A microsensing system for the <i>in vivo</i> real-time monitoring of local drug kinetics
At a Glance
Section titled âAt a Glanceâ| Metadata | Details |
|---|---|
| Publication Date | 2018-01-01 |
| Journal | Proceedings for Annual Meeting of The Japanese Pharmacological Society |
| Authors | Genki Ogata, Kai Asai, Yamato Sano, Madoka Takai, Hiroyuki Kusuhara |
| Institutions | Niigata University, The University of Tokyo |
| Analysis | Full AI Review Included |
Technical Documentation & Analysis: Boron-Doped Diamond Microsensors for In Vivo Drug Kinetics
Section titled âTechnical Documentation & Analysis: Boron-Doped Diamond Microsensors for In Vivo Drug Kineticsâ6CCVD Ref: BD-PK-2018-001 Source: Ogata G. et al. A microsensing system for the in vivo real-time monitoring of local drug kinetics (WCP2018 Poster Session, based on Nature Biomedical Engineering 1, 654-666, 2017).
Executive Summary
Section titled âExecutive SummaryâThis research validates the use of highly localized, needle-type Boron-Doped Diamond (BDD) microsensors for analyzing drug pharmacokinetics and pharmacodynamics in vivo. This application leverages the exceptional stability and electrochemical window of MPCVD diamond materials.
- Core Achievement: Successful development and deployment of a BDD microsensor system capable of continuous, real-time monitoring of localized drug concentration changes within living tissues.
- High Sensitivity & Speed: The sensor achieved high-speed kinetic tracking with a rapid time resolution of approximately 5 seconds.
- Micro-Scale Geometry: Utilized a needle-type sensor geometry with a tip diameter of approximately 40 ”m, confirming the feasibility of minimally invasive implantation for local analysis.
- Dual Functionality: The BDD sensor was integrated alongside a glass microelectrode to simultaneously measure localized drug concentration and corresponding cellular electrophysiological responses.
- Diverse Applications: The system was successfully applied to measure the localized action of diverse pharmaceuticals, including the diuretic Bumetanide (in the cochlea), the antiepileptic Lamotrigine (in the brain), and the anticancer drug Doxorubicin.
- Market Opportunity: This development positions BDD as the material of choice for next-generation, high-stability neurochemical and pharmaceutical monitoring tools, replacing conventional methods with poor sampling rates.
Technical Specifications
Section titled âTechnical SpecificationsâThe following parameters were extracted from the research abstract, outlining the key performance characteristics and material requirements for the microsensing system.
| Parameter | Value | Unit | Context |
|---|---|---|---|
| Sensor Material | Boron-Doped Diamond (BDD) | N/A | Enables stable, wide-potential electrochemistry |
| Sensor Type | Electrochemical Microsensor | N/A | Used for real-time drug concentration detection |
| Sensor Geometry | Needle-type | N/A | Designed for localized, deep-tissue insertion |
| Tip Diameter (Target) | ~40 | ”m | Critical dimension for minimal invasiveness |
| Time Resolution | ~5 | seconds | High rate required for real-time kinetics measurement |
| Environment of Use | In vivo (Real-Time) | N/A | Tested in guinea-pig cochlea and rat brain |
| Complementary Sensor | Glass Microelectrode | N/A | Used for simultaneous cellular electrophysiology monitoring |
| Drug Examples Monitored | Bumetanide, Lamotrigine, Doxorubicin | N/A | Demonstrates broad chemical applicability |
Key Methodologies
Section titled âKey MethodologiesâThe research focuses on the deployment and validation of a composite sensing platform designed for simultaneous measurement of pharmaceutical kinetics and physiological response in situ.
- Sensor Fabrication: Development of needle-type BDD electrodes optimized for high conductivity and geometric precision, featuring tip diameters around 40 ”m.
- System Integration: Creation of a dual-sensor platform pairing the BDD electrochemical sensor with a glass microelectrode for simultaneous monitoring of drug concentration and local electrical potential.
- Targeted Drug Delivery: Systemic administration (e.g., intravenous injection) of target drugs (Bumetanide, Lamotrigine, Doxorubicin) to animal models (in vivo).
- Real-Time Local Monitoring: Insertion of the microsensing system into specific, delicate tissues (e.g., guinea-pig cochlea, rat brain) to capture localized drug concentration changes over a high-time resolution (~5 seconds).
- Correlative Analysis: Direct correlation of the measured drug concentration profiles (pharmacokinetics) with simultaneous shifts in extracellular or local field potentials (pharmacodynamics), confirming functional impact.
6CCVD Solutions & Capabilities
Section titled â6CCVD Solutions & CapabilitiesâThis demanding applicationârequiring chemically stable, highly conductive, and geometrically precise micro-sensorsâis perfectly addressed by 6CCVDâs customized MPCVD diamond portfolio. We specialize in providing the foundational materials and fabrication services necessary to replicate and advance this research.
Applicable Materials
Section titled âApplicable MaterialsâThe sensitivity and stability requirements of the in vivo electrochemical sensor necessitate specific material characteristics only achievable with heavily boron-doped diamond.
| Material Solution | 6CCVD Offering | Application Rationale |
|---|---|---|
| Boron-Doped Diamond (BDD) | Heavy Boron Doped Polycrystalline Diamond (BDD-PCD) | Required for metallic conductivity, ultra-wide electrochemical window, and unparalleled electrochemical stability in biological media. |
| High Purity Substrates | SCD or High-Purity PCD Substrates | Used as robust base platforms for BDD film growth, ensuring mechanical integrity for needle-type geometries. |
Customization Potential for Microsensor Development
Section titled âCustomization Potential for Microsensor DevelopmentâReplicating the ~40 ”m needle tip and ensuring reliable electrical performance requires advanced manufacturing capabilities, all provided in-house by 6CCVD.
- Precision Thickness Control: We supply BDD layers from 0.1 ”m (thin film requirements) up to 500 ”m or thicker substrates (up to 10mm), providing the optimal mechanical stiffness required for invasive, needle-type geometries.
- Custom Geometries and Shaping: To achieve the required tip dimensions, 6CCVD offers advanced laser micro-shaping and precision dicing services on BDD wafers up to 125mm in size. This includes the ability to generate specific taper angles and tip radii down to the required micron scale.
- Electrode Contact Metalization: We provide internal metalization services essential for connecting the BDD working electrode to external electronics. Available stacks include standard Au, Pt, Pd, Ti, W, and Cu, optimized for biocompatibility and adhesion to diamond surfaces.
- Superior Surface Finish: For reproducible electrochemical performance, especially in micro-environments, surface smoothness is critical. 6CCVD guarantees ultra-low roughness polishing, with Ra typically < 5 nm for inch-size PCD/BDD wafers.
Engineering Support
Section titled âEngineering Supportâ6CCVDâs dedicated team of PhD-level material scientists and engineers understand the specific challenges of developing diamond-based bio- and neuro-sensors.
- We offer comprehensive support for determining the optimal Boron doping level and material architecture required to maximize electrochemical sensitivity and minimize fouling in complex in vivo matrices.
- Consultation services are available to assist researchers in designing custom wafer layouts, including integrated contact pads and microfluidic channels, for highly advanced bio-sensing projects utilizing the wide electrochemical capabilities of BDD.
For custom specifications or material consultation on BDD microsensors for neurochemistry or pharmaceutical monitoring, visit 6ccvd.com or contact our engineering team directly. Global shipping (DDU default, DDP available) ensures rapid delivery worldwide.
View Original Abstract
It is crucial to continuously measure local concentrations of systemically administered drugs in vivo in different organs and tissues. However, conventional methods require considerable samples quantities and have poor sampling rates. Additionally, they cannot address how drug kinetics correlates with target function over time. In this study, we developed a system with two different sensors. One is a needle-type of boron-doped diamond microsensor with tip diameter ïœ40 ”m. This sensor can detect change of drug concentrations with time resolution of ïœ5 seconds. The other is a glass microelectrode for monitoring cellular electrophysiological responses. We first tested the bumetanide, a blocker for Na+,K+,2Clâcotransporter blocker. This diuretic can induce deafness. In the guinea-pig cochlea injected intravenously with bumetanide, the changes of the drug concentration and the extracellular potential underlying hearing were simultaneously measured in real time. We further examined an antiepileptic drug lamotrigine, which inhibits Na+ channel, in the rat brain, and tracked its kinetics and at the same time the local field potentials mirroring neuronal activity. The action of the anticancer reagent doxorubicin was also monitored in vivo. This microsensing system may be applied to analyze pharmacokinetics and pharmacodynamics of various drugs at local sites.