Electrophysiological Electrodes Research Articles

Carbon monofilament electrodes for unit recording and functional MRI in same subjects

Extracellular electrophysiology and functional MRI are complementary techniques that provide information about cellular and network-level neural activity, respectively. However, electrodes for electrophysiology are typically made from metals, which cause significant susceptibility artifacts on MR images. Previous work has demonstrated that insulated carbon fiber bundle electrodes reduce the volume of magnetic susceptibility artifacts and can be used to record local field potentials (LFP), but the relatively large diameter of the probes make them unsuitable for multi- and single-unit recordings. Although single carbon fiber electrodes have recently been used to record single-unit activity, these probes require modifications in order to aid insertion and the use of these probes in fMRI has yet to be validated. Therefore, there is a need for a single-carbon fiber electrode design that (1) minimizes the volume of the susceptibility artifact, (2) can record from a wide frequency band that includes LFP and multi- and single-unit recording, and (3) is practical to insert without additional modifications. Here, we demonstrate that carbon-fiber electrodes made from single carbon monofilaments (35 μm in diameter) meet all of these criteria. Carbon monofilament electrodes modified with the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) have lower impedances and higher signal-to-noise ratio recordings than platinum-iridium electrodes, a current gold standard for chronic single-unit recording. Furthermore, these probes distort a significantly smaller volume of voxels compared to tungsten and platinum-iridium electrodes in agarose phantom and in vivo MR images, leading to higher contrast-to-noise ratio in regions proximal to the electrode implantation site during fMRI. Collectively, this work establishes that carbon monofilaments are a practical choice for combined electrophysiology-fMRI experiments.

A compartmentalized microfluidic chip with crisscross microgrooves and electrophysiological electrodes for modeling the blood-retinal barrier.

The interconnection of different tissue-tissue interfaces may extend organ-on-chips to a new generation of sophisticated models capable of recapitulating more complex organ-level functions. Single interfaces are largely recreated in organ-on-chips by culturing the cells on opposite sides of a porous membrane that splits a chamber in two or by connecting the cells of two adjacent compartments through microchannels. However, it is difficult to interconnect more than one interface using these approaches. To address this challenge, we present a novel microfluidic device where cells are arranged in parallel compartments and are highly interconnected through a grid of microgrooves, which facilitates paracrine signaling and heterotypic cell-cell contact between multiple tissues. In addition, the device includes electrodes on the substrate for the measurement of transepithelial electrical resistance (TEER). Unlike conventional methods for measuring the TEER where electrodes are on each side of the cell barrier, a method with only electrodes on the substrate has been validated. As a proof-of-concept, we have used the device to mimic the structure of the blood-retinal barrier by co-culturing primary human retinal endothelial cells (HREC), a human neuroblastoma cell line (SH-SY5Y), and a human retinal pigment epithelial cell line (ARPE-19). Cell barrier formations were assessed by a permeability assay, TEER measurements, and ZO-1 expression. These results validate the proposed microfluidic device with microgrooves as a promising in vitro tool for the compartmentalization and monitoring of barrier tissues.

(Invited) New Platforms for Multiplexing Electrochemical Measurements In Vivo

Complex behaviors depend on the coordination of the activities of ensembles of neurons and the release of neuromodulators such as dopamine. The mechanisms underlying such coordination are not well-understood due to a lack of instrumentation for combined and real-time monitoring of neuromodulator release and the activities of large ensembles of neurons. Here I describe a measurement platform that allows for the combined monitoring of electrophysiology from a high-density electrode array and dopamine dynamics from a carbon-fiber microelectrode. Integration of these two measurement systems was achieved through modification of the existing instrumentation. A shared grounded reference electrode was used in both systems to minimize electrical interference. Further, an optional solid-state-relay array positioned between the electrophysiological electrode array and amplifiers was added to provide additional electrical isolation. The capacity of the integrated measurement platform, termed DANA (Dopamine And Neural Activity), to measure action potentials (high frequency) and local-field oscillations (low frequency) was characterized in vitro using an artificial cerebral spinal fluid gelatin. In vivo recordings from the DANA platform in anesthetized rats demonstrated the ability of the system for near-simultaneous measurement of dopamine release and activity from multiple neurons both in distant brain regions (striatum and hippocampus) and within the same brain region (striatum). Furthermore, this system was shown to be sufficiently compact to measure activity in freely moving animals through recording of single-neuron activity, high-frequency local-field oscillations, and dopamine release. Fast scan cyclic voltammetry has been used extensively to monitor dynamic changes in neurotransmitters (e.g. dopamine, serotonin, norepinephrine) in real time. However, these measurements are limited in terms of the number of implantable sensors. This does not allow the coordinated chemical communication and interactions between groups of neurons to be mapped in the same animal. Additioanally, we present arrays of electrodes with biocompatible conducting polymers capable of measuring biogenic amines. Metal wires are coated with the electrochemical polymerization of the monomer 3,4-ethylenedioxythiophene (EDOT). After baking and rinsing, a film with a positively charged polymer backbone balanced by negatively charged tosylate ions is formed. These electrodes can then be easily integrated in mass-producible arrays, brining voltammetry on par with multiple probe recordings common in electrophysiology. These voltammetric recordings also require custom instrumentation that integrates low-noise operational amplifiers with high-performance data acquisition cards and software. The system presented is capable of recording from eight channels (with appropriate instrumentation). By electrically isolating each channel, they can be independently addressed and a different neurotransmitter can be measured at each sensor. This greatly increases the ability to map neurotransmitter release in the brain of animals in real time. Data measuring both dopamine and serotonin in different brain regions is presented.

Poly(3,4-ethylenedioxythiophene) (PEDOT) Derivatives: Innovative Conductive Polymers for Bioelectronics.

Poly(3,4-ethylenedioxythiophene)s are the conducting polymers (CP) with the biggest prospects in the field of bioelectronics due to their combination of characteristics (conductivity, stability, transparency and biocompatibility). The gold standard material is the commercially available poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS). However, in order to well connect the two fields of biology and electronics, PEDOT:PSS presents some limitations associated with its low (bio)functionality. In this review, we provide an insight into the synthesis and applications of innovative poly(ethylenedioxythiophene)-type materials for bioelectronics. First, we present a detailed analysis of the different synthetic routes to (bio)functional dioxythiophene monomer/polymer derivatives. Second, we focus on the preparation of PEDOT dispersions using different biopolymers and biomolecules as dopants and stabilizers. To finish, we review the applications of innovative PEDOT-type materials such as biocompatible conducting polymer layers, conducting hydrogels, biosensors, selective detachment of cells, scaffolds for tissue engineering, electrodes for electrophysiology, implantable electrodes, stimulation of neuronal cells or pan-bio electronics.

Platform to Enable Combined Measurement of Dopamine and Neural Activity.

Complex behaviors depend on the coordination of the activities of ensembles of neurons and the release of neuromodulators such as dopamine. The mechanisms underlying such coordination are not well-understood due to a lack of instrumentation for combined and real-time monitoring of neuromodulator release and the activities of large ensembles of neurons. Here we describe a measurement platform that allows for the combined monitoring of electrophysiology from a high-density electrode array and dopamine dynamics from a carbon-fiber microelectrode. Integration of these two measurement systems was achieved through modification of the existing instrumentation. A shared grounded reference electrode was used in both systems to minimize electrical interference. Further, an optional solid-state-relay array positioned between the electrophysiological electrode array and amplifiers was added to provide additional electrical isolation. The capacity of the integrated measurement platform, termed DANA (Dopamine And Neural Activity), to measure action potentials (high frequency) and local-field oscillations (low frequency) was characterized in vitro using an artificial cerebral spinal fluid gelatin. In vivo recordings from the DANA platform in anesthetized rats demonstrated the ability of the system for near-simultaneous measurement of dopamine release and activity from multiple neurons both in distant brain regions (striatum and hippocampus) and within the same brain region (striatum). Furthermore, this system was shown to be sufficiently compact to measure activity in freely moving animals through recording of single-neuron activity, high-frequency local-field oscillations, and dopamine release.

Mechanics of Fractal-Inspired Horseshoe Microstructures for Applications in Stretchable Electronics

Fractal-inspired designs represent an emerging class of strategy for stretchable electronics, which have been demonstrated to be particularly useful for various applications, such as stretchable batteries and biointegrated electrophysiological electrodes. The fractal-inspired constructs usually undergo complicated, nonlinear deformations under mechanical loading, because of the highly complex and diverse microstructures inherent in high-order fractal patterns. The underlying relations between the nonlinear mechanical responses and microstructure geometry are essential in practical applications, which require a relevant mechanics theory to serve as the basis of a design approach. Here, a theoretical model inspired by the mechanism of ordered unraveling is developed to study the nonlinear stress–strain curves and elastic stretchability for a class of fractal-inspired horseshoe microstructures. Analytic solutions were obtained for some key mechanical quantities, such as the elastic modulus and the tangent modulus at the beginning of each deformation stage. Both the finite-element analyses (FEA) and experiments were carried out to validate the model. Systematic analyses of the microstructure–property relationship dictate how to leverage the various geometric parameters to tune the multistage, J-shaped stress–strain curves. Moreover, a demonstrative example shows the utility of the theoretical model in design optimization of fractal-inspired microstructures used as electrophysiological electrodes, aiming to achieve maximum elastic stretchability for prescribed filling ratios. The results indicate a substantial enhancement (e.g., >4 times) of elastic stretchability by using fractal designs, as compared to traditional horseshoe designs. This study can serve as design guidelines of fractal-inspired microstructures in different stretchable electronic systems.

Nanomaterial-Enabled Dry Electrodes for Electrophysiological Sensing: A Review

Long-term, continuous, and unsupervised tracking of physiological data is becoming increasingly attractive for health/wellness monitoring and ailment treatment. Nanomaterials have recently attracted extensive attention as building blocks for flexible/stretchable conductors and are thus promising candidates for electrophysiological electrodes. Here we provide a review on nanomaterial-enabled dry electrodes for electrophysiological sensing, focusing on electrocardiography (ECG). The dry electrodes can be classified into contact surface electrodes, contact-penetrating electrodes, and noncontact capacitive electrodes. Different types of electrodes including their corresponding equivalent electrode–skin interface models and the sources of the noise are first introduced, followed by a review on recent developments of dry ECG electrodes based on various nanomaterials, including metallic nanowires, metallic nanoparticles, carbon nanotubes, and graphene. Their fabrication processes and performances in terms of electrode–skin impedance, signal-to-noise ratio, resistance to motion artifacts, skin compatibility, and long-term stability are discussed.

An implantable microelectrode array for simultaneous L-glutamate and electrophysiological recordings in vivo

L-glutamate, the most common excitatory neurotransmitter in the mammalian central nervous system (CNS), is associated with a wide range of neurological diseases. Because neurons in CNS communicate with each other both electrically and chemically, dual-mode (electric and chemical) analytical techniques with high spatiotemporal resolution are required to better understand glutamate function in vivo. In the present study, a silicon-based implantable microelectrode array (MEA) composed of both platinum electrochemical and electrophysiological microelectrodes was fabricated using micro-electromechanical system. In the MEA probe, the electrophysiological electrodes have a low impedance of 0.018 MΩ at 1 kHz, and the electrochemical electrodes show a sensitivity of 56 pA µM−1 to glutamate and have a detection limit of 0.5 µM. The MEA probe was used to monitor extracellular glutamate levels, spikes and local field potentials (LFPs) in the striatum of anaesthetised rats. To explore the potential of the MEA probe, the rats were administered to KCl via intraperitoneal injection. K+ significantly increases extracellular glutamate levels, LFP low-beta range (12–18 Hz) power and spike firing rates with a similar temporal profile, indicating that the MEA probe is capable of detecting dual-mode neuronal signals. It was concluded that the MEA probe can help reveal mechanisms of neural physiology and pathology in vivo. Abnormal transmission of L-glutamate can cause neurological disorders such as Parkinson's disease, stroke and epilepsy. In their search for effective treatments, researchers are deploying extensive efforts to understand this key neurotransmitter, which regulates receptors located at chemical synapses. However, their attempts often fail to analyze the syntrophic complexity of biochemical and electrical events occurring in neurons. Now, Xinxia Cai and co-workers from the Institute of Electronics, Chinese Academy of Sciences, Beijing, China, have developed a silicon-based probe that simultaneously measures L-glutamate levels and electrical activity at various locations in the brain with high spatial and temporal resolution. The implantable array combines electrochemical and electrophysiological microelectrodes created through MEMS and nanotechnology. The team expects it to provide insight into physiological and pathological pathways in live brain tissue, paving the way to new diagnostic and therapeutic approaches.

In vivo simultaneous intra- and extracellular potassium recordings using a micro-optrode

This technique proposes a new approach to correlate intra- and extracellular variations of the ionic concentrations in vivo by means of tapered optical waveguides coupled to standard electrophysiological electrodes to monitor in vivo simultaneously the intracellular and extracellular K+ concentration as well as the neighboring field potential. The optical fibers were tapered to a final diameter of approximately 10μm and were used to guide the excitation light deep into the tissue and to collect the fluorescence emanating from the intracellular milieu. This fiber was coupled to a double barrel ion-sensitive electrode forming a micro-optrode with a final diameter around 15μm. The method was successfully used to record the intracellular K+ evolution with the fluorescent indicator PBFI during three states: normal sleep-like patterns, paroxysmal seizures, and coma. While we could not disclose any phasic fluctuations of the intracellular K+ during normal sleep patterns, they were clearly present during seizures and coma. In the majority of cases (58%), paroxysmal discharges were associated with positive variations of the intracellular fluorescence of 62±5% corresponding to extracellular K+ increases of 2.04±0.4mM. In the remaining cases (42%) intracellular K+ dropped by 44.4±12% for an extracellular K+ increase of 2.62±0.47mM. We suggest that this differential behavior might reflect different cellular populations (glia vs. neurons, respectively). Comatose states were accompanied by an extracellular drop of K+ of 1.31±0.13mM, which was reflected, in all cases, by an intracellular K+ increase of 39±4%.

Four probe architecture using high spatial resolution single multi-walled carbon nanotube electrodes for electrophysiology and bioimpedance monitoring of whole tissue

We report the application of a sensor with a multielectrode architecture consisting of four single multiwalled carbon nanotube electrodes (sMWNT electrodes) with nanotube tip diameters of approximately 30 nm to stimulation, recording, and bioimpedance characterization of whole muscle. Parallel pairs of sMWNT electrodes achieve improved stimulation efficiency from a reduction in electrode impedance and enhanced signal-to-noise ratio by detecting endogenic signals from a larger population of electrically active cells. The sensor with a four sMWNT electrode configuration can monitor changes in whole tissue bioimpedance.

Imaging catheters for volumetric intraluminal ultrasound imaging

A real time three dimensional ultrasound imaging probe apparatus is configured to be placed inside a body. The apparatus comprises an elongated body having proximal and distal ends with an ultrasonic transducer phased array connected to and positioned on the distal end of the elongated body. The ultrasonic transducer phased array is positioned to emit and receive ultrasonic energy for volumetric forward scanning from the distal end of the elongated body. The ultrasonic transducer phased array includes a plurality of sites occupied by ultrasonic transducer elements. At least one ultrasonic transducer element is absent from at least one of the sites, thereby defining an interstitial site. A tool is positioned at the interstitial site. In particular, the tool can be a fiber optic lead, a suction tool, a guide wire, an electrophysiological electrode, or an ablation electrode. Related systems are also discussed.

Reduction of response time for potential in salt bridge reference electrodes for electrophysiology.

SATURATED or 3 molar potassium chloride salt bridges connected to a calomel half cell or a silver–silver chloride electrode are used extensively in electrochemistry and electrophysiology as reference electrodes for potential measurements. The 3 molar potassium chloride salt bridge electrode is used in electrophysiology primarily because the liquid junction potential from the salt bridge to physiological solutions is only a few millivolts and varies little at equilibrium when in different physiological solutions. Derivations for this liquid junction potential have been obtained1–3.