Effect of pH and gel electrolyte on safe charge injection and electrode degradation of platinum electrodes

Platinum (Pt) is a widespread electrode material choice for neural interfaces and electrochemical biosensors, due to its supposed electrochemical inertness. However, faradaic reactions can take place at Pt electrodes, including Pt oxide formation and reduction. Repeated redox cycles of Pt can lead to Pt dissolution, which may harm the tissue and significantly reduce electrode lifetime. In this study, we investigated how the electrolyte may influence Pt dissolution mechanisms during current pulsing. Two electrolyte characteristics were considered: pH and gelation. We confirmed that empirically reported tissue damage thresholds correlate with Pt oxide formation and reduction. Varying electrolyte pH occasioned a shift in recorded potentials, however, damage thresholds correlated with the same mechanisms for all pH values. The similar behaviour observed for pH values in the central range (4 ≤ pH ≤ 10) can be explained by variations of local pH at the electrode surface. Gel electrolytes behaved comparably to solutions, which was confirmed by statistical similarity tests. This study extends the knowledge about platinum electrochemistry and shows the necessity to carefully choose the stimulation protocol and the electrolyte to avoid platinum dissolution and tissue damage

The degradation of glial scar and enhancement of chronic intracortical recording electrode performance through the local delivery of dexamethasone and chondroitinase

The ability of conducting polymers such as poly(3,4-ethylenedioxythiophene) (PEDOT) to store a drug as a dopant and release it following electrical stimulus make them an intriguing coating possibility for intracortical electrodes, along with their ability to reduce electrode impedance. The mechanism allows for the release of an assortment of useful agents, including anti-inflammatory drugs and neuromodulatory chemicals. We evaluated the release capabilities of a multi-walled carbon nanotube (MWCNT)-doped PEDOT coating incorporating the anti-inflammatory steroid dexamethasone in vitro using sputtered-gold macroelectrodes, and then applied the coating to half of the electrodes within 16-shank platinum/iridium floating microelectrode arrays for chronic in vivo evaluation in rat visual cortex. Impedance measurement, neurophysiological recording, and cyclic voltammetric release stimulus (-0.9 V to 0.6 V, 1 V/s, 20 cycles) was performed daily to all channels. On the 11th day, histology was performed to quantitatively characterize inflammatory tissue response using OX42 (microglia) and GFAP (astroglia). Equivalent circuit analysis was performed to assist the interpretation of impedance data. Our results indicated that the MWCNT/PEDOT-coated gold macroelectrodes released double the amount of dexamethasone using passive release followed by CV stimulation (10 sets of 20 cycles) compared to passive release alone. Coatings applied to Pt/Ir microelectrodes reduced 1 kHz impedance in PBS by approximately 38%. Coated probes in vivo exhibited a significant decrease in 1 kHz impedance for the initial three days of implantation followed by an increase, between days 4 and 7, to values equivalent to those exhibited by uncoated probes. Neurophysiological recording performance of coated and uncoated probes remained equivalent for the duration of the experiment, in terms of signal-to-noise ratio and noise amplitude. Histology revealed no significant difference in tissue inflammatory response to coated and uncoated electrodes. Explant imaging revealed the presence of a membranous film enveloping coated electrodes, and equivalent circuit analysis suggested that the day 4-7 increase in 1 kHz impedance of coated electrodes was due to a decrease in effective surface area of the coatings as well as the core electrodes. Additional work was also performed developing a model for the in vivo microinjection of the enzyme Chondroitinase ABC into tissue surrounding implanted microelectrodes

A measurement setup and automated calculation method to determine the charge injection capacity of implantable microelectrodes

Producción CientíficaThe design of safe stimulation protocols for functional electrostimulation requires knowledge of the “maximum reversible charge injection capacity” of the implantable microelectrodes. One of the main difficulties encountered in characterizing such microelectrodes is the calculation of the access voltage Va. This paper proposes a method to calculate Va that does not require prior knowledge of the overpotential terms and of the electrolyte (or excitable tissue) resistance, which is an advantage for in vivo electrochemical characterization of microelectrodes. To validate this method, we compare the calculated results with those obtained from conventional methods for characterizing three flexible platinum microelectrodes by cyclic voltammetry and voltage transient measurements. This paper presents the experimental setup, the required instrumentation, and the signal processing.Ministerio de Economía y Competitividad ( Research project DPI2016-80391-C3-3-R

Multielectrode microstimulation for temporal lobe epilepsy

Multielectrode arrays may have several advantages compared to the traditional single macroelectrode brain electrical stimulation technique including less tissue damage due to implantation and the ability to deliver several spatio-temporal patterns of stimulation. Prior work on cell cultures has shown that multielectrode arrays are capable of completely stopping seizure-like spontaneous bursting events through a distributed asynchronous multi-site approach. In my studies, I used a similar approach for controlling seizures in a rat model of temporal lobe epilepsy. First, I developed a new method of electroplating in vivo microelectrode arrays for durably improving their impedance. I showed that microelectrode arrays electroplated through the new technique called sonicoplating, required the least amount of voltage in current controlled stimulation studies and also produced the least amplitude and duration of stimulation artifact compared to unplated, DC electroplated or pulse-plated microelectrodes. Second, using c-fos immunohistochemistry, I showed that 16-electrode sonicoplated microelectrode arrays can activate 5.9 times more neurons in the dorsal hippocampus compared to a single macroelectrodes while causing < 77% the tissue damage. Next, through open-loop multisite asynchronous microstimulation, I reduced seizure frequency by ~50% in the rodent model of temporal lobe epilepsy. Preliminary studies aimed at using the same stimulation protocol in closed-loop responsive and predictive seizure control did not stop seizures. Finally, through an internship at Medtronic Neuromodulation, I worked on developing and implementing a rapid algorithm prototyping research tool for closed-loop human deep brain stimulation applications.Ph.D

Comparison of Multiple Degrees of Electrode Surface Roughness: Impedance, Charge Storage Capacity, Biofouling and Biocompatibility

Devices called neural electrodes are generally used to record and / or stimulate neural activity whilst extracellularly interfacing with neurons. The ultimate goal of the field is to develop neural electrodes that can continuously record and / or stimulate neural activity for long periods of time (10+ years). Electrodes require low electrode impedance to enable good signal to noise ratio and a high capacity for chemically stable injection of charge (CSC) for stimulating neural activity. Electrode function typically deteriorates after a few months in-vivo due two factors: biofouling and local cellular response (glial scarring). Biofouling is theorised to be an accumulation of multiple proteins at the electrode surface. However this has only been backed up experimentally by single protein models in literature. Electrodes need to be able to combat the effects of biofouling and glial scarring. This study uses nanometre scale roughened gold (Au) electrodes. Electrode roughening has previously been shown to lower impedance, increase CSC and reduce glial response and the effects of biofouling. We compared multiple degrees of roughness with the aim of finding the optimal degree for improving impedance, CSC, biofouling and cellular response. We found that surface roughening increased impedance and only increased CSC for two only degrees of roughness. To find the optimal degree of roughness across conditions, we suspect a larger range of roughness may be necessary to lower impedance with our fabrication technique. This study is the first to use a multiprotein biofouling model. Contrary to literature, we found that incubation with protein decreased impedance, likely due to protein-protein interactions not accounted for in single protein models. Biocompatibility was improved for two degrees of Au roughness. Roughening of SU8, a polymer used to surround the electrodes, decreased biocompatibility. We also used artificial cerebral spinal fluid (aCSF) as an electrolyte, which is more chemically similar to in-vivo than commonly used phosphate buffered saline solution (PBS). The use aCSF as a medium was significant as the measures in aCSF were different from that in PBS

Multimodal Investigation of the Efficiency and Stability of Microstimulation using Electrodes Coated with PEDOT/CNT and Iridium Oxide

Electrical microstimulation is an invaluable tool in neuroscience research to dissect neural circuits, relate brain areas, and identify relationships between brain structure and behavior. In the clinic, electrical microstimulation has enabled partial restoration of vision, movement, sensation and autonomic functions. Recently, novel materials and new fabrication techniques of traditional metals have emerged such as iridium oxide and the conducting polymer PEDOT/CNT. These materials have demonstrated particular promise in the improvement in electrical efficiency. However, the in vivo stimulation efficiency and the in vivo stability of these materials have not been thoroughly characterized. In this dissertation, we use a multimodal approach to study the efficiency and stability of electrode-tissue interface using novel materials in microstimulation

Modulation of in Vivo Neural Network Activity with Electrochemically Controlled Delivery of Neuroactive Molecules

Neural interface technologies with implantable microelectrode arrays hold great promise for treating neural injuries or disorders. On neural electrode surfaces, conducting polymers can be electropolymerization with negatively charged molecules incorporated. When the polymer is reduced with negative current, dopant molecules are released from the polymer. This feature can be utilized to deliver neural transmitters and modulators from the electrodes to alter neural network activity. Previously, release of CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), an AMPA (2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl)propanoic acid) receptor antagonist in hippocampal neuron culture effectively suppressed local neural activity in a transient manner. In this study, we further advance this technology by characterizing the drug loading and release capacity from microelectrodes, expanding the range of candidate dopants, and demonstrating in vivo effectiveness in rat somatosensory (S1) barrel cortex. Firstly, to quantify the concentration of released drug, fluorescent model molecule was used and quantitatively assessed in a real time imaging system. Stimulation amplitude was varied to determine the amount of released drug from microelectrodes. Secondly, only negatively charged drugs have been effectively released in the past. In this study, zwitterionic transmitter γ-Aminobutyric acid (GABA) was successfully delivered with the technique, greatly expanding the applicable range for the technique. Finally, we used evoked response from barrel cortex to evaluate the release of DNQX (6,7-dinitroquinoxaline-2,3-dione), an analog of CNQX. The neural activity of barrel cortex reliably represents sensory stimuli from whiskers, hence provides an excellent in vivo network model for evaluating our neurochemical release system. Neural activity from multi-whisker stimulation was immediately and locally suppressed by released DNQX for one to six seconds, demonstrating the high spatial-temporal resolution of the technique. Furthermore, weaker activities were nearly abolished by released DNQX whilst stronger activities were less influenced, because the strong over-saturated neural input can only be partially antagonized. The system demonstrates successful modulation of neural network activity in a highly controllable manner. With the ease of being incorporated in existing neural implants without increasing the volume or complexity, this technology may find use in a wide range of neuroscience studies and potentially therapeutic devices

ELECTROCHEMICAL ANALYSIS SUPPORTED BY MACRO AND MICROELECTRODE ARRAY

The purpose of this project was to investigate cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) analytical techniques for enantioselective sensing at both a macroelectrode and a microelectrode array. The scale of the electrochemical cell was reduced from macro to micro dimensions to improve both the electroanalytical detection and the efficient use of chemicals. A microdevice was fabricated using photolithography and plasma bonding and consisting of a microelectrode array (MEA) of 306 microelectrodes, each with a diameter of 45 µm supported by a polydimethylsiloxane (PDMS) slab engraved with microfluidic channels. The electroanalytical performances of the microdevice were characterised using cyclic voltammetry and it was established that the metallisation process influenced the surface roughness of the electrode, and also affected the final response of the array. The microdevice was used for flow injection analysis using chronoamperometry and provided the capability to detect small changes of analyte concentration. The selective electro-oxidation of phenylethanol catalysed by TEMPO and (-)-sparteine at a macroelectrode and MEA was investigated. The CV analysis showed a reproducible selective oxidation in favour of the (-)-phenylethanol enantiomer. The performances of the electrodes were enhanced to improve their enantioselective capability, and to extend their application to biosensors by functionalising their surface with Self-Assembled Monolayers (SAM). The electrodes were modified with glutathione and cysteine chiral molecules to investigate their ability to recognise the proline enantiomers using EIS analysis. The electron transfer rate of the ferricyanide analyte at the cysteine monolayer was less in the presence of D proline than it was in the presence of L-proline, indicating the selective penetration of the enantiomer through the monolayer. The properties of the macroelectrode and MEA were extended to biological applications by modifying their surfaces with thiolated single stranded DNA