Modular glass chip system measuring the electric activity and adhesion of neuronal cells--application and drug testing with sodium valproic acid.

We developed a modular neurochip system by combining a small (16x16 mm2) glass neurochip (GNC) with a homemade head stage and commercial data acquisition hardware and software. The system is designed for the detection of the electric activity of cultivated nerve or muscle cells by a 52-microelectrode array (MEA). In parallel, cell adhesion can be registered from the electric impedance of an interdigitated electrode structure (IDES). The GNC was tested with various cell lines and primary cells. It is fully autoclavable and re-useable. Murine embryonic primary cells were used as a model system to correlate the electric activity and adhesion of neuronal networks in a drug test with sodium valproic acid. The test showed the advantage of the parallel IDES and MEA measurements, i.e. the parallel detection of cytotoxic and neurotoxic effects. Toxic exposure of the cells during neuronal network formation allows for the characterization of developmental neurotoxic effects even at drug concentrations below the EC50-value for acute neurotoxic effects. At high drug concentrations, the degree of cytotoxic damage can still be assessed from the IDES data in the event that no electric activity develops. The GNC provides optimal cell culture conditions for up to months in combination with full microscopic observability. The 4'' glass wafer technology allows for a high precision of the GNC structures and an economic production of our new system that can be applied in general and developmental toxicity tests as well as in the search for neuro-active compounds.