A Method Designed for Point-of-care System Monitoring Plasma Concentration of an Anticancer Molecular Targeting Drug with Diamond Electrode

At a Glance

Metadata	Details
Publication Date	2022-01-01
Journal	Proceedings for Annual Meeting of The Japanese Pharmacological Society
Authors	Takuro Saiki, Genki Ogata, Seishiro Sawamura, Olga Razvina, Kota Watanabe
Institutions	Niigata University, The University of Osaka
Analysis	Full AI Review Included

Technical Documentation & Analysis: BDD for Point-of-Care Drug Monitoring

Executive Summary

This research successfully validates the use of Boron-Doped Diamond (BDD) electrodes as a rapid, low-cost alternative to Liquid Chromatography-Mass Spectrometry (LC-MS) for Therapeutic Drug Monitoring (TDM).

Core Value Proposition: BDD electrodes enable rapid, easy, and low-cost drug monitoring, addressing the time and cost limitations of conventional LC-MS in personalized medicine.
Target Application: Point-of-care (POC) monitoring of plasma concentrations for the anticancer molecular targeting drug, pazopanib.
Speed and Efficiency: The total procedure time, including sample preparation and electrochemical measurement, was reduced to approximately 10 minutes.
Measurement Time: Drug concentration determination was achieved in a measurement time of only ~35 seconds.
Material Simplicity: The system utilized a simple BDD plate electrode (~26 mm²) without requiring complex chemical surface modifications.
Clinical Validation: Pharmacokinetic data obtained using the BDD sensor were consistent with LC-MS results across both rat models and clinical patient samples.
Commercial Readiness: A compact, palm-sized prototype system was successfully fabricated, demonstrating the potential for widespread, on-site deployment using minimal blood volumes (~60 µL).

Technical Specifications

The following hard data points were extracted regarding the BDD sensor performance and sample requirements:

Parameter	Value	Unit	Context
Electrode Material	Boron-Doped Diamond (BDD)	N/A	Advanced electrochemical material used for sensing
Electrode Area	~26	mm²	Size of the simple BDD plate electrode
Measurement Time (Drug Conc.)	~35	s	Time required for electrochemical determination
Total Procedure Time (TDM)	~10	min	Total time including sample preparation and measurement
Sample Volume (Plasma)	100	µL	Volume of rat plasma analyzed (exogenously mixed)
Sample Volume (Whole Blood)	~60	µL	Volume analyzed by the palm-sized prototype system
Target Analyte	Pazopanib	N/A	Anticancer molecular targeting drug (Tyrosine Kinase Inhibitor)
Validation Standard	LC-MS	N/A	Pharmacokinetic data consistency achieved
System Form Factor	Palm-sized	N/A	Prototype developed for on-site drug monitoring

Key Methodologies

The successful implementation of the BDD sensor relied on the intrinsic properties of the diamond material and streamlined electrochemical procedures:

Material Selection: Boron-Doped Diamond (BDD) was chosen as the electrode material due to its wide potential window, low background current, and exceptional stability, which are critical for complex biological samples like plasma.
Electrode Fabrication: A simple BDD plate electrode of approximately 26 mm² was fabricated and integrated into the sensor system.
Surface Preparation: The BDD electrode was utilized without any chemical surface modifications, simplifying the manufacturing process and reducing sensor cost.
Sample Handling: Minimal sample volumes were required (100 µL plasma or 60 µL whole blood), facilitating point-of-care use.
Electrochemical Measurement: The system performed rapid electrochemical analysis, determining drug concentration in approximately 35 seconds.
Pharmacokinetic Validation: The resulting pharmacokinetic data were rigorously compared against and found to be consistent with results obtained using the gold standard, but resource-intensive, LC-MS method.
System Miniaturization: The final strategy involved fabricating a compact, inexpensive, palm-sized prototype suitable for common use in clinical settings.

6CCVD Solutions & Capabilities

6CCVD is uniquely positioned to supply the high-quality, customized Boron-Doped Diamond (BDD) materials necessary to replicate, scale, and advance this point-of-care TDM technology.

Applicable Materials

To achieve the electrochemical stability and reproducibility required for clinical drug monitoring, 6CCVD recommends the following materials:

Heavy Boron-Doped PCD Wafers: Ideal for large-area electrodes or high-volume production of the simple plate electrode geometry used in this study. Our PCD material offers excellent conductivity and mechanical robustness.
BDD Thin Films on Insulating Substrates: For applications requiring microelectrode arrays or integration into complex microfluidic chips, 6CCVD can deposit highly uniform BDD films (0.1 µm to 500 µm thickness) on substrates like silicon or quartz.
Polishing Grade: For clinical reproducibility where minimizing biofouling is critical, 6CCVD can provide PCD surfaces polished to Ra < 5nm.

Customization Potential

The research utilized a specific 26 mm² electrode area. 6CCVD’s advanced manufacturing capabilities ensure precise material delivery tailored to specific device geometries:

Research Requirement	6CCVD Customization Service	Benefit to Researcher/Engineer
Specific Geometry (26 mm²)	Precision Laser Cutting & Shaping	We provide custom plates/wafers cut to exact dimensions, eliminating post-processing steps.
System Integration	Custom Metalization Services	In-house deposition of contact layers (e.g., Ti/Pt/Au, W/Cu) for robust electrical connection to the palm-sized device electronics.
Scalability	Large-Area BDD Production	Capability to supply BDD plates/wafers up to 125mm in diameter, supporting high-volume manufacturing of the compact sensor.
Thickness Control	SCD/PCD Thickness Control	Precise control over BDD layer thickness (0.1 µm to 500 µm) to optimize conductivity and cost efficiency for electrochemical sensing.

Engineering Support

6CCVD’s in-house team of PhD material scientists specializes in optimizing diamond properties for electrochemical applications. We offer consultation services to assist engineers and scientists with:

Doping Optimization: Tailoring the boron concentration to achieve the ideal conductivity and electrochemical window for specific analytes like tyrosine kinase inhibitors.
Surface Termination: Advising on optimal surface treatments (e.g., hydrogen or oxygen termination) to enhance sensitivity or selectivity for Therapeutic Drug Monitoring (TDM) projects.
Integration Challenges: Providing technical guidance on mounting, bonding, and metalization strategies for integrating BDD electrodes into compact, palm-sized POC systems.

For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly. We ship globally (DDU default, DDP available).

View Original Abstract

Measurement of plasma drug concentrations at a clinical site is essential for personalized medicine. For such purpose, the conventional liquid chromatography-mass spectrometry (LC-MS) method is unlikely to be suitable, owing to time and cost consumption. In this study, we describe an approach to rapid, easy, and low-cost drug monitoring with a boron-doped diamond (BDD) electrode, an advanced electrochemical material. As a test drug, we selected pazopanib, an inhibitor for multiple tyrosine kinase types. A small size sensor system with a simple BDD plate electrode of ~26 mm2 without any chemical modifications determined the drug concentration in a measurement time of ~35 s from 100 µL rat plasma, which was exogenously mixed with pazopanib. We showed that this system was also applicable to blood samples collected from healthy rats orally administrated with pazopanib as well as drug-treated patients with different cancer types. Notably, all the procedures, including sample preparation and electrochemical measurement, were completed in a short time of ~10 min. The pharmacokinetics data obtained by the BDD electrode were similar to the data determined by LC-MS. Finally, we fabricated a prototype of a palm-sized system, which successfully analyzed ~60 µL of rat blood. This strategy may contribute to advances in on-site drug monitoring.

Tech Support

Original Source

DOI: https://doi.org/10.1254/jpssuppl.95.0_2-yia-58