Detection Of Neurotransmitters Research Articles

Electrochemistry of Single-Vesicle Events.

Neuronal transmission relies on electrical signals and the transfer of chemical signals from one neuron to another. Chemical messages are transmitted from presynaptic neurons to neighboring neurons through the triggered fusion of neurotransmitter-filled vesicles with the cell plasma membrane. This process, known as exocytosis, involves the rapid release of neurotransmitter solutions that are detected with high affinity by the postsynaptic neuron. The type and number of neurotransmitters released and the frequency of vesicular events govern brain functions such as cognition, decision making, learning, and memory. Therefore, to understand neurotransmitters and neuronal function, analytical tools capable of quantitative and chemically selective detection of neurotransmitters with high spatiotemporal resolution are needed. Electrochemistry offers powerful techniques that are sufficiently rapid to allow for the detection of exocytosis activity and provides quantitative measurements of vesicle neurotransmitter content and neurotransmitter release from individual vesicle events. In this review, we provide an overview of the most commonly used electrochemical methods for monitoring single-vesicle events, including recent developments and what is needed for future research.

Carbon Nanotube Yarn Microelectrodes Promote High Temporal Measurements of Serotonin Using Fast Scan Cyclic Voltammetry.

Carbon fiber-microelectrodes (CFMEs) have been the standard for neurotransmitter detection for over forty years. However, in recent years, there have been many advances of utilizing alternative nanomaterials for neurotransmitter detection with fast scan cyclic voltammetry (FSCV). Recently, carbon nanotube (CNT) yarns have been developed as the working electrode materials for neurotransmitter sensing capabilities with fast scan cyclic voltammetry. Carbon nanotubes are ideal for neurotransmitter detection because they have higher aspect ratios enabling monoamine adsorption and lower limits of detection, faster electron transfer kinetics, and a resistance to surface fouling. Several methods to modify CFMEs with CNTs have resulted in increases in sensitivity, but have also increased noise and led to irreproducible results. In this study, we utilize commercially available CNT-yarns to make microelectrodes as enhanced neurotransmitter sensors for neurotransmitters such as serotonin. CNT-yarn microelectrodes have significantly higher sensitivities (peak oxidative currents of the cyclic voltammograms) than CFMEs and faster electron transfer kinetics as measured by peak separation (ΔEP) values. Moreover, both serotonin and dopamine are adsorption controlled to the surface of the electrode as measured by scan rate and concentration experiments. CNT yarn microelectrodes also resisted surface fouling of serotonin onto the surface of the electrode over thirty minutes and had a wave application frequency independent response to sensitivity at the surface of the electrode.

Quantitative detection of neurotransmitter using aptamer: From diagnosis to therapeutics

Neurotransmitters, the small molecule chemical messenger responsible for nervous system regulation and can control joy, fear, depression, insomnia, craving for carbohydrates, drugs, and alcohols. Variation in neurotransmitter levels is a characteristic manifestation of several neurological diseases. Accurate diagnosis of these diseases caused due to an imbalance in neurotransmitter level followed by impaired transmission of signals between neurons and other body parts remains a great challenge for the clinicians. Recent evidences reveal, artificial single-stranded nucleotides called 'aptamer' are widely used as biosensors, antibody substitutes, diagnostic agents, and for targeted therapy. These aptamers are superior candidate both for early detection and diagnosis of many neurological disorders caused due to suboptimal level of neurotransmitters. Presently, noninvasive neurotransmitter detection by aptamer has been found to be an easy, fast, and cost-effective choice. In addition, increased specificity, stability, affinity, and reproducibility of aptamers, high throughput screening of aptamer-based sensing platforms have been observed. Moreover, clinical applicability of aptamer has also proved to be efficacious, though still at a preliminary stage. Herein, we review salient features of aptamerbased sensing technology used for neurotransmitter detection particularly their chemical modifications, selection, assay development, immobilization, therapeutic efficiency, and stability for early diagnosis of diseases caused due to neurotransmitter imbalance.

Rationally Design of Near Infrared Light Responsive Micro‐Photoelectrodes for In Vivo Sensing of Neurotransmitter Molecules in Mouse Brain†

Summary of main observation and conclusionThe accurate quantification of neurotransmitter molecules is an indispensable means to reveal the physiological mechanisms of neuro movement in molecular level. However, existing detection strategies cannot fully meet practical needs, and the on‐site and in vivo detection of neurotransmitters in brain remains a great challenge. Here, we report the development of a near infrared light responsive photoelectrochemical (PEC) detection method for in vivo quantification of neurotransmitter dopamine in mouse brain. Under guidance of density function theory calculations, a combination strategy of non‐metal cation doping and defect engineering is introduced to rationally design the micro‐photoelectrodes with excellent biocompatibility and stability and implements the in vivo PEC detection of dopamine in mouse brain. It opens up a new way for the accurate in vivo detection of biomolecules and allows researchers to make novel inquiries for long‐standing questions in a new way.

Enzymatic Platforms for Sensitive Neurotransmitter Detection.

A convenient electrochemical sensing pathway was investigated for neurotransmitter detection based on newly synthesized silole derivatives and laccase/horseradish-peroxidase-modified platinum (Pt)/gold (Au) electrodes. The miniature neurotransmitter’s biosensors were designed and constructed via the immobilization of laccase in an electroactive layer of the Pt electrode coated with poly(2,6-bis(3,4-ethylenedioxythiophene)-4-methyl-4-octyl-dithienosilole) and laccase for serotonin (5-HT) detection, and a Au electrode modified with the electroconducting polymer poly(2,6-bis(selenophen-2-yl)-4-methyl-4-octyl-dithienosilole), along with horseradish peroxidase (HRP), for dopamine (DA) monitoring. These sensing arrangements utilized the catalytic oxidation of neurotransmitters to reactive quinone derivatives (the oxidation process was provided in the enzymes’ presence). Under the optimized conditions, the analytical performance demonstrated a convenient degree of sensitivity: 0.0369 and 0.0256 μA mM−1 cm−2, selectivity in a broad linear range (0.1–200) × 10−6 M) with detection limits of ≈48 and ≈73 nM (for the serotonin and dopamine biosensors, respectively). Moreover, the method was successfully applied for neurotransmitter determination in the presence of interfering compounds (ascorbic acid, L-cysteine, and uric acid).

In situ derivatization of Au nanoclusters via aurophilic interactions of a triphenylphosphine gold(i) salt with neurotransmitters and their rapid MALDI-TOF-MS detection in mice brain tissue extracts.

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) has attracted much attention for the detection of small molecules such as neurotransmitters due to its softness, high sensitivity, extensive compatibility and diverse mass analyzers. However, it has been really a difficult challenge to develop a highly specific organic compound as a matrix for the rapid, sensitive and selective detection of neurotransmitters. Herein, we report tris(triphenylphosphine)gold oxonium tetrafluoroborate ([Ph3PAu]3O+BF4-) for the first time as an efficient matrix for the rapid and simultaneous MALDI-MS detection of neurotransmitters. [Ph3PAu]3O+BF4- facilitates the in situ derivatization of gold nanoclusters (Au NCLs) during the interaction with neurotransmitters, which increases their ionization energy by absorbing more ultra-violet (UV) radiation during MALDI-TOF-MS detection. The results show that this [Ph3PAu]3O+BF4- matrix can exhibit a 10-fold faster response time compared to previously reported pyrylium matrices. In addition, [Ph3PAu]3O+BF4- can also provide the simultaneous derivatization of various neurotransmitters, including dopamine (DA), noradrenaline (NAd), serotonin (5-HT), γ-aminobutyric acid (GABA), histamine (H) and tyramine (TY), in mice brain tissue extracts, which can be detected in the MALDI-TOF-MS spectra.

Microelectrodes from PEDOT-carbon nanofiber composite for high performance neural recording, stimulation and neurochemical sensing

This present method describes a versatile approach for the electrochemical synthesis of a composite material of Poly (3,4-ethylenedioxythiophene) (PEDOT) and Carbon Nanofibers (CNFs) for neural interfaces and biosensing applications. Oxidized CNFs were utilized as dopants of PEDOT to prepare the composite coating through electrochemical deposition on microelectrodes arrays (MEA). The experimental results of this study showed that PEDOT:CNF microelectrodes exhibit remarkable electrochemical properties, combining low impedance, high surface area, high charge injection capability and reliable neurotransmitters monitoring using amperometric techniques. Taken together, these results suggest the great potential of PEDOT:CNF composite for developing next-generation multifunctional microelectrodes for applications in neural therapies.•A simple approach for the electrochemical synthesis of PEDOT:CNF composite material on microelectrodes for neural interfaces and neurochemical sensing.•PEDOT:CNF microelectrodes exhibit remarkable electrochemical properties, combining low impedance and high charge injection capabilities.•PEDOT:CNF microelectrodes allowed the reliable detection of neurotransmitters with improved sensitivity.

Real-time in vivo detection techniques for neurotransmitters: a review.

Functional synapses in the central nervous system depend on a chemical signal exchange process that involves neurotransmitter delivery between neurons and receptor cells in the neuro system. Abnormal neurotransmitter levels and distributions can cause intractable diseases involving descending/ascending modulatory pathways or dysfunctional organs. The detection of abnormal neurotransmitter levels is one of the most promising techniques in the diagnosis of brain diseases. Also, numerous effective methods for the detection of neurotransmitters in vivo have been fabricated. Nowadays, electrochemical, optical, magnetic, and microdialysis methods are among the main techniques used to detect neurotransmitters. Herein, we review current techniques for detecting eight types of neurotransmitters with a focus on in vivo neurotransmitter tracking methods intended for the real-time diagnosis of brain disorders.

The fabrication of a gold nanoelectrode-nanopore nanopipette for dopamine enrichment and multimode detection.

It is important to further improve the electrophysiology and electrochemistry techniques of neurotransmitter detection. Here, we report the development of multifunctional nanopipette-based integrated approaches for the detection of neurotransmitters. We successfully fabricated a nanopipette with two independent functional units at the apex, a nanopore and a gold nanoelectrode (GNE). The GNE shows good electrochemical response to dopamine (DA). Furthermore, both the nanopore and nanoelectrode can effectively enrich DA but not ascorbic acid by electrical means. The enriched DA is then detected and analysed with an obviously improved signal-to-noise ratio by electrochemical methods and surface-enhanced Raman spectroscopy (SERS). In addition, with the addition of silver nanoparticles during enrichment, up to 10 times increase of the Raman intensity of DA can be observed.

Recent advances in fast-scan cyclic voltammetry.

Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes (CFMEs) is a versatile electrochemical technique to probe neurochemical dynamics in vivo. Progress in FSCV methodology continues to address analytical challenges arising from biological needs to measure low concentrations of neurotransmitters at specific sites. This review summarizes recent advances in FSCV method development in three areas: (1) waveform optimization, (2) electrode development, and (3) data analysis. First, FSCV waveform parameters such as holding potential, switching potential, and scan rate have been optimized to monitor new neurochemicals. The new waveform shapes introduce better selectivity toward specific molecules such as serotonin, histamine, hydrogen peroxide, octopamine, adenosine, guanosine, and neuropeptides. Second, CFMEs have been modified with nanomaterials such as carbon nanotubes or replaced with conducting polymers to enhance sensitivity, selectivity, and antifouling properties. Different geometries can be obtained by 3D-printing, manufacturing arrays, or fabricating carbon nanopipettes. Third, data analysis is important to sort through the thousands of CVs obtained. Recent developments in data analysis include preprocessing by digital filtering, principal components analysis for distinguishing analytes, and developing automated algorithms to detect peaks. Future challenges include multisite measurements, machine learning, and integration with other techniques. Advances in FSCV will accelerate research in neurochemistry to answer new biological questions about dynamics of signaling in the brain.

Fundamentals of fast-scan cyclic voltammetry for dopamine detection.

Fast-scan cyclic voltammetry (FSCV) is used with carbon-fiber microelectrodes for the real-time detection of neurotransmitters on the subsecond time scale. With FSCV, the potential is ramped up from a holding potential to a switching potential and back, usually at a 400 V s-1 scan rate and a frequency of 10 Hz. The plot of current vs. applied potential, the cyclic voltammogram (CV), has a very different shape for FSCV than for traditional cyclic voltammetry collected at scan rates which are 1000-fold slower. Here, we explore the theory of FSCV, with a focus on dopamine detection. First, we examine the shape of the CVs. Background currents, which are 100-fold higher than faradaic currents, are subtracted out. Peak separation is primarily due to slow electron transfer kinetics, while the symmetrical peak shape is due to exhaustive electrolysis of all the adsorbed neurotransmitters. Second, we explain the origins of the dopamine waveform, and the factors that limit the holding potential (oxygen reduction), switching potential (water oxidation), scan rate (electrode instability), and repetition rate (adsorption). Third, we discuss data analysis, from data visualization with color plots, to the automated algorithms like principal components regression that distinguish dopamine from pH changes. Finally, newer applications are discussed, including optimization of waveforms for analyte selectivity, carbon nanomaterial electrodes that trap dopamine, and basal level measurements that facilitate neurotransmitter measurements on a longer time scale. FSCV theory is complex, but understanding it enables better development of new techniques to monitor neurotransmitters in vivo.

Three-Dimensional Microfluidic Platform with Neural Organoids: Model System for Unraveling Synapses.

Unraveling the large number of various signals in the brain under the influence of physical and chemical cues that govern the formation of individual neurons, axons, dendrites, and their functional synapses during the development of neural network is a challenging task. To understand this task, microfluidic devices equipped with microchannels for reconstitution of cell/tissue-culture environments have been studied. Microfluidic devices are emerging as powerful tools in neurobiology, since they are capable of controlling and manipulating the microenvironment of the brain in a precise manner. They can enhance the physiological relevance of three-dimensional (3D) cell culture by allowing spatial control over fluids in micrometer-sized channels. Recent technological advancement in designing microfluidic platforms for studying neural communication, disease progression, and detection of neurotransmitters enhance our fundamental knowledge and understanding. However, more such advanced and innovative interventions are required. This Viewpoint focuses on highlighting a few of them with future scope of further advancement in this field.

A Review of Neurotransmitters Sensing Methods for Neuro-Engineering Research

Neurotransmitters as electrochemical signaling molecules are essential for proper brain function and their dysfunction is involved in several mental disorders. Therefore, the accurate detection and monitoring of these substances are crucial in brain studies. Neurotransmitters are present in the nervous system at very low concentrations, and they mixed with many other biochemical molecules and minerals, thus making their selective detection and measurement difficult. Although numerous techniques to do so have been proposed in the literature, neurotransmitter monitoring in the brain is still a challenge and the subject of ongoing research. This article reviews the current advances and trends in neurotransmitters detection techniques, including in vivo sampling and imaging techniques, electrochemical and nano-object sensing techniques for in vitro and in vivo detection, as well as spectrometric, analytical and derivatization-based methods mainly used for in vitro research. The document analyzes the strengths and weaknesses of each method, with the aim to offer selection guidelines for neuro-engineering research.

Immobilization of glucose oxidase enzyme on NiAl-LDHs for application in microfluidic fuel cell and serotonin detection.

In this work, an enzymatic glucose oxidase (GOx) electrode immobilized on double layered hydroxides of NiAl (NiAl-LDHs) was developed for the detection of serotonin neurotransmitters that may be present in human blood samples and carry out the glucose oxidation present in this fluid for energy conversion, and can be applied as self-feeding electrodes in Lab-on-a-Chip devices. The self-feeding electrodes based on fuel cells have a very promising future in lab-on-a-chip devices because they do not occupy an external power source, their manufacturing processes are relatively simple and low cost, and can be developed for different applications such as the determination of biomolecules for diagnosis of various diseases.

Fluorescent Biosensors for Neurotransmission and Neuromodulation: Engineering and Applications.

Understanding how neuronal activity patterns in the brain correlate with complex behavior is one of the primary goals of modern neuroscience. Chemical transmission is the major way of communication between neurons, however, traditional methods of detection of neurotransmitter and neuromodulator transients in mammalian brain lack spatiotemporal precision. Modern fluorescent biosensors for neurotransmitters and neuromodulators allow monitoring chemical transmission in vivo with millisecond precision and single cell resolution. Changes in the fluorescent biosensor brightness occur upon neurotransmitter binding and can be detected using fiber photometry, stationary microscopy and miniaturized head-mounted microscopes. Biosensors can be expressed in the animal brain using adeno-associated viral vectors, and their cell-specific expression can be achieved with Cre-recombinase expressing animals. Although initially fluorescent biosensors for chemical transmission were represented by glutamate biosensors, nowadays biosensors for GABA, acetylcholine, glycine, norepinephrine, and dopamine are available as well. In this review, we overview functioning principles of existing intensiometric and ratiometric biosensors and provide brief insight into the variety of neurotransmitter-binding proteins from bacteria, plants, and eukaryotes including G-protein coupled receptors, which may serve as neurotransmitter-binding scaffolds. We next describe a workflow for development of neurotransmitter and neuromodulator biosensors. We then discuss advanced setups for functional imaging of neurotransmitter transients in the brain of awake freely moving animals. We conclude by providing application examples of biosensors for the studies of complex behavior with the single-neuron precision.

Amino bearing core-shell structured magnetic covalent organic framework nanospheres: Preparation, postsynthetic modification with phenylboronic acid and enrichment of monoamine neurotransmitters in human urine

Covalent organic frameworks (COFs) have been increasingly employed in separation science, including sample preparation. Herein we fabricated the amino bearing core-shell structured COFs nanospheres [Fe3O4@TpBD(NH2)2], and a novel magnetic boronate affinity adsorbent was synthesized by postsynthetic modification of the Fe3O4@TpBD(NH2)2 with 2-formylphenylboronic acid. The magnetic boronate affinity adsorbent possesses fast magnetic response and high binding capacity up to 1037 μmol g−1 for dopamine. Besides, it was used as an adsorbent for extraction of urinary monoamine neurotransmitters at neutral pH. A method for detection of the monoamine neurotransmitters was developed by coupling the magnetic solid phase extraction with high-performance liquid chromatography-fluorescence detection. Under the optimized conditions, a good analytical method was obtained in the linear dynamic range of 2–200 ng mL−1 with R2 between 0.9917 and 0.9966, with low limit of detection (0.31–0.54 ng mL−1) and limit of quantification (1.04–1.80 ng mL−1). The recoveries of the monoamine neurotransmitters were in the range of 86.3–115%, with relative standard deviations of 2.34–10.5% (intra-day) and 2.84–14.4% (inter-day). The method was successfully applied to the determination of the monoamine neurotransmitters in human urine samples. This work is of great importance for preparing functionalized core-shell structured magnetic covalent organic framework nanospheres, it also demonstrates the feasibility of the functionalized magnetic COFs as adsorbents in sample pretreatment.

Integrating Carbon Nanomaterials with Metals for Bio-sensing Applications

Age structure in most developed countries is changing fast as the average lifespan is increasing significantly, calling for solutions to provide improved treatments for age-related neurological diseases and disorders. In order to address these problems, a reliable way of recording information about neurotransmitters from in vitro and in vivo applications is needed to better understand neurological diseases and disorders as well as currently used treatments. Likewise, recent developments in medicine, especially with the opioid crisis, are demanding a swift move to personalized medicine to administer patient needs rather than population-wide averages. In order to enable the so-called personalized medicine, it is necessary to be able to do measurements in vivo and in real time. These actions require sensitive and selective detection of different analytes from very demanding environments. Current state-of-the-art materials are unable to provide sensitive and selective detection of neurotransmitters as well as the required time resolution needed for drug molecules at a reasonable cost. To meet these challenges, we have utilized different metals to grow carbon nanomaterials and applied them for sensing applications showing that there are clear differences in their electrochemical properties based on the selected catalyst metal. Additionally, we have combined atomistic simulations to support optimizing materials for experiments and to gain further understanding of the atomistic level reactions between different analytes and the sensor surface. With carbon nanostructures grown from Ni and Al + Co + Fe hybrid, we can detect dopamine, ascorbic acid, and uric acid simultaneously. On the other hand, nanostructures grown from platinum provide a feasible platform for detection of H2O2 making them suitable candidates for enzymatic biosensors for detection of glutamate, for example. Tetrahedral amorphous carbon electrodes have an ability to detect morphine, paracetamol, tramadol, and O-desmethyltramadol. With carbon nanomaterial-based sensors, it is possible to reach metal-like properties in sensing applications using only a fraction of the metal as seed for the material growth. We have also seen that by using nanodiamonds as growth catalyst for carbon nanofibers, it is not possible to detect dopamine and ascorbic acid simultaneously, although the morphology of the resulting nanofibers is similar to the ones grown using Ni. This further indicates the importance of the metal selection for specific applications. However, Ni as a continuous layer or as separate islands does not provide adequate performance. Thus, it appears that metal nanoparticles combined with fiber-like morphology are needed for optimized sensor performance for neurotransmitter detection. This opens up a new research approach of application-specific nanomaterials, where carefully selected metals are integrated with carbon nanomaterials to match the needs of the sensing application in question.

A core-shell molybdenum nanoparticles entrapped f-MWCNTs hybrid nanostructured material based non-enzymatic biosensor for electrochemical detection of dopamine neurotransmitter in biological samples

Dopamine (DA) is a critical neurotransmitter and has been known to be liable for several neurological diseases. Hence, its sensitive and selective detection is essential for the early diagnosis of diseases related to abnormal levels of DA. In this study, we reported novel molybdenum nanoparticles self-supported functionalized multiwalled carbon nanotubes (Mo NPs@f-MWCNTs) based core-shell hybrid nanomaterial with an average diameter of 40–45 nm was found to be the best for electrochemical DA detection. The Mo NPs@f-MWCNTs hybrid material possesses tremendous superiority in the DA sensing is mainly due to the large surface area and numerous electroactive sites. The morphological and structural characteristics of the as-synthesized hybrid nanomaterial were examined by XRD, Raman, FE-SEM, HR-TEM, EDX. The electrochemical characteristics and catalytic behavior of the as-prepared Mo NPs@f-MWCNTs modified screen-printed carbon electrode for the determination of DA were systematically investigated via electrochemical impedance spectroscopy, cyclic voltammetry, and amperometry. The results demonstrate that the developed DA biosensor exhibit a low detection limit of 1.26 nM, excellent linear response of 0.01 µM to 1609 µM with good sensitivity of 4.925 µA µM−1 cm−2. We proposed outstanding appreciable stability sensor was expressed to the real-time detection of DA in the real sample analysis of rat brain, human blood serum, and DA hydrochloride injection.

Carbon nanospikes have better electrochemical properties than carbon nanotubes due to greater surface roughness and defect sites

Carbon nanomaterials are used to improve electrodes for neurotransmitter detection, but what properties are important for maximizing those effects? In this work, we compare a newer form of graphene, carbon nanospikes (CNSs), with carbon nanotubes (CNTs) grown on wires and carbon fibers (CFs). CNS electrodes have a short, dense, defect-filled surface that produces remarkable electrochemical properties, much better than CNTs or CFs. The CNS surface roughness is 5.5 times greater than glassy carbon, while CNTs enhance roughness only 1.8-fold. D/G ratios are higher for CNS electrodes than CNT electrodes, an indication of more defect sites. For cyclic voltammetry of dopamine and ferricyanide, CNSs have both higher currents and smaller ΔEp values than CNTs and CFs. CNS electrodes also have a very low resistance to charge transfer. With fast-scan cyclic voltammetry (FSCV), CNS electrodes have enhanced current density for dopamine and cationic neurotransmitters due to increased adsorption to edge plane sites. This study establishes that not all carbon nanomaterials are equally advantageous for dopamine electrochemistry, but that short, dense nanomaterials that add defect sites provide improved current and electron transfer. CNSs are simple to mass fabricate on a variety of substrates and thus could be a favorable material for neurotransmitter sensing.

Hybrid Carbon Nanostructures for Direct Neuronal Interfacing

We have developed a concept of hybrid carbon nanomaterials, where different allotropes of carbon are integrated into a structure. In order to facilitate the long-term measurements in vivo, the cellular response at the bioelectric interface should be optimized. Indeed, failure of implant integration has been proposed to be the main reason for sensor failure in vivo. Most strategies to enhance electrode integration into target tissue exploit a protective layer or barrier on an electrode substrate. For the detection of neurotransmitters, this is not as suitable strategy, because 1) such films give rise to an increased background electrode capacitance and impedance, and 2) act as a diffusion barrier and as a result, a decreased amount of the analyte reaches the electrode surface and the kinetics is compromised. Here we demonstrate that we can regulate the cellular response just with the electrode material. Specifically, we will show that it is possible to combine the properties of different carbon allotropes to obtain hybrid materials with enhanced neural response. We will present three examples of the approach: (i) functionalized nanodiamonds on tetrahedral amorphous carbon (ta-C) (ii) multi-walled carbon nanotubes grown directly on top of ta-C and (iii) carbon nanofibres synthesized on top of ta-C thin films. We demonstrate that hybrid structures may promote neural integration as, for example, hydrogen–terminated nanodiamonds enhance neural cell viability and while not increasing glial cell viability. Moreover, carbon nanofibers show prominence for tuning the cellular response as their dimension match biologically relevant cues. We show that nanofiber dimensions significantly alter glial and neural cell adhesion as well as their morphology. The properties of the hybrid structures can be tailored, both geometrically and chemically, with high definition. Consequently, these materials possess exceptionally high potential to achieve optimal host response just with the electrode material.