The efforts to improve the treatment efficacy in blind patients with retinal degenerative diseases would greatly benefit from retinal activity feedback, which is lacking in current retinal implants. While the door for a bidirectional communication device that stimulates and records intraretinally has been opened by the recent use of silicon-based penetrating probes, the biological impact induced by the insertion of such rigid devices is still unknown. Here, we developed for the first time, flexible intraretinal probes and validated in vitro the acute biological insertion impact in mouse retinae compared to standard silicon-based probes. Our results show that probes based on flexible materials, such as polyimide and parylene-C, in combination with a narrow shank design 50 µm wide and 7 µm thick, and the use of insertion speeds as high as 187.5 µm/s will successfully penetrate the retina, reduce the footprint of the insertion to roughly 2 times the cross-section of the probe, and induce low dead cell counts, while keeping the vitality of the tissue and recording the neural activity at different depths.

Background: Significant progress toward the recovery of useful vision in blind patients with severe degenerative retinal diseases caused by photoreceptor death has been achieved with the development of visual prostheses that stimulate the retina electrically. However, currently used prostheses do not provide feedback about the retinal activity before and upon stimulation and do not adjust to changes during the remodeling processes in the retina. Both features are desirable to improve the efficiency of the electrical stimulation (ES) therapy offered by these devices. Accordingly, devices that not only enable ES but at the same time provide information about the retinal activity are beneficial. Given the above, a bidirectional communication strategy, in which inner retinal cells are stimulated and the output neurons of the retina, the ganglion cells, are recorded using penetrating microelectrode arrays (MEAs) is proposed. Methods: Custom-made penetrating MEAs with four silicon-based shanks, each one with three or four iridium oxide electrodes specifically designed to match retinal dimensions were used to record the activity of light-adapted wildtype mice retinas and degenerated retinas from rd10 mice in vitro. In addition, responses to high potassium concentration and to light stimulation in wildtype retinas were examined. Furthermore, voltage-controlled ES was performed. Results: The spiking activity of retinal ganglion cells (RGCs) was recorded at different depths of penetration inside the retina. Physiological responses during an increase of the extracellular potassium concentration and phasic and tonic responses during light stimulation were captured. Moreover, pathologic rhythmic activity was recorded from degenerated retinas. Finally, ES of the inner retina and simultaneous recording of the activity of RGCs was accomplished. Conclusion: The access to different layers of the retina with penetrating electrodes while recording at the same time the spiking activity of RGCs broadens the use and the

In the current work, we introduce a brand new line of versatile, flexible, and multifunctional MEA probes, the so-called Nano Neuro Net , or N 3 -MEAs. Material choice, dimensions, and room for further upgrade, were carefully considered when designing such probes in order to cover the widest application range possible. Proof of the operation principle of these novel probes is shown in the manuscript via the recording of extracellular signals, such as action potentials and local field potentials from cardiac cells and retinal ganglion cells of the heart tissue and eye respectively. Reasonably large signal to noise ratio (SNR) combined with effortless operation of the devices, mechanical and chemical stability, multifunctionality provide, in our opinion, an unprecedented blend. We show successful recordings of (1) action potentials from heart tissue with a SNR up to 13.2; (2) spontaneous activity of retinal ganglion cells with a SNR up to 12.8; and (3) local field potentials with an ERG-like waveform, as well as spiking responses of the retina to light stimulation. The results reveal not only the multi-functionality of these N 3 -MEAs, but high quality recordings of electrogenic tissues.

Graphene based devices have already proven to be extremely sensitive and very useful in a wide spectrum of bioelectronics research. In the manuscript we describe a method to fabricate arrays of graphene-based probes, requiring minimal number of fabrication steps, while maintaining overall device functionality. These polyimide-based probes are approximately 6 µm thick, therefore ultraflexible, yet robust and stable. Devices, such as graphene field effect transistors (GFETs) and graphene multielectrode arrays (GMEAs) have been designed, fabricated and tested for their performance. The flexible GFETs exhibit sensitivity, i.e. transconductance up to 700 µS/V, which an order of magnitude larger compared to typical silicon transistors. Multiple probe per wafer design allows us to fabricate different kinds of devices on one 4-inch wafer, consequently increasing a possible range of applications from e.g. retinal to cortical neuroprosthetics.