Electrochemical Detection of Neurotransmitters

Abstract

Neurotransmitters are important chemical messengers in the nervous system that play a crucial role in physiological and physical health. Abnormal levels of neurotransmitters have been correlated with physical, psychotic, and neurodegenerative diseases such as Alzheimer's, Parkinson's, dementia, addiction, depression, and schizophrenia. Although multiple neurotechnological approaches have been reported in the literature, the detection and monitoring of neurotransmitters in the brain remains a challenge and continues to garner significant attention. Neurotechnology that provides high-throughput, as well as fast and specific quantification of target analytes in the brain, without negatively impacting the implanted region is highly desired for the monitoring of the complex intercommunication of neurotransmitters. Therefore, it is crucial to develop clinical assessment techniques that are sensitive and reliable to monitor and modulate these chemical messengers and screen diseases. This review focuses on summarizing the current electrochemical measurement techniques that are capable of sensing neurotransmitters with high temporal resolution in real time. Advanced neurotransmitter sensing platforms that integrate nanomaterials and biorecognition elements are explored.

Keywords: biosensors; cyclic voltammetry; differential pulse voltammetry; electrochemical; fast scan cyclic voltammetry; neurotransmitters.

Figure 1

(A) Neurotransmitters (green) are exocytotically released into the synaptic cleft and diffuse into the extracellular matrix, bind to the receptors (blue), and trigger a series of downstream reactions (red) in the axon of other neurons. (B) A model electrode drawn to scale in a network of neurons. Adapted from [14].

Figure 2

Electrochemical oxidation of dopamine to dopamine quinone in a 2-electron oxidation when a potential is applied to the transducer.

Figure 3

Fast scan cyclic voltammetry (FSCV) of 1 µM histamine at different switching potentials, a holding potential of −0.4 V, and a scan rate of 400 V/s. (A) Peak current as the result of electrostatic adhesion of histamine. (B) Faradaic peaks upon the reduction of histamine. Reprinted with permission [35].

Figure 4

False color plot visualization of the change in concentration of dopamine and serotonin on single carbon nanotube. Reprinted with permission [36].

Figure 5

Fast scan cyclic voltammetry scans for 3,4-dihydroxyphenylacetic acid (DOPAC) with nafion (A) and polyethyleneimine (PEI) (B). Reprinted with permission [39].

Figure 6

Cross-sectional SEM images of carbon nanotube (CNT) yarn (A), PEI-CNT fiber (B), and acid spin CNT fiber (C). Reprinted with permission [43].

Figure 7

CV of 1 µM dopamine at 2000 V/s for (A) carbon fiber microelectrode (CFME) (B) CNT yarn, and (C) PEI-CNT fiber electrodes, demonstrating a consistent signal even at a high temporal resolution of PEI-CNT fibers. Reprinted with permission [43].

Figure 8

Differential pulse voltammetry (DPV) of dopamine (DA) and serotonin (5-HT) in the human serum conducted using (A) MWCNT—DHP film-coated GCE for (a) 0, (b) 0.05, (c) 0.1, (d) 0.2, (e) 0.4 µM DA and 5-HT. (B) DPVs of DA + 5-HT at nano-Au/PPyox/GCE with variously spiked concentrations: (a–i) 0, 0.05, 0.1, 0.25, 0.5, 0.8, 1.3, 1.8, 2.2 μM. Reprinted with permission [47,48].

Figure 9

DPV voltammograms of increasing concentrations of DA and AP at a f-MWCNT modified electrode. Reprinted with permission [49].

Figure 10

(A) DPV voltammograms of increasing concentrations of DA and EP in 0.1 M PBS at AgNPs-PCA-Au electrode. (B) Plot of current as a function of concentration of DA and EP. Reprinted with permission [51].

Figure 11

(A) CV voltammogram of 5 μM serotonin at the bare microelectrode (black), and the GR- FeTSPc functionalized probe (red). (B) Concentration of DA obtained in vivo every 10 m with the following experimental conditions: (a) administration group given Uncaria rhyunchophylla, (c) the control administration group given antipsychotics, (d) the negative control group given saline and 5- HT at (b) the negative control group, (e) control administration group, and (f) administration group. Reprinted with permission [60].

Figure 12

Astrocytes expressing GFP local to probe implantation (probe) and the adjacent area (distant) in vivo mice model. An increased density of astrocytes is associated with glial scarring. Reprinted with permission [61].

Figure 13

(A) A schematic of the implanted electrode. (B) Photograph of the implanted working electrode. (C) MRI of the striatal target site highlighted in purple. Reprinted with permission [62].