Biomedical applications of single molecule detection

The search for increased sensitivity of bio-analytical techniques has recently shifted from signal generation to detection. While enzyme amplifiers and chemiluminescent reporters developed by chemists over the last two decades gradually moved detection limits to the attomol level, it has taken engineers only a few years to reach single-molecule sensitivity with the development of new instrumentation. A number of different approaches have successfully achieved single-molecule fluorescence detection including confocal and near-field scanning optical microscopy, photon-counting cameras, fluorescence-correlation and time-gated spectroscopy. They detect labels immobilized on substrates, diffusing in solution and flowing in electro-osmotic and hydrodynamically focused streams. Biotechnology has created numerous applications for single-molecule detection. In research labs, it can dramatically increase the rate of DNA sequencing, screen libraries for products of directed evolution, and characterize compounds in drag discovery programs. In medical diagnostics, ultra-sensitive detection technologies can be used for genetic screening, detection of infectious diseases, or multi-analyte profiles It can be applied to immunoassays as well as DNA or RNA hybridization assays.