Related Experiment Video
Updated: Jun 2, 2025
08:40
Using a Cyclic Ion Mobility Spectrometer for Tandem Ion Mobility Experiments
Published on: January 20, 2022
4.2K
A Differential Ion Mobility Acoustic Ejection Mass Spectrometer System for Screening Isomerization-Mediating Enzyme
Biorxiv : the Preprint Server for Biology
|January 13, 2025
Summary
We developed DAEMS, a novel system combining differential ion mobility (DMS) and acoustic ejection mass spectrometry (AEMS), for ultra-high throughput screening. This method enables precise quantitation of metabolic isomers, crucial for drug discovery targeting pathogens.
Area of Science:
- Analytical Chemistry
- Biochemistry
- Metabolomics
Background:
- Metabolomics involves analyzing numerous structural isomers, necessitating advanced separation techniques.
- Current methods struggle with the high resolving power required for isomer separation.
- Isomerase enzymes are critical in metabolism and represent potential drug targets.
Purpose of the Study:
- To introduce and validate a novel high-throughput screening system, DAEMS, integrating differential ion mobility (DMS) with acoustic ejection mass spectrometry (AEMS).
- To demonstrate the capability of DAEMS for simultaneous quantitation of structural isomers in intermediary metabolism.
- To showcase DAEMS as a powerful tool for drug discovery by targeting pathogen-specific isomerases.
Main Methods:
- Development of the DAEMS system combining DMS and AEMS for ultra-high throughput sample introduction.
- Measurement of resolving powers for phosphoglycerate and citrate/isocitrate isomeric pairs.
- Comparison of DAEMS performance against a luminescence assay for pathogen-specific phosphoglycerate mutase (iPGM).
- Demonstration of DAEMS with other isomerases like chorismate mutase and triosephosphate isomerase.
Main Results:
- Achieved record ion mobility resolving powers of 1588 and 1948 for key metabolic isomer pairs.
- Successfully separated substrates and products of multiple isomerases at speeds compatible with high-throughput screening.
- Demonstrated simultaneous quantitation of structural isomers without internal standards.
- Validated DAEMS performance against a luminescence assay for iPGM.
Conclusions:
- DAEMS represents a significant advancement in mass spectrometry for high-throughput screening of metabolic isomers.
- The system offers unprecedented resolving power for complex metabolomic samples.
- DAEMS provides a versatile platform for drug discovery targeting isomerase enzymes in various diseases.
More Related Videos
08:56Detection of Regulated Ergot Alkaloids in Food Matrices by Liquid Chromatography-Trapped Ion Mobility Spectrometry-Time-of-Flight Mass Spectrometry
Published on: November 22, 2024
556
10:17High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry
Published on: April 23, 2019
9.6K
Related Concept Videos
01:12Electrospray Ionization (ESI) Mass Spectrometry
722
Higher molecular weight biomolecules are nonvolatile compounds that may decompose before ionizing or vaporizing during mass analysis with conventional electron impact ionization methods. Accordingly, electrospray ionization (ESI) is the favored method for vaporizing and ionizing biomolecules as it circumvents rapid fragmentation and enables the recording of mass signals for the entire biomolecule.
ESI utilizes electrical energy to transfer ions from the liquid phase of the sample into the...
ESI utilizes electrical energy to transfer ions from the liquid phase of the sample into the...
722
01:16Mass Spectrometers
5.1K
This lesson details the instrumentation of a mass spectrometer—a physical instrument to perform mass spectrometry on analyte molecules and record the characteristic mass spectra. This is achieved via three chief functions:
5.1K
01:19Mass Analyzers: Common Types
554
The quadrupole mass analyzer consists of four cylindrical metal rods arranged in a diamond carrying a DC voltage and a radio-frequency AC voltage. The motion of ions through the quadrupole depends on the field strength, causing only ions of a certain m/z to resonate successfully and strike the detector at a given field strength. Though the transmission rate for these analyzers is high, the exact elemental composition of the sample is not determined because of low resolution; however, they are...
554
01:21Chemical Ionization (CI) Mass Spectrometry
680
The molecular ion peak of a molecule in the mass spectrum provides vital information for molecular identification. However, conventional electron impact ionization can lead to the rapid dissociation of some molecular ions before they reach the detector. A milder ionization method is required to increase the lifetime of such ionized analyte molecules. Chemical ionization (CI) is a gas-phase protonation reaction useful for mass-analyzing analyte molecules that are easily protonated to yield the...
680
01:08Matrix-Assisted Laser Desorption Ionization (MALDI)
270
Matrix-assisted laser desorption ionization (MALDI) is a powerful analytical technique used in mass spectrometry. It enables the identification and characterization of various biomolecules, including proteins, peptides, nucleic acids, and carbohydrates. MALDI spectrometry is widely employed in biological and medical research, as well as in fields like pharmacology and biochemistry.
The analyte of interest, a biomolecule or a mixture of biomolecules, is mixed with a suitable matrix material. The...
The analyte of interest, a biomolecule or a mixture of biomolecules, is mixed with a suitable matrix material. The...
270
01:09Ion-Exchange Chromatography
348
Ion-exchange chromatography, or IEC, is a technique for separating ions based on their affinity for the stationary phase. The stationary phase is a cross-linked polymer resin with covalently attached ionic functional groups. The functional groups can be either positively charged (cation exchangers) or negatively charged (anion exchangers). A cation exchanger consists of a polymeric anion and active cations, while an anion exchanger is a polymeric cation with active anions. The choice of...
348