Overview: Electrochemical Sensors for Dopamine
Authors: Silue Tjerignimin , Mazafi Alon , Ben-Yoav Hadar , Peixoto Nathalia 
Published: February 2020

Dopamine (DA) is a neurotransmitter located in the ventral tegmental area of the midbrain, the substantia nigra pars compacta, and the arcuate nucleus of the hypothalamus of the human brain [1]. It is a critical puzzle piece in understanding neural behavior and in developing therapeutic intervention technologies for neurological disorders. Monitoring of extracellular DA concentration can serve as a clinically relevant biomarker for specific diseases states as well as a gateway to monitor treatment efficacy. Fluorescence, flow injections, Raman, chromatography and Fourier transform infrared (FTIR) are some examples of analytical techniques that have been reported in the literature [2-6] for the detection of neurotransmitters. Although they offer good selectivity and low limits of detection, they require complex steps and expensive instrumentation [7]. Electrochemical sensors, on the other hand, provide an inexpensive, easy, sensitive, rapid, and selective tool for detection of biomarkers of several diseases and can be easily embedded into portable, more efficient devices for targeted applications in both the clinical and diagnostic fields. In Parkinson’s disease for example, such sensors can be integrated with therapeutic interventions such as deep brain stimulation systems, to enhance the ability to continuously monitor dopamine and other neurotransmitters that are prone to fluctuations. Despite the obstacle of overlapping electrochemical signals in the brain due to the similarities in their molecular form, a wide range of sensors have been recently developed to detect different neurotransmitters in addition to DA, such as norepinephrine, serotonin in the presence of uric acid (UA) and ascorbic acid (AA) at an improved limit of detection, close to the physiologically relevant concentrations [8-12]. Some of the electrochemical sensors used in the detection of DA include carbon electrodes coated with Nafion, electrodes coated with non-conducting polymers, gold electrodes modified on self-assembled monolayers, and nanoparticles-based electrodes [7]. In recent years, nanoparticles-based electrodes have received attention due to their inherent electrocatalytic nature to accelerate the rate electrons transfer between specific molecules and the electrode, and thus improving the selectivity of the sensor towards neurotransmitters in the presence of UA and AA. The improvement of electrode materials with the power of electroanalysis techniques resulted in the improved detection of DA at nanomolar levels. This improved sensing performance has been achieved using techniques such as cyclic voltammetry, differential pulse voltammetry, square wave voltammetry, and fast-scan cyclic voltammetry, and by using electrodes under physiological conditions, in the presence of abundant interfering molecules such as UA and AA [7]. In all these techniques, the main shortcoming of electrochemical sensors is their lifetime. In order to truly offer a solution for long-term implants and neurotransmitter detection, the main bottleneck will be to design sensors that can reliably detect neurotransmitters for years. Currently, sensors only work for about 80 days in vitro [13-14] . Therefore, future research needs to expand on the development of sensors with straightforward fabrication procedure, low detection limit, high stability and good reproducibility for repeated determination of concentrations of neurotransmitters. This will further demonstrate electrochemical sensors as attractive candidates for applications in understanding the neural mechanisms in physiological disorders.

[1] Otmakhova, N.; Duzel, E.; Deutch, A. Y., and Lisman, J., In Intrinsically Motivated Learning in Nat. and Artificial Syst. (2013): 235-254.

[2] Wang, X.; Jin, B. and Lin, X., 2002., Anal. Sci. 18 (8) (2002): 931–933.

[3] Barreto, W. J.; Ponzoni, S.; and Sassi, P., (1998)., Spectrochim. Acta A: Mol. Biomol. Spectrosc. 55 (1) (1998): 65–72.

[4] Carrera, V.; Sabater, E.; Vilanova, E.; and Sogorb, M. A., J. Chromatogr. B 847 (2) (2007): 88–94.

[5] Secor, K. E.; and Glass, T. E., Org. Lett. 6 (21) (2004): 3727–3730.

[6] Du, J.; Shen, L.; and Lu, J., Anal. Chim. Acta. 489 (2) (2003): 183–189.

[7] Ribeiro, J. A.; Fernandes, P. M.; Pereira, C. M.; and Silva, F., Talanta 160 (2016): 653-679.

[8] Zhang, D.A.; Rand, E.; Marsh, M.; Andrews, R.J.; Lee, K.H.; Meyyappan, M.; and Koehne, J.E., Mol. Neurobiol. 48 (2013): 380–385.

[9] Azzopardi, C.; Azzopardi, M.; Muscat, R.; Camilleri, K.P., EMBC (2012): 3527–3530.

[10] Wan, J.; Xu, G.R.; Liu, Z.S., Int. J. Electrochem. Sci. 7 (2012): 12955–12962.

[11] Revin, S.B.; John, S.A., Analyst. 137 (2012): 209–215.

[12] Kamyabi, M.A.; Narimani, O.; Monfared, H.H., J Brazil Chem. Soc. 22 (2011): 468–477.

[13] Babaei, A.; and Taheri, A. R.; Sens. and Actuators B: Chem. 176 (2013): 543-551.

[14] Chen, A.; and Chatterjee, S.; Chem. Soc. Rev. 42.12 (2013): 5425-5438.