Electrochemical Study of the Catechol-Modified Chitosan System for Clozapine Treatment Monitoring

Abstract

This work presents a thorough electrochemical and reliability analysis of a sensing scheme for the antipsychotic clozapine. We have previously demonstrated a novel detection approach for this redox-active drug, highly effective in schizophrenia treatment, based on a catechol-modified chitosan film. The biomaterial film enables amplification of the oxidative current generated by clozapine through redox cycling. Here, we study critical electrochemical and material aspects of the redox cycling system to overcome barriers in point-of-care monitoring in complex biological samples. Specifically, we explore the electrochemical parameter space, showing that enhanced sensing performance depends on the presence of a reducing mediator as well as the electrochemical technique applied. These factors account for up to 1.75-fold and 2.47-fold signal enhancement, respectively. Looking at potential interferents, we illustrate that the redox cycling system allows for differentiation between selected redox-active species, clozapine's structurally largely analogous metabolite norclozapine as well as the representative catecholamine dopamine. Furthermore, we investigate material stability and fouling with reuse as well as storage. We find no evidence of film fouling due to clozapine; slow overall biomaterial degradation with successive use accounts for a 2.2% absolute signal loss and can be controlled for. Storage of the redox cycling system appears feasible over weeks when kept in solution with only 0.26%/day clozapine signal degradation, while ambient air exposure of three or more days reduces performance by 58%. This study not only advances our understanding of the catechol-modified chitosan system, but also further establishes the viability of applying it toward sensing clozapine in a clinical setting. Such point-of-care monitoring will allow for broader use of clozapine by increasing convenience to patients as well as medical professionals, thus improving the lives of people affected by schizophrenia through personalized medicine.

The interplay of electrode- and bio-materials in a redox-cycling-based clozapine sensor

“…As with gold, TiN also shows significant clozapine signal amplification with RCS modification, accompanied by a peak shift from 0.38 V to 0.54 V due to the slower overall kinetics from multiple reactions in redox cycling. However, the increase in current with RCS-TiN is much more pronounced at 7.54× compared to 2.86× for RCS-gold in PBS (the latter in line with previous data [9,18]). At the same time, while variability increases to 44% for RCS-gold, it reduces to 5% for RCS-TiN, reflecting an improvement in the signal-to-noise ratio by a factor of 9.2.…”

“…It is consistent, however, with part of the signal amplification with Pt-ref arising from its surface morphology combined with the kinetics-limited clozapine. In combination, the RCS film slows down diffusion, shifting the limitation from kinetics toward diffusion [18]. The depletion layer is thereby extended, which reduces the benefits of the nano-structured surface and outweighs that gained from the catalytic electrode surface.…”

Fusing Sensor Paradigms to Acquire Chemical Information: An Integrative Role for Smart Biopolymeric Hydrogels

“…Amplification of clozapine's oxidation and Ru 3+ reduction currents is illustrated by the cyclic voltammograms (CVs) in Figure c. Specifically, when a solution containing both clozapine (25 μ m ) and Ru 3+ (25 μ m ) was probed using the redox‐capacitor film, amplified oxidation and reduction currents were observed (compared to controls in which Ru 3+ was absent or the electrode was coated with a control chitosan film) …”

“…Interactive redox probing of clozapine. (a) Clozapine undergoes oxidative redox‐cycling with the catechol‐chitosan redox capacitor and this can be balanced by the reductive redox‐cycling of an added mediator (Ru 3+ ) . Redox‐cycling interactions (b) are thermodynamically constrained, (c) amplify output currents, and (d) couple output responses.…”

Connecting Biology to Electronics: Molecular Communication via Redox Modality

“…(A detailed description of redox‐cycling mechanism is provided in the following example.) Importantly, the catechol–chitosan redox‐capacitor film has been observed to exchange electrons with a wide range of oxidants and reductants (i.e., with a diverse range of mediators) and this includes biologically relevant oxidants and reductants …”