Fabrication and validation of an intraneural interface tailored for optic nerve stimulation

Technological progress in materials science and microengineering along with new discoveries in neuroscience have contributed to restore lost or impaired sensory functions by closely interfacing with the nervous system. Electronic devices have begun to be integrated within the body to artificially reproduce or record the electrical encoding of neural signals, the language of the nervous system. This has allowed us to restore the impaired communication between the missing or defective organ and the brain. As evidence of this, cochlear implants have returned hearing to millions of people world wide. On the other hand, there is no suitable solution yet for the 43 millions people who are currently blind. Nevertheless, several research groups and companies are trying to tackle this issue. So far, different devices have demonstrated the capability of restoring a certain degree of artificial vision, however, with limited success in delivering meaningful improvements in daily life activities. This is because, unlike hearing, vision is an extremely complex sense and requires higher stimulation resolution. Limitations of retinal prostheses have pushed further the investigation of other targets along the visual pathway, such as the optic nerve, the thalamus and the visual cortex. Among these, our group has started to explore the possibility of stimulating the optic nerve. The main advantages are the direct stimulation of the axon fibers and the access to the entire visual field with only one device. It is also interesting because it could work for those patients who are not eligible for retinal prostheses, due to severe eye trauma or retinal detachment, and it does not require optical transparency.In this thesis, we investigate stimulation strategies and materials to improve the outcome of optic nerve prostheses and make them one step closer to a viable option for blind patients. We first propose the use of machine learning algorithms to classify cortical activity upon electrical stimulation of the optic nerve. Secondly, we investigate a strategy to achieve higher spatial selectivity of the optic nerve stimulation. We design a three-dimensional (3D) multilayer concentric bipolar (CB) configuration and fabricate a modified version of the OpticSELINE. We validate the efficacy of the novel design during in-vivo experiments on rabbits and find that cortical activation is reduced when using the 3D multilayer CB electrodes compared to the classic monopolar configuration. In parallel, we explore the use of novel polymers, namely Off-Stoichiometry Thiol- Ene Epoxy (OSTE+), to design conformable neural interfaces. Their chemistry makes them a suitable candidate for easy integration in cleanroom processes and they show superior adhesion properties with respect to standard thin films currently in use. Hence, we characterise their usability as substrate and encapsulation for neural interfaces in-vitro and in-vivo. Lastly, we propose an alternative fabrication technique, ink-jet printing of platinum on flexible substrates, for neurophysiology applications. Altogether, the findings highlighted in this thesis will hopefully lead to a more in-depth investigation of the optic nerve prosthesis and can also be relevant for other applications in the field of neuroprosthetics.