Forty‐Year Evolution of High‐Throughput Mass Spectrometry

Covey, Thomas R.

doi:10.1002/9781119678496.ch1

High‐Throughput Mass Spectrometry in Drug Discovery 2023

DOI: 10.1002/9781119678496.ch1

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Forty‐Year Evolution of High‐Throughput Mass Spectrometry

Thomas R. Covey

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2024

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Cited by 1 publication

References 188 publications

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A Differential Ion Mobility Acoustic Ejection Mass Spectrometer System for Screening Isomerization-Mediating Enzyme Drug Targets

Bazargan,

Dranchak,

Liu

et al. 2024

Preprint

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We report the first implementation of ion mobility mass spectrometry combined with an ultra-high throughput sample intro-duction technology for high throughput screening (HTS). The system integrates differential ion mobility (DMS) with acoustic ejection mass spectrometry (AEMS), termed DAEMS, enabling the simultaneous quantitation of structural isomers that are the substrates and products of isomerase mediated reactions in intermediary metabolism. We demonstrate this potential by comparing DAEMS to a luminescence assay for the isoform of phosphoglycerate mutase (iPGM) distinctively present in pathogens offering an opportunity as a drug target for a variety of microbial and parasite borne diseases. The metabolome consists of many structural isomers that require for separation a mobility resolving power of more than 300. Resolving powers measured in collision cross section space of 1588 and 1948 for 2- and 3-phosphoglycerate and the citrate/isocitrate isomeric pairs respectively are shown. These are the highest reported ion mobility resolving powers for molecules from the metabolome reported to date. The potential for DAEMS as a generalized screening tool is demonstrated with the separation of the substrates and products of two additional isomerases that present as potential therapeutic targets, chorismate mutase and triosephosphate isomerase. The separations are achieved at speeds compatible with the sample introduction rates of AEMS providing sufficient data points to integrate the peaks for quantitation without the use of internal standards. DMS hyphenated with acoustic sample ejection MS provides a unique solution to high throughput mass spectrometry applications where isomer and other types of separations are required.

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A Differential Ion Mobility Acoustic Ejection Mass Spectrometer System for Screening Isomerization-Mediating Enzyme Drug Targets

Bazargan,

Dranchak,

Liu

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

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Forty‐Year Evolution of High‐Throughput Mass Spectrometry

Cited by 1 publication

References 188 publications

A Differential Ion Mobility Acoustic Ejection Mass Spectrometer System for Screening Isomerization-Mediating Enzyme Drug Targets

A Differential Ion Mobility Acoustic Ejection Mass Spectrometer System for Screening Isomerization-Mediating Enzyme Drug Targets

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