# A Review of Neurotransmitters Sensing Methods for Neuro-Engineering Research
## 2 Neurotransmitter Detection Methods
### Optical Sensing Techniques
#### 2.2.2 Fluorescence  
Fluorescence is the emission of photons by a molecule or material such as metal nanoparticles or quantum dots, following light stimulation at one or more specific wavelengths. It reflects the returns of electrons to their ground state after shifting into a higher energy state by the incident light. The electrons dissipate part of the received energy through vibrations and return to their ground state by emitting a photon with the remaining energy, which is typically lower than the incident one, yielding a longer emitted wavelength. For example, neurotransmitters including serotonin, dopamine and norepinephrine have been detected by fluorescence measurements carried out at 320 nm, with excitation at 279 nm [106].  
Although the fluorescence sensing method is sensitive, interfering compounds can seriously hinder its neurotransmitter detection efficiency. For example, 5-methoxyryptamine, N-acetylserotoninor melatoninin all affect serotonin detection [107]. Solvent extraction with few interfering materials may be avoided with ion exchange resin (Amberlite CG-50), which acts as a suitable vehicle for the refinement and concentration of serotonin from biological samples [108]. In addition, high-sensitivity fluorescence sensing of serotonin was achieved with ninhydrin, which acts as a fluorescence catalyst [109]. Fluorescence efficiency was also improved through the use of O-phthaldehyde (OPT) under heat and strong acid conditions [110]. This method requires only 50 mg of tissue samples, but the extraction, concentration and purification methods, and the assay method as well, are time consuming and the fluorescence intensity is low. Serotonin can also be detected in biological fluids using ethanol extraction, which enhances fluorescence intensity without any time-consuming steps [111]. However, this technique is not appropriate for repetitive analysis as serotonin in blood is rapidly oxidized by oxyhaemoglobin [111]. Adding ascorbic acid with dry ice acetone can avoid this oxidation [112]. Finally, combining fluorometric detection with HPLC reached a high sensitivity and selectivity for serotonin [113] and dopamine [114] with an LOD of 1 pM concentration, and a signal to noise ratio of 5.  
An in situ fluorescein-based neurotransmitter detection protocol was developed by [PERSON] et al. for the rapid and low-cost rapid detection of histamine. Dye-coated paper strips were used to detect histamine in various biological fluids, including human plasma and urine. The spectral analysis of the samples revealed that this technique can be used to detect histamine at concentrations as low as 24 nM [4].  
Fluorescent single-walled carbon nanotubes have been used to detect dopamine with an LOD of 11 nM [115]. The single-walled carbon nanotubes are modified with a DNA/RNA coronae that acts as a conformational switch, thus reversibly modulating the nanotube fluorescence. As reported by [PERSON] et al., by using a specific polymer wrapper, this technique can be used to detect other catecholamines with very high sensitivity and selectivity [115]. A similar work was reported by [PERSON] et al. with an improved LOD of 2.3 nM [116].