Simultaneous Detection of Dopamine and Serotonin-A Comparative Experimental and Theoretical Study of Neurotransmitter Interactions

Abstract

With the goal of accurately detecting and quantifying the amounts of dopamine (DA) and serotonin (5-HT) in mixtures of these neurotransmitters without using any labelling, we present a detailed, comparative computational and Raman experimental study. Although discrimination between these two analytes is achievable in such mixtures for concentrations in the millimolar range, their accurate quantification remains unattainable. As shown for the first time in this work, the formation of a new composite resulting from their interactions with each other is the main reason for this lack of quantification. While this new hydrogen-bonded complex further complicates potential analyte discrimination and quantification at concentrations characteristic of physiological levels (i.e., nanomolar concentrations), it can also open new avenues for its use in drug delivery and pharmaceutical research. This remark is based not only on chemical interactions analyzed here from both theoretical and experimental approaches, but also on biological relationship, with consideration of both functional and neural proximity perspectives. Thus, this research constitutes an important contribution toward better understanding of neural processes, as well as toward possible future development of label-free biosensors.

Keywords: computational analysis; dopamine; label-free optical biosensors; neurotransmitters; serotonin; simultaneous detection; surface-enhanced Raman spectroscopy.

Figure 1

Raman spectra of serotonin (5-HT) and dopamine (DA) at 10⁻² molar concentrations, for their mixtures at different ratios, as labeled. The spectra are vertically translated for easier visualization.

Figure 2

Statistical analysis of fraction of serotonin detected by fitting Raman measurements versus the actual fraction used in the sample preparation.

Figure 3

(a) Structural representation of serotonin—dopamine interaction and formation of a new 5-HT—DA complex through hydrogen bonding. Red and blue colors were used for oxygen and nitrogen atoms, respectively. (b) Theoretically calculated and experimentally measured Raman vibrations of 5-HT—DA composite. The spectra are vertically translated for easier visualization and appropriately labeled.

Figure 4

(a) Structural representation of new 5-HT—DA composite in the proximity of silver dimer after energy optimization. (b) Theoretically estimated and experimentally recorded Raman vibrational spectra of 5-HT—DA composite for a concentration of 10⁻⁸ M in the proximity of silver.

Figure 5

Overall averages of 140 Raman spectra recorded in different spots on SERS mixture samples with different ratios, as labeled (seven different time series acquisitions, of 20 spectra each and at 200 ms per spectrum). The individual Raman spectra of 5-HT and DA are also presented for comparison.