Screening and robotics

Saunders, K. Automation and robotics in ADME screening. Drug Discov. Today Technol. 2004, 1, 373-380. 

Ciossek, T, Julius, H., Wieland, H., Maier, T. and Beckers, T. (2008) A homogeneous cellular histone deacetylase assay suitable for compound profiling and robotic screening. Analytical Biochemistry,... 

Microbatch can be performed either manually or automatically (Chayen et ah, 1992). It is the simplest crystallization method and therefore can be easily performed in high-throughput trials. Current robots can dispense microbatch trials down to 1 nl volumes. Depending on the type of oils used to cover the trials, this technique can be harnessed for both screening and optimization experiments. 

Modern drug discovery approaches involve HTS, where, applying full automation and robotics, hundreds of molecules can be screened using several assays within a short time, and with very little amounts of compounds. In order to incorporate natural products in the modern HTS programmes, a natural product library (a collection of dereplicated natural products) needs to be built. Dereplication is the process by which one can eliminate recurrence or re-isolation of same or similar compounds from various extracts. A number of hyphenated techniques are used for dereplication, e.g. LC-PDA (liquid chromatography-photo-diode-array detector). 

The micro-mixer is supplied continuously with two carrier fluids, either two immiscible liquids or a gas and a liquid. During screening, pulses of the dissolved catalyst to be screened and the substrate are injected simultaneously by a pipetting robot. The pulses are then mixed in a micro-mixer and form short defined reacting segments that move along the tubular reactor. 

The operator s attention is still necessary during continuous screening modes, and he or she can be alerted via email or telephone of problems arising during off hours. Cooperation between assay development scientists and robotic engineers is required for reagent preparation and trouble shooting. Some of the operational issues of fully automated robotic systems include ... 

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