How does an electrochemical sensor turn a molecule into a signal?

A molecule in a sample has no idea it is being measured. To an electrochemical sensor, though, many molecules carry a built-in signature: at a certain electrical potential they can give up electrons (oxidation) or accept them (reduction). An electrochemical sensor turns that electron transfer into a current that we can measure, and that current tells us both what is there and how much of it.

Redox: where the signal comes from

Oxidation and reduction (redox) reactions move electrons between a molecule and an electrode surface. When an electroactive molecule reaches the electrode and the applied potential is high (or low) enough, electrons start to flow through the external circuit. More molecules reacting per second means a larger current. Under well-controlled conditions, this current is proportional to the concentration of the molecule in the solution, which is what makes quantitative analysis possible.

Three electrodes, three jobs

1. Working electrode: the surface where the reaction of interest takes place. Its material and surface (for example carbon, gold or a modified layer) decide how well the target reacts.

2. Reference electrode: a stable reference point (for example Ag/AgCl) against which the working-electrode potential is controlled.

3. Counter electrode: closes the electrical circuit and carries the current, so that the reference electrode does not have to.

An instrument called a potentiostat applies the potential between the working and reference electrodes and measures the current that flows between the working and counter electrodes.

Illustration: a three-electrode cell and a schematic differential-pulse-type voltammetric peak (not real data).

CV, DPV and SWV in plain words

A useful analogy is tuning an old radio. Sweeping the potential is like turning the dial: each molecule "broadcasts" at its own potential, and how loud the signal is tells you how much of it is present.

• Cyclic voltammetry (CV): the potential is swept forward and then back. The resulting plot shows where oxidation and reduction happen and how reversible the process is, so CV is mainly used to study a molecule's electrochemical behaviour.

• Differential pulse voltammetry (DPV): small potential pulses are applied on a slowly rising baseline, and the current is sampled just before and at the end of each pulse. Taking the difference reduces the background (charging) current, so the analyte appears as a sharp, well-defined peak.

• Square-wave voltammetry (SWV): a square-wave signal is applied on a staircase; forward and reverse currents are combined into one peak. It is fast and sensitive, which makes it popular for trace analysis.

In pulse techniques, the peak position helps identify the molecule, and the peak height (or area) is related to its concentration through a calibration curve made with standards.

Key takeaways

• Electrochemical sensors measure the electrons a molecule exchanges at an electrode surface.

• A three-electrode cell separates the jobs of reacting, referencing and carrying current.

• CV is used to understand a molecule; DPV and SWV are usually preferred to quantify it at low levels.

Voltammetry at SAOnS Lab

At SAOnS Lab, voltammetry is a daily tool: we study the electrochemical behaviour of drugs and biomarkers and develop voltammetric methods to measure them in pharmaceutical and biological samples. One example from our group is a study of the electrochemical behaviour of the drug ruxolitinib and its voltammetric assay in a drug product and human serum using different solid electrodes (Bilge et al., 2022).

Which voltammetric technique do you use most, and why? Get in touch with us to share your experience.

References

Elgrishi, N., Rountree, K., McCarthy, B. D., et al. (2018). A practical beginner's guide to cyclic voltammetry. Journal of Chemical Education, 95(2), 197–206. https://doi.org/10.1021/acs.jchemed.7b00361

Sandford, C., Edwards, M. A., Klunder, K. J., et al. (2019). A synthetic chemist's guide to electroanalytical tools for studying reaction mechanisms. Chemical Science, 10(26), 6404–6422. https://doi.org/10.1039/c9sc01545k

Bilge, S., Karadurmuş, L., Atıcı, E. B., et al. (2022). Electrochemical investigation of ruxolitinib: Sensitive voltammetric assay in drug product and human serum by using different solid electrodes. Electroanalysis, 34(8), 1318–1328. https://doi.org/10.1002/elan.202100625