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The resonance-enhanced absorption (REA) by metal clusters on a surface is an effective technique on which to base bio-optical devices. A four-layer device consisting of a metal mirror, a polymer or glass-type distance layer, a biomolecule interaction layer and a sub-monolayer of biorecognitively bound metal nano-clusters is reported. Experiments indicate a strong influence of the resonator homogeneity on the absorption maximum. Layer stability plays an important role in the overall performance of the device. Techniques and optimised lab protocols to set up biochips that use the REA process in the detection are presented. The sensors show one to three narrow reflection minima in the visible and or infra-red (IR) part of the spectrum and therefore they do not suffer from the spectral limitations associated with spherical gold colloids. Metal clusters (synthesised by thermal step reduction) as well as metal- dielectric shell clusters (synthesised by various shell deposition processes) are used to precisely shift the readout of the device to any frequency in the visible and near IR range. Disposable single-step protein chips, DNA assays as well as complex biochip arrays are established that use various DNA/RNA, antigen-antibody and protein-protein interaction systems.