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An electrochemical 3-hydroxybutyrate biosensor using phenazine-based electron mediators.

Jindian Liu1, Tianbao Yang2, Xue Li2

  • 1State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China; Eaglenos Sciences, Inc., 73 Tanmi Road, BLDG B2-2, Nanjing, 210044, Jiangsu, China.

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Summary

A novel electrochemical biosensor accurately detects 3-hydroxybutyrate (3-HB), a key marker for diabetic ketoacidosis. This rapid, point-of-care device utilizes a phenazine mediator for sensitive and selective 3-HB quantification.

Keywords:
3-HydroxybutyrateDiabetic ketoacidosisElectrochemical biosensorNAD-Dependent HBDHPhenazine mediatorPoint-of-care testing

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Area of Science:

  • Biomedical Engineering
  • Analytical Chemistry
  • Clinical Diagnostics

Background:

  • Accurate 3-hydroxybutyrate (3-HB) quantification is crucial for managing metabolic disorders like diabetic ketoacidosis.
  • Blood 3-HB is a superior indicator compared to traditional ketone tests, driving demand for point-of-care solutions.

Purpose of the Study:

  • To develop a sensitive and selective electrochemical biosensor for rapid 3-hydroxybutyrate (3-HB) detection.
  • To evaluate phenazine derivatives as redox mediators for enhanced biosensor performance.

Main Methods:

  • Systematic evaluation of three phenazine derivatives using molecular docking, solubility, and electrochemical analysis.
  • Integration of the optimal mediator (compound 3) with NAD-dependent 3-hydroxybutyrate dehydrogenase (HBDH) in an electrochemical biosensor.
  • Testing on screen-printed strips for stability, linearity, and interference from common biomolecules.

Main Results:

  • Compound 3 demonstrated excellent aqueous solubility, electrochemical stability, and a wide linear response (0.05-14 mM, R²=0.9993) within 20 seconds.
  • The biosensor maintained consistent performance after 5 days at 60°C with minimal signal drift.
  • Negligible interference (<±15% deviation) was observed from glucose, uric acid, ascorbic acid, lactic acid, and creatinine.

Conclusions:

  • Compound 3 is a highly effective electron mediator for electrochemical detection of 3-HB.
  • The developed biosensor shows significant potential for reliable point-of-care and clinical monitoring of 3-HB.