Matrix‐free high‐resolution imaging mass spectrometry with high‐energy ion projectiles

Abstract

The importance of imaging mass spectrometry (MS) for visualizing the spatial distribution of molecular species in biological tissues and cells is growing. We have developed a new system for imaging MS using MeV ion beams, termed MeV-secondary ion mass spectrometry (MeV-SIMS) here, and demonstrated more than 1000-fold increase in molecular ion yield from a peptide sample (1154 Da), compared to keV ion irradiation. This significant enhancement of the molecular ion yield is attributed to electronic excitation induced in the near-surface region by the impact of high energy ions. In addition, the secondary ion efficiency for biologically important compounds (>1 kDa) increased to more than 10(10) cm(-2), demonstrating that the current technique could, in principle, achieve micrometer lateral resolution. In addition to MeV-SIMS, peptide compounds were also analyzed with cluster-SIMS and the results indicated that in the former method the molecular ion yields increased substantially compared to the latter. To assess the capability of MeV-SIMS to acquire heavy-ion images, we have prepared a micropatterned peptide surface and successfully obtained mass spectrometric imaging of the deprotonated peptides (m/z 1153) without any matrix enhancement. The results obtained in this study indicate that the MeV-SIMS technique can be a powerful tool for high-resolution imaging in the mass range from 100 to over 1000 Da.

Submicron mass spectrometry imaging of single cells by combined use of mega electron volt time-of-flight secondary ion mass spectrometry and scanning transmission ion microscopy

“…16 This approach decouples effective lateral resolution from desorption and ionization spot size, so broad primary beam can be used. It has been recently demonstrated 17,18 that the use of MeV primary ions, instead of the keV energy ions that are used in conventional SIMS, significantly suppressed fragmentation and simultaneously enhanced the secondary ion yield, especially for higher mass molecules (100-1000 Da). An increase in yield of more than three orders of magnitude was demonstrated using peptide samples, making MeV TOF-SIMS a good candidate to perform molecular imaging at the submicron level.…”

A Processing Technique for Cell Surfaces Using Gas Cluster Ions for Imaging Mass Spectrometry

“…11) Researchers have long known that secondary ion yields from biomolecular samples increase using a primary ion beam in the MeV energy range, and we have investigated imaging mass spectrometry of biological samples using MeV ion beams. 12) In this experiment, for imaging mass spectrometry, we used a 6 MeV Cu 4ῌ ion beam provided by Kyoto University's 1.7 MV tandem accelerator. The sample holder was mounted on a piezoelectric stage (M-2689, MESS-TEK, Saitama, Japan), and the sample was scanned over a square area of 100 mm῎100 mm with a constant step size.…”

Inorganic mass spectrometry as a tool for characterisation at the nanoscale

“…On the other hand, although applications have been reported for imaging of biotissues using SIMS and SNMS, it should be stressed that the difficulties to desorb big proteins as well as the low sensitivity achieved are two important limitations of such MS techniques. The recent development of a new system for imaging MS using megaelectronvolt ion beams (MeV-SIMS) has demonstrated a more than 1,000-fold increase in molecular ion yield from a peptide sample (1,154 Da), compared with kiloelectronvolt ion irradiation [86]. This significant enhancement of the molecular ion yield is attributed to electronic excitation induced in the nearsurface region by the impact of high-energy ions, and these results indicate that the MeV-SIMS technique can be a powerful tool for high-resolution imaging in the mass range from 100 Da to over 1,000 Da.…”