A prototype of the microsensing system for i<i>n vivo</i> drug monitoring in the skin with diamond electrode
At a Glance
Section titled âAt a Glanceâ| Metadata | Details |
|---|---|
| Publication Date | 2022-01-01 |
| Journal | Proceedings for Annual Meeting of The Japanese Pharmacological Society |
| Authors | Norzahirah Ahmad, Seishiro Sawamura, Genki Ogata, Yasuaki Einaga, Hiroshi Hibino |
| Institutions | The University of Osaka, Keio University |
| Analysis | Full AI Review Included |
Technical Documentation & Analysis: BDD Microsensing for In Vivo Pharmacokinetics
Section titled âTechnical Documentation & Analysis: BDD Microsensing for In Vivo PharmacokineticsâExecutive Summary
Section titled âExecutive SummaryâThis research demonstrates the successful prototyping of a diamond-based microsensing system for real-time drug monitoring, highlighting the superior electrochemical properties of Boron-Doped Diamond (BDD) for biomedical applications.
- Application Focus: Development of a prototype microsensing system for real-time in vivo monitoring of drug pharmacokinetics (PK) in the dermal interstitial fluid.
- Core Technology: Utilizes a needle-type Boron-Doped Diamond (BDD) electrode, leveraging diamondâs wide potential window and stability for electrochemical detection via redox reaction.
- Target Analyte: The anticancer drug Doxorubicin was successfully detected, demonstrating the sensorâs utility in critical therapeutic monitoring.
- High Sensitivity: In vitro calibration confirmed the sensorâs ability to cover the crucial therapeutic window, ranging from 10 nM to 100 nM.
- Successful In Vivo Validation: The sensor tracked local PK in anesthetized rats for over one hour following intravenous injection.
- Quantified Results: Measured local PK parameters included a C<sub>max</sub> of 3.1 ± 1.4 nM and a T<sub>max</sub> of 33.6 ± 20.6 minutes (n = 7).
- Commercial Potential: The system provides a foundation for developing non-invasive, continuous monitoring devices capable of linking local measurements to systemic plasma PK data.
Technical Specifications
Section titled âTechnical SpecificationsâThe following hard data points were extracted from the research abstract, detailing the performance and context of the BDD microsensor.
| Parameter | Value | Unit | Context |
|---|---|---|---|
| Sensor Material | Boron-Doped Diamond (BDD) | N/A | Needle-type microelectrode |
| Detection Mechanism | Redox Reaction | N/A | Electrochemical sensing |
| Test Analyte | Doxorubicin | N/A | Anticancer drug |
| Therapeutic Window Covered | 10 - 100 | nM | In vitro calibration range |
| Applied Potential | Negative | Potential | Required to elicit current response |
| Monitoring Duration (In Vivo) | >1 | hour | Local PK tracking in rats |
| Peak Concentration (C<sub>max</sub>) | 3.1 ± 1.4 | nM | Measured local PK in dermis (n = 7) |
| Time to Peak (T<sub>max</sub>) | 33.6 ± 20.6 | mins | Measured local PK in dermis (n = 7) |
Key Methodologies
Section titled âKey MethodologiesâThe experimental procedure focused on validating the BDD microelectrodeâs performance from controlled in vitro environments to complex in vivo biological systems.
- Electrode Fabrication: A needle-type Boron-Doped Diamond (BDD) electrode was utilized, designed to access the local dermal interstitial fluid.
- Analyte Selection: Doxorubicin, an anticancer drug, was chosen as the test compound due to the clinical relevance of monitoring its pharmacokinetics (PK).
- Electrochemical Testing (In Vitro): The BDD microsensor was tested by applying a negative potential, which successfully elicited a current response corresponding to the Doxorubicin concentration.
- Calibration: A calibration curve was generated, confirming the sensorâs linearity and sensitivity across the therapeutic window (10-100 nM).
- Fluid Validation: Sensor performance was verified using collected interstitial fluids prior to live animal testing.
- Live In Vivo Testing: The sensor was inserted into the dermis layer of anesthetized live rats.
- PK Tracking: Following intravenous injection of Doxorubicin, the local PK profile was tracked continuously for over one hour.
- Systemic Correlation: A formula was applied to link the local dermal measurements to systemic plasma data, demonstrating applicability for real-time systemic PK monitoring.
6CCVD Solutions & Capabilities
Section titled â6CCVD Solutions & Capabilitiesâ6CCVD is the premier supplier of MPCVD diamond materials required to replicate, optimize, and scale this advanced biosensing technology. Our expertise in BDD synthesis and custom micro-fabrication directly addresses the needs of electrochemical sensor development.
Applicable Materials
Section titled âApplicable MaterialsâTo achieve the high sensitivity and stability required for in vivo redox sensing, 6CCVD recommends the following materials:
- Heavy Boron-Doped Diamond (BDD): This is the critical material. 6CCVD provides highly conductive BDD films and substrates with optimized doping levels, ensuring the low background current and wide potential window necessary for robust electrochemical detection of compounds like Doxorubicin.
- Polycrystalline Diamond (PCD) Substrates: BDD films are typically grown on high-quality PCD. We offer PCD wafers up to 125mm in diameter, enabling high-volume production of micro-sensor arrays.
Customization Potential
Section titled âCustomization PotentialâThe needle-type geometry and micro-scale nature of this sensor demand precision engineering. 6CCVD offers end-to-end customization services:
| Capability | 6CCVD Offering | Relevance to PK Sensor Development |
|---|---|---|
| Custom Dimensions | Plates/wafers up to 125mm (PCD). | Allows for large-scale fabrication of sensor arrays. |
| Thickness Control | SCD/PCD films from 0.1 ”m to 500 ”m. | Critical for controlling the active sensing area and mechanical strength of the needle tip. |
| Micro-Shaping | Advanced laser cutting and etching services. | Essential for creating the precise needle-type geometry required for dermal insertion. |
| Metalization | In-house deposition of Au, Pt, Pd, Ti, W, Cu. | Necessary for creating reliable electrical contacts (e.g., Ti/Au) to interface the BDD electrode with external monitoring electronics. |
| Surface Finish | Polishing to Ra < 5nm (Inch-size PCD). | Ensures a smooth, biocompatible surface finish for in vivo applications. |
Engineering Support
Section titled âEngineering Supportâ6CCVD understands that material quality is paramount in sensitive electrochemical applications.
- Our in-house PhD team provides expert consultation on optimizing BDD growth parameters (doping concentration, film thickness) to maximize sensor sensitivity and lifetime for Pharmacokinetic Monitoring and Biosensing projects.
- We offer global shipping (DDU default, DDP available) to ensure researchers worldwide receive high-specification MPCVD diamond materials quickly and reliably.
For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly.
View Original Abstract
Monitoring of plasma drug concentrations is required for effective pharmacotherapy. Repetitive collection of whole blood followed by analysis of plasma samples with conventional methods delays representation of crucial results. Skin is an easily accessible organ; a portion of systemically circulating drug molecules is diffused to the dermal interstitial fluid. Thus, the compoundâs pharmacokinetics (PK) in the fluid mirrors the plasma PK. To approach such local dermal space, here we describe a microsensing system with a needle-type boron-doped diamond (BDD) electrode, which detects chemical compounds by redox reaction. As a test analyte we chose an anticancer drug, doxorubicin. In an in vitro experiment with a BDD microsensor, doxorubicin elicited a current in response to applied negative potential. Calibration curve covered the therapeutic window (10â100 nM). The sensorâs performance was also tested in the collected interstitial fluids. Finally, the sensor was inserted into the dermis layer in anesthetized live rats; after doxorubicin was intravenously injected, the local PK was tracked for >1 hour with the Cmax and Tmax 3.1 ± 1.4 nM and 33.6 ± 20.6 mins, respectively (n = 7). By combining a formula linking the local measurements to plasma data, this microsensing system may be applicable to real-time monitoring of systemic PK.