Real-time intraocular antiglaucoma drugs measurement in porcine eyes using boron-doped diamond microelectrodes.
At a Glance
Section titled “At a Glance”| Metadata | Details |
|---|---|
| Publication Date | 2023-01-01 |
| Journal | Proceedings for Annual Meeting of The Japanese Pharmacological Society |
| Authors | Genki Ogata, Mao Yoneda, Risa Ogawa, Ai Hanawa, Kai Asai |
| Institutions | The University of Tokyo, Keio University |
| Analysis | Full AI Review Included |
Technical Documentation: Real-Time Biosensing using Boron-Doped Diamond (BDD)
Section titled “Technical Documentation: Real-Time Biosensing using Boron-Doped Diamond (BDD)”Source Paper: Real-time intraocular antiglaucoma drugs measurement in porcine eyes using boron-doped diamond microelectrodes. (Ogata et al., Keio Univ./Univ. of Tokyo Sch. Med.)
Executive Summary
Section titled “Executive Summary”This research validates the use of Boron-Doped Diamond (BDD) microelectrodes for high-temporal-resolution electrochemical monitoring in complex biological environments, a critical application for pharmaceutical development and clinical diagnostics.
- Application Focus: Real-time measurement of intraocular drug concentrations, specifically Timolol Maleate (TIM), an antiglaucoma agent.
- Problem Solved: Conventional methods (e.g., LC-MS/MS) require multiple samples and lack the temporal resolution necessary for continuous kinetic tracking ex vivo or in vivo.
- Material Solution: Boron-Doped Diamond (BDD) microelectrodes provide the necessary stability and electrochemical window for reliable sensing in aqueous humor.
- Key Achievement: Successful optimization and demonstration of continuous ex vivo monitoring of TIM concentration changes in enucleated porcine eyes.
- Commercial Value: Establishes BDD as the superior material platform for developing next-generation, high-resolution biosensors for pharmaceutical kinetics and ophthalmology.
Technical Specifications
Section titled “Technical Specifications”The following table summarizes the key parameters and functional requirements derived from the study, focusing on the material science and application context.
| Parameter | Value | Unit | Context |
|---|---|---|---|
| Electrode Material | Boron-Doped Diamond (BDD) | N/A | Required for wide potential window and stability in biological fluids. |
| Target Analyte | Timolol Maleate (TIM) | N/A | Sympathetic beta-receptor antagonist (antiglaucoma drug). |
| Measurement Environment | Aqueous Humor | N/A | Biological matrix collected from porcine eyes. |
| Device Geometry | Microelectrode | N/A | Necessary for localized, minimally invasive intraocular sensing. |
| Measurement Mode | Continuous ex vivo Monitoring | N/A | Demonstrates high temporal resolution tracking of drug kinetics. |
| Conventional Limitation | LC-MS/MS | N/A | Lacks the high temporal resolution achieved by BDD electrodes. |
Key Methodologies
Section titled “Key Methodologies”The research focused on optimizing the BDD electrode system for continuous, real-time drug monitoring in a complex biological matrix.
- BDD Microelectrode Development: Fabrication and preparation of Boron-Doped Diamond microelectrodes suitable for high-sensitivity electrochemical detection.
- Electrochemical Optimization: Optimization of the measurement method specifically tailored for the continuous detection of Timolol Maleate (TIM).
- Calibration Curve Generation: Obtaining precise calibration curves for each BDD microelectrode using aqueous humor collected from porcine eyes, ensuring accuracy within the target matrix.
- Continuous Ex Vivo Demonstration: Implementation of the optimized BDD microelectrodes to monitor the continuous changes in TIM concentration within enucleated porcine eyes.
6CCVD Solutions & Capabilities
Section titled “6CCVD Solutions & Capabilities”6CCVD is the world leader in MPCVD diamond manufacturing, providing the high-purity, custom-doped materials essential for replicating and advancing this critical biosensing research.
Applicable Materials
Section titled “Applicable Materials”To achieve the high sensitivity and stability required for electrochemical sensing in biological fluids, 6CCVD recommends the following materials:
- Heavy Boron-Doped Polycrystalline Diamond (PCD): Ideal for large-scale electrode arrays and microelectrode fabrication, offering high conductivity and mechanical robustness. Available in plates/wafers up to 125mm.
- Boron-Doped Single Crystal Diamond (SCD): Recommended for applications requiring the highest possible surface quality (Ra < 1nm) and superior material uniformity, critical for ultra-sensitive microelectrode performance.
- BDD Thickness Control: We offer precise BDD layer thickness control from 0.1µm up to 500µm, allowing researchers to optimize conductivity and minimize material usage.
Customization Potential
Section titled “Customization Potential”The development of microelectrodes for intraocular sensing requires precise geometry and robust integration. 6CCVD provides comprehensive services to meet these needs:
| Requirement | 6CCVD Capability | Specification Range |
|---|---|---|
| Substrate Size | Custom Plates and Wafers | Up to 125mm diameter (PCD) |
| Micro-Patterning | Precision Laser Cutting & Etching | Custom shapes and micro-geometries required for electrode arrays. |
| Surface Finish | Ultra-Low Roughness Polishing | Ra < 1nm (SCD) and Ra < 5nm (PCD) for optimal electrode-electrolyte interface. |
| Electrical Contacting | Custom Metalization | In-house deposition of biocompatible metals (Au, Pt, Ti, Pd, Cu) for robust electrical leads and sensor integration. |
| Substrate Thickness | Custom Substrates | Up to 10mm thick for robust handling and packaging. |
Engineering Support
Section titled “Engineering Support”The successful transition of BDD technology from laboratory proof-of-concept to reliable clinical or pharmaceutical tools requires deep material expertise. 6CCVD’s in-house PhD team specializes in optimizing diamond growth parameters (doping concentration, surface termination, and defect control) for electrochemical and biosensing applications.
We offer consultation services to assist researchers in material selection, electrode design, and integration strategies for similar pharmaceutical kinetics, ophthalmological diagnostics, and ex vivo monitoring projects.
For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly.
View Original Abstract
The primary treatment for glaucoma, the leading cause of intermediate vision impairment, involves administering ocular hypotensive drugs in topical eye drops. Observation of the real-time changes in the drugs through the cornea and reaching the anterior chamber is essential to improve or develop a safe, reliable, and effective medical treatment. Conventional methods such as LC-MS/MS are used to measure the temporal changes in the drug in the aqueous humor; however, this technique involves multiple measurements of the eyes of multiple test subjects to measure changes over time with high temporal resolution. To resolve this problem, we develop a measurement method that utilizes boron-doped diamond (BDD) microelectrodes to track the real-time drug concentrations in the anterior chamber of the eye. First, we optimize the method for continuously measuring timolol maleate (TIM), a sympathetic beta-receptor antagonist, and obtain the calibration curves of each BDD microelectrode in the aqueous humor collected from porcine eyes. Next, we demonstrate the continuous ex vivo monitoring of the TIM in the enucleated porcine eyes. The results suggest that changes in the intracameral TIM concentration can be monitored using BDD microelectrodes.