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Langmuir : the ACS Journal of Surfaces... Feb 2023In vivo sensing based on implantable microelectrodes has been widely used to monitor neurochemicals due to its high spatial and temporal resolution and engineering... (Review)
Review
In vivo sensing based on implantable microelectrodes has been widely used to monitor neurochemicals due to its high spatial and temporal resolution and engineering interface designability, which has become a powerful drive to decode the mysteries of degenerative diseases and regulate neural activity. Over the past few decades, with the development of a variety of advanced materials and technologies, encouraging progress has been made in quantifying various neurochemical transients. However, because of the complex chemical atmosphere including thousands of small and large biomolecules and the inherent low mechanical property of brain tissue, the design of a compatible microelectrode for the in vivo electrochemical tracking of neurochemicals with high selectivity and stability still faces great challenges. This Perspective presents a brief account of recent representative progress in the rational regulation of the microelectrode interface to resolve the questions of selectivity and sensitive decrease resulting from antiprotein adsorption, and how to decrease the mechanical mismatch of an implanted electrode with that of brain tissue. Possible future research directions on further addressing the above key issues and a more biocompatible microelectrode for in vivo long-time electrochemical analysis are also discussed.
Topics: Microelectrodes; Electrodes, Implanted
PubMed: 36689914
DOI: 10.1021/acs.langmuir.2c03267 -
Toxicological Sciences : An Official... Jan 2021Seizure liability remains a significant cause of attrition in drug discovery and development, leading to loss of competitiveness, delays, and increased costs. Current...
Seizure liability remains a significant cause of attrition in drug discovery and development, leading to loss of competitiveness, delays, and increased costs. Current detection methods rely on observations made in in vivo studies intended to support clinical trials, such as tremors or other abnormal movements. These signs could be missed or misinterpreted; thus, definitive confirmation of drug-induced seizure requires a follow-up electroencephalogram study. There has been progress in in vivo detection of seizure using automated video systems that record and analyze animal movements. Nonetheless, it would be preferable to have earlier prediction of seizurogenic risk that could be used to eliminate liabilities early in discovery while there are options for medicinal chemists making potential new drugs. Attrition due to cardiac adverse events has benefited from routine early screening; could we reduce attrition due to seizure using a similar approach? Specifically, microelectrode arrays could be used to detect potential seizurogenic signals in stem-cell-derived neurons. In addition, there is clear evidence implicating neuronal voltage-gated and ligand-gated ion channels, GPCRs and transporters in seizure. Interactions with surrounding glial cells during states of stress or inflammation can also modulate ion channel function in neurons, adding to the challenge of seizure prediction. It is timely to evaluate the opportunity to develop an in vitro assessment of seizure linked to a panel of ion channel assays that predict seizure, with the aim of influencing structure-activity relationship at the design stage and eliminating compounds predicted to be associated with pro-seizurogenic state.
Topics: Animals; Cells, Cultured; Electroencephalography; Humans; Microelectrodes; Neurons; Seizures
PubMed: 33165543
DOI: 10.1093/toxsci/kfaa167 -
ACS Applied Bio Materials Jul 2021Neural electrodes have been developed for the diagnosis and treatment of stroke, sensory deficits, and neurological disorders based on the electrical stimulation of...
Neural electrodes have been developed for the diagnosis and treatment of stroke, sensory deficits, and neurological disorders based on the electrical stimulation of nerve tissue and recording of neural electrical activity. A low interface impedance and large active surface area for charge transfer and intimate contact between neurons and the electrode are critical to obtain high-quality neural signal and effective stimulation without causing damage to both tissue and electrode. In this study, a nanostructured poly(3,4-ethylenedioxythiophene) (PEDOT) coating with lots of long protrusions was created via a one-step electrochemical polymerization from a dichloromethane solution without any rigid or soft templates. The nanostructures on the PEDOT coating were basically formed by intertwined PEDOT nanofibers, which further enhanced the active surface area. The fuzzy PEDOT-modified microelectrodes exhibited an impedance as low as 1 kΩ at 1 kHz, which is much lower than those produced from aqueous 3,4-ethylenedioxythiophene (EDOT) solution, and it was comparable with PEDOT films or composites created from/with template materials. Also, more than 150 times larger charge storage capacity density was obtained compared to the unmodified microelectrode. An in vitro biocompatibility test performed on PC12 cells and primary cells suggested that the PEDOT coatings support cell adhesion, growth, and neurite extension. These results suggest the great potential of the nanostructured PEDOT coating as an electroactive and biosafe intimate contact between the implanted neural electrode and neurons.
Topics: Animals; Bridged Bicyclo Compounds, Heterocyclic; Microelectrodes; Nanofibers; Neurons; Polymers; Rats
PubMed: 35006733
DOI: 10.1021/acsabm.1c00375 -
Advanced Science (Weinheim,... Nov 2023In situ physiological signals of in vitro neural disease models are essential for studying pathogenesis and drug screening. Currently, an increasing number of in vitro... (Review)
Review
In situ physiological signals of in vitro neural disease models are essential for studying pathogenesis and drug screening. Currently, an increasing number of in vitro neural disease models are established using human-induced pluripotent stem cell (hiPSC) derived neurons (hiPSC-DNs) to overcome interspecific gene expression differences. Microelectrode arrays (MEAs) can be readily interfaced with two-dimensional (2D), and more recently, three-dimensional (3D) neural stem cell-derived in vitro models of the human brain to monitor their physiological activity in real time. Therefore, MEAs are emerging and useful tools to model neurological disorders and disease in vitro using human iPSCs. This is enabling a real-time window into neuronal signaling at the network scale from patient derived. This paper provides a comprehensive review of MEA's role in analyzing neural disease models established by hiPSC-DNs. It covers the significance of MEA fabrication, surface structure and modification schemes for hiPSC-DNs culturing and signal detection. Additionally, this review discusses advances in the development and use of MEA technology to study in vitro neural disease models, including epilepsy, autism spectrum developmental disorder (ASD), and others established using hiPSC-DNs. The paper also highlights the application of MEAs combined with hiPSC-DNs in detecting in vitro neurotoxic substances. Finally, the future development and outlook of multifunctional and integrated devices for in vitro medical diagnostics and treatment are discussed.
Topics: Humans; Induced Pluripotent Stem Cells; Microelectrodes; Neurons; Neural Stem Cells; Nervous System Diseases
PubMed: 37863819
DOI: 10.1002/advs.202301828 -
Electrophoresis Jun 2022Glioblastoma multiforme is the most aggressive and invasive brain cancer consisting of genetically and phenotypically altering glial cells. It has massive heterogeneity...
Glioblastoma multiforme is the most aggressive and invasive brain cancer consisting of genetically and phenotypically altering glial cells. It has massive heterogeneity due to its highly complex and dynamic microenvironment. Here, electrophysiological properties of U87 human glioma cell line were measured based on a dielectrophoresis phenomenon to quantify the population heterogeneity of glioma cells. Dielectrophoretic forces were generated using a gold-microelectrode array within a microfluidic channel when 3 V and 100, 200, 300, 400, 500 kHz, 1, 2, 5, and 10 MHz frequencies were applied. We analyzed the dielectrophoretic behavior of 500 glioma cells, and revealed that the crossover frequency of glioma cells was around 140 kHz. A quantifying dielectrophoretic movement of the glioma cells exhibited three distinct glioma subpopulations: 50% of the glioma cells experienced strong, 30% of the cells were spread in the microchannel by moderate, and the rest of the cells experienced very weak positive dielectrophoretic forces. Our results demonstrated the dielectrophoretic spectra of U87 glioma cell line. Dielectrophoretic responses of glioma cells linked population heterogeneity to membrane properties of glioma cells rather than their size distribution in the population.
Topics: Brain Neoplasms; Electrophoresis; Glioblastoma; Humans; Microelectrodes; Microfluidics; Tumor Microenvironment
PubMed: 35366348
DOI: 10.1002/elps.202100374 -
Electrophoresis Jan 2020Electrical impedance is an established technique used for cell and particle characterization. The temporal and spectral resolution of electrical impedance have been used... (Review)
Review
Electrical impedance is an established technique used for cell and particle characterization. The temporal and spectral resolution of electrical impedance have been used to resolve basic cell characteristics like size and type, as well as to determine cell viability and activity. Such electrical impedance measurements are typically performed across the entire sample volume and can only provide an overall indication concerning the properties and state of that sample. For the study of heterogeneous structures such as cell layers, biological tissue, or polydisperse particle mixtures, an overall measured impedance value can only provide limited information and can lead to data misinterpretation. For the investigation of localized sample properties in complex heterogeneous structures/mixtures, the addition of spatial resolution to impedance measurements is necessary. Several spatially resolved impedance measurement techniques have been developed and applied to cell and particle research, including electrical impedance tomography, scanning electrochemical microscopy, and microelectrode arrays. This review provides an overview of spatially resolved impedance measurement methods and assesses their applicability for cell and particle characterization.
Topics: Animals; Cell Membrane; Cells, Cultured; Cytological Techniques; Dielectric Spectroscopy; Electric Impedance; Equipment Design; Humans; Mice; Microelectrodes; Microscopy, Electrochemical, Scanning; Tomography
PubMed: 31663624
DOI: 10.1002/elps.201900286 -
Cell and Tissue Research Mar 2022Neural probes are sophisticated electrophysiological tools used for intra-cortical recording and stimulation. These microelectrode arrays, designed to penetrate and... (Review)
Review
Neural probes are sophisticated electrophysiological tools used for intra-cortical recording and stimulation. These microelectrode arrays, designed to penetrate and interface the brain from within, contribute at the forefront of basic and clinical neuroscience. However, one of the challenges and currently most significant limitations is their 'seamless' long-term integration into the surrounding brain tissue. Following implantation, which is typically accompanied by bleeding, the tissue responds with a scarring process, resulting in a gliotic region closest to the probe. This glial scarring is often associated with neuroinflammation, neurodegeneration, and a leaky blood-brain interface (BBI). The engineering progress on minimizing this reaction in the form of improved materials, microfabrication, and surgical techniques is summarized in this review. As research over the past decade has progressed towards a more detailed understanding of the nature of this biological response, it is time to pose the question: Are penetrating probes completely free from glial scarring at all possible?
Topics: Cicatrix; Electrodes, Implanted; Gliosis; Humans; Microelectrodes
PubMed: 35029757
DOI: 10.1007/s00441-021-03567-9 -
Journal of Visualized Experiments : JoVE May 2023The protocol aims to uncover the properties of neuronal firing and network local field potentials (LFPs) in behaving mice carrying out specific tasks by correlating the...
The protocol aims to uncover the properties of neuronal firing and network local field potentials (LFPs) in behaving mice carrying out specific tasks by correlating the electrophysiological signals with spontaneous and/or specific behavior. This technique represents a valuable tool in studying the neuronal network activity underlying these behaviors. The article provides a detailed and complete procedure for electrode implantation and consequent extracellular recording in free-moving conscious mice. The study includes a detailed method for implanting the microelectrode arrays, capturing the LFP and neuronal spiking signals in the motor cortex (MC) using a multichannel system, and the subsequent offline data analysis. The advantage of multichannel recording in conscious animals is that a greater number of spiking neurons and neuronal subtypes can be obtained and compared, which allows the evaluation of the relationship between a specific behavior and the associated electrophysiological signals. Notably, the multichannel extracellular recording technique and the data analysis procedure described in the present study can be applied to other brain areas when conducting experiments in behaving mice.
Topics: Animals; Mice; Brain; Cardiac Electrophysiology; Consciousness; Data Analysis; Microelectrodes
PubMed: 37306412
DOI: 10.3791/65245 -
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 -
Critical Reviews in Analytical Chemistry 2022Dopamine (DA) is an essential type of neurotransmitter in the central nervous system. DA neurons usually exist as nuclei which are mainly found in the ventral tegmental... (Review)
Review
Dopamine (DA) is an essential type of neurotransmitter in the central nervous system. DA neurons usually exist as nuclei which are mainly found in the ventral tegmental area (VTN) and substantia nigra pars compacta (SNc). Parkinson's disease, epilepsy, schizophrenia and other diseases are all related to the abnormal metabolism of DA. Compared with traditional DA detection methods such as spectrophotometry and electrophoresis, electrochemical sensing technology has high detection efficiency, high sensitivity, fast and convenient real-time detection, which is recognized as the most effective method for measuring neurotransmitters in vivo. The working electrode of an electrochemical sensor can be generally divided into the conventional electrode and the microelectrode according to its size. The microelectrode shows excellent properties such as high sensitivity, high temporal resolution, and high spatial resolution while detecting DA, which makes it possible to detect neurotransmitters in vivo. In order to further investigate the role of DA in regulating action, emotion, and cognition, and to further clarify the relationship between DA abnormalities or lack and neurological diseases such as Parkinson, more and more researchers apply microelectrode-based electrochemistry sensing technology to detect DA in vivo. This article reviews recent applications of microelectrodes and the latest researches in DA detection in vivo, focusing on the following three types of microelectrodes: (1) non-nanomaterial-modified carbon fiber microelectrodes (CFE); (2) nanomaterial-modified microelectrodes; (3) microelectrode arrays (MEA).
Topics: Dopamine; Electrochemistry; Microelectrodes; Neurotransmitter Agents; Technology
PubMed: 32852227
DOI: 10.1080/10408347.2020.1811946