Microarray based optical biochip with nanometric resolution

摘要

The choice of metal clusters as signal transducers of molecular binding events is based on their about 1000 times higher extinction coefficients compared to conjugated chromophores. Using cluster based assays it is possible to visualize the binding of biomolecules at a given surface by a bound layer of ligand-modified metal clusters. The success of cluster visualization was mainly based on the significant signal stability contrary to chromophores and especially fluorophores. Cluster probes are not only efficient direct markers but within the past years became the basis of new devices employing cluster resonance, cluster field enhancement, and cluster-cluster interactions. Multilayered highly resonant systems clearly exhibit strong reflection minima induced by the resonant behavior of the metal cluster layer. At least one narrow reflection minimum can be shifted to the red or infra red spectral range and therefore far away from spherical gold colloids to be read by a 10μm resolution optical scanner type high density device. Even without employing near-field optics spatial resolution is within 100-500 nm. The setup enabled us to replace conventional ELISA assays overcoming the various technological limits as there are e.g. multiple incubation steps and spatial resolution. The focus of the development was to provide an optical biochip which allows detection of analytes based on arrays of proteins, DNA and high throughput-screening targets for drug discovery.