ToF-SIMS imaging with cluster ion beams

Xu, Jiyun; Ostrowski, Sara G.; Szakal, Christopher; Ewing, Andrew G.; Winograd, Nicholas

doi:10.1016/j.apsusc.2004.03.104

Cited by 43 publications

(37 citation statements)

References 10 publications

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“…Recent studies of freeze-dried Tetrahymena cells have shown that for the characteristic phosphocholine head group ion at m/z 185, there is a 50-fold signal increase with C 60 + primary ions compared with In + . 40 These data suggest that the increased signal levels can lead to better image resolution by improving the image contrast (number of counts per pixel). Recently, researchers have reported that it is possible to focus C 60 + ion beams to ∼200 nm diameter, which will lead to further improvements in the lateral resolution.…”

Section: Biological Imaging Of Tissues and Cellsmentioning

confidence: 97%

“…Xu and co-workers have shown that signal enhancements of >20,000 for (Phe) 4 (m/z 606.3) adsorbed on 75 µm polymer resin beads could be obtained by using C 60 + 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.…”

Section: Chemical Assaysmentioning

confidence: 99%

“…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.…”

Section: Chemical Assaysmentioning

confidence: 99%

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Why Is SIMS Underused in Chemical and Biological Analysis? Challenges and Opportunities

Walker

2008

Anal. Chem.

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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. 2,3It 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: Au n + , Bi n x+ , SF 5 + , and C 60 x+ . [4][5][6][7][8][9][10][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 not a comprehensive review of SIMS; for additional information, see Refs. 1-3 and 12-25.) IMAGE RESOLUTION AND CLUSTER ION SOURCESIn 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.

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Section: Biological Imaging Of Tissues and Cellsmentioning

confidence: 97%

Section: Chemical Assaysmentioning

confidence: 99%

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Why Is SIMS Underused in Chemical and Biological Analysis? Challenges and Opportunities

Walker

2008

Anal. Chem.

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“…This limits its use mostly to the analysis of low mass molecular and elemental ions. Recent developments in sample preparation methods [30][31][32] and the introduction of cluster primary ion sources (Au n m+ , Bi n m+ , C 60 + ) [33][34][35] have improved the secondary ion yields for lipids and small peptides. These developments have helped move the technique from applications in the domains of surface physics and solid state physics to the study of biological samples such as cells and tissue sections, where it proved to have an outstanding spatial resolution of few hundred nanometers compared to other mass spectrometry imaging methods.…”

Section: Introductionmentioning

confidence: 99%

Microscope mode secondary ion mass spectrometry imaging with a Timepix detector

Kiss

Jungmann

Smith

et al. 2013

Review of Scientific Instruments

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In-vacuum active pixel detectors enable high sensitivity, highly parallel time-and space-resolved detection of ions from complex surfaces. For the first time, a Timepix detector assembly was combined with a secondary ion mass spectrometer for microscope mode secondary ion mass spectrometry (SIMS) imaging. Time resolved images from various benchmark samples demonstrate the imaging capabilities of the detector system. The main advantages of the active pixel detector are the higher signal-to-noise ratio and parallel acquisition of arrival time and position. Microscope mode SIMS imaging of biomolecules is demonstrated from tissue sections with the Timepix detector.

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“…SIMS has demonstrated to be an excellent technique to image the distribution of elements and small organic molecules with spatial resolution around 100 nm [38,39]. It is currently undergoing a revival with the advent of novel primary ion beam types using molecular clusters (Gold or Bismuth cluster sources) [40] or larger molecules (C60) [41]. This approach extends the useful mass range into the realm of lipids [42] and cholesterol [43].…”

Section: Mass Spectrometric Imagingmentioning

confidence: 99%

Proteome imaging: A closer look at life's organization

Heeren

2005

Proteomics

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Imaging the proteome is a term that is used in many different contexts. The term implies that the entire cohort of proteins and their modifications are visualized. This unfortunately is not the case. In this mini-review, a concise overview is provided on different imaging technologies that are currently used to investigate the structure, function and dynamics of proteins and their organization. These techniques have been selected for review based on the unique insights they provide in subsets of the proteome. These techniques have been illustrated with practical examples of their merits. Mass spectrometry-based imaging technologies are playing a key role in proteome research and have been reviewed in more detail. They hold the promise of detailed molecular insight in the spatial organization of living system.

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ToF-SIMS imaging with cluster ion beams

Cited by 43 publications

References 10 publications

Why Is SIMS Underused in Chemical and Biological Analysis? Challenges and Opportunities

Why Is SIMS Underused in Chemical and Biological Analysis? Challenges and Opportunities

Microscope mode secondary ion mass spectrometry imaging with a Timepix detector

Proteome imaging: A closer look at life's organization

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