Affinity biosensing is one of many analytical techniques that have high potential for the detection of drug leads. In this thesis the use of ellipsometry, surface plasmon resonance (SPR) as well as quartz crystal microbalance (QCM) as screening methods in drug discovery are presented. In particularly, attention was given to the sensing surfaces and their incorporation in multi-sensor arrays, or biochips, for monitoring the specific affinity binding of low molecular weight molecules.

Silicon dioxide and gold surfaces were rendered porous and used as the biosensing surface. Porous surfaces enhanced the performance of the biosensor considerably, due to the increase in the capacity of binding ligands. In the case of porous silicon dioxide the increase in the response is 10-fold, while porous gold showed a 6-fold increase, when employing ellipsometric measurements. It was also shown that porous gold can successfully be incorporated in SPR systems when used as a biosensor, resulting in a small increase in sensitivity when employing rough gold surface and an 20-fold increase in case of thick porous gold layers, compared to planar surfaces. The surface area of the gold electrode on the crystals was increased by rendering the electrodes porous. This increased the response up to a factor 3. Thus, porous surfaces together with ellipsometry, SPR or QCM have the advantage of not requiring labelling, such as fluorescence, isotope or antigen tags, for achieving the necessary sensitivity.

Further, ellipsometric and SPR imaging systems were introduced employing a 1 cm² surface, containing 900 targets. These biochips are a step towards a faster highthroughput screening process. Two methods of fabrication of these biochips are shown: one based on wet etching of a silicon surface and the other on the preparation of so called tension wells on the silicon surface.

Affinity models were used throughout this work.Streptavidin was immobilised to the porous silicon to bind biotin and an oligopeptide, synthesised by means of combinatorial chemistry monitored with the ellipsometer. A protein model system consisting of anti-human myoglobin as analyte and sheep skeletal myoglobin as ligand was used in different concentrations. Measurements on the biochips were performed with carbohydrate model substances selected for six common lectins.