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Non-Enzymatic Selective Detection of Histamine in Fishery Product Samples on Boron-Doped Diamond Electrodes

MetadataDetails
Publication Date2025-07-29
JournalBiosensors
AuthorsHiroshi Aoki, Risa Miyazaki, Yasuaki Einaga
InstitutionsKeio University, National Institute of Advanced Industrial Science and Technology
AnalysisFull AI Review Included

This study presents a novel, non-enzymatic electrochemical sensor for the highly selective and rapid detection of histamine in fishery products, utilizing Boron-Doped Diamond (BDD) electrodes.

  • Core Innovation: Selective detection of histamine over histidine (the primary interferent) achieved by combining an Oxygen-Terminated BDD (O-BDD) surface with an optimized alkaline solution pH (pH 8.4).
  • Selectivity Mechanism: The negatively charged O-BDD surface leverages electrostatic interactions, attracting positively charged histamine (pKa = 9.75) while repelling negatively charged histidine (pI = 7.59), enabling selective oxidation in the +1.1 V to +1.2 V range (vs. Ag/AgCl).
  • Performance Metrics: The sensor demonstrated a highly linear response (R2 = 0.968) across the critical concentration range of 0-150 ppm in real fish extract samples.
  • Detection Limit: The calculated detection limit (LOD) was 20.9 ppm, which is suitable for monitoring histamine levels relative to international regulatory limits (e.g., FAO limit of 100 ppm average).
  • Validation: Histamine concentrations estimated via inverse regression matched certified values in unknown fish samples with high accuracy within the error range.
  • Engineering Advantage: The method eliminates the need for unstable enzymes, complex pretreatment, and specialized equipment (like HPLC), offering a robust, reusable, and rapid alternative suitable for on-site quality control.
ParameterValueUnitContext
Electrode MaterialBoron-Doped Diamond (BDD)-Grown on Si(100) wafers
BDD Film Thickness~40”mDeposition time 10 h
B/C Atomic Ratio1%Used in CVD synthesis
Microwave Power (CVD)5kWBDD deposition
Working Electrode Area0.28cm2Circular, 0.6 cm diameter
Optimized Measurement pH8.4-Used 0.5 M Na2HPO4 buffer
Selective Oxidation Potential Range+1.1 to +1.2Vvs. Ag/AgCl, for histamine detection
Histamine pKa9.75-Histamine is positively charged at pH 8.4
Histidine pI7.59-Histidine is negatively charged at pH 8.4
Linear Response Range0-150ppmIn fish extract samples
Detection Limit (LOD)20.9ppmCalculated at S/N = 3.0
Correlation Coefficient (R2)0.968-Linearity of calibration curve
LSV Scan Rate0.1V s-1Linear Sweep Voltammetry
Anodic Oxidation Potential (Cleaning)+3.0VApplied for 5 min to create O-BDD
Cathodic Reduction Potential (Cleaning)-3.0VApplied for 5 min

The sensor relies on Linear Sweep Voltammetry (LSV) using an Oxygen-Terminated BDD (O-BDD) working electrode in an alkaline phosphate buffer.

  1. BDD Electrode Preparation:

    • BDD films were grown on Si(100) wafers using microwave-plasma-assisted Chemical Vapor Deposition (CVD).
    • Carbon source: Acetone; Boron source: Trimethyl Borate (B/C ratio 1%).
    • Film thickness was approximately 40 ”m.
  2. Electrode Activation (O-BDD Surface):

    • The BDD electrode was electrochemically cleaned and activated using Chronoamperometry (CA) in 1× PBS.
    • Process sequence: Cathodic reduction at -3.0 V for 5 min, followed by anodic oxidation at +3.0 V for 5 min. This anodic step creates the necessary negatively charged oxygen termination (O-BDD) layer.
  3. Electrochemical Setup:

    • Three-electrode configuration: O-BDD (Working), Ag/AgCl (Reference, 3 M KCl salt bridge), and Pt (Auxiliary).
  4. Sample Extraction and pH Control:

    • Fish meat samples were mixed 1:2 (w/w) with 0.5 M Na2HPO4 buffer, resulting in a measurement solution pH of 8.4.
    • The mixture was centrifuged at 10,000 rpm for 10 min, and the supernatant was used for analysis.
  5. Measurement and Signal Processing:

    • LSV was performed by scanning the potential from 0.8 V to 1.6 V at 0.1 V s-1.
    • The sensor response was quantified by subtracting the baseline current at +0.95 V from the current measured at the selective oxidation potential of +1.15 V (iat +1.15 V - iat +0.95 V).
  6. Quantification:

    • A calibration curve was established using known histamine concentrations in fish extracts.
    • Unknown sample concentrations were determined using inverse estimation based on the derived linear regression equation.

This non-enzymatic BDD sensor technology is highly relevant for applications requiring rapid, stable, and accurate chemical sensing, particularly in the food safety sector.

  • Food Safety and Quality Control: Rapid, on-site screening and quantification of histamine in fishery products (fresh, frozen, canned fish, and fish sauces) to ensure compliance with regulatory limits (e.g., FDA, FAO, EU).
  • Supply Chain Monitoring: Implementation of continuous, real-time monitoring systems for biogenic amines during food storage and transport, leveraging the BDD electrode’s stability and robustness.
  • High-Throughput Testing: Use in food processing facilities for quick batch testing, replacing slower, labor-intensive methods like HPLC or fluorometric assays.
  • Harsh Environment Sensing: The chemical inertness and stability of BDD allow the sensor to operate reliably in high-salt or complex matrices (like fish sauces) where traditional organic or enzyme-based sensors degrade.
  • Electrochemical Platform Development: BDD electrodes serve as a robust, reusable platform for developing other non-enzymatic sensors targeting various amino acids and biological contaminants.
View Original Abstract

Histamine sensing that uses enzymatic reactions is the most common form of testing due to its selectivity for histamine. However, enzymes are difficult to store for long periods of time, and the inactivation of enzymes decreases the reliability of the results. In this study, we developed a novel, quick, and easily operated histamine sensing technique that takes advantage of the histamine redox reaction and does not require enzyme-based processes. Because the redox potential of histamine is relatively high, we used a boron-doped diamond (BDD) electrode that has a wide potential window. At pH 8.4, which is between the acidity constant of histamine and the isoelectric point of histidine, it was found that an oxygen-terminated BDD surface successfully detected histamine, both selectively and exclusively. Measurements of the sensor’s responses to extracts from fish meat samples that contained histamine at various concentrations revealed that the sensor responds linearly to the histamine concentration, thus allowing it to be used as a calibration curve. The sensor was used to measure histamine in another fish meat sample treated as an unknown sample, and the response was fitted to the calibration curve to perform an inverse estimation. When estimated in this way, the histamine concentration matched the certified value within the range of error. A more detailed examination showed that the sensor response was little affected by the histidine concentration in the sample. The detection limit was 20.9 ppm, and the linear response range was 0-150 ppm. This confirms that this sensing method can be used to measure standard histamine concentrations.