Considerable scientific and technological efforts have been devoted to develop neuroprostheses and hybrid bionic systems that link the human nervous system with electronic or robotic prostheses, with the main aim of restoring motor and sensory functions in disabled patients. A number of neuroprostheses use interfaces with peripheral nerves or muscles for neuromuscular stimulation and signal recording. Herein, we provide a critical overview of the peripheral interfaces available and trace their use from research to clinical application in controlling artificial and robotic prostheses. The first section reviews the different types of non-invasive and invasive electrodes, which include surface and muscular electrodes that can record EMG signals from and stimulate the underlying or implanted muscles. Extraneural electrodes, such as cuff and epineurial electrodes, provide simultaneous interface with many axons in the nerve, whereas intrafascicular, penetrating, and regenerative electrodes may contact small groups of axons within a nerve fascicle. Biological, technological, and material science issues are also reviewed relative to the problems of electrode design and tissue injury. The last section reviews different strate- gies for the use of information recorded from peripheral interfaces and the current state of control neuroprostheses and hybrid bionic systems.

A critical review of interfaces with the peripheral nervous system for the control of neuroprostheses and hybrid bionic systems

The promise of advanced neuroprosthetic systems to significantly improve the quality of life for a segment of the deaf, blind, or paralyzed population hinges on the development of an efficacious, and safe, multichannel neural interface for the central nervous system. The candidate implantable device that is to provide such an interface must exceed a host of exacting design parameters. The authors present a thin-film, polyimide-based, multichannel intracortical Bio-MEMS interface manufactured with standard planar photo-lithographic CMOS-compatible techniques on 4-in silicon wafers. The use of polyimide provides a mechanically flexible substrate which can be manipulated into unique three-dimensional designs. Polyimide also provides an ideal surface for the selective attachment of various important bioactive species onto the device in order to encourage favorable long-term reactions at the tissue-electrode interface. Structures have an integrated polyimide cable providing efficient contact points for a high-density connector. This report details in vivo and in vitro device characterization of the biological, electrical and mechanical properties of these arrays. Results suggest that these arrays could be a candidate device for long-term neural implants.

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Flexible polyimide-based intracortical electrode arrays with bioactive capability

This paper describes the development of a high-density electronic interface to the central nervous system. Silicon micromachined electrode arrays now permit the long-term monitoring of neural activity in vivo as well as the insertion of electronic signals into neural networks at the cellular level. Efforts to understand and engineer the biology of the implant/tissue interface are also underway. These electrode arrays are facilitating significant advances in our understanding of the nervous system, and merged with on-chip circuitry, signal processing, microfluidics, and wireless interfaces, they are forming the basis for a family of neural prostheses for the possible treatment of disorders such as blindness, deafness, paralysis, severe epilepsy, and Parkinson's disease.

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Wireless implantable microsystems: high-density electronic interfaces to the nervous system

In this review article, we focus on the various types of materials used in biomedical implantable devices, including the polymeric materials used as substrates and for the packaging of such devices. Polymeric materials are used because of the ease of fabrication, flexibility, and their biocompatible nature as well as their wide range of mechanical, electrical, chemical, and thermal behaviors when combined with different materials as composites. Biocompatible and biostable polymers are extensively used to package implanted devices, with the main criteria that include gas permeability and water permeability of the packaging polymer to protect the electronic circuit of the device from moisture and ions inside the human body. Polymeric materials must also have considerable tensile strength and should be able to contain the device over the envisioned lifetime of the implant. For substrates, structural properties and, at times, electrical properties would be of greater concern. Section 1 gives an introduction o...

Polymeric Biomaterials for Medical Implants and Devices

This study investigated the use of planar, silicon-substrate microelectrodes for chronic unit recording in the cerebral cortex. The 16-channel microelectrodes consisted of four penetrating shanks with four recording sites on each shank. The chronic electrode assembly included an integrated silicon ribbon cable and percutaneous connector. In a consecutive series of six rats, 5/6 (83%) of the implanted microelectrodes recorded neuronal spike activity for more than six weeks, with four of the implants (66%) remaining functional for more than 28 weeks. In each animal, more than 80% of the electrode sites recorded spike activity over sequential recording sessions during the postoperative time period. These results provide a performance baseline to support further electrode system development for intracortical neural implant systems for medical applications.

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Silicon-substrate intracortical microelectrode arrays for long-term recording of neuronal spike activity in cerebral cortex

Advanced microtechnologies offer new opportunities for the development of active implants that go beyond the design of pacemakers and cochlea implants. Examples of future implants include neural and muscular stimulators, implantable drug delivery systems, intracorporal monitoring devices and body fluid control systems. The active microimplants demand a high degree of device miniaturization without compromising on design flexibility and biocompatibility requirements. With the need for integrating various microcomponents for a complex retina stimulator device, we have developed a novel technique for microassembly and high-density interconnects employing flexible, ultra-thin polymer based substrates. Pads for interconnections, conductive lines, and microelectrodes were embedded into the polyimide substrate as thin films. Photolithography and sputtering has been employed to pattern the microstructures. The novel "MicroFlex interconnection (MFI)" technology was developed to achieve chip size package (CSP) dimensions without the requirement of using bumped flip chips (FC). The MFI is based on a rivet like approach that yields an electrical and mechanical contact between the pads on the flexible polyimide substrate and the bare chips or electronic components. Center to center bond pad distances smaller than 100 /spl mu/m were accomplished. The ultra thin substrates and the MFI technology was proven to be biocompatible. Electrical and mechanical tests confirmed that interconnects and assembly of bare chips are reliable and durable. Based on our experience with the retina stimulator implant, we defined design rules regarding the flexible substrate, the bond pads, and the embedded conductive tracks. It is concluded that the MFI opens new venues for a novel generation of active implants with advanced sensing, actuation, and signal processing properties.

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High density interconnects and flexible hybrid assemblies for active biomedical implants

It has been shown previously that peripheral nerve axons regenerate through microvias in silicon devices. A major challenge in the design of a biocompatible interface is to establish a reliable electrical and mechanical interconnection to signal-processing and transmission electronics which allows simultaneous multichannel recordings or stimulation of nerves. This paper describes the on-going work of developing a new generation of flexible and extremely light-weight electrode arrays with integrated cables. A process technology has been established to fabricate a multilayer device with micromachining methods, which overcomes the ‘classical’ separation of substrate and insulation layers. The micromachined electrodes exhibit promising mechanical stability and high insulation resistance.

A flexible, light-weight multichannel sieve electrode with integrated cables for interfacing regenerating peripheral nerves

A new interconnection technique has been developed that allows versatile multiple strand connections between microsensors, sensor arrays, and chips designed for wire bonding. The new technique has ...

“Microflex”—A New Assembling Technique for Interconnects

Different research groups are focusing their work on the development of a neural prostheses to aid patients suffering from blindness. In some diseases (retinitis pigmentosa or macula degeneration), degeneration of the photoreceptors often leaves the ganglion cell layer and the central vision system largely intact. This paper outlines the authors' approach of interfacing the retina with flexible multielectrode structures for ganglion cell stimulation. Results are given on the material selection for substrate materials and the design for flexible stimulation devices. By means of cytotoxicity testing, in a first step of an evaluation procedure, the biocompatibility of different substrate and coating materials has been investigated. The methods were sensitive to such a degree that even the influence of changes in process technology on the material was detected. Different geometric test structures have been created that led to the design of flexible, light-weighted stimulation devices with integrated cables. The devices were fabricated using micromachining technology. The authors used polyimide as substrate and insulation layers and platinum as electrode and interconnect metallization layers. The first structures were distributed to the partners for acute and chronic implantation in animal models.

Development of flexible stimulation devices for a retina implant system

For cell biosensors and for studying neural networks using planar electrode substrates, a suitable technique for positioning single cells on electrodes was needed. We reported a new method for fast and efficient positioning of single cells on ring electrodes by controlled suction through holes. We described the microfabrication of electrode substrates with microholes and the cell positioning procedure. L929 cells and Neuro 2A cells could be positioned in parallel without cell damage.

H. Beutel

Papers

High density interconnects and flexible hybrid assemblies for active biomedical implants

A flexible, light-weight multichannel sieve electrode with integrated cables for interfacing regenerating peripheral nerves

“Microflex”—A New Assembling Technique for Interconnects

Development of flexible stimulation devices for a retina implant system

Fast and precise positioning of single cells on planar electrode substrates