An integrated electrochemical microsystem for real-time treatment monitoring of clozapine in microliter volume samples from schizophrenia patients

Abstract

This work presents the development of an electrochemical microsystem for antipsychotic clozapine treatment monitoring in schizophrenia patients. In our previous work, we demonstrated clozapine detection directly in spiked whole blood samples of a healthy volunteer using a chitosan–carbon nanotube-modified microelectrode with external counter and reference electrodes. Here we present the miniaturization of our previous clozapine sensing approach and its clinical validation in real samples obtained from 10 schizophrenia patients. We observed a sensitivity of 0.02 ± 2.3 × 10-4 mA/cm2µM and 0.003 ± 2.6 × 10-4 mA/cm2µM and a limit of detection of 0.08 ± 9.2 × 10-4 µM and 0.45 ± 0.04 µM using chitosan–carbon nanotube-modified microelectrodes in a 20 µL volume of spiked capillary plasma and capillary whole blood. Following a calibration curve, which was obtained from spiked samples of patients prior to clozapine therapy administration, clozapine capillary plasma and whole blood levels were recovered from patients’ samples after treatment with clozapine. The developed electrochemical microsystem allows clozapine analysis in a microliter volume of finger-pricked whole blood samples of schizophrenia patients without using any pretreatment steps. By further miniaturization and integration of this sensor into a point-of-care testing device, schizophrenia treatment management can be improved.