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

Authors:
Quentin P Vanbellingen Nicolas Elie Michael J Eller Serge Della-Negra David Touboul Alain Brunelle

Rapid Commun Mass Spectrom 2015 Jul;29(13):1187-95

Institut de Chimie des Substances Naturelles, CNRS-ICSN UPR2301, Université Paris-Sud, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033000PMC
http://dx.doi.org/10.1002/rcm.7210DOI Listing
July 2015

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