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Mar 15, 2009 (Vol. 29, No. 6)

Advances in Label-Free Assay Screening

Advantages and Limitations of New Tools Such as RAP, Optical Biosensors, and SPR

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    Actelion Pharmaceuticals uses a proprietary technology to characterize coupling pathways of prototypic GPCR activation response in recombinant and nonrecombinant cells.

    Currently, most assays for detection of biologically relevant binding events use radioactive or fluorescent dyes to tag one or more molecules. The need for multiple reagents limits label-based assay flexibility and speed, particularly in HTS formats.

    In cell-based assays, label dependence may produce artifacts because of manipulation of cells either through label-induced toxicity or other effects and requirements for over-expression of targets or reporter proteins. Label-based assays may also necessitate several ligand immobilization and detection methods and serial experiments to yield sufficient information, contributing considerably to the cost of drug discovery and development.

    Recently, academic and industry scientists presented new techniques to facilitate label-free screening methods as assay tools for multiple applications at Select Biosciences’ “Screening, MedChem, and ADMET Europe” conference, held in Berlin last month.

    According to label-free assay developers, label-based assays restrict scientists to investigating one signaling pathway per ligand-receptor complex, and do not incorporate multiple-pathway readouts likely to be involved in a single ligand binding interaction. Cell-based label-free technologies, such as optical biosensors that leverage characteristics of cells that change in response to signal transduction may facilitate fast and accurate real-time readout capabilities for cell-based and other assays.

    Advantages and limitations of label-free technologies, including resonant acoustic profiling (RAP), optical biosensors, and microparticle-based surface plasmon resonance (SPR), were described at the ADMET meeting as well as progress in their use for drug discovery applications.

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