Safe Charge Injection Limit Research Articles

Minimizing Iridium Oxide Electrodes for High Visual Acuity Subretinal Stimulation.

Vision loss from diseases of the outer retina, such as age-related macular degeneration, is among the leading causes of irreversible blindness in the world today. The goal of retinal prosthetics is to replace the photo-sensing function of photoreceptors lost in these diseases with optoelectronic hardware to electrically stimulate patterns of retinal activity corresponding to vision. To enable high-resolution retinal prosthetics, the scale of stimulating electrodes must be significantly decreased from current designs; however, this reduces the amount of stimulating current that can be delivered. The efficacy of subretinal stimulation at electrode sizes suitable for high visual acuity retinal prosthesis are not well understood, particularly within the safe charge injection limits of electrode materials. Here, we measure retinal ganglion cell (RGC) responses in a mouse model of blindness to evaluate the stimulation efficacy of 10, 20, and 30 μm diameter iridium oxide electrodes within the electrode charge injection limits, focusing on measures of charge threshold and dynamic range. Stimulation thresholds were lower for smaller electrodes, but larger electrodes could elicit a greater dynamic range of spikes and recruited more ganglion cells within charge injection limits. These findings suggest a practical lower limit for planar electrode size and indicate strategies for maximizing stimulation thresholds and dynamic range.

Subthreshold Electrical Stimulation for Controlling Protein-Mediated Impedance Increases in Platinum Cochlear Electrode.

This study evaluated subthreshold biphasic stimulation pulses as a strategy to stabilize electrode impedance via control of protein adsorption. Following implantation, cochlear electrodes undergo impedance fluctuations thought to be caused by protein adsorption and/or inflammatory responses. Impedance increases can impact device power consumption, safe charge injection limits, and long-term stability of electrodes. Protein-mediated changes in polarization impedance (Zp) were measured by voltage transient responses to biphasic current pulses and electrochemical impedance spectroscopy, with and without protein solutions. Four subthreshold stimulation regimes were studied to assess their effects on protein adsorption and impedance; (1) symmetric charge-balanced pulses delivered continuously, (2) at 10% duty cycle, (3) at 1% duty cycle, and (4) an asymmetric charge balanced pulse delivered continuously with a cathodic phase twice as long as the anodic phase. The Zp of electrodes incubated in protein solutions without stimulation for 2 h increased by between ∼28% and ∼55%. Subthreshold stimulation reduced the rate at which impedance increased following exposure to all protein solutions. Decreases in Zp were dependent on the type of protein solution and the stimulation regime. Subthreshold stimulation pulses were more effective when delivered continuously compared to 1% and 10% duty cycles. These results support the potential of subthreshold stimulation pulses to mitigate protein-mediated increase in impedance. This research highlights the potential of clinically translatable stimulation pulses to mitigate perilymph protein adsorption on cochlear electrodes, a key phenomenon precursor of the inflammatory response.

Construction and electrochemical properties determination of carbon nanotubes/porous-network carbon micron tubes/silk fibroin composite film neural electrode

A novel carbon nanotubes/porous-network carbon micron tubes/silk fibroin (CPS) composite film neural electrode was presented and characterized. This electrode was fabricated through assembling dispersed carbon nanotubes (CNTs) by phytic acid onto the porous silk fibroin film. Afterward, the silk fibroin around the CNTs was carbonized by laser irradiation, producing porous-network carbon microtubes with good conductivity and biological compatibility. The structure of the CPS composite film was characterized by scanning electron microscopy and Raman spectroscopy. Cyclic voltammetry, electrochemical impedance spectroscopy, and safe charge injection limit (Qinj) of the CPS electrode were also measured by the three-electrode system, and the results exhibited outstanding electrochemical properties with the achieved Qinj of 5.7 mC/cm2. This work provides a promising approach for the preparation of a long-term implanted neural electrode with high charge injection ability and good biocompatibility.

Flexible, multichannel cuff electrode for selective electrical stimulation of the mouse trigeminal nerve

The trigeminal nerve (cranial nerve V), along with other cranial nerves, has in recent years become a popular target for bioelectric medicine due to its direct access to neuromodulatory centers. Trigeminal nerve stimulation is currently being evaluated as an adjunctive treatment for various neurodegenerative and neuropsychiatric diseases despite the mechanism of action being in question. In this work, we describe the development and validation of a novel neural interface for the infraorbital branch of the trigeminal nerve utilizing a thin film (TF) nerve cuff containing multiple electrode sites allowing for more selective stimulation of the nerve. We characterized the properties of the device using electrochemical impedance spectroscopy, cyclic voltammetry, voltage excursions, and in vivo testing. Electrochemical measurements demonstrate that the platinum-based electrodes possess a capacitive charge carrying mechanism suitable for stimulation of biological tissue with a safe charge injection limit of 73.13 μC/cm2. In vivo stimulation experiments show that the TF cuff can reliably stimulate nerve targets eliciting cortical responses similar to a silicone cuff electrode. Furthermore, selecting different pairs of stimulation electrodes on the TF cuff modulated the magnitude and/or spatial pattern of cortical responses suggesting that the device may be able to selectively stimulate different parts of the nerve. These results suggest that the TF cuff is a viable neural interface for stimulation of the infraorbital branch of the trigeminal nerve that enables future research examining the therapeutic mechanisms of trigeminal nerve stimulation.

Corrosion Study of Implanted Tin Electrodes Using Excessive Electrical Stimulation in Minipigs

(1) Background: Titanium nitride (TiN) electrodes have been used for implantable stimulation and sensing electrodes for decades. Nevertheless, there still is a discrepancy between the in vitro and in vivo determined safe charge injection limits. This study investigated the consequences of pulsing implanted electrodes beyond the in vivo safe charge injection limits. (2) Methods: The electrodes were implanted for a month and then pulsed at 20 mA and 50 mA and 200 Hz and 400 Hz. Afterwards, the electrodes were investigated using electrochemical and analytical methods to evaluate whether electrode degradation had occurred. (3) Results: Electrochemical tests showed that electrodes that pulsed at 20 mA and 200 Hz (lowest electrical dose) had a significantly lower charge injection capacity and higher impedance than the other used and unused electrodes. (4) Conclusions: The electrodes pulsed at the lowest electrical dose, for which no tissue damage was found, appeared to have degraded. Electrodes pulsed at higher electrical doses for which tissue damage did occur, on the other hand, show no significant degradation in electrochemical tests compared to unused implanted and not implanted electrodes. It is thus clear that the tissue surrounding the electrode has an influence on the charge injection properties of the electrodes and vice versa.

PEDOT: PSS coating on gold microelectrodes with excellent stability and high charge injection capacity for chronic neural interfaces

PEDOT: PSS has become one of the best choices as coating material of neural interfaces electrodes for its excellent biocompatibility, chemical steadiness and extremely inhomogeneous topography that facilitate reversible faradaic charge injection. However, chronic application of this material is still a matter of challenge for its poor adhesion to metallic electrodes. This study presents two new methods that increases stability and stimulation capacity of PEDOT: PSS (poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate)) coated neural interfaces electrodes. These improvements in the characteristics make PEDOT: PSS as a promising coating material for the long-term stable bidirectional neural application. The first process ensures long-term stability of PEDOT: PSS coating. The stability improvement is done by creating a rough and porous surface with selective iodine etching of Au electrodes. The pores act as anchors and increases mechanical bonding between PEDOT: PSS coating and electrode surface, hence the stability of the coating increases. PEDOT: PSS coating on iodine etched gold electrode showed 100% stability under strong ultrasonic stability test compared to non-etched electrodes. Long-term in vitro continuous stimulation for 7 days was performed to evaluate the stability of the coating. 1 μm thick PEDOT:PSS coating on iodine etched Au electrode completely survived under 604 million continuous current pulses that was evaluated by SEM image and electrochemical impedance spectroscopy (EIS). The second process improves the characteristics of PEDOT: PSS coated electrodes in terms of stimulation capacity. This is done by electrochemical modification of PEDOT: PSS coating surface by applying a cyclic voltammetry method. A perfect and effective method is developed by comparative analysis and optimizing the parameters of cyclic voltammetry. The PEDOT: PSS coating presented here (1 μm thick) reduces the impedance of bare Au electrode by around 99%. This electrochemical modification method further reduces the impedance of this PEDOT: PSS coated electrode by 33%. Moreover, this method reduces electrode polarization under stimulation by 30.5%. Reduced electrode impedance and polarization under stimulation are beneficial for increasing safe charge injection limit of the electrode for stimulation. Both processes facilitate the use of PEDOT: PSS coating as a true long-term stable and promising material on gold microelectrodes of neural interfaces.

Aligned Nanofibers from Polypyrrole/Graphene as Electrodes for Regeneration of Optic Nerve via Electrical Stimulation.

The damage of optic nerve will cause permanent visual field loss and irreversible ocular diseases, such as glaucoma. The damage of optic nerve is mainly derived from the atrophy, apoptosis or death of retinal ganglion cells (RGCs). Though some progress has been achieved on electronic retinal implants that can electrically stimulate undamaged parts of RGCs or retina to transfer signals, stimulated self-repair/regeneration of RGCs has not been realized yet. The key challenge for development of electrically stimulated regeneration of RGCs is the selection of stimulation electrodes with a sufficient safe charge injection limit (Q(inj), i.e., electrochemical capacitance). Most traditional electrodes tend to have low Q(inj) values. Herein, we synthesized polypyrrole functionalized graphene (PPy-G) via a facile but efficient polymerization-enhanced ball milling method for the first time. This technique could not only efficiently introduce electron-acceptor nitrogen to enhance capacitance, but also remain a conductive platform-the π-π conjugated carbon plane for charge transportation. PPy-G based aligned nanofibers were subsequently fabricated for guided growth and electrical stimulation (ES) of RGCs. Significantly enhanced viability, neurite outgrowth and antiaging ability of RGCs were observed after ES, suggesting possibilities for regeneration of optic nerve via ES on the suitable nanoelectrodes.

Laser patterning of platinum electrodes for safe neurostimulation

Objective. Laser surface modification of platinum (Pt) electrodes was investigated for use in neuroprosthetics. Surface modification was applied to increase the surface area of the electrode and improve its ability to transfer charge within safe electrochemical stimulation limits. Approach. Electrode arrays were laser micromachined to produce Pt electrodes with smooth surfaces, which were then modified with four laser patterning techniques to produce surface structures which were nanosecond patterned, square profile, triangular profile and roughened on the micron scale through structured laser interference patterning (SLIP). Improvements in charge transfer were shown through electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and biphasic stimulation at clinically relevant levels. A new method was investigated and validated which enabled the assessment of in vivo electrochemically safe charge injection limits. Main results. All of the modified surfaces provided electrical advantage over the smooth Pt. The SLIP surface provided the greatest benefit both in vitro and in vivo, and this surface was the only type which had injection limits above the threshold for neural stimulation, at a level shown to produce a response in the feline visual cortex when using an electrode array implanted in the suprachoroidal space of the eye. This surface was found to be stable when stimulated with more than 150 million clinically relevant pulses in physiological saline. Significance. Critical to the assessment of implant devices is accurate determination of safe usage limits in an in vivo environment. Laser patterning, in particular SLIP, is a superior technique for improving the performance of implant electrodes without altering the interfacial electrode chemistry through coating. Future work will require chronic in vivo assessment of these electrode patterns.

Poly(3,4-ethylenedioxythiophene)/multiwall carbon nanotube composite coatings for improving the stability of microelectrodes in neural prostheses applications

With the purpose of improving the stability of microelectrodes under continuous high charge density stimulation, which is required for neural prostheses applications such as visual prostheses, multiwall carbon nanotube (MWCNT)-doped poly(3,4-ethylenedioxythiophene) (PEDOT) composite films were coated onto a platinum microelectrode by electrochemical polymerization. Galvanostatically polymerized PEDOT/MWCNT films demonstrated superior characteristics compared to polystyrene sulfonate doping and potentiostatic polymerization, including a three-dimensional cone morphology and enhanced electrochemical performance (the safe charge injection limit reached 6.2mCcm−2 for cathodic-first pulses). Most important of all, the improved stability of the coatings has been revealed through stimulation for 96h using 3.0mCcm−2 current pulses in bicarbonate- and phosphate-buffered saline solution. Cell assays revealed that PEDOT/MWCNT films could promote the adhesion and neurite outgrowth of rat pheochromocytoma cells. Finally, platinum wires coated with PEDOT/MWCNT films were implanted into rat cortex for 6weeks for histological evaluation. Glial fibrillary acidic protein and neuronal nuclei staining revealed that the films elicit a lower tissue response compared to platinum implants. These results suggest that the galvanostatically polymerized PEDOT/MWCNT films can improve the stability of stimulation microelectrodes and that PEDOT/MWCNT is an excellent candidate material for electrode coating for neural prostheses applications.

PEDOT/MWCNT composite film coated microelectrode arrays for neural interface improvement

High-performance electrode materials play a crucial role at the interface of implantable neural electrode. To realize bidirectional transduction between neural tissue and neural microelectrodes, the electrode material must satisfy the function of stimulating and recording. As the number and density of electrode increase, tiny electrodes with high performance are needed in future bioengineering study. In this study, a method of electrochemically co-deposited poly(3,4-ethylenedioxythiophene)/multi-walled carbon nanotube (PEDOT/MWCNT) onto microelectrode arrays with 8 channels was investigated. After modification, the impedance, charge transfer ability and frequency response characteristic were improved simultaneously. Compared with bare golden electrode, the coated microelectrodes with a surface area of 615μm2 exhibited a particularly high safe charge injection limit of 7.74mC/cm2 and low impedance of 12kΩ at 1kHz. In vivo inferior colliculus implantation of rats revealed that the composite film coated microelectrodes showed higher signal to noise ratio recordings >15dB compared to 6dB SNR of bare gold microelectrodes.

A simple method for amino-functionalization of carbon nanotubes and electrodeposition to modify neural microelectrodes

Aiming to improve the charge transfer ability at the neural electrode interface, a new and simple method for amino-functionalization of carbon nanotubes (CNTs) has been attempted, and the amino-functionalized CNTs after quaternization were electrodeposited onto pretreated Pt microelectrodes using an 80V cell voltage in anhydrous solvent. The formation of amino-functionalized CNTs and electrodeposition of the functionalized CNTs were confirmed by Fourier transform infrared (FT-IR) spectroscopy and SEM images respectively. The deposited electrodes exhibited a reduction by 91% in the electrode impedance at 1kHz compared to smooth Pt electrodes. In addition, the CNT deposited electrodes possessed a large charge storage capacity, and provided an increased safe charge injection (Qinj) limit (1.6–2.0mC/cm2) that is ten times higher than that of Pt electrodes. Electrochemical stability is another important characteristic required by neural electrodes. It was found that the CNT deposited microelectrodes were very stable during electrical stimulation, which is highly desirable for implantable neural electrodes. In summary, this study developed an easy and mild coating method for elevating the safe charge injection limit of neural microelectrodes, which can be applied to neural prostheses such as visual prostheses.