tools-for-surface-treatment-silicon-planar-intracortical

Tools for Surface Treatment of Silicon Planar Intracortical Microelectrodes

Intracortical microelectrodes hold great therapeutic potential. But they are challenged with significant performance reduction after modest implantation ...

The University of Texas at Dallas

Recent initiatives in bioelectronic modulation of the nervous system by the NIH (SPARC), DARPA (ElectRx, SUBNETS) and the GlaxoSmithKline Bioelectronic Medicines effort are ushering in a new era of therapeutic electrical stimulation. These novel therapies are prompting a re-evaluation of established electrical thresholds for stimulation-induced tissue damage.

Tissue damage thresholds during therapeutic electrical stimulation.

Neural stimulation is well-accepted as an effective therapy for a wide range of neurological disorders. While the scale of clinical devices is relatively large, translational, and pilot clinical applications are underway for microelectrode-based systems. Microelectrodes have the advantage of stimulating a relatively small tissue volume which may improve selectivity of therapeutic stimuli. Current microelectrode technology is associated with chronic tissue response which limits utility of these devices for neural recording and stimulation. One approach for addressing the tissue response problem may be to reduce physical dimensions of the device. "Thinking small" is a trend for the electronics industry, and for implantable neural interfaces, the result may be a device that can evade the foreign body response.

Thinking Small: Progress on Microscale Neurostimulation Technology.

With recent interest in kilohertz frequency electrical stimulation for nerve conduction block, understanding the electrochemistry and role of electrode material is important for assessing the safety of these stimulus protocols. Here we describe an approach to determining electrode polarization in response to continuous kilohertz frequency sinusoidal current waveforms. We have also investigated platinum, iridium oxide, and titanium nitride as coatings for high frequency electrodes. The current density distribution at 50 kHz at the electrode-electrolyte interface was also modeled to demonstrate the importance of the primary current distribution in supporting charge injection at high frequencies.

Electrochemical characterization of high frequency stimulation electrodes: role of electrode material and stimulation parameters on electrode polarization.

Multisite implantable electrode arrays serve as a tool to understand cortical network connectivity and plasticity. Furthermore, they enable electrical stimulation to drive plasticity, study motor/sensory mapping, or provide network input for controlling brain-computer interfaces. Neurobehavioral rodent models are prevalent in studies of motor cortex injury and recovery as well as restoration of auditory/visual cues due to their relatively low cost and ease of training. Therefore, it is important to understand the chronic performance of relevant electrode arrays in rodent models. In this report, we evaluate the chronic recording and electrochemical performance of 16-channel Utah electrode arrays, the current state-of-the-art in pre-/clinical cortical recording and stimulation, in rat motor cortex over a period of 6 mo. The single-unit active electrode yield decreased from 52.8 ± 10.0 ( week 1) to 13.4 ± 5.1% ( week 24). Similarly, the total number of single units recorded on all electrodes across all arrays decreased from 106 to 15 over the same time period. Parallel measurements of electrochemical impedance spectra and cathodic charge storage capacity exhibited significant changes in electrochemical characteristics consistent with development of electrolyte leakage pathways over time. Additionally, measurements of maximum cathodal potential excursion indicated that only a relatively small fraction of electrodes (10-35% at 1 and 24 wk postimplantation) were capable of delivering relevant currents (20 µA at 4 nC/ph) without exceeding negative or positive electrochemical potential limits. In total, our findings suggest mainly abiotic failure modes, including mechanical wire breakage as well as degradation of conducting and insulating substrates. NEW & NOTEWORTHY Multisite implantable electrode arrays serve as a tool to record cortical network activity and enable electrical stimulation to drive plasticity or provide network feedback. The use of rodent models in these fields is prevalent. We evaluated chronic recording and electrochemical performance of 16-channel Utah electrode arrays in rat motor cortex over a period of 6 mo. We primarily observed abiotic failure modes suggestive of mechanical wire breakage and/or degradation of insulation.

Chronic recording and electrochemical performance of Utah microelectrode arrays implanted in rat motor cortex.

Neural implants offer solutions for a variety of clinical issues. While commercially available devices can record neural signals for short time periods, they fail to do so chronically, partially due to the sustained tissue response around the device. Our objective was to assess the correlation between device stiffness, a function of both material modulus and cross-sectional area, and the severity of immune response. Meta-analysis data were derived from nine previously published studies which reported device material and geometric properties, as well as histological outcomes. Device bending stiffness was calculated by treating the device shank as a cantilevered beam. Immune response was quantified through analysis of immunohistological images from each study, specifically looking at fluorescent markers for neuronal nuclei and astrocytes, to assess neuronal dieback and gliosis. Results demonstrate that the severity of the immune response, within the first 50 µm of the device, is highly correlated with device stiffness, as opposed to device modulus or cross-sectional area independently. In general, commercially available devices are around two to three orders of magnitude higher in stiffness than devices which induced a minimal tissue response. These results have implications for future device designs aiming to decrease chronic tissue response and achieve increased long-term functionality.

A Meta-Analysis of Intracortical Device Stiffness and Its Correlation with Histological Outcomes.

Clinical applications of implantable microelectrode arrays are currently limited by device failure due to, in part, mechanical and electrochemical failure modes. To overcome this challenge, there is significant research interest in the exploration of novel array architectures and encapsulation materials. Amorphous silicon carbide (a-SiC) is biocompatible and corrosion resistant, and has recently been employed as a coating on biomedical devices including planar microelectrode arrays. However, to date, the three-dimensional Utah electrode array (UEA) is the only array architecture which has been approved by the food and drug administration (FDA) for long-term human trials.

Chronic recording and electrochemical performance of amorphous silicon carbide-coated Utah electrode arrays implanted in rat motor cortex.

Neural electrodes enable the recording and stimulation of bioelectrical activity from the nervous system [...].

Editorial for the Special Issue on Neural Electrodes: Design and Applications.

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.

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

Highly aligned carbon nanotubes (HACNT sheets) have recently attracted great attention in developing high-performing ultrathin supercapacitors, which take advantage of the long-range alignment to improve electrochemical performance. While there are investigations into sandwich electrode CNT sheet devices, there are no known reports on interdigitated electrode (IDE) HACNT sheet microsupercapacitors (MSCs). This paper reports a facile method for rapidly fabricating high energy density ultrathin HACNT sheet-based MSCs with IDE planar configuration. Increasing the electrode thickness from 32 nm (5 layers) to 300 nm (50 layers) results in an approximately three times factor in performance. The 50 layer devices (MSC-50L) yield a top energy density of 10.52 mWhcm and power density of 19.33 Wcm, making its performance comparable to those of microbatteries with potential for further improvement. Additionally, incorporation of MnO nanoparticles (NPs) within the MSCs-50L improves specific capacitance (242 Fcm), energy density (33.7 mWhcm), and power density (31 Wcm), outperforming current thin-film MSCs and matching the performance of 3D MSCs. MSCs also demonstrate a long cycle life (7000 charge-discharge cycles) with less than 5% capacitance fade. These findings suggest that HACNT sheets have substantial potential as active electrode materials for ultrathin high energy density microscale power sources.

A High Energy Density 2D Microsupercapacitor Based on an Interconnected Network of a Horizontally Aligned Carbon Nanotube Sheet.

We have studied the charge-injection characteristics and electrochemical impedance of sputtered ruthenium oxide (RuO ) films as electrode coatings for neural stimulation and recording electrodes. RuO 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 RuO electrodes was found to be 54.6 ± 9.5 mC/cm (mean ± SD, n = 12), and the charge-injection capacity in a 0.2-ms cathodal current pulse was found to be 7.1 ± 0.3 mC/cm (mean ± SD, n = 15) at 0.6 V positive bias versus Ag|AgCl, in phosphate buffer saline at room temperature for ~250 nm thick films. In general, the RuO 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/cm (mean ± SD, n = 5) at 0.6 V bias versus Ag|AgCl at 630 nm film thickness. In addition, RuO films showed minimal changes in electrochemical characteristics over 1.5 billion cycles of constant current pulsing at a charge density of 408 μC/cm (8 nC/phase, 200 μs pulse width). The findings of low-impedance, high charge-injection capacity, and long-term pulsing stability suggest the suitability of RuO as a comparatively inexpensive and favorable choice of electrode material for neural stimulation and recording.

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

. Maximizing the stability of implanted neural interfaces will be critical to developing effective treatments for neurological and neuromuscular disorders. Our research aims to develop a stable neural interface using wireless communication and intrafascicular microelectrodes to provide highly selective stimulation of neural tissue.. We implanted a wireless floating microelectrode array into the left sciatic nerve of six rats. Over a 38 week implantation period, we recorded stimulation thresholds and movements evoked at each implanted electrode. We also tracked each animal's response to sensory stimuli and performance on two different walking tasks.. Presence of the microelectrode array inside the sciatic nerve did not cause any obvious motor or sensory deficits in the hindlimb. Visible movement in the hindlimb was evoked by stimulating the sciatic nerve with currents as low as 4.1A. Thresholds for most of the 96 electrodes we implanted were below 20A, and predictable recruitment of plantar flexion and dorsiflexion was achieved by stimulating rat sciatic nerve with the intrafascicular microelectrode array. Further, motor recruitment patterns for each electrode did not change significantly throughout the study.. Incorporating wireless communication and a low-profile neural interface facilitated highly stable motor recruitment thresholds and fine motor control in the hindlimb throughout an extensive 9.5 month assessment in rodent peripheral nerve. Results of this study indicate that use of the wireless device tested here could be extended to other applications requiring selective neural stimulation and chronic implantation.

Wireless microelectrode arrays for selective and chronically stable peripheral nerve stimulation for hindlimb movement.

Microelectrode arrays (MEAs) enable the recording of electrical activity from cortical neurons which has implications for basic neuroscience and neuroprosthetic applications. The design space for MEA technology is extremely wide where devices may vary with respect to the number of monolithic shanks as well as placement of microelectrode sites. In the present study, we examine the differences in recording ability between two different MEA configurations: single shank (SS) and multi-shank (MS), both of which consist of 16 recording sites implanted in the rat motor cortex. We observed a significant difference in the proportion of active microelectrode sites over the 8-week indwelling period, in which SS devices exhibited a consistent ability to record activity, in contrast to the MS arrays which showed a marked decrease in activity within 2 weeks post-implantation. Furthermore, this difference was revealed to be dependent on the depth at which the microelectrode sites were located and may be mediated by anatomical heterogeneity, as well as the distribution of inhibitory neurons within the cortical layers. Our results indicate that the implantation depth of microelectrodes within the cortex needs to be considered relative to the chronic performance characterization.

Influence of Implantation Depth on the Performance of Intracortical Probe Recording Sites.

. Trauma induced by the insertion of microelectrodes into cortical neural tissue is a significant problem. Further, micromotion and mechanical mismatch between microelectrode probes and neural tissue is implicated in an adverse foreign body response (FBR). Hence, intracortical ultra-microelectrode probes have been proposed as alternatives that minimize this FBR. However, significant challenges in implanting these flexible probes remain. We investigated the insertion mechanics of amorphous silicon carbide (a-SiC) probes with a view to defining probe geometries that can be inserted into cortex without buckling.. We determined the critical buckling force of a-SiC probes as a function of probe geometry and then characterized the buckling behavior of these probes by measuring force-displacement responses during insertion into agarose gel and rat cortex.Insertion forces for a range of probe geometries were determined and compared with critical buckling forces to establish geometries that should avoid buckling during implantation into brain. The studies show that slower insertion speeds reduce the maximum insertion force for single-shank probes but increase cortical dimpling during insertion of multi-shank probes.Our results provide a guide for selecting probe geometries and insertion speeds that allow unaided implantation of probes into rat cortex. The design approach is applicable to other animal models where insertion of intracortical probes to a depth of 2 mm is required.

Insertion mechanics of amorphous SiC ultra-micro scale neural probes.

Consistent transmission of data from wireless neural devices is critical for monitoring the condition and performance of stimulation electrodes. To date, no wireless neural interface has demonstrated the ability to monitor the integrity of chronically implanted electrodes through wireless data transmission.In this work, we present a method for wirelessly recording the voltage transient (VT) response to constant-current, cathodic-first asymmetric pulsing from a microelectrode array. We implanted six wireless devices in rat sciatic nerve and wirelessly recorded VT measurements throughout a 38 week implantation period.Electrode maximum cathodic potential excursion (E), access voltage, and driving voltage (extracted from each VT) remained stable throughout the 38 week study period. Average E(from an applied +0.6 V interpulse bias) in response to 4.7A, 200.2s pulses was 267 ± 107 mV at week 1 post-implantation and 282 ± 52 mV at week 38 post-implantation. Access voltage for the same 4.7A pulsing amplitude was 239 ± 65 mV at week 1 post-implantation and 268 ± 139 mV at week 38 post-implantation.The VT response recorded via reverse telemetry from the wireless microelectrode array did not significantly change over a 38 week implantation period and was similar to previously reported VTs from wired microelectrodes with the same geometry. Additionally, the VT response recorded wirelessly in phosphate buffered saline before and after device implantation appeared as expected, showing significantly less electrode polarization and smaller access voltage than the VT response.

Article	Year
Tissue damage thresholds during therapeutic electrical stimulation. Journal of neural engineering\| PubMed ID: 26792176	2016
Thinking Small: Progress on Microscale Neurostimulation Technology. Neuromodulation : journal of the International Neuromodulation Society\| PubMed ID: 29076214	2017
Electrochemical characterization of high frequency stimulation electrodes: role of electrode material and stimulation parameters on electrode polarization. Journal of neural engineering\| PubMed ID: 29205176	2018
Chronic recording and electrochemical performance of Utah microelectrode arrays implanted in rat motor cortex. Journal of neurophysiology\| PubMed ID: 30020844	2018
A Meta-Analysis of Intracortical Device Stiffness and Its Correlation with Histological Outcomes. Micromachines\| PubMed ID: 30424376	2018
Chronic recording and electrochemical performance of amorphous silicon carbide-coated Utah electrode arrays implanted in rat motor cortex. Journal of neural engineering\| PubMed ID: 31013489	2019
Editorial for the Special Issue on Neural Electrodes: Design and Applications. Micromachines\| PubMed ID: 31336980	2019
Activated iridium oxide film (AIROF) electrodes for neural tissue stimulation. Journal of neural engineering\| PubMed ID: 32947268	2020
A High Energy Density 2D Microsupercapacitor Based on an Interconnected Network of a Horizontally Aligned Carbon Nanotube Sheet. ACS applied materials & interfaces\| PubMed ID: 33100006	2020
Charge injection characteristics of sputtered ruthenium oxide electrodes for neural stimulation and recording. Journal of biomedical materials research. Part B, Applied biomaterials\| PubMed ID: 34259381	2022
Wireless microelectrode arrays for selective and chronically stable peripheral nerve stimulation for hindlimb movement. Journal of neural engineering\| PubMed ID: 34592725	2021
Influence of Implantation Depth on the Performance of Intracortical Probe Recording Sites. Micromachines\| PubMed ID: 34683209	2021
Insertion mechanics of amorphous SiC ultra-micro scale neural probes. Journal of neural engineering\| PubMed ID: 35263724	2022
Wireless transmission of voltage transients from a chronically implanted neural stimulation device. Journal of neural engineering\| PubMed ID: 35378519	2022

Stuart F. Cogan

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