High-Resolution Microscope-Mode Secondary Ion Mass Spectrometry Imaging

We report the development of a secondary ion mass spectrometry (SIMS) microscope-mode imaging instrument suitable for a wide range of applications in which high throughput is an advantage. By coupling time-of-flight mass spectrometry with pulsed ion extraction methods, the instrument can provide mass resolutions of <i>m</i>/Δ<i>m</i> ∼ 2000 across a mass range of <i>m</i>/<i>z</i> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mo>≳</mml:mo></mml:math> 1000. We show that the use of an ion imaging detector with a fast scintillator screen, yielding time-of-flight time resolutions of a few nanoseconds, improves the mass resolution further to <i>m</i>/Δ<i>m</i> ∼ 6900. Spatial resolutions of better than 5 μm were also obtained under optimum conditions. We demonstrate the capability of the instrument by imaging atomic and molecular ion species in mouse brain tissue sections, capturing a range of biologically relevant ions, including phospholipid and amino acid fragments, over millimeter length scales within minutes.