Indirect electrochemical detection of creatinine in human urine samples using a bare boron-doped diamond electrode
At a Glance
Section titled âAt a Glanceâ| Metadata | Details |
|---|---|
| Publication Date | 2025-07-01 |
| Journal | Bulletin of the Chemical Society of Japan |
| Authors | Ziping Zhang, Genki Ogata, Yasuaki Einaga |
| Institutions | Keio University |
| Analysis | Full AI Review Included |
Executive Summary
Section titled âExecutive SummaryâThis research presents a novel, simple, and highly effective non-enzymatic electrochemical method for the indirect detection of creatinine (CRE) in human urine using a bare Boron-Doped Diamond (BDD) electrode.
- Core Innovation: Successful quantification of CRE in complex human urine matrices without requiring any electrode modification, leveraging the inherent stability and wide potential window of bare BDD.
- Detection Mechanism: The method relies on a continuous electrochemical redox reaction involving CRE and added sodium nitrite (NaNO2) in a neutral solution (D-PBS, pH 6.4).
- High Sensitivity: A low limit-of-detection (LOD) of 0.0377 mg/dL (3.3 ”M) was achieved, which is significantly lower than the typical healthy urinary CRE range (4.4 to 18 mM).
- Clinical Validation: Results showed strong agreement with the conventional spectrophotometric Jaffé method, yielding a high correlation coefficient (R) of 0.9964.
- Robustness: The BDD electrode demonstrated excellent resistance to common urinary interferents (urea, glucose, uric acid, albumin, etc.) after 100-fold sample dilution, with current variations less than 5%.
- POCT Potential: This strategy offers a simple, low-cost, and rapid analytical technique suitable for Point-of-Care Testing (POCT) and long-term health management.
Technical Specifications
Section titled âTechnical Specificationsâ| Parameter | Value | Unit | Context |
|---|---|---|---|
| Electrode Material | Boron-Doped Diamond (BDD) | N/A | Bare, unmodified working electrode |
| Boron-Carbon (B/C) Ratio | 1 | % | Atomic ratio in BDD film |
| LOD (Limit of Detection) | 0.0377 (3.3) | mg/dL (”M) | Calculated in D-PBS (0.5 to 2.5 mg/dL range) |
| Linear Detection Range | 0.0377 to 200 (3.3 to 17.68) | mg/dL (mM) | Effective range for CRE detection |
| Coefficient of Determination (R2) | 0.9973 | N/A | Linearity for low-concentration CRE (0.5-2.5 mg/dL) |
| Correlation with Jaffé (R) | 0.9964 | N/A | Agreement between BDD and spectrophotometric methods |
| Interference Variation | <5 | % | Variation in DPV current compared to blank (after dilution) |
| BDD Grain Size | 2 to 5 | ”m | Polycrystalline diamond morphology |
| BDD sp3 Peak | 1333 | cm-1 | Confirmed by Raman spectroscopy |
| BDD Bandgap | 5.45 | eV | Intrinsic diamond property |
| Boron Activation Energy | 0.37 | eV | Mid-gap state introduction for conductivity |
Key Methodologies
Section titled âKey MethodologiesâThe experimental procedure involves BDD electrode fabrication, a specific electrochemical pre-treatment, and a two-step redox detection protocol using NaNO2 as a mediator.
1. BDD Electrode Fabrication (MPCVD)
Section titled â1. BDD Electrode Fabrication (MPCVD)â| Parameter | Value | Unit | Context |
|---|---|---|---|
| Substrate | Single-side silicon (100) | N/A | Polished with diamond powder |
| Deposition Method | Microwave Plasma-Assisted CVD (AX6500) | N/A | Used for BDD film growth |
| Carbon Source | Acetone | N/A | Used with Trimethyl borate (TMB) |
| Carrier Gas | H2 | N/A | Used during deposition |
| Total Pressure | 115 | Torr | Chamber pressure during 4-h reaction |
| Microwave Power | 5.00 | kW | Power used during deposition |
2. Electrochemical Detection Protocol
Section titled â2. Electrochemical Detection ProtocolâThe detection uses a 3-electrode system (BDD working, Ag/AgCl reference, BDD counter) in D-PBS (pH 6.4) containing 3 mg/dL NaNO2.
- Cleaning: BDD and cell cleaned via ultrasonication in ultrapure water (3 times, 5 min each).
- Surface Activation (CV): Cyclic Voltammetry (CV) cleaning in 0.1 M H2SO4, ranging from -3.0 to +3.0 V (vs. Ag/AgCl) for 40 cycles at 1 V/s.
- H-Termination (CA): Cathodic reduction using Chronoamperometry (CA) in 0.1 M H2SO4 at -3.0 V (vs. Ag/AgCl) for 5 min to obtain a stable H-termination surface.
- Oxidation Step (CA): Sample mixture oxidized at +1.5 V (vs. Ag/AgCl) for 30 s. This step generates protons, supporting a localized acidic environment necessary for the diazonium reaction among CRE, Cl-, and NaNO2.
- Reduction Step (DPV): Subsequent reduction measured using Differential Pulse Voltammetry (DPV) from 0.3 to -1.0 V. The reduction peak current at -0.15 V (vs. Ag/AgCl) is correlated with CRE concentration.
- Sample Preparation: Real urine samples were diluted 100-fold with D-PBS (pH 6.4) before testing to mitigate matrix effects.
Commercial Applications
Section titled âCommercial ApplicationsâThe use of highly stable, bare BDD electrodes for robust sensing in complex biological fluids positions this technology for several high-value commercial applications, particularly those requiring simplified, reliable, and portable analytical devices.
- Point-of-Care Testing (POCT):
- Development of portable, low-cost electrochemical sensors for rapid, non-invasive monitoring of renal function markers (CRE) in urine outside of centralized laboratories.
- Suitable for resource-limited settings due to the simplicity of the bare electrode setup (no complex modification layers needed).
- Clinical Diagnostics and Health Management:
- Monitoring of chronic kidney disease (CKD) progression and assessing glomerular filtration rate (GFR).
- Supporting therapy optimization in empirical diseases where renal function is critical.
- Detection of muscle wasting markers (CRE) in patients with conditions like heart failure.
- Sports and Anti-Doping Control:
- Rapid testing of urine dilution levels, often used as an indicator for masking stimulants or illegal drugs.
- BDD Electrode Manufacturing (Relevant to 6ccvd.com):
- The demonstrated robustness of BDD against biofouling and its wide potential window confirm its utility in electrochemical sensing products.
- Applications include high-stability electrodes for complex matrix analysis, water quality monitoring, and advanced electrochemistry where conventional electrodes fail due to fouling or narrow windows.
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.