Anal. Chem. 2008, 80, 8865–8870
Why Is SIMS Underused in Chemical and Biological Analysis? Challenges and Opportunities Amy V. Walker Washington University St. Louis Improvements have led to many developments in SIMS, including better 2D MS imaging, the ability to perform molecular depth profiling, and the development of 3D MS imaging. (To listen to a podcast about this feature, please go to the Analytical Chemistry website at pubs.acs.org/ac.) Imaging MS has the unique ability to acquire the spatial distribution of a wide range of atoms and molecules, including polymers, pharmaceuticals, lipids, proteins, and semiconductors, without the use of labels such as fluorescent tags. Secondary ion MS (SIMS) imaging has advantages over MALDI imaging: it has submicrometer resolution and requires no sample preparation. Although MALDI imaging has been very successful, particularly in biological applications,1 and has an increasing number of practitioners, SIMS imaging does not seem to be receiving the same amount of attention. In SIMS, ion beams are used to desorb molecules from surfaces; the mass of the molecules is then measured by MS. It was one of the first techniques developed for detecting organic molecules that were not amenable to electron impact ionization.2,3 It was largely overshadowed by other MS techniques, including ESI and MALDI, because in SIMS, it was difficult to desorb ions with m/z > 500, which makes the detection of large molecules very hard. In recent years, SIMS has undergone a renaissance with the advent of commercially available cluster ion sources: Aun+, Binx+, SF5+, and C60x+.4-11 These are easy to use, reliable, and have long lifetimes (g500 µA/h). Cluster ion beams produce secondary ions with much higher efficiencies than atomic ion sources do, thereby increasing secondary ion yields and decreasing sample damage. These improvements have led to many developments in SIMS technology, including better 2D MS imaging, the ability to perform molecular depth profiling, and the development of 3D MS imaging. In this article, I will highlight some of the new applications enabled by cluster primary ion beams, particularly in biological imaging, and I will discuss the challenges of implementing SIMS more widely. (This article is 10.1021/ac8013687 CCC: $40.75 2008 American Chemical Society Published on Web 12/01/2008
not a comprehensive review of SIMS; for additional information, see Refs. 1-3 and 12-25.) IMAGE RESOLUTION AND CLUSTER ION SOURCES In imaging MS, the image quality is determined by three different resolutions: mass, lateral, and depth. Mass resolution, m/∆m, is important because it determines the chemical specificity of the technique as well as its mass accuracy (through improved precision). For many years, commercially available TOF SIMS instruments have been able to produce m/∆m of several thousand in imaging mode. Analytical Chemistry, Vol. 80, No. 23, December 1, 2008
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Until recently, both the lateral and depth resolution of TOF SIMS made molecular imaging impossible. With TOF SIMS, imaging is normally performed by moving a focused, pulsed ion beam across the sample surface. The lateral resolution is the convolution of the signal intensity per pixel, sample preparation, and the characteristics of the SIMS instrument, such as the primary ion beam diameter. For many years, Ga+ liquid metal ion guns have been available that could be focused to spot sizes as small as 10 nm.26 However, this type of ion beam is not very efficient at ejecting molecular and other heavy ions (m/z g 100) from surfaces, resulting in image resolution 20,000 for (Phe)4 (m/z 606.3) adsorbed on 75 µm polymer resin beads could be obtained by using C60+ primary ions compared with using Ga+.40 Furthermore, the analysis was very fasts400 beads could be examined per second.40 TOF SIMS imaging is clearly a useful technique in high-throughput analyses. MOLECULAR DEPTH PROFILING SIMS can be used in static and dynamic modes. In static SIMS,
