Neural Stimulation Electrodes Research Articles

Electrochemical Characterization of As-Deposited and Oxygen-Functionalized Vertically Aligned Carbon Nanotubes for Use as a Neural Stimulation Electrode

not Available.

Contribution of Oxygen Reduction to Charge Injection on Platinum and Sputtered Iridium Oxide Neural Stimulation Electrodes

The extent to which oxygen reduction occurs on sputtered iridium oxide (SIROF) and platinum neural stimulation electrodes was quantified by cyclic voltammetry and voltage-transient measurements in oxygen-saturated physiological saline. Oxygen reduction was the dominant charge-admittance reaction on platinum electrodes during slow-sweep-rate cyclic voltammetry, contributing approximately 12 mC/cm(2) (88% of total charge) to overall cathodal charge capacity. For a 300-nm-thick SIROF electrode, oxygen reduction was a minor reaction contributing 1.3 mC/cm(2), approximately 3% of total charge. During current pulsing with platinum electrodes, oxygen reduction was observed at a level of 7% of the total injected charge. There was no indication of oxygen reduction on pulsed SIROF electrodes. A sweep-rate-dependent contribution of oxygen reduction was observed on penetrating SIROF microelectrodes (nominal surface area 2000 microm(2)) and is interpreted in terms of rate-limited diffusion of oxygen in electrolyte that penetrates the junction between the insulation and electrode shaft. For typical neural stimulation pulses, no oxygen reduction could be observed on penetrating SIROF microelectrodes. Based on the in vivo concentration of dissolved oxygen, it is estimated that oxygen reduction on platinum microelectrodes will contribute less than 0.5% of the total injected charge and considerably less on SIROF electrodes.

Electrochemical Analysis of Diamond and Platinum Electrodes for Neural Stimulation

not Available.

Analysis of high-perimeter planar electrodes for efficient neural stimulation

Planar electrodes are used in epidural spinal cord stimulation and epidural cortical stimulation. Electrode geometry is one approach to increase the efficiency of neural stimulation and reduce the power required to produce the level of activation required for clinical efficacy. Our hypothesis was that electrode geometries that increased the variation of current density on the electrode surface would increase stimulation efficiency. High-perimeter planar disk electrodes were designed with sinuous (serpentine) variation in the perimeter. Prototypes were fabricated that had equal surface areas but perimeters equal to two, three or four times the perimeter of a circular disk electrode. The interface impedance of high-perimeter prototype electrodes measured in vitro did not differ significantly from that of the circular electrode over a wide range of frequencies. Finite element models indicated that the variation of current density was significantly higher on the surface of the high-perimeter electrodes. We quantified activation of 100 model axons randomly positioned around the electrodes. Input–output curves of the percentage of axons activated as a function of stimulation intensity indicated that the stimulation efficiency was dependent on the distance of the axons from the electrode. The high-perimeter planar electrodes were more efficient at activating axons a certain distance away from the electrode surface. These results demonstrate the feasibility of increasing stimulation efficiency through the design of novel electrode geometries.

Sputtered iridium oxide films for neural stimulation electrodes

Sputtered iridium oxide films (SIROFs) deposited by DC reactive sputtering from an iridium metal target have been characterized in vitro for their potential as neural recording and stimulation electrodes. SIROFs were deposited over gold metallization on flexible multielectrode arrays fabricated on thin (15 microm) polyimide substrates. SIROF thickness and electrode areas of 200-1300 nm and 1960-125,600 microm(2), respectively, were investigated. The charge-injection capacities of the SIROFs were evaluated in an inorganic interstitial fluid model in response to charge-balanced, cathodal-first current pulses. Charge injection capacities were measured as a function of cathodal pulse width (0.2-1 ms) and potential bias in the interpulse period (0.0 to 0.7 V vs. Ag|AgCl). Depending on the pulse parameters and electrode area, charge-injection capacities ranged from 1-9 mC/cm(2), comparable with activated iridium oxide films (AIROFs) pulsed under similar conditions. Other parameters relevant to the use of SIROF on nerve electrodes, including the thickness dependence of impedance (0.05-10(5) Hz) and the current necessary to maintain a bias in the interpulse region were also determined.

Neural Stimulation and Recording Electrodes

Electrical stimulation of nerve tissue and recording of neural electrical activity are the basis of emerging prostheses and treatments for spinal cord injury, stroke, sensory deficits, and neurological disorders. An understanding of the electrochemical mechanisms underlying the behavior of neural stimulation and recording electrodes is important for the development of chronically implanted devices, particularly those employing large numbers of microelectrodes. For stimulation, materials that support charge injection by capacitive and faradaic mechanisms are available. These include titanium nitride, platinum, and iridium oxide, each with certain advantages and limitations. The use of charge-balanced waveforms and maximum electrochemical potential excursions as criteria for reversible charge injection with these electrode materials are described and critiqued. Techniques for characterizing electrochemical properties relevant to stimulation and recording are described with examples of differences in the in vitro and in vivo response of electrodes.

Chapter 11 Light‐Activated Ion Channels for Remote Control of Neural Activity

Light-activated ion channels provide a new opportunity to precisely and remotely control neuronal activity for experimental applications in neurobiology. In the past few years, several strategies have arisen that allow light to control ion channels and therefore neuronal function. Light-based triggers for ion channel control include caged compounds, which release active neurotransmitters when photolyzed with light, and natural photoreceptive proteins, which can be expressed exogenously in neurons. More recently, a third type of light trigger has been introduced: a photoisomerizable tethered ligand that directly controls ion channel activity in a light-dependent manner. Beyond the experimental applications for light-gated ion channels, there may be clinical applications in which these light-sensitive ion channels could prove advantageous over traditional methods. Electrodes for neural stimulation to control disease symptoms are invasive and often difficult to reposition between cells in tissue. Stimulation by chemical agents is difficult to constrain to individual cells and has limited temporal accuracy in tissue due to diffusional limitations. In contrast, ion channels that can be directly activated with light allow control with unparalleled spatial and temporal precision. The goal of this chapter is to describe light-regulated ion channels and how they have been tailored to control different aspects of neural activity, and how to use these channels to manipulate and better understand development, function, and plasticity of neurons and neural circuits.

Matrix-addressable, active electrode arrays for neural stimulation using organic semiconductors—cytotoxicity and pilot experiments in vivo

Organic field effect transistors can be integrated into micromachined polyimide-based neural stimulation electrode arrays in order to build active switching matrices. With this approach, a matrix of N × M electrode contacts requires only N + M interconnects to a stimulator when active switching elements are used instead of N × M interconnects. In this paper, we demonstrated that pentacene-based organic field effect transistors (OFETs) can be used to drive stimulation currents through neural electrodes in a physiological-like environment. In order to prove the general applicability as an implant material, the cytotoxicity of pentacene was evaluated with respect to potential effects on cell viability. The results of these tests indicate that extracts from pentacene inhibit neither proliferation nor metabolism of the tested mouse fibroblasts. However, some effect on cell spreading was observed when cells were in direct contact to pentacene for 48 h. In pilot experiments it was demonstrated for the very first time that pentacene transistors can be used as switching elements, acting as voltage-controlled current sources, capable of driving currents suitable for electrical stimulation of a peripheral nerve via a tripolar cuff electrode.

Finite Element Analysis of a Floating Microstimulator

Analytical solutions for voltage fields in a volume conductor are available only for ideal electrodes with radially symmetric contacts and infinitely extending substrates. Practical electrodes for neural stimulation may have asymmetric contacts and finite substrate dimensions and hence deviate from the ideal geometries. For instance, it needs to be determined if the analytical solutions are adequate for simulations of narrow shank electrodes where the substrate width is comparable to the size of the contacts. As an extension to this problem, a "floating" stimulator can be envisioned where the substrate would be finite in all directions. The question then becomes how small this floating stimulator can be made before its stimulation strength is compromised by the decrease in the medium impedance between the contacts as the contacts are approaching each other. We used finite element modeling to solve the voltage and current profiles generated by these radially asymmetric electrode geometries in a volume conductor. The simulation results suggest that both the substrate size and the bipolar contact separation influence the voltage field when these parameters are as small as a few times the contact size. Both of these effects are larger for increasing elevations from the contact surface, and even stronger for floating electrodes (finite substrate in all directions) than the shank-type electrodes. Location of the contacts on the floating electrode also plays a role in determining the voltage field. The voltage field for any device size and current, and any specific resistance of the volume conductor can be predicted from these results so long as the aspect ratios are preserved.

The influence of electrolyte composition on the in vitro charge-injection limits of activated iridium oxide (AIROF) stimulation electrodes

The effects of ionic conductivity and buffer concentration of electrolytes used for in vitro measurement of the charge-injection limits of activated iridium oxide (AIROF) neural stimulation electrodes have been investigated. Charge-injection limits of AIROF microelectrodes were measured in saline with a range of phosphate buffer concentrations from [PO43−] = 0 to [PO43−] = 103 mM and ionic conductivities from 2–28 mS cm−1. The charge-injection limits were insensitive to the buffer concentration, but varied significantly with ionic conductivity. Using 0.4 ms cathodal current pulses at 50 Hz, the charge-injection limit increased from 0.5 mC cm−2 to 2.1 mC cm−2 as the conductivity was increased from 2 mS cm−1 to 28 mS cm−1. An explanation is proposed in which the observed dependence on ionic conductivity arises from non-uniform reduction and oxidation within the porous AIROF and from uncorrected iR-drops that result in an overestimation of the redox potential during pulsing. Conversely, slow-sweep-rate cyclic voltammograms (CVs) were sensitive to buffer concentration with the potentials of the primary Ir3+/Ir4+ reduction and oxidation reactions shifting ∼300 mV as the buffer concentration decreased from [PO43−] = 103 mM to [PO43−] = 0 mM. The CV response was insensitive to ionic conductivity. A comparison of in vitro AIROF charge-injection limits in commonly employed electrolyte models of extracellular fluid revealed a significant dependence on the electrolyte, with more than a factor of 4 difference under some pulsing conditions, emphasizing the need to select an electrolyte model that closely matches the conductivity and ionic composition of the in vivo environment.

Fabrication and evaluation of conductive elastomer electrodes for neural stimulation

This study explored the feasibility of applying nanocomposites derived from conducting organic polymers and silicone elastomers to fabricate electrodes for neural stimulation. A novel combination of nanoparticulate polypyrrole polymerized within a processable elastomeric silicone host polymer was evaluated in vitro and in vivo. The electrical properties of the elastomeric conductors were strongly dependent on their composition, and mixtures were identified that provided high and stable conductivity. Methods were developed for incorporating conductive polymer–siloxane co-polymer nanocomposite and silicone insulating polymers into thin-layered structures for simple single-poled electrode fabrication. In vitro testing revealed that the materials were stable under continuous pulsing for at least 10 days. Single contact prototype nerve cuff electrodes were fabricated and device functionality was demonstrated in vivo following acute implantation. The results of this study demonstrate the feasibility of conductive elastomers for peripheral nerve stimulating electrodes. Matching the mechanical properties of cuff electrode to those of the underlying neural tissue is expected to improve the long-term tissue response to the presence of the electrode.

Neurotrophin‐eluting hydrogel coatings for neural stimulating electrodes

Improved sensory and motor prostheses for the central nervous system will require large numbers of electrodes with low electrical thresholds for neural excitation. With the eventual goal of reducing stimulation thresholds, we have investigated the use of biodegradable, neurotrophin-eluting hydrogels (i.e., poly(ethylene glycol)-poly(lactic acid), PEGPLA) as a means of attracting neurites to the surface of stimulating electrodes. PEGPLA hydrogels with release rates ranging from 1.5 to 3 weeks were synthesized. These hydrogels were applied to multielectrode arrays with sputtered iridium oxide charge-injection sites. The coatings had little impact on the iridium oxide electrochemical properties, including charge storage capacity, impedance, and voltage transients during current pulsing. Additionally, we quantitatively examined the ability of neurotrophin-eluting, PEGPLA hydrogels to promote neurite extension in vitro using a PC12 cell culture model. Hydrogels released neurotrophin (nerve growth factor, NGF) for at least 1 week, with neurite extension near that of an NGF positive control and much higher than extension seen from sham, bovine serum albumin-releasing boluses, and a negative control. These results show that neurotrophin-eluting hydrogels can be applied to multielectrode arrays, and suggest a method to improve neuron-electrode proximity, which could result in lowered electrical stimulation thresholds. Reduced thresholds support the creation of smaller electrode structures and high density electrode prostheses, greatly enhancing prosthesis control and function.

Potential-Biased, Asymmetric Waveforms for Charge-Injection With Activated Iridium Oxide (AIROF) Neural Stimulation Electrodes

The use of potential biasing and biphasic, asymmetric current pulse waveforms to maximize the charge-injection capacity of activated iridium oxide (AIROF) microelectrodes used for neural stimulation is described. The waveforms retain overall zero net charge for the biphasic pulse, but employ an asymmetry in the current and pulse widths of each phase, with the second phase delivered at a lower current density for a longer period of time than the leading phase. This strategy minimizes polarization of the AIROF by the charge-balancing second phase and permits the use of a more positive anodic bias for cathodal-first pulsing or a more negative cathodic bias for anodal-first pulsing to maximize charge injection. Using 0.4-ms cathodal-first pulses, a maximum charge-injection capacity of 3.3 mC/cm2 was obtained with an 0.6-V bias (versus Ag/AgCl) and a pulse asymmetry of 1:8 in the cathodal and anodal pulse widths. For anodal-first pulsing, a maximum charge capacity of 9.6 mC/cm2 was obtained with an asymmetry of 1:3 at an 0.1-V bias. These measurements were made in vitro in carbonate-buffered saline using microelectrodes with a 2000 microm2 surface area.

Fabrication and Characterization of Platinum-Iridium Electrodes with Micro-Structured Surfaces For Neural Stimulation Applications

AbstractControlled structuring of electrode surfaces on a microscopic scale is expected to decrease the impedance and improve the current injection capabilities of neural stimulation electrodes. We have identified conditions for the fabrication of micro-bumps on platinum-iridium alloy surfaces by means of KrF excimer laser (λ=248nm) irradiation under ambient conditions. A regular array of closely spaced micro-bumps with diameters of about 5µm and heights of about 3µm was generated on the polished face of a platinum-20%iridium wire with a diameter of 75µm. A projection system with a demagnification factor of 9 was used to image a mask with a pattern of circular-holes on the polished face of the wire. Several thousand pulses at a repetition rate of 10Hz and a fluence of 3.0 J/cm2 were applied to produce the micro-bumps. The modified electrode surfaces were studied by optical microscopy and scanning electron microscopy, and the results show the formation of micro-bumps of reproducible shape. Simple two-electrode AC impedance measurements in physiological saline in the frequency range of interest to neural stimulation applications show a considerable decrease in the impedance of micro-structured electrodes with respect to the impedance of a polished electrode.

A study of intra-cochlear electrodes and tissue interface by electrochemical impedance methods in vivo

This paper presents methods, results and analysis for measurements of the electrochemical impedance of platinum electrodes (∼0.43 mm 2) over a 6-month implantation in the cat cochlea. The study aimed to improve our understanding of the effects of tissue response on impedance behaviour. An increase in impedance in the post-operative period was evident with a rise of the distorted arc at high frequencies in the complex plane, correlating to anomalous charge transport at the electrode–tissue interface. The impedance at low frequencies generally showed a capacitive dispersion modelled as a constant phase element, indicating a blocking characteristic of the electrodes. The study suggests that a reduction and changes in composition of perilymph or extracellular fluid adjacent to the electrodes, as a consequence of tissue response, causes the elevated “contact impedance”. This affects the efficiency and quality of neural stimulating electrodes and neural recording electrodes. The finding of the crucial role of perilymph or extracellular fluid thin layer provides a new strategy for surface materials of neural electrodes, which is discussed in the paper. The interface characteristics must be considered during interpretation of studies undertaken in vitro or in acute experiments in vivo, where physiological fluid is abundant.

Electrochemical response of iridium oxide for implanted neural stimulating electrodes

The electrochemical behaviour of Ir oxide films, grown in neutral PBS saline solution has been examined in relation to their use as neural stimulating electrodes. It is shown that, if adequate growing conditions are chosen, this material is suitable for use as a neural prosthesis, since it is able to pass high values of charge density in a very reversible way, therefore without generating new products to the solution.

Non-invasive measurement of the input-output properties of peripheral nerve stimulating electrodes

A non-invasive method was developed to determine the input-output ( I O ) properties of peripheral nerve stimulating electrodes. An apparatus was fabricated to measure the 3-dimensional (3-D) isometric torque generated at the cat ankle joint by electrical activation of the sciatic nerve. The performance of the apparatus was quantified, and the utility of the method was demonstrated by measuring the recruitment properties of multiple contact nerve cuff electrodes. Torque-twitch waveforms, recruitment curves of peak torque as a function of stimulus current amplitude, and 2-D joint torque vectors were used to analyze the recruitment properties of the cuff. The peak of the twitch torque was an accurate measure of excitation even for muscles having fibers with varying speeds of contraction. The evoked twitch waveforms and torque vectors generated by selective stimulation of individual nerve branches with a hook electrode were compared to those produced by stimulation of the nerve trunk with the cuff electrode. These data allowed determination of the regions of the nerve trunk were activated by different electrode geometries and stimulus parameters. The positional stability of electrode recruitment properties could be quantified by measuring I O characteristics at different limb positions. The methods described are useful for characterization of neural stimulating electrodes and for studies of motor system physiology.

Integrity of ultramicro-stimulation electrodes determined from electrochemical measurements

Methods to control the quality of stimulation electrodes for human patients are desirable. The results of a comparative electrochemical evaluation of three types of ultramicroelectrodes presently used for neural stimulation are discussed. The iridium electrodes examined were fabricated from iridium wire or by thin film technology. Electrochemical protocols based on single cyclic voltammetry are proposed for quality control. Defective insulator-conductor seals have been modelled and the simulation provides the basis for the protocol. The porous metal produced by thin film methodology is detected. The consequences of these defective structures for activation to hydrous iridium oxide coated electrodes for neural stimulation are discussed.

The Pulse‐Clamp Method for Analyzing the Electrochemistry on Neural Stimulating Electrodes

A pulse‐clamp method has been developed for measuring the electrochemical processes occurring on neural stimulating electrodes in the 100 μs time frame of a typical stimulus pulse. By immediately following the controlled current stimulus pulse with a controlled potential step back to the prestimulus potential, we can measure the reversal of the reversible reactions that occurred during the stimulus pulse. Using this information we can then deduce the reaction that occurred during the stimulus pulse and how much charge went into each process. This method employs an electronic instrument that can be operated in (i) regulated current mode, (ii) regulated voltage mode, and (iii) open‐circuit mode with a switching time of 2 μs between modes. The frequency response of the instrument is linear up to 105 Hz, permitting reliable measurements in the 10 μs range. A series of experiments are described for 100 μs pulses applied to gold electrodes in 0.15M sulfuric acid. The results of these experiments show that: (i) the kinetics of the electrochemical reactions occurring on an electrode surface cannot be neglected and (ii) limiting the electrode potential to not exceed the evolution potential, determined with slow cyclic voltammetry, significantly underestimates the charge that can be injected without evolving .

The Pulse-Clamp method for analyzing neural stimulating electrodes

The Pulse-Clamp method for analyzing neural stimulating electrodes