Our aim is to establish an objective, easy-to-use technique to evaluate tissue irritation in vivo using non-invasive electrical impedance measurements. Such a technique would facilitate testing the biocompatibility of various materials, and also in quantifying skin diseases and other processes involving structural changes. It has been found that irritation of the oral mucosa not clinically or histologically discernible could be detected with a simple device based on electrical impedance techniques. Originally, the key problem was to focus the probing electrical field in order to minimize artefacts emanating from tissue layers of no interest. The device was then refined and applied to skin testing. It was found that irritation effects far below the limit of the commonly used visual readings could be detected. In this case, it is desirable to exclude from the measurement tissue layers with no diagnostic information, or at least reduce their influence. In this paper, the essential steps of the development of a multi-frequency depth selective device are reviewed.