Neural Electrode Arrays Research Articles

Device for the implantation of neural electrode arrays.

Electrode arrays used in neural recording and stimulation applications must be implanted carefully to minimize damage to the underlying tissue. A device has been designed to improve a surgeon's control over implantation parameters including depth, insertion velocity, and insertion force. The device has been designed to operate without contacting tissue and to respond to tissue movements in real time during insertion. This device uses an electrical motor to drive electrode arrays into tissue and allows for the monitoring of and response to electrode depth during insertion. A prototype device has been constructed and tests have been performed to determine the velocity and force characteristics of the motor when inside the device housing. Future versions of the device will use a custom-designed motor with longer linear travel, which will allow the insertion device to be held farther from tissue while still ensuring proper array insertion.

Flexible three-dimensional microelectrode array for neural applications

A neural electrode array design is proposed with 3mm long sharpened pillars made from an aluminum-based substrate. The array is composed by 25 electrically insulated pillars in a 5×5 matrix, in which each aluminum pillar was precisely machined via dicing saw technique. The result is an aluminum structure with high-aspect-ratio pillars (19:1), each with a tip radius of 10μm. A thin-film of platinum was deposited via sputtering technique to perform the ionic signal transduction. Each pillar was encapsulated with an epoxy resin insulating the entire pillar excluding the tip. This process resulted in mechanically robust electrodes each capable of withstanding loads up to 200mN before bending. The array implantation tests were conducted on agar gel at speeds of 50mm/min, 120mm/min and 180mm/min which resulted in average implantation forces of 119mN, 145mN and 150mN, respectively. Insertion and withdrawal tests were also performed in porcine cadaver brain showing a necessary force of 66mN for successful explantation. A three point flexural test demonstrated a displacement of 0.8mm before array's breakage. The electrode's impedance was characterized showing a near resistive impedance of 385Ω in the frequency range from 2kHz to 125kHz. The resultant array, as well as the fabrication technique, is an innovative alternative to silicon-based electrode solutions, avoiding some fabrication methods and limitations related to silicon and increasing the mechanical flexibility of the array.

The effect of micro-ECoG substrate footprint on the meningeal tissue response

Objective. There is great interest in designing implantable neural electrode arrays that maximize function while minimizing tissue effects and damage. Although it has been shown that substrate geometry plays a key role in the tissue response to intracortically implanted, penetrating neural interfaces, there has been minimal investigation into the effect of substrate footprint on the tissue response to surface electrode arrays. This study investigates the effect of micro-electrocorticography (micro-ECoG) device geometry on the longitudinal tissue response. Approach. The meningeal tissue response to two micro-ECoG devices with differing geometries was evaluated. The first device had each electrode site and trace individually insulated, with open regions in between, while the second device had a solid substrate, in which all 16 electrode sites were embedded in a continuous insulating sheet. These devices were implanted bilaterally in rats, beneath cranial windows, through which the meningeal tissue response was monitored for one month after implantation. Electrode site impedance spectra were also monitored during the implantation period. Main results. It was observed that collagenous scar tissue formed around both types of devices. However, the distribution of the tissue growth was different between the two array designs. The mesh devices experienced thick tissue growth between the device and the cranial window, and minimal tissue growth between the device and the brain, while the solid device showed the opposite effect, with thick tissue forming between the brain and the electrode sites. Significance. These data suggest that an open architecture device would be more ideal for neural recording applications, in which a low impedance path from the brain to the electrode sites is critical for maximum recording quality.

Next-generation flexible neural and cardiac electrode arrays

The electrical activities of the brain and heart have been recorded and analyzed for diverse clinical and pathological purposes. To construct an implantable system for monitoring the electrical activity effectively, flexible and stretchable electrode arrays that are capable of making conformal contacts on the curvilinear, soft, and dynamic surfaces of the target organs have been extensively researched. Among many strategies, the most representative approach is to fabricate electrode arrays on plastic substrates to achieve more intimate and conformal contact with the target organs. Further optimizations are along with the development of ultrathin and stretchable electronics. Advanced structural modifications, such as thinning the overall profile or applying a mesh-like electrode network, have shown the greatly enhanced conformability and deformability of the device, providing improved signal-to-noise ratios (SNRs). Furthermore, brittle but high-performance silicon transistors have been successfully incorporated in flexible forms by virtue of mechanics-based active electronics designs, enabling the construction of high-density arrays comprising hundreds of multiplexed electrodes that can be individually addressed by only a few external wires. This review summarizes these strategies and describes their strengths and weaknesses, and it suggests possible technologies for nextgeneration electrode arrays.

Neural Electrode Array Based on Aluminum: Fabrication and Characterization

A unique neural electrode design is proposed with 3 mm long shafts made from an aluminum-based substrate. The electrode is composed by 100 individualized shafts in a 10 × 10 matrix, in which each aluminum shafts are precisely machined via dicing-saw cutting programs. The result is a bulk structure of aluminum with 65 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">°</sup> angle sharp tips. Each electrode tip is covered by an iridium oxide thin film layer (ionic transducer) via pulsed sputtering, that provides a stable and a reversible behavior for recording/stimulation purposes, a 40 mC/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> charge capacity and a 145 Ω impedance in a wide frequency range of interest (10 Hz-100 kHz). Because of the non-biocompatibility issue that characterizes aluminum, an anodization process is performed that forms an aluminum oxide layer around the aluminum substrate. The result is a passivation layer fully biocompatible that furthermore, enhances the mechanical properties by increasing the robustness of the electrode. For a successful electrode insertion, a 1.1 N load is required. The resultant electrode is a feasible alternative to silicon-based electrode solutions, avoiding the complexity of its fabrication methods and limitations, and increasing the electrode performance.

Resorbable scaffold based chronic neural electrode arrays

We have developed a novel type of neural electrode array for future brain-machine interfaces (BMI) and neural implants requiring high resolution recording and stimulation on the surface of brain lesions or on the cortex. The devices differ on two points from commonly used thin film electrode arrays: first, the thin film backbone of the implant is exceptionally thin (down to 5 microns) and finely patterned into spring-like structures. This increases the flexibility of the electrode array and allows stretching and conforming better to a quasi spherical cavity surface. Second, the thin film backbone of the device is reinforced with a porous layer of resorbable chitosan. This design aims at minimal invasiveness and low mechanical irritation during prolonged use, while the chitosan matrix ensures the implant is stiff enough for practical handling during the implantation procedure and dissolves afterwards. Furthermore, the chitosan adds haemostatic and antiseptic properties to the implant and improves adhesion. In the article, the design and fabrication process are presented. In vitro and long term in vivo test results over a 12 month period are shown. By adopting the use of a resorbable scaffold-like material as main constituent of neural implants, the presented work opens up the possibility of applying tissue engineering techniques to further improve neural implant technology.

A Largely Deformable Surface Type Neural Electrode Array Based on PDMS

This paper describes a largely deformable surface type neural electrode array based on polydimethylsiloxane (PDMS) for cortical use. Noncracked and reliable metal patterns were fabricated successfully on PDMS substrate by employing an intermediate parylene layer. The mechanical and electrical stability of the fabricated electrode arrays was demonstrated by repeatable bending test using a custom-designed bending test module. Also the adhesion of the electrode structure consisting of PDMS, parylene and metal layers was proven by ASTM tape test. The electrode impedance was measured in phosphate buffered saline (PBS) solution at 37 (°) C over three months and analyzed using equivalent circuit models. Based on these results, it is concluded that the suggested electrode array provides a largely deformable structure with mechanical integrity and electrical stability, which can withstand mechanical stresses when inserted through a small trephination hole in the skull and expanded in the small room between the cortex and the skull without damage to the electrode array.

Neural Implants Containing a Resorbable Chitosan Matrix

Summary We have developed a novel type of neural electrode array for future brain-machine interfaces (BMIs) or neural prosthesis requiring high resolution recording and stimulation on the cortex. The microelectrode arrays developed comprise of a thin film stack of platinum and polyimide or Parylene C insulation, which is finely microstructured for increased flexibility. The electrode stack is temporarily reinforced with a matrix of porous chitosan, which resorbs after implantation. This design ensures low invasiveness and mechanical irritation during prolonged use, while the chitosan matrix ensures the implant is stiff enough for practical handling during the implantation procedure and is resorbed afterwards. Furthermore, it adds haemostatic and antiseptic properties to the implant. The design and fabrication process are presented. In vitro and long-term in vivo test results are shown, showing the suitability for the application targeted.

Seeding neural progenitor cells on silicon-based neural probes

Chronically implanted neural electrode arrays have the potential to be used as neural prostheses in patients with various neurological disorders. While these electrodes perform well in acute recordings, they often fail to function reliably in clinically relevant chronic settings because of glial encapsulation and the loss of neurons. Surface modification of these implants may provide a means of improving their biocompatibility and integration within host brain tissue. The authors proposed a method of improving the brain-implant interface by seeding the implant's surface with a layer of neural progenitor cells (NPCs) derived from adult murine subependyma. Neural progenitor cells may reduce the foreign body reaction by presenting a tissue-friendly surface and repair implant-induced injury and inflammation by releasing neurotrophic factors. In this study, the authors evaluated the growth and differentiation of NPCs on laminin-immobilized probe surfaces and explored the potential impact on transplant survival of these cells. Laminin protein was successfully immobilized on the silicon surface via covalent binding using silane chemistry. The growth, adhesion, and differentiation of NPCs expressing green fluorescent protein (GFP) on laminin-modified silicon surfaces were characterized in vitro by using immunocytochemical techniques. Shear forces were applied to NPC cultures in growth medium to evaluate their shearing properties. In addition, neural probes seeded with GFP-labeled NPCs cultured in growth medium for 14 days were implanted in murine cortex. The authors assessed the adhesion properties of these cells during implantation conditions. Moreover, the tissue response around NPC-seeded implants was observed after 1 and 7 days postimplantation. Significantly improved NPC attachment and growth was found on the laminin-immobilized surface compared with an unmodified control before and after shear force application. The NPCs grown on the laminin-immobilized surface showed differentiation potential similar to those grown on polylysine-treated well plates, as previously reported. Viable (still expressing GFP) NPCs were found on and in proximity to the neural implant after 1 and 7 days postimplantation. Preliminary examinations indicated that the probe's NPC coating might reduce the glial response at these 2 different time points. The authors' findings suggest that NPCs can differentiate and strongly adhere to laminin-immobilized surfaces, providing a stable matrix for these cells to be implanted in brain tissue on the neural probe's surface. In addition, NPCs were found to improve the astrocytic reaction around the implant site. Further in vivo work revealing the mechanisms of this effect could lead to improvement of biocompatibility and chronic recording performance of neural probes.

Three-dimensional micro-electrode array for recording dissociated neuronal cultures

This work demonstrates the design, fabrication, packaging, characterization, and functionality of an electrically and fluidically active three-dimensional micro-electrode array (3D MEA) for use with neuronal cell cultures. The successful function of the device implies that this basic concept-construction of a 3D array with a layered approach-can be utilized as the basis for a new family of neural electrode arrays. The 3D MEA prototype consists of a stack of individually patterned thin films that form a cell chamber conducive to maintaining and recording the electrical activity of a long-term three-dimensional network of rat cortical neurons. Silicon electrode layers contain a polymer grid for neural branching, growth, and network formation. Along the walls of these electrode layers lie exposed gold electrodes which permit recording and stimulation of the neuronal electrical activity. Silicone elastomer micro-fluidic layers provide a means for loading dissociated neurons into the structure and serve as the artificial vasculature for nutrient supply and aeration. The fluidic layers also serve as insulation for the micro-electrodes. Cells have been shown to survive in the 3D MEA for up to 28 days, with spontaneous and evoked electrical recordings performed in that time. The micro-fluidic capability was demonstrated by flowing in the drug tetrotodoxin to influence the activity of the culture.

Surface immobilization of neural adhesion molecule L1 for improving the biocompatibility of chronic neural probes: In vitro characterization

Silicon-based implantable neural electrode arrays are known to experience failure during long-term recording, partially due to host tissue responses. Surface modification and immobilization of biomolecules may provide a means to improve their biocompatibility and integration within the host brain tissue. Previously, the laminin biomolecule or laminin fragments have been used to modify the neural probe’s silicon surface to promote neuronal attachment and growth. Here we report the successful immobilization of the L1 biomolecule on a silicon surface . L1 is a neuronal adhesion molecule that can specifically promote neurite outgrowth and neuronal survival. Silane chemistry and the heterobifunctional coupling agent 4-maleimidobutyric acid N-hydroxysuccinimide ester (GMBS) were used to covalently bind these two biomolecules onto the surface of silicon dioxide wafers, which mimic the surface of silicon-based implantable neural probes. After covalent binding of the biomolecules, polyethylene glycol (PEG)–NH 2 was used to cap the unreacted GMBS groups. Surface immobilization was verified by goniometry, dual polarization interferometry, and immunostaining techniques. Primary murine neurons or astrocytes were used to evaluate the modified silicon surfaces. Both L1- and laminin-modified surfaces promoted neuronal attachment, while the L1-modified surface demonstrated significantly enhanced levels of neurite outgrowth ( p < 0.05). In addition, the laminin-modified surface promoted astrocyte attachment, while the L1-modified surface showed significantly reduced levels of astrocyte attachment relative to the laminin-modified surface and other controls ( p < 0.05) . These results demonstrate the ability of the L1-immobilized surface to specifically promote neuronal growth and neurite extension, while inhibiting the attachment of astrocytes, one of the main cellular components of the glial sheath. Such unique properties present vast potentials to improve the biocompatibility and chronic recording performance of neural probes.

Matrix-addressable, active electrode arrays for neural stimulation using organic semiconductors—cytotoxicity and pilot experiments in vivo

Organic field effect transistors can be integrated into micromachined polyimide-based neural stimulation electrode arrays in order to build active switching matrices. With this approach, a matrix of N × M electrode contacts requires only N + M interconnects to a stimulator when active switching elements are used instead of N × M interconnects. In this paper, we demonstrated that pentacene-based organic field effect transistors (OFETs) can be used to drive stimulation currents through neural electrodes in a physiological-like environment. In order to prove the general applicability as an implant material, the cytotoxicity of pentacene was evaluated with respect to potential effects on cell viability. The results of these tests indicate that extracts from pentacene inhibit neither proliferation nor metabolism of the tested mouse fibroblasts. However, some effect on cell spreading was observed when cells were in direct contact to pentacene for 48 h. In pilot experiments it was demonstrated for the very first time that pentacene transistors can be used as switching elements, acting as voltage-controlled current sources, capable of driving currents suitable for electrical stimulation of a peripheral nerve via a tripolar cuff electrode.

Fabrication and Characterization of Flexible, Microfabricated Neural Electrode Arrays Made from Liquid Crystal Polymer and Polynorbornene

ABSTRACTThis paper reports the development of flexible, neural electrode arrays made from liquid crystal polymer (LCP) and a polynorbornene (PNB) known by its trade name AvatrelTM. Each array consists of a single flexible, polymeric structure composed of an 8 mm-wide pad supporting eight Pt contacts connected to an ASIC mounting pad by a 5 cm-long, 2 mm-wide shaft carrying eight, 50 μm-wide Pt interconnect lines. The Pt conductors sit atop a 50 μm-thick base layer and are isolated from the environment except at the contacts by a capping layer of the same material as the base. In both cases, the devices were fabricated using conventional microfabrication techniques adapted for the particular polymeric material. In the case of LCP, the base structure was fabricated on 50 μm-thick sheets that were laminated and etched into the final structure. In contrast to LCP, PNB is spin castable and photodefinable, which enabled conventional photolithographic patterning techniques to be employed in a straightforward manner. The PNB-based devices could readily be fabricated, however issues related to LCP etching necessitated the development of a multi-step etch process to form the vias that expose the contacts. Electrodes made from both polymers could support electrical loads typical of stimulation applications without failing. A simple cell culture test suggests that Avatrel™ may be biocompatible, at least for short term applications.

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

Chronic recordings from micromachined neural electrode arrays often fail a few weeks after implantation primarily due to the formation of an astro-glial sheath around the implant. We propose a drug delivery system, from conducting polymer (CP) coatings on the electrode sites, to modulate the inflammatory implant-host tissue reaction. In this study, polypyrrole (PPy) based coatings for electrically controlled and local delivery of the ionic form of an anti-inflammatory drug, dexamethasone (Dex), was investigated. The drug was incorporated in PPy via electropolymerization of pyrrole and released in PBS using cyclic voltammetry (CV). FTIR analysis of the surface showed the presence of Dex and polypyrrole on the coated electrode. The thickness of the coated film was estimated to be ∼50 nm by ellipsometry. We are able to release 0.5 μg/cm 2 Dex in 1 CV cycle and a total of almost 16 μg/cm 2 Dex after 30 CV cycles. In vitro studies and immunocytochemistry on murine glial cells suggest that the released drug lowers the count of reactive astrocytes to the same extent as the added drug. In addition, the released drug is not toxic to neurons as seen by healthy neuronal viability in the released drug treated cells.

Dynamic control of extracellular environment in in vitro neural recording systems

A technique is presented for rapid fabrication of microfluidic channels on top of multichannel in vitro neural recording electrode arrays. The channels allow dynamic control of both stable and transient flow patterns over localized areas of the array, over biologically relevant timescales. A cellular model consisting of thermally sensitive dorsal root ganglion neurons was integrated into the devices. The device was used to demonstrate precise control of the extracellular microenvironment of individual cells on the array. Since the methods presented here are not specific to a particular cell type or neural recording system, the technique is amenable to a wide range of applications within the neuroscience field.