Novel high-sensitivity fluorescence polarization reader

摘要

Advances in functional genomics and combinatorial chemistry require improvements in current drug screening instrumentation: a drug discovery bottleneck has been generated by the inability of current technology to expeditiously explore such combinatorial libraries of drug candidates for new target identification. To alleviate this problem, the sample-throughput of screening instrumentation needs to improve without sacrificing and precision-both required for cost-effective, accurate lead identification. We have developed a new fluorescence polarization (FP) reader suitable for high-throughput screening (HTS) and ultra-HTS whose assay-performance and sample-throughput are both considerably improved over present state-of-the-art instrumentation. The Symmetry~(TM) reader possesses a number of features that differ from conventional HTS FP readers. These include: laser-based excitation; liquid crystal polarization optics that rapidly and accurately measure polarization states; and CCD detectors to capture emission from multiple wells. We show that the performance in assays relevant to the drug discovery process, such as G-protein coupled receptor-based assays, is significantly enhanced due to a dramatic improvement in precision. Furthermore, the CCD-detection system used can substantially improve sample throughput compared to sequential readers while maintaining high performance.