Development of the NCATS automated sample preparation workflow for NMR-based analysis platforms

Authors

• K Patra
• H Tu
• M Levine*

Abstract

Analytical chemistry is crucial for drug discovery, providing vital data like compound identity, purity, structure, target engagement, therapeutic activity, efficacy, and biomarkers. However, current methods are outdated, time-consuming, and detached from research workflows. To overcome these challenges, the Analytical Chemistry Core (ACC) at NCATS is developing automated workflows to enhance speed, efficiency, and reproducibility. The ACC focuses on automating NMR sample preparation, standardizing steps, and utilizing adaptable liquid handling platforms. This enables handling routine 1D and 2D NMR samples and specialized samples for NMR-based fragment screening and quantitative NMR analysis. The sample preparation workflow involves (i) stamping of stock solutions into 96-deep well plates, as well as 96-well LCMS plates for quality control handling a Beckman Coulter Biomek i7, (ii) dilution of the deep-well plates to desired concentration with desired deuterated solvent using a Beckman Coulter Biomek FXP, and (iii) sample transfer from plates to NMR tubes using a Sirius Automation MicroTasker. Customized protocols are being developed for this process to accommodate a variety of NMR analysis requirements. After data acquisition is complete, automated processing and analysis are performed through custom pipelines in Mestrelab Mnova Gears (MGears) software platform. The resulting spectral data is managed within Mnova DB, which can be accessed remotely through a web-based interface. The process thus far marks 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.

Scientific Focus Area: Research Support Services

This page was last updated on Monday, September 25, 2023