Continuous Square Wave Voltammetry for High Information Content Interrogation of Conformation Switching Sensors

[Image: see text] Square wave voltammetry (SWV) is a voltammetric technique for measuring Faradaic current while minimizing contributions from non-Faradaic processes. In square wave voltammetry, the potential waveform applied to a working electrode and the current sampling protocols followed are designed to minimize contributions from non-Faradaic processes (i.e., double layer charging) to improve voltammetric sensitivity. To achieve this, the current is measured at the end of each forward and reverse potential pulse after allowing time for non-Faradaic currents to decay exponentially. A consequence of sampling current at the end of a potential pulse is that the current data from the preceding time of the potential pulse are discarded. These discarded data can provide information about the non-Faradaic contributions as well as information about the redox system including charge transfer rates. In this paper, we introduce continuous square wave voltammetry (cSWV), which utilizes the continuous collection of current to maximize the information content obtainable from a single voltammetry sweep eliminating the need for multiple scans. cSWV enables acquiring a multitude of voltammograms corresponding to various frequencies and, thus, different scan rates from a single sweep. An application that benefits significantly from cSWV is conformation switching, functional nucleic acid sensors. We demonstrate the utility of cSWV on two representative small molecules targeting electrochemical, aptamer-based sensors. Moreover, we show that cSWV provides comparable results to those obtained from traditional square wave voltammetry, but with cSWV, we are able to acquire dynamic information about the sensor surfaces enabling rapid calibration and optimization of sensing performance. We also demonstrate cSWV on soluble redox markers. cSWV can potentially become a mainstay technique in the field of conformation switching sensors.