Alzheimer's disease (AD) is a progressive, fatal, neurodegenerative disorder for which only treatments of limited efficacy are available. Despite early mentions of dementia in the ancient literature and the first patient diagnosed in 1906, the underlying causes of AD are not well understood. This study examined the possible role of dopamine, a neurotransmitter that is involved in cognitive and motor function, in AD. We treated adult zebrafish (Danio rerio) with okadaic acid (OKA) to model AD and assessed the resulting behavioral and neurochemical changes. We then employed a latent learning paradigm to assess cognitive and motor function followed by neurochemical analysis with fast-scan cyclic voltammetry (FSCV) at carbon fiber microelectrodes to measure the electrically stimulated dopamine release. The behavioral assay showed that OKA treatment caused fish to have lower motivation to reach the goal chamber, resulting in impeded learning and decreased locomotor activity compared to controls. Our voltammetric measurements revealed that the peak dopamine overflow in OKA-treated fish was about one-third of that measured in controls. These findings highlight the profound neurochemical changes that may occur in AD. Furthermore, they demonstrate that applying the latent learning paradigm and FSCV to zebrafish is a promising tool for future neurochemical studies and may be useful for screening drugs for the treatment of AD.
- MeSH
- Alzheimer Disease * MeSH
- Zebrafish MeSH
- Dopamine * MeSH
- Carbon Fiber MeSH
- Okadaic Acid MeSH
- Microelectrodes MeSH
- Neurotransmitter Agents MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Objective.Understanding how the retina converts a natural image or an electrically stimulated one into neural firing patterns is the focus of on-going research activities.Ex vivo, the retina can be readily investigated using multi electrode arrays (MEAs). However, MEA recording and stimulation from an intact retina (in the eye) has been so far insufficient.Approach.In the present study, we report new soft carbon electrode arrays suitable for recording and stimulating neural activity in an intact retina. Screen-printing of carbon ink on 20μm polyurethane (PU) film was used to realize electrode arrays with electrodes as small as 40μm in diameter. Passivation was achieved with a holey membrane, realized using laser drilling in a thin (50μm) PU film. Plasma polymerized 3.4-ethylenedioxythiophene was used to coat the electrode array to improve the electrode specific capacitance. Chick retinas, embryonic stage day 13, both explanted and intact inside an enucleated eye, were used.Main results.A novel fabrication process based on printed carbon electrodes was developed and yielded high capacitance electrodes on a soft substrate.Ex vivoelectrical recording of retina activity with carbon electrodes is demonstrated. With the addition of organic photo-capacitors, simultaneous photo-electrical stimulation and electrical recording was achieved. Finally, electrical activity recordings from an intact chick retina (inside enucleated eyes) were demonstrated. Both photosensitive retinal ganglion cell responses and spontaneous retina waves were recorded and their features analyzed.Significance.Results of this study demonstrated soft electrode arrays with unique properties, suitable for simultaneous recording and photo-electrical stimulation of the retina at high fidelity. This novel electrode technology opens up new frontiers in the study of neural tissuein vivo.
- MeSH
- Electric Stimulation methods MeSH
- Microelectrodes MeSH
- Retina * physiology MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
A device with four parallel channels was designed and manufactured by 3D printing in titanium. A simple experimental setup allowed splitting of the mobile phase in four parallel streams, such that a single sample could be analysed four times simultaneously. The four capillary channels were filled with a monolithic stationary phase, prepared using a zwitterionic functional monomer in combination with various dimethacrylate cross-linkers. The resulting stationary phases were applicable in both reversed-phase and hydrophilic-interaction retention mechanisms. The mobile-phase composition was optimized by means of a window diagram so as to obtain the highest possible resolution of dopamine precursors and metabolites on all columns. Miniaturized electrochemical detectors with carbon fibres as working electrodes and silver micro-wires as reference electrodes were integrated in the device at the end of each column. Experimental separations were successfully compared with those predicted by a three-parameter retention model. Finally, dopamine was determined in human urine to further confirm applicability of the developed device.
In this work we report on the implementation of methods for data processing signals from microelectrode arrays (MEA) and the application of these methods for signals originated from two types of MEAs to detect putative neurons and sort them into subpopulations. We recorded electrical signals from firing neurons using titanium nitride (TiN) and boron doped diamond (BDD) MEAs. In previous research, we have shown that these methods have the capacity to detect neurons using commercially-available TiN-MEAs. We have managed to cultivate and record hippocampal neurons for the first time using a newly developed custom-made multichannel BDD-MEA with 20 recording sites. We have analysed the signals with the algorithms developed and employed them to inspect firing bursts and enable spike sorting. We did not observe any significant difference between BDD- and TiN-MEAs over the parameters, which estimated spike shape variability per each detected neuron. This result supports the hypothesis that we have detected real neurons, rather than noise, in the BDD-MEA signal. BDD materials with suitable mechanical, electrical and biocompatibility properties have a large potential in novel therapies for treatments of neural pathologies, such as deep brain stimulation in Parkinson's disease.
- MeSH
- Action Potentials MeSH
- Algorithms MeSH
- Boron chemistry MeSH
- Diamond chemistry MeSH
- Hippocampus physiology MeSH
- Rats MeSH
- Microelectrodes MeSH
- Neurons physiology MeSH
- Rats, Wistar MeSH
- Titanium chemistry MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The design and application of an inkjet-printed electrochemically reduced graphene oxide microelectrode for HT-2 mycotoxin immunoenzymatic biosensing is reported. A water-based graphene oxide ink was first formulated and single-drop line working microelectrodes were inkjet-printed onto poly(ethylene 2,6-naphthalate) substrates, with dimensions of 78 μm in width and 30 nm in height after solvent evaporation. The printed graphene oxide microelectrodes were electrochemically reduced and characterized by Raman and X-ray photoelectron spectroscopies in addition to microscopies. Through optimization of the electrochemical reduction parameters, differential pulse voltammetry were performed to examine the sensing of 1-naphthol (1-N), where it was revealed that reduction times had significant effects on electrode performance. The developed microelectrodes were then used as an immunoenzymatic biosensor for the detection of HT-2 mycotoxin based on carbodiimide linking of the microelectrode surface and HT-2 toxin antigen binding fragment of antibody (anti-HT2 (10) Fab). The HT-2 toxin and anti-HT2 (10) Fab reaction was reported by anti-HT2 immune complex single-chain variable fragment of antibody fused with alkaline phosphatase (anti-IC-HT2 scFv-ALP) which is able to produce an electroactive reporter - 1-N. The biosensor showed detection limit of 1.6 ng ∙ mL-1 and a linear dynamic range of 6.3 - 100.0 ng ∙ mL-1 within a 5 min incubation with 1-naphthyl phosphate (1-NP) substrate.
- MeSH
- Biosensing Techniques instrumentation MeSH
- Equipment Design MeSH
- Electrochemical Techniques instrumentation MeSH
- Graphite chemistry MeSH
- Antibodies, Immobilized chemistry MeSH
- Immunoenzyme Techniques instrumentation MeSH
- Microelectrodes MeSH
- Oxidation-Reduction MeSH
- Reagent Strips analysis MeSH
- T-2 Toxin analogs & derivatives analysis MeSH
- Publication type
- Journal Article MeSH
Cardiomyocytes (CM) placed on microelectrode array (MEA) were simultaneously probed with cantilever from atomic force microscope (AFM) system. This electric / nanomechanical combination in real time recorded beating force of the CMs cluster and the triggering electric events. Such "organ-on-a-chip" represents a tool for drug development and disease modeling. The human pluripotent stem cells included the WT embryonic line CCTL14 and the induced dystrophin deficient line reprogrammed from fibroblasts of a patient affected by Duchenne Muscular Dystrophy (DMD, complete loss of dystrophin expression). Both were differentiated to CMs and employed with the AFM/MEA platform for diseased CMs' drug response testing and DMD characterization. The dependence of cardiac parameters on extracellular Ca2+ was studied. The differential evaluation explained the observed effects despite variability of biological samples. The β-adrenergic stimulation (isoproterenol) and antagonist trials (verapamil) addressed ionotropic and chronotropic cell line-dependent features. For the first time, a distinctive beating-force relation for DMD CMs was measured on the 3D cardiac in vitro model.
- MeSH
- Biosensing Techniques * MeSH
- Cell Differentiation genetics MeSH
- Muscular Dystrophy, Duchenne physiopathology MeSH
- Dystrophin genetics MeSH
- Fibroblasts drug effects ultrastructure MeSH
- Induced Pluripotent Stem Cells metabolism ultrastructure MeSH
- Isoproterenol pharmacology MeSH
- Myocytes, Cardiac cytology MeSH
- Myocardial Contraction genetics physiology MeSH
- Humans MeSH
- Microelectrodes MeSH
- Microscopy, Atomic Force MeSH
- Verapamil pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: This study sought to evaluate the safety and short-term performance of a novel catheter for very high power-short duration (vHPSD) ablation in the treatment of paroxysmal atrial fibrillation. BACKGROUND: The vHPSD catheter is a novel contact force-sensing catheter optimized for temperature-controlled radiofrequency ablation with microelectrodes and 6 thermocouples for real-time temperature monitoring; the associated vHPSD algorithm modulates power to maintain target temperature during 90 W, 4 s lesions. METHODS: QDOT-FAST (Clinical Study for Safety and Acute Performance Evaluation of the THERMOCOOL SMARTTOUCH SF-5D System Used With Fast Ablation Mode in Treatment of Patients With Paroxysmal Atrial Fibrillation) is a prospective, multicenter, single-arm study enrolling patients with symptomatic paroxysmal atrial fibrillation indicated for catheter-based pulmonary vein isolation. Primary endpoints were short-term effectiveness (confirmation of entrance block in all targeted pulmonary veins after adenosine/isoproterenol challenge) and short-term safety (primary adverse events). Participants were screened for silent cerebral lesions by magnetic resonance imaging. Patients were followed for 3 months post-ablation. RESULTS: A total of 52 patients underwent ablation and completed follow-up. Pulmonary vein isolation was achieved in all patients using the study catheter alone, with total procedure and fluoroscopy times of 105.2 ± 24.7 min and 6.6 ± 8.2 min, respectively. Most patients (n = 49; 94.2%) were in sinus rhythm at 3 months. Two primary adverse events were reported: 1 pseudoaneurysm; and 1 asymptomatic thromboembolism. There were no deaths, stroke, atrioesophageal fistula, pulmonary vein stenosis, or unanticipated adverse device effects. Six patients had identified silent cerebral lesions-all classified as asymptomatic without clinical or neurologic deficits. CONCLUSIONS: This first-in-human study of a novel catheter with optimized temperature control demonstrated the clinical feasibility and safety of vHPSD ablation. Procedure and fluoroscopy times were substantially lower than historical standard ablation with point-by-point catheters. (Clinical Study for Safety and Acute Performance Evaluation of the THERMOCOOL SMARTTOUCH SF-5D System Used With Fast Ablation Mode in Treatment of Patients With Paroxysmal Atrial Fibrillation [QDOT-FAST]; NCT03459196).
- MeSH
- Equipment Design MeSH
- Atrial Fibrillation surgery MeSH
- Fluoroscopy MeSH
- Catheter Ablation * adverse effects instrumentation methods MeSH
- Catheters adverse effects MeSH
- Therapeutic Irrigation instrumentation MeSH
- Middle Aged MeSH
- Humans MeSH
- Microelectrodes MeSH
- Prospective Studies MeSH
- Aged MeSH
- Pulmonary Veins surgery MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Study MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
An electrochemical genosensor for the detection and quantification of Karlodinium armiger is presented. The genosensor exploits tailed primers and ferrocene labelled dATP analogue to produce PCR products that can be directly hybridised on a gold electrode array and quantitatively measured using square wave voltammetry. Tailed primers consist of a sequence specific for the target, followed by a carbon spacer and a sequence specifically designed not to bind to genomic DNA, resulting in a duplex flanked by single stranded binding primers. The incorporation of the 7-(ferrocenylethynyl)-7-deaza-2'-deoxyadenosine triphosphate was optimised in terms of a compromise between maximum PCR efficiency and the limit of detection and sensitivity attainable using electrochemical detection via hybridisation of the tailed, ferrocene labelled PCR product. A limit of detection of 277aM with a linear range from 315aM to 10 fM starting DNA concentration and a sensitivity of 122 nA decade-1 was achieved. The system was successfully applied to the detection of genomic DNA in real seawater samples.
- MeSH
- Biosensing Techniques instrumentation MeSH
- Deoxyadenine Nucleotides chemistry MeSH
- Equipment Design MeSH
- DNA analysis MeSH
- Electrochemical Techniques instrumentation MeSH
- Limit of Detection MeSH
- Metallocenes chemistry MeSH
- Microelectrodes MeSH
- Seawater analysis MeSH
- Oxidation-Reduction MeSH
- Polymerase Chain Reaction instrumentation MeSH
- Ferrous Compounds chemistry MeSH
- Publication type
- Journal Article MeSH
Deep brain stimulation of the globus pallidus internus is an effective symptomatic treatment for pharmacoresistant dystonic syndromes, where pathophysiological mechanisms of action are not yet fully understood. The aim of this review article is to provide an overview of state-of-the-art approaches for processing microelectrode recordings in dystonia; in order to define biomarkers to identify patients who will benefit from clinical deep brain stimulation. For this purpose, the essential elements of microelectrode processing are examined. Next, we investigate a real example of spike sorting processing in this field. Herein, we describe baseline elements of microrecording processing including data collection, preprocessing phase, features computation, spike detection and sorting and finally, advanced spike train data analysis. This study will help readers acquire the necessary information about these elements and their associated techniques. Thus, this study is supposed to assist during identification and proposal of interesting clinical hypotheses in the field of single unit neuronal recordings in dystonia
- MeSH
- Biomarkers MeSH
- Dystonia * therapy MeSH
- Electrophysiology methods MeSH
- Electric Stimulation Therapy methods MeSH
- Deep Brain Stimulation methods MeSH
- Humans MeSH
- Microelectrodes MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
AIM: Advances in neuroradiological planning techniques in deep brain stimulation have put the need for intraoperative electrophysiological monitoring into doubt. Moreover intraoperative monitoring prolongs surgical time and there is potential association between the use of microelectrodes and increased incidence of hemorrhagic complications. The aim of this study was to analyze the correlation between the anatomically planned trajectory and the final subthalamic electrode placement after electrophysiological monitoring in patients with Parkinson"s disease and its change with the increasing experience of the surgical team. MATERIAL AND METHODS: The trajectories of right (first implanted) and left electrodes were compared in the first 50 patients operated on (Group 1) and the next 50 patients (Group 2). RESULTS: In Group 1, 52% of central trajectories were on the right and 38% on the left; in Group 2, the percentage of central trajectories was 76% on the right and 78% on the left; the difference was statistically significant (p=0.021 and 0.001). The difference in the percentage of posterior trajectories reflecting brain shift between the right and left sides was statistically insignificant in Groups 1 (26% and 28%, p=0.999) and 2 (18% and 12%, p=0.549). The percentage of bilateral central electrodes was 14% and 62% in Groups 1 and 2, respectively. CONCLUSION: The correlation between anatomically planned trajectory and final electrode placement markedly improves with the number of patients. However the significant percentage of patients with final electrode trajectory differing from anatomically planned target supports the use of intraoperative monitoring.
- MeSH
- Deep Brain Stimulation methods MeSH
- Electrodes, Implanted MeSH
- Intraoperative Neurophysiological Monitoring * MeSH
- Clinical Competence MeSH
- Learning Curve * MeSH
- Middle Aged MeSH
- Humans MeSH
- Microelectrodes MeSH
- Subthalamic Nucleus physiology MeSH
- Parkinson Disease surgery MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
