# Nanomaterials-Based Electrochemical Sensors for
## 2 In Vitro Detection of Typical Neurotransmitters  
The introduction of the electrochemical techniques in neurochemical detection has created some significant advantages, such as portability, rapid response, low cost, and self-contained instrumentation. In this section, the recent advancements in the nanomaterials-based in vitro electrochemical analysis of the aforementioned common neurotransmitters is presented. _Epinephrine (EP)_, which is also known as adrenaline, is a catecholamine neurotransmitter. It increases the amount of glucose in the circulation via an enzymatic reaction to assist with fight or flight responses. The function of EP depends on its oxidation by an enzyme called amine oxidase, and its abnormal levels affect the regulation of blood pressure, heart rate, lipolysis, the immune system, and glycogen metabolism [33]. Parkinson's disease patients may have low amounts of EP in their bodies. In addition, EP has a positive impact on local sedative adsorption into the blood stream by narrowing the blood vessels, reducing toxic side effects, and increasing the duration of medicinal activity [34; 35]. Nanomaterials-based electrochemical sensors show high performance in the detection of EP in a wide range of concentrations. As shown in Figure 2, DPV and amperometry were employed to detect EP using a nanoporous sponge-like Au-Ag electrode, showing a systematic increase in the current density in the concentration range of 10-275 \(\upmu\)M and 25-500 \(\upmu\)M, respectively [36]. In the DPV method, the highest sensitivity (1.52 mA cm\({}^{-2}\) mM\({}^{-1}\)) and the lowest detection limit (5.05 \(\times\) 10\({}^{-6}\) M) were observed for the efficient detection of EP in the presence of ascorbic acid (AA). In contrast to bulk gold, this dealloyed nanoporous Au-Ag film showed high electrocatalytic activity for EP oxidation due to the nanosize effect of the electrode. As proposed in Figure 2C, the EP oxidation followed the electron transfer-chemical reaction-electron transfer (ECE) mechanism. The mechanisms of the electrochemical detection of neurotransmitters could be varied with the different neurotransmitters being investigated. In general, the loss of one or more electrons from the molecule leads to a change in functional groups, as well as a change in the molecule's structure. For example, in Figure 2, the first step of the oxidation of epinephrine involves the loss of two electrons and the formation of epinephrinequinone. The following step involves a further change of the structure to leucoadrenochrome via the formation of a five-membered ring. [PERSON] et al. reported highly ordered gold/aluminum oxide as a sensing platform for the detection of EP, showing high sensitivity of 2.05 mA cm\({}^{-2}\) mM\({}^{-1}\) and the lowest detection limit (2.43 \(\times\) 10\({}^{-6}\) M) in the presence of uric acid (UA) [37]. [PERSON] et al. modified a glassy carbon electrode (GCE) with CNTs and 2-(4-oxo-3-phenyl-3,4-dihydro-quinazolinyl)-\(N^{\prime}\)-phenyl-hydra-zinecarbothioamide for the simultaneous determination of EP and norepinephrine (NE) [38], where two well-defined peaks with a separation of 240 mV appeared in the SWV. In another study, ZnO-based molecularly imprinted polymer arrays were employed to detect EP in the presence of UA and AA using DPV with a sensitivity of 0.66 \(\mu\)A \(\mu\)M\({}^{-1}\), which was lower than that of some previously discussed work. This may be ascribed to its low crystallinity and the high resistance of the fabricated non-noble metal oxide-based materials [39]. As the electrochemical oxidation of EP and dopamine may occur at a similar electrode potential, the design of the nanomaterials is crucial for the real sample analysis for the selective detection of EP. One strategy that can be employed to improve the selectivity of the electrode is to modify the surface with some chemical moieties (e.g., functional groups) that have a higher affinity to EP over dopamine.