Nanoflow low pressure high peak capacity single dimension LC-MS/MS platform for high-throughput, in-depth analysis of mammalian proteomes

Anal Chem. 2012 Jun 5;84(11):5133-9. doi: 10.1021/ac2031404. Epub 2012 May 10.

Abstract

The use of narrow bore LC capillaries operated at ultralow flow rates coupled with mass spectrometry provides a desirable convergence of figures of merit to support high-performance LC-MS/MS analysis. This configuration provides a viable means to achieve in-depth protein sequence coverage while maintaining a high rate of data production. Here we explore potential performance improvements afforded by use of 25 μm × 100 cm columns fabricated with 5 μm diameter reversed phase particles and integrated electrospray emitter tips. These columns achieve a separation peak capacity of ≈750 in a 600-min gradient, with average chromatographic peak widths of less than 1 min. At room temperature, a pressure drop of only ≈1500 psi is sufficient to maintain an effluent flow rate of ≤10 nL/min. Using mouse embryonic stem cells as a model for complex mammalian proteomes, we reproducibly identify over 4000 proteins across duplicate 600 min LC-MS/MS analyses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromatography, Liquid / instrumentation
  • Chromatography, Liquid / methods*
  • Embryonic Stem Cells / chemistry*
  • High-Throughput Screening Assays
  • Mice
  • Molecular Sequence Data
  • Pressure
  • Proteome / analysis*
  • Reproducibility of Results
  • Tandem Mass Spectrometry / instrumentation
  • Tandem Mass Spectrometry / methods*
  • Temperature

Substances

  • Proteome