Successfully downscaling screening assays: Servier´s experience

The choice of the best suited multi-mode microplate reader is a key element for the success of High-Throughput Screening (HTS) campaigns. Sensitivity and speed of detection are two of the most important criteria to consider when choosing a microplate reader for HTS. Both can have a positive impact on data quality and cost savings in screening campaigns. 


Sensitivity helps saving money and time


Sensitivity directly affects data quality. However, it indirectly affects also the cost of a HTS campaign. Sensitive microplate readers allow for downscaling and miniaturization as high sensitivity makes it possible to move assays from 384- to 1536-well plates, or simply to further dilute expensive reagents while keeping the same plate format. This obviously results in cost savings. Additionally, sensitivity may also improve speed of detection. A highly sensitive microplate reader can deliver high quality data even with a limited amount of excitation flashes. Reducing the amount of flashes while keeping data quality (Z´) high, may provide a small saving in time for a single sample. However, when multiplied by 384 or 1536, and further by the amount of plates run in a day or for a campaign, the saving in time becomes significant. 


Servier´s screening facility


SERVIER’s HTS laboratory is equipped with several BMG LABTECH readers, including three generations of PHERAstars, a CLARIOstar and a NEPHELOstar. These instruments are currently used in primary and secondary HTS campaigns either as standalone instruments, coupled with stackers, or fully integrated into medium- and large size robotic platforms. Among them, the PHERAstars are typically dedicated for HTS applications, whereas the CLARIOstar and NEPHELOstar readers are most frequently used in assay development and post HTS activities. 


Miniaturization and downscaling: case studies


In this talk, Céline Legros, Project Manager of the Screening Assay Development Division at Servier, illustrates how BMG LABTECH readers have helped to optimize HTS screening campaigns through assay downscaling and miniaturization. This resulted in reagent and time savings while still delivering high-quality data to SERVIER’s drug discovery projects.

Three cases are discussed. The first is the successful downscaling of a HTRF® assay from the 384- to the 1536-well format. Miniaturization combined with “on-the-fly” detection (only one flash per well), and the further dilution of reagents, resulted in a significant cost reduction because of savings in reagents and time.

Improving the efficiency of a fluorescence quenching assay


The second example shows miniaturization of a fluorescence quenching assay from 384 to the 1536- well plate format. Also in this case, the detection of the fluorescence quenching assay by the reader delivered good Z´ values despite assay downscaling.

Finally, the third example shows the detection of a fast kinetic binding event measured on the CLARIOstar and the use of reagent injectors. For this assay a specific strategy was set up in order to cope with the fast kinetic and the amount of samples.

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