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The demands on flexible implants for recording of neural signals and electrical stimulating have increased in recent years with regard to their functionality, miniaturization, and spatial resolution. These requirements can be met best by embedding powerful complementary metal oxide semiconductor (CMOS) microchips into thin biocompatible polymer substrates. So-called chip-in-foil systems thus combine mechanical properties of a polymer substrate and performance of CMOS technology. The development of a process for direct transfer of multiple CMOS microchips (edge length

Application-specific integrated circuits (ASICs) embedded in polymers have been subject in implant manufacturing for the recent years. The increased functionality combined with good biocompatibility due to flexibility of thin implants makes them interesting for further studies. Thin-film ASICs can be used for the recording and processing of a high amount of biological signals, improving the performance of neural implants. Fabrication and analysis of gold and platinum thin-film connections are subject of this study, especially their capability as high frequency data transmission lines. Three layers of polyimide are used as flexible substrate and insulator of the traces. Various test structures were designed and fabricated, to investigate the resistance and reactance up to GHz frequencies, crosstalk and influence of vias between metallization layers. All conducting structures have a comparable design with a length of 50 mm and a metal thickness of 300 nm, while the line widths were varied. In this configuration gold and platinum thinfilm conductors are both suitable for high-frequency data transmission up to 100 MHz. This transmission frequency limit and impedances are unaffected by a wet environment and in accelerated aging tests. However, both metals show a high pass filter behavior, whose frequency behavior is mostly dependent by the self-inductance and resistance. A simplified ideal transmission model predicts the electrical behavior sufficiently and can be used to design the favored line impedance matching input impedances of the connected ASICs.

Micromachined devices with substrate-integrated electrodes are the key component in implantable microsystems—one important group of BIOMEMS for recording of neural signals or electrical stimulation of nerves. So far, electrodes have been located on only one side of the microsystems. In this paper a technology has been developed to fabricate multichannel microelectrodes that are located on the topside and the backside of a flexible device. The process technology for polyimide-based devices is described. Prototypes of shaft electrodes with double-sided electrodes have been fabricated and characterized with means of impedance spectroscopy. Results are discussed on scanning electron microscopy, cross sections and electrochemical characterizations of the electrodes. [Copyright &y& Elsevier]

Polymer‐derived carbon can serve as an electrode material in multimodal neural stimulation, recording, and neurotransmitter sensing platforms. The primary challenge in its applicability in implantable, flexible neural devices is its characteristic mechanical hardness that renders it difficult to fabricate the entire device using only carbon. A microfabrication technique is introduced for patterning flexible, cloth‐like, polymer‐derived carbon fiber (CF) mats embedded in polyimide (PI), via selective reactive ion etching. This scalable, monolithic manufacturing method eliminates any joints or metal interconnects and creates electrocorticography electrode arrays based on a single CF mat. The batch‐fabricated CF/PI composite structures, with critical dimension of 12.5 µm, are tested for their mechanical, electrical, and electrochemical stability, as well as to chemicals that mimic acute postsurgery inflammatory reactions. Their recording performance is validated in rat models. Reported CF patterning process can benefit various carbon microdevices that are expected to feature flexibility, material stability, and biocompatibility. [ABSTRACT FROM AUTHOR]

Glassy carbon (GC) has high potential to serve as a biomaterial in neural applications because it is biocompatible, electrochemically inert and can be incorporated in polyimide-based implantable devices. Miniaturization and applicability of GC is, however, thought to be partially limited by its electrical conductivity. For this study, ultra-conformable polyimide-based electrocorticography (ECoG) devices with different-diameter GC electrodes were fabricated and tested in vitro and in rat models. For achieving conformability to the rat brain, polyimide was patterned in a finger-like shape and its thickness was set to 8 µm. To investigate different electrode sizes, each ECoG device was assigned electrodes with diameters of 50, 100, 200 and 300 µm. They were electrochemically characterized and subjected to 10 million biphasic pulses—for achieving a steady-state—and to X-ray photoelectron spectroscopy, for examining their elemental composition. The electrodes were then implanted epidurally to evaluate the ability of each diameter to detect neural activity. Results show that their performance at low frequencies (up to 300 Hz) depends on the distance from the signal source rather than on the electrode diameter, while at high frequencies (above 200 Hz) small electrodes have higher background noises than large ones, unless they are coated with poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS). [ABSTRACT FROM AUTHOR]

A method for manufacturing flexible neural implants with low-ohmic wire traces and improved stimulation electrodes is presented together with the results of electrical characterization. The main objective is to reduce the resistance of the wire traces compared to currently used interconnects which are made from sputtered gold. This is achieved by electroplating to obtain a gold layer with a thickness of 2–3 μm. The resistance of the electroplated wire traces shows a reduction by a factor 30 and more compared to the sputtered wire traces. The electrode properties also improve (the electrode impedance is reduced to about a half due to the higher roughness of the gold surface) while the tests of the mechanical stability shows no increase in resistance when bending the implant up to 150,000 times in physiologic saline solution (0.9% NaCl) at 37 °C. [Copyright &y& Elsevier]

Optical stimulation of genetically modified nerve cells has become one of the state-of-the-art methods in neuroscience. This so-called optogenetic approach allows cell-type specific activation in comparison to more generalized electrical stimulation. Combinations of both stimulation modalities would be desirable to investigate effects in detail and specify differences. This work presents the design of a miniaturized optoelectronic device that allows optical and electrical activation at the same spot. Indium tin oxide (ITO), which is transparent to visible light, has been chosen as electrode material. Light emitting diodes were assembled on a polyimide substrate with integrated interconnection lines, directly behind the electrodes to compare optical with electrical stimulation. The optical transparency of the ITO-polyimide layer stack was investigated and showed sufficient transmission in the required wavelength range. ITO electrodes with diameters up to 1000 μm were electrochemically characterized using electrical impedance spectroscopy (EIS). Several diameters did show comparable results to platinum, a commonly used electrode material. Fully assembled devices were used in combination an ex vivo setting with genetically modified retina to demonstrate the functionality of this approach. Retinal ganglion cells were excited by both, optical and electrical stimulation at the same spot and signals were recorded via standard microelectrode arrays (MEA) as reference. The simultaneous stimulation and recording of directly evoked action potentials indicates a similar mode of action of the two stimulation modalities. Further engineering work is needed to transfer the presented and proven concept into devices for chronic implantation, might it be in animal or first-in-human studies. • Neural interface for optical and electrical activation at the same location. • Indium tin oxide electrodes are transparent to optogenetic relevant wavelengths. • Light emitting diodes assembled on polyimide directly behind electrode spots. • Ex vivo demonstration of concept on genetically modified retina. • Stimulation of ganglion cells and recording of directly evoked action potentials. [ABSTRACT FROM AUTHOR]

Polyimide sieve electrodes were implanted between the severed ends of the sciatic nerve in rats. The degree of axonal regeneration through the electrode was examined by physiological and histological methods from 2 to 12 months postimplantation. Regeneration was successful in the 30 animals implanted. Functional reinnervation of hindlimb targets progressed to reach maximal levels at 6 months. Comparatively, the reinnervation of distal plantar muscles was lower than that of proximal muscles and of digital nerves. The number of regenerated myelinated fibers increased from 2 to 6 months, when it was similar to control values. The majority of myelinated fibers crossing the via holes and regenerated through the distal nerve had a normal appearance. However, in a few cases decline of target reinnervation and loss of regenerated nerve fibers was found from 6 to 12 months postimplantation. Motor axons labeled by ChAT immunoreactivity regenerated scattered within minifascicles, although they were found at higher density at the periphery of the regenerated nerve. The number of ChAT-positive axons was markedly lower distally than proximally to the sieve electrode. [Copyright &y& Elsevier]

Abstract: Biomedical microimplants are used as neural prostheses to restore body functions after paraplegia by means of functional electrical stimulation (FES). This paper describes an approach of the integration of organic transistors into flexible biomedical microimplant for FES use. Encapsulation is used to ensure the electrical functionality of implants (insulation) and to protect them from the harsh environments in the human body. So far, biomedical microdevices have been fabricated using silicon or polyimide substrate, respectively. Highly flexible polyimide based microdevices that have been interfaced with nerves as neural prostheses showed excellent properties as implant material . Therefore, we have developed transistors on polyimide, which is used as flexible substrate. Gold was sputtered as gate, drain and source. Silicon oxide formed the gate insulator and pentacene (C14H22) was evaporated at ultra high vacuum (UHV) and 75°C substrate temperature as active layer in an organic field effect transistor (OFET). Parylene is used as encapsulation material. First transistors have been fabricated and characterized. So far, they are still in low scale integration. The first investigation on the electrical properties of the OFETs before and after encapsulation with Parylene at room temperature led to promising results. [Copyright &y& Elsevier]