High-throughput Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for Reaction Screening, Nano-scale synthesis and Bioanalysis

C.E. Credits: P.A.C.E. CE Florida CE


Current drug discovery workflows rely on the synthesis and bioactivity assessment of large compound libraries, both processes which heavily depend on high-throughput (HT) experimentation to be able to generate and test hundreds of thousands of molecules as fast as possible. Due to the speed and versatility required for such testing, mass spectrometry (MS) has recently become a relevant alternative for HT analysis. However, despite MS being inherently fast, in many cases it still requires sample work-up (e.g. SPE), separation (e.g. LC) or extensive dilution, steps that might decrease throughput or sensitivity. 

This talk describes a novel HT system capable of (i) reaction screening, (ii) nano-scale synthesis, and (iii) label-free biological assays. This platform is based on desorption electrospray ionization (DESI), a contactless ambient ionization method (i.e. ionization occurs in the ambient environment with little or no sample preparation) with high tolerance to complex matrices. This DESI-MS system allows for analysis of high-density arrays (up to 6,144 samples per plate) with throughputs better than 1 sample per second and using only 50 nL samples (pg-ng amounts of material).  The platform is fully automated, capable of 24/7 continuous operation, and it automatically records MS and MS/MS spectra. The utility of this system to screen several organic reactions and identify optimal conditions for particular transformations or to study reaction mechanisms has been demonstrated. Similarly, HT DESI-MS has been proven useful to perform biological analyses, such as the monitoring of enzymatic activity directly from complex matrices (e.g. buffers with high detergent or salt concentrations), removing completely the need for sample work-up without any detriment to the quantitative performance (RSDs < 10%, LODs typically in the nM range). The concepts, workflow and applications of this new HT technology will be all overviewed during this presentation. 

Learning Objectives:

1. Describe the method of desorption electrospray ionization (DESI) and why is it useful for the rapid and direct analysis of complex samples.

2. Outline the general workflow of a high-throughput analysis using automated DESI-MS.

3. Illustrate some applications of high-throughput DESI-MS for reaction screening, nano-scale synthesis and biological assays.

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