| Retinal prostheses are being developed to restore vision to patients suffering from retinal degenerations. These diseases result in the deterioration of photoreceptors in the sensory retina, but cell layers within the neural retina remain relatively intact and excitable. While results are encouraging from current prostheses, numerous challenges remain before retinal prosthetic devices can produce useful vision. This thesis work addresses some of the challenges.; The first part of this thesis focuses on applying micropatterning technologies to direct neuronal growth to individual electrodes for single cell stimulation. Microcontact printing was applied to align and pattern laminin across a microelectrode array, over which retinal ganglion cells (RGCs) were seeded and extended discrete neurites along the pattern to individual electrodes. The stimulation threshold currents of RGCs micropatterned to electrodes were found to be significantly less than those of non-patterned RGCs over a wide range of electrode-soma distances, as determined with calcium imaging techniques. Moreover, the stimulation threshold for micropatterned cells was found to be independent of electrode-soma distance. The stimulation results quantitatively demonstrate the potential benefits of a retinal prosthetic interface based on directed neuronal growth.; The second portion of this thesis presents a flexible microfluidic device that actuates neurotransmitter release for localized cell stimulation. The device is based on a polymer membrane with an aperture, through which the release of chemical pulses is controlled by microfluidic switching in an underlying channel network. The chemical release properties have been characterized using fluorescence microscopy as a function of pulse frequency and duration. Hippocampal neurons were cultured on the microdevices, and the neurotransmitter release properties were tuned to repeatedly elicit action potentials in cells seeded proximate to the aperture, including single cell stimulation at 2 Hz. The results establish the feasibility of a prosthetic interface based on localized neurotransmitter delivery to achieve safe and repeatable neuron stimulation.; This thesis addresses key limitations of current retinal prostheses by engineering interfaces that achieve high-resolution and physiological cell stimulation. The development of these novel technologies may provide the biomimetic approach that is necessary not only to treat retinal degenerations, but a variety of neurological disorders as well. |
