Ruthenium oxide based microelectrode arrays for in vitro and in vivo neural recording and stimulation

Abstract

We have characterized the in vitro and in vivo extracellular neural recording and stimulation properties of ruthenium oxide (RuOx) based microelectrodes. Cytotoxicity and functional neurotoxicity assays were carried out to confirm the in vitro biocompatibility of RuOx. Material extract assays, in accordance to ISO protocol "10993-5: Biological evaluation of medical devices", revealed no significant effect on neuronal cell viability or the functional activity of cortical networks. In vitro microelectrode arrays (MEAs), with indium tin oxide (ITO) sites modified with sputtered iridium oxide (IrOx) and RuOx in a single array, were developed for a direct comparison of electrochemical and recording performance of RuOx to ITO and IrOx deposited microelectrode sites. The impedance of the RuOx-coated electrodes measured by electrochemical impedance spectroscopy was notably lower than that of ITO electrodes, resulting in robust extracellular recordings from cortical networks in vitro. We found comparable signal-to-noise ratios (SNRs) for RuOx and IrOx, both significantly higher than the SNR for ITO. RuOx-based MEAs were also fabricated and implanted in the rat motor cortex to demonstrate manufacturability of the RuOx processing and acute recording capabilities in vivo. We observed single-unit extracellular action potentials with a SNR >22, representing a first step for neurophysiological recordings in vivo with RuOx based microelectrodes.

Monitoring Contractile Cardiomyocytes via Impedance Using Multipurpose Thin Film Ruthenium Oxide Electrodes

“…The frequency response of the setup using RuOx electrode and a Pt wire showed similar behavior; however, with seemingly an additional relaxation mechanism at the intermediate frequencies (between 5–1000 Hz). An impedance sweep of a flat RuOx electrode [ 12 ] did not show similar additional relaxation mechanism. This implies that this extra mechanism corresponds to the rough surface of our RuOx electrode.…”

“…It was also made sure that no air bubbles were present between the electrode and the membrane. Both the Pt and RuOx materials have been previously reported to be biocompatible in in vitro settings [ 9 , 12 , 25 , 34 ]. Therefore, cells viability was observed based solely on their contractile activities.…”

“…For instance, many works have shown different electrochemical modes of ruthenium oxide (RuOx) electrodes and their applications in in vitro studies. The electrode has been reported as a potentiometric pH electrode [ 7 , 8 ], an amperometric oxygen electrode [ 9 ], an amperometric nitric oxide electrode [ 10 , 11 ], as well as an electrophyiosology electrode [ 12 ]. This work presents another mode of operation, using the thin film RuOx electrode to observe the contractile activities of a human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) monolayer through electrical impedance spectroscopy (EIS), demonstrating the versatility of the presented RuOx electrode.…”

Electrophysiological Analysis of Brain Organoids: Current Approaches and Advancements

“…Recent advances in bioprinting have been utilized to demonstrate proof-of-concept for patterning and printing MEAs on soft material substrates with mechanical properties similar to brain tissue, assisting with biocompatibility ( Adly et al, 2018 ; Borda et al, 2020 ). To improve electrode properties (i.e., biocompatibility, impedance, structural integrity, transparency), many new materials have been used for design and coating, such as indium tin oxide, gold, titanium nitride, and ruthenium oxide, among others ( Jahnke et al, 2019 ; Koklu et al, 2019 ; Ryynänen et al, 2019 , 2020 ; Atmaramani et al, 2020 ). The continued development of MEAs incorporating these and other materials, as well as improved incorporation methods, may help improve signal-to-noise ratios and fidelity for brain organoid recordings.…”

W:Ti Flexible Transversal Electrode Array for Peripheral Nerve Stimulation: A Feasibility Study

“…Numerous materials have been used over the years and some of the most popular are platinum, platinum:iridium, gold, titanium nitride and tungsten [25], [48], [50]. More recently, some of the new emerging materials are PEDOT:PSS, carbon nanotubes [50], ruthenium oxide [51] and conductive elastomers composites [52]. Considering more traditional materials, tungsten has been described as a valuable material for neural signal recording [25], [48], [49], however, it has not been comprehensively investigated for its stimulation capabilities.…”