Neural Stimulation Electrodes Research Articles

Photoresist-less patterning of silicone substrates for thick film deposition

Traditionally, fabrication processes to produce microelectrode arrays for neural stimulating electrodes have employed photolithography and a photoresist layer to produce a pattern on a substrate which subsequently has a metal layer deposited. The deposited metal layer is then used to create stimulating electrodes that will ultimately be in close contact with neural tissue. While the process enables accurate fabrication at a reasonable cost, the use of photoresist in the process presents a number of issues. Photoresist is a contamination risk with the potential for chemicals to be absorbed into the silicone, which will then subsequently be in close proximity to neural structures, introducing a risk of toxicity. In addition, due to the use of flexible substrates such as silicone elastomer, patterning of films greater than 1μm thick can be difficult.Whilst an obvious solution would be to avoid using photoresist in the fabrication process, few alternatives have been systematically investigated. We investigated use of shadow masks fabricated from glass, brass and silicone elastomer, and exploitation of the natural tackiness of the silicone substrate for mask adhesion. All three mask materials attached well to silicone, but each presented differing degrees of difficulty during alignment and mask removal.Subsequently, thin gold films (∼20nm) and thick platinum films (∼8μm) were deposited on the silicone substrates using the shadow masks. We discuss the mask fabrication, pattern definition, the difficulties which arose, and the benefits of using shadow masks for the fabrication of medical devices.

Coatings of nanostructured pristine graphene-IrOx hybrids for neural electrodes: Layered stacking and the role of non-oxygenated graphene.

The need to enhance charge capacity in neural stimulation-electrodes is promoting the formation of new materials and coatings. Among all the possible types of graphene, pristine graphene prepared by graphite electrochemical exfoliation, is used in this work to form a new nanostructured IrOx-graphene hybrid (IrOx-eG). Graphene is stabilized in suspension by IrOx nanoparticles without surfactants. Anodic electrodeposition results in coatings with much smaller roughness than IrOx-graphene oxide. Exfoliated pristine graphene (eG), does not electrodeposit in absence of iridium, but IrOx-nanoparticle adhesion on graphene flakes drives the process. IrOx-eG has a significantly different electronic state than graphene oxide, and different coordination for carbon. Electron diffraction shows the reflection features expected for graphene. IrOx 1-2 nm cluster/nanoparticles are oxohydroxo-species and adhere to 10nm graphene platelets. eG induces charge storage capacity values five times larger than in pure IrOx, and if calculated per carbon atom, this enhancement is one order magnitude larger than the induced by graphene oxide. IrOx-eG coatings show optimal in vitro neural cell viability and function as cell culture substrates. The fully straightforward electrochemical exfoliation and electrodeposition constitutes a step towards the application of graphene in biomedical systems, expanding the knowledge of pristine graphene vs. graphene oxide, in bioelectrodes.

Soft, Flexible Freestanding Neural Stimulation and Recording Electrodes Fabricated from Reduced Graphene Oxide

There is an urgent need for conductive neural interfacing materials that exhibit mechanically compliant properties, while also retaining high strength and durability under physiological conditions. Currently, implantable electrode systems designed to stimulate and record neural activity are composed of rigid materials such as crystalline silicon and noble metals. While these materials are strong and chemically stable, their intrinsic stiffness and density induce glial scarring and eventual loss of electrode function in vivo. Conductive composites, such as polymers and hydrogels, have excellent electrochemical and mechanical properties, but are electrodeposited onto rigid and dense metallic substrates. In the work described here, strong and conductive microfibers (40–50 μm diameter) wet‐spun from liquid crystalline dispersions of graphene oxide are fabricated into freestanding neural stimulation electrodes. The fibers are insulated with parylene‐C and laser‐treated, forming “brush” electrodes with diameters over 3.5 times that of the fiber shank. The fabrication method is fast, repeatable, and scalable for high‐density 3D array structures and does not require additional welding or attachment of larger electrodes to wires. The electrodes are characterized electrochemically and used to stimulate live retina in vitro. Additionally, the electrodes are coated in a water‐soluble sugar microneedle for implantation into, and subsequent recording from, visual cortex.

Ultrananocrystalline diamond-CMOS device integration route for high acuity retinal prostheses.

High density electrodes are a new frontier for biomedical implants. Increasing the density and the number of electrodes used for the stimulation of retinal ganglion cells is one possible strategy for enhancing the quality of vision experienced by patients using retinal prostheses. The present work presents an integration strategy for a diamond based, high density, stimulating electrode array with a purpose built application specific integrated circuit (ASIC). The strategy is centered on flip-chip bonding of indium bumps to create high count and density vertical interconnects between the stimulator ASIC and an array of diamond neural stimulating electrodes. The use of polydimethylsiloxane (PDMS) housing prevents cross-contamination of the biocompatible diamond electrode with non-biocompatible materials, such as indium, used in the microfabrication process. Micro-imprint lithography allowed edge-to-edge micro-scale pattering of the indium bumps on non-coplanar substrates that have a form factor that can conform to body organs and thus are ideally suited for biomedical applications. Furthermore, micro-imprint lithography ensures the compatibility of lithography with the silicon ASIC and aluminum contact pads. Although this work focuses on 256 stimulating diamond electrode arrays with a pitch of 150μm, the use of indium bump bonding technology and vertical interconnects facilitates implants with tens of thousands electrodes with a pitch as low as 10μm, thus ensuring validity of the strategy for future high acuity retinal prostheses, and bionic implants in general.

Large charge-storage-capacity iridium/ruthenium oxide coatings as promising material for neural stimulating electrodes

Electrochemical and topographical/structural/morphological properties of thermally prepared Ir/Ru-oxide coatings of various compositions formed on a Ti substrate were investigated. An apparent electrochemically active surface area (AEASA) and charge storage capacity (CSC) were determined. The freshly-prepared Ir0.6Ru0.4-oxide coating was found to offer the largest AEASA and CSC; however, after exposing all the coatings to prolonged extreme electrochemical cycling in phosphate buffered saline pH 7.4, within a 5 V potential window (“torturing”), the Ir0.8Ru0.2-oxide coating yielded both the largest AEASA (1540 cm2) and CSC (27 mC cm−2). Under the same experimental condition, the Ir0.8Ru0.2-oxide coating was found to yield by a 56% higher CSC than the current state-of-the-art neural stimulating electrode, Ir-oxide, making it a good candidate for further optimization and possible application as a neural stimulating electrode.

Investigating the Interfacial Properties of Electrochemically Roughened Platinum Electrodes for Neural Stimulation

Platinum electrodes have been electrochemically roughened (roughness factors up to 430) and evaluated for use as neural stimulation electrodes. The roughened electrodes show superior interfacial properties with increasing surface roughness. The roughened electrode (fR = 250) has a charge injection limit of 1.0 mC cm(-2) (400 μs pulse width), which is superior to that of titanium nitride (0.87 mC cm(-2)) but comparable to that of carbon nanotubes (1.0-1.6 mC cm(-2)). The surface roughness can also be optimized for different neural stimulation applications based on the available charge density at a particular pulse width of stimulation. The roughened platinum electrodes demonstrated good mechanical stability under harsh ultrasonication and electrochemical stability under continuous biphasic stimulation, indicating the potential of this biological interface to be safe and stable.

Optical and electrochemical methods for determining the effective area and charge density of conducting polymer modified electrodes for neural stimulation.

Neural stimulation is used in the cochlear implant, bionic eye, and deep brain stimulation, which involves implantation of an array of electrodes into a patient's brain. The current passed through the electrodes is used to provide sensory queues or reduce symptoms associated with movement disorders and increasingly for psychological and pain therapies. Poor control of electrode properties can lead to suboptimal performance; however, there are currently no standard methods to assess them, including the electrode area and charge density. Here we demonstrate optical and electrochemical methods for measuring these electrode properties and show the charge density is dependent on electrode geometry. This technique highlights that materials can have widely different charge densities but also large variation in performance. Measurement of charge density from an electroactive area may result in new materials and electrode geometries that improve patient outcomes and reduce side effects.

A feasible way for the fabrication of single walled carbon nanotube/polypyrrole composite film with controlled pore size for neural interface

Single walled carbon nanotube (SWNT)/polypyrrole (PPy) composite films with controlled pore size and strong adhesive force was prepared as electrode material for improving the performance of neural electrodes. SWNT film with controlled pore size was first fabricated through electrophoresis with a merit that the pore size can be well tuned by changing the concentration of metal ions in the electrolyte. An ultrathin conformal PPy layer around SWNT bundles in a uniform manner within the entire films was subsequently obtained by pulsed electropolymerization. The adhesion of the SWNT coated electrodes was tested by repeatedly inserting the coated electrode into agar gel to demonstrate the better adhesive force of the coating. Electrochemical results showed that the SWNT/PPy coated metal electrodes have much lower impedance and higher charge storage capacity than the bare metal substrates. Further in vitro culture of rat pheochromocytoma (PC12) cells revealed that the porous SWNT/PPy composite film was non-toxic and well supported the growth of neurons. We demonstrate that the prepared composite film has potential applications in chronic implantable neural electrodes for neural stimulation and recording.

Layer-by-layer assembled nanorough iridium-oxide/platinum-black for low-voltage microscale electrode neurostimulation

Electrical neural stimulating electrodes play an important role in medical applications and improving health/medical conditions. However, size reduction for low-invasive electrodes creates issues with high electrolyte/electrode interfacial impedance and low charge-injection characteristics, which makes it impossible to stimulate neurons/cells. To overcome these limitations, we propose an electrode material for low-voltage microscale electrode neurostimulation that combines the advantages of low impedance of iridium oxide (IrOx) with the enhanced surface area of platinum black (Pt-black). Based on a simple, rapid, low-temperature electroplating process, herein a low impedance and high charge-injection electrode is fabricated by a layer-by-layer assembly of IrOx/Pt-black with nanoscale roughness. The assembled nanorough-IrOx/Pt-black electrode has an impedance of 32 Ωcm2 at 1kHz and a charge-injection delivery capacity (QCDC) of 46.7mCcm−2, which are 0.5 and 2.4 times the values for the same-sized IrOx/flat-Pt electrode, respectively. The stimulation capability of the nanorough-IrOx/Pt-black plated microelectrode is confirmed by in vivo stimulations of the sciatic nerve of a mouse. The threshold voltages of 8-μm-diameter and 11-μm-diameter electrodes are 700mV and 300mV, respectively. However, increasing the diameter of high QCDC nanorough-IrOx/Pt-black can further reduce the stimulation voltage. Consequently, nanorough-IrOx/Pt-black is applicable to low-voltage microscale electrode neurostimulations for powerful in vivo/in vitro electrophysiological measurements.

Spectroscopic studies of electrophoretically deposited hybrid HAp/CNT coatings on titanium

Carbon nanotubes deposited on the surface of the metal can be used in a wide variety of applications for modern medicine including: sensors and sensor array devices, electrodes for neural system stimulation, scaffolds for improved healing process for bone defects. Additionally it is debated if deposited on the surface of e.g. endoprosthesis, CNT coating can significantly increase the strength of the tissue/bone joint and stimulate a fast integration of the implant and the tissue.The aim of this paper is the analysis of the electrophoretically deposited nanocomposite coating made of hydroxyapatite nanoparticles and carbon nanotubes on the surface of titanium. The paper concentrates on the analysis of the layer’s structure and its bioactivity properties. The nanocomposite films were investigated using Raman Spectroscopy as well as AFM and SEM microscopy. The measurements were conducted at every stage of layer preparation and after bioactivity test. Bioactivity was evaluated by in vitro test in Simulated Body Fluid (SBF, 37°C, for 30days). It was shown that hybrid HAp/CNT layers are very attractive materials for modification of the surface of metallic orthopedic implants.

Biocompatibility and electrochemical assessment of boron doped nanocrystalline diamond electrodes for neural stimulation

Event Abstract Back to Event Biocompatibility and electrochemical assessment of boron doped nanocrystalline diamond electrodes for neural stimulation Cristian P. Pennisi1*, Maria Alcaide1, Stavros Papaioannou1, Suzan Meijs2, Andy Taylor3, 4, Milos Nesladek5 and Vladimir Zachar1 1 Aalborg University, Dept. of Health Science and Technology, Denmark 2 Aalborg University, Dept. of Health Science and Technology, Denmark 3 ASCR, Institute of Physics, Czechia 4 NANO6, Czechia 5 University Hasselt, IMEC, Belgium Neural prostheses are devices that use electrical impulses to restore sensory or motor deficits following trauma or neurological diseases. In implanted devices, electrodes located in close proximity to the neural tissue are in charge of delivering the electrical impulses generated in a stimulation unit. The electrodes for neural stimulation possess one or various contact sites comprising a metal, such as platinum or iridium oxide, or a ceramic, such as titanium nitride (TiN). Although these are non-toxic materials with excellent electrochemical properties, many of the currently used designs display a compromised long-term performance as a result of the foreign body reaction. The growth of encapsulation tissue around the contact sites increases the distance between the electrode and neural cells over time. As a consequence, it is necessary to inject larger currents in order to achieve cell activation, which might exceed the potential at which oxidation and reduction of water takes place causing irreversible damage to the electrode and tissue. In recent years, nanocrystalline diamond (NCD) films have emerged as a unique class of biomaterials, which hold promise for the fabrication of neural electrodes due to their chemical inertness, biocompatibility and outstanding electrical properties (Pennisi and Alcaide, 2014). In this talk, a series of studies assessing the biocompatibility and electrochemical performance of boron doped NCD films for application in neural stimulation electrodes is described. The fabrication of boron doped NCD test substrates and electrodes by microwave chemical vapor deposition is presented. Furthermore, surface characterization of these substrates by Raman spectroscopy and atomic force microscopy is shown. Results of in vitro studies using the test substrates comprise protein adsorption, cytotoxicity, and cell proliferation and adhesion assays. These results are presented to describe the effects of the surface properties of the NCD films on the biological responses. We demonstrate that an increased surface roughness is crucial to significantly reduce adhesion and proliferation of fibroblasts on the NCD surfaces (Alcaide et al., 2014). The electrochemical performance and the in vivo biocompatibility of the boron doped NCD films are assessed using monopolar electrodes. It is shown that while electrical parameters such as impedance and charge injection capacity are similar to that of control TiN electrodes, NCD electrodes display a much wider water potential window, ranging from -1.7 to 1.4 V (Meijs et al.,2013). Data from the in vivo biocompatibility studies is also analyzed, consisting on the histological and histomorphometric assessment of the fibrous capsule after 2 and 4 weeks of subcutaneous implantation in a rat model. We show that implantation of NCD electrodes is associated with no signs of chronic inflammation and a very thin fibrous capsule, which after two weeks of implantation exhibit an average thickness of 25 μm. In summary, this talk presents data demonstrating that the proposed boron doped NCD electrodes can be safely operated within a wide potential window and cause a minimal foreign body reaction upon implantation. Taken together, these results indicate that boron doped NCD films represent a promising approach to mitigate the issues associated with fibrous encapsulation of neural stimulation electrodes Acknowledgements This work was supported by the EU through the project MERIDIAN (Micro and Nano Engineered Bi-Directional Carbon Interfaces for Advanced Peripheral Nervous System Prosthetics and Hybrid Bionics), contract n. 280778-02.

Structural characterization of platinum foil for neural stimulating electrodes.

The objective of this study was to investigate the structural properties of a cold-rolled platinum foil used to manufacture multi-electrode spiral nerve cuffs. To attain this objective, 0.03-mm-thick cold-rolled platinum foil strips with 99.99 wt% purity were used. The resistivity measurements were made using a 4-point probe technique in which the strips were subjected to dynamic annealing in an argon atmosphere. The stored energy of platinum was recorded in an argon atmosphere using differential scanning calorimetry (DSC). Finally, the microstructure of the strips was investigated by optical microscopy. In the resistivity measurements, a small change is observed at ~280°C. This change could be explained as the partial recovery elicited by the decrease of dislocation density. Above 500°C, a significant decrease in resistivity was recorded, and the decrease reached a maximum at ~750°C. These results are consistent with the recrystallization trend detected in DSC, namely the DSC measurement detected very weak heat release during recrystallization, which was actually accumulated during the cold-working. This exothermal peak occurred in the temperature range 380-800°C.

Performance of conducting polymer electrodes for stimulating neuroprosthetics

Objective. Recent interest in the use of conducting polymers (CPs) for neural stimulation electrodes has been growing; however, concerns remain regarding the stability of coatings under stimulation conditions. These studies examine the factors of the CP and implant environment that affect coating stability. The CP poly(ethylene dioxythiophene) (PEDOT) is examined in comparison to platinum (Pt), to demonstrate the potential performance of these coatings in neuroprosthetic applications. Approach. PEDOT is coated on Pt microelectrode arrays and assessed in vitro for charge injection limit and long-term stability under stimulation in biologically relevant electrolytes. Physical and electrical stability of coatings following ethylene oxide (ETO) sterilization is established and efficacy of PEDOT as a visual prosthesis bioelectrode is assessed in the feline model. Main results. It was demonstrated that PEDOT reduced the potential excursion at a Pt electrode interface by 72% in biologically relevant solutions. The charge injection limit of PEDOT for material stability was found to be on average 30× larger than Pt when tested in physiological saline and 20× larger than Pt when tested in protein supplemented media. Additionally stability of the coating was confirmed electrically and morphologically following ETO processing. It was demonstrated that PEDOT-coated electrodes had lower potential excursions in vivo and electrically evoked potentials (EEPs) could be detected within the visual cortex. Significance. These studies demonstrate that PEDOT can be produced as a stable electrode coating which can be sterilized and perform effectively and safely in neuroprosthetic applications. Furthermore these findings address the necessity for characterizing in vitro properties of electrodes in biologically relevant milieu which mimic the in vivo environment more closely.

Physico-chemical properties of the Ti5O9 Magneli phase with potential application as a neural stimulation electrode.

This work offers a description of the physico-chemical and electrochemical properties of one of the titanium-based Magneli phases, known as TinO2n-1, for its possible application as an electrode for neural tissue stimulation in neural disorders and Central Nervous System (CNS) injuries. Ti5O9 is one of the less-known Magneli phases that exhibits high electronic conductivity and high chemical and thermal inertness. The material, prepared in a reducing atmosphere by ceramic methods, is composed of a porous surface responsible for most of its properties. Chemical and physical features of the surface were studied with the aim of establishing a relationship between them and the surface electrochemistry. The chemical composition of the surface was studied by XRD and XPS. The topography was studied by AFM and the morphology of the outer side of a fracture was observed by SEM. The conductivity was measured by the four point method in DC finding extremely high values, 9500 S cm-1 at 37 °C. The study of the surface electrochemistry in contact with media, which simulate physiological conditions, was carried out by cyclic voltammetry and EIS. With these measurements the charge injection mechanism has been elucidated, and the charge storage capacity of the material has been determined, finding higher values than those reported for other ceramic electrodes. Finally, cell cultures realised with neural cells were obtained from the cerebral cortex of E18 Wistar rat embryos. They were observed after 4 and 10 DIV and helped in the determination of the biocompatibility of the material.

Analysis of fractal electrodes for efficient neural stimulation

Planar electrodes are increasingly used in therapeutic neural stimulation techniques such as functional electrical stimulation, epidural spinal cord stimulation (ESCS), and cortical stimulation. Recently, optimized electrode geometries have been shown to increase the efficiency of neural stimulation by increasing the variation of current density on the electrode surface. In the present work, a new family of modified fractal electrode geometries is developed to enhance the efficiency of neural stimulation. It is shown that a promising approach in increasing the neural activation function is to increase the “edginess” of the electrode surface, a concept that is explained and quantified by fractal mathematics. Rigorous finite element simulations were performed to compute electric potential produced by proposed modified fractal geometries. The activation of 256 model axons positioned around the electrodes was then quantified, showing that modified fractal geometries required a 22% less input power while maintaining the same level of neural activation. Preliminary in vivo experiments investigating muscle evoked potentials due to median nerve stimulation showed encouraging results, supporting the feasibility of increasing neural stimulation efficiency using modified fractal geometries.

Integration of pre-aligned liquid metal electrodes for neural stimulation within a user-friendly microfluidic platform.

Electrical stimulation of nervous tissue is used clinically for the treatment of multiple neurological disorders and experimentally for basic research. With the increase of optical probes to record neuronal activity, simple and user-friendly methods are desired to stimulate neurons and their subcellular compartments for biological experimentation. Here we describe the novel integration of liquid metal electrodes with microfluidic culture platforms to accomplish this goal. We integrated electrode and cell channels into a single poly(dimethylsiloxane) (PDMS) chip, eliminating entirely the need to align electrodes with microchannels. We designed the electrode channels such that the metal can be injected by hand and when the device is non-covalently bound to glass. We demonstrated the biocompatibility of the electrodes for long-term cultures (12 days) using hippocampal neurons. We demonstrated the use of these electrodes to depolarize neurons and recorded neuronal activity using the calcium indicator dye, Fluo-4. We established optimal stimulation parameters that induce neuronal spiking without inducing damage. We showed that the liquid metal electrode evoked larger calcium responses in somata than bath electrodes using the same stimulus parameters. Lastly we demonstrated the use of these liquid metal electrodes to target and depolarize axons. In summary, the integration of liquid metal electrodes with neuronal culture platforms provides a user-friendly and targeted method to stimulate neurons and their subcellular compartments, thus providing a novel tool for future biological investigations.

Integration of pre-aligned liquid metal electrodes for neural stimulation within a user-friendly microfluidic platform

Integration of pre-aligned liquid metal electrodes for neural stimulation within a user-friendly microfluidic platform

Electrochemical Charge Storage Properties of Vertically Aligned Carbon Nanotube Films: Effects of Thermal Oxidation

Vertically aligned carbon nanotube (VACNT) films were synthesized and investigated in vitro for their potential use as a neural stimulation electrode. Materials and electrochemical (EC) characterization (cyclic voltammetry, electrochemical impedance spectroscopy, and high-rate potential transient measurements) were performed before and after flash oxidation in O2 at various temperatures and over a wide frequency range. The results showed distinct EC behavior within three ranges of treatment temperature. Oxidative thermal treatments that did not visibly etch the VACNT film caused a significant improvement in electrode performance compared to the as-deposited electrode. Surprisingly, flash oxidation within a narrow temperature range (400 < T ≤ 450 °C) selectively increased capacitance/charge injection at high frequencies (102–104 Hz). A phenomenological model is proposed to explain the temperature-dependent behavior and indicates the importance of modifying a porous coating to increase the charging rate rather than maximizing the total charge accumulated at long times for high-rate charge storage applications.

Ultra-nanocrystalline diamond electrodes: optimization towards neural stimulation applications

Diamond is well known to possess many favourable qualities for implantation into living tissue including biocompatibility, biostability, and for some applications hardness. However, conducting diamond has not, to date, been exploited in neural stimulation electrodes due to very low electrochemical double layer capacitance values that have been previously reported. Here we present electrochemical characterization of ultra-nanocrystalline diamond electrodes grown in the presence of nitrogen (N-UNCD) that exhibit charge injection capacity values as high as 163 µC cm−2 indicating that N-UNCD is a viable material for microelectrode fabrication. Furthermore, we show that the maximum charge injection of N-UNCD can be increased by tailoring growth conditions and by subsequent electrochemical activation. For applications requiring yet higher charge injection, we show that N-UNCD electrodes can be readily metalized with platinum or iridium, further increasing charge injection capacity. Using such materials an implantable neural stimulation device fabricated from a single piece of bio-permanent material becomes feasible. This has significant advantages in terms of the physical stability and hermeticity of a long-term bionic implant.

Electrochemical Charge Storage Properties of Vertically Aligned Carbon Nanotube Films: The Activation-Enhanced Length Effect

Improvement in the safety, efficacy, selectivity, and/or power consumption of devices used for neural stimulation requires a low impedance neural electrode interface that can rapidly store high charge densities without damaging the electrode or neural tissue. In this study, vertically aligned carbon nanotube (VACNT) films were synthesized and investigated in vitro for their potential use as a neural stimulation electrode. Materials and electrochemical (EC) characterization was performed prior and subsequent to EC activation, accomplished by slow potential cycling across the water window, to determine if activation improved the desired properties. EC characterization was performed at a wide range of frequencies using various techniques including cyclic voltammetry, electrochemical impedance spectroscopy, and high-rate potential transient measurements. The results indicated that EC activation, a technique often used to activate and greatly improve the performance of iridium oxide electrodes, was also favorable for VACNT electrodes. The effect of activation was more pronounced as the average length of the VACNTs was increased, especially at lower frequencies. The activation-enhanced length effect is believed to be a result of the VACNT film characteristics that are determined during the deposition process. A phenomenological model was developed to illustrate this concept and has important implications for various charge-storage applications.