Neural Stimulation Electrodes Research Articles

Fabrication of High-Performance Neural Stimulation Electrode through Pulsed Electrochemical Deposition of IrOx onto Nano-Porous Platinum

Abstract Electrodes for neural stimulation are pivotal in medical and brain science applications. This study aims to prepare novel neural stimulating electrodes with enhanced electrochemical performance and improved mechanical stability through a two-step electrochemical deposition process. Initially, a highly porous platinum (Porous-Pt) electrode with high nanoscale roughness is fabricated, followed by the incorporation of IrOx onto the Porous-Pt surface. The resulting IrOx/Porous-Pt electrode combines the advantages of both materials, offering low impedance, significantly increased CIC, and improved mechanical stability. Scanning electron microscopy revealed that the porous surface of the electrode consisting of sphere-shaped Pt nanoparticles offers a significant effective surface area, promoting strong adhesion and stability for uniform IrOx deposition onto Porous-Pt. This characteristic contributed to the long-term mechanical stability of the IrOx/Porous-Pt electrode.

The impact of chemical functionalization of carbon nanotubes on the electrochemical performance of carbon fiber/pyrocarbon/carbon nanotube composites as potential materials for electrodes for nerve cell stimulation

In this work, we propose a new carbon–carbon (C–C) composites as a potential materials for electrodes for neural stimulation in neurodegenerative disorders. The C–C composites were made via chemical vapour deposition (CVD) synthesis of pyrocarbon on carbon fibers, with subsequent thermal spray deposition of carbon nanotubes (CNT). Different CNT types were tested to evaluate their impact on electrochemical and biological performance. Materials were analyzed for microstructure, surface chemistry, and electrochemical properties, then tested using SH-SY5Y neuroblastoma cells for biological assessment. TheC–C composites coated with a hydroxy-terminated CNT demonstrated significantly enhanced electrochemical properties, inparticular increased cathodal charge capacity upto12.51mCcm−2, a wide safe potential window of −1.53 to 1.26 V, and decreased impedance, and cut-off frequency (fcut-off = 0.16 kHz). No acute negative biological responses of the materials were detected after 48 h of exposition. Such properties significantly outperform the properties of platinum, which is the basic element of platinum electrodes, demonstrating the excellent performance of the obtained composites and showing it may constitute the basic element of carbon electrodes for nerve stimulation in the future. Our work presents the method for obtaining biologically inert carbon composite micro-electrodes which can potentially be adapted to neural stimulation.

System of Implantable Electrodes for Neural Signal Acquisition and Stimulation for Wirelessly Connected Forearm Prosthesis.

There is great interest in the development of prosthetic limbs capable of complex activities that are wirelessly connected to the patient's neural system. Although some progress has been achieved in this area, one of the main problems encountered is the selective acquisition of nerve impulses and the closing of the automation loop through the selective stimulation of the sensitive branches of the patient. Large-scale research and development have achieved so-called "cuff electrodes"; however, they present a big disadvantage: they are not selective. In this article, we present the progress made in the development of an implantable system of plug neural microelectrodes that relate to the biological nerve tissue and can be used for the selective acquisition of neuronal signals and for the stimulation of specific nerve fascicles. The developed plug electrodes are also advantageous due to their small thickness, as they do not trigger nerve inflammation. In addition, the results of the conducted tests on a sous scrofa subject are presented.

Flexible a‐IGZO TFT‐Based Circuit for Active Addressing in Neural Stimulation Electrode Arrays

AbstractNeural interfaces have undergone significant advancements in recent decades, aiming for flexible, compact, and high‐density electrode arrays with a large number of channels. However, the scalability of these devices is often hindered by the number of wires needed to separately connect each electrode to external electronics. To address this limitation, thin‐film transistor (TFT)‐based electronic circuits offer a promising solution by enabling active addressing of stimulation electrodes and potentially increasing the channel count with fewer interconnections. This paper presents the integration of a circuit comprising two amorphous indium–gallium–zinc‐oxide (a‐IGZO) TFTs and a titanium nitride (TiN) electrode on a flexible polymer platform. This circuit precisely controls the electrode's On/Off states and the delivery of current for nerve stimulation. Characterization studies involving frequency and electrochemical analysis demonstrate the TFT‐based circuit's capability to operate at high frequencies, deliver biphasic stimulation pulses to the electrode, and store sufficient charge for effective neural stimulation. Moreover, the a‐IGZO TFTs exhibit remarkable stability during repeated gate voltage sweeps with minimal changes in electrical performance. This circuit has the potential to be extended to active‐matrix devices that enable electrode arrays with a high number of channels and enhanced spatial resolution, which is crucial for selective neural stimulation.

Electrochemical Properties of Sputtered Ruthenium Oxide Neural Stimulation and Recording Electrodes

A chronically stable electrode material with a low impedance for recording neural activity, and a high charge-injection capacity for functional electro-stimulation is desirable for the fabrication of implantable microelectrode arrays that aim to restore impaired or lost neurological functions in humans. For this purpose, we have investigated the electrochemical properties of sputtered ruthenium oxide (RuOx) electrode coatings deposited on planar microelectrode arrays, using an inorganic model of interstitial fluid (model-ISF) at 37 °C as the electrolyte. Through a combination of cyclic voltammetry (CV) and an electrochemical impedance spectroscopy (EIS) modelling study, we have established the contribution of the faradaic reaction as the major charge-injection contributor within the safe neural stimulation potential window of ±0.6 V vs. Ag|AgCl. We have also established the reversibility of the charge-injection process for sputtered RuOx film, by applying constant charge-per-phase current stimulations at different pulse widths, and by comparing the magnitudes of the leading and trailing access voltages during voltage transient measurements. Finally, the impedance of the sputtered RuOx film was found to be reasonably comparable in both its oxidized and reduced states, although the electronic contribution from the capacitive double-layer was found to be slightly higher for the completely oxidized film around 0.6 V than for its reduced counterpart around −0.6 V.

Engineering graphene-based electrodes for optical neural stimulation.

Graphene-based materials (GBMs) have been investigated in recent years with the aim of developing flexible interfaces to address a range of neurological disorders, where electrical stimulation may improve brain function and tissue regeneration. The recent discovery that GBM electrodes can generate an electrical response upon light exposure has inspired the development of non-genetic approaches capable of selectively modulating brain cells without genetic manipulation (i.e., optogenetics). Here, we propose the conjugation of graphene with upconversion nanoparticles (UCNPs), which enable wireless transcranial activation using tissue-penetrating near-infrared (NIR) radiation. Following a design of experiments approach, we first investigated the influence of different host matrices and dopants commonly used to synthesize UCNPs in the electrical response of graphene. Two UCNP formulations achieving optimal enhancement of electrical conductivity upon NIR activation at λ = 780 or 980 nm were identified. These formulations were then covalently attached to graphene nanoplatelets following selective hydroxyl derivatization. The resulting nanocomposites were evaluated in vitro using SH-SY5Y human neuroblastoma cells. NIR activation at λ = 980 nm promoted cell proliferation and downregulated neuronal and glial differentiation markers, suggesting the potential application of GBMs in minimally invasive stimulation of cells for tissue regeneration.

BIMMS: A versatile and portable system for biological tissue and electrode-tissue interface electrical characterization

The presented design is a low-cost, compact, and open-source USB-controlled platform for biological tissue and electrode-tissue interface electrical measurements, capable of potentiostatic and galvanostatic electrical impedance spectroscopy up to 10 MHz and cyclic voltammetry with voltage compliance of +−8 V and up to 2.4 mA while ensuring tissue-safety conditions. The data acquisition and generation are based on an Analog Discovery 2 platform (Digilent, USA). We provide accuracy analysis and comparisons with a commercially available calibrated impedance analyzer. Impedance measurements are demonstrated on implanted electrodes for neural stimulation and on an isolated ex-vivo calf brain as an example use case of the presented design.

ID:16079 The Importance of Instrumentation on Measurement of Safe Charge Injection Limits at Neural Stimulation Electrodes

The development of safe and efficacious neural stimulation protocols critically depends on the accurate assessment of charge injection limits that do not result in toxic byproducts of stimulation or evolution of oxygen/hydrogen gas at neural stimulation electrodes. Since the introduction of voltage transient or voltage excursion methods by Roblee et al. in 1990, this method has become a standard used by pre-clinical researchers for understanding the charge injection limits of different materials or electrode geometries. It has also become an important part of safety testing for clinical devices and common requirement by FDA reviewers in assessing device safety. Although voltage transient measurements have been commonly applied across neural engineering, assessment of charge injection limits in the presence of baseline voltage offsets at the stimulation electrode has been inconsistent across the literature. Additionally, voltage transient measurements have provided results for safe charge injection limits that are inconsistent with charge injection capacities measured using slow scan cyclic voltammetry as well as with in vitro and in vivo testing. These inconsistencies highlight the need for developing well validated methods for accurate assessment of charge injection limits across studies.

Harnessing the 2D Structure-Enabled Viscoelasticity of Graphene-Based Hydrogel Membranes for Chronic Neural Interfacing.

Stiffness and viscoelasticity of neural implants regulate the foreign body response. Recent studies have suggested the use of elastic or viscoelastic materials with tissue-like stiffness for long-term neural electrical interfacing. Herein, the authors find that a viscoelastic multilayered graphene hydrogel (MGH) membrane, despite exhibiting a much higher Young's modulus than nerve tissues, shows little inflammatory response after 8-week implantation in rat sciatic nerves. The MGH membrane shows significant viscoelasticity due to the slippage between graphene nanosheets, facilitating its seamless yet minimally compressive interfacing with nerves to reduce the inflammation caused by the stiffness mismatch. When used as neural stimulation electrodes, the MGH membrane can offer abundant ion-accessible surfaces to bring a charge injection capacity 1-2 orders of magnitude higher than its traditional Pt counterpart, and further demonstrates chronic neural therapy potential in low-voltage modulation of rat blood pressure. This work suggests that the emergence of 2D nanomaterials and particularly their unique structural attributes can be harnessed to enable new bio-interfacing design strategies.

Electrophoretic Deposition of Platinum Nanoparticles using Ethanol-Water Mixtures Significantly Reduces Neural Electrode Impedance

Platinum electrodes are critical components in many biomedical devices, an important example being implantable neural stimulation or recording electrodes. However, upon implantation, scar tissue forms around the electrode surface, causing unwanted deterioration of the electrical contact. We demonstrate that sub-monolayer coatings of platinum nanoparticles (PtNPs) applied to 3D neural electrodes by electrophoretic deposition (EPD) can enhance the electrode's active surface area and significantly lower its impedance. In this work we use ethanol-water mixtures as the EPD solvent, in contrast to our previous studies carried out in water. We show that EPD coating in 30 vol.% ethanol improves the device's electrochemical performance. Computational mesoscale multiparticle simulations were for the first time applied to PtNP-on-Pt EPD, revealing correlations between ethanol concentration, electrochemical properties, and coating homogeneity. Thereto, this optimum ethanol concentration (30 vol.%) balances two opposing trends: (i) the addition of ethanol reduces water splitting and gas bubble formation, which benefits surface coverage, and (ii) increased viscosity and reduced permittivity occur at high ethanol concentrations, which impair the coating quality and favoring clustering. A seven-fold increase in active surface area and significantly reduced in vitro impedance of the nano-modified neural stimulation electrode surfaces highlight the influence of ethanol-water mixtures in PtNP EPD.

Electrodeposited Platinum Iridium Enables Microstimulation With Carbon Fiber Electrodes

Ultrasmall microelectrode arrays have the potential to improve the spatial resolution of microstimulation. Carbon fiber (CF) microelectrodes with cross-sections of less than 8 μm have been demonstrated to penetrate cortical tissue and evoke minimal scarring in chronic implant tests. In this study, we investigate the stability and performance of neural stimulation electrodes comprised of electrodeposited platinum-iridium (PtIr) on carbon fibers. We conducted pulse testing and characterized charge injection in vitro and recorded voltage transients in vitro and in vivo. Standard electrochemical measurements (impedance spectroscopy and cyclic voltammetry) and visual inspection (scanning electron microscopy) were used to assess changes due to pulsing. Similar to other studies, the application of pulses caused a decrease in impedance and a reduction in voltage transients, but analysis of the impedance data suggests that these changes are due to surface modification and not permanent changes to the electrode. Comparison of scanning electron microscope images before and after pulse testing confirmed electrode stability.

Development and Characterization of Novel Conductive Sensing Fibers for In Vivo Nerve Stimulation.

Advancements in electrode technologies to both stimulate and record the central nervous system’s electrical activities are enabling significant improvements in both the understanding and treatment of different neurological diseases. However, the current neural recording and stimulating electrodes are metallic, requiring invasive and damaging methods to interface with neural tissue. These electrodes may also degrade, resulting in additional invasive procedures. Furthermore, metal electrodes may cause nerve damage due to their inherent rigidity. This paper demonstrates that novel electrically conductive organic fibers (ECFs) can be used for direct nerve stimulation. The ECFs were prepared using a standard polyester material as the structural base, with a carbon nanotube ink applied to the surface as the electrical conductor. We report on three experiments: the first one to characterize the conductive properties of the ECFs; the second one to investigate the fiber cytotoxic properties in vitro; and the third one to demonstrate the utility of the ECF for direct nerve stimulation in an in vivo rodent model.

In Vitro Electrochemical Properties of Titanium Nitride Neural Stimulating and Recording Electrodes as a Function of Film Thickness and Voltage Biasing.

Thin film titanium nitride (TiN), with a geometric surface area of 2,000 μm2, was deposited on planar test structures with thicknesses of 95, 185, 315, and 645 nm. Electrochemical measurements of electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and voltage transient (VT) were performed. We found that impedance values decreased and charge storage and charge injection capacities increased with increasing film thicknesses. Additionally, applying a anodic bias to TiN can increase the charge injection of the film to nearly double that of a non-biased film.

Design and Fabrication of Blue LED-Integrated Graphene Electrodes for Neural Stimulation and Signal Recording

Design and Fabrication of Blue LED-Integrated Graphene Electrodes for Neural Stimulation and Signal Recording

Closed-Loop Plantar Cutaneous Augmentation by Electrical Nerve Stimulation Increases Ankle Plantarflexion During Treadmill Walking.

Ankle plantarflexion plays an important role in forward propulsion and anterior-posterior balance during locomotion. This component of gait is often critically impacted by neurotraumas and neurological diseases. We hypothesized that augmenting plantar cutaneous feedback, via closed-loop distal-tibial nerve stimulation, could increase ankle plantarflexion during walking. To test the hypothesis, one intact rat walked on a motorized treadmill with implanted electronic device and electrodes for closed-loop neural recording and stimulation. Constant-current biphasic electrical pulse train was applied to distal-tibial nerve, based on electromyogram recorded from the medial gastrocnemius muscle, to be timed with the stance phase. The stimulation current threshold to evoke plantar cutaneous feedback was set at 30 μA (1·T), based on compound action potential evoked by stimulation. The maximum ankle joint angle at plantarflexion, during the application of stimulation currents of 3.3·T and 6.6·T, respectively, was increased from 149.4° (baseline) to 165.4° and 161.6°. The minimum ankle joint angle at dorsiflexion was decreased from 59.4° (baseline) to 53.1°, during the application of stimulation currents of 3.3·T, but not changed by 6.6·T. Plantar cutaneous augmentation also changed other gait kinematic parameters. Stance duty factor was increased from 51.9% (baseline) to 65.7% and 64.0%, respectively, by 3.3·T and 6.6·T, primarily due to a decrease in swing duration. Cycle duration was consistently decreased by the stimulation. In the control trial after two stimulation trials, a strong after-effect was detected in overall gait kinematics as well as ankle plantarflexion, suggesting that this stimulation has the potential for producing long-term changes in gait kinematics.

Charge injection characteristics of sputtered ruthenium oxide electrodes for neural stimulation and recording.

We have studied the charge-injection characteristics and electrochemical impedance of sputtered ruthenium oxide (RuOx ) films as electrode coatings for neural stimulation and recording electrodes. RuOx films were deposited by reactive DC magnetron sputtering, using a combination of water vapor and oxygen gas as reactive plasma constituents. The cathodal charge storage capacity of planar RuOx electrodes was found to be 54.6 ± 9.5mC/cm2 (mean ± SD, n=12), and the charge-injection capacity in a 0.2-ms cathodal current pulse was found to be 7.1 ± 0.3mC/cm2 (mean ± SD, n=15) at 0.6V positive bias versus Ag|AgCl, in phosphate buffer saline at room temperature for ~250 nm thick films. In general, the RuOx films exhibited high charge-injection capacities, with or without a positive interpulse bias, comparable to sputtered iridium oxide (SIROF) coatings. The charge-injection capacity increased monotonically with film thickness from 120 to 630 nm, and reached 11.30 ± 0.34 mC/cm2 (mean ± SD, n=5) at 0.6V bias versus Ag|AgCl at 630 nm film thickness. In addition, RuOx films showed minimal changes in electrochemical characteristics over 1.5 billion cycles of constant current pulsing at a charge density of 408 μC/cm2 (8nC/phase, 200 μs pulse width). The findings of low-impedance, high charge-injection capacity, and long-term pulsing stability suggest the suitability of RuOx as a comparatively inexpensive and favorable choice of electrode material for neural stimulation and recording.

Neural and electromyography PEDOT electrodes for invasive stimulation and recording

The conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) is increasingly used for implantable electrodes. This review discusses the key aspects of PEDOT-based implantable electrodes for neural recording, stimulation and electromyography.

Electrochemistry of Graphene Nanoplatelets Printed Electrodes for Cortical Direct Current Stimulation.

Possible risks stemming from the employment of novel, micrometer-thin printed electrodes for direct current neural stimulation are discussed. To assess those risks, electrochemical methods are used, including cyclic voltammetry, square-wave voltammetry, and electrochemical impedance spectroscopy. Experiments were conducted in non-deoxidized phosphate-buffered saline to better emulate living organism conditions. Since preliminary results obtained have shown unexpected oxidation peaks in 0–0.4 V potential range, the source of those was further investigated. Hypothesized redox activity of printing paste components was disproven, supporting further development of proposed fabrication technology of stimulating electrodes. Finally, partial permeability and resulting electrochemical activity of underlying silver-based printed layers of the device were pointed as the source of potential tissue irritation or damage. Employing this information, electrodes with corrected design were investigated, yielding no undesired redox processes.

Activated iridium oxide film (AIROF) electrodes for neural tissue stimulation

Objective. Iridium oxide films are commonly used as a high charge-injection electrode material in neural devices. Yet, few studies have performed in-depth assessments of material performance versus film thickness, especially for films grown on three-dimensional (instead of planar) metal surfaces in neutral pH electrolyte solutions. Further, few studies have investigated the driving voltage requirements for constant-current stimulation using activated iridium oxide (AIROF) electrodes, which will be a key constraint for future use in wirelessly powered neural devices. Approach. In this study, iridium microwire probes were activated by repeated potential pulsing in room temperature phosphate buffered saline (pH 7.1–7.3). Electrochemical measurements were recorded in three different electrolyte conditions for probes with different geometric surface areas (GSAs) as the AIROF thickness was increased. Main results. Maintaining an anodic potential bias during the inter-pulse interval was required for AIROF electrodes to deliver charge levels considered necessary for neural stimulation. Potential pulsing for 100–200 cycles was sufficient to achieve charge injection levels of 2.5 mC cm−2 (50 nC/phase in a biphasic pulse) in PBS with 2000 µm2 iridium probes. Increasing the electrode surface area to 3000 µm2 and 4000 µm2 significantly increased charge-injection capacity, reduced the driving voltage required to deliver a fixed amount of charge, and reduced polarization of the electrodes during constant-current pulsing. Significance. This study establishes methods for choosing an activation protocol and a desired GSA for three-dimensional iridium electrodes suitable for neural tissue insertion and stimulation, and provides guidelines for evaluating electrochemical performance of AIROF using model saline solutions.

Laminin coated diamond electrodes for neural stimulation

The performance of many implantable neural stimulation devices is degraded due to the loss of neurons around the electrodes by the body's natural biological responses to a foreign material. Coating of electrodes with biomolecules such as extracellular matrix proteins is one potential route to suppress the adverse responses that lead to loss of implant functionality. Concurrently, however, the electrochemical performance of the stimulating electrode must remain optimal to continue to safely provide sufficient charge for neural stimulation. We have previously found that oxygen plasma treated nitrogen included ultrananocrystalline diamond coated platinum electrodes exhibit superior charge injection capacity and electrochemical stability for neural stimulation (Sikder et al., 2019). To fabricate bioactive diamond electrodes, in this work, laminin, an extracellular matrix protein known to be involved in inter-neuron adhesion and recognition, was used as an example biomolecule. Here, laminin was covalently coupled to diamond electrodes. Electrochemical analysis found that the covalently coupled films were robust and resulted in minimal change to the charge injection capacity of diamond electrodes. The successful binding of laminin and its biological activity was further confirmed using primary rat cortical neuron cultures, and the coated electrodes showed enhanced cell attachment densities and neurite outgrowth. The method proposed in this work is versatile and adaptable to many other biomolecules for producing bioactive diamond electrodes, which are expected to show reduced the inflammatory responses in vivo.