# Nanomaterials-Based Electrochemical Sensors for
## 3 In Vivo Analysis of Neurotransmitters  
The in vivo electrochemical analysis of neurotransmitters can elucidate their real-time functionality in the brain and body. This type of analysis might be very useful for the monitoring, control, and potential manipulation of chemical changes that occur as the result of different diseases and to facilitate the diagnoses of diseases at their early stages. In this section, we describe the in vivo analysis of neurotransmitters in several live organisms, such as the chicken, fruit fly, and rat. The chick is often being used for in vivo analysis to provide prototype information of the brain and its functions. [PERSON] et al. attempted to simultaneously detect EP and NE levels in chick brains using high-performance liquid chromatography coupled with a coulometric detection method. This study revealed the role of neurotransmitters during the first day after hatching. The EP and NE presence in the cerebellum in different stages were monitored from the late embryonic period to the post-hatching period [127]. A carbon nanopipette electrode (CNPE) was employed to detect the presence of DA in _Drosophila melanogaster_ (fruit fly) [128]. The diameter of the tip was approximately 250 nm and exposed to different concentrations of DA under in vitro conditions. Subsequently, this electrode was used to detect the endogenous DA release in _Drosophila_ larvae, which confirmed that the CNPEs could be used for in vivo neuroscience investigations and inspired researchers to develop sensor implants for the localized measurement of neurotransmitters. These CNPEs are tunable with different dimensions, which may facilitate the implantation and monitoring of neurotransmitters in a small organism (e.g., _Drosophila_). The carbon-fiber microelectrode was employed to measure the DA and 5-HT in freely moving rats using DPV with wireless technologies [129]. In these technologies, Nafion-coated micro biosensors were surgically affixed within the prefrontal cortex in the brains of the rats; the sensors were activated to record signals that indicated the presence of DA and 5-HT. Moreover, a wearable, wireless, electrochemical instrument was developed for the detection of DA. A carbon-fiber microelectrode was surgically fixed in the caudate-putamen area of the brain in the rats, where fast-scan cyclic voltammetry (FSCV) was employed to detect DA and measure concentration of about 1 uM with the duration of 4 s [130]. These sensing strategies represent the possibility of a compact, wearable, wireless, battery-powered electrochemical device for the real-time monitoring of neurotransmitters with high sensitivity and low-power consumption. Another in vivo method for the detection of DA was designed under the consideration of the reduction of biofouling (Figure 9) [131]. The combination of photochemistry with electrochemical analysis provided a sensing strategy for the selective recognition of DA with a sensitivity of 0.15 nM. For this method, the author used DA as a sensitizer and target molecule, where the rationale behind the use of the photoelectrochemical method related to the prediction that it would provide a self-cleaning ability to the electrode [132]. In Figure 10, DA release was induced by ACh, which was injected into larval stage _Drosophila melanogaster Canton S_ by pressure injection. The current was measured with a carbon-fiber microelectrode using FSCV. The shape of the voltammogram confirmed the release of DA, while the brain was under the influence of ACh [133]. As shown in Figure 11, the quantification of 5-HT was performed in an embryonic zebrafish intestine under physiological conditions with the implanted microelectrodes at different sites in the intestine, where the DPV showed a well-defined peak at 360 mV versus the Ag/AgCl electrode. The information obtained from this study has been used in the study of development mechanisms and the control of gastrointestinal functions [134].