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Label-free electrochemical immunosensor for porcine gelatin using a boron-doped diamond electrode <i>via</i> diazonium salt electrografting

MetadataDetails
Publication Date2025-06-09
JournalJournal of Electrochemical Science and Engineering
AuthorsIrkham Irkham, Fadli Taufik Abdillah, Muhammad Ihda H.L. Zein, Adisyahputra, N. ZAHRA
AnalysisFull AI Review Included
  • Novel Platform: A label-free electrochemical immunosensor was successfully developed using a Boron-Doped Diamond (BDD) electrode for the selective and sensitive detection of porcine gelatin.
  • Robust Functionalization: Stable covalent immobilization was achieved via electrografting of aryl diazonium salt (4-aminobenzoic acid, 4-ABA), providing a robust interface for subsequent biomolecule attachment.
  • Oriented Antibody Binding: Anti-porcine gelatin antibodies were immobilized via Protein A using EDC/NHS coupling, ensuring optimal orientation and preserving the Fab region for target binding.
  • High Sensitivity: The sensor demonstrated excellent analytical performance, achieving a low Limit of Detection (LoD) of 142.15 pg mL-1.
  • Label-Free Detection: Detection relies on monitoring the current suppression of the [Fe(CN)6]3-/4- redox probe using Differential Pulse Voltammetry (DPV), simplifying the assay and reducing cost compared to labeled systems.
  • High Specificity: Specificity testing confirmed exclusive response to porcine gelatin, showing negligible cross-reactivity (± 7.3% current change) toward bovine gelatin.
  • Optimized Protocol: Operational parameters were optimized using the Box-Behnken design, resulting in a rapid detection protocol requiring only 60 min for antibody incubation and 15 min for antigen incubation.
ParameterValueUnitContext
Sensing PlatformBoron-Doped Diamond (BDD)N/AWorking electrode material
Detection Limit (LoD)142.15pg mL-1Analytical performance
Linear Regression (R)0.9854N/ACorrelation coefficient of calibration curve
Coefficient of Determination (R2)0.9711N/ALinearity over tested range
DPV Potential Range-0.3 to +0.7VMeasurement range (vs. Ag/AgCl)
DPV Scan Rate0.008V s-1Measurement parameter
CV Scan Rate (Electrografting)100mV s-1BDD modification step
Redox Probe System0.01 M K3[Fe(CN)6] in 0.1 M KClN/ADPV measurement solution
Optimal Antibody Dilution1:500N/AOptimized concentration (Box-Behnken)
Antibody Incubation Time (Rapid Protocol)60minTime used for rapid detection protocol
Gelatin Incubation Time (Optimal)15minTime used for rapid detection protocol
Bovine Gelatin Cross-Reactivity± 7.3%Current change upon exposure (indicating high specificity)

The immunosensor fabrication involves a multi-step surface modification process on the BDD electrode:

  1. BDD Surface Activation (Diazonium Electrografting):

    • The BDD electrode was modified by electro-grafting 4-aminobenzoic acid (4-ABA) in 37% HCl solution, cooled to 0 °C.
    • Electrografting was performed using 11 consecutive cyclic scans in the potential range of 0 to +0.8 V at a scan rate of 100 mV s-1. This process covalently bonds the diazonium-derived film (containing carboxylic acid groups) to the BDD surface.
  2. Protein A Immobilization:

    • Protein A was immobilized onto the diazonium film using EDC/NHS coupling chemistry to activate the carboxyl groups for stable amide bond formation.
    • The electrode was incubated in a solution containing Protein A (0.5 mg mL-1), EDC (4.8 mg mL-1), and NHS (2.87 mg mL-1) for 1 hour at 4 °C.
  3. Anti-Porcine Gelatin Antibody Immobilization:

    • Anti-porcine gelatin antibodies (0.1 g mL-1 stock, 500× dilution) were incubated on the Protein A-modified electrode.
    • The optimized incubation time for the rapid protocol was set to 60 minutes at 4 °C.
  4. Surface Blocking:

    • The electrode surface was blocked with 1% Bovine Serum Albumin (BSA) solution for 30 minutes at room temperature to prevent non-specific adsorption.
  5. Antigen Detection (Binding):

    • Standard porcine gelatin solution (0.5 ng mL-1) was applied to the electrode.
    • The optimized incubation time for antigen binding was 15 minutes at room temperature.
  6. Electrochemical Readout:

    • Detection was performed using Differential Pulse Voltammetry (DPV) with 40 ”L of 0.01 M K3[Fe(CN)6] in 0.1 M KCl as the redox probe.
    • The binding of the non-conductive gelatin antigen causes a measurable decrease in the DPV peak current, providing a label-free signal.
  • Halal and Kosher Certification: Provides a rapid, highly specific, and reliable method for verifying the absence of prohibited animal-derived ingredients (specifically porcine gelatin) in food, cosmetic, and pharmaceutical products.
  • Food Authentication and Fraud Detection: Used by regulatory bodies and food manufacturers for quality control and detecting adulteration in processed foods, such as candies, dairy, and meat substitutes.
  • Pharmaceutical Quality Control: Verification of the source material (porcine vs. bovine) used in gelatin capsules and other drug excipients, where source control is critical for regulatory compliance.
  • Point-of-Care (POC) Biosensing Devices: The BDD platform’s stability, wide potential window, and the simplicity of the label-free electrochemical detection mechanism are ideal for developing portable, robust, on-site testing kits.
  • Advanced Carbon Electrode Functionalization: The aryl diazonium electrografting technique provides a versatile, stable chemical platform for immobilizing various biological recognition elements (antibodies, aptamers) onto inert carbon surfaces for diverse biosensing applications.
View Original Abstract

Porcine gelatin is widely used in the food and pharmaceutical industries due to its favorable functional properties and low cost. However, its presence in consumer products raises serious concerns for individuals with dietary restrictions based on religious, ethical, or health considerations. In this study, a label-free electrochemical immunosensor was developed using a boron-doped diamond electrode modified with aryl diazonium salt for the selective and sensitive detection of porcine gelatin. The diazonium electrografting enabled stable covalent immobilization of anti-porcine gelatin antibodies via protein A, preserving anti­body orientation and activity. Experimental parameters were optimized using the Box-Behnken design, yielding ideal conditions of 500× antibody concentration, 60 min antibody incubation, and 15 min gelatin incubation. Detection was performed using differential pulse voltammetry with [Fe(CN)₆]3-/4- as a redox probe, allowing label-free monitoring of anti­body-antigen interactions based on changes in current. The immunosensor demonstrated excellent analytical performance, with a detection limit of 142.15 pg mL-1. Specificity testing confirmed that the sensor responds exclusively to porcine gelatin, showing no cross-reactivity with bovine gelatin. These results demonstrate that the proposed immunosensor provides a rapid, highly sensitive, and specific platform for porcine gelatin detection, offering great potential for food authentication and halal verification.