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Sensors (Basel, Switzerland) Jan 2013Determining the effective concentration (i.e., activity) of ions in and around living cells is important to our understanding of the contribution of those ions to... (Review)
Review
Determining the effective concentration (i.e., activity) of ions in and around living cells is important to our understanding of the contribution of those ions to cellular function. Moreover, monitoring changes in ion activities in and around cells is informative about the actions of the transporters and/or channels operating in the cell membrane. The activity of an ion can be measured using a glass microelectrode that includes in its tip a liquid-membrane doped with an ion-selective ionophore. Because these electrodes can be fabricated with tip diameters that are less than 1 μm, they can be used to impale single cells in order to monitor the activities of intracellular ions. This review summarizes the history, theory, and practice of ion-selective microelectrode use and brings together a number of classic and recent examples of their usefulness in the realm of physiological study.
Topics: Animals; Calibration; Cell Membrane; Ion-Selective Electrodes; Ionophores; Ions; Microelectrodes
PubMed: 23322102
DOI: 10.3390/s130100984 -
Advanced Materials (Deerfield Beach,... Mar 2014Recent advances in nanotechnology have generated wide interest in applying nanomaterials for neural prostheses. An ideal neural interface should create seamless... (Review)
Review
Recent advances in nanotechnology have generated wide interest in applying nanomaterials for neural prostheses. An ideal neural interface should create seamless integration into the nervous system and performs reliably for long periods of time. As a result, many nanoscale materials not originally developed for neural interfaces become attractive candidates to detect neural signals and stimulate neurons. In this comprehensive review, an overview of state-of-the-art microelectrode technologies provided fi rst, with focus on the material properties of these microdevices. The advancements in electro active nanomaterials are then reviewed, including conducting polymers, carbon nanotubes, graphene, silicon nanowires, and hybrid organic-inorganic nanomaterials, for neural recording, stimulation, and growth. Finally, technical and scientific challenges are discussed regarding biocompatibility, mechanical mismatch, and electrical properties faced by these nanomaterials for the development of long-lasting functional neural interfaces.
Topics: Animals; Biocompatible Materials; Humans; Microelectrodes; Nanostructures; Neural Prostheses; Neurons
PubMed: 24677434
DOI: 10.1002/adma.201304496 -
Sensors (Basel, Switzerland) Feb 2022Here, we report a novel technology for the fabrication of copper-electroplating-modified liquid metal microelectrodes. This technology overcomes the complexity of the...
Here, we report a novel technology for the fabrication of copper-electroplating-modified liquid metal microelectrodes. This technology overcomes the complexity of the traditional fabrication of sidewall solid metal electrodes and successfully fabricates a pair of tiny stable solid-contact microelectrodes on both sidewalls of a microchannel. Meanwhile, this technology also addresses the instability of liquid metal electrodes when directly contacted with sample solutions. The fabrication of this microelectrode depends on controllable microelectroplating of copper onto the gallium electrode by designing a microelectrolyte cell in a microfluidic chip. Using this technology, we successfully fabricate various microelectrodes with different microspacings (from 10 μm to 40 μm), which were effectively used for capacitive sensing, including droplet detection and oil particle counting.
Topics: Copper; Electroplating; Gallium; Microelectrodes; Microfluidic Analytical Techniques; Microfluidics
PubMed: 35270966
DOI: 10.3390/s22051820 -
Journal of Neurophysiology Mar 2017Microelectrode amperometric biosensors are widely used to measure concentrations of analytes in solution and tissue including acetylcholine, adenosine, glucose, and...
Microelectrode amperometric biosensors are widely used to measure concentrations of analytes in solution and tissue including acetylcholine, adenosine, glucose, and glutamate. A great deal of experimental and modeling effort has been directed at quantifying the response of the biosensors themselves; however, the influence that the macroscopic tissue environment has on biosensor response has not been subjected to the same level of scrutiny. Here we identify an important issue in the way microelectrode biosensors are calibrated that is likely to have led to underestimations of analyte tissue concentrations. Concentration in tissue is typically determined by comparing the biosensor signal to that measured in free-flow calibration conditions. In a free-flow environment the concentration of the analyte at the outer surface of the biosensor can be considered constant. However, in tissue the analyte reaches the biosensor surface by diffusion through the extracellular space. Because the enzymes in the biosensor break down the analyte, a density gradient is set up resulting in a significantly lower concentration of analyte near the biosensor surface. This effect is compounded by the diminished volume fraction (porosity) and reduction in the diffusion coefficient due to obstructions (tortuosity) in tissue. We demonstrate this effect through modeling and experimentally verify our predictions in diffusive environments. Microelectrode biosensors are typically calibrated in a free-flow environment where the concentrations at the biosensor surface are constant. However, when in tissue, the analyte reaches the biosensor via diffusion and so analyte breakdown by the biosensor results in a concentration gradient and consequently a lower concentration around the biosensor. This effect means that naive free-flow calibration will underestimate tissue concentration. We develop mathematical models to better quantify the discrepancy between the calibration and tissue environment and experimentally verify our key predictions.
Topics: Animals; Biosensing Techniques; Brain; Brain Chemistry; Calibration; Diffusion; Enzymes; Humans; Microelectrodes; Models, Neurological
PubMed: 27927788
DOI: 10.1152/jn.00788.2016 -
Journal of Neural Engineering Sep 2020Implantable neuroelectronic interfaces have enabled breakthrough advances in the clinical diagnosis and treatment of neurological disorders, as well as in fundamental... (Review)
Review
Implantable neuroelectronic interfaces have enabled breakthrough advances in the clinical diagnosis and treatment of neurological disorders, as well as in fundamental studies of brain function, behavior, and disease. Intracranial electroencephalography (EEG) mapping with stereo-EEG (sEEG) depth electrodes is routinely adopted for precise epilepsy diagnostics and surgical treatment, while deep brain stimulation has become the standard of care for managing movement disorders. Intracortical microelectrode arrays for high-fidelity recordings of neural spiking activity have led to impressive demonstrations of the power of brain-machine interfaces for motor and sensory functional recovery. Yet, despite the rapid pace of technology development, the issue of establishing a safe, long-term, stable, and functional interface between neuroelectronic devices and the host brain tissue still remains largely unresolved. A body of work spanning at least the last 15 years suggests that safe, chronic integration between invasive electrodes and the brain requires a close match between the mechanical properties of man-made components and the neural tissue. In other words, the next generation of invasive electrodes should be soft and compliant, without sacrificing biological and chemical stability. Soft neuroelectronic interfaces, however, pose a new and significant surgical challenge: bending and buckling during implantation that can preclude accurate and safe device placement. In this topical review, we describe the next generation of soft electrodes and the surgical implantation methods for safe and precise insertion into brain structures. We provide an overview of the most recent innovations in the field of insertion strategies for flexible neural electrodes such as dissolvable or biodegradable carriers, microactuators, biologically-inspired support structures, and electromagnetic drives. In our analysis, we also highlight approaches developed in different fields, such as robotic surgery, which could be potentially adapted and translated to the insertion of flexible neural probes.
Topics: Animals; Culicidae; Electrodes, Implanted; Gels; Humans; Magnets; Microelectrodes
PubMed: 32759476
DOI: 10.1088/1741-2552/abacd7 -
Neurobiology of Disease Jul 2019The cellular activity underlying human focal seizures, and its relationship to key signatures in the EEG recordings used for therapeutic purposes, has not been well... (Review)
Review
The cellular activity underlying human focal seizures, and its relationship to key signatures in the EEG recordings used for therapeutic purposes, has not been well characterized despite many years of investigation both in laboratory and clinical settings. The increasing use of microelectrodes in epilepsy surgery patients has made it possible to apply principles derived from laboratory research to the problem of mapping the spatiotemporal structure of human focal seizures, and characterizing the corresponding EEG signatures. In this review, we describe results from human microelectrode studies, discuss some data interpretation pitfalls, and explain the current understanding of the key mechanisms of ictogenesis and seizure spread.
Topics: Brain; Electrodes, Implanted; Electroencephalography; Epilepsy; Humans; Microelectrodes; Neurons; Seizures
PubMed: 30898669
DOI: 10.1016/j.nbd.2019.03.015 -
NeuroImage Jul 2022Human neuronal activity, recorded in vivo from microelectrodes, may offer valuable insights into physiological mechanisms underlying human cognition and...
PURPOSE
Human neuronal activity, recorded in vivo from microelectrodes, may offer valuable insights into physiological mechanisms underlying human cognition and pathophysiological mechanisms of brain diseases, in particular epilepsy. Continuous and long-term recordings are necessary to monitor non predictable pathological and physiological activities like seizures or sleep. Because of their high impedance, microelectrodes are more sensitive to noise than macroelectrodes. Low noise levels are crucial to detect action potentials from background noise, and to further isolate single neuron activities. Therefore, long-term recordings of multi-unit activity remains a challenge. We shared here our experience with microelectrode recordings and our efforts to reduce noise levels in order to improve signal quality. We also provided detailed technical guidelines for the connection, recording, imaging and signal analysis of microelectrode recordings.
RESULTS
During the last 10 years, we implanted 122 bundles of Behnke-Fried hybrid macro-microelectrodes, in 56 patients with pharmacoresistant focal epilepsy. Microbundles were implanted in the temporal lobe (74%), as well as frontal (15%), parietal (6%) and occipital (5%) lobes. Low noise levels depended on our technical setup. The noise reduction was mainly obtained after electrical insulation of the patient's recording room and the use of a reinforced microelectrode model, reaching median root mean square values of 5.8 µV. Seventy percent of the bundles could record multi-units activities (MUA), on around 3 out of 8 wires per bundle and for an average of 12 days. Seizures were recorded by microelectrodes in 91% of patients, when recorded continuously, and MUA were recorded during seizures for 75 % of the patients after the insulation of the room. Technical guidelines are proposed for (i) electrode tails manipulation and protection during surgical bandage and connection to both clinical and research amplifiers, (ii) electrical insulation of the patient's recording room and shielding, (iii) data acquisition and storage, and (iv) single-units activities analysis.
CONCLUSIONS
We progressively improved our recording setup and are now able to record (i) microelectrode signals with low noise level up to 3 weeks duration, and (ii) MUA from an increased number of wires . We built a step by step procedure from electrode trajectory planning to recordings. All these delicate steps are essential for continuous long-term recording of units in order to advance in our understanding of both the pathophysiology of ictogenesis and the neuronal coding of cognitive and physiological functions.
Topics: Action Potentials; Drug Resistant Epilepsy; Electrodes, Implanted; Epilepsy; Humans; Microelectrodes; Neurons; Seizures
PubMed: 35318150
DOI: 10.1016/j.neuroimage.2022.119116 -
Nature Communications Jul 2022Human brain organoids replicate much of the cellular diversity and developmental anatomy of the human brain. However, the physiology of neuronal circuits within...
Human brain organoids replicate much of the cellular diversity and developmental anatomy of the human brain. However, the physiology of neuronal circuits within organoids remains under-explored. With high-density CMOS microelectrode arrays and shank electrodes, we captured spontaneous extracellular activity from brain organoids derived from human induced pluripotent stem cells. We inferred functional connectivity from spike timing, revealing a large number of weak connections within a skeleton of significantly fewer strong connections. A benzodiazepine increased the uniformity of firing patterns and decreased the relative fraction of weakly connected edges. Our analysis of the local field potential demonstrate that brain organoids contain neuronal assemblies of sufficient size and functional connectivity to co-activate and generate field potentials from their collective transmembrane currents that phase-lock to spiking activity. These results point to the potential of brain organoids for the study of neuropsychiatric diseases, drug action, and the effects of external stimuli upon neuronal networks.
Topics: Brain; Humans; Induced Pluripotent Stem Cells; Microelectrodes; Neurons; Organoids
PubMed: 35906223
DOI: 10.1038/s41467-022-32115-4 -
Scientific Reports Aug 2022Long-term implantable neural interfacing devices are able to diagnose, monitor, and treat many cardiac, neurological, retinal and hearing disorders through nerve...
Long-term implantable neural interfacing devices are able to diagnose, monitor, and treat many cardiac, neurological, retinal and hearing disorders through nerve stimulation, as well as sensing and recording electrical signals to and from neural tissue. To improve specificity, functionality, and performance of these devices, the electrodes and microelectrode arrays-that are the basis of most emerging devices-must be further miniaturized and must possess exceptional electrochemical performance and charge exchange characteristics with neural tissue. In this report, we show for the first time that the electrochemical performance of femtosecond-laser hierarchically-restructured electrodes can be tuned to yield unprecedented performance values that significantly exceed those reported in the literature, e.g. charge storage capacity and specific capacitance were shown to have improved by two orders of magnitude and over 700-fold, respectively, compared to un-restructured electrodes. Additionally, correlation amongst laser parameters, electrochemical performance and surface parameters of the electrodes was established, and while performance metrics exhibit a relatively consistent increasing behavior with laser parameters, surface parameters tend to follow a less predictable trend negating a direct relationship between these surface parameters and performance. To answer the question of what drives such performance and tunability, and whether the widely adopted reasoning of increased surface area and roughening of the electrodes are the key contributors to the observed increase in performance, cross-sectional analysis of the electrodes using focused ion beam shows, for the first time, the existence of subsurface features that may have contributed to the observed electrochemical performance enhancements. This report is the first time that such performance enhancement and tunability are reported for femtosecond-laser hierarchically-restructured electrodes for neural interfacing applications.
Topics: Cross-Sectional Studies; Electrodes; Electrodes, Implanted; Lasers; Microelectrodes; Nerve Tissue; Nervous System
PubMed: 35978090
DOI: 10.1038/s41598-022-18161-4 -
Biosensors & Bioelectronics Jan 2021Three-dimensional microelectrode arrays (3D MEAs) have emerged as promising tools to detect electrical activities of tissues or organs in vitro and in vivo, but... (Review)
Review
Three-dimensional microelectrode arrays (3D MEAs) have emerged as promising tools to detect electrical activities of tissues or organs in vitro and in vivo, but challenges in achieving fast, accurate, and versatile monitoring have consistently hampered further advances in analyzing cell or tissue behaviors. In this review, we discuss emerging 3D MEA technologies for in vitro recording of cardiac and neural cellular electrophysiology, as well as in vivo applications for heart and brain health diagnosis and therapeutics. We first review various forms of recent 3D MEAs for in vitro studies in context of their geometry, materials, and fabrication processes as well as recent demonstrations of 3D MEAs to monitor electromechanical behaviors of cardiomyocytes and neurons. We then present recent advances in 3D MEAs for in vivo applications to the heart and the brain for monitoring of health conditions and stimulation for therapy. A brief overview of the current challenges and future directions of 3D MEAs are provided to conclude the review.
Topics: Biosensing Techniques; Brain; Heart; Microelectrodes; Neurons
PubMed: 33059168
DOI: 10.1016/j.bios.2020.112687