Just-in-Time Compound Pooling Increases Primary Screening Capacity without Compromising Screening Quality.

Area of Science:

• Drug Discovery
• Chemical Biology
• High-Throughput Screening

Background:

• Compound pooling in primary screening has historically faced challenges, often due to issues with long-term storage of compound mixtures.
• Traditional high-throughput screening (HTS) typically employs a one-compound-per-well approach, limiting screening capacity as compound libraries expand.

Purpose of the Study:

• To develop an innovative compound pooling strategy to enhance primary screening capacity.
• To address limitations associated with long-term storage of multiplexed compound libraries.
• To maintain data quality while increasing the efficiency of screening campaigns.

Main Methods:

• Development of a novel
• just-in-time
• compound pooling technique.
• Utilizing acoustic dispensing for precise compound addition directly into assay wells immediately before the assay.
• Implementation and evaluation of the method in pilot studies and a large-scale screen of over 2 million compounds.

Main Results:

• The
• just-in-time
• pooling method effectively doubles the capacity of primary screening.
• Pilot studies and a large-scale screen demonstrated the method's feasibility and effectiveness.
• No significant reduction in the ability to detect screening hits was observed for many targets.

Conclusions:

• The novel
• just-in-time
• compound pooling strategy offers a viable solution to increase screening capacity.
• This method circumvents storage-related issues inherent in traditional compound pooling.
• The approach holds promise for enhancing the efficiency of drug discovery efforts by enabling larger-scale primary screens.