Toward Optogenetic Hearing Restoration.

The cochlear implant (CI) is considered the most successful neuroprosthesis as it enables speech comprehension in the majority of the million otherwise deaf patients. In hearing by electrical stimulation of the auditory nerve, the broad spread of current from each electrode acts as a bottleneck that limits the transfer of sound frequency information. Hence, there remains a major unmet medical need for improving the quality of hearing with CIs. Recently, optogenetic stimulation of the cochlea has been suggested as an alternative approach for hearing restoration. Cochlear optogenetics promises to transfer more sound frequency information, hence improving hearing, as light can conveniently be confined in space to activate the auditory nerve within smaller tonotopic ranges. In this review, we discuss the latest experimental and technological developments of optogenetic hearing restoration and outline remaining challenges en route to clinical translation.

Angle-dependent light scattering in tissue phantoms for the case of thin bone layers with predominant forward scattering.

The cochlea forms a key element of the human auditory system in the temporal bone. Damage to the cochlea continues to produce significant impairment for sensory reception of environmental stimuli. To improve this impairment, the optical cochlear implant forms a new research approach. A prerequisite for this method is to understand how light propagation, as well as scattering, reflection, and absorption, takes place within the cochlea. We offer a method to study the light distribution in the human cochlea through phantom materials which have the objective to mimic the optical behavior of bone and Monte-Carlo simulations. The calculation of an angular distribution after scattering requires a phase function. Often approximate functions like Henyey-Greenstein, two-term Henyey-Greenstein or Legendre polynomial decompositions are used as phase function. An alternative is to exactly calculate a Mie distribution for each scattering event. This method provides a better fit to the data measured in this work.

On the Fabrication and Characterization of Polymer-Based Waveguide Probes for Use in Future Optical Cochlear Implants.

Improved hearing restoration by cochlear implants (CI) is expected by optical cochlear implants (oCI) exciting optogenetically modified spiral ganglion neurons (SGNs) via an optical pulse generated outside the cochlea. The pulse is guided to the SGNs inside the cochlea via flexible polymer-based waveguide probes. The fabrication of these waveguide probes is realized by using 6" wafer-level micromachining processes, including lithography processes such as spin-coating cladding layers and a waveguide layer in between and etch processes for structuring the waveguide layer. Further adhesion layers and metal layers for laser diode (LD) bonding and light-outcoupling structures are also integrated in this waveguide process flow. Optical microscope and SEM images revealed that the majority of the waveguides are sufficiently smooth to guide light with low intensity loss. By coupling light into the waveguides and detecting the outcoupled light from the waveguide, we distinguished intensity losses caused by bending the waveguide and outcoupling. The probes were used in first modules called single-beam guides (SBGs) based on a waveguide probe, a ball lens and an LD. Finally, these SBGs were tested in animal models for proof-of-concept implantation experiments.

High-Density µLED-Based Optical Cochlear Implant With Improved Thermomechanical Behavior.

This study reports the realization of an optical cochlear implant (oCI) with optimized thermomechanical properties for optogenetic experiments. The oCI probe comprises 144 miniaturized light-emitting diodes (µLEDs) distributed along a bendable, 1.5-cm-long, 350-µm-wide and 26-µm-thick probe shaft, individually controlled via a n × p matrix interconnection. In contrast to our earlier approach based on polyimide (PI) and epoxy resin with different thermal expansion coefficients, the µLEDs and interconnecting wires are now embedded into a triple-layer stack of a single, biocompatible, and highly transparent epoxy material. The new material combination results in a pronounced reduction of thermomechanical bending in comparison with the material pair of the earlier approach. We developed a spin-coating process enabling epoxy resin layers down to 5 µm at thickness variations of less than 7% across the entire carrier wafer. We observed that the cross-linking of epoxy resin layers strongly depends on the spin-coating parameters which were found to be correlated to a potential separation of epoxy resin components of different densities. Furthermore, various metallization layers and corresponding adhesion promoting layers were investigated. We identified the combination of silicon carbide with a titanium-based metallization to provide the highest peeling strength, achieving an adhesion to epoxy improved by a factor of two. In order to obtain a high process yield, we established a stress-free implant release using the electrochemical dissolution of a sacrificial aluminum layer. The direct comparison of oCI probe variants using a single epoxy material and the combination of PI and epoxy resin revealed that the epoxy-resin-only probe shows minimal thermomechanical probe bending with a negligible hysteresis. The thermal probe characterization demonstrated that the temperature increase is limited to 1 K at µLED DC currents of up to 10 mA depending on the stimulation duration and the medium surrounding the probe. The optical output power and peak wavelengths of the new oCI variant were extracted to be 0.82 mW and 462 nm when operating the µLEDs at 10 mA, 10 kHz, and a duty cycle of 10%. The optical power corresponds to a radiant emittance of 407 mW/mm2, sufficient for optogenetic experiments using channelrhodopsin-2.

Phosphor-based light conversion for miniaturized optical tools.

This paper describes the application of phosphor-based light conversion for its use in optogenetic experiments to tailor the wavelength of light emitted from implantable miniaturized light sources. Gallium-nitride-based blue light-emitting diodes are used in combination with orthosilicate phosphor immersed in an epoxy matrix and emitting in the yellow wavelength range. The miniaturization of the phosphor-containing polymer droplets toward diameters as small as 300 µm provides the compatibility with implantable optical probes. The parameter study applied here varied the concentration of the phosphor material in the polymer matrix as well as the droplet height in order to tailor the characteristics of blue-to-yellow light conversion.