An Electrochemical Sensor of Theophylline on a Boron-Doped Diamond Electrode Modified with Nickel Nanoparticles

At a Glance

Metadata	Details
Publication Date	2023-10-20
Journal	Sensors
Authors	Prastika Krisma Jiwanti, Anis Puspita Sari, Siti Wafiroh, Yeni Wahyuni Hartati, Jarnuzi Gunlazuardi
Institutions	Airlangga University, Tokyo University of Science
Citations	17
Analysis	Full AI Review Included

Executive Summary

This study successfully developed a highly precise and selective electrochemical sensor for theophylline by modifying a Boron-Doped Diamond (BDD) electrode with Nickel Nanoparticles (NiNPs) via a simple electrodeposition method.

Enhanced Performance: The BDD/NiNP sensor achieved a superior Signal/Background (S/B) ratio of 6.63, significantly higher than the unmodified BDD (1.98), primarily due to a substantial reduction in background current.
Low Limit of Detection (LOD): The sensor demonstrated a low LOD of 2.79 µM, making it suitable for monitoring theophylline within the critical therapeutic range (55 to 110 µM in plasma).
Surface Area Increase: NiNP modification increased the electrochemically active surface area 8-fold, from 0.0011 cm² (BDD) to 0.0081 cm² (BDD/NiNP), enhancing electrocatalytic activity.
High Accuracy and Precision: Validation in artificial urine samples yielded an excellent recovery of 105.10% and high precision, with a Relative Standard Deviation (%RSD) of 1.65%.
Selectivity and Stability: The sensor exhibited strong selectivity against common biological interferents, including D-glucose, urea, and ammonium sulfate.
Cost-Effective Modification: The use of non-precious nickel nanoparticles provides a sustainable and low-cost alternative to noble metal modifications for electrochemical sensing.

Technical Specifications

Parameter	Value	Unit	Context
Active Surface Area (BDD/NiNP)	0.0081	cm²	Calculated via Randles-Sevcik equation
Active Surface Area (BDD)	0.0011	cm²	Unmodified electrode baseline
Limit of Detection (LOD)	2.79	µM	BDD/NiNP sensor performance
Linear Concentration Range	30 to 100	µM	Theophylline sensing range
Signal/Background (S/B) Ratio	6.63	N/A	BDD/NiNP (Optimum pH 3.0)
Sensitivity (BDD/NiNP)	0.3002	µA/µM	Calibration curve slope
Theophylline Oxidation Potential	+1.30	V (vs Ag/AgCl)	Measured via SWV
Optimum pH for Sensing	3.0	N/A	0.1 M Phosphate Buffer Solution (PBS)
Oxidation Mechanism	Irreversible, diffusion-controlled	N/A	Involves 2 protons and 2 electrons
Relative Standard Deviation (%RSD)	1.36	%	Reproducibility (n=8)
Recovery (Artificial Urine)	105.10	%	Real sample analysis
Average Deposited Ni Particle Size	82.27	nm	SEM analysis
NiNP Electrodeposition Potential	-1.2	V	Chronoamperometry setting
NiNP Electrodeposition Time	250	s	Chronoamperometry setting

Key Methodologies

BDD Pretreatment: The BDD electrode was cleaned by sonication in 1-propanol and ultrapure water (5 min each). Electrochemical optimization was performed using Cyclic Voltammetry (CV) in 0.1 M H₂SO₄ (40 scans, 1 V/s scan rate, -2.0 V to +2.0 V range).
NiNP Modification: Nickel Nanoparticles were deposited onto the BDD surface using chronoamperometry.
Deposition Recipe: The precursor solution was 1 mM NiSO₄ in 0.1 M acetic buffer (pH 5.5). A constant potential of -1.2 V (vs Ag/AgCl) was applied for 250 s.
Material Characterization: The modified BDD/NiNP electrode was analyzed using Scanning Electron Microscopy (SEM) to confirm homogeneous deposition (average particle size 82.27 nm) and X-ray Photoelectron Spectroscopy (XPS) to verify the presence of metallic Ni (Ni⁰) and Ni(OH)₂ species.
Electrochemical Analysis: Square Wave Voltammetry (SWV) and Cyclic Voltammetry (CV) were used for theophylline detection. The optimal supporting electrolyte was determined to be 0.1 M PBS at pH 3.0.
Performance Validation: The sensor was tested for linearity (30-100 µM), LOD, selectivity (against urea, D-glucose, ammonium sulfate), and reproducibility (%RSD < 5%).
Real Sample Testing: The standard addition method was applied to artificial urine samples spiked with 60 µM theophylline to determine accuracy and recovery.

Commercial Applications

Therapeutic Drug Monitoring (TDM): Enables rapid, accurate, and portable monitoring of theophylline levels in patient blood or urine, crucial for managing asthma and chronic pulmonary disorders due to the drug’s narrow therapeutic window.
Point-of-Care (POC) Diagnostics: The simplicity and stability of the BDD/NiNP platform are ideal for developing robust, handheld electrochemical sensors for clinical use outside of centralized laboratories.
Sustainable Electrocatalysis: Utilizes abundant and low-cost nickel as an effective electrocatalyst, reducing reliance on expensive and scarce noble metals (e.g., Au, Pt) in sensor manufacturing.
High-Performance Sensor Platforms: The BDD substrate offers exceptional chemical inertness, low background current, and a wide potential window, making it a preferred material for harsh environment sensing and complex biological matrices.
Pharmaceutical Quality Control: Provides a sensitive and precise method for quality assurance testing of drug concentrations in pharmaceutical formulations.

View Original Abstract

Theophylline is a drug with a narrow therapeutic range. Electrochemical sensors are a potentially effective method for detecting theophylline concentration to prevent toxicity. In this work, a simple modification of a boron-doped diamond electrode using nickel nanoparticles was successfully performed for a theophylline electrochemical sensor. The modified electrode was characterized using a scanning electron microscope and X-ray photoelectron spectroscopy. Square wave voltammetry and cyclic voltammetry methods were used to study the electrochemical behavior of theophylline. The modified nickel nanoparticles on the boron-doped diamond electrode exhibited an electrochemically active surface area of 0.0081 cm2, which is larger than the unmodified boron-doped diamond’s area of 0.0011 cm2. This modified electrode demonstrated a low limit of detection of 2.79 µM within the linear concentration range from 30 to 100 µM. Moreover, the modified boron-doped diamond electrode also showed selective properties against D-glucose, ammonium sulfate, and urea. In the real sample analysis using artificial urine, the boron-doped diamond electrode with nickel nanoparticle modifications achieved a %recovery of 105.10%, with a good precision of less than 5%. The results of this work indicate that the developed method using nickel nanoparticles on a boron-doped diamond electrode is promising for the determination of theophylline.

Tech Support

Original Source

DOI: https://doi.org/10.3390/s23208597

References

2013 - Theophylline [Crossref]
2020 - Systemic medications in chronic obstructive pulmonary disease: Use and outcomes [Crossref]
2016 - Design, synthesis, anticancer, antimicrobial actiities and molecular docking studies of theophylline containing acetylenes and theo-phylline containing 1,2,3-triazoles with variant nucleoside derivatives [Crossref]
2017 - Pre-diction of serum theophylline concentrations and cytochrome P450 1A2 activity by analyzing urinary metabolites in preterm infants [Crossref]
2010 - Rapid determination of methylxanthines in real samples by high-performance liquid chromatography using the new FastGradient® narrow-bore monolithic column [Crossref]
2019 - Carbon nanoparticle-protected RNA aptasensor for amplified fluorescent determination of theophylline in serum based on nuclease-aided signal amplification [Crossref]
2019 - Derivative UV-spectroscopic determination of theophyl-line, salbutamol sulfate and glycerylguaicolate in syrup mixture [Crossref]
2018 - Highly sensitive gold nanoparticle-based electrochemical aptasensor for the-ophylline detection [Crossref]
2018 - Highly sensitive determination of the-ophylline based on graphene quantum dots modified electrode [Crossref]