Adding precise nanoliter volume capabilities to liquid-handling automation for compound screening experimentation

Miniaturizing experimental sample volumes to the nanoliter volume range is one of the most economical ways to perform mid- and high-throughput compound screening experiments. Existing automation platforms for nanoliter fluid handling can be bulky, expensive, and require periodic calibration to provide consistent liquid dispensing. In addition, even with frequent calibration, significant instrument-to-instrument variation in low-volume dispensing can occur between different instrument platforms. Many of these issues can be addressed by the use of PocketTips. PocketTips are tips with a defined internal pocket designed to hold specific nanoliter volumes of compound dissolved in dimethylsulfoxide. Although the overall liquid-handling process with PocketTips uses the aspirate/dispense features of the specific liquid-handling device being used, the dispensed nanoliter volume is solely based on the dimensions of the pocket of the PocketTip and thus, the liquid-handling device itself need not have nanoliter dispensing capabilities. In this report, we demonstrate the performance of PocketTips on different automation platforms. In addition, we used a cell-based ?-lactamase reporter assay system to demonstrate that compound delivery by PocketTips compares favorably with a standard compound addition technique.