Electrochemical microelectrode degradation monitoring: in situ investigation of platinum corrosion at neutral pH

Objective. The stability of platinum and other noble metal electrodes is critical for neural implants, electrochemical sensors, and energy sources. Beyond the acidic or alkaline environment found in most electrochemical studies, the investigation of electrode corrosion in neutral pH and chloride containing electrolytes is essential, particularly regarding the long-term stability of neural interfaces, such as brain stimulation electrodes or cochlear implants. In addition, the increased use of microfabricated devices demands the investigation of thin-film electrode stability. Approach. We developed a procedure of electrochemical methods for continuous tracking of electrode degradation in situ over the complete life cycle of platinum thin-film microelectrodes in a unique combination with simultaneous chemical sensing. We used chronoamperometry and cyclic voltammetry to measure electrode surface and analyte redox processes, together with accelerated electrochemical degradation. Main results. We compared degradation between thin-film microelectrodes and bulk electrodes, neutral to acidic pH, different pulsing schemes, and the presence of the redox active species oxygen and hydrogen peroxide. Results were confirmed by mechanical profilometry and microscopy to determine material changes on a nanometer scale. We found that electrode degradation is mainly driven by repeated formation and removal of the platinum surface oxide, also within the electrochemical stability window of water. There was no considerable difference between thin-film micro- and macroscopic bulk electrodes or in the presence of reactive species, whereas acidic pH or extending the potential window led to increased degradation. Significance. Our results provide valuable fundamental information on platinum microelectrode degradation under conditions found in biomedical applications. For the first time, we deployed a unified method to report quantitative data on electrode degradation up to a defined endpoint. Our method is a widely applicable framework for comparative long-term studies of sensor and neural interface stability.

Three-dimensional in vitro model of the device-tissue interface reveals innate neuroinflammation can be mitigated by antioxidant ceria nanoparticles

The recording instability of neural implants due to neuroinflammation at the device-tissue interface (DTI) is a primary roadblock to broad adoption of brain-machine interfaces. While a multiphasic immune response, marked by glial scaring, oxidative stress (OS), and neurodegeneration, is well-characterized, the independent contributions of systemic and local innate immune responses are not well-understood. Three-dimensional primary neural cultures provide a unique environment for studying the drivers of neuroinflammation by decoupling the innate and systemic immune systems, while conserving an endogenous extracellular matrix and structural and functional network complexity. We created a three-dimensional in vitro model of the DTI by seeding primary cortical cells around microwires. Live imaging of microtissues over time revealed independent innate neuroinflammation, marked by increased OS, decreased neuronal density, and increased functional connectivity. We demonstrated the use of this model for therapeutic screening by directly applying drugs to neural tissue, bypassing low bioavailability through the in vivo blood brain barrier. As there is growing interest in long-acting antioxidant therapies, we tested efficacy of perpetual antioxidant ceria nanoparticles, which reduced OS, increased neuronal density, and protected functional connectivity. Overall, our avascular in vitro model of the DTI exhibited symptoms of OS-mediated innate neuroinflammation which were mitigated by antioxidant intervention.

Efficient Inference of Sensitivity to Electrical Stimulation from Intrinsic Electrical Properties of Primate Retinal Ganglion Cells

High-fidelity sensory neural implants must be calibrated to precisely activate specific cells via extracellular stimulation. However, collecting and analyzing the required electrical stimulation data may be difficult in the clinic. A potential solution is to infer stimulation sensitivity from intrinsic electrical properties. Here, this inference was tested using large-scale high-density stimulation and recording from macaque retinal ganglion cells ex vivo. Electrodes recording larger spikes exhibited lower activation thresholds, with distinct trends for somas and axons, and consistent trends across cells and retinas. Thresholds for somatic electrodes increased with distance from the axon initial segment. Responses were inversely related to thresholds, and exhibited a steeper dependence on injected current for axonal than somatic electrodes. Dendritic electrodes were largely ineffective for eliciting spikes. Biophysical simulations qualitatively reproduced these findings. Inference of stimulation sensitivity was employed in simulated visual reconstruction, revealing that the approach could improve the function of future high-fidelity retinal implants.

Plasma Enhanced Atomic Layer Deposition of Iridium Oxide for Application in Miniaturized Neural Implants

High quality recording of neuronal activities and electrical stimulation require neurotechnical implants with appropriate electrode material. Iridium oxide (IrOx) is an excellent choice of material due to its biocompatibility, low electrochemical impedance, superior charge injection capacity, corrosion resistance, longevity, and electrochemical stability. Plasma enhanced atomic layer deposition (PE-ALD) and a suitable precursor, like (Methylcyclopentadienyl) (1,5- cyclooctadiene) iridium, could be a promising technique to produce highly conformal and performant IrOx-films at low temperatures and low costs. Various studies have reported the deposition of iridium oxide, but usually at very high temperatures. These processes are not suitable for polymer substrates and limit the use of such post-processing together with active implants. In this work the (Methylcyclopentadienyl) (1,5-cyclooctadiene) iridium(I) ((MeCp)Ir(COD)) precursor was used as a promising approach for depositing IrOx-films using low temperature PE-ALD. This precursor is normally used for chemical vapour deposition processes. First experiments were carried out on silicon substrates at deposition temperatures of 110 C°. The precursor was heated up to 75 °C and oxygen plasma was used as coreactant. The deposited films were analysed with EDX and AFM, showing a smooth surface and a promising ratio between the elements iridium and oxygen.

The Rules of Pulsatile Neurostimulation

Electrical stimulation of neural responses is used both scientifically in brain mapping studies and in many clinical applications such as cochlear, vestibular, and retinal implants. Due to safety considerations, stimulation of the nervous system is restricted to short biphasic pulses. Despite decades of research and development, neural implants are far from optimal in their ability to restore function and lead to varying improvements in patients. In this study, we provide an explanation for how pulsatile stimulation affects individual neurons and therefore leads to variability in restoration of neural responses. The explanation is grounded in the physiological response of channels in the axon and represented with mathematical rules that predict firing rate as a function of pulse rate, pulse amplitude, and spontaneous activity. We validate these rules by showing that they predict recorded vestibular afferent responses in macaques and discuss their implications for designing clinical stimulation paradigms and electrical stimulation-based experiments.

A Biomimetic, SoC-Based Neural Stimulator for Novel Arbitrary-Waveform Stimulation Protocols

Novel neural stimulation protocols mimicking biological signals and patterns have demonstrated significant advantages as compared to traditional protocols based on uniform periodic square pulses. At the same time, the treatments for neural disorders which employ such protocols require the stimulator to be integrated into miniaturized wearable devices or implantable neural prostheses. Unfortunately, most miniaturized stimulator designs show none or very limited ability to deliver biomimetic protocols due to the architecture of their control logic, which generates the waveform. Most such designs are integrated into a single System-on-Chip (SoC) for the size reduction and the option to implement them as neural implants. But their on-chip stimulation controllers are fixed and limited in memory and computing power, preventing them from accommodating the amplitude and timing variances, and the waveform data parameters necessary to output biomimetic stimulation. To that end, a new stimulator architecture is proposed, which distributes the control logic over three component tiers – software, microcontroller firmware and digital circuits of the SoC, which is compatible with existing and future biomimetic protocols and with integration into implantable neural prosthetics. A portable prototype with the proposed architecture is designed and demonstrated in a bench-top test with various known biomimetic output waveforms. The prototype is also tested in vivo to deliver a complex, continuous biomimetic stimulation to a rat model of a spinal-cord injury. By delivering this unique biomimetic stimulation, the device is shown to successfully reestablish the connectivity of the spinal cord post-injury and thus restore motor outputs in the rat model.