MICROELECTRODE ARRAY FOR CAPACITIVE TRANSDUCTION OF RETINAL RESPONSES

Neural degenerative diseases and traumatic injuries to the eye affect millions of people worldwide, motivating the development of neural prosthetic interfaces to restore sensory or motor function in affected individuals. Advances in neural sensing and stimulation interface technology will allow a more comprehensive understanding of neural function while leading to the development of hybrid biological-electronic sensor devices for robust, functioning neural prosthetic systems. Current techniques of neural activity sensing employ multi-electrode arrays (MEAs) that typically incorporate metal electrodes vi and measure currents via an electrochemical junction, leading to corrosion and charge transfer across the electrode-tissue interface. High-density neural interface technology will require active circuitry within the implant; the device must withstand corrosion and induce minimal damage at the electrode/tissue interface. The work shown here demonstrates a prototype neural interface device based on capacitive coupling through hafnium oxide encapsulation of a novel 3D device architecture, advancing neural sensing technology toward long-term implantable neural interfaces. The functionalization of biosensors interfaced with neural tissue is important to ensure that the active components of the sensor are fully protected from the surrounding biological environment. Self-assembled monolayers (SAMs) have been extensively studied as coatings for implantable devices due to their ability to tailor surface properties and relative ease of film formation. We report a series of studies aimed at investigating the stability of phosphonate self-assembled monolayers, octdecylphosphonic acid (ODPA) or perfluorophosphonic acid (PFPA) on various oxide surfaces (SiO2, TiO2, Al2O3 and HfO2) to serve as the biotic-abiotic interface of the prototype neural device developed here. The monolayers were deposited by a series of techniques including selfassembly from solution, tethering by aggregation and growth and Langmuir-Blodgett (LB). SAMs prepared by LB were primarily used in our stability investigations because they were found to be the most uniform and reproducible. All films deposited on oxidecoated substrates were characterized by means of water contact angle measurements, spectroscopic ellipsometry, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). XPS data conclusively showed covalent phosphonate formation on vii all substrates except SiO2, which had background spectra that interfered with the data analysis. AFM images of SAMs formed on SiO2 and TiO2 showed significant surface reorganization upon exposure to water within 30 minutes. SAMs formed on Al2O3 and HfO2 were much more stable upon exposure to water. PFPA SAMs on HfO2 were found to be the most stable SAMs studied here in either water or phosphate buffer at room temperature. This is the first report of a SAM-oxide system showing stability for an extended period of time, greater than 20 days. These data suggest that phosphonate SAMs should be considered for implantable neural devices that require longer-term stability under aqueous conditions. To examine the encoding and processing of information by networks of neurons, microelectrode arrays (MEAs) have been developed and applied, but evolving scientific questions and biomedical applications require higher density sampling and wider spatial coverage. The integration of 3D electrodes can provide closer contact with neurons to facilitate detection and resolution of single cell action potentials. The fabrication methods implemented here allows reliable fabrication of a novel MEA consisting of probes with dimensions of a few microns, unlike most other approaches to 3D electrode arrays, which produce structures on the scale of tens of microns or more. The device incorporates over 3,800 micro pillar electrodes, grouped into 60 independent sensors for compatibility with existing electronics, spread over an area of 750 μm; each sensor site consists of an 8x8 array of micropillars, interconnected by a lead to an output pad of the device. Individual 3D pillars are 3 μm in diameter with a height of 8 μm. Our experience has suggested that such microstructured probes can achieve more intimate contact with viii the surface of neural tissue, and enhance the quality of neuronal recordings. Electrochemical impedance spectroscopy (EIS) at 1 kHz measured average magnitude and phase shift of 710 W and 17°, respectively, for a single sensor site. These values confirm the robustness of our fabrication process for developing highly conductive 3D microelectrodes. The results shown here demonstrate high-density, three-dimensional microfabrication technology that was applied to the development of an advanced capacitive sensor array for neural tissue. Applications in sensing technology now require electro-neural interface devices to withstand corrosion and induce minimal damage at the electrode/tissue interface. We have developed a platform suitable for hermetic sealing and have shown encapsulation through atomic layer deposition of hafnium oxide over the active components of the device to overcome the direct current limitations of existing MEA technology. EIS was used to study the oxide deposition on the 3D micro pillar sensor array to ensure a pinhole-free dielectric coating. The characteristic impedance magnitudes increase up to 3 orders of magnitude upon oxide deposition and the phase indicates fully capacitive sensor sites. The fabrication process and electrochemical impedance study shown here, demonstrates the usefulness of such techniques for building high-density 3D arrays that can be fully encapsulated with a protective dielectric coating. This work advances the technology towards capacitive sensing of retinal neurons with a robust, non-invasive sensing device. ix Sensing retinal neurons with the 3D micropillar array developed here was performed for direct current and capacitive configurations of the device. Electroretinograms (ERGs) were recorded and the overall performance of the device was analyzed. The devices showed good consistency across all 60 Pt electrode clusters during characterization and when interfaced with retinal tissue. ERGs were recorded by more than 80% of the direct current electrode sites and the performance was evenly distributed around the mean response. This performance surpasses previous reports of 3D electrode arrays interfaced with retinal tissue, where typically 1-6 electrode signals are recorded successfully. Encapsulation of the device platform was achieved and successful recordings of ERG signals were shown. This work is the first report of sensing the overall electrical behavior of retinal tissue with a coupled capacitive MEA. x Table of