PROJECT SUMMARY Support is requested for the purchase of an Echo 650 acoustic liquid handler with Access workstation to replace the Janus NanoHead, the existing and aging low volume liquid handler purchased in 2008 within the Molecular Screening and Protein Expression Facility at The Wistar Institute in Philadelphia. This instrument upgrade is critical for the Facility to continue to provide state-of-the-art support for the development of robust, high-throughput biochemical and cell-based assays required for drug discovery. Indeed, Wistar has made a commitment to academic drug discovery by recruiting its first medicinal chemist, Dr. Joseph M. Salvino, who is the Principal Investigator of this application. Dr. Salvino and nine other major and minor users who hold a combined 17 unique NIH grants (R01/R35/R61/P01/UM1/U54/DP2) have requested the Echo 650 with Access workstation to develop improved biochemical and cell-based assays that generate better data which will enable more informed decision making regarding novel structure-activity relationships. There are currently no similar instruments that are accessible to Wistar investigators. The Echo 650 is a highly accurate, low volume, non-contact liquid handler that moves nanoliter volumes of liquid from one microplate to another using sound waves. Using direct dilution, it can determine the potencies of small molecules with better precision as opposed to traditional serial dilution. The miniaturization of such assays also reduces research costs. The Access workstation is the stacker unit integrated with the Echo 650 which allows for automated plate handling necessary for high-throughput screening and hit picking of active compounds. Because there is no contact between source plates, this technology eliminates compound carry-over and protects the integrity of existing compounds in storage plates. The preliminary data described in this application demonstrate that the Echo 650 is a superior technology to our existing Janus Nanohead. In addition, we also show that we have the necessary infrastructure to miniaturize our assays to 1536-well format. This instrument will significantly upgrade our capabilities regarding assay miniaturization while simultaneously increasing the quality of our data. The unit will be housed in the Molecular Screening and Protein Expression Facility, overseen by Dr. Salvino and managed by Mr. Joel Cassel. Both Dr. Salvino and Mr. Cassel have over 40 years aggregate experience in the pharmaceutical industry. The facility is well regarded and cumulatively ranked with a score of “Exceptional” at the 2018 NIH/NCI Cancer Center support Grant (CCSG) review. We are seeking to upgrade our existing low volume liquid handling technology to a superior state of the art, non-contact nanoliter liquid handling technology in the Echo 650 with Access workstation in order to optimally support the academic drug discovery initiatives of The Wistar Institute.