Fast and sensitive flow-injection mass spectrometry metabolomics by analyzing sample-specific ion distributions

Nat Commun. 2020 Jun 24;11(1):3186. doi: 10.1038/s41467-020-17026-6.

Abstract

Mass spectrometry based metabolomics is a widely used approach in biomedical research. However, current methods coupling mass spectrometry with chromatography are time-consuming and not suitable for high-throughput analysis of thousands of samples. An alternative approach is flow-injection mass spectrometry (FI-MS) in which samples are directly injected to the ionization source. Here, we show that the sensitivity of Orbitrap FI-MS metabolomics methods is limited by ion competition effect. We describe an approach for overcoming this effect by analyzing the distribution of ion m/z values and computationally determining a series of optimal scan ranges. This enables reproducible detection of ~9,000 and ~10,000 m/z features in metabolomics and lipidomics analysis of serum samples, respectively, with a sample scan time of ~15 s and duty time of ~30 s; a ~50% increase versus current spectral-stitching FI-MS. This approach facilitates high-throughput metabolomics for a variety of applications, including biomarker discovery and functional genomics screens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Flow Injection Analysis / methods*
  • Flow Injection Analysis / standards
  • High-Throughput Screening Assays
  • Humans
  • Ions / chemistry
  • Lipidomics / methods
  • Mass Spectrometry / methods*
  • Mass Spectrometry / standards
  • Metabolomics / methods*
  • Metabolomics / standards
  • Serum / chemistry
  • Serum / metabolism

Substances

  • Ions