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H.A. Fishman, M.C. Peterman, M.F. Marmor, M.S. Blumenkranz; The Artificial Synapse Chip: Multi-Cellular Neurotransmitter-Based Retinal Stimulation . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5080.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Nearly all retinal prosthetics have focused on electrical stimulation of the nervous system. We are developing a novel prosthetic interface for the retina based on neurotransmitter delivery. In the past, we demonstrated the ability to stimulate individual rat pheochromacytoma cells (PC12 cell line) using microfluidic delivery through micron-sized apertures. This delivery was highly reproducible, very controllable, and quantifiable, but this early stage device was limited to a single stimulation site and crude microfluidics. We show now the construction of a chip of implantable size with multiple stimulation sites and improved fluidic delivery. Methods: Using silicon microfabrication techniques, we created a 2x2 arrays of 5 µm apertures in thin (500 nm) silicon nitride membranes, with open access to both sides of the apertures. Fluidic delivery channels within a photodefinable polymer (SU-8) are aligned to each aperture and attached to one side of the membrane. Neurotransmitters are delivered through these channels, using pressure-driven or electroosmotic flow. Excitable cells (PC12) are cultured on the surface of the device and imaged using Ca2+-sensitive dyes with a laser-scanning, confocal microscope. Results: We fabricated chips so that the microfluidic channel for each aperture (stimulation "pixel") was individually addressable by an electronic signal. A valve-less and highly efficient pumping system, based on an electroosmotic flow, activated the release of neurotransmitter from each aperture in the array. Depending on the microfluidic reservoir, each aperture could be triggered to release a different neurotransmitter. When PC12 cells were cultured on the chip surface, we could stimulate individual cells that were near specific apertures, with a limit of resolution of a ~5-10 µm in diameter. Devices made from a flexible polymer, covering 1.5 x 1.5 mm2 with a thickness of 250 µm, have been successfully implanted into the rabbit subretinal space. Conclusions: We show the construction of an implantable multi-stimulation neurotransmitter based prosthetic device. It can stimulate cells neurochemically in a reproducible and controllable manner at an array of locations. Our next goal is to evaluate retinal stimulation from within the subretinal and epiretinal space.
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