In vivo measurements with robust silicon-based multielectrode arrays with extreme shaft lengths

In this paper, manufacturing and in vivo testing of extreme-long Si-based neural microelectrode arrays are presented. Probes with different shaft lengths (15–70 mm) are formed by deep reactive ion etching and have been equipped with platinum electrodes of various configurations. In vivo measurements on rats indicate good mechanical stability, robust implantation, and targeting capability. High-quality signals have been recorded from different locations of the cerebrum of the rodents. The accompanied tissue damage is characterized by histology

Controlling the Biocompatibility and Mechanical Effects of Implantable Microelectrodes to Improve Chronic Neural Recordings in the Auditory Nervous System

Implantable microelectrodes are useful for monitoring neural response patterns in the auditory cortex, however chronic neural recordings can often deteriorate with time (e.g. impedance measures across electrode arrays generally increase monotonically over the first 7 days post-implant). This problem is caused by the increasing spatial distribution of reactive tissue responses (corresponding to changes in impedance spectra along the electrode-tissue-interface). Therefore, the design of microelectrode probes must ensure that the neuronal ensembles lie within a cylindrical radius of the recording electrodes. In this chapter, chronic neural recording failure is examined via cortical spike patterns, histological analyses, indentation experiments, and finite element models. Next, the microfabrication of the “Utah” electrode array and the “Michigan” probe is compared to determine how their size, shape, and geometry address: (1) the spatial distribution of neurons (as related to recording quality); (2) the initial penetrating profile (as related to insertion killzones); (3) the reactive cell responses (as related to glial encapsulation); (4) the anchoring of the probe’s position in the tissue (as related to micromotions) and (5) the embedding of various bioactive reagents (ex: growth factors, anti-inflammatory drugs, etc.). Finally, a novel hydrogel “Dropping Method” is proposed for controlling the biocompatibility and mechanical properties at the electrode-tissue-interface

A tailored biocompatible neural interface for long term monitoring in neural networks

Neural interface electrodes that can record from neurons in the brain for long periods of time will be of great importance to unravel how the brain accomplishes its functions. However, current electrodes usually cause significant glia reactions and loss of neurons within the adjacent brain parenchyma. To address this challenge, a novel, polymer-based neural probe, with protrusions tailored to the target tissue, was developed to investigate which probe properties affect the development of a glial scar and neuronal cell death surrounding probes. After many cycles of testing – refinements, promising recordings of neural activity were obtained in both cerebellum and cortex cerebri (papers I-III). In paper IV, we evaluated the importance of mechanical flexibility and demonstrated that probe flexibility has a significant impact on the astroglial scar, but not on the loss of neurons nearby. Moreover, by embedding the dummy probes in a gelatin matrix that dissolves shortly following implantation, neuronal cell death surrounding chronically (6 weeks) implanted electrodes was, for the first time, abolished. In paper V, sensory processing in primary somatosensory cortex during an episode of hyperalgesia was monitored using implanted neural interfaces in order to further evaluate the probe functionality and usefulness in neurophysiological research. By tracking the development of primary and secondary hyperalgesia as well as allodynia in the sensory cortex, we demonstrate the usefulness of our new neural interface and its capability to differentially and simultaneously record neural signals in different cortical laminae in awake freely moving animals

Doctor of Philosophy

dissertationBy enabling neuroprosthetic technologies, neural microelectrodes can greatly improve diagnostic and treatment options for millions of individuals living with limb loss, paralysis, and sensory and autonomic neural disorders. However, clinical use of these devices is restricted by the limited functional lifetimes of implanted electrodes, which are commonly less than a few years. One cause is the evolution of damage to dielectric encapsulation that insulates microelectrodes from the physiological environment. Fluid penetration and exposure to an aggressive immunological response over time may weaken encapsulating films and cause electrical shunting. This reduces electrode impedance, diverts electrical signal away from target tissue, and causes multi-channel crosstalk. To date, no neural microelectrode encapsulating material or design approach has reliably resolved this issue. We employ the parylene C-encapsulated Utah Electrode Array (UEA), a silicon-micromachined neural interface FDA-cleared for human use, to execute three aims that address this challenge through investigations of new materials, electrode designs, and testing methods. We first evaluate a novel bilayer encapsulating film comprised of atomic layer deposited Al2O3 and parylene C, testing this film using UEAs and devices with UEA-relevant topography. Contrasting with previous work employing simplified planar structures, the incorporation of neural electrode features on test structures revealed failure modes pointing to the dissolution of Al2O3 over time. Our results emphasize the need for dielectric coatings resistant to water degradation as well as test methods that take electrode features into account. In our second aim, we show through finite element modeling and aggressive in vitro testing that use of degenerately doped silicon as a conductive neural electrode material can mitigate the consequences of encapsulation damage, owing to the high electrochemical impedance of silicon. Our final aim compares oxidative in vitro aging to long-term in vivo material damages and finds clear evidence that such in vitro testbeds may help predict certain in vivo damage modes. By pairing this testing with absorption and emission spectroscopic characterization modalities, we identify contributors to material damage and future design solutions. Our results will inform future material and testing choices, to improve the resilience of neural electrode dielectric encapsulation and enhance the longevity of neuroprostheses

Carbon Fiber Microelectrode Arrays for Neuroprosthetic and Neuroscience Applications.

The aim of this work is to develop, validate, and characterize the insertion mechanism, tissue response, and recording longevity of a new high-density carbon fiber microelectrode array. This technology was designed to significantly improve the field of penetrating microelectrodes while simultaneously accommodating the variable needs of both neuroscientists and neural engineers. The first study presents the fabrication and insertion dynamics of a high-density carbon fiber electrode array using a dual sided printed circuit board platform. The use of this platform has pushed electrode density to limits not seen in other works. This necessitated the use of an encapsulation method that served to temporarily stiffen the fibers during insertion, but did not enter the brain as many other shuttles do for other probe designs. The initial findings in this work informed the development of an even higher density array using a silicon support structure as a backbone. The second study reports on the tissue reaction of chronically implanted carbon fiber electrode arrays as compared to silicon electrodes. Due to their smaller footprint, the reactive response to carbon fibers should be greatly attenuated, if not non-existent. Results show a scarring response to the implanted silicon electrode with elevated astrocyte and microglia activity coupled to a local decrease in neuronal density. The area implanted with the carbon fiber electrodes showed a varied response, from no detectable increase in astrocytic or microglial activity to an elevated activation of both cell types, but with no detectable scars. Neuronal density in the carbon fiber implant region was unaffected. The data demonstrates that the small carbon fiber profile, even in an array configuration, shows an attenuated reactive response with no visible scaring. The final study reports on the viability of chronically implanted high-density carbon fiber arrays as compared to more traditional silicon planar arrays with comparable site sizes. While most new probe technologies or designs are able to demonstrate proof of concept functionality in acute preparations, very few show the ability to record chronic unit activity. This study aims to provide a comprehensive analysis of electrophysiology data collected over implant durations ranging from 3 – 5 months.PhDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111557/1/parasp_1.pd

Doctor of Philosophy

dissertationBiomedical implantable devices have been developed for both research and clinical applications, to stimulate and record physiological signals in vivo. Chronic use of biomedical devices with thin-film-based encapsulation in large scale is impeded by their lack of long-term functionality and stability. Biostable, biocompatible, conformal, and electrically insulating coatings that sustain chronic implantation are essential for chip-scale implantable electronic systems. Even though many materials have been studied to for this purpose, to date, no encapsulation method has been thoroughly characterized or qualified as a broadly applicable long-term hermetic encapsulation for biomedical implantable devices. In this work, atomic layer deposited Al2O3 and Parylene C bi-layer was investigated as encapsulation for biomedical devices. The combination of ALD Al2O3 and CVD Parylene C encapsulation extended the lifetime of coated interdigitated electrodes (IDEs) to up to 72 months (to date) with low leakage current of ~ 15 pA. The long lifetime was achieved by significantly reducing moisture permeation due to the ALD Al2O3 layer. Moreover, the bi-layer encapsulation separates the permeated moisture (mostly at the Al2O3 and Parylene interface) from the surface contaminants (mostly at the device and Al2O3 interface), preventing the formation of localized electrolyte through condensation. Al2O3 works as an inner moisture barrier and Parylene works as an external ion barrier, preventing contact of AI2O3 with liquid water, and slowing the kinetics of alumina corrosion. Selective removal of encapsulation materials is required to expose the active sites for interacting with physiological environment. A self-aligned mask process with three steps was developed to expose active sites, composed of laser ablation, oxygen plasma etching, and BOE etching. Al2O3 layer was found to prevent the formation of microcracks in the iridium oxide film during laser ablation. Bi-layer encapsulated iridium oxide had higher charge injection capacity and similar electrochemical impedance compared with Parylene C coated iridium oxide film after deinsulation. The Al2O3 and Parylene C bi-layer encapsulation was applied to Utah electrode array (UEA)-based neural interfaces to study its long-term performance. The median tip impedance of the bi-layer encapsulated wired Utah electrode array increased slowly during the 960 days of equivalent soak testing at 37 °C. Impedance for Parylene coated UEA dropped 50% to 75% within 6 months. In addition, bi-layer coated fully integrated Utah array-based wireless neural interfaces had stable power-up frequencies at ~910 MHz and constant RF signal strength of -50 dBm during the 1044 days of equivalent soaking time at 37 °C. This is much longer than lifetime achieved with Parylene C coating, which was about one year at room temperature

Signal-to-Noise Ratio Enhancement Using Graphene-Based Passive Microelectrode Arrays

This work is aimed toward the goal of investigating the influence of different materials on the signal-to-noise ratio (SNR) of passive neural microelectrode arrays (MEAs). Noise reduction is one factor that can substantially improve neural interface performance. The MEAs are fabricated using gold, indium tin oxide (ITO), and chemical vapor deposited (CVD) graphene. 3D-printed Nylon reservoirs are then adhered to the glass substrates with identical MEA patterns. Reservoirs are filled equally with a fluid that is commonly used for neuronal cell culture. Signal is applied to glass micropipettes immersed in the solution, and response is measured on an oscilloscope from a microprobe placed on the contact pad external to the reservoir. The time domain response signal is transformed into a frequency spectrum, and SNR is calculated from the ratio of power spectral density of the signal to the power spectral density of baseline noise at the frequency of the applied signal. We observed as the magnitude or the frequency of the input voltage signal gets larger, graphene-based MEAs increase the signal-to-noise ratio significantly compared to MEAs made of ITO and gold. This result indicates that graphene provides a better interface with the electrolyte solution and could lead to better performance in neural hybrid systems for in vitro investigations of neural processes

Developing Next-generation Brain Sensing Technologies - A Review.

Advances in sensing technology raise the possibility of creating neural interfaces that can more effectively restore or repair neural function and reveal fundamental properties of neural information processing. To realize the potential of these bioelectronic devices, it is necessary to understand the capabilities of emerging technologies and identify the best strategies to translate these technologies into products and therapies that will improve the lives of patients with neurological and other disorders. Here we discuss emerging technologies for sensing brain activity, anticipated challenges for translation, and perspectives for how to best transition these technologies from academic research labs to useful products for neuroscience researchers and human patients