Detection Of Neurotransmitters Research Articles

Analysis of Catecholamines and Pterins in Inborn Errors of Monoamine Neurotransmitter Metabolism-From Past to Future.

Inborn errors of monoamine neurotransmitter biosynthesis and degradation belong to the rare inborn errors of metabolism. They are caused by monogenic variants in the genes encoding the proteins involved in (1) neurotransmitter biosynthesis (like tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC)), (2) in tetrahydrobiopterin (BH4) cofactor biosynthesis (GTP cyclohydrolase 1 (GTPCH), 6-pyruvoyl-tetrahydropterin synthase (PTPS), sepiapterin reductase (SPR)) and recycling (pterin-4a-carbinolamine dehydratase (PCD), dihydropteridine reductase (DHPR)), or (3) in co-chaperones (DNAJC12). Clinically, they present early during childhood with a lack of monoamine neurotransmitters, especially dopamine and its products norepinephrine and epinephrine. Classical symptoms include autonomous dysregulations, hypotonia, movement disorders, and developmental delay. Therapy is predominantly based on supplementation of missing cofactors or neurotransmitter precursors. However, diagnosis is difficult and is predominantly based on quantitative detection of neurotransmitters, cofactors, and precursors in cerebrospinal fluid (CSF), urine, and blood. This review aims at summarizing the diverse analytical tools routinely used for diagnosis to determine quantitatively the amounts of neurotransmitters and cofactors in the different types of samples used to identify patients suffering from these rare diseases.

Nanodiamond Coating Improves the Sensitivity and Antifouling Properties of Carbon Fiber Microelectrodes.

Nanodiamonds (NDs) are carbon nanomaterials with a core diamond crystalline structure and crystal defects, such as graphitic carbon and heteroatoms, on their surface. For electrochemistry, NDs are promising to increase active sites and decrease fouling, but NDs have not been studied for neurotransmitter electrochemistry. Here, we optimized ND coatings on microelectrodes and found that ND increases the sensitivity for neurotransmitters with fast-scan cyclic voltammetry detection and decreases electrochemical and biofouling. Different sizes and functionalizations of NDs were tested, and ND suspensions were drop-casted onto carbon-fiber microelectrodes (CFMEs). The 5 nm ND-H and 5 nm ND-COOH formed thick coatings, while the 15 and 60 nm ND-COOH formed more sparse coatings. With electrochemical impedance spectroscopy, 5 nm ND-H and 5 nm ND-COOH had high charge-transfer resistance, while 15 and 60 nm ND-COOH had low charge-transfer resistance. ND-COOH (15 nm) was optimal, with the best electrocatalytic properties and current for dopamine. Sensitivity was enhanced 2.1 ± 0.2 times and the limit of detection for dopamine improved to 3 ± 1 nM. ND coating increased current for other cations such as serotonin, norepinephrine, and epinephrine, but not for the anion ascorbic acid. Moreover, NDs decreased electrochemical fouling from serotonin and 5-hydroxyindoleacetic acid, and they also decreased biofouling in brain slice tissue by 50%. The current at biofouled ND-coated electrodes is similar to the signal of pristine, unfouled CFMEs. The carboxylated ND-modified CFMEs are beneficial for neurotransmitter detection because of easy fabrication, improved limit of detection, and antifouling properties.

Electrochemical Detection of Dopamine Based on Functionalized Electrodes

The rapid electrochemical identification and quantification of neurotransmitters being a challenge in the ever-growing field of neuroelectronics, we aimed to facilitate the electrochemical selective detection of dopamine by functionalizing commercially available electrodes through the deposition of a thin film containing pre-formed gold nanoparticles. The influence of different parameters and experimental conditions, such as buffer solution, fiber material, concentration, and cyclic voltammetry (CV) cycle number, were tested during neurotransmitter detection. In each case, without drastically changing the outcome of the functionalization process, the selectivity towards dopamine was improved. The detected oxidation current for dopamine was increased by 92%, while ascorbic acid and serotonin oxidation currents were lowered by 66% under the best conditions. Moreover, dopamine sensing was successfully achieved in tandem with home-made triple electrodes and an in-house built potentiostat at a high scan rate mode.

Trends in Synthetic Diamond for Electrochemical Applications

Trends in Synthetic Diamond for Electrochemical Applications

Integration of Micro-Patterned Carbon Fiber Mats into Polyimide for the Development of Flexible Implantable Neural Devices.

Polymer-derived carbon as neural electrode material has recently been subject of interest due to its ability to act as a multimodal platform for simultaneous recording and stimulation of neural activity and neurotransmitter detection. Its mechanical properties and the inverse fabrication protocol commonly used for the manufacturing of pyrolyzed carbon thin-film devices, however, only allow for its use as the electrode material and not as material for interconnects and other conductive components. In this study -for the first time-a process to fabricate flexible neural devices entirely made of carbon fibers (CFs) and polyimide (PI) was developed. The devices consist of carbonized polyacrylonitrile (PAN) fiber mats embedded in polyimide, which were patterned into the desired shapes using reactive ion etching (RIE). This method allowed for the fabrication of miniaturized, flexible and conductive carbon components with critical dimensions of 12.5 μm. Tensile tests were performed to evaluate the mechanical stability of the CF/PI composite, to detect potential electrical resistance changes due to bending and to study the adhesion of different PI layers onto each other. A strong mechanical interlock between CFs and PI was demonstrated and no significant change in the resistance of the CFs was detected after 100k cycles of tensile bending (r = 3 mm). The fabrication approach proposed here successfully yielded entirely metal-free and entirely flexible electrodes. It opens the door to further studies with the guarantee of highly stable electrodes, both mechanically and electrically.

Sensitive detection of dopamine using a platinum microelectrode modified by reduced graphene oxide and gold nanoparticles

Platinum wire microelectrodes generally exhibited properties of low sensitivity but are easily contaminated where it comes to dopamine detection. In this paper, a platinum wire modified with gold nanoparticles (AuNPs) and reduced graphene oxide (rGO) was used to electrochemically detect dopamine in vivo. Electrochemical performances of microelectrodes (before and after surface modification) were investigated by impedance spectroscopy and cyclic voltammetry. The results showed that AuNPs/rGO composites significantly increase the electrode surface area and improve the electrocatalytic property of platinum wires. The modified electrodes exhibited excellent sensitivity for dopamine detection (LOD=16.57nM), as well as ascendant selectivity (simultaneous detection of ascorbic acid, dopamine, and uric acid), reproducibility (R.S.D.=3.98%), and stability (≫100 repetitive potential sweeps, 1-week lifespan). In vivo experiments showed that the proposed AuNPs/rGO electrode was also capable of detecting dopamine in complex physiological environments, particularly in the striatum of anesthetized rats. Hence, the proposed electrodes provided a potential application in in vivo multiplexing neurotransmitter detection in further research.

Toward MRI and Optical Detection of Zwitterionic Neurotransmitters: Near-Infrared Luminescent and Magnetic Properties of Macrocyclic Lanthanide(III) Complexes Appended with a Crown Ether and a Benzophenone Chromophore.

Thanks to their versatile magnetic and luminescence features, lanthanide complexes have gained a central position in biomedical imaging as magnetic resonance imaging (MRI) contrast agents and optical imaging probes. In addition, appropriate chemical design allows modification of the magnetic relaxation properties of GdIII complexes and the optical properties of visible- or near-infrared (NIR)-emitting lanthanide chelates upon interaction with various biomarkers, which makes them ideal candidates for the creation of responsive agents. In this Forum Article, we demonstrate such design principles as well as the difficulties encountered in the context of neurotransmitter (NT) detection. Lanthanide(III) complexes of a macrocyclic ligand incorporating a benzophenone chromophore and a monoazacrown ether (LnL3) have been synthesized as responsive probes to monitor amino acid NTs either in MRI (Ln = Gd) or in NIR optical detection (Ln = Nd or Yb). The parameters characterizing the water exchange and rotational dynamics of the gadolinium(III) complex were assessed by 17O NMR and 1H NMRD. In the presence of zwitterionic NTs, the inner-sphere water molecule is replaced by the carboxylate function of the NTs in the gadolinium(III) complex, leading to a decrease of the longitudinal relaxivity from 6.7 to 2-2.5 mM-1 s-1 (300 MHz and 37 °C). The apparent affinity constants range from Ka = 35 for γ-aminobutyric acid (GABA) to 80 M-1 for glycine and glutamate, and there is no selectivity with respect to hydrogen carbonate (Ka = 232; pH 7.4). The gadolinium(III) complex interacts with human serum albumin (HSA), resulting in a 60% increase in the relaxivity (20 MHz, 37 °C) in the absence of NTs. The HSA-bound complex, however, was revealed to be less responsive to NTs because of displacement of the GdIII-bound water by HSA, which was confirmed by the hydration number calculated from luminescence lifetimes of the HSA-bound europium(III) complex. The creation of an imaging agent suitable for NIR detection of NTs for an enhanced sensitivity in biological systems using the benzophenone (BP) moiety as the sensitizer of lanthanide luminescence was also attempted. Upon excitation at 300 nm of the BP chromophore in aqueous solutions of NdL3 and YbL3, characteristic NIR emissions of NdIII and YbIII were observed because of 4F3/2 → 4IJ (J = 9/2-13/2) and 2F5/2 → 2F7/2 transitions, respectively, indicating that this chromophore is a suitable antenna. Despite these promising results, luminescence titrations of NdIII and YbIII complexes with NTs were not conclusive because of chemical conversion of the ligand triggered by light, preventing quantitative analysis. The observed photochemical reaction of the ligand is strongly dependent on the nature of the lanthanide chelated; it is considerably slowed down in the presence of NdIII and EuIII.

Gold Nanoparticle Modified Carbon Fiber Microelectrodes for Enhanced Neurochemical Detection.

For over 30 years, carbon-fiber microelectrodes (CFMEs) have been the standard for neurotransmitter detection. Generally, carbon fibers are aspirated into glass capillaries, pulled to a fine taper, and then sealed using an epoxy to create electrode materials that are used for fast scan cyclic voltammetry testing. The use of bare CFMEs has several limitations, though. First and foremost, the carbon fiber contains mostly basal plane carbon, which has a relatively low surface area and yields lower sensitivities than other nanomaterials. Furthermore, the graphitic carbon is limited by its temporal resolution, and its relatively low conductivity. Lastly, neurochemicals and macromolecules have been known to foul at the surface of carbon electrodes where they form non-conductive polymers that block further neurotransmitter adsorption. For this study, we modify CFMEs with gold nanoparticles to enhance neurochemical testing with fast scan cyclic voltammetry. Au3+ was electrodeposited or dipcoated from a colloidal solution onto the surface of CFMEs. Since gold is a stable and relatively inert metal, it is an ideal electrode material for analytical measurements of neurochemicals. Gold nanoparticle modified (AuNP-CFMEs) had a stability to dopamine response for over 4 h. Moreover, AuNP-CFMEs exhibit an increased sensitivity (higher peak oxidative current of the cyclic voltammograms) and faster electron transfer kinetics (lower ΔEP or peak separation) than bare unmodified CFMEs. The development of AuNP-CFMEs provides the creation of novel electrochemical sensors for detecting fast changes in dopamine concentration and other neurochemicals at lower limits of detection. This work has vast applications for the enhancement of neurochemical measurements. The generation of gold nanoparticle modified CFMEs will be vitally important for the development of novel electrode sensors to detect neurotransmitters in vivo in rodent and other models to study neurochemical effects of drug abuse, depression, stroke, ischemia, and other behavioral and disease states.

(Invited) Brief Historical Overview and Current Status of Electrochemical Neurotransmitter Detection

Abnormal neurotransmitter concentrations are associated with serious disorders including traumatic brain injury, Parkinson’s and Alzheimer’s diseases, epilepsy, and chronic pain. Understanding the causes and potential cures of these disorders requires highly selective, sensitive, and responsive neurotransmitter detection. From its inception in the early 1970s, electrochemical neurotransmitter detection has become a vibrant research field that is addressing the need for sensitive, real-time quantitative neurotransmitter analysis. Electrochemical techniques can detect both electroactive and nonelectroactive species but different materials and methods are used depending on how easily the species of interest can be electrolyzed and distinguished from other analytes. Electrode materials and design have evolved from being macroscale devices for sensing one analyte at a single electrode to the point that there now exist microscale electrode arrays, some of which are capable of simultaneously monitoring multiple neurotransmitters. In addition, some electrode arrays are flexible in order to more amenably be integrated into soft, living tissue for real-time in vivo monitoring. After a brief historical overview, this presentation summarizes the current state of electrochemical neurotransmitter detection by highlighting notable examples, applications, challenges and future directions. Figure 1

A Novel Target Receptor Design and Biosensing Platform Using RAFT Polymer-Based Molecular Templating

In this work, we propose a novel biosensing platform based on a single-chain molecularly templated polymer. We have utilized reversible addition-fragmentation chain transfer (RAFT) technique to synthesize a polymer-based target receptor consisting of N-isopropylacrylamide (NIPAM) as a backbone and methacrylic acid (MAA) and 4-vinylpyridine (4-VP) as functional monomers. In addition, vinylferrocene (VF) was incorporated into the polymer as a redox reporter. 4-nitrophenol (4-NP) was chosen as a model target for templating. The sensing platform was implemented by immobilizing the polymers on gold electrode surface, forming a brush-like polymer layer. As the target molecules bind to the polymer receptor, the polymer undergoes conformational change which can be detected via electrochemical methods. The proposed sensing platform is aimed to detect small species such as neurotransmitters and neurotoxins with high specificity. One of the major challenges with biochemical sensor is achieving selectivity in analyte detection and therefore, a highly selective target receptor is needed [1]. One strategy to achieving this goal is the technique known as molecular templating or molecularly imprinted polymers (MIP) [2] where the polymer receptors are synthesized in the presence of the ‘template’ molecule to capture its chemical and structural motifs. Traditionally, the molecularly imprinted polymers were highly crosslinked 3-dimensional structures with the target binding sites embedded within the bulk polymer. However, the challenge with this architecture is that the response time is slow (due to the analyte having to penetrate the polymer layer to find the receptors) and removing the bound target species is difficult, rendering this approach not suitable for real-time continuous monitoring applications. In our approach, we propose a single-chain templated polymer-based target receptor as a recognition element for chemical detection. We have chosen 4-nitrophenol (4-NP), one of the priority toxicants according to the US Environmental Protection Agency, as our model target analyte. The process for preparing the templated polymers is shown in Figure 1. Briefly, N-isopropylacrylamide (NIPAM), functional monomers, redox label, RAFT agent, initiator and the template monomers were added in a solvent for molecule assembly. Next, after removing the dissolved oxygen inside the mixed solution, the polymerization was initiated. Figure 2 illustrates the working principle of the proposed biosensing platform. After molecular assembly (a), The polymers are prepared via RAFT-polymerization (b) to ensure uniformity in the molecular weight, followed by removing the template from the polymer via dialysis (c). Once the templates are fully removed, the synthesized target receptors are attached onto the gold electrode, forming a brush-like monolayer assembly (d). During analyte detection, when the target binds to the molecular receptor, the conformation of the polymer changes which can be measured electrochemically using the redox tags (vinyl ferrocene) (e). The selective target rebinding is based on the weak interaction between the functional monomers in the polymer and 4-NP such as hydrogen bonding and the π-πstacking force (f). The immobilization of polymer on gold surface is confirmed using electrochemical impedance spectroscopy (EIS). As shown in Figure 3, the impedance is gradually increased with the incubation time, indicating successful attachment of the polymer on the gold surface. Figure 4 shows the process of determining the binding affinity of the templated polymers using gold nanoparticles (AuNPs) and UV-vis. Figure 5 (a) indicates that the MIP exhibits higher affinity toward 4-NP compared with the NIP. In Figure 5 (b), the selectivitymolecular templating is demonstrated by comparing wtih 3-nitrophenol (3-NP). In Figure 6, it is shown that, as the concentration increased, the charge transfer is promoted in the MIP due to the collapsing of the polymer upon target recognition. NIP, on the other hand, shows negligible response to the 4-NP, indicating no significant conformational change for the polymers. Figure 7 (a) summarizes the calibration curves for both MIP and NIP. The templated polymer-based sensor shows a linear response to 4-NP solution, indicating that the proposed target receptor and the sensing platform is capable of detecting 4-NP. Figure 7 (b) shows the calibration curves when the templated polymer-based sensor is exposed to either 4-NP or 3-NP, suggesting a promising specificity towards 4-NP. In summary, an electrochemical sensing platform has been successfully developed, and the selectivity of the 4-NP imprinted polymers has been confirmed. The results demonstrate that 4-NP imprinted polymer undergoes a conformation change during specific target recognition. We envision that the proposed sensing platform can potentially be used in other applications such as neurotransmitter detection and drug delivery monitoring.

Latest Trends in Electrochemical Sensors for Neurotransmitters: A Review.

Neurotransmitters are endogenous chemical messengers which play an important role in many of the brain functions, abnormal levels being correlated with physical, psychotic and neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease. Therefore, their sensitive and robust detection is of great clinical significance. Electrochemical methods have been intensively used in the last decades for neurotransmitter detection, outclassing more complicated analytical techniques such as conventional spectrophotometry, chromatography, fluorescence, flow injection, and capillary electrophoresis. In this manuscript, the most successful and promising electrochemical enzyme-free and enzymatic sensors for neurotransmitter detection are reviewed. Focusing on the activity of worldwide researchers mainly during the last ten years (2010–2019), without pretending to be exhaustive, we present an overview of the progress made in sensing strategies during this time. Particular emphasis is placed on nanostructured-based sensors, which show a substantial improvement of the analytical performances. This review also examines the progress made in biosensors for neurotransmitter measurements in vitro, in vivo and ex vivo.

Defect Sites Modulate Fouling Resistance on Carbon-Nanotube Fiber Electrodes.

Carbon nanotube (CNT) fiber electrodes have become increasingly popular electrode materials for neurotransmitter detection with fast-scan cyclic voltammetry (FSCV). The unique properties of CNT fiber electrodes like increased electron transfer, sensitivity, waveform application frequency independence, and resistance to fouling make them ideal biological sensors for FSCV. In particular, their resistance to fouling has been observed for several years, but the specific physical properties which aid in fouling resistance have been debated. Here, we investigate the extent to which the presence of defect sites on the surface attenuate both chemical and biological fouling with FSCV. We compared traditional carbon-fiber microelectrodes (CFMEs) to pristine CNTs and functionalized CNTs. CFMEs and functionalized CNTs are highly disordered with a great deal of defect sites on the surface. The pristine CNTs have fewer defects compared to the purposefully functionalized CNTs and CFMEs. All electrode surfaces were characterized by a combination of scanning electron microscopy (SEM), Raman spectroscopy, and energy dispersive spectroscopy (EDS). Chemical fouling was studied using serotonin, a popular neurotransmitter notoriously known for electrode fouling. To assess biological fouling, electrodes were implanted in brain tissue for 2 h. Defect sites on the carbon were shown to resist biofouling compared to pristine CNTs but were detrimental for serotonin detection. Overall, we provide insight into the extent to which the electrode surface dictates fouling resistance with FSCV. This work provides evidence that careful considerations of the surface of the CNT material are needed when designing sensors for fouling resistance.

In situ detection of neurotransmitters and epileptiform electrophysiology activity in awake mice brains using a nanocomposites modified microelectrode array

A novel nanocomposites modified microelectrode array (MEA) was designed and fabricated for in situ detection of neurotransmitters (glutamate and dopamine) and electrophysiology activity. The MEAs were implanted into the hippocampus of four epileptic mice to detect the neuron activity along with their behaviours. Six spontaneous seizures were recorded, with each seizure having 5 periods. From the normal to the pre-seizure period, both the concentrations of neurotransmitters and the intensities of electrophysiology activities increased by 20%–70%. During the seizure period, the glutamate level dramatically increased to approximately 10 times its normal, while the dopamine level sharply decreased to approximately one third of the normal; the spike firing rate and the power of the local field potential significantly increased more than three-fold. During the inhibitory period, neurotransmitters and electrophysiology activities were significantly inhibited, and then they gradually returned to normal. These results revealed that seizures were highly correlated with glutamate, dopamine and electrophysiology activity and abnormalities in the neuron activity appeared earlier than any abnormal behaviour. Moreover, synchronized changes of these multiple signals in the pre-seizure period could be used to predict seizures. This novel MEA provides an effective technology and a new perspective for understanding the epileptic mechanism.

EM-Wave Biosensors: A Review of RF, Microwave, mm-Wave and Optical Sensing.

This article presents a broad review on optical, radio-frequency (RF), microwave (MW), millimeter wave (mmW) and terahertz (THz) biosensors. Biomatter-wave interaction modalities are considered over a wide range of frequencies and applications such as detection of cancer biomarkers, biotin, neurotransmitters and heart rate are presented in detail. By treating biological tissue as a dielectric substance, having a unique dielectric signature, it can be characterized by frequency dependent parameters such as permittivity and conductivity. By observing the unique permittivity spectrum, cancerous cells can be distinguished from healthy ones or by measuring the changes in permittivity, concentration of medically relevant biomolecules such as glucose, neurotransmitters, vitamins and proteins, ailments and abnormalities can be detected. In case of optical biosensors, any change in permittivity is transduced to a change in optical properties such as photoluminescence, interference pattern, reflection intensity and reflection angle through techniques like quantum dots, interferometry, surface enhanced raman scattering or surface plasmon resonance. Conversely, in case of RF, MW, mmW and THz biosensors, capacitive sensing is most commonly employed where changes in permittivity are reflected as changes in capacitance, through components like interdigitated electrodes, resonators and microstrip structures. In this paper, interactions of EM waves with biomatter are considered, with an emphasis on a clear demarcation of various modalities, their underlying principles and applications.

Cavity Carbon-Nanopipette Electrodes for Dopamine Detection.

Microelectrodes are typically used for neurotransmitter detection, but nanoelectrodes are not because there is a trade-off between spatial resolution and sensitivity that is dependent on surface area. Cavity carbon-nanopipette electrodes (CNPEs), with tip diameters of a few hundred nanometers, have been developed for nanoscale electrochemistry. Here, we characterize the electrochemical performance of CNPEs with fast-scan cyclic voltammetry (FSCV) for the first time. Dopamine detection using cavity CNPEs, with a depth equivalent to a few radii, is compared with that using open-tube CNPEs, an essentially infinite geometry. Open-tube CNPEs have very slow temporal responses that change over time as the liquid rises in the CNPE. However, a cavity CNPE has a fast temporal response to a bolus of dopamine that is not different from that of a traditional carbon-fiber microelectrode. Cavity CNPEs, with tip diameters of 200-400 nm, have high currents because the small cavity traps and increases the local dopamine concentration. The trapping also leads to an FSCV frequency-independent response and the appearance of cyclization peaks that are normally observed only with large concentrations of dopamine. CNPEs have high dopamine selectivity over ascorbic acid (AA) because of the repulsion of AA by the negative electric field at the holding potential and the irreversible redox reaction. In mouse-brain slices, cavity CNPEs detected exogenously applied dopamine, showing they do not clog in tissue. Thus, cavity CNPEs are promising neurochemical sensors that provide spatial resolution on the scale of hundreds of nanometers, which is useful for small model organisms or for locations near specific cells.

Ions-free electrochemically synthetized in aqueous media flake-like CuO nanostructures as SERS reproducible substrates for the detection of neurotransmitters.

The process of catalytic destruction of tumor cells can be strengthened by introducing copper(II) oxide nanostructures (CuONSs) with receptor's agonists/antagonists immobilized on their surface. Here we show a simple and reliable electrochemical method for the fabrication ions-free flake-like CuO nanostructures in a surfactant/ions free aqueous environment. For the determination of the metal surface plasmon, size, rheology, and structure of the fabricated nanostructures ultraviolet-visible (UV-Vis), Fourier-transform infrared (FT-IR), Raman, and X-ray photoelectron (XPS) spectroscopies as well as scanning electron microscope (SEM), high-resolution transmission electron microscopy with energy dispersive X-ray (HDTEM-EDS), X-ray powder diffraction (XRD), and dynamic light scattering (DLS) analysis were used. The fabricated nanostructures were used as highly sensitive, uniform, and reproducible sensors of a natural ligand (bombesin) of some types of metabotropic seven transmembrane G protein-coupled superfamily receptors (GPCRs), which are over-express on the surface of many malignant tumors. Surface-enhanced Raman scattering (SERS) was used to monitor the geometry of adsorbate, separate, enrich, and detect various bombesin C-terminal fragments. It has been shown that the type of used substrate, surface development, and ions present in the solution have little effect on the mode of adsorption.

NIR Biosensing of Neurotransmitters in Stem Cell-Derived Neural Interface Using Advanced Core-Shell Upconversion Nanoparticles.

Nondestructive neurotransmitter detection and real-time monitoring of stem cell differentiation are both of great significance in the field of neurodegenerative disease and regenerative medicine. Although luminescent biosensing nanoprobes have been developed to address this need, they have intrinsic limitations such as autofluorescence, scattering, and phototoxicity. Upconversion nanoparticles (UCNPs) have gained increasing attention for various biomedical applications due to their high photostability, low auto-fluorescent background, and deep tissue penetration; however, UCNPs also suffer from low emission intensities due to undesirable energy migration pathways. To address the aforementioned issue, a single-crystal core-shell-shell "sandwich" structured UCNP is developed that is designed to minimize deleterious energy back-transfer to yield bright visible emissions using low power density excitations. These UCNPs show a remarkable enhancement of luminescent output relative to conventional β-NaYF4:Yb,Er codoped UCNPs and β-NaYF4:Yb,Er@NaYF4:Yb "active shell" alike. Moreover, this advanced core-shell-shell UCNP is subsequently used to develop a highly sensitive biosensor for the ultrasensitive detection of dopamine released from stem cell-derived dopaminergic-neurons. Given the challenges of in situ detection of neurotransmitters, the developed NIR-based biosensing of neurotransmitters in stem cell-derived neural interfaces present a unique tool for investigating single-cell mechanisms associated with dopamine, or other neurotransmitters, and their roles in neurological processes.

Direct Electrochemical Detection of Glutamate, Acetylcholine, Choline, and Adenosine Using Non-Enzymatic Electrodes.

Non-electroactive neurotransmitters such as glutamate, acetylcholine, choline, and adenosine play a critical role in proper activity of living organisms, particularly in the nervous system. While enzyme-based sensing of this type of neurotransmitter has been a research interest for years, non-enzymatic approaches are gaining more attention because of their stability and low cost. Accordingly, this focused review aims to give a summary of the state of the art of non-enzymatic electrochemical sensors used for detection of neurotransmitter that lack an electrochemically active component. In place of using enzymes, transition metal materials such as those based on nickel show an acceptable level of catalytic activity for neurotransmitter sensing. They benefit from fast electron transport properties and high surface energy and their catalytic activity can be much improved if their surface is modified with nanomaterials such as carbon nanotubes and platinum nanoparticles. However, a general comparison reveals that the performance of non-enzymatic biosensors is still lower than those that use enzyme-based methods. Nevertheless, their excellent stability demonstrates that non-enzymatic neurotransmitter sensors warrant additional research in order to advance them toward becoming an acceptable replacement for the more expensive enzyme-based sensors.

Paper-Based Electrochemical Biosensors for Point-of-Care Testing of Neurotransmitters

Neurotransmitters are important biological molecules related to several nervous system diseases (NSDs). Point-of-care testing (POCT) of neurotransmitters is of great importance in preclinical research and early diagnosis of NSDs. Among various POCT platforms, paper-based electrochemical biosensors have achieved great advances in detection of neurotransmitters, thus taking a significant role in POCT of neurotransmitters nowadays. This review gives an overview of the recent advances of paper-based electrochemical biosensors for POCT of neurotransmitters. We first introduce the types of neurotransmitters and biological sample sources mainly used for neurotransmitter detection. Second, we review the components and the traditional fabrication technologies for paper-based electrochemical POCT biosensors, and then the functional modification methods of biosensor surfaces and three-dimensional fabrication methods for further enhancement of their detection performance. Then, we list examples of paper-based electrochemical biosensors used for detecting different neurotransmitters in biological samples. Last, we give a conclusion and promising development direction of paper-based electrochemical biosensors for neurotransmitters detection. The purpose of this review is to introduce the paper-based electrochemical biosensors as an emerging technology for POCT of neurotransmitters, offering a reference for readers and researchers for early diagnosis of NSDs using POCT technologies.

Motor inhibition efficiency in healthy aging: the role of γ-aminobutyric acid.

The ability to cancel a motor response is critical for optimal functioning in various facets of daily life. Hence, efficient inhibitory motor control is a key function throughout the lifespan. Considering the fact that inhibitory motor function gradually declines with advancing age, it is not surprising that the study of motor inhibition in this age group is gaining considerable interest. In general, we can distinguish between two prominent types of motor inhibition, namely proactive and reactive inhibition. Whereas the anticipation for upcoming stops (proactive inhibition) appears readily preserved at older age, the ability to stop an already planned or initiated action (reactive inhibition) generally declines with advancing age. The differential impact of aging on proactive and reactive inhibition at the behavioral level prompts questions about the neural architecture underlying both types of inhibitory motor control. Here we will not only highlight the underlying structural brain properties of proactive and reactive inhibitory control but we will also discuss recent developments in brain-behavioral approaches, namely the registration of neurochemical compounds using magnetic resonance spectroscopy. This technique allows for the direct detection of the primary inhibitory neurotransmitter in the brain, i.e., γ-aminobutyric acid, across the broader cortical/subcortical territory, thereby opening new perspectives for better understanding the neural mechanisms mediating efficient inhibitory control in the context of healthy aging. Ultimately, these insights may contribute to the development of interventions specifically designed to counteract age-related declines in motor inhibition.