The screening of large compound libraries to identify hit compounds involves a number of laborious liquid-handling stages. Plate preparation for compound screening and bioassays involves sample transfer from compound storage plates or vials, serial dilutions, assay plate preparation, and replication. These processes require repetitive, accurate, and time-consuming pipetting as well as meticulous sample labeling and management.
With an escalating number of compounds, small molecules or fragments, and RNAi libraries, automated liquid handling has become a fundamental requirement for high-throughput screening throughout the drug discovery industry.
Automated liquid-handling instruments such as those in the mosquito® product range (TTP LabTech) allow rapid, accurate, and reproducible compound dispensing and assay plate setup, reducing the turn-around time from compound synthesis to assay-ready plates.
In addition, the ability to miniaturize assays using nanoliter liquid-handling instruments reduces the use of expensive reagents, helping to preserve the often limited quantities of valuable compounds or samples.
Following a primary screen it is common for only a small percentage (1–3%) of compounds to be identified as active, requiring further study with secondary screening. At this secondary screening stage, individual samples need to be cherry picked from stock compound plates and new plate formats need to be set up for further biological assays.
Traditional manual or semi-automated methods are unable to deliver the speed or throughput required for the efficient removal of hit samples from large numbers of compound storage or “mother” plates.
In addition, instruments used for plate replication are often unable to cherry pick individual samples from a plate and can be limited for transferring samples between plate sizes (i.e., 384 well plates to 96 well plates or vice versa). Therefore the use of a dedicated automated liquid handler capable of rapidly cherry picking individual hit compounds as well as plate reformatting can significantly enhance the compound screening workflow.
Incorporation of suitable tracking software and 2-D barcodes on the screening platform enable efficient sample tracking and recording, thereby eliminating the potential for manual data input error.