General HTS Assay Prerequisites

A certain level of automation is a prerequisite for an efficient HTS laboratory. Initially, higher productivity and freedom from performing repetitive tasks has been a major motivator to introduce laboratory automation [39]. However, as the equipment became more sophisticated, miniaturization of the assay volume and increased parallelization became important in order to reduce screening costs and to respond to increasing pressure on program cycle times. In general, the microplate has established itself as the major assay platform, starting with the 96-well plate initially used for diagnostics, and being the first major step towards parallelization. The pressure to reduce the costs of screening, combined with technical improvements in pipetting equipment and plate manufacture, has led to increased use of higher-density plates with 384 and 1536 wells. Despite the clear advantage in reagent savings, the use of smaller volumes is more demanding on the equipment used for liquid handling and detection. Thus, the reduction of assay volumes can lead to compromised assay parameters, especially due to stronger evaporation effects and changed surface-to-volume ratios.

Although the number of screened wells per unit time is an easily measurable and objective performance parameter, this does not directly define the desired output, which is the efficient identification of novel lead structures. As a consequence, further emphasis must be given to novel screening strategies and physiologically relevant screening approaches. Advanced screening approaches using cellular read-outs are one of means by which this goal may be achieved.

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