# A Review of Neurotransmitters Sensing Methods for Neuro-Engineering Research
## 2 Neurotransmitter Detection Methods
### Electrochemistry
#### 2.3.1 Fast-Scan Cyclic Voltammetry (FSCV)  
Voltammetry relies on measuring the current flowing between two electrodes, a working electrode and a counter electrode, subjected to a voltage difference during a redox chemical reaction. The working electrode is responsible for the redox current and the counter electrode maintains a constant potential while passing a current to counter the redox events at the working electrode. In practice, it is difficult to make this set up work and a third electrode, called the reference electrode, is added to relieve the counter electrode of maintaining the voltage difference. In FSCV, the applied voltage is a repetitive ramp with a high slew rate [174]. During FSCV scans, an electroactive neurotransmitter near the working electrode rapidly oxidizes and transfers electrons to the electrode surface, thus generating a faradic current [175]. A reduction faradic current of approximately the same order as the oxidation current is also observed [174]. FSCV can be based on carbon-fiber electrodes to detect indolamines such as serotonin, and catecholamines such as adrenalin, noradrenalin and dopamine as illustrated in Figure 3[176], since they can be oxidized at low voltage [177]. FSCV can be used for in vitro as well as in vivo experiments in single neurons, brain slices, and anesthetized or moving animals such as a rat with a small headstage fixed on the head [178]. When used for neurotransmitter sensing, FSCV consists first of maintaining the electrode potential beneath the oxidizing potential of the neurotransmitter of interest (e.g., -0.4 V for dopamine with an Ag/AgCl reference electrode). Then, the electrode potential is increased above the neurotransmitter oxidizing potential (around 1.0 V) at a high scan rate, usually 400 V/s. The duration of each cycle is 100 ms [177; 179; 180], and the measured current depends on the neurotransmitter concentration. The main difference between FSCV and Cyclic Voltammetry (CV) is the very high scan rate used in FSCV. Indeed, the scan rate can be much higher than 400 V/s and the duration of each cycle can vary depending on application. It has been reported that FSCV is more convenient for neurotransmitter sensing in in vivo experiments because it has a better resolution than CV. However, both techniques should be able to detect the same molecules. If the molecule is not detectable with CV at high concentration, we should not expect it to be detected through FSCV either. Each voltammogram (current vs. voltage curves) is unique to a substance and can be used to identify neurotransmitters as illustrated in Figure 4[180]. Indeed, the voltammogram depends on the molecule's properties such as its electron transfer rate and chemical stability [181]. Those factors determine the positions and shapes of the reduction and oxidation peaks, as well as their relative amplitudes [181]. As the current generated at the oxidation voltage corresponds to the concentration fluctuation versus time, it represents the changes in neurotransmitter concentration upon external stimulation [182]. FSCV based on in vivo dopamine sensing in the rat brain was demonstrated with Nafion-coated microelectrodes [183], tungsten-coated microelectrodes [184] and carbon fibre microelectrodes [183] to measure sub-micromolar changes in the concentration of dopamine upon stimulus. To enhance the sensitivity and selectivity of this technique for dopamine, electrode surface functionalization is needed such as modified carbon paste solid electrodes [185; 186] and electrically-treated carbon micro-electrodes [187]. Electrode functionalization with polymers was also investigated, such as Nafion-coated electrode which is specific to cationic species such as dopamine, serotonin [188], clay-modified electrodes [189], electroactive polymer such as polypyrrole coated [190], poly (N,N-dimethylaniline)-modified electrodes [191], and uncoated carbon fiber microelectrodes [192]. A higher sensitivity is achieved by extending the anodic scan rate to +1400 V/s.