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Boron-Doped Nanocrystalline Diamond Electrodes for Neural Interfaces - In vivo Biocompatibility Evaluation

At a Glance

Section titled “At a Glance”
MetadataDetails
Publication Date2016-03-07
JournalFrontiers in Neuroscience
AuthorsMaría José Alcaide, Andrew Taylor, Morten Voss Fjorback, Vladimir Zachar, Cristian Pablo Pennisi
InstitutionsAalborg University, Czech Academy of Sciences, Institute of Physics
Citations46
AnalysisFull AI Review Included

Technical Documentation & Analysis: Boron-Doped Diamond for Neural Interfaces

Section titled “Technical Documentation & Analysis: Boron-Doped Diamond for Neural Interfaces”

Executive Summary

Section titled “Executive Summary”

This analysis focuses on the superior in vivo biocompatibility of Boron-Doped Nanocrystalline Diamond (BDD) electrodes for chronic neural interfaces, validating BDD as a critical material for next-generation neuroprosthetics.

  • Superior Biocompatibility: BDD electrodes demonstrated significantly milder inflammatory reactions and thinner fibrous encapsulation layers compared to conventional Titanium Nitride (TiN) controls.
  • Chronic Stability: The thin encapsulation layer (median thickness approximately 18 ”m at 4 weeks) suggests BDD minimizes the foreign body reaction, crucial for stable, long-term performance of implantable neural devices.
  • Reduced Impedance Pathway: A thinner fibrous capsule directly correlates to a reduced impedance pathway, ensuring efficient transmission of electrical signals for chronic stimulation and recording.
  • High Material Quality: High-quality BDD films were synthesized via Microwave Plasma Enhanced Chemical Vapor Deposition (MPCVD), achieving a high sp3/sp2 ratio (94%) and heavy boron incorporation (4.4E + 21 cm-3).
  • Performance Equivalence: The overall local tissue response to BDD implants was not significantly different from that observed for the inert bare Ti6Al4V alloy controls.
  • Application Focus: These findings confirm BDD films are an appropriate material to support stable performance in implantable neurostimulation devices, such as those used for treating urinary incontinence.

Technical Specifications

Section titled “Technical Specifications”

The following hard data points were extracted from the research concerning the BDD film synthesis and resulting biological performance.

ParameterValueUnitContext
Diamond Material TypeBoron-Doped Nanocrystalline Diamond (BDD)N/AUsed for neural electrodes
Substrate MaterialTi6Al4V Alloy (Grade 5)N/ABase material for metallic contact
Nanodiamond Seed Size4-6nmUsed for seeding prior to CVD growth
Methane Concentration (CH4)2.5%In H2 gas mixture (97.5% H2)
Boron/Carbon Ratio (B/C)15000ppmBoron dopant concentration via Trimethylboron
Average Boron Incorporation4.4E + 21cm-3Measured in BDD layers
Diamond Quality Ratio94%sp3/sp2 ratio via Raman spectroscopy
Electrode Impedance (Cited)200ΩAt 1 kHz, suitable for neural stimulation
Fibrous Capsule Thickness (BDD, 4 weeks)~18”mMedian thickness, significantly thinner than TiN (p < 0.01)
Inflammatory Reaction Score (BDD)MinimalN/AEquivalent to bare Ti, lower than TiN (p < 0.01)

Key Methodologies

Section titled “Key Methodologies”

The BDD films were synthesized using advanced MPCVD techniques, followed by rigorous in vivo testing and histological analysis.

  1. Substrate Preparation: Ti6Al4V alloy (Grade 5) electrodes (6 mm2 surface area) were seeded with a nanodiamond dispersion (4-6 nm crystal size).
  2. MPCVD Growth: BDD films were grown using a Microwave Plasma Enhanced Chemical Vapor Deposition (CVD) apparatus with a linear antenna delivery system operating at low pressures.
  3. Gas Recipe: A gas mixture of 2.5% CH4 + 97.5% H2 was used, with Trimethylboron (TMB) introduced as the boron dopant at a B/C ratio of 15000 ppm.
  4. Surface Characterization: Scanning Electron Microscopy (SEM) assessed morphology (dense array of sharp-edged crystallites). Raman spectroscopy confirmed high quality (94% sp3/sp2 ratio) and boron incorporation (4.4E + 21 cm-3).
  5. In Vivo Model: Twelve adult Wistar rats were used in a subcutaneous implantation model. Electrodes (BDD, TiN, and bare Ti controls) were implanted for 2 and 4 weeks.
  6. Histological Analysis: Tissue sections (4-5 ”m thick) were stained (Hematoxylin and Eosin, Masson’s Trichrome) to quantify fibrous capsule thickness and score inflammation and neovascularization adjacent to the implant interface.

6CCVD Solutions & Capabilities

Section titled “6CCVD Solutions & Capabilities”

6CCVD specializes in providing the high-quality, custom diamond materials and fabrication services required to replicate and advance this critical research in neural interfacing. Our MPCVD expertise ensures the precise control over doping and morphology necessary for stable chronic implants.

Requirement from Research Paper6CCVD Solution & CapabilityTechnical Advantage & Sales Driver
Boron-Doped Nanocrystalline Diamond (BDD)Heavy Boron Doped PCD/NCD (Polycrystalline/Nanocrystalline Diamond) wafers and plates.We deliver BDD films with precision doping (e.g., B/C ratios up to 15000 ppm or higher) to achieve the low impedance (200 Ω at 1 kHz) and high conductivity required for neurostimulation applications.
Custom Substrate DepositionDeposition on Customer-Supplied Substrates. We routinely handle complex geometries and specialized materials like Ti6Al4V, ceramics, and silicon for neural probes.Ensures seamless integration of high-quality BDD films onto specialized, pre-fabricated electrode arrays, maintaining structural integrity and adhesion (critical for preventing delamination).
Large Area HomogeneityWafers up to 125 mm Diameter. Our MPCVD systems provide uniform, high-quality PCD/NCD films across large areas, essential for scaling up production from rat models to human-sized devices.Guarantees consistent electrochemical and biocompatibility performance across entire production batches, reducing variability in clinical devices.
Precise Film ThicknessSCD/PCD Thickness Control (0.1 ”m to 500 ”m). We offer precise control over film thickness, allowing optimization for mechanical flexibility and electrochemical stability.Enables the fabrication of robust yet minimally invasive neural probes, balancing mechanical strength with signal integrity.
Integrated MetalizationCustom Metal Stacks (Au, Pt, Pd, Ti, W, Cu). We provide internal metalization services directly onto the diamond surface.Eliminates the need for external processing steps, offering a single-source solution for fully functional, metalized BDD electrodes ready for packaging and implantation.
Surface Finish RequirementsUltra-Low Roughness Polishing. Polishing capabilities down to Ra < 5 nm for inch-size PCD/BDD.A smooth, high-quality surface finish is crucial for minimizing protein fouling and further enhancing the already superior biocompatibility demonstrated by BDD.

Engineering Support: 6CCVD’s in-house PhD team specializes in diamond electrochemistry and material science and can assist researchers and engineers with material selection, doping optimization, and custom fabrication recipes for chronic neural stimulation and recording projects.

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

View Original Abstract

Boron-doped nanocrystalline diamond (BDD) electrodes have recently attracted attention as materials for neural electrodes due to their superior physical and electrochemical properties, however their biocompatibility remains largely unexplored. In this work, we aim to investigate the in vivo biocompatibility of BDD electrodes in relation to conventional titanium nitride (TiN) electrodes using a rat subcutaneous implantation model. High quality BDD films were synthesized on electrodes intended for use as an implantable neurostimulation device. After implantation for 2 and 4 weeks, tissue sections adjacent to the electrodes were obtained for histological analysis. Both types of implants were contained in a thin fibrous encapsulation layer, the thickness of which decreased with time. Although the level of neovascularization around the implants was similar, BDD electrodes elicited significantly thinner fibrous capsules and a milder inflammatory reaction at both time points. These results suggest that BDD films may constitute an appropriate material to support stable performance of implantable neural electrodes over time.

Tech Support

Section titled “Tech Support”

Original Source

Section titled “Original Source”

References

Section titled “References”
  1. 2008 - Nanocrystalline diamond: in vitro biocompatibility assessment by MG63 and human bone marrow cells cultures [Crossref]
  2. 2009 - A diamond-based biosensor for the recording of neuronal activity [Crossref]
  3. 2015 - Nanostructured platinum grass enables superior impedance reduction for neural microelectrodes [Crossref]
  4. 2011 - Synthesis and characterization of multilayered diamond coatings for biomedical implants [Crossref]
  5. 2013 - Nanostructured diamond coatings for orthopaedic applications [Crossref]
  6. 2009 - A novel diamond microprobe for neuro-chemical and -electrical recording in neural prosthesis [Crossref]
  7. 2008 - Neural stimulation and recording electrodes [Crossref]
  8. 2001 - Origin of the 1150 cm-1 Raman mode in nanocrystalline diamond [Crossref]
  9. 2013 - In vivo pH monitoring using boron doped diamond microelectrode and silver needles: application to stomach disorder diagnosis [Crossref]
  10. 2012 - In vivo assessment of cancerous tumors using boron doped diamond microelectrode [Crossref]

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