In vitro neurotoxicology tests based on the coupling of brain slices to silicon microelectrode arrays

• Forschungsstelle: EU FRP
• Projektnummer: 97.0279
• Projekttitel Englisch: In vitro neurotoxicology tests based on the coupling of brain slices to silicon microelectrode arrays

Schlüsselwörter (Englisch)

Microelectrode arrays; brain slices; organotypic cultures; electrophysiology

Alternative Projektnummern (Englisch)

EU project number: BIO4CT972307

Forschungsprogramme (Englisch)

EU-programme: 4. Frame Research Programme - 4.1 Biotechnology

Kurzbeschreibung (Englisch)

See abstract

Partner und Internationale Organisationen (Englisch)

University of Genova (I), Odense University (DK), University of Copenhagen (DK), WWU, Münster (D), BioLogic (F)

Abstract (Englisch)

Neurotoxic effects can be caused by a large variety of chemical substances encountered in industry and daily life. At present, in vivo animal tests are mainly used for screening neurotoxicity of different substances. The development of reliable in vitro tests as an alternative to the in vivo ones is thus of great interest.
The aim of this project was to develop a tool for in vitro screening of neurotoxic agents. The rationale is that neuronal damage leads to changes in, or a loss of the electrophysiological activity of brain slices and organotypic slice cultures and therefore, electrophysiological recordings can be used as indicators of neurotoxicity. The methodology used relies on the in vitro monitoring of the extracellular activity of cultured neurones couples to a microelectrode array (MEA).
The task of the IMT was the development and fabrication of the microelectrode arrays for multi-site, long-term stimulation and recording of acute and organotypic brain slice cultures. Constraints arising from technological and biological issues have been taken into consideration for optimising the MEAs in terms of cell culture survival, electrical performance (electrode/cell coupling) and reliability.
The outcome of this development is a technological platform based on the thin-film technology, silicon micromachining and electrodeposition for the realisation of planar and/or 3-dimensional Pt microelectrode arrays integrated on a planar or a perforated silicon/silicon nitride substrate. Altogether six generations of MEAs with either double elliptical (34 electrodes) or a rectangular (32 electrodes) geometries have been realised and evaluated. Continuously upgraded during the project the resulting catalogue of devices comprises next to the silicon -integrated devices also MEAs integrated on glass substrates.

The printed circuit board supporting the MEAs have been designed to fit the slice chamber developed by the project partners. Following a complete electrical and biocompatibility evaluations of the MEAs, stimulation and recordings using both brain slices and organotypic brain slice cultures have been performed. Applying new experimental protocols developed within the project, the neurotoxicological tests have been successfully performed demonstrating the functionality and stability of the MEAs.

Datenbankreferenzen (Englisch)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 97.0279