A watertight acrylic-free titanium recording chamber for electrophysiology in behaving monkeys.

Neurophysiological recording in alert monkeys requires the creation of a permanent aperture in the skull for repeated insertion of microelectrodes. Most laboratories use polymethyl methacrylate to attach a recording chamber over the skull opening. Here, we describe a titanium chamber that fastens to the skull with screws, using no polymethyl methacrylate. The gap between the base of the chamber and the skull is filled with hydroxyapatite, forming a watertight gasket. As the chamber base osseointegates with the skull, the hydroxyapatite is replaced with bone. Rather than having a finite lifetime, the recording chamber becomes more firmly anchored the longer it is in place. It has a small footprint, low profile, and needs little maintenance to control infection. Toilette consists of occasional application of betadine to clean the scalp margin, followed by application of neomycin, polymyxin, and bacitracin ointment. Antibiotic is also placed inside the chamber to suppress bacterial proliferation. Thickening of the dura within the chamber can be prevented by regular application of mitocycin C and/or bevacizumab, an antibody against vascular endothelial growth factor. By conducting an e-mail survey, this protocol for chamber maintenance was compared with procedures used in 37 other vision research laboratories. Refinement of appliances and techniques used for recordings in awake monkeys promises to increase the pace of scientific discovery and to benefit animal welfare.

A high-density carbon fiber neural recording array technology.

OBJECTIVE: Microwire and Utah-style neural recording arrays are the predominant devices used for cortical neural recording, but the implanted electrodes cause a significant adverse biological response and suffer from well-studied performance degradation. Recent work has demonstrated that carbon fiber electrodes do not elicit this same adverse response, but these existing designs are not practically scalable to hundreds or thousands of recording sites. We present technology that overcomes these issues while additionally providing fine electrode pitch for spatial oversampling. APPROACH: We present a 32-channel carbon fiber monofilament-based intracortical neural recording array fabricated through a combination of bulk silicon microfabrication processing and microassembly. This device represents the first truly two-dimensional carbon fiber neural recording array. The density, channel count, and size scale of this array are enabled by an out-of-plane microassembly technique in which individual fibers are inserted through metallized and isotropically conductive adhesive-filled holes in an oxide-passivated microfabricated silicon substrate. MAIN RESULTS: Five-micron diameter fibers are spaced at a pitch of 38 microns, four times denser than state of the art one-dimensional arrays. The fine diameter of the carbon fibers affords both minimal cross-section and nearly three orders of magnitude greater lateral compliance than standard tungsten microwires. Typical [Formula: see text] impedances are on the order of hundreds of kiloohms, and successful in vivo recording is demonstrated in the motor cortex of a rat. 22 total units are recorded on 20 channels, with unit SNR ranging from 1.4 to 8.0. SIGNIFICANCE: This is the highest density microwire-style electrode array to date, and this fabrication technique is scalable to a larger number of electrodes and allows for the potential future integration of microelectronics. Large-scale carbon fiber neural recording arrays are a promising technology for reducing the inflammatory response and increasing the information density, particularly in neural recording applications where microwire arrays are already used.

Reliability of parylene-based multi-electrode arrays chronically implanted in adult rat brains, and evidence of electrical stimulation on contact impedance.

OBJECTIVE: The goal of this study was to evaluate the long-term behavior of the surface electrode through electrochemical characterization and follow-up of implanted parylene/platinum microelectrodes. APPROACH: To this aim, we designed and manufactured specific planar electrodes for cortical implantation for a rat model. This work was included in the INTENSE® project, one of the goals of which was to prove the feasibility of selective neural recording or stimulation with cuff electrodes around the vagus nerve. MAIN RESULTS: After a 12-week implantation in a rat model, we can report that these microelectrodes have withstood in vivo use. Regarding the biocompatibility of the electrodes (materials and manufacturing process), no adverse effect was reported. Indeed, after the three-month implantation, we characterized limited tissue reaction beneath the electrodes and showed an increase and a stabilization of their impedance. Interestingly, the follow-up of the electrochemical impedance combined with electrical stimulation highlighted a drop in the impedance up to 60% at 1 kHz after ten minutes of electrical stimulation at 110 Hz. SIGNIFICANCE: This study gives evidence of the biocompatibility of the parylene platinum contact array designed for the project and confirms the effect of stimulation on the contact impedance.

Electrode fabrication and interface optimization for imaging of evoked peripheral nervous system activity with electrical impedance tomography (EIT).

OBJECTIVE: Non-invasive imaging techniques are undoubtedly the ideal methods for continuous monitoring of neural activity. One such method, fast neural electrical impedance tomography (EIT) has been developed over the past decade in order to image neural action potentials with non-penetrating electrode arrays. APPROACH: The goal of this study is two-fold. First, we present a detailed fabrication method for silicone-based multiple electrode arrays which can be used for epicortical or neural cuff applications. Secondly, we optimize electrode material coatings in order to achieve the best accuracy in EIT reconstructions. MAIN RESULTS: The testing of nanostructured electrode interface materials consisting of platinum, iridium oxide, and PEDOT:pTS in saline tank experiments demonstrated that the PEDOT:pTS coating used in this study leads to more accurate reconstruction dimensions along with reduced phase separation between recording channels. The PEDOT:pTS electrodes were then used in vivo to successfully image and localize the evoked activity of the recurrent laryngeal fascicle from within the cervical vagus nerve. SIGNIFICANCE: These results alongside the simple fabrication method presented here position EIT as an effective method to image neural activity.

A review on mechanical considerations for chronically-implanted neural probes.

This review intends to present a comprehensive analysis of the mechanical considerations for chronically-implanted neural probes. Failure of neural electrical recordings or stimulation over time has shown to arise from foreign body reaction and device material stability. It seems that devices that match most closely with the mechanical properties of the brain would be more likely to reduce the mechanical stress at the probe/tissue interface, thus improving body acceptance. The use of low Young's modulus polymers instead of hard substrates is one way to enhance this mechanical mimetism, though compliance can be achieved through a variety of means. The reduction of probe width and thickness in comparison to a designated length, the use of soft hydrogel coatings and the release in device tethering to the skull, can also improve device compliance. Paradoxically, the more compliant the device, the more likely it will fail during the insertion process in the brain. Strategies have multiplied this past decade to offer partial or temporary stiffness to the device to overcome this buckling effect. A detailed description of the probe insertion mechanisms is provided to analyze potential sources of implantation failure and the need for a mechanically-enhancing structure. This leads us to present an overview of the strategies that have been put in place over the last ten years to overcome buckling issues. Particularly, great emphasis is put on bioresorbable polymers and their assessment for neural applications. Finally, a discussion is provided on some of the key features for the design of mechanically-reliable, polymer-based next generation of chronic neuroprosthetic devices.

Evaluating the in vivo glial response to miniaturized parylene cortical probes coated with an ultra-fast degrading polymer to aid insertion.

OBJECTIVE: Despite the feasibility of short-term neural recordings using implantable microelectrodes, attaining reliable, chronic recordings remains a challenge. Most neural recording devices suffer from a long-term tissue response, including gliosis, at the device-tissue interface. It was hypothesized that smaller, more flexible intracortical probes would limit gliosis by providing a better mechanical match with surrounding tissue. APPROACH: This paper describes the in vivo evaluation of flexible parylene microprobes designed to improve the interface with the adjacent neural tissue to limit gliosis and thereby allow for improved recording longevity. The probes were coated with an ultrafast degrading tyrosine-derived polycarbonate (E5005(2K)) polymer that provides temporary mechanical support for device implantation, yet degrades within 2 h post-implantation. A parametric study of probes of varying dimensions and polymer coating thicknesses were implanted in rat brains. The glial tissue response and neuronal loss were assessed from 72 h to 24 weeks post-implantation via immunohistochemistry. MAIN RESULTS: Experimental results suggest that both probe and polymer coating sizes affect the extent of gliosis. When an appropriate sized coating dimension (100 µm × 100 µm) and small probe (30 µm × 5 µm) was implanted, a minimal post-implantation glial response was observed. No discernible gliosis was detected when compared to tissue where a sham control consisting of a solid degradable polymer shuttle of the same dimensions was inserted. A larger polymer coating (200 µm × 200 µm) device induced a more severe glial response at later time points, suggesting that the initial insertion trauma can affect gliosis even when the polymer shuttle degrades rapidly. A larger degree of gliosis was also observed when comparing a larger sized probe (80 µm × 5 µm) to a smaller probe (30 µm × 5 µm) using the same polymer coating size (100 µm × 100 µm). There was no significant neuronal loss around the implantation sites for most device candidates except the group with largest polymer coating and probe sizes. SIGNIFICANCE: These results suggest that: (1) the degree of mechanical trauma at device implantation and mechanical mismatches at the probe-tissue interface affect long term gliosis; (2) smaller, more flexible probes may minimize the glial response to provide improved tissue biocompatibility when used for chronic neural signal recording; and (3) some degree of glial scarring did not significantly affect neuronal distribution around the probe.

Analysis of Al2O3-parylene C bilayer coatings and impact of microelectrode topography on long term stability of implantable neural arrays.

OBJECTIVE: Performance of many dielectric coatings for neural electrodes degrades over time, contributing to loss of neural signals and evoked percepts. Studies using planar test substrates have found that a novel bilayer coating of atomic-layer deposited (ALD) Al2O3 and parylene C is a promising candidate for neural electrode applications, exhibiting superior stability to parylene C alone. However, initial results from bilayer encapsulation testing on non-planar devices have been less positive. Our aim was to evaluate ALD Al2O3-parylene C coatings using novel test paradigms, to rigorously evaluate dielectric coatings for neural electrode applications by incorporating neural electrode topography into test structure design. APPROACH: Five test devices incorporated three distinct topographical features common to neural electrodes, derived from the utah electrode array (UEA). Devices with bilayer (52 nm Al2O3 + 6 µm parylene C) were evaluated against parylene C controls (N ⩾ 6 per device type). Devices were aged in phosphate buffered saline at 67 °C for up to 311 d, and monitored through: (1) leakage current to evaluate encapsulation lifetimes (>1 nA during 5VDC bias indicated failure), and (2) wideband (1-105 Hz) impedance. MAIN RESULTS: Mean-times-to-failure (MTTFs) ranged from 12 to 506 d for bilayer-coated devices, versus 10 to >2310 d for controls. Statistical testing (log-rank test, α = 0.05) of failure rates gave mixed results but favored the control condition. After failure, impedance loss for bilayer devices continued for months and manifested across the entire spectrum, whereas the effect was self-limiting after several days, and restricted to frequencies <100 Hz for controls. These results correlated well with observations of UEAs encapsulated with bilayer and control films. SIGNIFICANCE: We observed encapsulation failure modes and behaviors comparable to neural electrode performance which were undetected in studies with planar test devices. We found the impact of parylene C defects to be exacerbated by ALD Al2O3, and conclude that inferior bilayer performance arises from degradation of ALD Al2O3 when directly exposed to saline. This is an important consideration, given that neural electrodes with bilayer coatings are expected to have ALD Al2O3 exposed at dielectric boundaries that delineate electrode sites. Process improvements and use of different inorganic coatings to decrease dissolution in physiological fluids may improve performance. Testing frameworks which take neural electrode complexities into account will be well suited to reliably evaluate such encapsulation schemes.

In vivo monitoring of extracellular glutamate in the brain with a microsensor.

Recent discoveries have revealed that glutamatergic neurotransmission in the central nervous system is mediated by a dynamic interplay between neurons and astrocytes. To enhance our understanding of this process, the study of extracellular glutamate is crucial. At present, microdialysis is the most frequently used analytical technique to monitor extracellular glutamate levels directly in the brain. However, the neuronal and physiological origin of the detected glutamate levels is questioned as they do not fulfil the classical release criteria for exocytotic release, such as calcium dependency or response to the sodium channel blocker tetrodotoxine (TTX). It is hypothesized that an analytical technique with a higher spatial and temporal resolution is required. Glutamate microsensors provide a promising analytical solution to meet this requirement. In the present study, we applied a 10 micro m diameter hydrogel-coated glutamate microsensor to monitor extracellular glutamate levels in the striatum of anesthetized rats. To explore the potential of the microsensor, different pharmacological agents were injected in the vicinity of the sensor at an approximate distance of 100 micro m. It was observed that KCl, exogenous glutamate, kainate and the reuptake inhibitor DL-threo-beta-benzyloxyaspartate (DL-TBOA) increased the extracellular glutamate levels significantly. TTX decreased the basal extracellular glutamate levels approximately 90%, which indicates that the microsensor is capable of detecting neuronally derived glutamate. This is one of the first studies in which a microsensor is applied in vivo on a routine base, and it is concluded that microsensor research can contribute significantly to improve our understanding of the physiology of glutamatergic neurotransmission in the brain.

Electrocoating carbon fiber microelectrodes with Nafion improves selectivity for electroactive neurotransmitters.

A method which improves carbon fiber microelectrode selectivity for cationic amines by electrocoating the fiber with a thin film of the ionic polymer, Nafion, is described. The selectivity and response speed of these electrodes for the detection of electroactive cationic and anionic species found in brain extracellular fluid was evaluated using differential pulse voltammetry and chronoamperometry and compared to uncoated fibers. Carbon fiber microelectrodes electrocoated with Nafion are highly sensitive to cationic amines such as dopamine and serotonin and have minimal sensitivity to anions such as ascorbic acid and uric acid at physiological concentrations.

Improved methods for construction of carbon fibre electrodes for extracellular spike recording.

Microelectrodes using single carbon fibres as the conducting element have been used since 1979 for electrophysiological measurements in vivo and in vitro. However, there is still considerable discussion about the manufacture of these electrodes, and no overall agreement as to the best way to minimise electrode noise. In this article we describe some revised methods for carbon fibre electrode manufacture, which we believe, gives the lowest noise performance for spike recording in vivo.

Sampling glutamate and GABA with microdialysis: suggestions on how to get the dialysis membrane closer to the synapse.

Microdialysis is currently optimized to sample the extrasynaptic pool. As such, the technique has facilitated discovery of ischemia-induced excitotoxic glutamate overflow (Benveniste H, Drejer J, Schousboe A, Diemer NH, 1987, Regional cerebral glucose phosphorylation and blood flow after insertion of a microdialysis fiber through the dorsal hippocampus in the rat. J. Neurochem., 49, 729-734) and adenosinergic sleep drive (Porkka-Heiskanen T, Strecker RE, Thakkar M, Bjorkum AA, Greene RW, McCarley RW, 1997, Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science, 276 (5316), 1265-1268); and is proving essential for clinical monitoring of glutamate and cellular metabolites in stroke and head trauma (Sarrafzadeh AS, Sakowitz OW, Kiening KL, Benndorf G, Lanksch WR, Unterberg AW. Bedside microdialysis: a tool to monitor cerebral metabolism in subarachnoid hemorrhage patients? Crit. Care Med. 2002, 30 (5): 1062-1070). Study of the origin of extrasynaptic glutamate sampled with microdialysis has advanced understanding of extrasynaptic signal processing (Baker DA, Xi ZX, Shen H, Swanson CJ, Kalivas PW. The origin and neuronal function of in vivo nonsynaptic glutamate. J. Neurosci. 2002, 22 (20): 9134-9141; Baker DA, McFarland K, Lake RW, Shen H, Tang XC, Toda S, Kalivas PW, 2003, Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse. Nat. Neurosci., 6, 743-749) in the CNS. Microdialysis studies furthermore demonstrate that synaptic pools of some neurotransmitters spill into the extrasynaptic space. For this reason, microdialysis has provided a window into the synaptic pool that has significantly advanced understanding of neurotransmitter control of behavior (Tanda G, Pontieri FE, Di Chiara G, 1997, Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism. Science, 276, 2048-2050). Nonetheless, ability to sample synaptic pools of neurotransmitters is limited. Here we summarize evidence that microdialysis often fails to sample synaptic pools of neurotransmitters, such as glutamate and GABA because of rapid clearance and limited diffusion of these neurotransmitters from the synapse. Moreover, we consider means to move the dialysis membrane closer to the synapse to facilitate sampling of the synaptic pool of these neurotransmitters by minimizing tissue trauma, decreasing probe size and increasing temporal resolution.

In vivo microelectrode track reconstruction using magnetic resonance imaging.

To obtain more precise anatomical information about cortical sites of microelectrode recording and microstimulation experiments in alert animals, we have developed a non-invasive, magnetic resonance imaging (MRI) technique for reconstructing microelectrode tracks. We made microelectrode penetrations in the brains of anesthetized rats and marked sites along them by depositing metal, presumably iron, with anodic monophasic or biphasic current from the tip of a stainless steel microelectrode. The metal deposits were clearly visible in the living animal as approximately 200 microm wide hypointense punctate marks using gradient echo sequences in a 4.7T MRI scanner. We confirmed the MRI findings by comparing them directly to the postmortem histology in which the iron in the deposits could be rendered visible with a Prussian blue reaction. MRI-visible marks could be created using currents as low as 1 microA (anodic) for 5 s, and they remained stable in the brains of living rats for up to nine months. We were able to make marks using either direct current or biphasic current pulses. Biphasic pulses caused less tissue damage and were similar to those used by many laboratories for functional microstimulation studies in the brains of alert monkeys.

Simultaneous real-time amperometric measurement of catecholamines and serotonin at carbon fibre 'dident' microelectrodes.

Amperometry allows real-time measurement of in vivo electrochemical signals, albeit with no capacity to identify the constituents of the signal. In the present study, differential amperometry was used to monitor catecholamine and serotonin (5-HT) simultaneously at the same location. 'Dident' carbon fibre microelectrodes (microelectrodes with two working electrodes in a single assembly) were constructed and coated with Nafion to prevent poisoning on contact with brain tissue. One electrode (channel A) was held at +200 mV versus Ag/AgCl to monitor catecholamines selectively. This potential is too low to oxidise 5-HT. The second electrode (channel B), recording faradaic current at +500 mV versus Ag/AgCl, measured the sum of catecholamine and 5-HT oxidation. The 5-HT current component was the difference of channel B minus channel A. With appropriate balancing of the two channels, it is possible to record catecholamines and 5-HT simultaneously at the same dident microelectrode. Examples of measurements in striatum, cortex and locus coeruleus are shown.

Ultrastructure at carbon fiber microelectrode implantation sites after acute voltammetric measurements in the striatum of anesthetized rats.

This work seeks to establish the feasibility of characterizing the ultrastructure of brain tissue disruption associated with the implantation of carbon fiber voltammetric microelectrodes. In vivo recording was performed by fast scan cyclic voltammetry in conjunction with carbon fiber microelectrodes (3.5 microm radius) in the striatum of rats anesthetized with chloral hydrate. After 4 h of in vivo recording, the microelectrodes were removed from the brain and the animals underwent intracardial perfusion. Brain tissue was collected and sectioned in the horizontal plane perpendicular to the axis of the microelectrodes. With microelectrodes of a conventional single barreled design, the tissue tracks were often too small to be followed by light microscopy to the point of deepest penetration, which would correspond to the implantation site of the carbon fiber itself. The enlarged tissue tracks formed by the implantation of double barreled electrodes, however, could be followed to their termination by light microscopy. Anatomical mapping was used to identify the fields laying 100 microm deeper than the deepest trace of such tracks. Electron microscopy of these fields revealed a spot of tissue damage presumed to be associated with the implantation site of the carbon fiber microelectrode. The spot of maximal tissue damage had a radius of 2.5 microm and was surrounded by an annular region with a width of 4 microm that contained a mix of healthy and damaged elements. Beyond this annular region, i.e. beyond 6.5 microm from the center of the spot of maximal damage, signs of microelectrode-associated damage were rare and consisted primarily of neurons with darkened cytoplasm.

A method for direct thalamic stimulation in fMRI studies using a glass-coated carbon fiber electrode.

Recent fMRI studies are of interest in exploring long-range interactions between different brain structures and the functional activation of specific brain regions by known neuroanatomical pathways. One of the experimental approaches requires the invasive implantation of an intracranial electrode to excite specific brain structures. In the present report, we describe a procedure for the production of a glass-coated carbon fiber electrode and the use of this electrode for direct activation of the brain in fMRI studies. The glass-coated carbon fiber microelectrode was implanted in the medial thalamus of anaesthetized rats and T2*-weighted gradient echo images in the sagittal plane obtained on a 4.7 T system (Biospec BMT 47/40) during electrical stimulation of the medial thalamus. The image quality obtained using this electrode was acceptable without reduction of the signal-to-noise ratio and image distortion. Cross-correlation analysis showed that the signal intensities of activated areas in the ipsilateral anterior cingulate cortex were significantly increased by about 4-5% during medial thalamus stimulation. The present study shows that glass-coated carbon fiber electrodes are suitable for fMRI studies and can be used to investigate functional thalamocingulate activation.

A new approach to neural cell culture for long-term studies.

We have developed a new method for culturing cells that maintains their health and sterility for many months. Using conventional techniques, primary neuron cultures seldom survive more than 2 months. Increases in the osmotic strength of media due to evaporation are a large and underappreciated contributor to the gradual decline in the health of these cultures. Because of this and the ever-present likelihood of contamination by airborne pathogens, repeated or extended experiments on any given culture have until now been difficult, if not impossible. We surmounted survival problems by using culture dish lids that form a gas-tight seal, and incorporate a transparent hydrophobic membrane (fluorinated ethylene-propylene) that is selectively permeable to oxygen (O(2)) and carbon dioxide (CO(2)), and relatively impermeable to water vapor. This prevents contamination and greatly reduces evaporation, allowing the use of a non-humidified incubator. We have employed this technique to grow dissociated cortical cultures from rat embryos on multi-electrode arrays. After more than a year in culture, the neurons still exhibit robust spontaneous electrical activity. The combination of sealed culture dishes with extracellular multi-electrode recording and stimulation enables study of development, adaptation, and very long-term plasticity, across months, in cultured neuronal networks. Membrane-sealed dishes will also be useful for the culture of many other cell types susceptible to evaporation and contamination.

Can voltammetry measure nitrogen monoxide (NO) and/or nitrites?

Recently, voltammetry with carbon fibre electrodes (CFE) has been implemented for real time measurement of nitrogen monoxide (NO) indicating that it is oxidised at the potential value of nitrites, approximately +700 mV. In contrast, here we show that modified CFE can monitor NO at oxidation potentials different than that of nitrites, i.e. +550 mV. Indeed, at +550 mV a significant increase of amperometric current levels was obtained when NO but not nitrites, were added to a phosphate buffer saline solution (PBS). Differential pulse voltammetry (DPV) supports these findings as two oxidation peaks were obtained when examining air preserved NO; peak 1 at +550 mV and peak 2 at +700 mV, respectively. In contrast, only peak 2 was monitored when nitrites or a solution of NO oxidised in air was added to PBS. Biological support to these in vitro data comes from the observation that the relaxation of an adrenaline-contracted aortic ring produced via addition of NO is concomitant with peak 1 at +550 mV. The relaxation is almost completed before the appearance of peak 2 at +700 mV. Furthermore, in vivo experiments performed in the striatum of rats show that the amperometric signal monitored at +550 mV is responsive to glutamatergic stimulation or inhibition of NO synthase.

An improved method with a long-shanked glass micropipette and ultrasonography for drug injection into deep brain structure of the monkey.

We describe an improved method to inject drug into deep brain structure of the macaque monkey. A Teflon-coated tungsten wire for extracellular recording was passed through a long-shanked (4-5 cm) glass micropipette, which was then attached to a microsyringe with dental impression material. The surface of the micropippete was coated with Teflon to reduce acoustic artifact in ultrasound imaging. Thereby, it was possible to identify the micropipette in the brain with B-mode ultrasonography. Extracellular recording combined with electrical stimulation in the input source of the target nucleus was also helpful to determine the location of the micropipette. Here, we demonstrate injection of a neuronal tracer, wheat germ agglutinin conjugated to horseradish peroxidase, into the medial mammillary nucleus of the Japanese monkey.

Feasibility of using silicon-substrate recording electrodes within the auditory nerve.

The use of penetrating, silicon-substrate (i.e., "thin-film") probes within a cross-section of a sensory nerve offers the possibility of assessing the pattern and extent of fiber excitation within the nerve. We used acute cat preparations to assess the feasibility of this technique for recordings within the auditory nerve trunk. Four probe configurations fabricated by the University of Michigan Center for Neural Communication Technology were evaluated using acoustic and electric stimuli. Our main concerns were the nature of the recorded potentials and the degree of spatial selectivity provided by these probes. We also made some basic assessments of electrode-tissue compatibility. The recorded potentials were characterized as field potentials with varying degrees of spatial selectivity. In some cases, responses to pure tones demonstrated good spatial selectivity, with unique responses recorded by different electrode sites. When electrode sites were positioned at different longitudinal positions along the nerve trunk, responses with latencies characteristic of each site were recorded. These results indicate that thin-film electrodes are capable of providing spatially specific response information from sensory nerves. However, in the case of feline auditory nerves, place-specific responses were inconsistently observed, making it difficult to use this technique to obtain detailed cochleotopic maps of neural excitation. More productive results may be possible from other peripheral nerves with less complex spatial arrangements of fibers.

Long-term reliability of Al2O3 and Parylene C bilayer encapsulated Utah electrode array based neural interfaces for chronic implantation.

OBJECTIVE: We focus on improving the long-term stability and functionality of neural interfaces for chronic implantation by using bilayer encapsulation. APPROACH: We evaluated the long-term reliability of Utah electrode array (UEA) based neural interfaces encapsulated by 52 nm of atomic layer deposited Al2O3 and 6 µm of Parylene C bilayer, and compared these to devices with the baseline Parylene-only encapsulation. Three variants of arrays including wired, wireless, and active UEAs were used to evaluate this bilayer encapsulation scheme, and were immersed in phosphate buffered saline (PBS) at 57 °C for accelerated lifetime testing. MAIN RESULTS: The median tip impedance of the bilayer encapsulated wired UEAs increased from 60 to 160 kΩ during the 960 days of equivalent soak testing at 37 °C, the opposite trend to that typically observed for Parylene encapsulated devices. The loss of the iridium oxide tip metallization and etching of the silicon tip in PBS solution contributed to the increase of impedance. The lifetime of fully integrated wireless UEAs was also tested using accelerated lifetime measurement techniques. The bilayer coated devices had stable power-up frequencies at ∼910 MHz and constant radio-frequency signal strength of -50 dBm during up to 1044 days (still under testing) of equivalent soaking time at 37 °C. This is a significant improvement over the lifetime of ∼100 days achieved with Parylene-only encapsulation at 37 °C. The preliminary samples of bilayer coated active UEAs with a flip-chip bonded ASIC chip had a steady current draw of ∼3 mA during 228 days of soak testing at 37 °C. An increase in the current draw has been consistently correlated to device failures, so is a sensitive metric for their lifetime. SIGNIFICANCE: The trends of increasing electrode impedance of wired devices and performance stability of wireless and active devices support the significantly greater encapsulation performance of this bilayer encapsulation compared with Parylene-only encapsulation. The bilayer encapsulation should significantly improve the in vivo lifetime of neural interfaces for chronic implantation.