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.

This paper reports on the fabrication and application of microneedles for the electroporation of adherently growing cells and intracellular recording with focus on the influence on external factors on the cell behavior. Patch-on-chip methods such as patch-clamp have been applied mostly to individual cells in suspension. However, in the human body most of cells are adherently growing cells, which motivated the development of a new chip design. The chip contains an array of 64 microneedles occupying a total area of approximately 1 mm 2. The microneedles are fabricated using dry etching of silicon, followed by an insulation, metallization and passivation. The passivation layer is opened at the tip of the needles in order to expose the metal for cell positioning via dielectrophoresis, cell electroporation, as well as intracellular recording. Various needles with diameters in the sub-micron range and heights below 10 ?m have been fabricated. Heart muscle cells, fibroblasts, and primary neuronal cells of mice were grown on these microneedle arrays. To electrically access the intracellular space, the cells were electroporated with a voltage of ±2 V. Preliminary tests show that more than 80 % of the cells could successfully be porated. ©2008 IEEE

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We report the investigation of the interfaces between microneedle arrays and cell cultures in patch-on-chip systems by using Focused Ion Beam (FIB) preparation and Scanning Electron Microscopy (SEM). First, FIB preparations of micro chips are made to determine the size and shape of the designed microneedles. In this essay, we investigate the cell-substrate interaction, especially the cell adhesion, and the microneedle's potential cell penetration. For this purpose, cross-sectional preparation of these hard/soft hybrid structures is performed by the FIB technology. By applying the FIB technology followed by high-resolution imaging with SEM, new insights into the cell-substrate interface can be received. One can clearly distinguish between cells that are only in contact with microneedles and cells that are penetrated by microneedles. A stack of slice images is collected by the application of the slice-and-view setup during FIB preparation and is used for three-dimensional reconstruction of cells and micro-needles.