# A Review of Neurotransmitters Sensing Methods for Neuro-Engineering Research
## 1 Introduction
### Concluding Remarks on Neurotransmitters  
Several chemical substances have been identified as neurotransmitters and others have yet to be discovered. As reported in Table 1, the concentration of these substances in the brain is very low and they are often only produced in specific regions; for example, L-aspartate is mostly produced in the hippocampus while dopamine is produced in the hypothalamus and substantia nigra. Nevertheless, they are among the most important substances that the body produces. They are involved in many vital functions such as vision, learning, sleep and emotions among others, and their dysfunction can lead to serious health issues, including anxiety, depression, schizophrenia, Parkinson's and Alzheimer's diseases among others. Given their important roles in the central nervous system and the severity of disorders linked to their dysfunctions, the accurate detection and measurement of neurotransmitters are among the most important challenges in neuroscience.  
Given the importance of their detection, several articles reviewed the advances and challenges in neurotransmitter detection. [PERSON] et al. [1] reviewed analytical and quantitative in vivo neurotransmitter monitoring techniques based on electrochemical and imaging approaches. Cross-species PET (positron-emission tomography) imaging advances and trends for neurotransmitter detection in brain have been surveyed by [PERSON] et al. [5]. Electrochemical sensing based on nanomaterial has been extensively surveyed by [PERSON] et al. [7]. The microelectronics interface design consideration was summarized in a review by [PERSON] and [PERSON] [9]. Advances in nanomaterials and polymer-based sensors and their potential for in situ optical neurotransmitters detection application were reported in a review by [PERSON] [10]. Other works detailed the detection methodology for a specific neurotransmitters detection technique have been reported [8; 11; 12; 14]. However, all those reviews lack a comparison of the strengths and weaknesses of the surveyed techniques. This work aims to provide such as comparison and highlight the guidelines for choosing a given neurotransmitter detection technique. The remaining of this article reviews the different methods used for their sensing and detection. It includes classical methods such as microdialysis and analytical chemistry-based methods, as well as more recent research techniques such as optical and in vivo electrochemical sensing for a faster response, instrument miniaturization, high sensitivity and selectivity. The classical techniques such as microdialysis are well studied and can be used for neurotransmitter sampling for clinical purposes in hospitals. On the other hand, the cytotoxicity of the materials used by the other techniques such as nano-object optical sensing methods is not fully studied. Thus, despite their high sensitivity and selectivity, these techniques are currently only used for in vitro research.  
\begin{table}
\begin{tabular}{p{142.3 pt} p{142.3 pt} p{142.3 pt} p{142.3 pt}} \hline \hline
**Name** & **Formula** & **Localization/ Concentrations** & **Role and Pathology** \\ \hline Glutamate & HO & Widespread in brain and spinal cord./ 1 uM [78], 1.4 uM [79] & Involved in learning, memory, vision, epilepsy, schizophrenia, excitotoxicity & Involved in learning, memory, vision, epilepsy, schizophrenia, excitotoxicity & Involved in learning, memory, vision, epilepsy, schizophrenia, excitotoxicity \\ L-aspartate &