Optical biosensors in drug discovery

Optical biosensors have been commercially available since the early 1990s, and have been used extensively in many areas of research in life sciences.Optical biosensors use the evanescent-wave phenomenon to characterize interactions between 'receptors' attached to the biosensor surface and 'ligands' in solution above the surface.Many of the best-known optical biosensors use surface plasmon resonance. Binding of molecules in solution to surface-immobilized receptors alters the refractive index of the medium near the surface. This change can be monitored in real time to accurately measure the amount of bound analyte, its affinity for the receptor and the association and dissociation kinetics of the interaction.Most importantly, binding affinities and kinetics can be determined using very low amounts of compound without the need for prior chemical or radiolabelling.An extremely wide range of molecules can by analysed, from low-molecular-mass drugs to multiprotein complexes, with interaction affinities ranging from millimolar to picomolar in strength.This article includes descriptions of the following application areas for biosensors in drug discovery:Ligand fishing.Conformation of high-throughput screening (HTS) hits using optical biosensors as an information-rich secondary screen.Real-time characterization of interaction kinetics and affinities of confirmed hits.Integration with mass spectometry in proteomics.Determination of drug binding to serum proteins.Adsorption of a drug to membrane interfaces.Process control and production for Good Laboratory Practice (GLP)/Good Manufacturing Practice (GMP) validation.Analysis of clinical samples.Screening against membrane receptors.Development of multiplexed assays for high-information-content, high-throughput screening.