Surface engineered titanium nitride for implantable, soft-surface neural interfacing electrodes

Abstract

Implantable neural interfacing electrodes are conduits for the flow of uni- or bi-directional information between the nervous system and an electrically-active device. Many electrodes, including those in widespread clinical use and those currently under investigation, suffer from three prominent limitations, these being poor electrochemical properties, susceptibility towards fibrous encapsulation, and lack of neural interfacing. Such factors are heavily influenced by the chemistry, morphology, and mechanical properties of the electrode material. This work focuses on a variety of surface engineering techniques applied systematically to titanium nitride (TiN) electrodes with the aim of improving the limiting aspects described. When compared to more established alternatives like platinum (Pt), platinum/iridium (Pt/Ir) alloys, and iridium oxide (IrOx), TiN is a relatively recent addition to the repertoire of suitable materials for chronic neural interfacing electrodes. In its porous and over-stoichiometric form, the transition metal nitride has demonstrated superior electrochemical properties to Ptbased devices, and is broadly described in literature as an electrochemical double-layer capacitor. However, through exclusionary experiments in protonated and non-protonated electrolytes, the porous TiN electrodes in this work were shown to engage in both pseudocapacitance and double-layer capacitance, the former of which constitutes the majority of capacitive action at ~79%. The reversible faradaic reactions were linked to oxygen vacancies in the surface oxide (TiO2) and their cyclic regeneration through nitrogen dopants in the overstoichiometric TiN. This mechanism allowed the electrodes to retain their electrochemical properties (i.e., impedance and charge storage capacity (CSCC)) even with 10,000 charge/discharge cycles at 1 Vs-1 . A prominent issue with porous TiN electrodes, fibrous encapsulation in vivo, was addressed by increasing the surface roughness of the Ti6Al4V alloy prior to PVD. Increasing the root mean square roughness (Rq) of the TiN surface from 0.2 to 4.0 µm was effective in this regard, successfully mitigating the proliferation of fibroblasts and effectively reducing the number of viable cells by 62%. This result was achieved without any adverse effects to the electrochemical behaviour. The TiN electrodes deposited on the roughened substrates exhibited identical impedance and CSCC measurements to the original. Despite the improved fouling resistance and superior electrochemistry as compared to traditional electrode materials (Pt, Pt/Ir, etc.), the properties of TiN could not compete with new, frontier electrode designs. To tackle this shortcoming, a layer of conductive polymer PEDOT:PSS (poly(3,4- ethylenedioxythiophene) polystyrene sulfonate) was electrodeposited onto the roughened TiN electrodes. At the maximum permissible thickness of ~ 9 µm, the polymer successfully reduced the impedance at 1 Hz (|Z|1Hz) by 77% and increased the CSCC at 1 Vs-1 by 52% as compared to the TiN. These improvements were attributed to the porous, nodular structure of the polymer which effectively enlarged the electrochemical surface area of the electrode. Moreover, the large intrinsic pseudocapacitance exhibited by PEDOT:PSS and its wide water window further served to set the TiN/PEDOT:PSS electrodes apart from other materials presently being evaluated for their application in chronic neural interfacing. The electrodes even exhibit superior performance in comparison to frontier materials like carbon nanotubes and to the gold standard within the field, IrOx. The electrochemical properties, namely high capacitance and low impedance, were even retained with 10,000 charge/discharge cycles at a scan rate of 1 Vs-1 , with 20 minutes of ultrasonication at 45 kHz, and in protein-containing electrolytes over 24 hours of immersion The electrodes were made more resistant to fouling and simultaneously more hospitable to neural growth via the electrodeposition of a calcium alginate hydrogel layer. Using a process of anodic electrogelling, thin, bioresorbable gels were successfully grown onto the PEDOT:PSS surface. Following the gradual dissolution of the hydrogel in physiological liquid, the original electrochemical properties of the electrode were almost completely regained. This outcome revealed that the adopted processing procedure of the gel had minimal impact on the characteristics of PEDOT:PSS. Through cell culture experiments, the alginate-coated electrodes were shown to impede both fibroblast attachment and proliferation, resulting in 72% less viable cells on the surfaces after 72 hours as compared to the PEDOT:PSS. Furthermore, both PEDOT:PSS and alginate-coated electrodes were observed to support the adhesion and differentiation of SH-SY5Y cells into neuron-type cells having fusiform morphologies and process extensions. In contrast, TiN surfaces did not allow this differentiation to occur, despite many adherent and proliferating SH-SYFY cells observed on the electrodes. This behaviour was attributed to the stiffness mismatch between the flexible cells and the rigid ceramic, highlighting the importance of soft-surface neural interfacing. The PEDOT:PSS and alginate-coated electrodes thus have significant potential for bio-integration in addition to the benefits of excellent electrochemical properties and resistance to fibrous fouling.