Linda Rudmann

Let There Be Light—Optoprobes for Neural Implants

Over the past decades, optical technologies have entered neural implant technologies. Applications such as optogenetics, near-infrared spectroscopy (NIRS), and direct-near-infrared stimulation (NIS) request technical devices that combine electrical and optical recording as well as stimulation capabilities using light sources and/or optical sensors. Optoprobes are the technical devices that meet these requirements. This paper provides basic insights into optogenetic mechanisms, the background of NIRS and NIS, and focuses on fundamental requirements of technical systems from a biological background. The state of the art of optoprobes is reviewed and attention is drawn on the potential long-term stability of these technical devices for chronic neural implants. Further, material selection for stiff and flexible devices, applicable light sources, waveguide and coupling concepts, packaging paradigms as well as system assembly and integration aspects are discussed in view of biocompatible and biostable devices. This paper also considers the physical background of light scattering and heat generation when light sources are implanted into biological tissue.

Integrated optoelectronic microprobes

Optogenetics opened not only new exciting opportunities to interrogate the nervous system but also requires adequate probes to facilitate these wishes. Therefore, a multidisciplinary effort is essential to match these technical opportunities with biological needs in order to establish a stable and functional material-tissue interface. This in turn can address an optical intervention of the genetically modified, light sensitive cells in the nervous system and recording of electrical signals from single cells and neuronal networks that result in behavioral changes. In this review, we present the state of the art of optoelectronic probes and assess advantages and challenges of the different design approaches. At first, we discuss mechanisms and processes at the material-tissue interface that influence the performance of optoelectronic probes in acute and chronic implantations. We classify optoelectronic probes by their property of delivering light to the tissue: by waveguides or by integrated light sources at the sites of intervention. Both approaches are discussed with respect to size, spatial resolution, opportunity to integrate electrodes for electrical recording and potential interactions with the target tissue. At last, we assess translational aspects of the state of the art. Long-term stability of probes and the opportunity to integrate them into fully implantable, wireless systems are a prerequisite for chronic applications and a transfer from fundamental neuroscientific studies into treatment options for diseases and clinical trials.

Fused silica microlenses for hermetic packages as part of implantable optrodes.

The request for stable and reliable devices is tremendous in the field of optogenetics. So far, no device which is called optrode, encapsulating the needed light source hermetically, can be found. We therefore introduce a novel optrode concept consisting of polyimide, silicone as well as a silicon- and fused silica-based hermetic package. One of the main features of the hermetic package is the integration of custom-made microlenses. These microlenses are fabricated using thermal reflow of photoresist. Chosen parameters for remelting the photoresist AZ9260 are 2 min @ 160 °C. An additional dry etching step is introduced to transfer the resist pattern into a fused silica substrate. We were able to fabricate lenses in diameters ranging from 25 μm to 1300 μm. The focal lengths of the etched lenses vary from 630 μm to 5500 μm for lens diameter ranging from 200 μm to 900 μm. Deviations of the transferred pattern to an ideal sphere range from 0.055 % and -0.151 % to 0.040 % and -0.003 % (300 μm and 700 μm lens diameter) and can be neglected.

Mechanical deformation of thin film platinum under electrical stimulation.

Thin-film-based electrodes used to interact with nervous tissue often fail quickly if used for electrical stimulation, impairing their translation into long-term clinical applications. We initiated investigations about the mechanical load on thin-film electrodes caused by the fact of electrical stimulation. Platinum electrodes of Ø 300μm on a polyimide carrier were subjected to approximately 50 000 asymmetrical, biphasic stimulation pulses in vitro. The electrodes surface was investigated optically by means of white-light interferometry. The structural expansion for the metallic surface subjected to stimulation was measured to reach roughly 30%. The study points towards a failure mechanism of thin-films being of mechanical nature, inherent to the unavoidable electrochemical processes involved (change in lattice constants) during electrical stimulation at the electrodes surface. Based on further scientific facts, we set 3 hypotheses for the exact mechanisms involved in the failure of thin-films used for electrical stimulation, opening a new door for research and improvement of novel neuroprosthetic devices.

Investigations on different epoxies for electrical insulation of microflex structures

The microflex interconnection (MFI) technique is often used to connect electrically and mechanically thin film ribbons or electrodes with a solid substrate like screen printed ceramics. For stabilization reasons epoxy is used to fix the MFI structure. As epoxy tends to form cracks when surrounded by water or electrolytes we are eager to find an epoxy which provides sufficient insulation between the single channels of the MFI structure also in a moist surrounding. Therefore we designed a device to investigate the insulating properties of different epoxies (Uhu Plus Endfest 300, Epo-Tek 353ND and 353ND-T) immersed in saline solution. For comparison reasons we use as well only silicone rubber (Nusil MED-1000) instead of epoxy. We performed the experiment for 23 weeks at 60 °C, which corresponds to 26 months at body temperature. The epoxy of preference is the Epo-Tek 353ND-T as it develops no failures and insulates all channel pairs of the MFI structures electrically over the whole period of experiment.

Design considerations for miniaturized optical neural probes

Neural probes are designed to selectively record from or stimulate nerve cells. In optogenetics it is desirable to build miniaturized and long-term stable optical neural probes, in which the light sources can be directly and chronically implanted into the animals to allow free movement and behavior. Because of the size and the beam shape of the available light sources, it is difficult to target single cells as well as spatially localized networks. We therefore investigated design considerations for packages, which encapsulate the light source hermetically and have integrated hemispherical lens structures that enable to focus the light onto the desired region, by optical simulations. Integration of a biconvex lens into the package lid (diameter = 300 μm, material: silicon carbide) increased the averaged absolute irradiance ηA by 298 % compared to a system without a lens and had a spot size of around 120 μm. Solely integrating a plano-convex lens (same diameter and material) results in an ηA of up to 227 %.

Development of a desiccant based dielectric for monitoring humidity conditions in miniaturized hermetic implantable packages

Abstract Lifetime estimation of implanted electronics in hermetic packages requires the prediction of the humidity induced lifetime. Classical approaches are limited in applications where miniaturized packages and a buffered humidity at low values are being utilized. An approach to overcome these limitations is described and investigations on suitable materials and measurement setups are presented. The findings support the usability of a Zeolite-silicone based desiccant system as a dielectric for a new type of online sensor. The future exploitation of this new sensing principle can allow the monitoring and prediction of humidity conditions inside of highly reliable miniaturized hermetic implantable packages.