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Intracortical microelectrode arrays (MEAs) are valuable tools for neuroscience research, and their potential clinical use has been demonstrated. However, their inability to function reliably over chronic time points has limited their clinical translation. MEA failure is highly correlated with foreign body response (FBR), and therapeutics have been used to reduce FBR and improve device function, with drugs such as minocycline showing promising results in vivo. To avoid issues associated with systemic drug delivery, device coatings can be used to for therapeutic delivery. One method to locally deliver minocycline is a layer-by-layer (LBL) coating that consists of multiple trilayers of gelatin type A, minocycline, and dextran sulfate; however, the coating's impact on device function was previously unknown. This work characterized 10, 20, and 30 trilayer coatings and then evaluated their effect on device function. Cumulative minocycline release and coating thickness increased with the number of trilayers, agreeing with observations in previous studies. Atomic force microscopy images were used to calculate surface roughness of the coatings, which significantly increased from 10 to 20 trilayers and then remained relatively constant upon increasing to 30 trilayers. Scanning electron microscopy images confirmed that trilayers coated the MEAs. Electrochemical impedance spectroscopy (EIS) and charge carrying capacity (CCC) were used to evaluate the coating's effect on MEA electrochemical behavior over 3 weeks while the coated MEAs soaked in PBS. The 10 trilayer coatings slightly decreased CCC, while 20 and 30 trilayers initially increased CCC. CCC of all trilayers gradually increased as the MEAs soaked in PBS. All trilayers initially increased MEA impedance magnitude and reduced the phase angle at low frequencies. Impedance magnitude at 1 kHz and 15 kHz decreased toward their initial precoated values for all trilayers as the MEAs soaked in PBS. Overall, these results show that the LBL coatings did not significantly impact MEA function.

During neural stimulation it is important to ensure charge transfer does not cause tissue damage. The safe range for stimulation is often defined by the oxidation/reduction of water. However, many biological molecules, such as ascorbic acid (AA), have lower oxidation potentials than water. Due to its low oxidation potential and high concentrations in the brain, we examined the role of AA oxidation during neural stimulation. By measuring the voltage transients during current-controlled stimulation we show significant AA oxidation occurs at stimulation levels typically deemed safe. These results highlight the importance of considering the effect of electrical stimulation on biological molecules.

Electrical stimulation of the nervous system is used clinically to treat diseases such as epilepsy and there is increasing research using electrical stimulation to treat diseases and disorders where traditional pharmaceuticals are not effective. The performance of a device used for neural stimulation depends on its ability to reliably transfer the necessary charge to elicit a physiological response in a manner that is safe for both the tissue and electrode. Electrode materials that transfer charge via faradaic and non-faradaic mechanisms are used for neural stimulation. Electrodes that deliver charge via faradaic processes can accommodate the high amplitudes required for stimulation, but the faradaic reactions change the chemical composition of the surrounding tissue. Electrodes that deliver charge by charging and discharging the capacitive double layer typically deliver less charge than faradaic electrodes, however, they are attractive for neural stimulation because they do not change the chemical composition of the surrounding tissue. Titanium nitride (TiN) is an electrode material that has been used for non-faradaic charge transfer. This work evaluates the performance of TiN electrodes used for chronic peripheral nerve stimulation. To discriminate between electrode changes due to the chronic implantation versus stimulation, a separate set of TiN electrodes were subjected to continuous current-controlled biphasic pulsing in vitro. Methods: Nerve cuffs having four 0.39 mm2 rectangular TiN electrode sites were implanted around the cervical vagus nerve of male Brown Norway rats. The experimental procedures complied with the guidelines for the care and use of laboratory animals and were approved by the University of Florida Institutional Animal Care and Use Committee. Animals were chronically stimulated using current-controlled, charge-balanced biphasic cathode leading pulses. All electrochemical measurements were made with an Autolab potentiostat (PG- STAT12, Eco Chemie, Utrecht, The Netherlands). Electrochemical Impedance Spectroscopy (EIS) was measured using a cuff electrode site as the working electrode, and a bone screw as the reference and counter electrode. The Open Cell Potential (OCP) was measured prior to each measurement and was used as the pseudo zero for the EIS 20 mV peak-to-peak sinusoidal perturbation (wave type = 15 sines). The frequency was swept logarithmically downward from 100kHz to 50Hz. The in vitro electrical aging was performed on a separate set of TiN electrodes with the same specifications that were used in vivo. The electrodes were subjected to continuous current-controlled biphasic pulsing to replicate the amount of charge delivered over the lifetime of an implanted electrode. EIS and cyclic voltammetry (CV) were measured periodically throughout the pulsing. Results: The impedance magnitude increased over the duration of implantation for all animals. However, there appeared to be no relation between the impedance magnitude and amount of stimulation applied.The electrode potential was measured throughout the pulsing and showed a gradual increase over time in the electrode polarization during the anodic and cathodic phases. Electrochemical impedance spectroscopy and cyclic voltammetry were taken periodically throughout the pulsing and showed progressive changes in charge transfer for stimulated electrodes (figure 1B,C) , whereas electrode sites not subjected to stimulation had minimal changes (figure 1A). Stimulated electrodes also showed signs of electrode damage, such as delamination, that were not observed for unstimulated electrodes. Conclusion: Future work will focus on additional analysis of explanted cuffs to directly measure the influence of the in vivo environment. Figure 1