Artificial Retina with Three-Dimensional Microelectrodes of Liquid Metals for Vision Restoration

Inherited retinal degenerative diseases can lead to both gradual loss or permanent damage of photoreceptor cells, resulting in the impairment of vision, or even blindness. However, as inner retinal neurons can be preserved even when this degeneration of photoreceptor cells, various approaches by stimulating the inner retinal neurons to restore vision have been developed. Electronic retinal prosthesis, which uses photo-responsive devices to electrically stimulate inner retinal neurons, has emerged as a promising approach to restore vision. Over the past decade, this electronic retinal prosthesis has been adapted to clinical trials, although being still limited by low visual acuity. One of the main limitations is the low proximity that results from the unconformities between the retina and the implant. Since the stimulation threshold that elicits retinal responses strongly depends on the electrode-cell distance, it is important to reduce this distance. Also, the imprecise stimulation on the epiretinal surface caused by this low proximity can inevitably excite the axons of retinal ganglion cells (RGCs), generating irregular visual perceptions to patients. In this regard, 3D electrodes show promise for effectively stimulating the nervous system, dramatically reducing this electrode-cell distance by positioning the stimulation site adjacent to the target cell. Also, compared to the electrodes that have flat surfaces, these 3D electrodes enable their stimulation to selective local areas, bypassing neurons that should not be stimulated, thereby providing excellent selectivity and high spatial resolution. However, previous 3D neural electrodes have been formed using rigid solid-state materials, showing a significant mismatch of mechanical properties at their interface with soft biological tissues, which can directly damage the soft retina, or cause inflammatory responses within the retina.<br/>Herein, we present an artificial retina where flexible ultrathin phototransistors are integrated with 3D microelectrodes of liquid metals. These phototransistors directly convert light into electrical stimuli, stimulating the retina through our soft 3D microelectrodes. The flexible ultrathin layer of this artificial retina can be conformably laminated on the innermost surface of the retina, directly stimulating the RGCs using the softly protrudent pillars of 3D liquid-metal electrodes. The developments of this artificial retina include several unique strategies as follows: First, these 3D microelectrodes can enhance the proximity to the target cells and provide effective charge injections to elicit neural responses in the RGCs. These soft stimulation electrodes are directly printed in a pillar shape on the top surfaces of the drain electrodes to overcome the geometrical gap at the interface between the device and the locally nonuniform surface of degenerative retina, enhancing the proximity to the target RGCs. Here, these 3D electrodes can be printed with desired heights to selectively reach target cells. Also, the Pt nanoclusters locally coated only on the tip of these 3D electrodes show advantages to reducing the impedance of the stimulation electrodes, and injecting charges effectively into the retinal neurons. Second, their low Young’s modulus owing to their liquid form, can minimize the undesired damage to the interfacing biological tissues. Third, unsupervised machine learning approach can effectively classify the evoked spikes, and the results indicate the potential for the selective stimulation of RGC somas using our 3D microelectrodes. Lastly, in-vivo experiments using a retinal degeneration mouse model demonstrate that the spatiotemporal distribution of neural responses on their retina can be mapped under selective localized illumination areas of light, suggesting the restoration of their vision.