Electrochemical Detection of Glutamate and Histamine Using Redox-Labeled Stimuli-Responsive Polymer as a Synthetic Target Receptor

Glutamate (Glu) and histamine (His) are two major neurotransmitters that play many critical roles in brain physiological functions and neurological disorders. Therefore, specific and sensitive monitoring of Glu and His is essential in the diagnosis and treatment of various mental health and neurodegenerative disorders. Both being nonelectroactive species, direct electrochemical detection of Glu and His has been challenging. Herein, we report a stimuli-responsive polymer-based biosensor for the electrochemical detection of Glu and His. The polymer-based target receptors consist of a linear chain stimuli-responsive templated polymer hybrid that is labeled with an osmium-based redox-active reporter molecule to elicit conformation-dependent electrochemical responses. The polymers are then attached to a gold electrode to implement an electrochemical sensor. The cyclic voltammetry (CV) and square-wave voltammetry (SWV) results confirmed the polymers’ conformational changes due to the specific target (i.e., Glu and His) recognition and the corresponding electrochemical detection capabilities. The voltammetry results indicate that this biosensor can be used as a “signal-on” and “signal-off” sensors for the detection of Glu and His concentrations, respectively. The developed biosensor also showed excellent regeneration capability by fully recovering the initial current signal after being rinsed with deionized water. To further validate the polymer’s utility as a target bioreceptor, the surface plasmon resonance (SPR) technique was used to characterize the binding affinity between the designed polymers and the target chemical. The SPR results exhibited the equilibrium dissociation constants (K_D) of 2.40 μM and 1.54 μM for the polymer–Glu and polymer–His interactions, respectively. The results obtained in this work strongly suggest that the proposed sensing technology could potentially be used as a platform for monitoring nonelectroactive neurochemicals from animal models.