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The Analyst Jun 2021Traditional studies of enzymatic activity rely on the combined kinetics of millions of enzyme molecules to produce a product, an experimental approach that may wash out... (Review)
Review
Traditional studies of enzymatic activity rely on the combined kinetics of millions of enzyme molecules to produce a product, an experimental approach that may wash out heterogeneities that exist between individual enzymes. Evaluating these properties on an enzyme-by-enzyme basis represents an unambiguous means of elucidating heterogeneities; however, the quantification of enzymatic activity at the single-enzyme level is fundamentally limited by the maximum catalytic rate, k, inherent to a given enzyme. For electrochemical methods measuring current, single enzymes must turn over greater than 10 molecules per second to produce a measurable signal on the order of 10 A. Enzymes with this capability are extremely rare in nature, with typical k values for biologically relevant enzymes falling between 1 and 10 000 s. Thus, clever amplification strategies are necessary to electrochemically detect the vast majority of enzymes. This review details the progress toward the electroanalytical detection and evaluation of single enzyme kinetics largely focused on the nanoimpact method, a chronoamperometric detection strategy that monitors the change in the current-time profile associated with stochastic collisions of freely diffusing entities (e.g., enzymes) onto a microelectrode or nanoelectrode surface. We discuss the experimental setups and methods developed in the last decade toward the quantification of single molecule enzymatic rates. Special emphasis is given to the limitations of measurement science in the observation of single enzyme activity and feasible methods of signal amplification with reasonable bandwidth.
Topics: Diffusion; Electrochemical Techniques; Enzymes; Kinetics; Microelectrodes; Proteins
PubMed: 33881059
DOI: 10.1039/d1an00230a -
Journal of Neuroscience Methods Jan 2022Insertion of a microelectrode into the brain to record/stimulate neurons damages neural tissue and blood vessels and initiates the brain's wound healing response. Due to... (Review)
Review
Insertion of a microelectrode into the brain to record/stimulate neurons damages neural tissue and blood vessels and initiates the brain's wound healing response. Due to the large difference between the stiffness of neural tissue and microelectrode, brain micromotion also leads to neural tissue damage and associated local immune response. Over time, following implantation, the brain's response to the tissue damage can result in microelectrode failure. Reducing the microelectrode's cross-sectional dimensions to single-digit microns or using soft materials with elastic modulus close to that of the neural tissue are effective methods to alleviate the neural tissue damage and enhance microelectrode longevity. However, the increase in electrical impedance of the microelectrode caused by reducing the microelectrode contact site's dimensions can decrease the signal-to-noise ratio. Most importantly, the reduced dimensions also lead to a reduction in the critical buckling force, which increases the microelectrode's propensity to buckling during insertion. After discussing brain micromotion, the main source of neural tissue damage, surface modification of the microelectrode contact site is reviewed as a key method for addressing the increase in electrical impedance issue. The review then focuses on recent approaches to aiding insertion of flexible microelectrodes into the brain, including bending stiffness modification, effective length reduction, and application of a magnetic field to pull the electrode. An understanding of the advantages and drawbacks of the developed strategies offers a guide for dealing with the buckling phenomenon during implantation.
Topics: Brain; Cross-Sectional Studies; Electric Impedance; Electrodes, Implanted; Microelectrodes
PubMed: 34678387
DOI: 10.1016/j.jneumeth.2021.109388 -
Journal of Neural Engineering Oct 2020While the positive correlation between impedance and noise of microelectrodes is well known, their quantitative relationship is too rarely described. Knowledge of this...
OBJECTIVE
While the positive correlation between impedance and noise of microelectrodes is well known, their quantitative relationship is too rarely described. Knowledge of this relationship provides useful information for both microsystems engineers and electrophysiologists.
APPROACH
We discuss the physical basis of noise in recordings with microelectrodes, and compare measurements of impedance spectra to noise of microelectrodes.
MAIN RESULTS
Microelectrode recordings intrinsically include thermal noise, [Formula: see text], with the real component of impedance integrated over the recording frequency band. Impedance spectroscopy allows the quantitative prediction of thermal noise. Optimization of microelectrode noise should also consider the contribution of amplifier noise. These measures enable a quantitative evaluation of microelectrodes' recording quality which is more informative than common but limited comparisons based on the impedance magnitude at 1 kHz.
SIGNIFICANCE
Improved understanding of the origin of microelectrode noise will support efforts to produce smaller yet low noise microelectrodes, capable of recording from higher numbers of neurons. This tutorial is relevant for single microelectrodes, tetrodes, neural probes and microelectrode arrays, whether used in vitro or in vivo.
Topics: Electric Impedance; Electrodes, Implanted; Equipment Design; Microelectrodes; Neurons
PubMed: 33055360
DOI: 10.1088/1741-2552/abb3b4 -
Advanced Healthcare Materials Jun 2021Electrical microstimulation has enabled partial restoration of vision, hearing, movement, somatosensation, as well as improving organ functions by electrically... (Review)
Review
Electrical microstimulation has enabled partial restoration of vision, hearing, movement, somatosensation, as well as improving organ functions by electrically modulating neural activities. However, chronic microstimulation is faced with numerous challenges. The implantation of an electrode array into the neural tissue triggers an inflammatory response, which can be exacerbated by the delivery of electrical currents. Meanwhile, prolonged stimulation may lead to electrode material degradation., which can be accelerated by the hostile inflammatory environment. Both material degradation and adverse tissue reactions can compromise stimulation performance over time. For stable chronic electrical stimulation, an ideal microelectrode must present 1) high charge injection limit, to efficiently deliver charge without exceeding safety limits for both tissue and electrodes, 2) small size, to gain high spatial selectivity, 3) excellent biocompatibility that ensures tissue health immediately next to the device, and 4) stable in vivo electrochemical properties over the application period. In this review, the challenges in chronic microstimulation are described in detail. To aid material scientists interested in neural stimulation research, the in vitro and in vivo testing methods are introduced for assessing stimulation functionality and longevity and a detailed overview of recent advances in electrode material research and device fabrication for improving chronic microstimulation performance is provided.
Topics: Electric Stimulation; Electrodes, Implanted; Microelectrodes
PubMed: 34029008
DOI: 10.1002/adhm.202100119 -
Journal of Neural Engineering Apr 2022The micro-electrode array (MEA) is a cell-culture surface with integrated electrodes used for assays of electrically excitable cells and tissues. MEAs have been a...
The micro-electrode array (MEA) is a cell-culture surface with integrated electrodes used for assays of electrically excitable cells and tissues. MEAs have been a workhorse in the study of neurons and myocytes, owing to the scalability and millisecond temporal resolution of the technology. However, traditional MEAs are opaque, precluding inverted microscope access to modern genetically encoded optical sensors and effectors.. To address this gap, transparent MEAs have been developed. However, for many labs, transparent MEAs remain out of reach due to the cost of commercially available products, and the complexity of custom fabrication. Here, we describe an open-source transparent MEA based on the OpenEphys platform (Siegle2017045003).We demonstrate the performance of this transparent MEA in a multiplexed electrical and optogenetic assay of primary rat hippocampal neurons.This open-source transparent MEA and recording platform is designed to be accessible, requiring minimal microelectrode fabrication or circuit design experience. We include low-noise connectors for seamless integration with the Intan Technologies headstage, and a mechanically stable adaptor conforming to the 24-well plate footprint for compatibility with most inverted microscopes.
Topics: Animals; Microelectrodes; Neurons; Optogenetics; Rats
PubMed: 35349992
DOI: 10.1088/1741-2552/ac620d -
Neuromodulation : Journal of the... Aug 2022Microelectrode arrays offer a means to probe the functional circuitry of the brain and the promise of cortical neuroprosthesis for individuals suffering from paralysis... (Review)
Review
OBJECTIVES
Microelectrode arrays offer a means to probe the functional circuitry of the brain and the promise of cortical neuroprosthesis for individuals suffering from paralysis or limb loss. These devices are typically comprised of one or more shanks incorporating microelectrode sites, where the shanks are positioned by inserting the devices along a straight path that is normal to the brain surface. The lack of consistent long-term chronic recording technology has driven interest in novel probe design and approaches that go beyond the standard insertion approach that is limited to a single velocity or axis. This review offers a description of typical approaches and associated limitations and surveys emergent methods for implantation of microelectrode arrays, in particular those new approaches that leverage embedded microactuators and extend the insertion direction beyond a single axis.
MATERIALS AND METHODS
This review paper surveys the current technologies that enable probe implantation, repositioning, and the capability to record/stimulate from a tissue volume. A comprehensive literature search was performed using PubMed, Web of Science, and Google Scholar.
RESULTS
There has been substantial innovation in the development of microscale and embedded technology that enables probe repositioning to maintain quality recordings in the brain. Innovations in material science have resulted in novel strategies for deployable structures that can record from or stimulate a tissue volume. Moreover, new developments involving magnetically steerable catheters and needles offer an alternative approach to "pull" rather than "push" a probe into the tissue.
CONCLUSION
We envision the emergence of a new generation of probes and insertion methodologies for neuromodulation applications that enable reliable chronic performance from devices that can be positioned virtually anywhere in the brain.
Topics: Brain; Electrodes, Implanted; Humans; Microelectrodes
PubMed: 33438369
DOI: 10.1111/ner.13355 -
Sensors (Basel, Switzerland) Nov 2022In recent decades, microelectrodes have been widely used in neuroscience to understand the mechanisms behind brain functions, as well as the relationship between neural... (Review)
Review
In recent decades, microelectrodes have been widely used in neuroscience to understand the mechanisms behind brain functions, as well as the relationship between neural activity and behavior, perception and cognition. However, the recording of neuronal activity over a long period of time is limited for various reasons. In this review, we briefly consider the types of penetrating chronic microelectrodes, as well as the conductive and insulating materials for microelectrode manufacturing. Additionally, we consider the effects of penetrating microelectrode implantation on brain tissue. In conclusion, we review recent advances in the field of in vivo microelectrodes.
Topics: Microelectrodes; Electrophysiological Phenomena; Brain; Neurons; Electric Conductivity; Electrodes, Implanted
PubMed: 36501805
DOI: 10.3390/s22239085 -
Biosensors Dec 2022Neurons communicate through complex chemical and electrophysiological signal patterns to develop a tight information network. A physiological or pathological event... (Review)
Review
Neurons communicate through complex chemical and electrophysiological signal patterns to develop a tight information network. A physiological or pathological event cannot be explained by signal communication mode. Therefore, dual-mode electrodes can simultaneously monitor the chemical and electrophysiological signals in the brain. They have been invented as an essential tool for brain science research and brain-computer interface (BCI) to obtain more important information and capture the characteristics of the neural network. Electrochemical sensors are the most popular methods for monitoring neurochemical levels in vivo. They are combined with neural microelectrodes to record neural electrical activity. They simultaneously detect the neurochemical and electrical activity of neurons in vivo using high spatial and temporal resolutions. This paper systematically reviews the latest development of neural microelectrodes depending on electrode materials for simultaneous in vivo electrochemical sensing and electrophysiological signal recording. This includes carbon-based microelectrodes, silicon-based microelectrode arrays (MEAs), and ceramic-based MEAs, focusing on the latest progress since 2018. In addition, the structure and interface design of various types of neural microelectrodes have been comprehensively described and compared. This could be the key to simultaneously detecting electrochemical and electrophysiological signals.
Topics: Microelectrodes; Brain; Neurons
PubMed: 36671894
DOI: 10.3390/bios13010059 -
The Analyst Feb 2020Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes (CFMEs) is a versatile electrochemical technique to probe neurochemical dynamics in vivo. Progress in... (Review)
Review
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.
Topics: Data Analysis; Electrochemistry; Microelectrodes; Time Factors
PubMed: 31922162
DOI: 10.1039/c9an01925a -
Small (Weinheim An Der Bergstrasse,... Feb 2020A balanced concentration of ions is essential for biological processes to occur. For example, [H ] gradients power adenosine triphosphate synthesis, dynamic changes in...
A balanced concentration of ions is essential for biological processes to occur. For example, [H ] gradients power adenosine triphosphate synthesis, dynamic changes in [K ] and [Na ] create action potentials in neuronal communication, and [Cl ] contributes to maintaining appropriate cell membrane voltage. Sensing ionic concentration is thus important for monitoring and regulating many biological processes. This work demonstrates an ion-selective microelectrode array that simultaneously and independently senses [K ], [Na ], and [Cl ] in electrolyte solutions. To obtain ion specificity, the required ion-selective membranes are patterned using microfluidics. As a proof of concept, the change in ionic concentration is monitored during cell proliferation in a cell culture medium. This microelectrode array can easily be integrated in lab-on-a-chip approaches to physiology and biological research and applications.
Topics: Animals; Cell Line; Cell Proliferation; Culture Media; Ions; Mice; Microelectrodes; Microfluidics
PubMed: 31965738
DOI: 10.1002/smll.201906436