Contact-free centrifuged-based microplate washer for UCSF Small Molecule Discovery Center core facility

About This Grant

Project summary/abstract Academic drug discovery centers (ADDCs) have emerged as a key resource and core facility for two distinct and interrelated pursuits: (1) the practice of chemical biology, with the discovery of chemical tools and probes to dissect biological mechanisms, and (2) the identification of small molecule ‘hits’ against molecular targets or cellular phenotypes as starting points for drug discovery. The Small Molecule Discovery Center at UCSF is one of the pioneering ADDCs and has deep expertise in diverse state-of-the-art hit-identification strategies, from biophysical fragment-based drug discovery (FBDD) to complex microscopy-based screens. Among the major advances in the industrialization of the drug discovery process over the past few decades is miniaturization of assay volume, from 96-well to 384-well to 1536-well plate formats. 1536-well plates incorporate assay volumes on the order of 2-microliters, offering much faster screening – leading to increased chemical diversity screened – as well as reduced consumption of precious or expensive assay components. One of the greatest challenges in running multi-step assays in 1536-well plates is the addition of liquids and their removal—usually by aspiration. The quality of liquid exchanges dramatically affects the performance of multi- component and multi-step screening assays. The development and commercialization of a centrifugation-based approach to liquid removal from 1536-well plates allows the running of high throughput cell-based and molecular- based drug screening assays. The Small Molecule Discovery Center at UCSF currently lacks the ability to evacuate the contents of 1536-well plates-which limits us to 384-well formats for assays requiring the evacuation and exchange of liquids. We are requesting a BlueWasher for our integrated robotic automation screening platform, which incorporates roboticized plate handling, liquid handing, automated incubation, and imaging systems for both biochemical- and cell-based assay formats. We are also requesting funds for an integrated robotic arm and plate hotels (BlueBench) to run multi-plate high throughput screens in batch mode. The increase in scale and efficiency that the incorporation of this equipment will provide to the Small Molecule Discovery Center core facility in moving from 384-well to 1536-well format will significantly increase the impact of Center’s work for UCSF PIs and project teams. Both the quantitative and qualitative aspects of increased the chemical diversity explored and the robustness and reproducibility of the assays will contribute to increased productivity for the Center in achieving its research services and shared-use goals.