Time-of-flight secondary ion mass spectrometry imaging of biological samples with delayed extraction for high mass and high spatial resolutions

Rapid Commun Mass Spectrom. 2015 Jul 15;29(13):1187-95. doi: 10.1002/rcm.7210.

Abstract

Rationale: In Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS), pulsed and focused primary ion beams enable mass spectrometry imaging, a method which is particularly useful to map various small molecules such as lipids at the surface of biological samples. When using TOF-SIMS instruments, the focusing modes of the primary ion beam delivered by liquid metal ion guns can provide either a mass resolution of several thousand or a sub-µm lateral resolution, but the combination of both is generally not possible.

Methods: With a TOF-SIMS setup, a delayed extraction applied to secondary ions has been studied extensively on rat cerebellum sections in order to compensate for the effect of long primary ion bunches.

Results: The use of a delayed extraction has been proven to be an efficient solution leading to unique features, i.e. a mass resolution up to 10000 at m/z 385.4 combined with a lateral resolution of about 400 nm. Simulations of ion trajectories confirm the experimental determination of optimal delayed extraction and allow understanding of the behavior of ions as a function of their mass-to-charge ratio.

Conclusions: Although the use of a delayed extraction has been well known for many years and is very popular in MALDI, it is much less used in TOF-SIMS. Its full characterization now enables secondary ion images to be recorded in a single run with a submicron spatial resolution and with a mass resolution of several thousand. This improvement is very useful when analyzing lipids on tissue sections, or rare, precious, or very small size samples.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebellum*
  • Image Processing, Computer-Assisted / methods
  • Rats
  • Spectrometry, Mass, Secondary Ion / instrumentation
  • Spectrometry, Mass, Secondary Ion / methods*