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Localized Neurotransmitter Release for Use in a Prototype Retinal Interface

¹From the Department of Applied Physics, E. L. Ginzton Laboratory, and the ³Departments of Chemical Engineering and ⁴Ophthalmology, Stanford University School of Medicine, Stanford, California; and the ²Department of Electrical Engineering, Stanford University, Stanford, California.

PURPOSE. Current neural prostheses use electricity as the mode of stimulation, yet information transfer in neural circuitry is primarily through chemical transmitters. To address this disparity, this study was conducted to devise a prototype interface for a retinal prosthetic based on localized chemical delivery. The goal was to determine whether fluidic delivery through microfabricated apertures could be used to stimulate at single-cell dimensions.

METHODS. A drug delivery system was microfabricated based on a 5- or 10-µm aperture in a 500-nm thick silicon nitride membrane to localize and limit transmitter release. The aperture overlies a microfluidic delivery channel in a silicone elastomer. To demonstrate the effectiveness of this transmitter-based prosthesis, rat pheochromocytoma cells (PC12 cell line) were grown on the surface of the device to test the precision of stimulation, using bradykinin as a stimulant and measuring fluorescence from the calcium indicator, fluo-4.

RESULTS. The extent of stimulation could be controlled accurately by varying the concentration of stimulant, from a single cell adjacent to the aperture to a broad area of cells. The stimulation radius was as small as 10 µm, corresponding to stimulation volumes as small as 2 pL. The relationship between the extent of stimulation and concentration was linear.

CONCLUSIONS. The demonstration of localized chemical stimulation of excitable cells illustrates the potential of this technology for retinal prostheses. Although this is only a proof of concept of neurotransmitter stimulation for a retinal prosthesis, it is a significant first step toward mimicking neurotransmitter release during synaptic transmission.

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