# Nanomaterials-Based Electrochemical Sensors for
## 3 In Vivo Analysis of Neurotransmitters
[PERSON] and [PERSON] reported on the development CNT-modified microelectrodes for the detection of 5-HT with reduced electrode biofouling from the oxidation byproducts of serotonin. In this work, the effect of nanotubes on the electron transfer kinetics, electrode response time, electrode fouling, and the in vivo detection of DA and 5-HT were  
Figure 10: Acetylcholine-stimulated dopamine release in a _Drosophila melanogaster_ ventral nerve cord (VNC). (**A**) Image showing electrode and stimulating pipet placed in VNC. (**B**)Acetylcholine (1.8 pmol) stimulated dopamine release measured with fast-scan cyclic voltammetry (FSCV). (**C**) Evoked dopamine concentration as a function of the amount of acetylcholine [133]. Copyright 2018, Elsevier. Figure 9: In vivo measurements of dopamine release using a PEDOT/Nafion-coated carbon-fiber microelectrode. Current versus time traces were extracted from the color plot at the peak oxidation potential for dopamine (~600 mV). The representative cyclic voltammograms were taken from the vertical white dashed line on the color plots. (**A**) Dopamine release was electrically evoked by stimulation (black bar, 40 pulses at 60 Hz, \(\pm\)150 \(\upmu\)A, 2 ms per phase) of the medial forebrain bundle and monitored in the nucleus accumbens of a Sprague-Dawley rat. (**B**) Spontaneous transients recorded in the nucleus accumbens of an isoflurane-anesthetized Sprague-Dawley rat [131]. Copyright 2015, American Chemical Society. studied [135]. It was suggested that a larger electrode with nanotube coatings and slow electrochemical analysis might not be suitable for the in vivo analysis of neurotransmitters. FSCV and fast-scan controlled adsorption voltammetry (FSCAV) have been used to detect the presence of serotonin and its raised levels in the hippocampus of mice [136]. This study demonstrated the detection of an ambient extracellular serotonin level of 64.9 nM. The obtained electrochemical data was validated using a pharmacological approach, and interference by DA and NE were avoided. A poly (3,4-ethylenedioxythiophene)/CNT-modified acupuncture needle was used for the real-time detection of 5-HT in a rat [137]. Figure 12 shows the insertion of the electrode into the limb of an intraperitoneal anesthetized rat. During the addition of different concentrations of 5-HT through microinjection, the amperometric response was recorded at an applied constant potential of 0.5 V. The modified acupuncture needle served as sensing platform. This detection approach is like spiked sample analysis. Further research and development is required to monitor and detect the presence of ultralow concentrations of neurotransmitters. Figure 11: **(A)** Insertion of the electrochemical microsensor into the intact embryonic intestine between the posterior swim bladder and the end of the intestine at 5 dpf. The arrowhead indicates the swim bladder and the arrow shows the point of insertion of the microelectrodes. **(B)** 5-HT immunohistochemistry reveals a subset of enteric neurons (arrows), as well as enterochromaffin cells within the epithelium (arrowheads). Enteric neurons are on the periphery of the intestine between the thin circular and longitudinal smooth muscle layers. Enterochromaffin cells, which are situated more toward the basal surface of the epithelium, sense the contents of the lumen (asterisk) using thin processes. **(C)** Typical differential pulse voltammogram obtained in vivo with the implanted microelectrode as shown in **(A)**. The supporting electrolyte was E3 medium [134]. Copyright 2010, American Chemical Society. L-Glu was detected using a Pt microelectrode with an enzyme (GluOx) and Nafion-incorporated coating where potassium chloride (70 mM and 120 mM) induced release of L-Glu was studied in the striatum and frontal cortex of the anesthetized rat [138]. The signal durations for low levels of KCl at the frontal cortex were lower, whereas, for high concentrations, there was an increase in the signal duration.