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Intelligent Microelectrodes Array for Schizophrenia Treatment Monitoring
1 , 2 , 3 , 4 , * 2
1  Nanobioelectronics Laboratory (NBEL), Department of Biomedical Engineering,Ben-Gurion University of the Negev
2  Nanobioelectronics Laboratory (NBEL), Department of Biomedical Engineering, Ben-Gurion University of the Negev
3  Beer-Sheva Mental Health Center
4  Maryland Psychiatric Research Center, University of Maryland School of Medicine

Published: 14 November 2020 by MDPI in 7th International Electronic Conference on Sensors and Applications session Posters
Abstract:

Schizophrenia (SCZ) is a chronic mental disorder that affects 23 million people worldwide. Clozapine (CLZ) is the most effective antipsychotic medication for treatment-resistant SCZ patients. Despite the superior efficacy of CLZ, it is dramatically underutilized due to the unavailable objective tests to measure CLZ efficacy. Several redox biomarkers in the blood have been correlated to CLZ efficacy. Yet, existing analytical methods change the levels of the molecules, their redox state, and eventually destroy the sample. By bridging the analytical gap and profiling the redox biomarkers, rapid and accurate CLZ treatment efficacy monitoring can be provided. Our overall goal is to develop a novel intelligent electrochemical biosensor based on an array of microelectrodes for CLZ treatment efficacy analysis. Here, we present the fabrication of the microelectrodes array, modification of the array with diffusion-limiting films, and characterization of the film’s effect on the generated electrochemical activity. The novelty of the biosensor lies within an array of microelectrodes modified with the positively charged biopolymer chitosan generating a set of complex electrochemical signals that are analyzed by using intelligent chemometric models. To achieve our goal, we microfabricated an array of 24 gold microelectrodes (100-µm-diameter working and 1,500-µm-diameter counter electrodes) by using photolithography and thin film deposition techniques. We used a 1.2% chitosan solution and applied cathodic current to electrodeposit thin films of chitosan onto the microelectrodes. To fabricate chitosan films with similar thicknesses and different densities, we measured the relationship between the thickness of the electrodeposited film and the applied electrodeposition current for 90s and 180s durations. A similar wet chitosan thickness (57.6±0.8 µm) was successfully achieved with 510 nA for 90s and 950 nA for 180s durations. Moreover, different dry chitosan thicknesses were obtained for 90s (10.7±0.1 µm) and 180s (13.2±0.6 µm) durations. Therefore, we calculated the porosity of the electrodeposited films as the ratio between the thicknesses of the wet and the dry films (5.38±0.09 and 4.36±0.20 at 510 nA for 90s and 950 nA for 180s, respectively). Furthermore, we used cyclic voltammetry to characterize the permeability of the modified films by measuring the ratio of the electrochemical signals generated from differently charged redox molecules (negatively charged ferrocyanide, neutral ferrocene, and positively charged hexaammineruthenium) before and after the modification. Statistical T-test analysis of the resulted permeabilities revealed significant differences for the charged molecules (P=0.85% for ferrocyanide; P=4.57% for hexaammineruthenium), while no significant difference was observed for the neutral molecule ferrocene. By providing a new way to analyze molecular profiles in blood, we anticipate establishing a new detection scheme for CLZ treatment efficacy that will help to transform schizophrenia management.

Keywords: Schizophrenia, Microelectrode array, Biosensor, Chitosan, Chemometrics
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