particle basis; these parameters are critically important to the performance of an electrocatalyst.…”

“…This method has recently been used to study particle size, porosity, and heterogenous catalytic rates on a single‐particle basis; these parameters are critically important to the performance of an electrocatalyst. While a wide variety of systems have been analyzed through particle‐electrode impacts, several typical schemes have emerged. In the simplest case, the particle is directly reduced or oxidized upon electrode impact, as in the oxidation of Ag nanoparticles .…”