Label-free high-throughput screening via acoustic ejection mass spectrometry put into practice

Area of Science:

• Analytical Chemistry
• Biochemistry
• Drug Discovery

Background:

• Acoustic droplet ejection-open port interface-mass spectrometry (ADE-OPI-MS) is a novel label-free analytical technique suitable for high-throughput screening (HTS).
• The adoption of ADE-OPI-MS is hindered by a lack of data on its robustness for HTS campaigns involving millions of samples in complex matrices.
• This study addresses the need for demonstrating ADE-OPI-MS applicability in large-scale drug discovery efforts.

Purpose of the Study:

• To present the first fully automated HTS campaign using ADE-OPI-MS technology.
• To identify inhibitors of a metabolic enzyme from a library exceeding one million compounds.
• To showcase the assay development, validation, and adaptation for HTS requirements.

Main Methods:

• Development and validation of an assay for HTS using ADE-OPI-MS.
• Adaptation of the ADE-OPI-MS technique for a >1 million compound library screening.
• Refinement of capillary cleaning protocols to ensure robustness during automated HTS.

Main Results:

• Successful execution of a fully automated HTS campaign utilizing ADE-OPI-MS.
• Identification of metabolic enzyme inhibitors from a large compound library.
• Demonstration of the critical role of capillary cleaning in achieving HTS success.

Conclusions:

• The study unequivocally demonstrates the applicability of ADE-OPI-MS for HTS-based drug discovery.
• ADE-OPI-MS is a viable and robust technology for screening large compound libraries.
• The findings pave the way for broader adoption of ADE-OPI-MS in pharmaceutical research.