Thin-film Electrode Array Research Articles

Origami-inspired soft fluidic actuation for minimally invasive large-area electrocorticography

Electrocorticography is an established neural interfacing technique wherein an array of electrodes enables large-area recording from the cortical surface. Electrocorticography is commonly used for seizure mapping however the implantation of large-area electrocorticography arrays is a highly invasive procedure, requiring a craniotomy larger than the implant area to place the device. In this work, flexible thin-film electrode arrays are combined with concepts from soft robotics, to realize a large-area electrocorticography device that can change shape via integrated fluidic actuators. We show that the 32-electrode device can be packaged using origami-inspired folding into a compressed state and implanted through a small burr-hole craniotomy, then expanded on the surface of the brain for large-area cortical coverage. The implantation, expansion, and recording functionality of the device is confirmed in-vitro and in porcine in-vivo models. The integration of shape actuation into neural implants provides a clinically viable pathway to realize large-area neural interfaces via minimally invasive surgical techniques.

On the Design, Fabrication, and Characterization of a Novel Thin-Film Electrode Array for Use in Cochlear Implants.

Thin-film electrode arrays (TFEAs) have been developed as an alternative to conventional electrode arrays (CEAs) used in cochlear implants. However, TFEAs produced by microfabrication techniques have not yet been used clinically because their structural and mechanical properties are far from those of CEAs. The aim of this study is to design, fabricate, and investigate the mechanical and tribological behavior and evaluate the performance of different TFEA designs. Finite Element Analysis (FEA) is performed to determine the elastic properties of several designs. A custom-build experimental setup is designed to observe the tribological behavior in different speeds and environments where frictional (lateral) and vertical force (normal force) are measured on a flat surface and within artificial cochlea. According to the FEA results, the maximum stiffness of the CEA is 37.93 mN/mm and 0.363 mN/mm and TFEA-4 has a maximum stiffness of 39.08 mN/mm and 0.306 mN/mm in the longitudinal and transverse axes, respectively. It is shown experimentally that adding a dummy wire to the carrier of the EA enhances both its longitudinal and transverse stiffness, thereby postponing the initiation of dynamic sliding due to the elevated buckling limit. It is also revealed that the type of TFEA support structure affects both normal and frictional forces, as well as the coefficient of friction.

NeuroBus - Architecture for an Ultra-Flexible Neural Interface.

This article presents the system architecture for an implant concept called NeuroBus. Tiny distributed direct digitizing neural recorder ASICs on an ultra-flexible polyimide substrate are connected in a bus-like structure, allowing short connections between electrode and recording front-end with low wiring effort and high customizability. The small size (344 μm × 294 μm) of the ASICs and the ultraflexible substrate allow a low bending stiffness, enabling the implant to adapt to the curvature of the brain and achieving high structural biocompatibility. We introduce the architecture, the integrated building blocks, and the post-CMOS processes required to realize a NeuroBus, and we characterize the prototyped direct digitizing neural recorder front-end as well as polyimide-based ECoG brain interface. A rodent animal model is further used to validate the joint capability of the recording front-end and thin-film electrode array.

Unsupervised neural decoding of signals recorded by thin-film electrode arrays implanted in muscles using autoencoding with a physiologically derived optimisation criterion

We present an autoencoder that learns the discharge times of individual motor units (MU) by processing multichannel electromyogram (EMG) recordings obtained by electrode arrays implanted in muscles, thereby providing a neural interface with the spinal cord. To this end, after preprocessing of the EMG via convolutive sphering, the encoder is constrained to apply an orthogonal transformation to the spatial data and the optimisation criterion enforces a temporal sparsity constraint. These constraints are based on the theoretical modelling of EMG generation. This decomposition method was evaluated on both simulated and experimental signals. For simulated signals, with a ratio of 1.5 between observations and sources, the average detection accuracy was 94% for up to 60 sources for SNR 20 dB. Moreover, the detection accuracy did not significantly decrease when decreasing the SNR to values as low as 0 dB. Experimental signals were collected in humans with thin-film invasive electrodes implanted in the tibialis anterior muscle. The results showed an accuracy on experimental data >90%. Moreover, the proposed method outperformed a state-of-the-art blind source separation approach in terms of the number of reliably detected motor units. In conclusion, we have proposed the first fully unsupervised neural network approach to the problem of neural decoding of intramuscular EMG time series by translating the available theoretical knowledge on the signal properties into an autoencoding architecture tailored to the decomposition problem.

A CMOS-based highly scalable flexible neural electrode interface.

Perception, thoughts, and actions are encoded by the coordinated activity of large neuronal populations spread over large areas. However, existing electrophysiological devices are limited by their scalability in capturing this cortex-wide activity. Here, we developed an electrode connector based on an ultra-conformable thin-film electrode array that self-assembles onto silicon microelectrode arrays enabling multithousand channel counts at a millimeter scale. The interconnects are formed using microfabricated electrode pads suspended by thin support arms, termed Flex2Chip. Capillary-assisted assembly drives the pads to deform toward the chip surface, and van der Waals forces maintain this deformation, establishing Ohmic contact. Flex2Chip arrays successfully measured extracellular action potentials ex vivo and resolved micrometer scale seizure propagation trajectories in epileptic mice. We find that seizure dynamics in absence epilepsy in the Scn8a+/- model do not have constant propagation trajectories.

Biocompatibility and electrochemical characterization of new thin-film electrode arrays for monitoring, recording and stimulation of brain activity

Biocompatibility and electrochemical characterization of new thin-film electrode arrays for monitoring, recording and stimulation of brain activity

Electrochemical Testing of a New Polyimide Thin Film Electrode for Stimulation, Recording, and Monitoring of Brain Activity.

Subdural electrode arrays are used for monitoring cortical activity and functional brain mapping in patients with seizures. Until recently, the only commercially available arrays were silicone-based, whose thickness and lack of conformability could impact their performance. We designed, characterized, manufactured, and obtained FDA clearance for 29-day clinical use (510(k) K192764) of a new thin-film polyimide-based electrode array. This study describes the electrochemical characterization undertaken to evaluate the quality and reliability of electrical signal recordings and stimulation of these new arrays. Two testing paradigms were performed: a short-term active soak with electrical stimulation and a 29-day passive soak. Before and after each testing paradigm, the arrays were evaluated for their electrical performance using Electrochemical Impedance Spectroscopy (EIS), Cyclic Voltammetry (CV) and Voltage Transients (VT). In all tests, the impedance remained within an acceptable range across all frequencies. The different CV curves showed no significant changes in shape or area, which is indicative of stable electrode material. The electrode polarization remained within appropriate limits to avoid hydrolysis.

Topographical EEG Recordings of Visual Evoked Potentials in Mice using Multichannel Thin-film Electrodes.

Visual evoked potentials (VEP) allow the characterization of visual function in preclinical mouse models. Various methods exist to measure VEPs in mice, from non-invasive EEG, subcutaneous single-electrodes, and ECoG to fully invasive intracortical multichannel visual cortex recordings. It can be useful to acquire a global, topographical EEG-level characterization of visual responses previous to local intracortical microelectrode measurements in acute experimental settings. For example, one use case isto assess global cross-modal changes in VEP topography in deafness models before studying its effects on a local intracortical level. Multichannel epicranial EEG is a robust method to acquire such an overview measure of cortical visual activity.Multichannel epicranial EEG provides comparable results through a standardized, consistent approach to, for example, identify cross-modal, pathological, or age-related changes in cortical visual function. The current study presents a method to obtain the topographical distribution of flash-evoked VEPs with a 32-channel thin-film EEG electrode array in anesthetized mice. Combined with analysis in the time and frequency domain, this approach allows fast characterization and screening of the topography and basic visual properties of mouse cortical visual function, which can be combined with various acute experimental settings.

333 First FDA Cleared Thin Film Electrode for Intracranial Recording and Monitoring of Brain Activity – Device Testing and Initial Clinical Use

INTRODUCTION: Subdural strip and grid (SDG) electrodes are routinely used for pre-surgical evaluation of patients with drug resistant epilepsy (DRE). Although these electrodes have been in the US market since their first FDA clearance in 1985, their fabrication, materials and properties have hardly changed. They are made of silicone, are thick (>0.5 mm), manufactured by hand, and do not optimally conform to brain convolutions. Technological solutions that overcome these limitations are needed. METHODS: Thin film electrode (0.08 mm) arrays were manufactured from polyimide with platinum contacts (multiple configurations, 3 mm contact diameter, spaced 10 mm apart). Electrochemical and electrical testing include electrolyte interface impedance, cyclic voltammetry and other impedance and isolation tests, according to the International Electrotechnical Commission 60601 for proving device safety and performance. Biocompatibility was tested using standard methods according to International Organization for Standardization 10993. Post-market data were collected employing a user feedback questionnaire using a rating scale (1 to 5, with 5 being the highest). RESULTS: Thin film electrodes passed all electrochemical, electrical and biocompatibility testing required for FDA clearance (obtained Nov 2019). Electrodes (n = 19) were used in clinical practice between Nov 23, 2020 and May 3, 2021 in the epilepsy monitoring units and for intraoperative monitoring (IOM) for recording brain activity in (a) DRE patients undergoing evaluation for potential surgical resection, and (b) patients undergoing tumor resection. Users (neurosurgeons; n = 6) provided ratings between 4 and 5 regarding the properties (thickness, flexibility, weight), features (ease of placement, conformability to the brain areas) and performance (qualitative signal recording quality) of the electrodes during surgical implantation. CONCLUSION: This is the first thin film electrode technology FDA cleared for use in clinical practice. The properties of these thin, flexible polyimide electrode arrays may overcome many limitations of the existing technology. Initial clinical use indicated that the technology is feasible for surgical implantation with greater flexibility compared to silicone based cortical electrodes.

A microfabricated, 3D-sharpened silicon shuttle for insertion of flexible electrode arrays through dura mater into brain

Objective. Electrode arrays for chronic implantation in the brain are a critical technology in both neuroscience and medicine. Recently, flexible, thin-film polymer electrode arrays have shown promise in facilitating stable, single-unit recordings spanning months in rats. While array flexibility enhances integration with neural tissue, it also requires removal of the dura mater, the tough membrane surrounding the brain, and temporary bracing to penetrate the brain parenchyma. Durotomy increases brain swelling, vascular damage, and surgical time. Insertion using a bracing shuttle results in additional vascular damage and brain compression, which increase with device diameter; while a higher-diameter shuttle will have a higher critical load and more likely penetrate dura, it will damage more brain parenchyma and vasculature. One way to penetrate the intact dura and limit tissue compression without increasing shuttle diameter is to reduce the force required for insertion by sharpening the shuttle tip. Approach. We describe a novel design and fabrication process to create silicon insertion shuttles that are sharp in three dimensions and can penetrate rat dura, for faster, easier, and less damaging implantation of polymer arrays. Sharpened profiles are obtained by reflowing patterned photoresist, then transferring its sloped profile to silicon with dry etches. Main results. We demonstrate that sharpened shuttles can reliably implant polymer probes through dura to yield high quality single unit and local field potential recordings for at least 95 days. On insertion directly through dura, tissue compression is minimal. Significance. This is the first demonstration of a rat dural-penetrating array for chronic recording. This device obviates the need for a durotomy, reducing surgical time and risk of damage to the blood-brain barrier. This is an improvement to state-of-the-art flexible polymer electrode arrays that facilitates their implantation, particularly in multi-site recording experiments. This sharpening process can also be integrated into silicon electrode array fabrication.

32-channel mouse EEG: Visual evoked potentials

BackgroundMeasuring visual evoked potentials (VEP) by means of EEG allows the quasi non-invasive assessment of visual function in mice. Such sensory phenotyping is important to screen for genetic or aging effects on vision in preclinical mouse models. Thus, a standardized EEG-like approach for the assessment of sensory evoked potentials in mice is desirable. New methodWe describe a method to obtain the topographical distribution of flash evoked VEPs with 32-channel thin-film EEG electrode arrays in anesthetized mice. Further, we provide suggestions for the optimal choice of adequate digital filtering, referencing, and stimulus parameters for fast and reliable assessment of VEP parameters and distribution. Results32-channel thin-film electrodes provided clear information on the VEP topography across the skull. Re-referencing, such as bipolar, common average, and local average montages could be used to further refine the information on VEP topography. A balanced choice of digital high-pass filter, signal averaging and stimulus rate allowed to minimize measurement duration and at the same time assured good VEP signal-to-noise ratio. Comparison with existing methodsSubdermal electrodes or single skull screws provide only limited topographical information of the VEP. Assessment of VEPs with 32-channel thin-film electrodes can provide comparable signal quality with superior spatial resolution and standardized topographical and hemispheric information of VEP distribution. ConclusionsEEG-like thin-film electrodes are an efficient tool for fast, comprehensive sensory phenotyping with topographical information in mice. This is a step towards the use of standardized mouse EEG to characterize EEG biomarkers in mouse models of human diseases.

Anisotropic etching in (3 1 1) Si to fabricate sharp resorbable polymer microneedles carrying neural electrode arrays

Polymer microneedles that get resorbed after insertion in the body have several interesting applications, for example in the insertion of ultra-flexible electrode arrays in neural tissue. In this work, we explore the use of molds created by etching in (3 1 1) silicon as a basis for the fabrication of such microneedles. Such molds can be etched anisotropically to much sharper angles compared to standard (1 0 0) silicon. It is demonstrated that sharp poly lactic-co-glycolic acid (PLGA) microneedles can be fabricated using the molds. It is also shown that by simple thermal bonding the fabricated PLGA microneedles can be combined with a ultra-flexible polyimide-based thin-film electrode array.

Design, Fabrication, and Evaluation of a Parylene Thin-Film Electrode Array for Cochlear Implants.

To improve the existing manually assembled cochlear implant electrode arrays, a thin-film electrode array (TFEA) was microfabricated having a maximum electrode density of 15 sites along an 8-mm length, with each site having a 75 μm × 1.8 μm (diameter× height) disk electrode. The microfabrication method adopted photoresist transferring, lift-off, two-step oxygen plasma etching, and fuming nitric acid release to reduce lift-off complexity, protect the metal layer, and increase the release efficiency. Systematic in vitro characterization showed that the TFEA's bending stiffness was 6.40 × 10-10 N·m2 near the base and 1.26 × 10-10N·m2 near the apex. The TFEA electrode produced an average impedance of 16 kΩ and a maximum current limit of 800 μA, measured with 1-kHz sinusoidal current using monopolar stimulation in saline. A TFEA prototype was implanted in a cat cochlea to obtain in vivo measurements of electrically evoked auditory brainstem and inferior colliculus responses to monopolar stimulation with 41-μs/phase biphasic pulses. Both physiological responses produced a threshold of ∼300 μA and a dynamic range of 5-8 dB above the threshold. Compared with existing arrays, the present TFEA had 104 times less bending stiffness, 97% less electrode area, and comparable physiological thresholds. Using a simplified structure and stable fabrication method, the present TEFA produced physical and physiological performance comparable to existing commercial devices. The present TFEA represents a step closer toward an automated process replacing the labor-intensive and expensive manual assembly of the cochlear implant electrode arrays.

Study of the Carrier-Aided Thin Film Electrode Array Design for Cochlear Insertion.

The micro-fabricated thin film electrode array (TFEA) has been a promising design for cochlear implants (CIs) because of its cost-effectiveness and fabrication precision. The latest polymer-based cochlear TFEAs have faced difficulties for cochlear insertion due to the lack of structural stiffness. To stiffen the TFEA, dissolvable stiffening materials, TFEAs with different structures, and TFEAs with commercial CIs as carriers have been invested. In this work, the concept of enhancing a Parylene TFEA with Kapton tape as a simpler carrier for cochlear insertion has been proved to be feasible. The bending stiffness of the Kapton-aided TFEA was characterized with an analytical model, a finite element model, and a cantilever bending experiment, respectively. While the Kapton tape increased the bending stiffness of the Parylene TFEA by 103 times, the 6-μm-thick TFEA with a similar Young’s modulus, as a polyimide, in turn significantly increased the bending stiffness of the 170-μm-thick Kapton carrier by 60%. This result indicated that even the TFEA is ultra-flexible and that its bending stiffness should not be neglected in the design or selection of its carrier.

(Invited) Carbon Nanomaterials for High-Resolution, Multimodal Neural Interfaces

Unraveling and controlling neural processes underlying cognition, sensation, volitional movement and neurological disorders require implantable electrodes capable of decoding the activity of millions of neurons at millisecond resolution, over months to years and without inducing foreign-body reactions. Since Luigi Galvani discovery of bioelectricity, metals have been used as electrode materials. Metals, however, are dramatically inadequate to address the chemical, optical and mechanical properties of neural cells: they are stiff, unstable in physiological environment and can induce severe mechanical and neurotoxic damage to the soft tissues. Furthermore, recent advances in neuroscience methods for imaging, stimulating and inhibiting neural activity are emerging as powerful tools, but there is no available material that can simultaneously provide optical, electronic, magnetic and electrochemical properties to interface with neural microcircuits across multiple modalities. Carbon-based nanomaterials like carbon nanotubes (CNT) and graphene combine intrinsically high mass-specific surface area, electrical conductivity, mechanical strength, flexibility, low magnetic susceptibility mismatch with tissues and biological stability, which makes them uniquely suited for interfacing with neural circuits. We have engineered CNT fibers into cellular-scale size microelectrodes for chronic recording and stimulating neural activity. CNT fibers have superior electrochemical impedance and charge transfer properties compared to metal probes of the same size, which allows minimizing implant footprint without affecting the efficiency of transduction of biological ionic currents across the electrode/tissue interface. In vivo biocompatibility, effective deep-brain stimulation and stable chronic recording neural recordings demonstrate the feasibility of CNT fiber microelectrodes for high-fidelity, minimally invasive neural interfaces. To study the wiring diagrams of neural circuits and elucidate the fundamental mechanisms giving rise to behavior and disease at high spatial and temporal resolution, we have also developed transparent graphene-based optoelectronic neural interfaces for simultaneous electrophysiology and imaging. By leveraging the optical and electronic properties of graphene we have fabricated thin-film multichannel electrode arrays with >90% transparency from the UV to the near-infrared range, making them compatible with most of the conventional and fluorescence-based neuroimaging modalities. Example of applications of these optoelectronic graphene devices are chronic platforms for in vivo optical and electrical recordings of neural microcircuits involved in epilepsy generation.

Optimization of cochlear implant stimulation resolution using an intracochlear electric potential model

Designing an electrode array with a high stimulation resolution (SR) is the main challenge in cochlear implant development. In this work, a thin-film electrode array (TFEA) and partial tripolar (pTP) mode were combined in the design stage to optimize the SR. A finite-element model of the intracochlear electric potential Ve incorporating a TFEA and pTP mode was built and validated using previous experimental measurements. Based on this model, the SR was analyzed by using a defined stimulation factor Vs, which takes both the amplitude and bandwidth of Ve into account. A co-simulation method integrating the model and genetic algorithm was employed to maximize Vs with an optimized parameter set including the electrode diameter d, electrode interval g, and compensation coefficient σ. The results indicated that a TFEA combined with pTP mode outperforms their individual utilization to improve the SR and that d has an independent negative correlation with the SR, but it is more effective and feasible to consider all three parameters in the design stage with the proposed model and co-simulation optimization method. In our design, the optimized parameters were d = 150 μm, g = 200.5 μm, and σ = 0.746.

Extracellular matrix proteins as temporary coating for thin-film neural implants

Objective. This study investigates the suitability of a thin sheet of extracellular matrix (ECM) proteins as a resorbable coating for temporarily reinforcing fragile or ultra-low stiffness thin-film neural implants to be placed on the brain, i.e. microelectrocorticographic (µECOG) implants. Approach. Thin-film polyimide-based electrode arrays were fabricated using lithographic methods. ECM was harvested from porcine tissue by a decellularization method and coated around the arrays. Mechanical tests and an in vivo experiment on rats were conducted, followed by a histological tissue study combined with a statistical equivalence test (confidence interval approach, 0.05 significance level) to compare the test group with an uncoated control group. Main results. After 3 months, no significant damage was found based on GFAP and NeuN staining of the relevant brain areas. Significance. The study shows that ECM sheets are a suitable temporary coating for thin µECOG neural implants.

The effect of surgery and intracerebral injections on motor skill learning in rats: results from a database analysis

Male Long-Evans rats are often used to investigate neural mechanisms of learning in the motor system. Successful acquisition of a skilled motor task is influenced by various variables such as animal supplier and batch membership. In this retrospective analysis of our laboratory database, we investigate how head and brain surgery as well as intracerebral injections that were performed to address particular scientific questions affect motor learning. Overall, invasive interventions (n=90) slow the acquisition of a skilled-reaching task when compared to naïve animals (n=184; P=0.01). With respect to subgroups, this detrimental effect widely differs between particular procedures: whereas epidural implantations of thin-film electrode arrays and punctual injection through pre-implanted cannulas into primary motor cortex (M1) do not interfere with learning, skill acquisition is slowed after chronic infusion using osmotic minipumps into M1 and skill acquisition is lastingly impaired after bilateral cannula implantation within the dorsal striatum. In line with previous reports, breeder-specific differences could be observed in the analysis of the overall population. In summary, interventions may impair learning-behavior in an unpredictable fashion. Thus, a comparison of behavioral data to a naïve population is recommended to be aware of these drawbacks.

Thin-film micro-electrode stimulation of the cochlea in rats exposed to aminoglycoside induced hearing loss

The multi-channel cochlear implant (CI) provides sound and speech perception to thousands of individuals who would otherwise be deaf. Broad activation of auditory nerve fibres when using a CI results in poor frequency discrimination. The CI also provides users with poor amplitude perception due to elicitation of a narrow dynamic range. Provision of more discrete frequency perception and a greater control over amplitude may allow users to better distinguish speech in noise and to segregate sound sources. In this research, thin-film (TF) high density micro-electrode arrays and conventional platinum ring electrode arrays were used to stimulate the cochlea of rats administered sensorineural hearing loss (SNHL) via ototoxic insult, with neural responses taken at 434 multiunit clusters in the central nucleus of the inferior colliculus (CIC). Threshold, dynamic range and broadness of response were used to compare electrode arrays. A stronger current was required to elicit CIC threshold when using the TF array compared to the platinum ring electrode array. TF stimulation also elicited a narrower dynamic range than the PR counterpart. However, monopolar stimulation using the TF array produced more localised CIC responses than other stimulation strategies. These results suggest that individuals with SNHL could benefit from micro stimulation of the cochlea using a monopolar configuration which may provide discrete frequency perception when using TF electrode arrays.

Integration of temperature sensors in polyimide-based thin-film electrode arrays

Abstract Continuous monitoring of the tissue temperature surrounding implantable devices could be of great advantage. The degree and duration of the immune activation in response to the implant, which is responsible for signal deterioration, could be inferred from the associated temperature raise and the heating caused by electrical or optogenetical stimulation could be accurately controlled. Within this work, a thin-film platinum RTD embedded in polyimide and a readout system based on the Wheatstone bridge configuration are presented. The RTD offers a sensitivity of 8.5 Ω· °C−1 and a precision of 4.1 Ω. The accuracy of the complete system calibrated for temperatures ranging from 34 to 41 °C lies between the classes A and B defined by the standard IEC 751, which correspond to tolerances of ±0.22 and ±0.48 °C at 37 °C, respectively.