Analytical chemistry is an essential component of the drug discovery and development process delivering vital data and analysis such as compound identity and purity, structural conformation, target engagement, therapeutic activity and efficacy, and omics-related biomarkers. Despite this wealth of information, analytical methods and technologies can be antiquated, time-consuming, and often disconnected from research workflows. The Analytical Chemistry Core (ACC) at the National Center for Advancing Translational Sciences (NCATS) is developing automated workflows to overcome common bottlenecks in analytical sample preparation and data analysis procedures. This will improve overall speed, efficiency, and reproducibility. Current efforts have focused on an automated NMR sample preparation protocol for utilization in a variety of experimental and analysis platforms. While a few commercial solutions exist, the technology is far from ubiquitous and the majority of NMR sample preparation within labs is still performed manually. Through the standardization of procedural steps and the use of adaptable liquid handling platforms, we are not only able to accommodate the large quantity of routine 1D and 2D NMR samples but also prepare specialized samples for NMR-based fragment screening and quantitative NMR (qNMR) analysis. The sample preparation workflow involves (i) a Tecan FreedomEVO liquid handler to create a stock solution of each sample, (ii) a Sirius Automation OmniTasker to dispense aliquots of the stocks into deep-well 96-well plates, and (iii) a Sirius Automation MicroTasker for dilution to appropriate concentrations and subsequent transfer to NMR tubes. After data acquisition is complete for the requisite NMR experiments, automated processing and analysis is performed with various custom pipelines designed and implemented utilizing Mestrelab Mnova Gears (MGears). The resulting spectral data is stored and managed within Mnova DB where it can be accessed remotely through a web-based interface. This is a significant advancement in our goal of a fully automated NMR platform for the preparation, data acquisition, data processing, and analytical analysis of chemically diverse samples as part of drug discovery and development initiatives.
