Selectively Probing Neurochemicals in Living Animals with Electrochemical Systems

Abstract

Neurochemicals are essential molecules presented in the central nervous system that are primarily involved in neural activity and signaling. Neurochemical abnormalities resulted from genetic or environmental changes can lead to several behavioral and neurological disorders, including Alzheimer's and Parkinson's diseases. It is therefore imperative to employ detection systems of the optimal selectivity and spatio‐temporal resolution to ascertain the specific molecular basis particular to the pathological process. Electrochemical systems featuring excellent temporal‐spatial resolution and designable electrode interface are arguably the most versatile and widely used approaches for sensing of neurochemicals in living brain environment. Nevertheless, there are still many challenges that must be addressed to enable highly selective, sensitive, and stable in vivo electrochemical sensors and facilitate their development for emerging applications ranging from early diagnosis of brain diseases to designing potential curative treatments. Here, we provide a brief overview of the application of electrochemical sensors and biosensors in the analysis of neurochemicals in living animals. In particular, we highlight recent advances in modulating the physicochemical properties of electrode that can lead to in vivo sensors with exceptional selectivity. In addition, future trends of highly selective in vivo electrochemical systems are prospected.

Recent Progress on Highly Selective and Sensitive Electrochemical Aptamer-based Sensors

“…Small biological molecules, such as neurotransmitters, metabolites and cell secretions play a vital regulatory role in the biological system [134][135][136] . The detection of biological small molecules is of great significance for understanding the mechanism of biological activities and disease monitoring.…”

New Opportunities of Electrochemistry for Monitoring, Modulating, and Mimicking the Brain Signals

“…The voltammetric current intensity could determine the reactant concentration, marking the beginning of the deciphering of chemical signals of living brains. Later on, invention of the carbon fiber electrode (CFE) with a diameter no more than dozens of micrometers brought crucial improvements in spatiotemporal resolution, sensitivity, and biocompatibility. , This tiny electrode effectively minimizes the background charging current and promotes mass transport by spherical diffusion, leading to fast-scan cyclic voltammetry (FSCV) for selectively monitoring fast neurotransmitter release. − Morphological or chemical tailoring of CFE surface can endow it with high anti-interference − and antifouling ability, − enabling accurate real-time amperometric or potentiometric measurements in vivo . When equipped on a patch-clamp current amplifier, a microdisk CFE positioned on top of cells can record the quantum or subquantum release transients of exocytosis by single-cell amperometry, and nanotip CFE inserted inside the cells can count the molecules packed in neurotransmitter vesicles by intracellular vesicle impact electrochemical cytometry. − Literally, the CFE technique greatly fueled the evolution of the modern electrochemistry toolbox available for in situ monitoring of diverse chemical signals on cultured neurons, brain slices, and intact brains in awake animals …”

Electrochemical Conjugation of Aptamers on a Carbon Fiber Microelectrode Enables Highly Stable and Selective In Vivo Neurosensing

“…Exploring the chemical activity of the brain at the molecular level is necessary for a comprehensive understanding of brain function and neurologic diseases. [1] However, in the central nervous system (CNS), the coexistence of a great number of similarly structured neurochemicals and fast changes in the chemical composition and distribution [2] pose great challenges for probing specific neurochemicals with adequate spatiotemporal resolution in vivo. [3] Although significant advances in both imaging [4] and electrochemical techniques [5] offer plausible approaches to probe neurochemical dynamics, the lower requirements of intracellular molecular engineering [6] and specialized electrochemical platforms offer greater applicability for measuring rapid neurotransmitter dynamics in the brain with molecular precision.…”