Anita Pongrácz

Neurobiochemical changes in the vicinity of a nanostructured neural implant

Neural interface technologies including recording and stimulation electrodes are currently in the early phase of clinical trials aiming to help patients with spinal cord injuries, degenerative disorders, strokes interrupting descending motor pathways, or limb amputations. Their lifetime is of key importance; however, it is limited by the foreign body response of the tissue causing the loss of neurons and a reactive astrogliosis around the implant surface. Improving the biocompatibility of implant surfaces, especially promoting neuronal attachment and regeneration is therefore essential. In our work, bioactive properties of implanted black polySi nanostructured surfaces (520–800 nm long nanopillars with a diameter of 150–200 nm) were investigated and compared to microstructured Si surfaces in eight-week-long in vivo experiments. Glial encapsulation and local neuronal cell loss were characterised using GFAP and NeuN immunostaining respectively, followed by systematic image analysis. Regarding the severity of gliosis, no significant difference was observed in the vicinity of the different implant surfaces, however, the number of surviving neurons close to the nanostructured surface was higher than that of the microstructured ones. Our results imply that the functionality of implanted microelectrodes covered by Si nanopillars may lead to improved long-term recordings.

In Vivo Measurements With Robust Silicon-Based Multielectrode Arrays With Extreme Shaft Lengths

In this paper, manufacturing and in vivo testing of extreme-long Si-based neural microelectrode arrays are presented. Probes with different shaft lengths (15-70 mm) are formed by deep reactive ion etching and have been equipped with platinum electrodes of various configurations. In vivo measurements on rats indicate good mechanical stability, robust implantation, and targeting capability. High-quality signals have been recorded from different locations of the cerebrum of the rodents. The accompanied tissue damage is characterized by histology.

An O18 study of the interaction between carbon monoxide and dry thermal SiO2 at 1100 °C

The mechanisms of oxygen exchange between thermal silicon oxide films and carbon monoxide have been studied using O-18 as an isotopic tracer. SiO2 layers of natural isotopic composition, obtained by thermal oxidation of silicon, were exposed at 1100 degrees C to (CO)-C-13-O-18 gas at pressures ranging from 50 to 350 mbars. O-18 concentration depth profiles were determined using the nuclear narrow resonance profiling technique with the narrow resonance near 151 keV in the reaction O-18(p,alpha)N-15. The results show that oxygen exchange takes place via two distinct processes and a mechanism for each process is proposed in the present work. The diffusion coefficient of CO molecules in the silica and the oxygen exchange frequency between CO and the silica are also determined.

A Multimodal, SU-8-Platinum - Polyimide Microelectrode Array for Chronic In Vivo Neurophysiology

Utilization of polymers as insulator and bulk materials of microelectrode arrays (MEAs) makes the realization of flexible, biocompatible sensors possible, which are suitable for various neurophysiological experiments such as in vivo detection of local field potential changes on the surface of the neocortex or unit activities within the brain tissue. In this paper the microfabrication of a novel, all-flexible, polymer-based MEA is presented. The device consists of a three dimensional sensor configuration with an implantable depth electrode array and brain surface electrodes, allowing the recording of electrocorticographic (ECoG) signals with laminar ones, simultaneously. In vivo recordings were performed in anesthetized rat brain to test the functionality of the device under both acute and chronic conditions. The ECoG electrodes recorded slow-wave thalamocortical oscillations, while the implanted component provided high quality depth recordings. The implants remained viable for detecting action potentials of individual neurons for at least 15 weeks.

Simultaneous in vivo recording of local brain temperature and electrophysiological signals with a novel neural probe

OBJECTIVE Temperature is an important factor for neural function both in normal and pathological states, nevertheless, simultaneous monitoring of local brain temperature and neuronal activity has not yet been undertaken. APPROACH In our work, we propose an implantable, calibrated multimodal biosensor that facilitates the complex investigation of thermal changes in both cortical and deep brain regions, which records multiunit activity of neuronal populations in mice. The fabricated neural probe contains four electrical recording sites and a platinum temperature sensor filament integrated on the same probe shaft within a distance of 30 µm from the closest recording site. The feasibility of the simultaneous functionality is presented in in vivo studies. The probe was tested in the thalamus of anesthetized mice while manipulating the core temperature of the animals. MAIN RESULTS We obtained multiunit and local field recordings along with measurement of local brain temperature with accuracy of 0.14 °C. Brain temperature generally followed core body temperature, but also showed superimposed fluctuations corresponding to epochs of increased local neural activity. With the application of higher currents, we increased the local temperature by several degrees without observable tissue damage between 34-39 °C. SIGNIFICANCE The proposed multifunctional tool is envisioned to broaden our knowledge on the role of the thermal modulation of neuronal activity in both cortical and deeper brain regions.

On the Fabrication Parameters of Buried Microchannels Integrated in In-Plane Silicon Microprobes

This paper aims the characterization of buried microchannels in silicon realized by deep reactive ion etching. The effects of dry etching parameters on the integrability into hollow microprobes are thoroughly investigated from both technological and functional aspects. Results are supposed to give physiology related probe designers a deeper insight into microfabrication-related issues.

Effect of nanostructures on anchoring stem cell-derived neural tissue to artificial surfaces

OBJECTIVE Chronic application of brain implants monitoring or modulating neuronal activity are hindered by the foreign body response of the tissue. Topographical modification of implant surfaces may reduce negative tissue response by imitating the structure of the extracellular matrix and therefore affecting the attachment and behavior of neural cells. APPROACH In our in vitro study, the effect of nanostructuring was investigated on two commercially used neural implant materials: silicon and platinum. The adhesion, survival and arrangement of neural stem cells (NE4C) and microglial cells (BV2) were investigated and compared to nanostructured and flat Si and Pt surfaces using cell viability studies and fluorescent microscopy image analysis. MAIN RESULTS Our data indicated that neural cells established strong adhesive couplings with each other, instead of binding to the artificial surfaces. SIGNIFICANCE The phenomena resemble some features of in vivo separation of living tissue from the implanted artificial material, providing an in vitro model for studying immune response.

Deep-brain silicon multielectrodes with surface-modified Pt recording sites

Extreme-long (up to 70 mm) Si neural multielectrodes are presented for the first time. Probes with different shaft lengths (15-70 mm) were formed by deep reactive ion etching and have been equipped with Pt recording sites of various configurations. In vivo measurements on rodents indicated good mechanical stability, robust implantation and targeting capability, and high quality signals from different locations of the cerebrum have been recorded. The accompanied tissue damage was characterized by histology. With platinum electroplating, electrical impedance reduction was achieved, the improved charge transfer capability was characterized by cyclic voltammetry.