TY - JOUR
T1 - A platinum black-modified microelectrode for in situ olanzapine detection in microliter volumes of undiluted serum
AU - Shukla, Rajendra P.
AU - Belmaker, Robert H.
AU - Bersudsky, Yuly
AU - Ben-Yoav, Hadar
N1 - Funding Information:
and by the Marcus Endowment Fund both at Ben-Gurion University of the Negev. The authors also wish to thank the Krietman School for the Mid-way Negev fellowship for their support. 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, and Roxana Golan for expert assistance with the SEM system. We gratefully acknowledge financial support from the Brain and Behavior Research Foundation NARSAD Young Investigator Grant and the Jeanne Marie Lee Investigator Grant (Grant 26038) for funding this project. This research was also supported in part by the Helmsley Charitable Trust through the Agricultural, Biological and Cognitive Robotics Initiative Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Funding Information:
We gratefully acknowledge financial support from the Brain and Behavior Research Foundation NARSAD Young Investigator Grant and the Jeanne Marie Lee Investigator Grant (Grant 26038) for funding this project. This research was also supported in part by the Helmsley Charitable Trust through the Agricultural, Biological and Cognitive Robotics Initiative?and by the Marcus Endowment Fund both at Ben-Gurion University of the Negev. The authors also wish to thank the Krietman School for the Mid-way Negev fellowship for their support. 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, and Roxana Golan for expert assistance with the SEM system.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Olanzapine is a thienobenzodiazepine compound. It is one of the newer types of antipsychotic drugs used in the treatment of schizophrenia and other psychotic disorders. Several methods have been reported for analyzing olanzapine in its pure form or combined with other drugs and in biological fluids. These methods include high-performance liquid chromatography and liquid chromatography-tandem mass spectroscopy. Although many of the reported methods are accurate and sensitive, they require the use of sophisticated equipment, lack in situ analysis, and require expensive reagents. Moreover, several of these methods are cumbersome, require prolonged sample pretreatment, strict control of pH, and long reaction times. Here we present the development of a miniaturized electrochemical sensor that will enable minimally invasive, real-time, and in situ monitoring of olanzapine levels in microliter volumes of serum samples. For this purpose, we modified a microfabricated microelectrode with a platinum black film to increase the electrocatalytic activity of the microelectrode towards olanzapine oxidation; this improved the overall selectivity and sensitivity of the sensor. We observed in recorded voltammograms the anodic current dose response characteristics in microliter volumes of olanzapine-spiked serum samples that resulted in a limit of detection of 28.6 ± 1.3 nM and a sensitivity of 0.14 ± 0.02 µA/cm2 nM. Importantly, the platinum black-modified microelectrode exhibited a limit of detection that is below the clinical threshold (65–130 nM). Further miniaturizing and integrating such sensors into point-of-care devices provide real-time monitoring of olanzapine blood levels; this will enable treatment teams to receive feedback and administer adjustable olanzapine therapy.
AB - Olanzapine is a thienobenzodiazepine compound. It is one of the newer types of antipsychotic drugs used in the treatment of schizophrenia and other psychotic disorders. Several methods have been reported for analyzing olanzapine in its pure form or combined with other drugs and in biological fluids. These methods include high-performance liquid chromatography and liquid chromatography-tandem mass spectroscopy. Although many of the reported methods are accurate and sensitive, they require the use of sophisticated equipment, lack in situ analysis, and require expensive reagents. Moreover, several of these methods are cumbersome, require prolonged sample pretreatment, strict control of pH, and long reaction times. Here we present the development of a miniaturized electrochemical sensor that will enable minimally invasive, real-time, and in situ monitoring of olanzapine levels in microliter volumes of serum samples. For this purpose, we modified a microfabricated microelectrode with a platinum black film to increase the electrocatalytic activity of the microelectrode towards olanzapine oxidation; this improved the overall selectivity and sensitivity of the sensor. We observed in recorded voltammograms the anodic current dose response characteristics in microliter volumes of olanzapine-spiked serum samples that resulted in a limit of detection of 28.6 ± 1.3 nM and a sensitivity of 0.14 ± 0.02 µA/cm2 nM. Importantly, the platinum black-modified microelectrode exhibited a limit of detection that is below the clinical threshold (65–130 nM). Further miniaturizing and integrating such sensors into point-of-care devices provide real-time monitoring of olanzapine blood levels; this will enable treatment teams to receive feedback and administer adjustable olanzapine therapy.
KW - Antipsychotic olanzapine
KW - Electrochemical sensors
KW - Point-of-care testing
KW - Reduced graphene oxide
KW - Serum
KW - Therapeutic drug monitoring
UR - http://www.scopus.com/inward/record.url?scp=85077638745&partnerID=8YFLogxK
U2 - 10.1007/s00702-019-02139-0
DO - 10.1007/s00702-019-02139-0
M3 - Article
C2 - 31907607
AN - SCOPUS:85077638745
VL - 127
SP - 291
EP - 299
JO - Journal of Neural Transmission
JF - Journal of Neural Transmission
SN - 0300-9564
IS - 2
ER -