(1287-D) FluidCore: An Automated Purification Platform for a Centralized Sample Purification and Processing Workflow

Abstract: The concepts of throughput and cycle time are of great importance in drug discovery and development. As such, translational scientists aim to increase experimental capacity and reduce the timeline for the advancement of therapeutics. This is essential to expedite the delivery of treatments to patients. The development of an efficient method for the transfer of compounds from Medicinal Chemistry to Compound Management enables a faster turnaround between small molecule synthesis and biological assays. To facilitate this, the NCATS Analytical Chemistry Core (ACC) created a centralized sample purification and processing workflow where internally synthesized compounds progress from submission of a crude reaction mixture to storage of the purified final compound in 5 days. By having the ACC conduct the majority of sample purifications, medicinal chemists are afforded more time to focus on compound synthesis thus establishing a more effective workflow. To ensure a high sample throughput, standardized purification methods were developed to consistently accommodate diverse chemotypes. While this workflow has been highly successful in increasing productivity, purification remains a significant bottleneck and the involvement of manual steps affects efficiency. Current efforts are focused on improving our sample purification and processing pipeline through the development of an automated purification platform, which can operate as a stand-alone system or an integrated module within an automated chemistry laboratory. The design of this innovative system, called FluidCore, is centered around a custom Tecan Evo liquid handler as the sample injection and fraction collection bed outfitted with two independent robotic arms for parallel operations. A Waters analytical UPLC-MS and an Autopurification preparative HPLC-MS system have been incorporated to create a single automated platform. The integration of an SPT Labtech Lab2Lab system enables pneumatic transport of crude samples to the UPLC-MS for analytical analysis. The resultant spectral data will be processed by Virscidian Analytical Studio software to generate work lists of optimized methods for use in preparative purification. Automated purity analysis of the collected fractions to determine consolidation protocols with simultaneous purification of the subsequent sample will result in a significant time savings. Data storage and management will be handled by our custom LIMS with a web-based interface allowing for convenient data retrieval and review.