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Indirect electrochemical detection of creatinine in human urine samples using a bare boron-doped diamond electrode

MetadataDetails
Publication Date2025-07-01
JournalBulletin of the Chemical Society of Japan
AuthorsZiping Zhang, Genki Ogata, Yasuaki Einaga
InstitutionsKeio University
AnalysisFull AI Review Included

Technical Documentation & Analysis: Bare BDD Electrodes for Creatinine Detection

Section titled “Technical Documentation & Analysis: Bare BDD Electrodes for Creatinine Detection”

This documentation analyzes the successful application of bare Boron-Doped Diamond (BDD) electrodes for the indirect electrochemical detection of creatinine (CRE) in human urine, highlighting the material’s superior performance for Point-of-Care Testing (POCT) applications.

  • Core Achievement: Demonstrated a simple, non-enzymatic, and modification-free electrochemical method for detecting creatinine in complex human urine matrices using a bare BDD electrode.
  • Material Advantage: BDD’s intrinsic properties—wide potential window, low background current, and strong resistance to biofouling—enable robust detection without the need for complex surface modification layers common in other sensors.
  • High Sensitivity: Achieved a low Limit of Detection (LOD) of 0.0377 mg/dL (3.3 ”M), significantly below the healthy urinary CRE range (4.4 to 18 mM), confirming suitability for clinical use.
  • Methodology: Utilized a continuous electrochemical redox approach (Chronoamperometry oxidation followed by Differential Pulse Voltammetry reduction) in the presence of NaNO2.
  • Clinical Relevance: Results showed excellent agreement with the standard spectrophotometric JaffĂ© method, validating the strategy for real-world urinary CRE monitoring and early disease diagnosis.
  • 6CCVD Value Proposition: 6CCVD specializes in high-quality, customizable MPCVD BDD material, capable of replicating the exact B/C ratio and deposition conditions required for this high-performance sensor.
ParameterValueUnitContext
Limit of Detection (LOD)0.0377 (3.3)mg/dL (”M)Low concentration detection in D-PBS
Linear Range (Low Conc.)0.5 to 2.5mg/dLTested range for 100-fold diluted urine
Linear Range (High Conc.)0.0377 to 200mg/dLOverall linear performance range
Coefficient of Determination (R2)0.9973N/ACalibration curve linearity at -0.15 V
Electrode Area0.36cm2Working and Counter Electrode size
BDD Doping Ratio (B/C)1%Atomic Boron-to-Carbon ratio
Deposition Pressure115TorrMPCVD chamber pressure
Microwave Power5.00kWPower used during 4-hour deposition
Grain Size (Polycrystalline)2 to 5”mSurface morphology characterization
Electrochemical ProtocolCA (+1.5 V, 30 s) followed by DPVV, sIndirect redox detection sequence

The research successfully fabricated and utilized a bare BDD electrode via Microwave Plasma-Assisted Chemical Vapor Deposition (MPCVD) on a silicon substrate.

  1. Substrate Preparation: Single-side silicon (100) wafers were polished using diamond powder (~1 ”m) and cleaned via ultrasonication.
  2. BDD Film Deposition (MPCVD):
    • System: AX6500 MPCVD system.
    • Sources: Acetone (Carbon source) and Trimethyl Borate (TMB) (Boron source).
    • Carrier Gas: H2.
    • Recipe Parameters: Atomic B/C ratio of 1%, total pressure of 115 Torr, and microwave power of 5.00 kW for 4 hours.
  3. Electrode Pre-treatment (Cleaning): The BDD surface was cleaned using Cyclic Voltammetry (CV) in 0.1 M H2SO4 (40 cycles, 1 V/s) followed by cathodic reduction (CA at -3.0 V vs. Ag/AgCl for 5 min) to achieve an H-termination surface.
  4. Indirect Electrochemical Detection:
    • Sample Preparation: Urine samples were diluted 100-fold in D-PBS (pH 6.4) with 3 mg/dL NaNO2 added.
    • Oxidation Step (CA): Applied +1.5 V (vs. Ag/AgCl) for 30 s to generate localized acidic environment and initiate diazonium reaction.
    • Reduction Step (DPV): Measured the reduction current using Differential Pulse Voltammetry (DPV) from +0.3 V to -1.0 V (vs. Ag/AgCl) to quantify the generated diazonium salt, which correlates linearly with CRE concentration.

6CCVD is uniquely positioned to supply the high-specification BDD material required to replicate and scale this advanced electrochemical sensor technology. Our expertise in MPCVD diamond growth ensures precise control over doping, thickness, and surface finish, critical for achieving the reported sensitivity and robustness.

To replicate or extend this research, 6CCVD recommends the following materials:

  • Heavy Boron-Doped Polycrystalline Diamond (PCD): Essential for electrochemical applications requiring high conductivity and a wide potential window. We can precisely match the required 1% B/C ratio used in this study, ensuring optimal performance and reproducibility.
  • Silicon Substrates: We offer BDD films deposited on standard silicon (100) wafers, matching the substrate used in the paper for easy integration into existing semiconductor fabrication lines.
  • BDD Thickness: 6CCVD supplies BDD films in the range of 0.1 ”m to 500 ”m thickness, allowing researchers to optimize the film depth for specific sensor designs and mechanical stability.

The success of this bare BDD electrode relies on precise material engineering. 6CCVD offers comprehensive customization services to meet specific research needs:

Requirement from Paper6CCVD Customization CapabilitySales Advantage
Electrode Dimensions (0.36 cm2)Custom laser cutting and dicing services.We can supply plates up to 125 mm (PCD) for high-throughput array fabrication and scale-up, far exceeding laboratory-scale plates.
BDD Recipe Matching (1% B/C, 115 Torr)In-house MPCVD expertise for precise doping and growth parameter control.Guaranteed material consistency and performance matching the published results, reducing R&D time.
Surface Finish (Bare Electrode)Ultra-high quality polishing services.We achieve surface roughness (Ra) of < 5 nm for inch-size PCD, ensuring the smooth, stable, and low-capacitance surface critical for low background current and robust detection.
Future IntegrationInternal metalization capability (Au, Pt, Ti, W, Cu).For integrating the BDD sensor into microfluidic or POCT devices, 6CCVD can deposit custom metal contact pads or interconnects directly onto the diamond surface.

The paper highlights BDD’s superior resistance to biofouling and matrix effects, making it ideal for complex biofluids like urine. 6CCVD’s in-house PhD team specializes in diamond electrochemistry and can assist engineers and scientists with:

  • Material Selection: Consulting on optimizing B/C ratios and film thickness for specific electrochemical applications (e.g., high-sensitivity detection, flow cells).
  • Surface Termination: Guidance on achieving and maintaining the optimal H-termination surface required for stable electrochemical performance in complex media.
  • Scale-Up Strategy: Support for transitioning from laboratory-scale 0.36 cm2 electrodes to large-area, high-volume manufacturing of Creatinine POCT sensors.

For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly.

View Original Abstract

Abstract Electrochemical sensors have been recognized as a promising candidate in point-of-care testing, which is due to their sensitivity, time-saving, low cost, and portability. This work aims to develop a simple and sustainable electrochemical method to measure creatinine (CRE) in real urine. While the present electrochemical sensors for CRE detection rely on the modified electrodes for sensing CRE, our work simply used a bare boron-doped diamond (BDD) electrode without any modification to detect CRE in the urine samples. This method consists of a continuous electrochemical redox reaction of CRE with the addition of NaNO2 in the neutral solution. By using this method, CRE in the range of 0.0377 mg/dL (3.3 ÎŒM) to 200 mg/dL (17.68 mM) exhibits linear performance on the BDD electrode. The results are in good agreement with the JaffĂ© method obtained from the typical spectrophotometric analysis. This strategy has the potential to detect urinary CRE, which could be clinically valuable.