To achieve selective electrical interfacing to the neural system it is necessary to approach neuronal elements on a scale of micrometers. This necessitates microtechnology fabrication and introduces the interdisciplinary field of neurotechnology, lying at the juncture of neuroscience with microtechnology. The neuroelectronic interface occurs where the membrane of a cell soma or axon meets a metal microelectrode surface. The seal between these may be narrow or may be leaky. In the latter case the surrounding volume conductor becomes part of the interface. Electrode design for successful interfacing, either for stimulation or recording, requires good understanding of membrane phenomena, natural and evoked action potential generation, volume conduction, and electrode behavior. Penetrating multimicroelectrodes have been produced as one-, two-, and three-dimensional arrays, mainly in silicon, glass, and metal microtechnology. Cuff electrodes circumvent a nerve; their selectivity aims at fascicles more than at nerve fibers. Other types of electrodes are regenerating sieves and cone-ingrowth electrodes. The latter may play a role in brain-computer interfaces. Planar substrate-embedded electrode arrays with cultured neural cells on top are used to study the activity and plasticity of developing neural networks. They also serve as substrates for future so-called cultured probes.

Selective electrical interfaces with the nervous system.

Cell-based impedance biosensing is an emerging technology that can be used to non-invasively and instantaneously detect and analyze cell responses to chemical and biological agents. This article highlights the fabrication and measurement technologies of cell impedance sensors, and their application in toxin detection and anti-cancer drug screening. We start with an introduction that describes the capability and advantages of cell-based sensors over conventional sensing technology, followed by a discussion of the influence of cell adhesion, spreading and viability during cell patterning on the subsequent impedance measurements and sensing applications. We then present an electronic circuit that models the cell-electrode system, by which the cellular changes can be detected in terms of impedance changes of the circuit. Finally, we discuss the current status on using cell impedance sensors for toxin detection and anti-cancer drug screening.

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Cellular impedance biosensors for drug screening and toxin detection.

Some embodiments of the present invention provide stimulation systems and components for selective stimulation and/or neuromodulation of one or more nerve root ganglia through implantation of an electrode on, in or around a nerve root ganglia. Some other embodiments of the present invention provide methods for selective neurostimulation of one or more dorsal root ganglia as well as techniques for applying neurostimulation to the spinal cord. Still other embodiments of the present invention provide stimulation systems and components for selective stimulation and/or neuromodulation of one or more nerve root ganglia through implantation of an electrode on, in or around a nerve root ganglia in combination with a pharmacological agent.

Methods for stimulating a nerve root ganglion

The paper reports on the deposition of iridium oxide thin films by dc reactive magnetron sputtering and their characterization by surface analysis methods (X-ray diffraction, scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy) and electrochemical techniques (cyclic voltammetry, electrochemical impedance spectroscopy, and galvanostatic square waves) The sputtering process was investigated by applying the method of generic curves An optimal combination of sputtering parameters has been established [40 standard cubic centimeters per minute (sccm) argon/8-12 sccm oxygen/40% effective pump power/100 W dc power/cold sputtering] that yields stable microporous amorphous films with a highly extended surface These films have shown an excellent electrochemical reversibility in physiological saline solution with a safe potential range of -12 to 13 V vs Ag/AgCl reference electrode, a charge delivery capacity of 90-95 mC/cm 2 , a constant impedance of 70-80 Ω in the frequency range of 100 kHz down to 05-10 Hz, and a quick response to bipolar current pulses with a safe charge per phase of 2 mC/cm 2 /ph The demonstrated remarkable electrochemical characteristics combined with their established long-term mechanical stability and corrosion resistance allow one to recommend the use of sputtered iridium oxide films as an ideal electrode material for neural stimulation

Sputtered Iridium Oxide Films as Charge Injection Material for Functional Electrostimulation

Publisher Summary This chapter discusses efforts from a number of groups that lay the groundwork for an in vitro approach to study the population coding. Most researchers studying population coding are working with intact, living animals. The cultured neuronal networks lack many features of real brains, but they retain many others. They develop organotypic synaptic connections and exhibit a rich variety of distributed patterns of electrical activity. Progress in multi-electrode array technology, optical recording, and multi-photon microscopy, made it possible that every cell in a cultured monolayer network can be observed, monitored, stimulated, and manipulated with temporal resolution in the sub millisecond range, and spatial resolution in the submicron range, in a non-destructive manner. The nascent field of population coding in networks of cultured neurons is poised for rapid expansion. Neural cell culture, long-term multi-electrode recording and stimulation, and multi-single-unit optical recording are now accessible to many labs. Computers are fast and cheap enough to allow real-time spike analysis and stimulus generation, which makes it possible to give cultured networks a simulated body to behave with, and an environment to interact with. By allowing the culture to behave and receive sensory input, meaning can be ascribed to the patterns of electrical activity it produces, and persistent changes in network activity can be thought of as learning.

Distributed processing in cultured neuronal networks.

Characterization and optimization of microelectrode arrays for in vivo nerve signal recording and stimulation

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.

Fast and precise positioning of single cells on planar electrode substrates

For single-cell-biosensor applications and for studying neural networks using planar electrode substrates often the position of cells on detectors is necessary. Here, the authors present a new method for fast placement of single cells on ring electrodes by suction on suction holes. They describe the fabrication of a micromachined planar electrode substrate with suction holes and the placement of L929 cells and Neuro 2A cells on particular positions. The results are discussed regarding the deciding factors for placement. Finally, applications of the authors' cell placement technique to form patterned neural networks are outlined.

T. Matthies

Papers

Characterization and optimization of microelectrode arrays for in vivo nerve signal recording and stimulation

Fast and precise positioning of single cells on planar electrode substrates

A novel cell-positioning technique for extracellular recording and impedance measurement on single cells using planar electrode substrates