Flexible, high-resolution cortical arrays with large coverage capture microscale high-frequency oscillations in patients with epilepsy.

OBJECTIVE: Effective surgical treatment of drug-resistant epilepsy depends on accurate localization of the epileptogenic zone (EZ). High-frequency oscillations (HFOs) are potential biomarkers of the EZ. Previous research has shown that HFOs often occur within submillimeter areas of brain tissue and that the coarse spatial sampling of clinical intracranial electrode arrays may limit the accurate capture of HFO activity. In this study, we sought to characterize microscale HFO activity captured on thin, flexible microelectrocorticographic (µECoG) arrays, which provide high spatial resolution over large cortical surface areas. METHODS: We used novel liquid crystal polymer thin-film µECoG arrays (.76-1.72-mm intercontact spacing) to capture HFOs in eight intraoperative recordings from seven patients with epilepsy. We identified ripple (80-250 Hz) and fast ripple (250-600 Hz) HFOs using a common energy thresholding detection algorithm along with two stages of artifact rejection. We visualized microscale subregions of HFO activity using spatial maps of HFO rate, signal-to-noise ratio, and mean peak frequency. We quantified the spatial extent of HFO events by measuring covariance between detected HFOs and surrounding activity. We also compared HFO detection rates on microcontacts to simulated macrocontacts by spatially averaging data. RESULTS: We found visually delineable subregions of elevated HFO activity within each µECoG recording. Forty-seven percent of HFOs occurred on single 200-µm-diameter recording contacts, with minimal high-frequency activity on surrounding contacts. Other HFO events occurred across multiple contacts simultaneously, with covarying activity most often limited to a .95-mm radius. Through spatial averaging, we estimated that macrocontacts with 2-3-mm diameter would only capture 44% of the HFOs detected in our µECoG recordings. SIGNIFICANCE: These results demonstrate that thin-film microcontact surface arrays with both highresolution and large coverage accurately capture microscale HFO activity and may improve the utility of HFOs to localize the EZ for treatment of drug-resistant epilepsy.

Advances in Penetrating Multichannel Microelectrodes Based on the Utah Array Platform.

The Utah electrode array (UEA) and its many derivatives have become a gold standard for high-channel count bi-directional neural interfaces, in particular in human subject applications. The chapter provides a brief overview of leading electrode concepts and the context in which the UEA has to be understood. It goes on to discuss the key advances and developments of the UEA platform in the past 15 years, as well as novel wireless and system integration technologies that will merge into future generations of fully integrated devices. Aspects covered include novel device architectures that allow scaling of channel count and density of electrode contacts, material improvements to substrate, electrode contacts, and encapsulation. Further subjects are adaptations of the UEA platform to support IR and optogenetic simulation as well as an improved understanding of failure modes and methods to test and accelerate degradation in vitro such as to better predict device failure and lifetime in vivo.

Effect of bias voltage and temperature on lifetime of wireless neural interfaces with Al 2O3 and parylene bilayer encapsulation.

The lifetime of neural interfaces is a critical challenge for chronic implantations, as therapeutic devices (e.g., neural prosthetics) will require decades of lifetime. We evaluated the lifetime of wireless Utah electrode array (UEA) based neural interfaces with a bilayer encapsulation scheme utilizing a combination of alumina deposited by Atomic Layer Deposition (ALD) and parylene C. Wireless integrated neural interfaces (INIs), equipped with recording version 9 (INI-R9) ASIC chips, were used to monitor the encapsulation performance through radio-frequency (RF) power and telemetry. The wireless devices were encapsulated with 52 nm of ALD Al2O3 and 6 µm of parylene C, and tested by soaking in phosphate buffered solution (PBS) at 57 °C for 4× accelerated lifetime testing. The INIs were also powered continuously through 2.765 MHz inductive power and forward telemetry link at unregulated 5 V. The bilayer encapsulated INIs were fully functional for ∼35 days (140 days at 37 °C equivalent) with consistent power-up frequencies (∼910 MHz), stable RF signal (∼-75 dBm), and 100 % command reception rate. This is ∼10 times of equivalent lifetime of INIs with parylene-only encapsulation (13 days) under same power condition at 37 °C. The bilayer coated INIs without continuous powering lasted over 1860 equivalent days (still working) at 37 °C. Those results suggest that bias stress is a significant factor to accelerate the failure of the encapsulated devices. The INIs failed completely within 5 days of the initial frequency shift of RF signal at 57 °C, which implied that the RF frequency shift is an early indicator of encapsulation/device failure.

SELF ALIGNED TIP DEINSULATION OF ATOMIC LAYER DEPOSITED AL2O3 AND PARYLENE C COATED UTAH ELECTRODE ARRAY BASED NEURAL INTERFACES.

The recently developed alumina and Parylene C bi-layer encapsulation improved the lifetime of neural interfaces. Tip deinsulation of Utah electrode array based neural interfaces is challenging due to the complex 3D geometries and high aspect ratios of the devices. A three-step self-aligned process was developed for tip deinsulation of bilayer encapsulated arrays. The deinsulation process utilizes laser ablation to remove Parylene C, O2 reactive ion etching to remove carbon and Parylene residues, and buffered oxide etch to remove alumina deposited by atomic layer deposition, and expose the IrOx tip metallization. The deinsulated iridium oxide area was characterized by scanning electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy to determine the morphology, surface morphology, composition, and electrical properties of the deposited layers and deinsulated tips. The alumina layer was found to prevent the formation of micro cracks on iridium oxide during the laser ablation process, which has been previously reported as a challenge for laser deinsulation of Parylene films. The charge injection capacity, charge storage capacity, and impedance of deinsulated iridium oxide were characterized to determine the deinsulation efficacy compared to Parylene-only insulation. Deinsulated iridium oxide with bilayer encapsulation had higher charge injection capacity (240 vs 320 nC) and similar electrochemical impedance (2.5 vs 2.5 kΩ) compared to deinsulated iridium oxide with only Parylene coating for an area of 2 × 10-4 cm2. Tip impedances were in the ranges of 20 to 50 kΩ, with median of 32 KΩ and standard deviation of 30 kΩ, showing the effectiveness of the self-aligned deinsulation process for alumina and Parylene C bi-layer encapsulation. The relatively uniform tip impedance values demonstrated the consistency of tip exposures.

Smart Hydrogel Swelling State Detection Based on a Power-Transfer Transduction Principle.

Stimulus-responsive (smart) hydrogels are a promising sensing material for biomedical contexts due to their reversible swelling change in response to target analytes. The design of application-specific sensors that utilize this behavior requires the development of suitable transduction concepts. The presented study investigates a power-transfer-based readout approach that is sensitive to small volumetric changes of the smart hydrogel. The concept employs two thin film polyimide substrates with embedded conductive strip lines, which are shielded from each other except at the tip region, where the smart hydrogel is sandwiched in between. The hydrogel's volume change in response to a target analyte alters the distance and orientation of the thin films, affecting the amount of transferred power between the two transducer parts and, consequently, the measured sensor output voltage. With proper calibration, the output signal can be used to determine the swelling change of the hydrogel and, consequently, to quantify the stimulus. In proof-of-principle experiments with glucose- and pH-sensitive smart hydrogels, high sensitivity to small analyte concentration changes was found along with very good reproducibility and stability. The concept was tested with two exemplary hydrogels, but the transduction principle in general is independent of the specific hydrogel material, as long as it exhibits a stimulus-dependent volume change. The application vision of the presented research is to integrate in situ blood analyte monitoring capabilities into standard (micro)catheters. The developed sensor is designed to fit into a catheter without obstructing its normal use and, therefore, offers great potential for providing a universally applicable transducer platform for smart catheter-based sensing.

Development of a feline model for preclinical research of a new translabyrinthine auditory nerve implant.

Cochlear implants are among the most successful neural prosthetic devices to date but exhibit poor frequency selectivity and the inability to consistently activate apical (low frequency) spiral ganglion neurons. These issues can limit hearing performance in many cochlear implant patients, especially for understanding speech in noisy environments and in perceiving or appreciating more complex inputs such as music and multiple talkers. For cochlear implants, electrical current must pass through the bony wall of the cochlea, leading to widespread activation of auditory nerve fibers. Cochlear implants also cannot be implanted in some individuals with an obstruction or severe malformations of the cochlea. Alternatively, intraneural stimulation delivered via an auditory nerve implant could provide direct contact with neural fibers and thus reduce unwanted current spread. More confined current during stimulation can increase selectivity of frequency fiber activation. Furthermore, devices such as the Utah Slanted Electrode Array can provide access to the full cross section of the auditory nerve, including low frequency fibers that are difficult to reach using a cochlear implant. However, further scientific and preclinical research of these Utah Slanted Electrode Array devices is limited by the lack of a chronic large animal model for the auditory nerve implant, especially one that leverages an appropriate surgical approach relevant for human translation. This paper presents a newly developed transbullar translabyrinthine surgical approach for implanting the auditory nerve implant into the cat auditory nerve. In our first of a series of studies, we demonstrate a surgical approach in non-recovery experiments that enables implantation of the auditory nerve implant into the auditory nerve, without damaging the device and enabling effective activation of the auditory nerve fibers, as measured by electrode impedances and electrically evoked auditory brainstem responses. These positive results motivate performing future chronic cat studies to assess the long-term stability and function of these auditory nerve implant devices, as well as development of novel stimulation strategies that can be translated to human patients.

Flexural bending to approximate cortical forces exerted by electrocorticography (ECoG) arrays.

Objective.The force that an electrocorticography (ECoG) array exerts on the brain manifests when it bends to match the curvature of the skull and cerebral cortex. This force can negatively impact both short-term and long-term patient outcomes. Here we provide a mechanical characterization of a novel liquid crystal polymer (LCP) ECoG array prototype to demonstrate that its thinner geometry reduces the force potentially applied to the cortex of the brain.Approach.We built a low-force flexural testing machine to measure ECoG array bending forces, calculate their effective flexural moduli, and approximate the maximum force they could exerted on the human brain.Main results.The LCP ECoG prototype was found to have a maximal force less than 20% that of any commercially available ECoG arrays that were tested. However, as a material, LCP was measured to be as much as 24× more rigid than silicone, which is traditionally used in ECoG arrays. This suggests that the lower maximal force resulted from the prototype's thinner profile (2.9×-3.25×).Significance.While decreasing material stiffness can lower the force an ECoG array exhibits, our LCP ECoG array prototype demonstrated that flexible circuit manufacturing techniques can also lower these forces by decreasing ECoG array thickness. Flexural tests of ECoG arrays are necessary to accurately assess these forces, as material properties for polymers and laminates are often scale dependent. As the polymers used are anisotropic, elastic modulus cannot be used to predict ECoG flexural behavior. Accounting for these factors, we used our four-point flexure testing procedure to quantify the forces exerted on the brain by ECoG array bending. With this experimental method, ECoG arrays can be designed to minimize force exerted on the brain, potentially improving both acute and chronic clinical utility.

Intraoperative microseizure detection using a high-density micro-electrocorticography electrode array.

One-third of epilepsy patients suffer from medication-resistant seizures. While surgery to remove epileptogenic tissue helps some patients, 30-70% of patients continue to experience seizures following resection. Surgical outcomes may be improved with more accurate localization of epileptogenic tissue. We have previously developed novel thin-film, subdural electrode arrays with hundreds of microelectrodes over a 100-1000 mm2 area to enable high-resolution mapping of neural activity. Here, we used these high-density arrays to study microscale properties of human epileptiform activity. We performed intraoperative micro-electrocorticographic recordings in nine patients with epilepsy. In addition, we recorded from four patients with movement disorders undergoing deep brain stimulator implantation as non-epileptic controls. A board-certified epileptologist identified microseizures, which resembled electrographic seizures normally observed with clinical macroelectrodes. Recordings in epileptic patients had a significantly higher microseizure rate (2.01 events/min) than recordings in non-epileptic subjects (0.01 events/min; permutation test, P = 0.0068). Using spatial averaging to simulate recordings from larger electrode contacts, we found that the number of detected microseizures decreased rapidly with increasing contact diameter and decreasing contact density. In cases in which microseizures were spatially distributed across multiple channels, the approximate onset region was identified. Our results suggest that micro-electrocorticographic electrode arrays with a high density of contacts and large coverage are essential for capturing microseizures in epilepsy patients and may be beneficial for localizing epileptogenic tissue to plan surgery or target brain stimulation.

In Vivo Monitoring of Glucose Using Ultrasound-Induced Resonance in Implantable Smart Hydrogel Microstructures.

A novel glucose sensor is presented using smart hydrogels as biocompatible implantable sensing elements, which eliminates the need for implanted electronics and uses an external medical-grade ultrasound transducer for readout. The readout mechanism uses resonance absorption of ultrasound waves in glucose-sensitive hydrogels. In vivo glucose concentration changes in the interstitial fluid lead to swelling or deswelling of the gels, which changes the resonance behavior. The hydrogels are designed and shaped such as to exhibit specific mechanical resonance frequencies while remaining sonolucent to other frequencies. Thus, they allow conventional and continued ultrasound imaging, while yielding a sensing signal at specific frequencies that correlate with glucose concentration. The resonance frequencies can be tuned by changing the shape and mechanical properties of the gel structures, such as to allow for multiple, colocated implanted hydrogels with different sensing characteristics or targets to be employed and read out, without interference using the same ultrasound transducer, by simply toggling frequencies. The fact that there is no need for any implantable electronics, also opens up the path toward future use of biodegradable hydrogels, thus creating a platform that allows injection of sensors that do not need to be retrieved when they reach the end of their useful lifespan.

Catheter-mounted smart hydrogel ultrasound resonators for intravenous analyte monitoring.

Continuous monitoring of drug concentrations in blood plasma can be beneficial to guide individualized drug administration. High interpatient variability in required dosage and a small therapeutic window of certain drugs, such as anesthetic medications, can cause risks and challenges in accurate dosing during administration. In this work, we present a sensing platform concept using a smart hydrogel micro resonator sheet with medical ultrasound readout that is integrated on the top of a catheter. This concept is validated in-vitro using glucose as an easy to access and handle target analyte. In the case of continuous glucose measurement, our novel catheter-mounted sensing platform allows the detection of glucose concentrations in the range of 0 mM to 12 mM. While these experiments use a well-known glucose-sensitive smart hydrogel for proof-of-principle experiments, this new sensing platform is intended to provide the basis for continuous monitoring of various intravenously applied medications. Selectivity to different drugs, e.g., fentanyl, can be accomplished by developing a corresponding smart hydrogel composition.Clinical Relevance- Many intravenous medications, especially anesthetics, show considerable pharmacokinetic inter-subject variability. Continuous monitoring of intravenous analyte concentrations would enable individualizing the administration of these drugs to the specific patient.

Flexible, high-resolution thin-film electrodes for human and animal neural research.

Objective.Brain functions such as perception, motor control, learning, and memory arise from the coordinated activity of neuronal assemblies distributed across multiple brain regions. While major progress has been made in understanding the function of individual neurons, circuit interactions remain poorly understood. A fundamental obstacle to deciphering circuit interactions is the limited availability of research tools to observe and manipulate the activity of large, distributed neuronal populations in humans. Here we describe the development, validation, and dissemination of flexible, high-resolution, thin-film (TF) electrodes for recording neural activity in animals and humans.Approach.We leveraged standard flexible printed-circuit manufacturing processes to build high-resolution TF electrode arrays. We used biocompatible materials to form the substrate (liquid crystal polymer; LCP), metals (Au, PtIr, and Pd), molding (medical-grade silicone), and 3D-printed housing (nylon). We designed a custom, miniaturized, digitizing headstage to reduce the number of cables required to connect to the acquisition system and reduce the distance between the electrodes and the amplifiers. A custom mechanical system enabled the electrodes and headstages to be pre-assembled prior to sterilization, minimizing the setup time required in the operating room. PtIr electrode coatings lowered impedance and enabled stimulation. High-volume, commercial manufacturing enables cost-effective production of LCP-TF electrodes in large quantities.Main Results. Our LCP-TF arrays achieve 25× higher electrode density, 20× higher channel count, and 11× reduced stiffness than conventional clinical electrodes. We validated our LCP-TF electrodes in multiple human intraoperative recording sessions and have disseminated this technology to >10 research groups. Using these arrays, we have observed high-frequency neural activity with sub-millimeter resolution.Significance.Our LCP-TF electrodes will advance human neuroscience research and improve clinical care by enabling broad access to transformative, high-resolution electrode arrays.

Wafer-scale fabrication of penetrating neural microelectrode arrays.

The success achieved with implantable neural interfaces has motivated the development of novel architectures of electrode arrays and the improvement of device performance. The Utah electrode array (UEA) is one example of such a device. The unique architecture of the UEA enables single-unit recording with high spatial and temporal resolution. Although the UEA has been commercialized and been used extensively in neuroscience and clinical research, the current processes used to fabricate UEA's impose limitations in the tolerances of the electrode array geometry. Further, existing fabrication costs have led to the need to develop less costly but higher precision batch fabrication processes. This paper presents a wafer-scale fabrication method for the UEA that enables both lower costs and faster production. More importantly, the wafer-scale fabrication significantly improves the quality and tolerances of the electrode array and allow better controllability in the electrode geometry. A comparison between the geometrical and electrical characteristics of the wafer-scale and conventional array-scale processed UEA's is presented.

Smart Hydrogel Micromechanical Resonators with Ultrasound Readout for Biomedical Sensing.

One of the main challenges for implantable biomedical sensing schemes is obtaining a reliable signal while maintaining biocompatibility. In this work, we demonstrate that a combination of medical ultrasound imaging and smart hydrogel micromechanical resonators can be employed for continuous monitoring of analyte concentrations. The sensing principle is based on the shift of the mechanical resonance frequencies of smart hydrogel structures induced by their volume-phase transition in response to changing analyte levels. This shift can then be measured as a contrast change in the ultrasound images due to resonance absorption of ultrasound waves. This concept eliminates the need for implanting complex electronics or employing transcutaneous connections for sensing biomedical analytes in vivo. Here, we present proof-of-principle experiments that monitor in vitro changes in ionic strength and glucose concentrations to demonstrate the capabilities and potential of this versatile sensing platform technology.

Neural electrode resilience against dielectric damage may be improved by use of highly doped silicon as a conductive material.

BACKGROUND: Dielectric damage occurring in vivo to neural electrodes, leading to conductive material exposure and impedance reduction over time, limits the functional lifetime and clinical viability of neuroprosthetics. We used silicon micromachined Utah Electrode Arrays (UEAs) with iridium oxide (IrOx) tip metallization and parylene C dielectric encapsulation to understand the factors affecting device resilience and drive improvements. NEW METHOD: In vitro impedance measurements and finite element analyses were conducted to evaluate how exposed surface area of silicon and IrOx affect UEA properties. Through an aggressive in vitro reactive accelerated aging (RAA) protocol, in vivo parylene degradation was simulated on UEAs to explore agreement with our models. Electrochemical properties of silicon and other common electrode materials were compared to help inform material choice in future neural electrode designs. RESULTS: Exposure of silicon on UEAs was found to primarily affect impedance at frequencies >1kHz, while characteristics at 1 kHz and below were largely unchanged. Post-RAA impedance reduction of UEAs was mitigated in cases where dielectric damage was more likely to expose silicon instead of IrOx. Silicon was found to have a per-area electrochemical impedance >10×higher than many common electrode materials regardless of doping level and resistivity, making it best suited for use as a low-shunting conductor. COMPARISON WITH EXISTING METHODS: Non-semiconductor electrode materials commonly used in neural electrode design are more susceptible to shunting neural interface signals through dielectric defects, compared to highly doped silicon. CONCLUSION: Strategic use of silicon and similar materials may increase neural electrode robustness against encapsulation failures.

Low-Cost Microfluidic Sensors with Smart Hydrogel Patterned Arrays Using Electronic Resistive Channel Sensing for Readout.

There is a strong commercial need for inexpensive point-of-use sensors for monitoring disease biomarkers or environmental contaminants in drinking water. Point-of-use sensors that employ smart polymer hydrogels as recognition elements can be tailored to detect almost any target analyte, but often suffer from long response times. Hence, we describe here a fabrication process that can be used to manufacture low-cost point-of-use hydrogel-based microfluidics sensors with short response times. In this process, mask-templated UV photopolymerization is used to produce arrays of smart hydrogel pillars inside sub-millimeter channels located upon microfluidics devices. When these pillars contact aqueous solutions containing a target analyte, they swell or shrink, thereby changing the resistance of the microfluidic channel to ionic current flow when a small bias voltage is applied to the system. Hence resistance measurements can be used to transduce hydrogel swelling changes into electrical signals. The only instrumentation required is a simple portable potentiostat that can be operated using a smartphone or a laptop, thus making the system suitable for point of use. Rapid hydrogel response rate is achieved by fabricating arrays of smart hydrogels that have large surface area-to-volume ratios.

Thermal impact of an active 3-D microelectrode array implanted in the brain.

A chronically implantable, wireless neural interface device will require integrating electronic circuitry with the interfacing microelectrodes in order to eliminate wired connections. Since the integrated circuit (IC) dissipates a certain amount of power, it will raise the temperature in surrounding tissues where it is implanted. In this paper, the thermal influence of the integrated 3-D Utah electrode array (UEA) device implanted in the brain was investigated by numerical simulation using finite element analysis (FEA) and by experimental measurement in vitro as well as in vivo. The numerically calculated and experimentally measured temperature increases due to the UEA implantation were in good agreement. The experimentally validated numerical model predicted that the temperature increases linearly with power dissipation through the UEA, with a slope of 0.029 degree C/mW over the power dissipation levels expected to be used. The influences of blood perfusion, brain metabolism, and UEA geometry on tissue heating were also investigated using the numerical model.

Characterization of a-SiC(x):H thin films as an encapsulation material for integrated silicon based neural interface devices.

A fully integrated, wireless neural interface device is being developed to free patients from the restriction and risk of infection associated with a transcutaneous wired connection. This device requires a hermetic, biocompatible encapsulation layer at the interface between the device and the neural tissue to maintain long-term recording/stimulating performance of the device. Hydrogenated amorphous silicon carbide (a-SiC(x):H) films deposited by a plasma enhanced chemical vapor deposition using SiH(4), CH(4), and H(2) precursors were investigated as the encapsulation layer for such device. Si-C bond density, measured by Fourier transform infrared absorption spectrometer, suggests that deposition conditions with increased hydrogen dilution, increased temperature, and low silane flow typically result in increase of Si-C bond density. From the variable angle spectroscopic ellipsometry measurement, no dissolution of a-SiC(x):H was observed during soaking tests in 90°C phosphate buffered saline. Conformal coating of the a-SiC(x):H in Utah electrode array was observed by scanning electron microscope. Electrical properties were studied by impedance spectroscopy to investigate the performance of a-SiC(x):H as an encapsulation layer, and the results showed long term stability of the material.

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.

Lifetime assessment of atomic-layer-deposited Al2O3-Parylene C bilayer coating for neural interfaces using accelerated age testing and electrochemical characterization.

The lifetime and stability of insulation are critical features for the reliable operation of an implantable neural interface device. A critical factor for an implanted insulation's performance is its barrier properties that limit access of biological fluids to the underlying device or metal electrode. Parylene C is a material that has been used in FDA-approved implantable devices. Considered a biocompatible polymer with barrier properties, it has been used as a substrate, insulation or an encapsulation for neural implant technology. Recently, it has been suggested that a bilayer coating of Parylene C on top of atomic-layer-deposited Al2O3 would provide enhanced barrier properties. Here we report a comprehensive study to examine the mean time to failure of Parylene C and Al2O3-Parylene C coated devices using accelerated lifetime testing. Samples were tested at 60°C for up to 3 months while performing electrochemical measurements to characterize the integrity of the insulation. The mean time to failure for Al2O3-Parylene C was 4.6 times longer than Parylene C coated samples. In addition, based on modeling of the data using electrical circuit equivalents, we show here that there are two main modes of failure. Our results suggest that failure of the insulating layer is due to pore formation or blistering as well as thinning of the coating over time. The enhanced barrier properties of the bilayer Al2O3-Parylene C over Parylene C makes it a promising candidate as an encapsulating neural interface.

Deep-tissue light delivery via optrode arrays.

We establish performance characteristics of needle-type waveguides in three-dimensional array architectures as light delivery interfaces into deep tissue for applications, such as optogenetic and infrared (IR) neural stimulation. A single optrode waveguide achieves as high as 90% transmission efficiency, even at tissue depths >1 mm. Throughout the visible and near-IR spectrum, the effective light attenuation through the waveguide is ∼3 orders of magnitude smaller than attenuation in tissue/water, as confirmed by both simulation and experimental results. Light emission profiles from the optrode tips into tissue were also measured. Beam widths of 70 to 150 µm and full-angle divergence ranging from 13 to 40 deg in tissue can be achieved. These beam characteristics satisfy a wide range of requirements for targeted illumination in neural stimulation.