Direct Determination of a Small-Molecule Drug, Valproic Acid, by an Electrically-Detected Microcantilever Biosensor for Personalized Diagnostics

Huang, Long-Sun; Gunawan, Christian; Yen, Yi-Kuang; Chang, Kai-Fung

doi:10.3390/bios5010037

Cited by 11 publications

(7 citation statements)

References 30 publications

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“…21,22 Some biosensor studies were also performed to determine VAL. 23,24 All these methods are chromatography-based and they are time consuming and include cumbersome multiple-step procedures for sample preparation such as solvent extraction, evaporation, and derivatization. Only biosensors can be separated from other techniques due to based theory.…”

Section: Introductionmentioning

confidence: 99%

Square wave voltammetric determination of valproic acid in pharmaceutical Preparations

Acar¹,

Onar²

2016

Turk J Chem

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The electrochemical behavior of valproic acid (VAL) was investigated using square wave voltammetry, cyclic voltammetry, and sampled direct current polarography and a new square wave voltammetric method was developed for determination of VAL in pharmaceutical preparations. VAL showed two reduction peaks at about-0.2 V and-0.8 V vs. Ag/AgCl 3 M KCl with a hanging mercury drop electrode in 0.05 M pH 3.3 Britton-Robinson (BR) buffer. These peaks were named peak I and peak II, respectively. The types of limiting current of both peaks were determined as diffusion controlled based on cyclic voltammetry studies. A linear calibration graph was obtained in the range 1.46 × 10 −4-1.0 × 10 −3 M. The limit of detection (LOD) and limit of quantification (LOQ) were 1.09 × 10 −4 M (21.05 µ g/mL) and 1.10 × 10 −4 M (144.20 µ g/mL), respectively. Recovery studies for the accuracy of the method were performed by adding known amounts of VAL and it was found to be 109.67 ± 4.85%. The proposed method was successfully applied to pharmaceutical products on the market.

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Section: Introductionmentioning

confidence: 99%

Square wave voltammetric determination of valproic acid in pharmaceutical Preparations

Acar¹,

Onar²

2016

Turk J Chem

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“…Drug monitoring is important since VA displays therapeutic efficiency for plasma concentrations in the range 50-100 ppm, but can induce toxicity for higher concentrations. Analytical techniques reported in the literature for VA determination include high liquid performance chromatography (HPLC) with different detection systems, gas chromatography coupled with mass spectrometry (GC-MS), capillary electrophoresis and immunological assay, among others [35][36][37][38][39][40][41][42][43][44][45][46][47]. Most of these techniques usually involve a previous derivatization step in order to render the analyte suitable for detection.…”

Section: Introductionmentioning

confidence: 99%

Synergistic effect of MoS2 and diamond nanoparticles in electrochemical sensors: determination of the anticonvulsant drug valproic acid

et al. 2018

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The authors describe an electrochemical sensor based on the use of diamond nanoparticles (DNPs) and molybdenum disulfide (MoS) platelets. The sensor was applied to the voltammetric determination of the anticonvulsant valproic acid which was previously derivatized with ferrocene. The MoS platelets were obtained by an exfoliation method, and the DNPs were directly dispersed in water and subsequently deposited on a glassy carbon electrode (GCE). The sensor response was optimized in terms of the solvent employed for dispersing the MoS nanomaterial and the method for modifying the GCE. Sensors consisting of a first layer of MoS dispersed in ethanol/water and a second layer of DNPs give better response. The single steps of sensor construction were characterized by atomic force microscopy and electrochemical impedance spectroscopy. The differential pulse voltammetric response of the GCE (measured at +0.18 V vs. Ag/AgCl) was compared to that of sensors incorporating only one of the nanomateriales (DNPs or MoS). The formation of a hybrid MoS-DNP structure clearly improves performance. The GCE containing both nanomaterials exhibits high sensitivity (740 µA ⋅ mM ⋅ cm), a 0.27 μM detection limit, and an 8% reproducibility (RSD). The sensor retained 99% of its initial response after 45 days of storage. Graphical abstract Electrochemical sensor by co-immobilization of MoS and diamond nanoparticles (DNP). The formation of a hybrid MoS-DNP structure enhances the performance of the sensor towards valproic acid derivatized with a ferrocene group, when compared with sensors incorporating only DNP or MoS.

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“…Microcantilever (MCL) -based biosensor is one of the label-free molecular sensing methods which has been developed and applied in many fields, such as clinical diagnostics 1,2 , homeland security 3 , environmental monitoring 4,5 and small molecule detection for therapeutic drug monitoring (TDM) purpose [6][7][8] . The static-mode operated MCL-based biosensor with electrical readout is especially provided with real-time detection, high sensitivity, and system miniaturization, which is potentially portable for personal diagnosis.…”

mentioning

confidence: 99%

“…The static-mode operated MCL-based biosensor with electrical readout is especially provided with real-time detection, high sensitivity, and system miniaturization, which is potentially portable for personal diagnosis. In previous studies, the piezoresistive MCL biosensing chips fabricated by using MEMS process was employed for drug concentration monitoring of valproic acid 6 and phenytoin 7 . Although those works demonstrated enough drug detection ranges for TDM, device sensitivities were limited and additional temperature control systems were needed, which cannot satisfy the demands of personal diagnostic devices.…”

mentioning

confidence: 99%

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A CMOS MEMS-based Membrane-Bridge Nanomechanical Sensor for Small Molecule Detection

Yen

Chiu

2020

Sci Rep

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Small molecule compounds are necessary to detect with high sensitivity since they may cause a strong effect on the human body even in small concentrations. But existing methods used to evaluate small molecules in blood are inconvenient, costly, time-consuming, and do not allow for portable usage. In response to these shortcomings, we introduce a complementary metal-oxide-semiconductor biomicroelectromechanical system (cMoS BioMeMS) based piezoresistive membrane-bridge (MB) sensor for detecting small molecule (phenytoin) concentrations as the demonstration. Phenytoin is one of anticonvulsant drugs licensed for the management of seizures, which has a narrow therapeutic window hence a level of concentration monitoring was needed. The MB sensor was designed to enhance the structural stability and increase the sensitivity, which its signal response increased 2-fold higher than that of the microcantilever-based sensor. The MB sensor was used to detect phenytoin in different concentrations from 5 to 100 μg/mL. The limit of detection of the sensor was 4.06 ± 0.15 μg/mL and the linear detection range was 5-100 μg/mL, which was within the therapeutic range of phenytoin concentration (10-20 μg/mL). Furthermore, the MB sensor was integrated with an on-chip thermal effect eliminating modus and a reaction tank on a compact chip carrier for disposable utilization. The required amount of sample solution was only 10 μL and the response time of the sensor was about 25 minutes. The nano-mechanical MB sensing method with thermal effect compensation is specific, sensitive, robust, affordable and well reproducible; it is, therefore, an appropriate candidate for detecting small molecules.

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Direct Determination of a Small-Molecule Drug, Valproic Acid, by an Electrically-Detected Microcantilever Biosensor for Personalized Diagnostics

Cited by 11 publications

References 30 publications

Square wave voltammetric determination of valproic acid in pharmaceutical Preparations

Square wave voltammetric determination of valproic acid in pharmaceutical Preparations

Synergistic effect of MoS2 and diamond nanoparticles in electrochemical sensors: determination of the anticonvulsant drug valproic acid

A CMOS MEMS-based Membrane-Bridge Nanomechanical Sensor for Small Molecule Detection

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