Maximizing Electrochemical Information: A Perspective on Background-Inclusive Fast Voltammetry

Abstract

This perspective encompasses a focused review of the literature leading to a tipping point in electroanalytical chemistry. We tie together the threads of a "revolution" quietly in the making for years through the work of many authors. Long-held misconceptions about the use of background subtraction in fast voltammetry are addressed. We lay out future advantages that accompany background-inclusive voltammetry, particularly when paired with modern machine-learning algorithms for data analysis.

Figure 1

Predictive drift modeling generalizes in vivo. Reproduced from Meunier, C. J.; McCarty, G. S.; Sombers, L. A. Anal. Chem. 2019, 91, 7319–7327 (ref (24)). Copyright 2019, American Chemical Society.

Figure 2

(A) Test set performance using an FSCV-PCR model trained on background-subtracted voltammograms for varying dopamine concentrations at pH 7.4 and (B) versus varying pH at constant dopamine (0 nM). (C,D) The same test set performance using an FSCV-elastic net model trained on nonbackground-subtracted data. Reproduced from Kishida, K. T.; Saez, I.; Lohrenz, T.; Witcher, M. R.; Laxton, A. W.; Tatter, S. B.; White, J. P.; Ellis, T. L.; Phillips, P. E. M.; Montague, P. R. Proc. Natl. Acad. Sci. U.S.A.2016, 113, 200–205 (ref (30)). https://creativecommons.org/licenses/by/4.0/.

Figure 3

Model loadings analysis by analyte for rapid pulse voltammetry. Large loadings for dopamine and serotonin in the early portions of specific steps indicate the model is gaining analyte-specific information from portions of the current traces dominated by capacitive current. Reproduced from Movassaghi, C. S.; Perrotta, K. A.; Yang, H.; Iyer, R.; Cheng, X.; Dagher, M.; Fillol, M. A.; Andrews, A. M. Anal. Bioanal. Chem. 2021, 413, 6747–6767 (ref (11)). http://creativecommons.org/licenses/by/4.0/.

Figure 4

Dopamine (DA) predictions from FSCV data containing 120 mM K⁺ for an actual value of 500 nM dopamine. Reproduced from Johnson, J. A.; Hobbs, C. N.; Wightman, R. M. Anal. Chem. 2017, 89, 6166–6174 (ref (21)). Copyright 2017, American Chemical Society.

Figure 5

Analyte-specific equivalent circuit voltammograms for dopamine (DA), norepinephrine (NE), and epinephrine (EP). Reproduced from Park, C.; Hwang, S.; Kang, Y.; Sim, J.; Cho, H. U.; Oh, Y.; Shin, H.; Kim, D. H.; Blaha, C. D.; Bennet, K. E. Anal. Chem. 2021, 93, 15861–15869 (ref (14)). Copyright 2021, American Chemical Society.

Figure 6

Analyte (dopamine (DA), norepinephrine (NE), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA)) predictions from randomized pulse voltammetry. Reproduced with permission from Montague, P. R.; Lohrenz, T.; White, J.; Moran, R. J.; Kishida, K. T. bioRxiv Preprint, 2019 (ref (65)). Copyright 2019, The Authors.