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

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.