Towards spatially resolved impedance analysis of adherent cells

Commercial impedance sensing systems nowadays contain only one electrode or a connected set of electrodes per well. For some applications it would be of great interest to measure the impedance spectrum of areas of a cell culture separately, e.g. in large culture flasks or for cells that do not form homogeneous cell layers. Fraunhofer IPA is developing an integrated impedance analyzer for spatially resolved measurements. An impedance analyzer circuit with multiplexers to address several sensors sequentially that is small enough to be integrated in a microwell plate was already designed and validated. The frequency range of the impedance analyzer is 100Hz to 100kHz and thus covers the range required for cell analysis. For the sensors, interdigitated electrode structures (IDES) on the surface of the well were used. In order to realize an array of individually addressable electrodes, it is essential to build up isolated crossings of traces. This necessitated a manufacturing method which could create a structured composite of isolating and conducting layers. In order to enable optical monitoring of the cell culture, the substrate should be transparent. Inkjet printing was identified as a promising technology for this task. Using a silver-ink, very fine electrode structures (line/spacing: 50µm) could be applied on the substrate. To reinforce the silver layer, a copper layer was added galvanically and covered with a gold coating. The biocompatible substrate was a polyethylennaphthalat (PEN) foil which is transparent in the visible spectrum. The insulating layer necessary for conductor path crossings were not yet implemented. In a first trial, cultivation of 3T3 fibroblasts on the printed electrode structures was successful.