Silicon-substrate microelectrode arrays for parallel recording ofneural activity in peripheral and cranial nerves

A new process for the fabrication of regeneration microelectrode arrays for peripheral and cranial nerve applications is presented. This type of array is implanted between the severed ends of nerves, the axons of which regenerate through via holes in the silicon and are thereafter held fixed with respect to the microelectrodes. The process described is designed for compatibility with industry-standard CMOS or BiCMOS processes (it does not involve high-temperature process steps nor heavily-doped etch-stop layers), and provides a thin membrane for the via holes, surrounded by a thick silicon supporting rim. Many basic questions remain regarding the optimum via hole and microelectrode geometries in terms of both biological and electrical performance of the implants, and therefore passive versions were fabricated as tools for addressing these issues in on-going work. Versions of the devices were implanted in the rat peroneal nerve and in the frog auditory nerve. In both cases, regeneration was verified histologically and it was observed that the regenerated nerves had reorganized into microfascicles containing both myelinated and unmyelinated axons and corresponding to the grid pattern of the via holes. These microelectrode arrays were shown to allow the recording of action potential signals in both the peripheral and cranial nerve settings, from several microelectrodes in parallel     

Fabrication and characterization of nonplanar microelectrode array circuits for use in arthroscopic diagnosis of cartilage diseases

A process to fabricate nonplanar microelectrode array circuits was developed and the microelectrodes were characterized. These platinum microelectrode arrays are for recording streaming potential signals generated during indentation of articular cartilage. The nonplanar substrate was produced by permanent deformation of a 7-in-diameter circular stainless-steel wafer to form 32 semi-spherical caps (radius of curvature = 4.65 mm and height = 250 microm) at the periphery. The wafer was covered with a 2.5-microm-thick layer of insulating polyimide. Standard microelectronic processes were applied to produce 32 circuits (60 mm long x 4 mm wide) with 37 exposed circular microelectrodes (diameter = 100 microm) centered over each semi-spherical cap. A 2.5-microm-thick photodefinable polyimide layer encapsulated the conducting lines. Capacitances between one microelectrode and either another microelectrode or the metallic substrate were 14.6 +/- 2.0 and 34.4 +/- 3.3 pF, respectively, at 100 Hz. The impedance of the microelectrodes in a 0.15 M saline bath (PBS) was 0.25 +/- 0.08 Mohms while the crosstalk (Vinduced/Vapplied) between two microelectrodes was 0.20 +/- 0.11%, at 100 Hz. Indentation measurements were performed on articular cartilage in vitro showing,streaming potentials that indicate electrode-tissue contact times and generation of streaming potentials.     

Regeneration microelectrode array for peripheral nerve recordingand stimulation

A microelectrode array capable of recording from and stimulating peripheral nerves at prolonged intervals after surgical implantation has been demonstrated. The microelectrode array, fabricated on a silicon substrate perforated by multiple holes (referred to as via holes), is implanted between the ends of a surgically severed nerve. Regenerating tissue fixes the device in place to provide a stable mapping between the microelectrodes and the axons in the nerve. Processes were developed for the fabrication of thin-film iridium microelectrodes, micromachined via holes, and silicon nitride passivation layers. All fabrication methods were designed to be compatible with standard CMOS/BiCMOS processes to allow for on-chip signal processing circuits in future designs. Such arrays, implanted in the peroneal nerves of rats, were used to record from and stimulate the nerves at up to 13 months postoperatively.     

基于Parylene的柔性微电极阵列微加工工艺研究

基底集成的柔性微电极阵列(MEAs)从一个全新的角度演绎了植入式神经系统,对神经进行电刺激并记录神经电信号.以一种新型聚合物材料聚对二甲苯(parylene)为基底,制备出了用于神经接口的柔性神经微电极阵列.采用MEMS加工技术,设计了一种基于parylene柔性神经微电极阵列的加工工艺方法,并讨论了在流片过程中的关键问题,如掩膜层的选择、电极的剥离及焊接与封装等.该柔性微电极阵列在用于视觉假体的神经接口方面具有独特的应用优势.     

A flexible perforated microelectrode array for extended neuralrecordings

A flexible and perforated 32-element planar microelectrode array has been fabricated and used to measure evoked potentials in brain slices. Electrodes are spaced 200 microns apart in a 4 x 8 array and are sandwiched between layers of insulating polyimide. The polyimide sandwich is lifted off its substrate, making it flexible so that it could shape to contoured tissues. Prior to lift off, holes are etched to expose recording sites 15 microns in diameter and to create perforations which allow increased circulation of artificial cerebrospinal fluid to the recording surface of the tissue and, hence, increased viability. Comparisons of evoked potentials measured over time showed an average increase of 10 h to the viability of the slice while using the perforated versus nonperforated arrays.     

Polyimide-related design considerations in a bipolar technology

It is found that a spurious leakage path from the emitter to the collector of a lateral p-n-p or a trench-defined n-p-n device may be induced by the applied collector voltage. This voltage influences the surface potential at the emitter-base junction through the charging of the polyimide used as interlevel dielectric or as trench fill, respectively. A simple model of the effect is developed, and several successful process features are discussed     

Microelectrode array fabrication by electrical discharge machining and chemical etching

Wire electrical discharge machining (EDM), with a complementary chemical etching process, is explored and assessed as a method for developing microelectrode array assemblies for intracortically recording brain activity. Assembly processes based on these methods are highlighted, and results showing neural activity successfully recorded from the brain of a mouse using an EDM-based device are presented. Several structures relevant to the fabrication of microelectrode arrays are also offered in order to demonstrate the capabilities of EDM.     

All Biodisintegratable Hydrogel Biohybrid Neural Interfaces with Synergistic Performances of Microelectrode Array Technologies,Tissue Scaffolding,and Cell Therapy

Biohybrid neural interfaces (BHNIs) are a new class of neuromodulating devices that integrate neural microelectrode arrays (MEAs) and cell transplantation to improve treatment of nerve injuries and disorders. However, current BHNI devices are made from abiotic materials that are usually bio-passive, non-biodisintegratable, or rigid, which restricts encapsulated cell activity and host nerve reconstruction and frequently leads to local tissue inflammation. Herein, the first MEA composed of all disintegratable hydrogel tissue scaffold materials with synergistic performances of tissue conformal adhesiveness, MEA technologies, tissue scaffolding and stem cell therapy on a time scale appropriate for nerve tissue repair is proposed. In particular, the MEA conductive tracks are made from extracellular matrix (ECM)-based double-cross-linked dual-electrically conductive hydrogel (ECH) systems with robust tissue-mimicking chemical/physical properties, electrical conductivity, and an affinity for neural progenitor stem cells. Meanwhile, the MEA hydrogel substrate prepared from transglutaminase-incorporated gelatin/silk precursors simultaneously promotes gelation and interfacial adhesion between all MEA stacks, leading to rapid and scalable device integration. When the full hydrogel MEA is subjected to various mechanical stimuli and moisture, it is structurally stable with a low impedance (4 ± 3 kΩ) comparable to a recently reported benchmark. With seamless lamination around peripheral nerve fibers, the device permits successive neural signal monitoring for wound condition evaluation, while demonstrating synergistic effects of spatiotemporally controlled electrical stimulation and cell transplantation to accelerate restoration of motor function. This BHNI is completely degraded by 1 month thus eliminating the need for surgical retrieval to stably remain, interact, and further fuse with host tissues, successfully exhibiting compatible integration of biology and an implanted electrical system.     

A system for MEA-based multisite stimulation

The capability for multisite stimulation is one of the biggest potential advantages of microelectrode arrays (MEAs). There remain, however, several technical problems which have hindered the development of a practical stimulation system. An important design goal is to allow programmable multisite stimulation, which produces minimal interference with simultaneous extracellular and patch or whole cell clamp recording. Here, we describe a multisite stimulation and recording system with novel interface circuit modules, in which preamplifiers and transistor transistor logic-driven solid-state switching devices are integrated. This integration permits PC-controlled remote switching of each substrate electrode. This allows not only flexible selection of stimulation sites, but also rapid switching of the selected sites between stimulation and recording, within 1.2 ms. This allowed almost continuous monitoring of extracellular signals at all the substrate-embedded electrodes, including those used for stimulation. In addition, the vibration-free solid-state switching made it possible to record whole-cell synaptic currents in one neuron, evoked from multiple sites in the network. We have used this system to visualize spatial propagation patterns of evoked responses in cultured networks of cortical neurons. This MEA-based stimulation system is a useful tool for studying neuronal signal processing in biological neuronal networks, as well as the process of synaptic integration within single neurons.     

An implantable optrode composed of fiber and flexible thin-film electrode

An implantable optrode composed of fiber and multi-channel flexible thin-film electrode is developed. The flexible recording electrode is made from polyimide and is wrapped around the optical fiber. The front end of the fiber is tapered by wet etching. With the tapered shape, the light can leak from the sidewall of the fiber, and the tapered tip makes it easy to be implanted. The flexible electrode is attached with its recording sites aligning to the tapered part on the fiber. With this method, the fiber acts as an optical waveguide, as well as a support probe for flexible thin-film electrode. This novel device simplifies the fabrication process and decreases the size of the optrode. The device works well in vivo and the optical caused spike can be recorded with signal-to-noise ratio of 6:1.     

光敏聚酰亚胺在硫化镉紫外器件中的应用

介绍了光敏聚酰亚胺的特性及应用情况,将其引入到硫化镉紫外器件制作中,通过实验研究开发并掌握一种正性光敏聚酰亚胺的光刻工艺,亚胺化后将其作为硫化镉器件的表面钝化层,经过实验验证其粘附牢固度和光电性能满足使用要求。同时该光敏聚酰亚胺的应用能够简化近40%的制作工艺,提高了硫化镉紫外器件的生产效率和成品率。     

Current transient in polyimide-passivated InP/InGaAs heterojunction bipolar transistors: systematic experiments and physical model

We present the first comprehensive experimental investigation of base current transient in InP/InGaAs heterojunction bipolar transistors (HBTs) induced by polyimide passivation, and its influence on the device characteristics. We have confirmed that the trapping and detrapping of static charge in the polyimide at the polyimide/semiconductor interface is the root cause for the current transient effect. Experimental and theoretical evidence indicates that the base current transient is caused by the change of the base-emitter junction surface potential as a result of the decrease in the number of trapped electrons in the polyimide film. A physical model accounting for the time-dependence of surface recombination current induced by electron detrapping in the polyimide is derived and predicts the current transient behavior. The physical understanding is helpful for further optimization of polyimide passivation process for HBTs.     

Post-CMOS electrode formation and isolation for on-chip temperature-controlled electrochemical sensors

A low-cost post-CMOS fabrication process enabling the formation of thermally controlled and isolated microelectrode array sites suitable for biomimetic and bioelectronic protein attachment on existing CMOS circuitry has been developed and implemented in the fabrication of an electrochemical array system for biosensing applications.     

Thin-film multielectrode arrays for a cochlear prosthesis

The design and fabrication of flexible thin-film microelectrode arrays for use in a cochlear prosthesis are described. The electrode array is designed to be inserted through the round window of the cochlea into the spiral scala tympani chamber of the cochlea. A lifetime of decades under stimulation is sought. The electrode array is comprised of photolithographically defined platinum-on-tantalum conductors sandwiched between polyimide layers. A liquid polyimide is used, which polymerizes in two stages. After the first stage of curing, the polyimide is susceptible to photolithographic etching, allowing patterned access holes to be cut into the top layer of the insulating sandwich. After the second cure, the polymer becomes inert biocompatible Kapton. The processing techniques and the electrode test results are presented.     

A 3-d 160-site microelectrode array for cochlear nucleus mapping

A 3-D application-specific microelectrode array has been developed for physiological studies in guinea pig cochlear nucleus (CN). The batch-fabricated silicon probes contain integrated parylene cables and use a boron etch-stop to define 15μm-thick shanks and limit tissue displacement. Targeting the ventral (three probes) and dorsal (two probes) subnuclei, the custom four-shank 32-site probes are combined in a slotted block platform having a 1.18-mm (2) footprint. The device has permitted, for the first time, high-density 3-D in vivo studies of ventral CN to dorsal CN connections, stimulating with 1000 μm (2) sites in one subnucleus while recording with 177 μm (2) sites in the other. Through these experiments, it has demonstrated the efficacy of bimodal silicon arrays to better understand the central nervous system at the circuit level. The 160 electrode sites also provide a high-density neural interface, which is an essential aspect of auditory prosthesis prototypes.     

The application of polyimide/silicon nitride dual passivation to AlxGa1−xN/GaN high electron mobility transistors

PECVD silicon nitride passivation is quite frequently done at the end of AlGaN/GaN HEMT fabrication before substrate back-side lapping. However, the PECVD silicon nitride process is likely to produce pinholes in the passivation film. A very thick PECVD silicon nitride film may produce mechanical stress on the underlying device. Polyimide passivation has also been known to be effective for AlGaN/GaN HEMT and it can also serve as a stress buffer. However, polyimide can take up water while PECVD silicon nitride is a good diffusion barrier for water, etc. Thus it is expected that a dual PECVD silicon nitride/polyimide passivation will be a better choice than just a single layer of PECVD silicon nitride or polyimide. In this paper, we will demonstrate the application of a dual PECVD silicon nitride/polyimide passivation to AlGaN/GaN HEMT process.     

DC and microwave noise transient behavior of InP/InGaAs doubleheterojunction bipolar transistor (DHBT) with polyimide passivation

DC and microwave noise transient behavior of InP/InGaAs double heterojunction bipolar transistor (DHBT) with polyimide passivation is reported in this paper for the first time. The base transient current is believed to be due to the change of surface potential near the base-emitter junction perimeter at the polyimide/emitter interface resulting from a decrease in the amount of trapped electrons in the polyimide. We also find that the surface potential on the sidewall of collector-emitter affected by the charge trapping and detrapping in polyimide may induce a parasitic polyimide field effect transistor along the surface of the base-collector junction which results in an excess collector transient current. These base and collector current transients result in associated transient of broadband shot noise. The time dependence of microwave noise figures due to the excess transients is also investigated. The better understanding of the mechanisms of the noise transient behavior of the InP HBT device is very useful to improve the device and circuit reliability     

Microelectrode array on folding polyimide ribbon for epidural mapping of functional evoked potentials

This paper describes a flexible polyimide microelectrode ribbon with a bending structure for epidural recording. Bending the ribbon establishes good electro-mechanical contact of the electrodes to the cortex. Impedance spectroscopy and noise measurements in vitro were used to characterize the electrodes. Our in vivo experiments then successfully achieved synchronized neuronal activity and evoked potential patterns useful for understanding brain function and for finding cortical function.     

MicroPen direct-write deposition of polyimide

Polyimide has been widely used as structural or sacrificial material in MEMS device fabrication. However, all the typical methods for processing polyimide are based on lithographic technique, which are time-consuming, expensive and non-flexible. In this paper, we propose a novel approach for depositing polyimide patterns by the microPen direct-write deposition technique, which is CAD direct-driven, maskless, rapid-prototyping, and diverse materials integration. Material and device for the microPen direct-write deposition of polyimide technique are presented in detail, and the influences of direct-writing parameters, such as extrusive gas–pressure, direct-writing velocity and the tip-to-substrate distance, on the profile of the deposited polyimide pattern are discussed. Using commercial gold paste (Au) as the structural layer material and polyimide as the sacrificial layer, a micro air-bridge array is successfully fabricated by the microPen direct-write deposition technique, which shows its potential applications in the area of MEMS device fabrication.     

Electrochemistry on microcircuits. I: Copper microelectrodes in oxalic acid media

Microelectrode size and connections are the two main limitations to conceive microelectrode arrays with a micrometric scale to study the electrochemical phenomena involved in the damascene process. A new chip consisting of an array of microelectrodes realized in an industrial CMOS process addresses these issues. This new fabrication technique for the realization of copper microelectrode arrays was reported. The design and the manufacturing of this device were aimed at studying the behaviour of copper by electrochemical measurements at small scale in media of interest for the microelectronic industry.In this paper, the design and the manufacturing of microelectrode array composed of copper electrode couples of various geometries were described. An advanced photolithography technique developed for the semiconductor industry was used to fabricate them. The tools permitting their characterization are also presented in order to study the wet processes involved in the damascene process by various electrochemical techniques, namely voltammetry and electrochemical impedance measurements.