Neurotransmitters (NTs) are crucial regulatory molecules responsible for maintaining the neurophysiological functioning of the brain. Dysregulated levels of certain NTs, such as dopamine, serotonin, norepinephrine, epinephrine, glutamate, and gamma-aminobutyric acid, are often correlated with the pathogenesis of neurodegenerative diseases that involve the progressive and selective loss of structure or function of neuronal systems. Therefore, the identification and validation of relevant biomarkers are essential to diagnose these diseases much earlier. However, the quantitative analysis of NTs is challenging because of their dynamic release and presence of low concentrations. Accordingly, nanocomposite (NC)-based electrochemical sensors have been studied extensively and are gaining tremendous interest due to their high sensitivity, response rate, stability, portability, ease of use in point-of-care diagnostics, amenability to microprocessing, and low cost. In this review, we first briefly discuss the potential biomarkers of neurodegenerative diseases, NC-based electrochemical sensors and their advantages and disadvantages, and the properties of the NCs, which further increase the sensor performance. Finally, we summarized the future perspectives of NC-based electrochemical sensors in the clinical set-up for NTs detection to identify research gaps.

Enzyme-based portable amperometric biosensors are precise and low-cost medical devices used for rapid cancer biomarker screening. Sarcosine (Sar) is an ideal biomarker for prostate cancer (PCa). Because human serum and urine contain complex interfering substances that can directly oxidize at the electrode surface, rapid Sar screening biosensors are relatively challenging and have rarely been reported. Therefore, highly sensitive and selective amperometric biosensors that enable real-time measurements within <1.0 min are needed. To achieve this, a chitosan–polyaniline polymer nanocomposite (CS–PANI NC), a carrier for dispersing mesoporous carbon (MC), was synthesized and modified on a screen-printed carbon electrode (SPCE) to detect hydrogen peroxide (H₂O₂). The sarcosine oxidase (SOx) enzyme-immobilized CS–PANI–MC-2 ternary NCs were referred to as supramolecular architectures (SMAs). The excellent electron transfer ability of the SMA-modified SPCE (SMA/SPCE) sensor enabled highly sensitive H₂O₂ detection for immediate trace Sar biomarker detection. Therefore, the system included an SMA/SPCE coupled to a portable potentiostat linked to a smartphone for data acquisition. The high catalytic activity, porous architecture, and sufficient biocompatibility of CS–PANI–MC ternary NCs enabled bioactivity retention and immobilized SOx stability. The fabricated biosensor exhibited a detection limit of 0.077 μM and sensitivity of 8.09 μA mM⁻¹ cm⁻² toward Sar, demonstrating great potential for use in rapid PCa screening.

Disposable sensors are inexpensive, user-friendly sensing tools designed for rapid single-point measurements of a target. Disposable sensors have become more and more essential as diagnostic tools due to the growing demand for quick, easy-to-access, and reliable information related to the target. Dopamine (DA), a prevalent catecholamine neurotransmitter in the human brain, is associated with central nervous system activities and directly promotes neuronal communication. For the sensitive and selective estimation of DA, an enzyme-free amperometric sensor based on polyaniline-doped multi-walled carbon nanotubes (PANI-MWCNTs) drop-coated disposable screen-printed carbon electrodes (SPCEs) was fabricated. This PANI-MWCNTs-2/SPCE sensor boasts exceptional accuracy and sensitivity when working directly with ex vivo mouse brain homogenates. The sensor exhibited a detection limit of 0.05 μM (S/N = 3), and a wide linear range from 1.0 to 200 μM. The sensor’s high selectivity to DA amidst other endogenous interferents was recognized. Since the constructed sensor is enzyme-free yet biocompatible, it exhibited high stability in DA detection using ex vivo mouse brain homogenates extracted from both Parkinson’s disease and control mice models. This research thus presents new insights into understanding DA release dynamics at the tissue level in both of these models.

Bacterial infections in fish farms increase mass mortality and rapid detection of infection can help prevent its widespread. Lactate is an important biomarker for early diagnosis of bacterial infections in farmed olive flounder (Paralichthys olivaceus). To determine the lactate levels, we designed a disposable amperometric biosensor based on Prussian blue nanozyme and lactate oxidase (LOX) entrapped in copolymer-reduced graphene oxide (P-rGO) on screen-printed carbon electrodes. Because LOX is inherently unstable, P-rGO nanosheets were utilized as a base matrix to immobilize it. After optimization in terms of enzyme loading, operating potential, and pH, the biosensor displayed maximum current responses within 5 s at the applied potential of –0.1 V vs. internal Ag/AgCl. The biosensor had Langmuir-type response in the lactate concentration range from 10 µM to 1.6 mM, a dynamic linear response range of 10–100 µM, a sensitivity of 15.9 µA mM⁻¹ cm⁻², and a lower detection limit of 3.1 µM (S/N = 3). Additionally, the biosensor featured high reproducibility, good selectivity, and stability till four weeks. Its practical applicability was tested in olive flounder infected by Streptococcus parauberis against the uninfected control. The results were satisfactory compared to those of a standard colorimetric assay kit, validating our method.

A simple one-step electrochemical deposition/activation of graphitic carbon nitride (g-C₃N₄) is highly desired for sensor configurations and remains a great challenge. Herein, we attempt an electrochemical route to exfoliate the g-C₃N₄ nanosheets in an aqueous solution of pH 7.0 for constructing a sensor, which is highly sensitive for the detection of serotonin (5-HT). The significance of our design is to exfoliate the g-C₃N₄ nanosheets, a strong electrocatalyst for 5-HT detection. Investigations regarding the effect of neutral pH (pH 7.0) on the bulk g-C₃N₄ and g-C₃N₄ nanosheets, physical characterization, and electrochemical studies were extensively carried out. We demonstrate that the g-C₃N₄ nanosheets have a significant electrocatalytic effect for the 5-HT detection in a dynamic linear range from 500 pM to 1000 nM (R² = 0.999). The limit of detection and sensitivity of the designed 5-HT sensor was calculated to be 150 pM and 1.03 µA µM⁻¹ cm⁻², respectively. The proposed sensor has great advantages such as high sensitivity, good selectivity, reproducibility, and stability. The constructed g-C₃N₄ nanosheets-based sensor platform opens new feasibilities for the determination of 5-HT even at the picomolar/nanomolar concentration range.

Melatonin (MT), a pineal gland hormone, regulates the sleep/wake cycle and is a potential biomarker for neurodegenerative disorders, depression, hypertension, and several cancers, including prostate cancer and hepatocarcinoma. The amperometric detection of MT was achieved using a sensor customized with ruthenium-incorporated carbon spheres (Ru–CS), possessing C- and O-rich catalytically active Ru surfaces. The non-covalent interactions and ion–molecule adducts between Ru and CS favor the formation of heterojunctions at the sensor–analyte interface, thus accelerating the reactions towards MT. The Ru–CS/Screen-printed carbon electrode (SPCE) sensor demonstrated the outstanding electrocatalytic oxidation of MT owing to its high surface area and heterogeneous rate constants and afforded a lower detection limit (0.27 μM), high sensitivity (0.85 μA μM ⁻¹ cm⁻²), and excellent selectivity for MT with the co-existence of crucial neurotransmitters, including norepinephrine, epinephrine, dopamine, and serotonin. High concentrations of active biomolecules, such as ascorbic acid and tyrosine, did not interfere with MT detection. The practical feasibility of the sensor for MT detection in pharmaceutical samples was demonstrated, comparable to the data provided on the product labels. The developed amperometric sensor is highly suitable for the quality control of medicines because of its low cost, simplicity, small sample size, speed of analysis, and potential for automation.