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Microsensing systems using diamond electrode for <i>in vivo </i>and <i>in vitro</i> detection of drug kinetics

MetadataDetails
Publication Date2021-01-01
JournalProceedings for Annual Meeting of The Japanese Pharmacological Society
AuthorsHiroshi Hibino
InstitutionsPharmac, The University of Osaka
AnalysisFull AI Review Included

Technical Documentation: Diamond Electrodes for High-Speed Drug Kinetics Sensing

Section titled “Technical Documentation: Diamond Electrodes for High-Speed Drug Kinetics Sensing”

This document analyzes the requirements for developing advanced microsensing systems utilizing diamond electrodes for in vivo and in vitro drug kinetics detection, focusing on how 6CCVD’s specialized MPCVD diamond materials and fabrication services meet these demanding specifications.


The research demonstrates the critical role of diamond electrodes in accelerating pharmacological research by enabling high-speed, accurate drug kinetics measurement in complex biological environments.

  • Core Value Proposition: Diamond electrodes provide a state-of-the-art platform for electrochemistry, facilitating high-speed and accurate measurement of drug concentrations in real-time.
  • Dual Sensing Approach: Two distinct microsensing systems were developed: one for in vivo real-time monitoring and one for rapid in vitro quantification.
  • In Vivo Application: A needle-type diamond microelectrode was successfully used to measure pharmacokinetics (PK) and pharmacodynamics (PD) in localized areas of rodent organs (inner ear and brain).
  • In Vitro Efficiency: A rapid procedure quantified drugs (e.g., Pazopanib) in small biological samples (~100 µL blood), completing the entire process in just 10 minutes.
  • Material Requirement: The success hinges on the use of highly conductive, chemically inert diamond material suitable for microelectrode fabrication.
  • Clinical Impact: These strategies significantly contribute to advances in drug development and the acceleration of tailored medicine.

The following table summarizes the key operational parameters and material requirements extracted from the research abstract.

ParameterValueUnitContext
Electrode MaterialConductive DiamondN/AEssential for robust electrochemistry in biological media
Electrode Geometry (In Vivo)Needle-typeN/ARequired for minimally invasive, localized insertion into organs
Sample Volume (In Vitro)~100µLSmall aliquot of blood required for rapid quantification
Analysis Time (In Vitro)10minTotal process time for quantifying multi-kinase inhibitor (Pazopanib)
Application EnvironmentIn Vivo / In VitroN/AReal-time PK/PD measurement in live animals and biological samples
Test AnalytesLamotrigine, PazopanibN/AAntiepileptic, Multi-kinase inhibitor, and Ototoxic Diuretic

The research employed specialized techniques focusing on the unique properties of diamond for electrochemical sensing in biological systems.

  1. Development of Microsensing Systems: Two distinct, high-speed microsensing platforms were engineered using diamond electrodes to overcome the challenges of conventional pharmacological measurement.
  2. Needle Electrode Fabrication: Fabrication of needle-type diamond electrodes was necessary to create a drug monitoring microsensor capable of targeting local areas within live animal organs.
  3. Integrated Sensing Platform: The diamond electrode was paired with a glass microelectrode to simultaneously detect drug concentration changes and cellular/tissue electrical activities.
  4. Real-Time PK/PD Measurement: Systemically administered compounds (ototoxic diuretic, lamotrigine) were monitored in real time within the inner ear and brain of rodents.
  5. Rapid In Vitro Quantification: A procedure was established to rapidly and easily determine drug concentrations (Pazopanib) using only a small volume (~100 µL) of blood sample.

6CCVD is uniquely positioned to supply the advanced MPCVD diamond materials and custom fabrication services required to replicate, scale, and extend this critical pharmacological research. The high chemical inertness, wide potential window, and mechanical robustness of our diamond materials are ideal for demanding in vivo and in vitro electrochemical applications.

To achieve the necessary conductivity and stability for electrochemical sensing in biological fluids, Boron-Doped Diamond (BDD) is the required material.

  • Primary Material: Heavy Boron Doped PCD or SCD (BDD).
    • Justification: BDD provides the necessary metallic conductivity, extreme chemical inertness, and stability against biofouling, which is crucial for reproducible measurements in complex biological matrices (blood, tissue fluid).
  • Substrate Material: High-Purity SCD or PCD Wafers.
    • Justification: These serve as the robust, high-quality precursors for fabricating the needle-type microelectrodes, ensuring mechanical strength for in vivo insertion.

The fabrication of needle-type microelectrodes and integrated sensors requires precise shaping and reliable electrical contacts, capabilities that 6CCVD provides in-house.

Research Requirement6CCVD Customization ServiceTechnical Specification Match
Microelectrode GeometryCustom Laser Cutting & ShapingWe can process SCD/PCD plates up to 125mm into complex geometries required for needle-type sensors, ensuring high aspect ratio and precision.
Electrical InterfacingCustom MetalizationInternal capability for depositing highly conductive and biocompatible contacts (e.g., Au, Pt, Ti) onto the BDD surface for reliable connection to external circuitry.
Surface FinishUltra-Low Roughness PolishingPolishing services achieve Ra < 1nm (SCD) or Ra < 5nm (PCD), minimizing non-specific protein adsorption and maximizing electrochemical signal integrity.
Thickness ControlPrecision Thickness GrowthWe offer BDD layers from 0.1µm to 500µm, allowing researchers to optimize the active sensing area and overall device resistance.

6CCVD’s in-house PhD team specializes in MPCVD growth and material optimization for electrochemical applications. We can assist researchers in selecting the optimal boron doping concentration and crystal orientation (for SCD) to maximize sensitivity and stability for similar Drug Kinetics and Pharmacological Sensing projects.

For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly. We offer global shipping (DDU default, DDP available) for seamless delivery of your custom diamond solutions.

View Original Abstract

High-speed and accurate measurement of drug kinetics in in vivo microenvironment or small aliquot of biological sample is crucial for basic and applied researches in pharmacology. To address this issue is challenging with conventional methods. We developed two different microsensing systems using diamond electrode, a state-of-the-art material for electrochemistry. First technique targets local area of a few organs in live animals. The analytical platform harbors a drug monitoring microsensor composed of needle-type diamond electrode and a glass microelectrode that detects cellular and tissue electrical activities. For test analytes an ototoxic loop diuretic and an antiepileptics lamotrigine were selected; pharmacokinetics and pharmacodynamics of the systemically administrated compounds were measured in real time in the inner ear and brain of rodents, respectively. In each case, the behavior of the drug concentration clearly differed from change of the electrical signals. Second, we described a procedure to rapidly and easily determine drug concentrations in ~100 µL blood sample. With the package of this micro-measurement, we quantified pazopanib, a multi-kinase inhibitor―all the processes were completed in 10 min. The strategies shown here would contribute to advances in drug development and accelerate tailored medicine.