Detection Of Neurotransmitters Research Articles

Functional Organic Electrochemical Transistor-Based Biosensors for Biomedical Applications

Organic electrochemical transistors (OECTs), as an emerging device for the development of novel biosensors, have attracted more and more attention in recent years, demonstrating their promising prospects and commercial potential. Functional OECTs have been widely applied in the field of biosensors due to their decisive advantages, such as high transconductance, easy functionalization, and high integration capability. Therefore, this review aims to provide a comprehensive summary of the most recent advances in the application of functional OECT-based biosensors in biomedicine, especially focusing on those biosensors for the detection of physiological and biochemical parameters that are critical for the health of human beings. First, the main components and basic working principles of OECTs will be briefly introduced. In the following, the strategies and key technologies for the preparation of functional OECT-based biosensors will be outlined and discussed with regard to the applications of the detection of various targets, including metabolites, ions, neurotransmitters, electrophysiological parameters, and immunological molecules. Finally, the current main issues and future development trends of functional OECT-based biosensors will be proposed and discussed. The breakthrough in functional OECT-based biosensors is believed to enable such devices to achieve higher performance, and thus, this technology could provide new insight into the future field of medical and life sciences.

Uncovering efficient sensing properties of vanadium disulfide (VS2) nanosheets towards specific neurotransmitters: A DFT prospective

Designing efficient nanosensors based on ultrathin materials for the detection of neurotransmitters is crucial for biosensing applications. In this work, using spin-polarized density functional theory (DFT) calculations, structural, electronic, magnetic, and adsorption of the selected neurotransmitters, such as dopamine (DA) and histamine (HA), were investigated using light transition metals dichalcogenides, vanadium disulfide (VS2) nanosheets. It was revealed that DA and HA adsorbed relatively weakly on pristine (p-VS2) as well as single sulfur (S) Vacancy-induced (SV-VS2). However, the introduction of selected transition metals (TMs) dopants, such as cobalt (Co), iron (Fe), and nickel (Ni), significantly improved the adsorption of DA and HA. Among the studied systems, Ni-doped VS2 (Fe-doped VS2) exhibited the strongest adsorption toward DA (HA) with an adsorption energy of −2.00 (−1.28) eV, which is promising for practical sensing applications. Charge analysis revealed that both DA and HA acted as charge donors to the TMs-doped VS2. Upon DA/HA adsorptions, quantifiable variations were observed in the electronic structures and magnetic properties of TMs-doped VS2, which were studied through band structures, spin-polarized density of states, and work function calculations. Lastly, for the practical detection capabilities at diverse pressure and temperature settings, we employed the Langmuir adsorption model. It was found that TMs-doped VS2 detected DA and HA at concentrations ranging from tens of ppt to ppm levels, respectively. We strongly believe that our findings will contribute towards the development of highly effective nanosensors based on TMs-doped VS2 nanosheets for the detection of DA, and HA.

Direct and rapid detection of serum amino acid and monoamine neurotransmitters to assist the diagnosis of panic disorder

Direct and rapid detection of serum amino acid and monoamine neurotransmitters to assist the diagnosis of panic disorder

Flavonoids from mulberry leaves exhibit sleep-improving effects via regulating GABA and 5-HT receptors

Ethnopharmacological relevanceMulberry leaf (Folium Mori) is a dried leaf of the dicotyledonous mulberry tree and is a homologous food and medicine. Treating insomnia with it is a common practice in traditional Chinese medicine. But still, its potential sleep-improving mechanism remains to be elucidated. Aim of reviewPotential bioactive components and mechanisms of the sleep-improving effect of purified flavone from mulberry leaves (MLF) were explored through in vivo experiments, network pharmacology analysis, and molecular experimental validation. Materials and methodsThe mice model was established by pentobarbital sodium induction to evaluate the sleep-improving effect of MLF. The MLF's chemical composition was identified through a liquid chromatograph quadrupole time-of-flight mass spectrometer (Q-TOF LC/MS) to elucidate its sleep-improving active ingredient. At last, the underlying mechanism of MLF's sleep-improving effect was elucidated through neurotransmitter detection (ELISA), network pharmacology analysis, and molecular experimental validation (quantitative real-time PCR and western blotting). ResultsMLF could dramatically reduce sleep latency by 35%, prolong sleep duration by 123%, and increase the sleep rate of mice through increasing γ-aminobutyric acid (GABA) and serotonin (5-HT) release in serum, hypothalamus, and hippocampus. Q-TOF LC/MS identified 17 flavonoid components in MLF. Network pharmacological analysis suggested that the key sleep-improving active ingredients in MLF might be quercetin, kaempferol, morin, and delphinidin. The key path for MLF to improve sleep might be the tryptophan metabolism and neuroactive ligand-receptor interaction, and the key targets might be gamma-aminobutyric acid type A receptor subunit alpha2 Gene (GABRA2) and serotonin 1A (5-HT1A) receptors. ConclusionsMLF has shown significant sleep-improving effects in mice and may take effect through regulating the GABA and 5-HT receptors.

Region of interest determination algorithm of lensless calcium imaging datasets.

Advances in fluorescence imaging technology have been crucial to the progress of neuroscience. Whether it was specific expression of indicator proteins, detection of neurotransmitters, or miniaturization of fluorescence microscopes, fluorescence imaging has improved upon electrophysiology, the gold standard for monitoring brain activity, and enabled novel methods to sense activity in the brain. Hence, we developed a lightweight and compact implantable CMOS-based lensless Ca2+ imaging device for freely moving transgenic G-CaMP mouse experiments. However, without a lens system, determination of regions of interest (ROI) has proven challenging. Localization of fluorescence activity and separation of signal from noise are difficult. In this study, we report an ROI selection method using a series of adaptive binarizations with a gaussian method and morphological image processing. The parameters for each operation such as the kernel size, sigma and footprint size were optimized. We then validated the utility of the algorithm with simulated data and freely moving nociception experiments using the lensless devices. The device was implanted in the dorsal raphe nucleus to observe pain-related brain activity following a formalin test to stimulate pain. We observed significant increases in fluorescence activity after formalin injection compared to the control group when using the ROI determination algorithm.

Expanding the Materials Palette for Organic Electrochemical Transistor Channels Via Electropolymerization and Functionalized Pyrrole, Thiophene, and Aniline Monomers

Electrochemical transistors are electrolyte-gated devices that permit large signal amplification, ionic-to-electronic signal transduction, and controlled variable resistance. Given that their porous channel materials enable volumetric interaction with the adjacent electrolyte, OECT offer increased detection sensitivity compared to other electrolyte-gated devices such as field-effect transistors (FET).Although these OECT devices have demonstrated utility in a wide range of applications, from neuromorphic computing platforms to bioelectronic devices, they are still in an early stage of development. As a result, a limited range of channel materials have been investigated. Because the magnitude of signal amplification in OECT is directly proportional to the channel transconductance, the vast majority of OECT studies have employed highly-conductive spin-coated formulations of polyethylenedioxythiophene:poly(styrene sulfonate) (PEDOT:PSS) as the active material. While PEDOT-PSS exhibits many desirable qualities for an OECT channel material (e.g., biocompatibility, high transconductance, relatively low mechanical modulus, and responsivity to aqueous ions and bioanalytes), the material has general susceptibility to changes in the ionic strength of the solution it is measuring, which limits its utility for ion-specific detection and in systems for which changes in ionic strength necessarily accompany the other specific changes that the OECT seeks to detect or influence (i.e. neurotransmitter detection). In addition, the material is almost exclusively deposited via spin-coating, which requires a premade solution of pre-determined physical characteristics (concentration, molecular weight, dopant-to-monomer ratio), and therefore limits the ability to for higher-throughput investigation of wide varieties of material configurations.Although electropolymerization of conducting polymers like polypyrrole, polythiophene, and polyaniline is well-studied, only a few isolated reports1,2 have evaluated the benefits of electropolymerization for OECT channel fabrication and performance (i.e., compared to spin-coating or vapor-phase polymerization). However, in a more general sense, electropolymerization provides several additional advantages for OECT channel fabrication:(1) reduce the total time and cost associated with device preparation by reducing the total number of required microfabrication steps;(2) permit higher-throughput methods for fabricating channels with diverse characteristics and dopants;(3) use dopants that allow operation in either depletion or accumulation mode (versus spin-coated PEDOT-PSS, which operates only in depletion mode);(4) enable facile control over channel thickness and form-factor during synthesis;(5) increase control over material properties that influence both electronic and ionic conductivity, such as polymer chain length/stiffness, spacing, and electrostatic affinity;(6) provide a strategy for using electrochemical synthesis to tune the channel transconductance.Unfortunately, there have so far been only isolated repots of electropolymerized OECT channels, and no systematic studies. In this report, our research team will demonstrate the effect of electrosynthesis parameters on channel material characteristics and device performance (i.e., total channel capacity, transconductance, ionic/electronic conductivity, and overall electrochemical impedance). We examined the influence of electrodeposition method (galvanostatic, potentiostatic, linear sweep voltammetry), monomer type, the total degree of polymerization, and the dopant used during electrosynthesis (comparing small, labile dopants such as chloride or tosylate, versus larger semi-labile dopants such as dodecyl benzene sulfonate, versus large immobile polymer dopants such as PSS). We also quantify the impact of introducing different functionalities (e.g., amine, carboxy, sulfonic acid) to the pyrrole, aniline, and thiophene monomers used to fabricate the channels). These functionalities provide motifs for addition functionalization (e.g. using carbodiimide chemistry) with enzymes, biorecognition elements, or redox signaling molecules.Finally, we will present the steps we have taken to implement these devices within organ-on-a-chip systems, and demonstrate the utility of our devices for studying the formation and longitudinal evolution of neural networks within in vitro neuronal colonies. References S. Wustoni, T.C. Hidalgo, A. Hama, D. Ohayon, A. Savva, N. Wei, N. Wehbe, S. Inal. In Situ Electrochemical Synthesis of a Conducting Polymer Composite for Multimetabolite Sensing. Adv. Mater. Technol. 2020, 5, 1900943. L. Zhang, T.L. Andrew. Deposition Dependent Ion Transport in Doped Conjugated Polymer Films: Insights for Creating High-Performance Electrochemical Devices. Adv. Mater. Interfaces 2017, 4, 1700873.

Detection of Hydrogen Ions Resulting from the Inhibition of Acetylcholinesterase Using Indium Tin Oxide-Coated Nanostructures for Pesticide Sensing

The neurotransmitter acetylcholine (ACh) is hydrolyzed by acetylcholinesterase (AChE) into acetic acid and choline to terminate synaptic transmission (1). Organophosphorus (OPs) found in pesticides induce toxicity in organisms by irreversibly binding to AChE, leading to the phosphorylation of the serine residue at the active site. ACh cannot undergo hydrolysis by the phosphorylated enzyme, resulting in excessive stimulation of nerves and muscles, akin to a nerve agent (2). Our objective is to develop a rapid detection tool for determining the levels of pesticide residues in dairy products. In this study, we measured the release of hydrogen ions (H+) resulting from the hydrolysis of ACh by AChE, serving as an indirect method to evaluate the inhibitory effect of OPs on AChE. To detect the signals of H+ released during ACh decomposition, we used ITO-coated nanostructures modified with 3-aminopropyl trimethoxysilane (APTMS) as a sensing substrate integrated into the extended gate of a field-effect transistor (EGFET) biosensor. The amino group at the end of APTMS can bond with H+. By monitoring the changes in electrical signal from the EGFET biosensor, it is possible to know the concentration of H+ in the solution. The output characteristics (Id-Vd) of the APTMS-modified ITO-VASiNW EGFET were measured using ACh solutions at different concentrations. A correlation was observed between Id and ACh concentration within the tested range, exhibiting a sensitivity of 0.016 mA1/2 / mM and an R2 value of 0.9. A lower concentration of H+ indicates a more pronounced inhibitory effect on AChE by OPs and suggests higher levels of pesticide residues. References (1) Colović, M. B., Krstić, D. Z., Lazarević-Pašti, T. D., Bondžić, A. M., & Vasić, V. M. (2013). Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol, 11(3), 315-335.(2) Rajagopalan, V., Venkataraman, S., Rajendran, D. S., Vinoth Kumar, V., Kumar, V. V., & Rangasamy, G. (2023). Acetylcholinesterase biosensors for electrochemical detection of neurotoxic pesticides and acetylcholine neurotransmitter: A literature review. Environmental Research, 227, 115724. Figure 1

Ultrasensitive Electrochemical Sensor for Catecholamine Detection Using Stable Covalent pH Sensitive Thin Films

Electrochemical detection of catecholamine neurotransmitters has been widely studied and possess lots of potential for the onsite analysis. Electrochemical sensors, however, have limitations that are due to strong interfering species that exist in the same sample matrix as the analyte of interest. In addition, the stability of the fabricated electrochemical sensor is important for reusability and reproducibility. Our research group activities have focused on fabricating stable thin films of electrocatalysts (phthalocyanines) and their graphene conjugates using covalent coupling reactions and electrografting method. The formed thin films exhibited excellent stability, electroanalytical and electrocatalytic properties. The flexible structural modification of phthalocyanines allowed for the incorporation of pH sensitive functional group and different metal ions for electrocatalysis. The use of pH sensitive electrocatalysts is a step away from using insulating and negatively charged polymers for screening interferents. The evaluation of modified electrodes were conducted in the negative and positively charged redox systems, such as [Fe(CN)6]3-/4- and [Ru(NH3)6]2+/3+. Excellent electrocatalytic properties were obtained and the electrodes could detect the neurotransmitters selectively and screen-off ascorbic acid, uric acid using the solution pH.

(Invited) Laser-Induced Graphene for Improved Electrochemical Biosensors

Laser-induced graphene (LIG) has emerged as a promising technique for fabricating porous graphene electrodes for many applications, including biosensors and medical devices. However, improving electrochemical properties of LIG hinges on not only understanding the kinetics and energetics governing the physicochemical process of lasing, but also the tunability of surface chemistry and morphology of the produced LIG. This talk reveals the spatiotemporal laser control for achieving different LIG morphology and atomic structures with demonstrations of seamless transitions between conductive networked LIG structures and insulating fibrous LIG morphologies. The effect of laser fluence and multi-pass lasing on LIG morphology and properties will be shown. In addition, molecular engineering of the polymer substrate is explored for controlling the chemical and physical properties of the produced LIG. Finally, the electrochemical detection of neurotransmitters in the nanomolar range will be demonstrated. Our results show that heteroatom doping of graphene is possible by including sulfur or fluorine atoms into the backbone of the polyimide synthesized by two-step polycondensation. Accordingly, both the surface hydrophobicity and sensing sensitivity are shown to depend on the heteroatom-doping content. Taken together, our work paves the way for scalable fabrication of functional graphene-based electrodes and coatings on polymers for flexible and wearable electronics, as well as implantable devices, such as neural probes.

All-Diamond Boron-Doped Microelectrodes for Neurochemical Sensing with Fast-Scan Cyclic Voltammetry.

Neurochemical sensing with implantable devices has gained remarkable attention over the last few decades. A promising area of this research is the progress of novel electrodes as electrochemical tools for neurotransmitter detection in the brain. The boron-doped diamond (BDD) electrode is one such candidate that previously has been reported for its excellent electrochemical properties, including a wide working potential, superior chemical inertness and mechanical stability, good biocompatibility and resistance to fouling. Meanwhile, limited research has been conducted on the BDD as a microelectrode for neurochemical detection. Our team has developed a freestanding, all diamond microelectrode consisting of a boron-doped polycrystalline diamond core, encapsulated in an insulating polycrystalline diamond shell, with a cleaved planar tip for electrochemical sensing. This all-diamond electrode is advantageous due to its - (1) batch fabrication using wafer technology that eliminates traditional hand fabrication errors and inconsistencies, (2) absence of metal-based wires, or foundations, to improve biocompatibility and flexibility, and (3) sp 3 carbon surface with resistance to biofouling, i.e. adsorption of proteins or unwanted molecules at the electrode surface in a biological environment that impedes overall electrode performance. Here, we provide findings on further in vitro testing and development of the freestanding boron-doped diamond microelectrode (BDDME) for neurotransmitter detection using fast scan cyclic voltammetry (FSCV). In this report, we elaborate on - 1) an updated fabrication scheme and work flow to generate all diamond BDDMEs, 2) slow scan cyclic voltammetry measurements of reference and target analytes to understand basic electrochemical behavior of the electrode, and 3) FSCV characterization of common neurotransmitters, and overall favorability of serotonin (5-HT) detection. The BDDME showed a 2-fold increased FSCV response for 5-HT in comparison to dopamine (DA), with a limit of detection of 0.16 µM for 5-HT and 0.26 µM for DA. These results are intended to expand on the development of the next generation BDDME and guide future in vivo experiments, adding to the growing body of literature on implantable devices for neurochemical sensing.

Nanosize Controllable Two‐Dimensional (Cu–S)n Metal–Organic Framework Hybrid With Reduced Graphene Oxide by In Situ Microwave and Hydrothermal Synthesis for Electrochemical Neurotransmitter Detection

ABSTRACTWe present a groundbreaking technique for controllably synthesizing nanosized semiconductive two‐dimensional (2D) (Cu–S)n metal–organic framework (MOF)/graphene nanocomposites for electrochemical sensing of neurotransmitter 2‐phenethylamine (PEA). The (Cu–S)n MOF size is controlled by graphene oxide proportions, enhancing electrocatalytic activity. The modified electrode exhibits a surface area increase from 0.0639 to 0.1906 cm2 and impressive limit of detection (0.0156 and 0.004 μM) within linear ranges of 15–200 μM and 1–10 μM, offering exceptional selectivity, reproducibility, and repeatability for biosensing.

A mechanical nano sensor based on magnetic-mediated sensitization for 5-HT detection

The real-time detection of neurotransmitters had attracted more attention due to the potential to provide vital information for pathology research, disease diagnosis, and clinical efficacy evaluation. Here, a magnetic-mediated nano sensor was developed to improve sensitivity for detection of serotonin (5-HT). The PDMS membrane doped with magnetic particles serves as a conversion element, enhancing the deformation of the thin film caused by surface stress under the action of a magnetic field and amplifying the resistance response signal of the nano sensor. The 5-HT detection associated with neurotransmitter diseases serve as a proof of concept revealing the magnetic sensitization. The detection limit of the 5-HT was decreased to 3.21 nM in the linear range of 5–500 nM, which was lower than that of the nano sensor without magnetic field. The clinical 5-HT samples were also been accurately detected, indicating a positive application potential of the as-prepared magnetic-mediated nano sensor. All these results reveal the high sensitivity and practicality of the as-prepared magnetic-mediated nano sensor and provide a new method for neurotransmitter diseases diagnosis.

Convenient and Accurate Detection of Dopamine and Glucose by Modifying Carbon Fiber Electrodes

Fast, sensitive, and low-cost high-performance detectors have gradually become an indispensable tool for people to keep healthy, and sensors are the key devices of detection equipment. In this work, a ZnO nanocrystal modified carbon fiber electrode was prepared using a hydrothermal method, and on this basis, a galvanostatic point deposition method was used to load copper nanoparticles to prepare a sensor electrode. Scanning electron microscopy and X-ray diffraction were used to comprehensively analyze composition, morphology, and environmental adaptability of the prepared electrodes. The DPV test was used to verify the enhanced effect of ZnO nanorods on neurotransmitter detection. The ZnO/CF showed an obvious electrical signal (0.22 V, 4 × 10−5A) in the detection of dopamine (DA) solution, and the Cu-NPs/ZnO/CF also showed excellent detection results in the glucose detection experiment., providing two excellent examples for the development of low-cost electrochemical sensors. The electrodes can specifically detect DA in the presence of ascorbic acid and uric acid, and the detection limit of the electrode for detecting DA is about 0.4 μM. In addition, the Cu-NPs/ZnO/CF electrode successfully realized the enzyme-free detection of glucose, and the detection limit could reach 0.5 μM.

Fluorescence microscopy for brain activity imaging: one-photon microscopy and its application to pharmacological research

The development of genetically-encoded fluorescent probes for the detection of intracellular calcium ions and various neurotransmitters has progressed significantly in recent years, and there is a growing need for techniques that rapidly and efficiently image these signals in the living brain for pharmacological studies of the central nervous system. In this article, we discuss one-photon fluorescence microscopy techniques used for brain activity imaging, particularly wide-field imaging and head-mounted miniaturized microscopy, and introduce their basic principles, recent advances, and applications in pharmacological research. Wide-field calcium imaging is suitable for mesoscopic observation of cortical activity during behavioral tasks in head-fixed awake mice, while head-mounted miniaturized microscopes can be attached to the animal's head to image brain activity associated with naturalistic behaviors such as social behavior and sleep. One-photon microscopy allows for the development of a simple and cost-effective imaging system using an affordable excitation light source such as a light-emitting diode. Its excitation light illuminates the entire field of view simultaneously, making it easy to perform high-speed imaging using a high-sensitivity camera. In contrast, the short wavelength of the excitation light limits the field of observation to areas on or near the brain surface due to its strong light scattering. Moreover, the out-of-focus fluorescence makes it difficult to obtain images with a high signal-to-noise ratio and spatial resolution. The use of one-photon microscopy in brain activity imaging has been limited compared to two-photon microscopy, but its advantages have recently been revisited. Therefore, this technique is expected to become a useful method for pharmacologists to visualize the activity of the living brain.

MeNPs-PEDOT Composite-Based Detection Platforms for Epinephrine and Quercetin.

The development of low-cost, sensitive, and simple analytical tools for biomolecule detection in health status monitoring is nowadays a growing research topic. Sensing platforms integrating nanocomposite materials as recognition elements in the monitoring of various biomolecules and biomarkers are addressing this challenging objective. Herein, we have developed electrochemical sensing platforms by means of a novel fabrication procedure for biomolecule detection. The platforms are based on commercially available low-cost conductive substrates like glassy carbon and/or screen-printed carbon electrodes selectively functionalized with nanocomposite materials composed of Ag and Au metallic nanoparticles and an organic polymer, poly(3,4-ethylenedioxythiophene). The novel fabrication method made use of alternating currents with controlled amplitude and frequency. The frequency of the applied alternating current was 100 mHz for the polymer deposition, while a frequency value of 50 mHz was used for the in situ electrodeposition of Ag and Au nanoparticles. The selected frequency values ensured the successful preparation of the composite materials. The use of readily available composite materials is intended to produce cost-effective analytical tools. The judicious modification of the organic conductive matrix by various metallic nanoparticles, such as Ag and Au, extends the potential applications of the sensing platform toward a range of biomolecules like quercetin and epinephrine, chosen as benchmark analytes for proof-of-concept antioxidant and neurotransmitter detection. The sensing platforms were tested successfully for quercetin and epinephrine determination on synthetic and real samples. Wide linear response ranges and low limit-of-detection values were obtained for epinephrine and quercetin detection.

All-MXene electronic tongue for neurotransmitters detection

Neurotransmitters (NTs) are molecules produced by neurons that act as the body's chemical messengers. Their abnormal levels in the human system have been associated with many disorders and neurodegenerative diseases, which makes the monitoring of NTs fundamentally important. Specifically for clinical analysis and understanding of brain behavior, simultaneous detection of NTs at low levels quickly and reliably is imperative for disease prevention and early diagnosis. However, the methods currently employed are usually invasive or inappropriate for multiple NTs detection. Herein, we developed a MXene-based impedimetric electronic tongue (e-tongue) for sensitive NT monitoring, using Nb2C, Nb4C3, Mo2C, and Mo2Ti2C3 MXenes as sensing units of the e-tongue, and Principal Component Analysis (PCA) as the data treatment method. The high specific surface area, distinct electrical properties, and chemical stability of the MXenes gave rise to high sensitivity and good reproducibility of the sensor array toward NT detection. Specifically, the e-tongue detected and differentiated multiple NTs (acetylcholine, dopamine, glycine, glutamate, histamine, and tyrosine) at concentrations as low as 1 nmol L−1 and quantified NTs present in a mixture. Besides, analyses performed with interferents and actual samples confirmed the system's potential to be used in clinical diagnostics. The results demonstrate that the MXene-based e-tongue is a suitable, rapid, and simple method for NT monitoring with high accuracy and sensitivity.

A Conjugated Polymer-Based Portable Smartphone Platform for Sensitive and Point-Of-Care Detection of Monoamine Neurotransmitter.

The precise and effective detection of neurotransmitters (NTs) is crucial for clinical investigation of neuronal processes, and timely monitoring of NT-related chronic diseases. However, sensitive detection of specific NT with unprecedented selectivity is highly challenging due to similarities in chemical and electronic structures of various interfering neurochemicals. Herein, an anionic conjugated polyelectrolyte Poly[(9,9-bis(4'-sulfonatobutyl)fluorene-co-alt-1,4-phenylene) sodium], PFPS was rationally designed and synthesized for amplified detection and point-of-care (PoC) determination of monoamine neurotransmitter, serotonin (5-Hydroxy tryptamine or 5-HT, also diagnostic biomarker of carcinoid tumor) in human blood plasma. The PFPS displayed a remarkable sensing response with an exceptionally high fluorescence quenching constant of 1.14×105 M-1 and an ultralow detection limit of 0.67 μM or 0.142 ppm, much below the clinical range. Furthermore, a smartphone-enabled portable platform was constructed for real-time onsite detection of 5-HT by quantification of visual fluorescence response of PFPS into RGB values using a color recognizer android application. The smartphone platform could be readily applied for convenient, non-invasive PoC testing of 5-HT levels in complex biological fluids accurately and is expected to revolutionize clinical diagnosis and personalized health care devices.

Multifunctional Nanomaterials for Advancing Neural Interfaces: Recording, Stimulation, and Beyond.

ConspectusNeurotechnology has seen dramatic improvements in the last three decades. The major focus in the field has been to design electrical communication platforms with high spatial resolution, stability, and translatability for understanding and affecting neural pathways. The deployment of nanomaterials in bioelectronics has enhanced the capabilities of conventional approaches employing microelectrode arrays (MEAs) for electrical interfaces, allowing the construction of miniaturized, high-performance neuroelectronics (Garg, R.; et al. ACS Appl. Nano Mater. 2023, 6, 8495). While these advancements in the electrical neuronal interface have revolutionized neurotechnology both in scale and breadth, an in-depth understanding of neurons' interactions is challenging due to the complexity of the environments where the cells and tissues are laid. The activity of large, three-dimensional neuronal systems has proven difficult to accurately monitor and modulate, and chemical cell-cell communication is often completely neglected. Recent breakthroughs in nanotechnology have provided opportunities to use new nonelectric modes of communication with neurons and to significantly enhance electrical signal interface capabilities. The enhanced electrochemical activity and optical activity of nanomaterials owing to their nonbulk electronic properties and surface nanostructuring have seen extensive utilization. Nanomaterials' enhanced optical activity enables remote neural state modulation, whereas the defect-rich surfaces provide an enormous number of available electrocatalytic sites for neurochemical detection and electrochemical modulation of cell microenvironments through Faradaic processes. Such unique properties can allow multimodal neural interrogation toward generating closed-loop interfaces with access to more complete neural state descriptors. In this Account, we will review recent advances and our efforts spearheaded toward utilizing nanostructured electrodes for enhanced bidirectional interfaces with neurons, the application of unique hybrid nanomaterials for remote nongenetic optical stimulation of neurons, tunable nanomaterials for highly sensitive and selective neurotransmitter detection, and the utilization of nanomaterials as electrocatalysts toward electrochemically modulating cellular activity. We highlight applications of these technologies across cell types through nanomaterial engineering with a focus on multifunctional graphene nanostructures applied though several modes of neural modulation but also an exploration of broad material classes for maximizing the potency of closed-loop bioelectronics.

Sparfloxacin/Gold Nanoparticles Modified Electrochemical Sensor for the Determination of Dopamine

Background: The development of facile, reliable, and sensitive electrochemical sensors for neurotransmitter detection is of utmost importance in biomedical research. Objectives: In this study, we proposed a novel approach for the synthesis of gold nanoparticles (AuNPs) using sparfloxacin as a reducing and stabilizing agent and further utilized as-prepared AuNPs for the construction of an electrochemical sensor to detect dopamine. Methods: The synthesis of AuNPs was achieved through a simple method where sparfloxacin acted as both a reducing and stabilizing agent. The AuNPs were investigated by using UV-visible spectroscopy, field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), elemental mapping (Emap), and X-ray diffraction (XRD). Results: The synthesised AuNPs were used to develop an electrochemical sensor for the detection of dopamine molecules. The fabricated electrochemical sensor demonstrated remarkable sensitivity and selectivity toward dopamine sensing. This sensor exhibited a good linear detection of dopamine in micromolar concentrations. Moreover, the sensor showed excellent stability and reproducibility. Conclusion: This novel electrochemical sensor holds significant potential for practical applications in neuroscience and clinical diagnosis, offering a rapid and sensitive method for dopamine detection. The utilization of sparfloxacin/AuNPs provides a promising avenue for the development of advanced electrochemical sensors with enhanced performance and wider applications in the detection of other neurotransmitters and biomolecules.

Vanadium Single Atoms Embedded in MoS2 Enabled Gut-Brain Axis Neurotransmitter Detection at pM Levels.

The detection of monoamine neurotransmitters is of paramount importance as the neurotransmitters are the chemical messengers regulating the gut-brain axis (GBA). It requires real-time, ultrasensitive, and selective sensing of the neurotransmitters in the gastric/intestinal fluid. However, multi-components present in the gastric/intestinal fluid make sensing challenging to achieve in terms of ultra-high sensitivity and selectivity. Herein, an approach is introduced to utilize vanadium single atom catalytic (SAC) centers in van der Waals MoS2 (V-MoS2) to selectively detect real-time serotonin (5-HT) in artificial gastric/intestinal fluid. The synergetic effect of V-SACs and the surface S-bonds on the MoS2 surface, enables an extremely wide range of 5-HT detection (from 1pM to 100µM), with optimum selectivity and interference resistance. By combining density functional theory calculations and scanning transmission electron microscopy, it is concluded that the V-SACs embedded in the MoS2 network create active sites that greatly facilitate the charge exchange between the material and the 5-HT molecules. This result allows the 5-HT detection in GBA studies to be more reliable, and the material tunability provides a general platform to achieve real-time and multi-component detection of other monoamine neurotransmitters in GBA such as dopamine and norepinephrine.