We describe a mass spectrometry (MS) analytical platform resulting from the novel integration of acoustic droplet ejection (ADE) technology, an open-port interface (OPI), and electrospray ionization (ESI) MS that creates a transformative system enabling high-speed sampling and label-free analysis. The ADE technology delivers nanoliter droplets in a touchless 20 manner with high speed, precision and accuracy; subsequent sample dilution within the OPI, in concert with the capabilities of modern ESI-MS, eliminates the laborious sample preparation and method development required in current approaches. This platform is applied to a variety of experiments, including high-throughput (HT) pharmacology screening, label-free in situ enzyme kinetics, in vitro and in vivo adsorption, distribution, metabolism, elimination, pharmacokinetic 25 (PK) and biomarker analysis, and HT parallel medicinal chemistry.One Sentence Summary: ADE-OPI-MS is a transformational analytical platform that increases mass spectrometry utility via sub-second speed and non-contact sampling.Mass is a fundamental molecular characteristic, and the advent of mass spectrometry (MS) to 30
High-throughput
experimentation (HTE) has emerged as an important
tool in drug discovery, providing a platform for preparing large compound
libraries and enabling swift reaction screening over wide-ranging
conditions. Recent advances in automated high-density, material-sparing
HTE have necessitated the development of rapid analytics with sensitivity
and resolution sufficient to identify products and/or assess reaction
performance in a timely and data-rich manner. Combination of an ultrathroughput
(UT) reader platform with Acoustic Droplet Ejection-Open Port Interface-Mass
Spectrometry (ADE-OPI-MS) provides the requisite speed and sensitivity.
Herein, we report the application of ADE-OPI-MS to HTE in the areas
of parallel medicinal chemistry and reaction screening.
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