Catechol-modified chitosan system as a bio-amplifier for schizophrenia treatment analysis

Clozapine remains the most effective antipsychotic for management of schizophrenia, one of the most challenging mental disorders. Yet, this medication is underutilized due to the frequent blood draws associated with monitoring adverse side effects and maintaining effective drug levels in the body. Lab-on-a-chip (LOC)-based diagnostics at the point-of-care could decrease the burden on patients and doctors, enable personalized medicine, and improve treatment outcomes. Towards that goal, we present the development of an electrochemically active biomaterial probe to facilitate monitoring of clozapine as part of patient's treatment regimen. The probe consists of the naturally derived polymer chitosan modified with catechol to provide a redox capacitor system, allowing for significant amplification. We demonstrate a 3-fold increase of the electrochemical signal generated by clozapine with the catechol-modified chitosan system over bare gold electrodes. The improved signal-to-noise ratio and overall performance of the bio-amplifier yield a detection limit below 1 μM, thus sufficient for the clinically relevant range of 1-3 μM. We further characterize the robustness of the biomaterial system with respect to re-use and storage, and demonstrate retention of its amplification characteristics when implemented on an electrochemical microchip. Our results align well with the clinical requirements and represent a critical first step in developing a point-of-care device for improved and personalized schizophrenia treatment.