A reduced-graphene oxide-modified microelectrode for a repeatable detection of antipsychotic clozapine using microliters-volumes of whole blood

Rajendra P Shukla; Remi Cazelles; Deanna L Kelly; Hadar Ben-Yoav

doi:10.1016/j.talanta.2019.120560

A reduced-graphene oxide-modified microelectrode for a repeatable detection of antipsychotic clozapine using microliters-volumes of whole blood

Talanta. 2020 Mar 1:209:120560. doi: 10.1016/j.talanta.2019.120560. Epub 2019 Nov 14.

Authors

Rajendra P Shukla¹, Remi Cazelles¹, Deanna L Kelly², Hadar Ben-Yoav³

Affiliations

¹ Nanobioelectronics Laboratory (NBEL), Department of Biomedical Engineering and Ilse Katz Institute of Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel.
² Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, 21228, United States.
³ Nanobioelectronics Laboratory (NBEL), Department of Biomedical Engineering and Ilse Katz Institute of Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel. Electronic address: benyoav@bgu.ac.il.

PMID: 31892051
DOI: 10.1016/j.talanta.2019.120560

Abstract

Antipsychotic clozapine is the most effective medication currently available for schizophrenia. However, clozapine is dramatically underutilized due to its harsh side effects that are not effectively monitored. By continuously monitoring clozapine blood levels, such as use of an implantable glucometer, which has transformed diabetes management, the treatment can be optimized and side effects will be minimized. Currently, none of the methods for clozapine detection show the ability to repeatedly measure clozapine in whole blood without pretreatment steps. Here we propose using a microelectrode modified with reduced graphene oxide-a material that was used for repeatable measurements in implantable electrochemical devices. We present the successful direct electrodeposition of reduced-graphene oxide coating onto microelectrodes. Systematic characterization of the electrodeposition technique parameters (i.e., the technique scan rate and the number of cycles) revealed their effect on the electrochemical activity and the structural properties (the film thickness and roughness) of the films. The developed reduced-graphene oxide-modified microelectrode exhibited the feasibility to detect clozapine in microliters-volume-samples of whole blood with a limit-of-detection and a sensitivity of 0.64 ± 0.04 μM and 19.6 ± 1.3 μA/cm²μM, respectively. Moreover, the reduced graphene oxide-modified microelectrodes exhibited high repeatability (retaining 94.6% of the electrochemical signal after 10 repeats), reproducibility (3.6% relative standard deviation), and storage stability (retaining 89% of the electrochemical signal after 4 weeks). Finally, relative recovery studies of 0.5, 1, and 2 μM clozapine concentrations resulted in 108 ± 4.0%, 112 ± 3.5%, and 103 ± 2.2%, respectively. Future studies should investigate the microelectrode fouling mechanisms in whole blood and explore methods to overcome fouling.

Keywords: Clozapine; Electrochemical sensors; Implantable sensors; Reduced-graphene oxide; Schizophrenia; Therapeutic drug monitoring.

Publication types

Evaluation Study

MeSH terms

Antipsychotic Agents / blood*
Clozapine / blood*
Drug Monitoring / instrumentation
Electrochemical Techniques / instrumentation*
Equipment Design
Graphite / chemistry*
Humans
Limit of Detection
Microelectrodes
Oxidation-Reduction

Substances

Antipsychotic Agents
graphene oxide
Graphite
Clozapine