TY - JOUR
T1 - A reduced-graphene oxide-modified microelectrode for a repeatable detection of antipsychotic clozapine using microliters-volumes of whole blood
AU - Shukla, Rajendra P.
AU - Cazelles, Remi
AU - Kelly, Deanna L.
AU - Ben-Yoav, Hadar
N1 - Funding Information:
We gratefully acknowledge financial support from the Brain and Behavior Research Foundation NARSAD Young Investigator and the Jeanne Marie Lee Investigator Grant (Grant 26038 ) for funding the project. This research was also supported in part by the Helmsley Charitable Trust through the Agricultural, Biological and Cognitive Robotics Initiative at Ben-Gurion University of the Negev . The authors also thank the Krietman School for the Mid-way Negev fellowship and the Marcus Postdoctoral Fellowships in Water Sciences Program for their support. The authors also thank Professor Haim Belmaker for fruitful discussions and guidance. Lastly, the authors thank Yacov Bernstein for expert assistance with the thermal evaporator and the E-gun, Alexander Kozlovsky for assistance with the mask aligner, Rotem Manor for assistance with the stylus profiler, Nadav Dharan and Abraham Reiner for assistance with the dicing saw, Jürgen Jopp for expert assistance with the AFM system, Roxana Golan for expert assistance with the SEM system, and Leila Zeiri for expert assistance with the Raman system. Appendix A
Funding Information:
We gratefully acknowledge financial support from the Brain and Behavior Research Foundation NARSAD Young Investigator and the Jeanne Marie Lee Investigator Grant (Grant 26038) for funding the project. This research was also supported in part by the Helmsley Charitable Trust through the Agricultural, Biological and Cognitive Robotics Initiative at Ben-Gurion University of the Negev. The authors also thank the Krietman School for the Mid-way Negev fellowship and the Marcus Postdoctoral Fellowships in Water Sciences Program for their support. The authors also thank Professor Haim Belmaker for fruitful discussions and guidance. Lastly, the authors thank Yacov Bernstein for expert assistance with the thermal evaporator and the E-gun, Alexander Kozlovsky for assistance with the mask aligner, Rotem Manor for assistance with the stylus profiler, Nadav Dharan and Abraham Reiner for assistance with the dicing saw, J?rgen Jopp for expert assistance with the AFM system, Roxana Golan for expert assistance with the SEM system, and Leila Zeiri for expert assistance with the Raman system.
Publisher Copyright:
© 2019 The Authors
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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.
KW - Clozapine
KW - Electrochemical sensors
KW - Implantable sensors
KW - Reduced-graphene oxide
KW - Schizophrenia
KW - Therapeutic drug monitoring
UR - http://www.scopus.com/inward/record.url?scp=85075365838&partnerID=8YFLogxK
U2 - 10.1016/j.talanta.2019.120560
DO - 10.1016/j.talanta.2019.120560
M3 - Article
C2 - 31892051
AN - SCOPUS:85075365838
SN - 0039-9140
VL - 209
JO - Talanta
JF - Talanta
M1 - 120560
ER -
