Fluorescent-Based Neurotransmitter Sensors: Present and Future Perspectives

Abstract

Neurotransmitters (NTs) are endogenous low-molecular-weight chemical compounds that transmit synaptic signals in the central nervous system. These NTs play a crucial role in facilitating signal communication, motor control, and processes related to memory and learning. Abnormalities in the levels of NTs lead to chronic mental health disorders and heart diseases. Therefore, detecting imbalances in the levels of NTs is important for diagnosing early stages of diseases associated with NTs. Sensing technologies detect NTs rapidly, specifically, and selectively, overcoming the limitations of conventional diagnostic methods. In this review, we focus on the fluorescence-based biosensors that use nanomaterials such as metal clusters, carbon dots, and quantum dots. Additionally, we review biomaterial-based, including aptamer- and enzyme-based, and genetically encoded biosensors. Furthermore, we elaborate on the fluorescence mechanisms, including fluorescence resonance energy transfer, photon-induced electron transfer, intramolecular charge transfer, and excited-state intramolecular proton transfer, in the context of their applications for the detection of NTs. We also discuss the significance of NTs in human physiological functions, address the current challenges in designing fluorescence-based biosensors for the detection of NTs, and explore their future development.

Keywords: biomaterials; biosensing; fluorescence; nanomaterials; neurotransmitters.

Figure 1

(a) Schematic representation of the FRET-based sensing platform of dopamine sensing as well as (b) diagrammatic representation of (1) electron-transfer process and (2) charge-transfer process from excited-state CDs to the ground state of dopamine–quinone. Reprinted from ref. [20]. Copyright (2020) with permission from Elsevier.

Figure 2

The mechanism of DA quenching the fluorescence of N-CQDs. (a) The PL lifetime decays of N-CQDs in the presence and absence of DA. (b) Schematic diagram of the transfer of electrons from N-CQDs to dopamine quinones. (c) The TEM of N-CQDs in the presence of DA. Reprinted from ref. [22]. Copyright (2020) with permission from Elsevier.

Figure 3

(A) Molecular structures of probe SNCN-AE and SNC-AE. (B) Sensing mechanism for detecting AChE. Reprinted from ref. [25]. Copyright (2023) with permission from Elsevier.

Figure 4

Sensing mechanism of GSH-DHLA-Ag nanoclusters and His-Ag nanoclusters for the ratio detection of DA. Reprinted from ref. [34]. Copyright (2020) with permission from Elsevier.

Figure 5

Mechanism for dopamine detection using FAM-labeled aptamers and AuNPs. Reprinted from ref. [36] Copyright (2016) with permission from Elsevier.

Figure 6

The Schematic diagram shows the basic mechanism of neurotransmission, neurotransmitters, and fluorescence sensing. Release of neurotransmitters from presynaptic neurons and individual biosensors are capable of detecting depending on the concentration and distribution of the probes by fluorescence signal intensity.

Figure 7

Illustration of major neurotransmitters and their functions.

Figure 8

GE biosensors. Reprinted from ref. [168]. Copyright (2019) with permission from Elsevier.