# A Review of Neurotransmitters Sensing Methods for Neuro-Engineering Research
## 3 Neurotransmitter Detection Techniques' Guidelines  
The surveyed neurotransmitter detection techniques all have strengths and weaknesses as shown in Table 2. The suitability of a technique over the others depends on the intended application. For instance, in vivo usable techniques are better than those only usable in vitro for clinical applications, but this often comes with more complexity, lower sensitivity and/or selectivity, and higher cost. In addition, the methods with higher sensitivity and selectivity are often bulkier and require complex and time-consuming manipulations. Nuclear medicine tomographic imaging offers high spatial resolution, but the equipment is expensive, making these techniques only suitable for diagnostic purposes where the functional studies and accurate localization of neurotransmitters in the brain are needed. In addition, since they are not suitable for neurotransmitter concentration detection, they must be used with techniques that have higher concentration sensibility to get accurate neurotransmitter concentration measurements. In hospitals and research laboratories, they can be used with microdialysis or analytical chemistry techniques such as HPLC. Figure 7: Microdialysis probe. A microdialysis probe is formed by a semipermeable membrane and perfused at a constant flow. Molecules will be able to diffuse across the membrane according to their gradient [209]. Analytical chemistry techniques may require costly equipment, but, as they are traditionally used in most bio-chemical laboratories for various chemical analyses, this equipment is available for most neuroscientists. In addition to cost, their inconvenience is that they require complex manipulations and are time consuming. On the other hand, microdialysis, sometimes used in conjunction with other methods such as HPLC, is one of the most used neurotransmitter detection methods for clinical use. It is well studied and can be used for continuously monitoring drug or metabolite concentrations in the extracellular fluid of virtually any tissue. However, as with all invasive detection techniques, it presents practical and ethical limitations for most researchers. Moreover, its temporal and spatial resolution is very limited when compared to nuclear medicine tomographic imaging. With the rapid development of innovative technologies, and the emergence of multidisciplinary research outcomes in biomedical engineering, the current research tends to focus on more compact, portable and implantable neurotransmitter sensors. As a result, several techniques have been proposed or revisited. For instance, the electrochemical detection technique is reputed to be easy to implement in an implantable device, in addition to being cost effective. However, due to its low selectivity and the complexity of in-vivo chemical/molecular monitoring, its usage in real world applications still needs improvements in terms of reliability and selectivity. In addition, not all neurotransmitters can receive or yield electrons in a redox reaction on an electrode surface. Thus, only reactive neurotransmitters such as dopamine can be detected by using an electrochemical method without electrode functionalization. The electrochemical approach is also closely dependent on the electrode surface, which reacts with the targeted molecule. Thus, it is not possible to guarantee the stability and quality of the electrode for a long time; although it is possible to detect a good signal over a small number of detection cycles, the electrode degradation becomes significant as the number of cycles grows. This affects the number of electrons that can be trapped by the electrode, hence lowering the sensed current. Consequently, in terms of engineering, it is impossible to guarantee consistent results over time. That is the reason why, for instance, in the case of glucose sensors, the commercial products are based on one-time usage electrodes in order to guarantee result reliability.