Neuroelectronic interfacing with cultured multielectrode arrays toward a cultured probe

Efficient and selective electrical stimulation and recording of neural acti vity in peripheral, spinal, or central pathways requires multielectrode arr ays at micrometer scale. At present, wire arrays in brain, flexible linear arrays in the cochlea and cuff arrays around nerve trunks are in experiment al and/or clinical use. Two-and three-dimensional brush-like arrays and sie ve arrays, with around 100 electrode sites, have been proposed, fabricated in microtechnology, and/or tested in a number of labs. As there are no "blueprints " for the exact positions of neurons, an insert able multielectrode has to be designed in a redundant way. Even then, the e fficiency of a multielectrode will be less than 100 %, as not even, electro de will contact a neural axon or soma. Therefore, "cultured probe" devices are being developed. i.e., cell-culture d planar multielectrode arrays (MEAs). They may. enhance efficiency and sel ectivity because neural cells have been grown over and around each electrod e site as electrode-specific local networks. If after implantation, collate ral sprouts branch from a motor fiber (ventral horn area) and if they can b e guided and contacted to each "host " network, a very selective and effici ent interface will result. Four basic aspects of the design and development of a cultured probe, coate d 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 elec trode-cell interface, is a very, helpful technique, which shows whether a c ell is covering an electrode and how strong the sealing is. Second, the die lectrophoretic trapping method directs cells efficiently to desired spots o n the substrate, and cells remain viable after the treatment. The number of cells trapped is dependent on the electric field parameters and the occurr ence of a secondary force, a fluid,flow (cis a result of field-induced heat ing). It was found that the viability of trapped cortical cells it-as not i nfluenced by, the electric field (3 V-pp, 14 MHz). Third, cells must adhere to the surface of the substrate and form networks, which are locally confi ned, to one electrode site. For that, chemical modification of the substrat e and electrode areas with various coatings, such as polyethyleneimine (PEI ) and fluorocarbon monolayers promotes or inhibits adhesion of cells. The o ptimal diameter of local circular neurophilic areas and the separation dist ance between them has been investigated. Good results are obtained on wells with a diameter of 150 mum and a separation distance of 90 mum between the wells. Finally, it is shown how PEI patterning, by a stamping technique, s uccessfully guides outgrowth of collaterals from a neonatal rat lumbar spin al cord explant, after six days in culture.