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MP13 - Impedimetric Detection of COVID Proteins on Functionalized Boron Doped Diamond Electrodes – is the Redox Marker Necessary?

MetadataDetails
Publication Date2025-01-01
AuthorsAnna Olejnik, Robert Bogdanowicz
AnalysisFull AI Review Included

This research investigates the use of functionalized Boron Doped Diamond (BDD) electrodes for the impedimetric detection of COVID-19 Receptor Binding Domain (RBD) proteins, focusing on optimizing the measurement protocol.

  • Core Technology: Electrochemical Impedance Spectroscopy (EIS) applied to BDD electrodes functionalized with Angiotensin Convertase Enzyme (ACE2) receptors.
  • Key Finding (Marker Necessity): Detection was successful both with and without the standard external redox marker (hexaferrocyanide).
  • Performance Improvement: Marker-free detection achieved a significantly lower Limit of Detection (LOD) of 6 pg/L, representing an 8.3x improvement over the standard marker protocol (LOD = 50 pg/L).
  • Sensitivity Trade-off: The marker-free approach showed higher sensitivity (1 kΩ/dec vs. 300 Ω/dec) but suffered from larger initial impedance and higher deviation from linearity due to 1/f noise.
  • Stability Trade-off: The standard protocol (with marker) offered superior electrode stability and repeatability, despite its lower sensitivity and the inconvenience of adding an external compound.
  • Linear Range: The quantitative linear detection range remained consistent for both methods, spanning four orders of magnitude (0.05 µg/L to 1 mg/L).
ParameterValueUnitContext
Electrode MaterialBoron Doped Diamond (BDD)N/APrepared via microwave-assisted CVD
Target AnalyteRBD proteinN/AReceptor Binding Domain of SARS-CoV-2
Receptor LayerACE2N/AUsed for specific functionalization
Measurement TechniqueEISN/AElectrochemical Impedance Spectroscopy
Detection SignalImaginary Impedance (Z”)Measured at 1 Hz frequency
Electrolyte1X Tris buffered salineN/ANeutral aqueous solution (pH = 7.2)
Redox Marker (When Used)Hexaferrocyanide (II/III)1 mMExternal redox couple concentration
Linear Detection Range0.05 µg/L to 1 mg/LConcentrationRange consistent for both methods
LOD (Marker-Free)6pg/LLimit of Detection (LOD = 3.3 SD / a)
LOD (With Marker)50pg/LLimit of Detection (LOD = 3.3 SD / a)
Sensitivity (Marker-Free)1kΩ/decSlope of Z” vs. log(Concentration)
Sensitivity (With Marker)300Ω/decSlope of Z” vs. log(Concentration)

The biosensor fabrication and testing relied on established electrochemical and materials science techniques:

  1. Electrode Synthesis: Boron doped diamond (BDD) electrodes were prepared using a microwave-assisted Chemical Vapor Deposition (CVD) process.
  2. Receptor Functionalization: The BDD surface was functionalized with ACE2 receptors, targeting COVID proteins, following methods detailed in prior work [2].
  3. Measurement Environment: Detection was performed in a neutral aqueous solution (1X Tris buffered saline, pH = 7.2).
  4. Standard Protocol (Marker): The analyte solution was supplemented with 1 mM of the external hexaferrocyanide (II/III) redox couple, which typically serves to amplify the chemical signal by increasing charge transfer resistance upon binding.
  5. Marker-Free Protocol (Novel): The measurement was repeated without the addition of the external redox couple.
  6. Signal Acquisition: The quantitative detection signal was extracted by monitoring the imaginary part of the impedance (Z”) specifically at a low frequency of 1 Hz.
  7. Performance Quantification: The Limit of Detection (LOD) was calculated using the standard approach: LOD = 3.3 SD / a, where ‘a’ is the slope derived from the linear fit of the lowest concentration points.

This technology leverages the stability and electrochemical properties of BDD for high-performance biosensing, relevant to several commercial sectors:

  • Rapid Diagnostics (Point-of-Care): Development of cost-efficient, fast, and reliable electrochemical sensors for viral proteins (e.g., SARS-CoV-2, Influenza) suitable for decentralized testing.
  • High-Sensitivity Biosensing: Applications requiring ultra-low detection limits (pg/L range) in clinical, environmental, or food safety monitoring where traditional methods lack sensitivity.
  • Electrochemical Sensor Platforms: Utilizing BDD as a robust, chemically inert, and stable electrode material for next-generation electrochemical transducers, particularly in harsh or complex biological media.
  • Simplified Sensor Design: Implementation of marker-free sensing protocols reduces the complexity and cost of consumables, simplifying the operational procedure for commercial devices.
  • Drug and Antibody Screening: Creating stable, reusable platforms for monitoring molecular binding events (receptor-antigen) via impedance changes, useful in pharmaceutical research and development.