Christian Boehler

Improved polyimide thin-film electrodes for neural implants

Thin-film electrode arrays for neural implants are necessary when large integration densities of stimulating or recording channels are required. However, delamination of the metallic layers from the polymer substrate leads to early failure of the device. Based on new adhesion studies of polyimide to SiC and diamond-like carbon (DLC) the authors successfully fabricated a 232-channel electrode array for retinal stimulation with improved adhesion. Layers of SiC and DLC were integrated into the fabrication procedure of polyimide-platinum (Pt) arrays to create fully coated metal wires, which adhere to the polyimide substrate even after 1 year of accelerated aging in saline solution. Studies on the inter-diffusion of Pt and SiC were conducted to establish an optimal thickness for a gold core of the platinum tracks, which is used for reducing the electrical track resistance. Furthermore, the electrochemical behaviour of the stimulating contacts coated with IrOx were studied in a long-term pulse tests over millions of pulses showing no deterioration of the coating.

A detailed insight into drug delivery from PEDOT based on analytical methods: Effects and side effects

The possibility to release drugs from conducting polymers, like polypyrrole or poly(3,4-ethylenedioxythiophene) (PEDOT), has been described and investigated for a variety of different substances during the last years, showing a wide interest in these release systems. A point that has not been looked at so far however is the possibility of other substances, next to the intended ones, leaving the polymer film under the high voltage excursions during redox sweeping. In this study we target this weakness of commonly used detection methods by implementing a high precision analytical method (high-performance liquid chromatography) that allows a separation and subsequently a detailed quantification of all possible release products. We could identify a significantly more complex release behavior for a PEDOT:Dex system than has been assumed so far, revealing the active release of the monomer upon redox activation. The released EDOT could thereby be shown to result from the bulk material, causing a considerable loss of polymer (>10% during six release events) that could partly account for the observed degradation or delamination effects of drug-eluting coatings. The monomer leakage was found to be substantially higher for a PEDOT:Dex film compared to a PEDOT:PSS sample. This finding indicates an overestimation of drug release if side products are mistaken for the actual drug mass. Moreover the full picture of released substances implements the need for further studies to reduce the monomer leakage and identify possible adverse effects, especially in the perspective of releasing an anti-inflammatory substance for attenuation of the foreign body reaction toward implanted electrodes.

Nanostructured platinum grass enables superior impedance reduction for neural microelectrodes

Micro-sized electrodes are essential for highly sensitive communication at the neural interface with superior spatial resolution. However, such small electrodes inevitably suffer from high electrical impedance and thus high levels of thermal noise deteriorating the signal to noise ratio. In order to overcome this problem, a nanostructured Pt-coating was introduced as add-on functionalization for impedance reduction of small electrodes. In comparison to platinum black deposition, all used chemicals in the deposition process are free from cytotoxic components. The grass-like nanostructure was found to reduce the impedance by almost two orders of magnitude compared to untreated samples which was lower than what could be achieved with conventional electrode coatings like IrOx or PEDOT. The realization of the Pt-grass coating is performed via a simple electrochemical process which can be applied to virtually any possible electrode type and accordingly shows potential as a universal impedance reduction strategy. Elution tests revealed non-toxicity of the Pt-grass and the coating was found to exhibit strong adhesion to the metallized substrate.

Long-Term Stable Adhesion for Conducting Polymers in Biomedical Applications: IrOx and Nanostructured Platinum Solve the Chronic Challenge

Conducting polymers (CPs) have frequently been described as outstanding coating materials for neural microelectrodes, providing significantly reduced impedance or higher charge injection compared to pure metals. Usability has until now, however, been limited by poor adhesion of polymers like poly(3,4-ethylenedioxythiophene) (PEDOT) to metallic substrates, ultimately precluding long-term applications. The aim of this study was to overcome this weakness of CPs by introducing two novel adhesion improvement strategies that can easily be integrated with standard microelectrode fabrication processes. Iridium Oxide (IrOx) demonstrated exceptional stability for PEDOT coatings, resulting in polymer survival over 10 000 redox cycles and 110 days under accelerated aging conditions at 60 °C. Nanostructured Pt was furthermore introduced as a purely mechanical adhesion promoter providing 10-fold adhesion improvement compared to smooth Pt substrates by simply altering the morphology of Pt. This layer can be realized in a very simple process that is compatible with any electrode design, turning nanostructured Pt into a universal adhesion layer for CP coatings. By the introduction of these adhesion-promoting strategies, the weakness of CP-based neural probes can ultimately be eliminated and true long-term stable use of PEDOT on neural probes will be possible in future electrode generations.

Anti-inflammatory polymer electrodes for glial scar treatment: bringing the conceptual idea to future results

Conducting polymer films offer a convenient route for the functionalization of implantable microelectrodes without compromising their performance as excellent recording units. A micron thick coating, deposited on the surface of a regular metallic electrode, can elute anti-inflammatory drugs for the treatment of glial scarring as well as growth factors for the support of surrounding neurons. Electro-activation of the polymer drives the release of the substance and should ideally provide a reliable method for controlling quantity and timing of release. Driving signals in the form of a constant potential (CP), a slow redox sweep or a fast pulse are all represented in literature. Few studies present such release in vivo from actual recording and stimulating microelectronic devices. It is essential to bridge the gap between studies based on release in vitro, and the intended application, which would mean release into living and highly delicate tissue. In the biological setting, signals are limited both by available electronics and by the biological safety. Driving signals must not be harmful to tissue and also not activate the tissue in an uncontrolled manner. This review aims at shedding more light on how to select appropriate driving parameters for the polymer electrodes for the in vivo setting. It brings together information regarding activation thresholds for neurons, as well as injury thresholds, and puts this into context with what is known about efficient driving of release from conducting polymer films.

Silicone rubber and thin-film polyimide for hybrid neural interfaces — A MEMS-based adhesion promotion technique

Strong permanent adhesion between thin-film polyimide (BPDA-PPD) and silicone rubber (MED-1000) was achieved through deposition of a chemically-transitive intermediate adhesion promoting layer. Plasma-enhanced chemical vapor deposition (PECVD) of SiC and SiO2 was used to grow a thin 50 nm layer directly on a 5 μm thin polyimide substrate. The deposition at low pressures permitted the fabrication of an adaptive covalent bond transition from sp2-hybridized carbon (in polyimide) towards the sp3 bonding in SiC, continuing to SiO2 which provides a good bonding partner for one-component poly-dimethyl siloxane (PDMS). The fabricated laminates together with reference probes containing no adhesion promoting layer were subjected to intense accelerated aging at 125°C and 130 kPa (pressure cooker) over 96 hrs in phosphate buffered saline solution. While the reference polyimide-PDMS laminates failed just after 30 min in the pressure cooker, no failure was detected on samples using the proposed adhesion promoter technique. Mechanical loading of the samples resulted in cohesive crack formation at the polyimide, propagating across the bulk with no evidence of adhesive failure between any of the materials. The strong permanent adhesion brings the fabrication of hybrid neural interfaces one step forward, achieving the combination of thin-film manufacturing and PDMS.

A Simple Approach for Molecular Controlled Release based on Atomic Layer Deposition Hybridized Organic-Inorganic Layers

On-demand release of bioactive substances with high spatial and temporal control offers ground-breaking possibilities in the field of life sciences. However, available strategies for developing such release systems lack the possibility of combining efficient control over release with adequate storage capability in a reasonably compact system. In this study we present a new approach to target this deficiency by the introduction of a hybrid material. This organic-inorganic material was fabricated by atomic layer deposition of ZnO into thin films of polyethylene glycol, forming the carrier matrix for the substance to be released. Sub-surface growth mechanisms during this process converted the liquid polymer into a solid, yet water-soluble, phase. This layer permits extended storage for various substances within a single film of only a few micrometers in thickness, and hence demands minimal space and complexity. Improved control over release of the model substance Fluorescein was achieved by coating the hybrid material with a conducting polymer film. Single dosage and repetitive dispensing from this system was demonstrated. Release was controlled by applying a bias potential of ±0.5 V to the polymer film enabling or respectively suppressing the expulsion of the model drug. In vitro tests showed excellent biocompatibility of the presented system.

A blister-test apparatus for studies on the adhesion of materials used for neural electrodes

A blister test apparatus has been developed, which allows a quantitative adhesion analysis of thin-film metallizations on polymers manufactured in cleanroom conditions suitable for micromachining of neural electrode arrays. The device is capable of pressurizing metallic membranes at wafer level, monitoring the pressure and the height of the developing blister while detecting the moment of delamination, allowing the calculation of the adhesion energy between metal film and polymer. The machine is designed for quantitative long-term studies of materials used in neural microelectrode arrays.

Iridium Oxide (IrOx) serves as adhesion promoter for conducting polymers on neural microelectrodes

Conducting polymers (CPs) as functional coatings on microelectrodes enable the realization of neural probes with superior electrical properties compared to metallized probes. Besides significantly lower impedance and enhanced charge delivery capacity, CPs further feature the possibility to release drugs from their bulk which can be done exclusively from these materials. Thus the usage of CPs at the neural interface for recording or stimulation of neural tissue is of great interest. A drawback that has however been observed at usage of conducting polymers in vitro and in vivo is the weak adhesion of the polymer to the substrate which ultimately leads to delamination of the coatings. This effect has limited the applicability of polymer coatings on neural probes despite their overall promising potential. In our study we address this gap by introducing Iridium Oxide (IrOx) as adhesion promoter for long-term stabilization of CP films. Exaggerated stressing protocols revealed superior adhesion of the polymer to the rough structure of IrOx and electrochemical measurements indicated unrestricted polymer functionality. With the herein proposed strategy a major obstacle of using conducting polymers at the neural interface could be efficiently targeted and thus applicability of CPs for neural interfaces can be extended in future electrode generations.

Accurate neuronal tracing of microelectrodes based on PEDOT-dye coatings

Penetrating microelectrode probes offer the opportunity to precisely monitor neuronal signals over several months. After the experimental end point, histological methods are used to analyze the tissue and to correlate recorded signals to histological findings. However, accurate retroactive tracing of the position of individual microelectrodes is currently hampered by the lack of suitable techniques to mark their positions. Here we describe a poly (3, 4-ethylene dioxythiophene) (PEDOT) based microelectrode coating, which is optimized for an active, electrochemically controllable release of the neuronal tracer DiI. The tracer is incorporated into the polymer coating by an ion exchange mechanism. Active cycling showed a 3.6 times higher dye incorporation rate compared to reference samples which were solely immersed in the dye. A bi-layer system was used to optimize drug storage ability and could suppress passive leakage of DiI from the film by more than a factor 6. The PEDOT/dye system was characterized in vitro in terms of its ability to store the dye over the time course of the experiment, deliver a precise quantity upon electroactivation and continuously support stable recordings throughout an implantation.