Edgar Specker

Die Aufgabe ist die Anfertigung von Screening Platten für die Screening Unit und die Bereitstellung von Hitpicking Platten für die konzentrationsabhängige Validierung der Hits. Es führt die Reinheitskontrolle per LC-MS durch und hilft dem Nutzer bei der Priorisierung der Hitlisten. Die Bibliothek enthält 80.000 Substanzen, davon sind 40.000 kommerziell erworben, 10.000 aus der Akadmie eingesammelt und weitere 30.0000 Substanzen aus einer Naturstoffbibliothek abgeleitet.

The Compound Management was initiated in 2010 to facilitate the access for the academic community to a state-of-the-art compound management facility and was upgraded over the last decade. Initially, it started as an integral part of the Screening Unit and the Medicinal Chemistry group before it became an independent Core Faciltiy in 01/2020. At first, a REMP storage system hosted a compound library of 37.000 compound. Due to the higher demand of the constantly growing commercial and academic libraries an upgrade to the automated KIWI storage system was required with a larger capacity of 110.000 compounds. Today, it manages a diversity library of 43.000 compounds and a fragment library of 4000 compounds purchased from different commercial vendors. Over the years a academic library of about 8000 compounds was collected from a huge variety of academic chemistry groups together with 20.000 natural product derived compounds from Analyticon Discovery GmbH. In 2019, it moved next to the laboratories of the EU-OPENSCREEN ERIC where both infrastructures will benefit from each other using theirs synergies while maintaining their different strategic and scientific operations. The ultimate goals of the Core Facility is the provision of screening plates for the primary screening at the Screening Unit, the preparation of hitpicking plates in order to conduct concentration-dependent validations of primary hits, the QC-controls of these hits and the support of users to prioritize their hit lists. 

The Compound Management manages the central compound collection of the FMP using a Liconic-KIWI storage systems combined with a FreedomEvo pipetting system (Tecan).  The collection is extended by donations of academic chemists, 4000 biology-annotated compounds (Selleck library) and a natural product collection of 20.000 cpds from AnalytiCon Discovery which assembles a smart library collections of 75.000 compounds ready to screen. The automated storage system provides a capacity of about 110.000 cpds with a total number of 220.000 tubes stored at -20° C. The Compound Management actively collects compound collections from academic chemists and currently holds about 8.000 unique donated cpds.
The collection of commercially available compounds has been financed by the FMP in cooperation with the Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch (MDC), the Helmholtz-Zentrum für Infektionsforschung (HZI), and the University of Konstanz. The design and selection of compounds is based on a maximum common substructure analysis of the World Drug Index (WDI).
The project-oriented chemical synthesis and optimization of small molecules is supported by medicinal chemists, drug modellers and structural biologists at the Institute on the basis of individual cooperations.

The KIWI Store (LiCONiC AG) offer fully automated storage and retrieval of compounds with a total number of 220.000 tubes organized in 96-tube racks. The tubes contain 200 µl DMSO solutions for each compound at concentrations of 10 mM in DMSO. Individual tubes are identified by a 2D-barcode at bottom and the racks by 1D-barcodes. The provided technology enables individual sample access and manipulation by simply pushing the tube through the source rack to an empty destination rack.The automated selection of individual tubes in the -20°C freezer also o ffers the benefits of minimizing freeze/thaw cycles, library cleaning and compression, and avoiding oxidation and water uptake. This is especially important for the unique compounds donated from academic chemists and protects the long term storage. Furthermore this technology enables  for generation of target specific sub libraries .The software tracks the samples at all stages and allows them to be chosen for retrieval from imported sample lists or queries. After samples are picked in the -20 °C environment they are delivered in delivery racks for further processing. The delivery rack is returned to the KIWI Store and the software automatically updates the location of the rack inside the store. 

Dr. Martin Neuenschwander (Screening Unit) has programmed a visual basic script allowing the communication between the relational database of the KIWI Store and the file-based system of the Freedom EVO liquid handling workstation, creating a fully automated liquid handling and sample management platform. 
The task of hit picking from 96 tube racks to reformat to the 384 screening plates runs on a routine basis. Furthermore work lists for desolvation of solid compounds in glass vials automatically drive the liquid handling module to transfer the calculated DMSO volumes in order to create a 10 mM concentration. Later, the solution in transferred to 96 tube racks and deliveres in a automated fashion to the KIWI Store.