ABSTRACT
The growth of high throughput screening (HTS) for pharmaceutical drug discovery has been fueled by several technological developments over the past decade. A substantial number of HTS applications were enabled by the advances in instrumentation, molecular biology and biochemistry leading to facile adaptation of biochemical activity screens into microplate formats. Now assays based on absorbance, fluorescence, epifluorescence, luminescence, scintillation detection and related techniques can be automated to the point where hundreds, even thousands of compounds can be screened per day. Manufacturers of liquid handling systems and detection instruments have responded to these trends, so that an entire paradigm has been created. Candidate assays make it to the HTS arena to the extent they can be run in this format. Thus one now sees ELISA and enzyme inhibition assays run in standard microplates, cell-based and membrane particulate assays run in filtration plates, fluorometric assays run in black or white opaque plates, and 8- and 12-channel pipetting systems designed to accomodate this format (1–4). For the forseeable future, any new technique must be similarly capable of adaptation to this format. Fluorescence polarization (FP), a nearly ideal technique for automation, has only recently become available in a microplate reader form. As we will see, FP’s proven record in clinical immunoassays carries over directly into the HTS environment.
