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Introducing Nanoscale Electrochemistry in Small-Molecule Detection for Tackling Existing Limitations of Affinity-Based Label-Free Biosensing Applications

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    Introducing Nanoscale Electrochemistry in Small-Molecule Detection for Tackling Existing Limitations of Affinity-Based Label-Free Biosensing Applications
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    • Don Hui Lee
      Don Hui Lee
      Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea
      Center for Nanomedicine, Institute for Basic Science (IBS), Seoul 03722, Republic of Korea
      More by Don Hui Lee
    • Won-Yong Lee*
      Won-Yong Lee
      Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea
      Center for Nanomedicine, Institute for Basic Science (IBS), Seoul 03722, Republic of Korea
      *Email: [email protected]
      More by Won-Yong Lee
    • Jayoung Kim*
      Jayoung Kim
      Department of Medical Engineering, College of Medicine, Yonsei University, Seoul 03722, Republic of Korea
      *Email: [email protected]
      More by Jayoung Kim
      Orcidhttps://orcid.org/0000-0003-2946-8478
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    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2023, 145, 32, 17767–17778
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    https://doi.org/10.1021/jacs.3c04458
    Published August 1, 2023
    Copyright © 2023 American Chemical Society
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    Abstract

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    Electrochemical sensing techniques for small molecules have progressed in many applications, including disease diagnosis and prevention as well as monitoring of health conditions. However, affinity-based detection for low-abundance small molecules is still challenging due to the imbalance in target-to-receptor size ratio as well as the lack of a highly sensitive signal transducing method. Herein, we introduced nanoscale electrochemistry in affinity-based small molecule detection by measuring the change of quantum electrochemical properties with a nanoscale artificial receptor upon binding. We prepared a nanoscale molecularly imprinted composite polymer (MICP) for cortisol by electrochemically copolymerizing β-cyclodextrin and redox-active methylene blue to offer a high target-to-receptor size ratio, thus realizing “bind-and-read” detection of cortisol as a representative target small molecule, along with extremely high sensitivity. Using the quantum conductance measurement, the present MICP-based sensor can detect cortisol from 1.00 × 10–12 to 1.00 × 10–6 M with a detection limit of 3.93 × 10–13 M (S/N = 3), which is much lower than those obtained with other electrochemical methods. Moreover, the present MICP-based cortisol sensor exhibited reversible cortisol sensing capability through a simple electrochemical regeneration process without cumbersome steps of washing and solution change, which enables “continuous detection”. In situ detection of cortisol in human saliva following circadian rhythm was carried out with the present MICP-based cortisol sensor, and the results were validated with the LC–MS/MS method. Consequently, this present cortisol sensor based on nanoscale MICP and quantum electrochemistry overcomes the limitations of affinity-based biosensors, opening up new possibilities for sensor applications in point-of-care and wearable healthcare devices.

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    • Details on quantum EIS with data conversion; estimation of MICP thickness; binding kinetics studies; LC–MS/MS method; SEM images and UV–vis spectra of each polymer film; TEM images and EDS analysis of MICP; XPS analysis of β-CD, MB, and MICP; comparison of the quantum electrochemical method and other traditional electrochemical methods; ion concentration test; continuous monitoring of saliva cortisol; size effect test; EIS and DPV analysis; cortisol adsorption–desorption isotherms; and selectivity test (PDF)

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    Cite this: J. Am. Chem. Soc. 2023, 145, 32, 17767–17778
    Click to copy citationCitation copied!
    https://doi.org/10.1021/jacs.3c04458
    Published August 1, 2023
    Copyright © 2023 American Chemical Society
    Request reuse permissions

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