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The development of nanoscale electrochemistry since the mid-1980s has been predominately coupled with steady-state voltammetric (i-E) methods. This research has been driven by the desire to understand the mechanisms of very fast electrochemical reactions, by electroanalytical measurements in small volumes and unusual media, including in vivo measurements, and by research on correlating electrocatalytic activity, e.g., O2 reduction reaction, with nanoparticle size and structure. Exploration of the behavior of nanoelectrochemical structures (nanoelectrodes, nanoparticles, nanogap cells, etc.) of a characteristic dimension λ using steady-state i-E methods generally relies on the well-known relationship, λ2 ∼ Dt, which relates diffusional lengths to time, t, through the coefficient, D. Decreasing λ, by performing measurements at a nanometric length scales, results in a decrease in the effective timescale of the measurement, and provides a direct means to probe the kinetics of steps associated with very rapid electrochemical reactions. For instance, steady-state voltammetry using a nanogap twin-electrode cell of characteristic width, λ ∼ 10 nm, allows investigations of events occurring at timescales on the order of ∼100 ns. Among many other advantages, decreasing λ also increases spatial resolution in electrochemical imaging, e.g., in scanning electrochemical microscopy, and allows probing of the electric double layer. This Introductory Lecture traces the evolution and driving forces behind the "λ2 ∼ Dt" steady-state approach to nanoscale electrochemistry, beginning in the late 1950s with the introduction of the rotating ring-disk electrode and twin-electrode thin-layer cells, and evolving to current-day investigations using nanoelectrodes, scanning nanocells for imaging, nanopores, and nanoparticles. The recent focus on so-called "single-entity" electrochemistry, in which individual and very short redox events are probed, is a significant departure from the steady-state approach, but provides new opportunities to probe reaction dynamics. The stochastic nature of very fast single-entity events challenges current electrochemical methods and modern electronics, as illustrated using recent experiments from the authors' laboratory.

We report a case series of ozonated autohemotherapy of four COVID-19 patients, classified as critically ill (1 patient), severe (1 patient), and moderate (2 patients). Each ozonated autohemotherapy treatment was performed at a concentration of 40 μg/ml of ozone per 100 ml of blood. The number of treatments varied from 1 to 9 depending on the disease severity. All 4 patients, including 1 critically ill patient with severe acute respiratory distress syndrome (ARDS) and life-threatening refractory hypoxemia, recovered uneventfully and were discharged from the hospital after viral clearance. The younger sibling of the critically ill patient was also diagnosed with COVID-19 and developed ARDS with hypoxemia, who received mechanical ventilation through an endotracheal tube and extracorporeal membrane oxygenation (ECMO) support. The overall medical cost for 18 days spent in the intensive care unit (ICU) and 56 days of hospitalization was $139,935 USD. On the other hand, our critically ill patient underwent 9 ozonated autohemotherapy treatments and spent 10 days in the ICU and was discharged on hospital day 30; his hospitalization cost amounted to $15,466.50 USD. This case series suggests that ozonated autohemotherapy may be an alternative noninvasive medical treatment for COVID-19 patients.

Biological nanopores provide a unique single-molecule sensing platform to detect target molecules based on their specific electrical signatures. The γ-hemolysin (γ-HL) protein produced by Staphylococcus aureus is able to assemble into an octamer nanopore with a ~2.3 nm diameter β-barrel. Herein, we demonstrate the first application of γ-HL nanopore for DNA structural analysis. To optimize conditions for ion-channel recording, the properties of the γ-HL pore (e.g., conductance, voltage-dependent gating, ion-selectivity) were characterized at different pH, temperature, and electrolyte concentrations. The optimal condition for DNA analysis using γ-HL corresponds to 3 M KCl, pH = 5, and T = 20 ⁰C. The γ-HL protein nanopore is able to translocate dsDNA at about ~20 bp/ms, and the unique current-signature of captured dsDNA can directly distinguish guanine-to-inosine substitutions at the single-molecule level with ~99% accuracy. The slow dsDNA threading and translocation processes indicate this wild-type γ-HL channel has potential to detect other base modifications in dsDNA.