Towards analytically useful two-dimensional Fourier transform ion cyclotron resonance mass spectrometry

Abstract

Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) achieves high resolution and mass accuracy, allowing the identification of the raw chemical formulae of ions in complex samples. Using ion isolation and fragmentation (MS/MS), we can obtain more structural information, but MS/MS is time-and sampleconsuming because each ion must be isolated before fragmentation. In 1987, Pfändler et al. proposed an experiment for 2D FT-ICR MS in order to fragment ions without isolating them and to visualize the fragmentations of complex samples in a single 2D mass spectrum, like 2D NMR spectroscopy. Because of limitations of electronics and computers, few studies have been conducted with this technique. The improvement of modern computers and the use of digital electronics for FT-ICR hardware now make it possible to acquire 2D mass spectra over a broad mass range. The original experiments used in-cell collisioninduced dissociation, which caused a loss of resolution. Gas-free fragmentation modes such as infrared multiphoton dissociation and electron capture dissociation allow one to measure high-resolution 2D mass spectra. Consequently, there is renewed interest to develop 2D FT-ICR MS into an efficient analytical method. Improvements introduced in 2D NMR spectroscopy can also be transposed to 2D FT-ICR MS. We describe the history of 2D FT-ICR MS, introduce recent improvements, and present analytical applications to map the fragmentation of peptides. Finally, we provide a glossary which defines a few keywords for the 2D FT-ICR MS field.

Differentiating Fragmentation Pathways of Cholesterol by Two-Dimensional Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

“…In 2D FT-ICR MS, correlation between precursor and fragment ions is achieved through ion radius modulation of the precursor ions during the encoding sequence (see Scheme 1) according to the cyclotron frequency of the precursor ions [7]. Unlike standard MS/MS, the fragmentation patterns in 2D FT-ICR MS are measured in a parallel manner.…”

“…Scheme 2 shows a diagram of a 2D mass spectrum and how to interpret it. Significant lines in a 2D mass spectrum include the autocorrelation line, which shows the m/z of all the precursors, horizontal fragment ion scans, which show the fragmentation pattern of a given precursor ion, and vertical scans, which show all the precursors of a given fragment ion [7].…”

2D FT-ICR MS of Calmodulin: A Top-Down and Bottom-Up Approach

“…These are the so-called neutralloss lines, and show the loss of neutrals by precursor ions. Vertical precursor ion spectra and neutral-loss spectra can be easily extracted from 2D maps, constituting information readily available only in 2D MS [13].…”

“…With recent improvements in computer technology and the improvements in ion fragmentation techniques for FT-ICR MS, an interest to develop 2D FT-ICR MS into an efficient analytical method was renewed [13]. The original 2D MS experiments were conducted using in-cell collisional dissociation [8], with a consistent loss of resolution resulting from fragmentation at a high orbital radius leading to magnetron expansion of the fragment cloud and ion loss.…”

Efficient denoising algorithms for large experimental datasets and their applications in Fourier transform ion cyclotron resonance mass spectrometry

“…Only now, with the increased power of computers, can this technology prove its use in particular in proteomics or metabolomics (see ref. 37 for a recent review). Twodimensional FT-ICR MS maps the fragmentation patterns of ions in complex samples without prior ion isolation and affords important structural information.…”