André Mercanzini

In Vivo Electrical Impedance Spectroscopy of Tissue Reaction to Microelectrode Arrays

The goal of this experiment was to determine the electrical properties of the tissue reaction to implanted microelectrode arrays. We describe a new method of analyzing electrical impedance spectroscopy data to determine the complex impedance of the tissue reaction as a function of postimplantation time. A model is used to extract electrical model parameters of the electrode-tissue interface, and is used to isolate the impedance of the tissue immediately surrounding the microelectrode. The microelectrode arrays consist of microfabricated polyimide probes, incorporating four 50-mum-diameter platinum microelectrodes. The devices were implanted in the primary motor cortex of adult rats, and measurements were performed for 12 weeks. Histology was performed on implants at three time points in one month. Results demonstrate that the tissue reaction causes a rapid increase in bioimpedance over the first 20 days, and then stabilizes. This result is supported by histological data.

Controlled release nanoparticle-embedded coatings reduce the tissue reaction to neuroprostheses

Controlled release coatings were developed for neuroprostheses with the aim of combating the tissue reaction following implantation in the brain. The coatings consist of poly(propylene sulfide) drug-eluting nanoparticles embedded in a poly(ethylene oxide) matrix. The nanoparticles are loaded with dexamethasone, an anti-inflammatory drug known to have an effect on the cells activated during the damage caused by implantation. The nanoparticles are not affected by the coating process and the drug remains bioactive after it is released. The coating was applied to microfabricated cortical neuroprostheses consisting of platinum and polyimide. Coated drug-eluting devices were implanted in the cortex of rats. After implantation the matrix dissolves, exposing the electrode surfaces, while the nanoparticles remain in the vicinity of the tissue-implant interface. Using electrical impedance spectroscopy and comparative histology, a long-term decrease in the tissue response in comparison to control devices was observed. These coatings can therefore be used to increase the reliability and long-term efficacy of neuroprostheses.

Demonstration of cortical recording and reduced inflammatory response using flexible polymer neural probes

We present the fabrication, characterization, use in cortical recording and histological results of a flexible implantable neural probe. The device is microfabricated in polyimide and platinum, allowing for greater flexibility. It incorporates two layers of platinum electrodes, which greatly reduces the size of neural probes and limits the insertion damage. In recording experiments, acute in-vivo measurements were performed in the mouse cortex. Local field potential, single- and multi-neuron activity were simultaneously recorded. We demonstrate using immunohistochemistry techniques reduced inflammation at the implantation site for microfabricated polyimide neural probes. We therefore show that the major advantage of using polymer probes over silicon probes is the reduced damage due to insertion and probe-brain compliance mismatch.

Technology developments to initiate a next generation of Cochlear Implants

In the framework of the EU-supported research project Healthy Aims, we developed a range of novel electrode arrays and related technologies for use in hearing prosthesis. This paper summarizes our ongoing research activities on alternative electrode manufacturing routes, functional electrode interfaces and smart intra-cochlear and intra- modiolus electrode arrays.

Controlled Release Drug Coatings on Flexible Neural Probes

We present the development, characterization and in vivo validation of a novel drug eluting coating that has been applied to flexible neural probes. The coating consists of drug eluting nanoparticles loaded with an anti-inflammatory drug embedded in a biodegradable polymer. The drug eluting coating is applied to flexible polymer neural probes with platinum electrodes. The drug eluting device is implanted in one hemisphere of a rat, while a control device is implanted in the opposite hemisphere. Impedance measurements are performed to determine the effect of the drug eluting coating on the tissue reaction surrounding the probe and the electrical characteristics of the devices. Probes that are coated with drug eluting coatings show better long term impedance characteristics over control probes. These coatings can be used to increase the reliability and long term success of neural prostheses.

The Effect of Biodegradable Drug Release Coatings on the Electrical Characteristics of Neural Electrodes

This study describes how drug eluting coatings affect the signal quality of implantable microelectrodes. Polyimide-Platinum neural probes were micro fabricated and coated with a biodegradable polymer loaded with drug eluting nanoparticles. Electrical impedance spectroscopy was used to study how the coating affects electrical recording and stimulation characteristics. The measurements were performed in vitro and it was found that the biodegradable film slightly modified the measured impedance phase by +3deg at 10 kHz but not the magnitude. This change in impedance is permanent but does not adversely affect the recording and stimulation characteristics of the device. This result demonstrates the compatibility of controlled release drug coatings with neural probes.