Currently, neurostimulation holds the capability of treating symptoms associated with epilepsy, essential tremor, depression, migraine, incontinence, Parkinson's, Tourette's, and other diseases and disorders. Given the constant evolution in the field of biomedical technology and the increasing demand for advanced solutions in neural interface technology, addressing challenges associated with conventional neural electronic implant packaging becomes crucial. Conventional packaging often results in bulkiness, limited proximity to the target tissue, and potential complications, prompting an emerging need to miniaturize and soften the packaging. While flexible substrates like polyimide, parylene C, polyurethane, and silicone elastomers have been explored by the neural implants industry, the ongoing shift towards fully implantable, biocompatible, and flexible active implants calls for a more tailored packaging approach. This Ph.D. research aims to provide a comprehensive investigation and overview of utilizing polymers as substrate and encapsulation materials for neural implants, examining both the advantages and challenges associated with their use. In particular, the study will look into the latent potential offered by thermoplastic polymers, with a specific focus on thermoplastic polyurethane (TPU) and liquid crystal polymer (LCP), as these polymers offer a unique blend of properties that make them promising candidates to significantly impact neural interface technology. In Chapter 2, a thorough literature review investigates polymers commonly used in neural implants. This chapter not only explains the reactions happening when implants are put into the body but also emphasizes the basic requirements for implantation. The chapter focuses on the main properties and advantages of various polymers, distinguishing between thermoset and thermoplastic polymers. Some examples of using these polymers as substrate and coating materials for passive neural interfaces, together with the insights into the associated processing steps, are presented in this chapter. Furthermore, the chapter looks into the ways of integrating electronic chips into passive implants, presenting a detailed review of bonding techniques, bumping technologies, and adhesive types, as well as showing examples of existing active neural implants. Chapter 3 continues the exploration by focusing on thin film encapsulation materials on flexible LCP substrates. Using HfO2-based atomic-layer-deposition multilayers, a hybrid ParC-ALD multilayer, and an LCP coating layer, this chapter systematically evaluates how well these coatings work through various testing methods. T-peel, water-vapor-transmission-rate (WVTR), and long-term electrochemical-impedance-spectrometry tests give valuable insights into the effectiveness of these coatings, emphasizing the advantage that can be offered by thermoplastic LCP-LCP coating-substrate interfaces. Chapter 4 presents the fabrication method for a thermoplastic polyurethane-based electrode array with high-resolution gold interconnects employing the following techniques: thermocompression bonding, electroplating, laser direct imaging-based lithography, and laser ablation. The integrity of this electrode array is evaluated under conditions simulating the human body environment, involving soak tests at different temperatures and in-vivo tests. The extended evaluation includes electrochemical and optical transparency tests to further enhance our understanding of how well the electrode array performs in different situations. Chapter 5 shows the integration of ASICs into the previously described polyurethane-based electrode array. Using flip-chip bonding technology, this integration involves connecting ultra-thin chips to gold metallization tracks using an anisotropic conductive adhesive. The successful combination of these components represents a significant step toward creating polymer-based active neural interfaces. The concluding Chapter 6 summarizes the key findings and contributions of the thesis. It not only highlights the scientific progress made in using thermoplastic polymers for neural interfaces but also emphasizes the successful integration of ASICs into a polyurethane-based electrode array. The chapter ends with suggestions for future research directions and improvements. In essence, this thesis provides an exploration of polymer-based flexible neural interfaces, particularly focusing on the unique properties of LCP and TPU thermoplastics. This work introduces polyurethane as a novel addition to the portfolio of biocompatible polymers used as both substrate and coating material for neural interfaces. The combination of biocompatibility, flexibility, microfabrication compatibility, and optical transparency, together with the developed fabrication process technology for high-density and high-resolution soft neural implants, contributes to and expands the toolkit available for developing fully implantable soft neural active implants.@en

Liquid crystal polymer (LCP) has gained wide interest in the electronics industry largely due to its flexibility, stable insulation and dielectric properties and chip integration capabilities. Recently, LCP has also been investigated as a biocompatible substrate for the fabrication of multielectrode arrays. Realizing a fully implantable LCP-based bioelectronic device, however, still necessitates a low form factor packaging solution to protect the electronics in the body. In this work, we investigate two promising encapsulation coatings based on thin-film technology as the main packaging for LCP-based electronics. Specifically, a HfO2–based nanolaminate ceramic (TFE1) deposited via atomic layer deposition (ALD), and a hybrid Parylene C-ALD multilayer stack (TFE2), both with a silicone finish, were investigated and compared to a reference LCP coating. T-peel, water-vapour transmission rate (WVTR) and long-term electrochemical impedance spectrometry (EIS) tests were performed to evaluate adhesion, barrier properties and overall encapsulation performance of the coatings. Both TFE materials showed stable impedance characteristics while submerged in 60 °C saline, with TFE1-silicone lasting more than 16 months under a continuous 14V DC bias (experiment is ongoing). The results presented in this work show that WVTR is not the main factor in determining lifetime, but the adhesion of the coating to the substrate materials plays a key role in maintaining a stable interface and thus longer lifetimes.@en

Our limited understanding of the nervous system forms a bottleneck which impedes the effective treatment of neurological disorders. In order to improve patient outcomes it is highly desirable to interact with the nervous tissue at the resolution of individual cells. As neurons number in the billions and transmit signals electrically, high-density, cellular-resolution microelectrode arrays will be a useful tool for both treatment and research.This paper investigates the advantages and versatility of laser-patterning technologies for the development of such high-density microelectrode arrays in flexible polymer substrates. In particular, it aims to elucidate the mechanisms involved in laser patterning of thin polymers on top of thin metal layers. For this comparative study, a pulsed picosecond laser (Schmoll Picodrill) with two separate wavelengths (1064 nm (infrared (IR)) and 355 nm (ultraviolet (UV))) was used. A 5 $\mu$ m thick electroplated layer of gold (Au) was used to form the microelectrodes. Laser-patterning was investigated to expose the Au electrodes when encapsulated by two different thermoplastic polymers: thermoplastic polyurethane (TPU), and Parylene-C, with thicknesses of maximum 25 $\mu$ m. The electrode diameter and the distance between electrodes were reduced down to 35 $\mu$ m and 30 $\mu$ m, respectively. The structures were evaluated using optical microscopy and white light interferometry and the results indicated that both laser wavelengths can be successfully used to create high-density microelectrode arrays in polymer substrates. However, due to the lower absorption coefficient of metals in the IR spectrum, a higher uniformity of the exposed Au layer was observed when IR-based lasers were used. This paper provides more insight into the mechanisms involved in laser-patterning of thin film polymers and demonstrates that it can be a reliable and cost-effective method for the rapid prototyping of thin-film neural interfaces.@en

This work aims to develop a smart neural interface with transparent electrodes to allow for electrical monitoring of the site of interest during optogenetic stimulation of the spinal cord. In this paper, a microfabrication process for the wafer-level development of such a compact, active, transparent and flexible implant is presented. Graphene has been employed to form the transparent array of electrodes and tracks, on top of which chips have been bonded using flip-chip bonding techniques. To provide high flexibility, soft encapsulation, using polydimethylsiloxane (PDMS) has been used. Making use of the "Flex-to-Rigid" (F2R) technique, cm-size graphene-on-PDMS structures have been suspended and characterized using Raman spectroscopy to qualitatively evaluate the graphene layer, together with 2-point measurements to ensure the conductivity of the structure. In parallel, flip-chip bonding processes of chips on graphene structures were employed and the 2-point electrical measurement results have shown resistance values in the range of kΩ for the combined tracks and ball-bonds.@en

Electronic components in the form of application-specific integrated circuits (ASICs) establishing the communication between the body and the implant, such as stimulation and recording, have, nowadays, become essential elements for current and future generations of implantable devices, as medicine is looking into substituting its traditional pharmaceuticals with electroceuticals, or bioelectronic medicines.1 Protection of implant components inside the body is a mandatory important step to ensure longevity and reliable performance of the device. The package of the implant should act as a bidirectional diffusion barrier protecting the electronics of the device from body liquids, and also preventing diffusion of toxic materials from the implant towards the tissue, at the same time matching tissue mechanical properties. Current implants do not completely fulfil the desired properties mentioned above, facing different kinds of challenges. For soft implants made on polymer substrates and using polymer as an outer layer, encapsulation challenges happen at the interfaces of the polymer with other components inside the implant, as water ingress and condensation, which leads to electronics failure, happens there. In this work, an embedding process developed at Fraunhofer IZM2 and used in semiconductor packaging field for chip encapsulation is being tailored to be used for protecting implantable ASICs. Such a method, which is based on a lamination process using heat and pressure, will reduce the critical interface points at the polymer-to-polymer contact due to the merging of polyurethane layers during the embedding process. Furthermore, flip chip bonding will allow to avoid long interconnects, as the interconnection bumps can be made on the whole chip area and redistributed on the polymer substrate. In the proposed process, biocompatible polyurethane is employed and gold metallisation is used to form electrodes and connect them to extremely thin (10-30 μm) ASICs. The developed embedding process technology will ensure homogeneous distribution of mechanical stresses and longer reliability, resulting uninterrupted long-term use of smart implants @en

Electronic components in the form of application-specific integrated circuits (ASICs) establishing the communication between the body and the implant, such as stimulation and recording, have, nowadays, become essential elements for current and future generations of implantable devices, as medicine is looking into substituting its traditional pharmaceuticals with electroceuticals, or bioelectronic medicines [1].
Protection of implant components inside the body is a mandatory important step to ensure longevity and reliable performance of the device. The package of the implant should act as a bidirectional diffusion barrier protecting the electronics of the device from body liquids, and also preventing diffusion of toxic materials from the implant towards the tissue. At the same time the implant’s outer layer should match the tissue’s mechanical properties in order not to cause scar growth around the implant or damage the body.
Current implants do not completely fulfill the desired properties mentioned above, either lacking hermeticity or softness.
In this work, an embedding process developed at Fraunhofer IZM [2] and used in the semiconductor packaging field for chip encapsulation is proposed to be modified and used for protecting implantable ASICs. Such a method will have a number of advantages, such as miniaturization, in comparison with conventional titanium case packaging. Furthermore, embedding allows to avoid long interconnects, which can be a crucial problem for the device implanted inside a constantly moving body. The other advantage is that the geometry of these interconnects can be well controlled, and the amount of contact pads can be higher than in widely used wire bonding technology, because the distribution of solder bumps during embedding can take place on the whole chip area.
In the proposed process, biocompatible polymer materials, such as ParyleneC and Polyurethane, together with thin glass films will be employed to provide the implant with the required hermeticity and at the same time flexibility. The developed embedding process technology will ensure homogeneous distribution of mechanical stresses, resulting in high reliability for uninterrupted long-term use of smart implants.
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