Key Points
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Optical biosensors have been commercially available since the early 1990s, and have been used extensively in many areas of research in life sciences.
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Optical biosensors use the evanescent-wave phenomenon to characterize interactions between 'receptors' attached to the biosensor surface and 'ligands' in solution above the surface.
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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.
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Most importantly, binding affinities and kinetics can be determined using very low amounts of compound without the need for prior chemical or radiolabelling.
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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.
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This article includes descriptions of the following application areas for biosensors in drug discovery:
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Ligand fishing.
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Conformation of high-throughput screening (HTS) hits using optical biosensors as an information-rich secondary screen.
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Real-time characterization of interaction kinetics and affinities of confirmed hits.
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Integration with mass spectometry in proteomics.
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Determination of drug binding to serum proteins.
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Adsorption of a drug to membrane interfaces.
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Process control and production for Good Laboratory Practice (GLP)/Good Manufacturing Practice (GMP) validation.
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Analysis of clinical samples.
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Screening against membrane receptors.
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Development of multiplexed assays for high-information-content, high-throughput screening.
Abstract
Optical biosensors that exploit surface plasmon resonance, waveguides and resonant mirrors have been used widely over the past decade to analyse biomolecular interactions. These sensors allow the determination of the affinity and kinetics of a wide variety of molecular interactions in real time, without the need for a molecular tag or label. Advances in instrumentation and experimental design have led to the increasing application of optical biosensors in many areas of drug discovery, including target identification, ligand fishing, assay development, lead selection, early ADME and manufacturing quality control. This article reviews important advances in optical-biosensor instrumentation and applications, and also highlights some exciting developments, such as highly multiplexed optical-biosensor arrays.
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Acknowledgements
M. A. C. wishes to acknowledge Affinity Sensors, Artificial Sensing Instruments, Aviv Instruments, Biacore, Farfield Sensors, Graffinity Pharmaceuticals, HTS Biosystems, IBIS, Luna Analytics, Nippon Lasers, Prolinx and SRU Biosystems for critical revision of the manuscript, for providing access to images and for the information contained in online table 1.
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Glossary
- BIOSENSOR
-
A device that uses biological receptors to detect analytes in a sample.
- EVANESCENT-WAVE PHENOMENON
-
Total internal reflection of light at a surface–solution interface produces an electromagnetic field, or evanescent wave, that extends a short distance (∼100–200 nm) into the solution. SPR is an evanescent- wave phenomenon that occurs at certain metallic surfaces.
- BIOTIN
-
The streptavidin/biotin system has one of the largest free energies of association observed for noncovalent binding of a protein and small ligand in aqueous solution (KD = 0.1 pM). The complexes are also extremely stable over a wide range of temperature and pH.
- NEPHELOMETRY
-
The measurement of solution turbidity or 'cloudiness'. It can be used to study drug solubility and microbial growth, and for immunological tests.
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Cooper, M. Optical biosensors in drug discovery. Nat Rev Drug Discov 1, 515–528 (2002). https://doi.org/10.1038/nrd838
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DOI: https://doi.org/10.1038/nrd838
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