Online electrochemical systems for continuous neurochemical measurements with low-potential mediator-based electrochemical biosensors as selective detectors

Abstract

This study demonstrates a new strategy to develop online electrochemical systems (OECSs) for continuously monitoring neurochemicals by efficiently integrating in vivo microdialysis with an oxidase-based electrochemical biosensor with low-potential electron mediators to shuttle the electron transfer of the oxidases. By using thionine and xanthine oxidase (XOD) as examples of low-potential mediators and oxidases, respectively, we demonstrate that the use of low-potential mediators to shuttle the electron transfer of oxidases would offer a new approach to the development of oxidase-based biosensors with theoretical and technical simplicity. To construct the XOD-based biosensor, thionine was adsorbed onto carbon nanotubes and used to shuttle the electron transfer of XOD. The XOD-based biosensor was positioned into an electrochemical cell that was directly coupled with in vivo microdialysis to form an online electrochemical system (OECS) for continuous and selective measurements of the substrate of XOD (with hypoxanthine as an example). The OECS based on the low-potential mediators is highly selective against the species endogenously existing in the brain system, which is attributed to the low operation potential benefited from the low redox potentials of the mediators. Moreover, the OECS demonstrated here is stable and reproducible and could thus be envisaged to find some interesting applications in physiological and pathological investigations. This study essentially offers a new strategy to develop online electrochemical systems, which is of great importance in understanding the molecular basis of physiological and pathological events.

In Vivo Analysis with Electrochemical Sensors and Biosensors

“…MET-based biosensors normally use additional electron transfer mediators to shuttle electrons between electrode and distant FAD active sites, yielding much higher current response than DET-based biosensors do. As a matter of fact, MET-based biosensors have gained more research attention and effort from neurochemists for their in vivo applications in amperometric, real-time neurochemical biosensing and continuous monitoring of neurochemicals in brain microdialysate with an OECS. − Recent years have witnessed a rapid development of MET-based in vivo electrochemical biosensors, as summarized below.…”

“…New low-potential mediators were also explored for in vivo purposes. Zhang et al developed a xanthine oxidase (XOD)-based OECS, in which thionine was adsorbed onto CNTs and used to shuttle electrons between XOD and CNT-modified electrodes . The biosensor was demonstrated to be highly selective against endogenous species during continuous monitoring of xanthine in the brain.…”

In Vivo Electrochemical Sensors for Neurochemicals: Recent Update

“…Being one critical factor, immobilization of mediators and enzymes onto the electrode surface impacts redox potential of mediators, enzyme activity, as well as electron transfer between mediators and enzymes, therefore dramatically influencing the sensor performance. Attempts have been made on both immobilization matrixes and processes. − As an example to highlight novel immobilization matrixes, Ma et al. first applied the metal–organic framework to coimmobilize mediator and enzyme on the electrode surface to prepare in vivo biosensors …”

Advancements in Brain Research: The In Vivo/In Vitro Electrochemical Detection of Neurochemicals

“…Continuous efforts in coupling analytical methods with microdialysis have substantially improved its time resolution to seconds, challenging the initial notion of a poor time resolution associated with microdialysis [ 22 , 23 , 24 , 25 ]. Recent advancements, especially coupling microdialysis with biosensors [ 26 , 27 , 28 ], have revolutionized its capabilities. This combination leads to a sensitive analysis, low detection limit, and prevents analyte degradation.…”