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Creation of a point-of-care therapeutics sensor using protein engineering, electrochemical sensing and electronic integration

Author

Listed:
  • Rong Cai

    (Rice University)

  • Chiagoziem Ngwadom

    (Rice University)

  • Ravindra Saxena

    (Rice University
    Rice University)

  • Jayashree Soman

    (Rice University)

  • Chase Bruggeman

    (Michigan State University)

  • David P. Hickey

    (Michigan State University)

  • Rafael Verduzco

    (Rice University)

  • Caroline M. Ajo-Franklin

    (Rice University
    Rice University
    Rice University)

Abstract

Point-of-care sensors, which are low-cost and user-friendly, play a crucial role in precision medicine by providing quick results for individuals. Here, we transform the conventional glucometer into a 4-hydroxytamoxifen therapeutic biosensor in which 4-hydroxytamoxifen modulates the electrical signal generated by glucose oxidation. To encode the 4-hydroxytamoxifen signal within glucose oxidation, we introduce the ligand-binding domain of estrogen receptor-alpha into pyrroloquinoline quinone-dependent glucose dehydrogenase by constructing and screening a comprehensive protein insertion library. In addition to obtaining 4-hydroxytamoxifen regulatable engineered proteins, these results unveil the significance of both secondary and quaternary protein structures in propagation of conformational signals. By constructing an effective bioelectrochemical interface, we detect 4-hydroxytamoxifen in human blood samples as changes in the electrical signal and use this to develop an electrochemical algorithm to decode the 4-hydroxytamoxifen signal from glucose. To meet the miniaturization and signal amplification requirements for point-of-care use, we harness power from glucose oxidation to create a self-powered sensor. We also amplify the 4-hydroxytamoxifen signal using an organic electrochemical transistor, resulting in milliampere-level signals. Our work demonstrates a broad interdisciplinary approach to create a biosensor that capitalizes on recent innovations in protein engineering, electrochemical sensing, and electrical engineering.

Suggested Citation

  • Rong Cai & Chiagoziem Ngwadom & Ravindra Saxena & Jayashree Soman & Chase Bruggeman & David P. Hickey & Rafael Verduzco & Caroline M. Ajo-Franklin, 2024. "Creation of a point-of-care therapeutics sensor using protein engineering, electrochemical sensing and electronic integration," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45789-9
    DOI: 10.1038/s41467-024-45789-9
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    3. Neil Vasan & José Baselga & David M. Hyman, 2019. "A view on drug resistance in cancer," Nature, Nature, vol. 575(7782), pages 299-309, November.
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