FLUORESCENCE CORRELATIONS, SINGLE-MOLECULE DETECTION AND LARGE NUMBERSCREENING - APPLICATIONS IN BIOTECHNOLOGY

Fluorescence correlation spectroscopy (FCS), when carried out under co nditions with low background as obtained in very small volume elements , is a powerful tool for examining molecular interactions as well as t heir time dependence. Interactions of biological importance which can be analyzed are hybridization between nucleic acid primers and DNA or RNA targets, between peptide ligands and isolated as well as cell-boun d receptors, between antigen and antibodies. Since the interaction can be analyzed rapidly in small volumes without the need for separating unbound from bound ligand, an important application of FCS is envisage d in large-scale drug screening. The sensitivity has been advanced to the point that detection of single dye molecules is possible in the su bmillisecond range. This opens up the possibility for detecting rare e vents such as the appearance of pathogens in the early phase of infect ion or mutants exhibiting unusual properties when screening combinator ial libraries.