Supramolecular sensing systems that rely on signal amplification are discussed. Signal amplification implies that the presence of a single analyte results in the production of a multitude of reporter molecules. Two conceptually different approaches towards signal amplification have been identified: catalysis and multivalency. In the first case the presence of an analyte activates a catalyst, whereas in the second case an analyte affects simultaneously multiple reporters through a multivalent architecture (polymer, supramolecular aggregate, nanoparticle, etc.). Particularly efficient signal amplification occurs where the analyte induces a cascade of amplification pathways by combining catalysis and multivalency. It is the scope of this chapter to give an illustration of the creative approaches developed by chemists, while trying to reveal the underlying conceptual connectivity. The examples are classified depending on the target analyte: DNA, small (bio)molecules, and proteins, which are all of relevance for biomedical applications.
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