Patrick Ruther

Characterization of parylene C as an encapsulation material for implanted neural prostheses

The applicability of parylene C as an encapsulation material for implanted neural prostheses was characterized and optimized. The adhesion of parylene C was tested on different substrate materials, which were commonly used in neural prostheses and the efficiency of different adhesion promotion methods was investigated. On Si(3)N(4), platinum, and on a first film of parylene C, a satisfactory adhesion was achieved with Silane A-174, which even withstood standard steam sterilization. The adhesion to gold and polyimide could not be improved sufficiently with the tested methods. Furthermore, tensile tests and measurements of the degree of crystallinity were performed on untreated, on steam sterilized, and on annealed parylene C layers to investigate the influence of thermal treatment. This led to more brittle and stiffer films due to an increase in the crystalline portion in the parylene layers. Finally, an electrochemical impedance spectroscopy was used to test if a parylene C layer was able to protect a metallic structure against corrosion on a Si(3)N(4) substrate. The results indicated that this could be only possible by treating the substrate with Silane A-174. To receive parylene C layers with a good encapsulation performance, it is important to consider the materials, which are used in the neural prosthesis, to find the best suited process parameters.

Mechanisms of Fibroblast Cell Therapy for Dystrophic Epidermolysis Bullosa: High Stability of Collagen VII Favors Long-term Skin Integrity

Here, we report on the first systematic long-term study of fibroblast therapy in a mouse model for recessive dystrophic epidermolysis bullosa (RDEB), a severe skin-blistering disorder caused by loss-of-function of collagen VII. Intradermal injection of wild-type (WT) fibroblasts in >50 mice increased the collagen VII content at the dermal-epidermal junction 3.5- to 4.7-fold. Although the active biosynthesis lasted <28 days, collagen VII remained stable and dramatically improved skin integrity and resistance to mechanical forces for at least 100 days, as measured with a digital 3D-skin sensor for shear forces. Experiments using species-specific antibodies, collagen VII-deficient fibroblasts, gene expression analyses, and cytokine arrays demonstrated that the injected fibroblasts are the major source of newly deposited collagen VII. Apart from transitory mild inflammation, no adverse effects were observed. The cells remained within an area <or=10 mm of the injection site, and did not proliferate, form tumors, or cause fibrosis. Instead, they became gradually apoptotic within 28 days. These data on partial restoration of collagen VII in the skin demonstrate the excellent ratio of clinical effects to biological parameters, support suitability of fibroblast-based therapy approaches for RDEB, and, as a preclinical test, pave way to human clinical trials.

Fabrication technology for silicon-based microprobe arrays used in acute and sub-chronic neural recording

This work presents a new fabrication technology for silicon-based neural probe devices and their assembly into two-dimensional (2D) as well as three-dimensional (3D) microprobe arrays for neural recording. The fabrication is based on robust double-sided deep reactive ion etching of standard silicon wafers and allows full 3D control of the probe geometry. Wafer level electroplating of gold pads was performed to improve the 3D assembly into a platform. Lithography-based probe-tracking features for quality management were introduced. Probes for two different assembly methods, namely direct bonding to a flexible micro-cable and platform-based out-of-plane interconnection, were produced. Systems for acute and sub-chronic recordings were assembled and characterized. Recordings from rats demonstrated the recording capability of these devices.

A wireless multi-channel recording system for freely behaving mice and rats.

To understand the neural basis of behavior, it is necessary to record brain activity in freely moving animals. Advances in implantable multi-electrode array technology have enabled researchers to record the activity of neuronal ensembles from multiple brain regions. The full potential of this approach is currently limited by reliance on cable tethers, with bundles of wires connecting the implanted electrodes to the data acquisition system while impeding the natural behavior of the animal. To overcome these limitations, here we introduce a multi-channel wireless headstage system designed for small animals such as rats and mice. A variety of single unit and local field potential signals were recorded from the dorsal striatum and substantia nigra in mice and the ventral striatum and prefrontal cortex simultaneously in rats. This wireless system could be interfaced with commercially available data acquisition systems, and the signals obtained were comparable in quality to those acquired using cable tethers. On account of its small size, light weight, and rechargeable battery, this wireless headstage system is suitable for studying the neural basis of natural behavior, eliminating the need for wires, commutators, and other limitations associated with traditional tethered recording systems.

ENHANCING THE YIELD OF HIGH-DENSITY ELECTRODE ARRAYS THROUGH AUTOMATED ELECTRODE SELECTION

Recently developed CMOS-based microprobes contain hundreds of electrodes on a single shaft with inter-electrode distances as small as 30 μm. So far, neuroscientists needed to select electrodes manually from hundreds of electrodes. Here we present an electronic depth control algorithm that allows to select electrodes automatically, hereby allowing to reduce the amount of data and locating those electrodes that are close to neurons. The electrodes are selected according to a new penalized signal-to-noise ratio (PSNR) criterion that demotes electrodes from becoming selected if their signals are redundant with previously selected electrodes. It is shown that, using the PSNR, interneurons generating smaller spikes are also selected. We developed a model that aims to evaluate algorithms for electronic depth control, but also generates benchmark data for testing spike sorting and spike detection algorithms. The model comprises a realistic tufted pyramidal cell, non-tufted pyramidal cells and inhibitory interneurons. All neurons are synaptically activated by hundreds of fibers. This arrangement allows the algorithms to be tested in more realistic conditions, including backgrounds of synaptic potentials, varying spike rates with bursting and spike amplitude attenuation.

GaN-based micro-LED arrays on flexible substrates for optical cochlear implants

Currently available cochlear implants are based on electrical stimulation of the spiral ganglion neurons. Optical stimulation with arrays of micro-sized light-emitting diodes (µLEDs) promises to increase the number of distinguishable frequencies. Here, the development of a flexible GaN-based micro-LED array as an optical cochlear implant is reported for application in a mouse model. The fabrication of 15 µm thin and highly flexible devices is enabled by a laser-based layer transfer process of the GaN-LEDs from sapphire to a polyimide-on-silicon carrier wafer. The fabricated 50 × 50 µm2 LEDs are contacted via conducting paths on both p- and n-sides of the LEDs. Up to three separate channels could be addressed. The probes, composed of a linear array of the said µLEDs bonded to the flexible polyimide substrate, are peeled off the carrier wafer and attached to flexible printed circuit boards. Probes with four µLEDs and a width of 230 µm are successfully implanted in the mouse cochlea both in vitro and in vivo. The LEDs emit 60 µW at 1 mA after peel-off, corresponding to a radiant emittance of 6 mW mm−2.

Multidimensional CMOS in-plane stress sensor

This paper reports a novel multidimensional complementary metal-oxide semiconductor (CMOS) based stress sensor. The device uses an octagonal n-well in a p-substrate and eight peripheral contacts enabling the current to be switched in eight directions rotated by an angle of /spl pi//4. By taking full advantage of the piezoresistive behavior of single-crystal silicon, the measurement of all in-plane stress tensor components, i.e., /spl sigma//sub xx/, /spl sigma//sub yy/, and /spl sigma//sub xy/, is demonstrated. This information is derived from the zeroth and second angular-order Fourier components of voltage signals parallel and perpendicular to the switched current. Nonlinearities of the system are reduced by proper bias conditions using a center contact. The device was calibrated by applying defined normal stresses using a bending bridge setup. The device behavior was modeled including piezoresistive effects and the junction field effect by a combination of the finite element method and a nonlinear simulation program with integrated circuits emphasis (SPICE) network simulation using junction field effect transistor (JFET) elements. Stress sensitivities of 200 /spl mu/V V/sup -1/ MPa/sup -1/ are demonstrated for the determination of the three stress components.

Brain–computer interfaces: an overview of the hardware to record neural signals from the cortex

Brain-computer interfaces (BCIs) record neural signals from cortical origin with the objective to control a user interface for communication purposes, a robotic artifact or artificial limb as actuator. One of the key components of such a neuroprosthetic system is the neuro-technical interface itself, the electrode array. In this chapter, different designs and manufacturing techniques will be compared and assessed with respect to scaling and assembling limitations. The overview includes electroencephalogram (EEG) electrodes and epicortical brain-machine interfaces to record local field potentials (LFPs) from the surface of the cortex as well as intracortical needle electrodes that are intended to record single-unit activity. Two exemplary complementary technologies for micromachining of polyimide-based arrays and laser manufacturing of silicone rubber are presented and discussed with respect to spatial resolution, scaling limitations, and system properties. Advanced silicon micromachining technologies have led to highly sophisticated intracortical electrode arrays for fundamental neuroscientific applications. In this chapter, major approaches from the USA and Europe will be introduced and compared concerning complexity, modularity, and reliability. An assessment of the different technological solutions comparable to a strength weaknesses opportunities, and threats (SWOT) analysis might serve as guidance to select the adequate electrode array configuration for each control paradigm and strategy to realize robust, fast, and reliable BCIs.

CMOS-Based High-Density Silicon Microprobe Arrays for Electronic Depth Control in Intracortical Neural Recording

This paper reports on a novel high-density CMOS-based silicon microprobe array for intracortical recording applications. In contrast to existing systems, CMOS multiplexing units are integrated directly on the slender, needle-like probe shafts. Single-shaft probes and four-shaft combs have been realized with 188 and 752 electrodes, respectively, with a pitch of 40 μm arranged in two columns along 4-mm-long probe shafts. Rather than performing a mechanical translation of the probe shaft relative to the brain tissue to optimize the distance between electrodes and neurons, the electrode position is adjusted by electronically switching between the different electrodes along the shaft. The paper presents the probe concept, the CMOS circuitry design, the applied post-CMOS fabrication process, and the assembled probe systems.

Microprobe Array with Low Impedance Electrodes and Highly Flexible Polyimide Cables for Acute Neural Recording

This paper reports on a novel type of silicon- based microprobes with linear, two and three dimensional (3D) distribution of their recording sites. The microprobes comprise either single shafts, combs with multiple shafts or 3D arrays combining two combs with 9, 36 or 72 recording sites, respectively. The electrical interconnection of the probes is achieved through highly flexible polyimide ribbon cables attached using the MicroFlex Technology which allows a connection part of small lateral dimensions. For an improved handling, probes can be secured by a protecting canula. Low-impedance electrodes are achieved by the deposition of platinum black. First in vivo experiments proved the capability to record single action potentials in the motor cortex from electrodes close to the tip as well as body electrodes along the shaft.