# A Review of Neurotransmitters Sensing Methods for Neuro-Engineering Research
## 2 Neurotransmitter Detection Methods
### Optical Sensing Techniques
#### 2.2.3 Forster Resonance Energy Transfer (FRET) and Photoinduced Electron Transfer (PIET)  
FRET is based on the radiation-free transfer of energy from a \"donor\" fluorophore to an \"acceptor\" fluorophore [117; 118]. Upon excitation, the electrons at the valence band of the donor move to a higher energy or conduction band, and then immediately return to the lower energy state. Thus, an emission of light at different wavelengths is observed [119]. The quenchers (acceptors) absorb the energy from the donors in the excited state. Consequently, an energy transfer and subsequent quenching of the donor fluorophore is observed, while the acceptor fluorophore sees an increase in its emission intensity [120]. The quenchers are normally organic dyes, quantum dots (QDs), nanoparticles or biological molecules with an absorption spectrum close to the emission spectrum of the donor.  
For instance, dopamine can quench the fluorescence of QDs [121; 122; 123]. Quinone, an oxidized form of dopamine, is considered as an electron acceptor. When the QDs are excited to a higher energy state, their electrons are pushed to the lowest vacant molecular orbital of quinone and, then, the electrons which are transferred back to the valence band of the quantum dot induce a quenched state of QDs. The rate of electron transfer depends on the pH and concentration of the oxidized dopamine in the solution [124]. QDs can transfer energy to molecules able to generate singlet oxygen [125]. Dopamine can thus behave as a photosensitizer by generating singlet oxygen through auto-oxidation. In alkaline solutions, functionalized quantum dots are conjugated to dopamine via hydrogen bonding which can be oxidized to quinone, leading to quenching the fluorescence of the quantum dots with a high LOD of 0.3 nM [122; 126; 127]. Hybrid quantum dots with natural thiol containing molecules on the surface have good solubility and high selectivity for dopamine in biological fluids, for a high LOD of 0.8 nM [128].  
As cadmium-based quantum dots are expensive and toxic, they have been replaced by more affordable ZnO quantum dots that are biocompatible and environmentally-friendly for dopamine sensing [129]. Fluorescence detection techniques without heavy metal ions release were developedthrough the use of natural amino-acids as surface coating to show a high LOD of 875 pM [130]. Considering the heavy metal toxicity and environmental hazards [131], graphene quantum dots are preferred to semiconductor based quantum dots due to their environmentally-friendly properties [132], excellent water stability (neurotransmitters are always in aqueous solutions), stable photoluminescence and high electrical conductivity [133]. Polyproc microsphere-graphene core-shell hybrid systems for dopamine open a new prospect for sensing dopamine with LOD of 10 pM in real-time sensing [134].  
Gold nanoparticles are also excellent acceptors to replace the traditional organic quenchers [135] for photoinduced electron transfer based dopamine sensing [136]. Gold nanoparticles can be functionalized with aptamers, which are single-stranded nucleic acids with a specific affinity to one molecule--for example, dopamine. They are screened by an in vitro selection technique named SELEX (systematic evolution of ligands by exponential enrichment) [137, 138]. Dopamine binding aptamers prevent the aggregation of gold nanoparticles upon NaCl addition. Following the addition of dopamine, it is conjugated to the dopamine binding aptamer, leaving unprotected nanoparticles. The later aggregate, resulting in the fluorescence quenching of rhodamine B. The fluorescence intensity is proportional to dopamine concentration with an LOD of 2 nM [139].