A Dual Approach of an Oil–Membrane Composite and Boron-Doped Diamond Electrode to Mitigate Biofluid Interferences

At a Glance

Metadata	Details
Publication Date	2021-12-02
Journal	Sensors
Authors	Madeleine DeBrosse, Yuchan Yuan, Michael Brothers, Aleksandar Karajić, Jeroen van Duren
Institutions	United States Air Force Research Laboratory, University of Cincinnati
Citations	3
Analysis	Full AI Review Included

Technical Documentation & Analysis: Boron-Doped Diamond for Biofluid Sensing

Executive Summary

This research validates the superior performance of Boron-Doped Diamond (BDD) electrodes combined with a hydrophobic oil-membrane composite for electrochemical biosensing in complex biofluids.

Dual Mitigation Strategy: The system successfully mitigates both solvent effects (water electrolysis suppression by BDD) and solute effects (foulant blocking by the oil membrane).
Detection Limit Improvement: BDD electrodes achieved up to a 365-fold reduction in the Limit of Detection (LOD) compared to traditional gold electrodes in buffer solution.
Foulant Resistance: The oil-membrane protection scheme maintained near-ideal LOD performance (as low as 1.8 µM for hexacyanoferrate) even after 18 hours of exposure to raw human serum.
Material Advantage: BDD’s wide potential window and inherent chemical stability are leveraged to reduce background current and enhance sensor functionality in fluid environments.
Generalizability: This approach is highly generalizable, enabling current enzymatic and electrochemical sensors to function effectively in raw biofluids, paving the way for nanomolar (nM) detection limits.
6CCVD Relevance: The successful implementation relies on high-quality, tunable Boron-Doped Polycrystalline Diamond (PCD BDD) material, a core offering of 6CCVD.

Technical Specifications

The following hard data points summarize the performance metrics achieved using the BDD electrodes in buffer and protected serum environments.

Parameter	Value	Unit	Context
Maximum LOD Reduction	365	Fold	BDD vs Gold in 1× PBS (Hexacyanoferrate)
BDD LOD (Ideal Buffer)	1.03 ± 0.43	µM	Hexacyanoferrate (II/III) in 1× PBS
Gold LOD (Ideal Buffer)	116 ± 63	µM	Hexacyanoferrate (II/III) in 1× PBS
BDD LOD (Serum, Protected)	1.8 ± 1.3	µM	Castor Oil Membrane Protection (Hexacyanoferrate)
BDD LOD (Serum, Protected)	7.3 ± 4.2	µM	Castor Oil Membrane Protection (Hexaammineruthenium)
BDD Sensitivity (Protected)	7.8 ± 2.8	AC/mM	Castor Oil Membrane (Hexacyanoferrate)
BDD Sheet Resistivity	3 to 8	Ω·cm	Confirmed semiconductive property
Electrochemical Cleaning Potential (BDD)	0 to 2.2	V	In 0.5 M H₂SO₄, 120 scans
Incubation Time (Membrane Test)	18	h	Exposure to human serum

Key Methodologies

The experimental success hinges on precise material preparation and a novel protective setup.

Material Selection: Conductive O-terminated Boron-Doped Polycrystalline Diamond (BDD) films were grown on conductive silicon wafers.
Electrode Fabrication: A well-defined 2-mm diameter electrode area was created using Kapton® polyimide tape insulation, adhered to a 1.25-mm acrylic backing, and sealed with marine epoxy.
Electrochemical Cleaning: BDD electrodes were electrochemically cleaned in 0.5 M H₂SO₄ under an extended potential range (0 to 2.2 V, 120 scans) to maintain the oxygen-terminated surface.
Protection Setup: A 3D-printed U-boat setup, coated with FluoroPel 1601 V fluoropolymer, was used to separate the biofluid (human serum) from the buffer solution.
Membrane Composite: A polycarbonate track-etch (PCTE) membrane (1 µm diameter pore size) was impregnated with Castor Oil (a robust hydrophobic barrier) and placed between the fluid compartments.
Measurement Technique: Two-step chronocoulometry (CC) with a 30-s step was used to monitor signal change as a function of redox-active probe concentration (Hexacyanoferrate (II/III) and Hexaammineruthenium (II/III)).

6CCVD Solutions & Capabilities

6CCVD is uniquely positioned to supply the advanced diamond materials and customization services required to replicate and extend this high-performance biosensing research.

Applicable Materials

The research utilized conductive, O-terminated BDD on a silicon substrate. 6CCVD provides materials engineered for this exact application:

Polycrystalline Boron-Doped Diamond (PCD BDD): Available in custom dimensions up to 125mm wafers. We specialize in tuning the boron doping concentration (heavy, medium, or light) to optimize conductivity (metal-like vs. semiconductive) and electrocatalytic activity, directly addressing the need for highly conductive substrates noted in the paper.
Custom Surface Termination: The paper used O-terminated BDD. 6CCVD offers precise control over surface termination (Oxygen, Hydrogen, or Fluorine) to minimize solvent-specific inner-sphere interactions and maximize the potential window, crucial for low-noise electrochemical detection.
Substrate Options: While the paper used conductive silicon, 6CCVD can supply BDD films on various substrates (including intrinsic diamond, silicon, or custom ceramics) up to 10mm thick.

Customization Potential

The fabrication process described requires precise material handling, cutting, and integration. 6CCVD offers comprehensive in-house services to streamline device development:

Custom Service	Research Requirement Addressed	6CCVD Capability
Custom Dimensions & Cutting	2-mm diameter electrode area defined by Kapton tape.	Precision laser cutting and shaping of BDD wafers to exact specifications, eliminating manual masking steps and improving reproducibility.
Metalization	Gold sputtering used for electrical contact.	Internal metalization capability (Au, Pt, Ti, Pd, W, Cu) for creating robust, low-resistance ohmic contacts directly on the BDD surface, ready for integration.
Polishing & Surface Quality	Requires inert, low-fouling surface (Ra < 5nm).	High-quality polishing services for PCD (Ra < 5nm for inch-size wafers) and SCD (Ra < 1nm), ensuring minimal non-specific adsorption and optimal sensor performance.

Engineering Support

The authors noted significant batch-to-batch variability in BDD measurements, attributed to fluctuations in dopant concentration and polycrystallinity. This variability is a major hurdle in transitioning research to reliable commercial devices.

Reproducibility Control: 6CCVD’s MPCVD growth process is optimized for high uniformity and reproducibility. Our expert material scientists can develop and lock down specific BDD recipes (doping level, sp² content) to ensure consistent electrocatalytic properties across batches, solving the variability challenge noted in the paper.
Application Optimization: 6CCVD’s in-house PhD team specializes in material selection for advanced electrochemical applications, including low-concentration biosensing and biofluid interference mitigation. We provide consultation to match the optimal BDD properties (e.g., heavy doping for metal-like behavior vs. light doping for maximum potential window) to specific target analytes (hydrophobic hormones, small-molecule drugs, etc.).

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

View Original Abstract

Electrochemical biosensors promise a simple method to measure analytes for both point-of-care diagnostics and continuous, wearable biomarker monitors. In a liquid environment, detecting the analyte of interest must compete with other solutes that impact the background current, such as redox-active molecules, conductivity changes in the biofluid, water electrolysis, and electrode fouling. Multiple methods exist to overcome a few of these challenges, but not a comprehensive solution. Presented here is a combined boron-doped diamond electrode and oil-membrane protection approach that broadly mitigates the impact of biofluid interferents without a biorecognition element. The oil-membrane blocks the majority of interferents in biofluids that are hydrophilic while permitting passage of important hydrophobic analytes such as hormones and drugs. The boron-doped diamond then suppresses water electrolysis current and maintains peak electrochemical performance due to the foulant-mitigation benefits of the oil-membrane protection. Results show up to a 365-fold reduction in detection limits using the boron-doped diamond electrode material alone compared with traditional gold in the buffer. Combining the boron-doped diamond material with the oil-membrane protection scheme maintained these detection limits while exposed to human serum for 18 h.

Tech Support

Original Source

DOI: https://doi.org/10.3390/s21238063

References

2019 - Accessing analytes in biofluids for peripheral biochemical monitoring [Crossref]
2017 - What Are Clinically Relevant Levels of Cellular and Biomolecular Analytes? [Crossref]
2019 - Achievements and Challenges for Real-Time Sensing of Analytes in Sweat within Wearable Platforms [Crossref]
2020 - From the beaker to the body: Translational challenges for electrochemical, aptamer-based sensors [Crossref]
2020 - Consideration of Sample Matrix Effects and “biological” Noise in Optimizing the Limit of Detection of Biosensors [Crossref]
1986 - Permeability of small nonelectrolytes through lipid bilayer membranes [Crossref]
2019 - Intrinsic Membrane Permeability to Small Molecules [Crossref]
2018 - Drug permeability profiling using cell-free permeation tools: Overview and applications [Crossref]