title: Time-of-flight secondary ion mass spectrometry imaging of biological samples with delayed extraction for high mass and high spatial resolutions.
abstract: BACKGROUND
  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.
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS-ICSN UPR2301, Université Paris-Sud, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.
authors.forename: Quentin P
authors.initials: QP
authors.lastname: Vanbellingen
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS-ICSN UPR2301, Université Paris-Sud, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Elie
authors.affiliation: Institut de Physique Nucléaire, UMR8608, IN2P3-CNRS, Université Paris-Sud, 91406, Orsay, France.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Eller
authors.affiliation: Institut de Physique Nucléaire, UMR8608, IN2P3-CNRS, Université Paris-Sud, 91406, Orsay, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Della-Negra
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS-ICSN UPR2301, Université Paris-Sud, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.
authors.forename: David
authors.initials: D
authors.lastname: Touboul
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS-ICSN UPR2301, Université Paris-Sud, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Brunelle
mesh_terms: D000818:Animals; D002531:Cerebellum; D007091:Image Processing, Computer-Assisted / Q000379:methods; D051381:Rats; D018629:Spectrometry, Mass, Secondary Ion / Q000295:instrumentation / Q000379:methods*