An Automated Approach to Efficiently Reformat a Large Collection of Compounds

Abstract

Large-scale screening of small organic compounds has become a standard and essential practice in the early discovery of chemical entities with potential therapeutic use. To effectively support high-throughput screening campaigns, compound collections have to be in suitable formats, which requires a process known as compound reformatting. Here we report our approach to reformat the newly-established chemical repository of a large-scale screening facility at St. Jude Children’s Research Hospital, which comprises more than half a million compounds, mostly from commercial sources. We highlight the timeline for a reformatting process, the importance of standardizing the operational procedures, and the advantages and disadvantages of using automation. The end result of our reformatting process is the concurrent generation of copies for long-term storage, screening, and “cherry-picking”; all of which facilitate compound management and high-throughput screening.

Development of a fully automated platform for agar-based measurement of viable bacterial growth

“…The user writes methods which link together operations at different stations to perform the desired assay. Third party vendors offer similar software packages, such as HighRes Biosolutions Cellario (Beverly, MA) [10] or Thermo Scientific Momentum (Waltham, MA); [11] however, having full control to modify the scheduling architecture and instrument control source code provides an extra degree of freedom when building this and other novel workflows.…”

A protocol for high-throughput screening of histone lysine demethylase 4 inhibitors using TR-FRET assay

“… For compounds in powders, dissolve them in DMSO to prepare stock solutions at 10 mM. For primary single dose screen, compound stock solutions in DMSO are pre-arrayed in barcoded 384-well compound plates (Corning 3656) ( Cui et al., 2011 ; Lin et al., 2021 ) at 10 μL/well in areas of columns 3-to-12 and 15-to-24; wells in columns 1, 2, 13 and 14 are empty ( Figure 1 A).

Figure 1 Plate layouts for primary single dose screen and for dose response test (A) Plate layout for primary single dose screen.

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Design and operation of an automated high-throughput monoclonal antibody facility

“…Subsequently, automation has been applied to a vast array of different scientific applications. Some of these applications are on a significantly large scale, such as the fully automated liquid handling 'barns' that pharmaceutical companies use to manage the millions of compounds they test and synthesise every year (Cui et al 2011;Schmitt et al 2010), or the automated liquid handling with integrated testing and detection instrumentation for ultra high throughput screening of those compounds (Michael et al 2008). On the other end of the scale is the relatively low throughput but fully automated in vivo sample collection system used in pharmacokinetic and other pre-clinical studies (Clark et al 2011;Aryal et al 2012).…”