Drift Subtraction for Fast-Scan Cyclic Voltammetry Using Double-Waveform Partial-Least-Squares Regression

Background-subtracted fast-scan cyclic voltammetry (FSCV) provides a method for detecting molecular fluctuations with high spatiotemporal resolution in the brain of awake and behaving animals. The rapid scan rates generate large background currents that are subtracted to reveal changes in analyte concentration. Although these background currents are relatively stable, small changes do occur over time. These changes, referred to as electrochemical drift, result in background-subtraction artifacts that constrain the utility of FSCV, particularly when quantifying chemical changes that gradually occur over long measurement times (minutes). The voltammetric features of electrochemical drift are varied and can span the entire potential window, potentially obscuring the signal from any targeted analyte. We present a straightforward method for extending the duration of a single FSCV recording window. First, we have implemented voltammetric waveforms in pairs that consist of a smaller triangular sweep followed by a conventional voltammetric scan. The initial, abbreviated waveform is used to capture drift information that can serve as a predictor for the contribution of electrochemical drift to the subsequent full voltammetric scan using partial-least squares regression (PLSR). This double-waveform partial-least-squares regression (DW-PLSR) paradigm permits reliable subtraction of the drift component to the voltammetric data. Here, DW-PLSR is used to improve quantification of adenosine, dopamine, and hydrogen peroxide fluctuations occurring >10 min from the initial background position, both in vitro and in vivo. The results demonstrate that DW-PLSR is a powerful tool for evaluating and interpreting both rapid (seconds) and gradual (minutes) chemical changes captured in FSCV recordings over extended durations.