An electrochemical micro-system for clozapine antipsychotic treatment monitoring

Clozapine is the most effective antipsychotic medication for schizophrenia, but it is underutilized because of the inability to effectively monitor its treatment efficacy and side effects. In this work, we demonstrate the first analytical micro-system for real-time monitoring of clozapine serum levels. An electrochemical lab-on-A-chip is developed and integrated with a catechol-chitosan redox cycling system. The microfabricated device incorporates 4 electrochemical reaction chambers with the capability of analyzing microliter-volume samples. Integration of the catechol-chitosan film amplifies the clozapine oxidative signal and improves the signal-to-noise ratio, which addresses sensitivity and selectivity challenges. Optimization of the redox cycling system fabrication parameters and analysis of various electrochemical techniques and data processing approaches is implemented to maximize clozapine detection performance. The device is tested with buffer samples containing clozapine and demonstrates a sensitivity of 54 μC mL cm^-2 μg^-1 and a limit-of-detection of 0.8 μg mL^-1, a sensing performance similar to a counterpart macro-scale benchtop system. Importantly, the feasibility to differentiate between 0.33 μg mL^-1 and 3.27 μg mL^-1 clozapine concentrations in human serum without any preceding dilution or filtering procedures is demonstrated, a significant step towards utilizing point-of-care testing micro-systems for schizophrenia treatment management. With these micro-systems, we envision more effective and safe treatment that will enable fewer visits to the clinicians, decrease costs and patient burden.