Neuroelectronic interfacing with cultured multielectrode arrays toward a cultured probe

Efficient and selective electrical stimulation and recording of neural activity in peripheral, spinal, or central pathways requires multielectrode arrays at micrometer scale. ¿Cultured probe¿ devices are being developed, i.e., cell-cultured planar multielectrode arrays (MEAs). They may enhance efficiency and selectivity because neural cells have been grown over and around each electrode site as electrode-specific local networks. If, after implantation, collateral sprouts branch from a motor fiber (ventral horn area) and if they can be guided and contacted to each ¿host¿ network, a very selective and efficient interface will result. Four basic aspects of the design and development of a cultured probe, coated with rat cortical or dorsal root ganglion neurons, are described. First, the importance of optimization of the cell-electrode contact is presented. It turns out that impedance spectroscopy, and detailed modeling of the electrode-cell interface, is a very helpful technique, which shows whether a cell is covering an electrode and how strong the sealing is. Second, the dielectrophoretic trapping method directs cells efficiently to desired spots on the substrate, and cells remain viable after the treatment. The number of cells trapped is dependent on the electric field parameters and the occurrence of a secondary force, a fluid flow (as a result of field-induced heating). It was found that the viability of trapped cortical cells was not influenced by the electric field. Third, cells must adhere to the surface of the substrate and form networks, which are locally confined, to one electrode site. For that, chemical modification of the substrate and electrode areas with various coatings, such as polyethyleneimine (PEI) and fluorocarbon monolayers promotes or inhibits adhesion of cells. Finally, it is shown how PEI patterning, by a stamping technique, successfully guides outgrowth of collaterals from a neonatal rat lumbar spinal cord explant, after six days in cultur

Classification of Surface Geoelectric Arrays

We have found in the geophysical literature more than ninety different surface geoelectric arrays, fulfilling an updated definition (specifying the current feeding, the potential difference measurement and the geometry of the electrodes). Several composite configurations, with widely varying geometry, have also been collected. We have presented the geoelectric arrays in a systematic way and with a unified notation. The classification is based on three divalent parameters: “superposition” of measurements, “focusing” of currents and “colinearity” of the array, creating 8 groups of geoelectric arrays. For the simplest group (the group of nonfocused, nonsuperposed, colinear arrays) we cover all theoretically possible arrays. For the other groups – due to the infinite variety – we collected only the already existing arrays, but it is easy to create further example arrays. The proposed classification may facilitate a systematic comparison of properties of different arrays and inspire testing new arrays, to find optimal configurations for actual field problems. Finally, the classification certainly helps to avoid rediscovering already published arrays

Adhesion and patterning of cortical neurons on polyethylenimine and fluorocarbon-coated surfaces

Adhesion and patterning of cortical neurons was investigated on isolated islands of neuron-adhesive polyethylenimine (PEI) surrounded by a neuron-repellent fluorocarbon (FC) layer. In addition, the development of fasciculated neurites between the PEI-coated areas was studied over a time period of 15 days. The patterns consisted of PEI-coated wells (diameter 150 /spl mu/m, depth 0.5 /spl mu/m) which were etched in a coating of fluorocarbon (FC) on top of polyimide (PI) coated glass. The separation distance between the PEI-coated wells were varied between 10 and 90 /spl mu/m. This paper shows that chemical patterns of PEI and FC result in highly compliant patterns of adhering cortical neurons after 1 day in vitro. Interconnecting neurite fascicles between PEI-coated wells were especially present on patterns with a separation distance of 10 /spl mu/m after 8 days in vitro. A significant lower number of interconnecting neurite fascicles was observed on 20 /spl mu/m separated patterns. Effective isolation of neurons into PEI-coated wells was achieved on patterns with a separation distance of 80 /spl mu/m as no interconnecting neurite fascicles were observed

In vivo measurements with robust silicon-based multielectrode arrays with extreme shaft lengths

In this paper, manufacturing and in vivo testing of extreme-long Si-based neural microelectrode arrays are presented. Probes with different shaft lengths (15–70 mm) are formed by deep reactive ion etching and have been equipped with platinum electrodes of various configurations. In vivo measurements on rats indicate good mechanical stability, robust implantation, and targeting capability. High-quality signals have been recorded from different locations of the cerebrum of the rodents. The accompanied tissue damage is characterized by histology

3d plasmonic nanoantennas integrated with mea biosensors

Plasmonic 3D nanoantennas are integrated on multielectrode arrays. These biosensors can record extracellular activity and enhance Raman signals from living neurons

Adhesion and growth of electrically-active cortical neurons on polyethyleimine patterns microprinted on PEO-PPO-PEO triblockcopolymer-coated hydrophobic surfaces

This paper describes the adhesion and growth of dissociated cortical neurons on chemically patterned surfaces over a time period of 30 days. The presence of neurons was demonstrated by measurement of spontaneous bioelectrical activity on a micropatterned multielectrode array. Chemical patterns were prepared with a combination of neurophobic layers of polyethylenoxide-polypropylenoxide-polyethylenoxide (PEO-PPO-PEO) triblockcopolymers adsorbed onto hydrophobic surfaces and neurophilic microprinted tracks of polyethylenimine (PEI). Results showed that commercially available PEO-PPO-PEO triblockcopolymers F108 and F127 (Synperonics, ICI) significantly reduced the adhesion of neuronal tissue when adsorbed on hydrophobic Polyimide (PI) and Fluorocarbon (FC) surfaces over a time period of eight days. In general, both F108- and F127-coated PI displayed equal or better neurophobic background properties after 30 days. Viability of neuronal tissue after 30 days on PEI microprinted F108- and F127-coated PI was comparable with relatively high viability factors between 0.9 and 1 (scale from 0 to 1). Summarizing, the strategy to combine the neurophobic adsorbed triblock-copolymers F108 and F127 onto hydrophobic surfaces with neurophilic microprinted PEI resulted in relatively long-term neuronal pattern preservation with high numbers of viable neurons present after 30 days

Critical brain networks

Highly correlated brain dynamics produces synchronized states with no behavioral value, while weakly correlated dynamics prevents information flow. We discuss the idea put forward by Per Bak that the working brain stays at an intermediate (critical) regime characterized by power-law correlations.Comment: Contribution to the Niels Bohr Summer Institute on Complexity and Criticality (2003); to appear in a Per Bak Memorial Issue of PHYSICA

Analysis of Cultured Neuronal Networks Using Intraburst Firing Characteristics

It is an open question whether neuronal networks, cultured on multielectrode arrays, retain any capability to usefully process information (learning and memory). A necessary prerequisite for learning is that stimulation can induce lasting changes in the network. To observe these changes, one needs a method to describe the network in sufficient detail, while stable in normal circumstances. We analyzed the spontaneous bursting activity that is encountered in dissociated cultures of rat neocortical cells. Burst profiles (BPs) were made by estimating the instantaneous array-wide firing frequency. The shape of the BPs was found to be stable on a time scale of hours. Spatiotemporal detail is provided by analyzing the instantaneous firing frequency per electrode. The resulting phase profiles (PPs) were estimated by aligning BPs to their peak spiking rate over a period of 15 min. The PPs reveal a stable spatiotemporal pattern of activity during bursts over a period of several hours, making them useful for plasticity and learning studies. We also show that PPs can be used to estimate conditional firing probabilities. Doing so, yields an approach in which network bursting behavior and functional connectivity can be studied

Flexible Microfabricated Parylene Multielectrode Arrays for Retinal Stimulation and Spinal Cord Field Modulation

The first flexible parylene-based multielectrode arrays (MEAs) designed for functional electrical stimulation (FES) in retinal prostheses, and the extension of this technology toward enabling reflex-arc neuromodulation in cases of spinal cord damage or transection, are presented. A single metal layer 16 × 16 retinal electrode array of 125 μm-diameter thin-film Ti/Pt electrodes and lines of 12 μm-pitch has been fabricated as a demonstration of this technology. To allow for even higher density arrays, a novel dual-layer process has also been implemented that enables leads to pass under overlying electrodes without making electrical contact to them. A biomimetic parylene-based electrode array consisting of 1024 electrodes of highly variable spacing, 60 of which have been connected in this manner, has been fabricated according to this paradigm. A parylene-parylene annealing process has also been developed to increase device longevity under accelerated-lifetime saline soak conditions. Surgical tests of novel anatomically-conformal geometries that enable such parylene-based electrode systems to interact with their neuronal targets of interest while causing minimal mechanical damage to tissues or to the implants are also presented. The use of these flexible electrode arrays in spinal cord stimulation experiments in animal models has proven their efficacy in stimulating neurons