Peer Reviewed: Organic SIMS of Biologic Tissue

Todd, Peter J.; McMahon, John M.; Short, R.T.; McCandlish, Carl A.

doi:10.1021/ac971763g

Cited by 60 publications

(52 citation statements)

References 14 publications

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“…Most of the outer layer of cell membranes in the brain is either phosphatidylcholine or sphingomyelin [3][4][5], and both compounds yield abundant m/z 184. Thus, detection of phosphocholine is consistent with the chemistry of low dose or static SIMS [6], a surface analytical method, and the fact that most of the surface of a tissue sample is comprised of compounds yielding phosphocholine secondary ions, m/z 184.The utility of SIMS for mapping phoshocholine is based on the observation that emission of phosphocholine secondary ions is heterogeneous across the tissue section surface [7]. Moreover, secondary m/z 184 images of adult rat brain show a direct correlation with optical images of stained tissue sections [8].…”

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confidence: 78%

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Secondary ion images of the developing rat brain

Todd

McMahon

McCandlish

2004

J. Am. Soc. Mass Spectrom.

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Secondary ion images were obtained from sections of rat brain over a 21 day postnatal period, using the intensity of m/z 184, phosphocholine. When compared with corresponding optical images of similar, but stained sections from the same animal, the secondary ion images appear to reflect less developed brains. During development, myelination occurs after axon extension. Apparently, myelination obscures the source of secondary m/z 184, phosphatidylcholine, from the analyzing ion probe; absenting myelination, secondary ion images show no physiological features. (J Am Soc Mass Spectrom 2004, 15, 1116 -1122) © 2004 American Society for Mass Spectrometry I mages obtained by a variety of methods-optical, secondary electron, nuclear magnetic resonance, etc., are integral to the philosophy of all branches of medicine. Among mass spectral methods, secondary ion mass spectrometry (SIMS) and imaging matrix assisted laser desorption (iMALDI) mass spectrometry are the major players in this arena [1]. These are both emerging methods, and as such, it is necessary to establish that not only are results consistent with known mass spectrometry, but also with known biomedicine.Secondary ions are emitted from tissue at virtually every m/z. We identify secondary ions by tandem mass spectrometry (MS/MS), and map the emission of ions whose structure we know. We then try to interpret the images in the context of known anatomy physiology. For example, the major peak in the secondary ion mass spectrum of almost any collection of animal cells is m/z 184, phosphocholine. Phosphocholine is unique among secondary ions emitted from tissue in that its structure has been verified by MS/MS [2], a method permitting distinction of phosphocholine from other sources of m/z 184 such as epinephrine. The secondary phosphocholine ion derives from the head group of phosphatidylcholine, (PC in the shorthand of biochemists) a major constituent of the animal cell membrane. Most of the outer layer of cell membranes in the brain is either phosphatidylcholine or sphingomyelin [3][4][5], and both compounds yield abundant m/z 184. Thus, detection of phosphocholine is consistent with the chemistry of low dose or static SIMS [6], a surface analytical method, and the fact that most of the surface of a tissue sample is comprised of compounds yielding phosphocholine secondary ions, m/z 184.The utility of SIMS for mapping phoshocholine is based on the observation that emission of phosphocholine secondary ions is heterogeneous across the tissue section surface [7]. Moreover, secondary m/z 184 images of adult rat brain show a direct correlation with optical images of stained tissue sections [8]. Regions of the brain containing a high density of cells such as cerebral cortex or the caudate/putamen yield an intense m/z 184 secondary ion signal, whereas acellular regions such as the corpus callosum or external capsule yield little or no m/z 184 secondary emission. In the adult, these acellular regions of the brain are very dense in cell projections (axons), many of which ar...

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“…The utility of SIMS for mapping phoshocholine is based on the observation that emission of phosphocholine secondary ions is heterogeneous across the tissue section surface [7]. Moreover, secondary m/z 184 images of adult rat brain show a direct correlation with optical images of stained tissue sections [8].…”

mentioning

confidence: 99%

Secondary ion images of the developing rat brain

Todd

McMahon

McCandlish

2004

J. Am. Soc. Mass Spectrom.

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“…The development in this area until 1997 has been excellently reviewed [3]. However, SIMS is based on the outcome of the impact of a high energy primary ion onto a target, and the yield of large molecular fragments, necessary for the identification of the original molecule, seems to be limited [3]. Results presented in recent years are still at the level of localizing molecular fragments like phosphocholine (m=z ¼ 184) [4], vitamin A fragment-1 [5], or OH and CN [6].…”

Section: Introductionmentioning

confidence: 99%

Bioimaging TOF‐SIMS: localization of cholesterol in rat kidney sections

Nygren¹,

Malmberg²,

Kriegeskotte³

et al. 2004

FEBS Letters

106

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Here, we show the localization of a whole organic molecule in biological tissue using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Rat kidneys were sectioned by cryoultramicrotomy and dried at room temperature. The samples were covered with a thin silver layer and analyzed in an imaging TOF-SIMS instrument equipped with a Ga þ -source. The cholesterol signal showed a high concentration in the nuclear areas of the epithelial cells and a lower concentration over areas representing the basal lamina of renal tubules. A more diffuse distribution of cholesterol was also found over areas representing the cytoplasm or plasma membrane of the epithelial cells.

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“…The secondary ion yields from the compounds within these systems are generally very low, and initial work on cells and tissue sections were mainly limited to mapping phospholipid headgroups [1,2], which produce a fragment ion that is very efficiently detected with SIMS. Recent developments such as commercially available cluster ion sources [3][4][5], and the sample pre-treatment techniques involving matrix addition [6] and metal deposition [7], have provided methods for increasing secondary ion yields from organic surfaces, and when applied to cells and tissue allow a greater wealth of information to be obtained [8 -15].…”

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Suppression and enhancement of secondary ion formation due to the chemical environment in static-secondary ion mass spectrometry

Jones

Lockyer

Kordys

et al. 2007

J. Am. Soc. Mass Spectrom.

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Through analyzing mixtures of compounds of known gas-phase basicities, the importance of this property on the secondary ions emitted from a surface under primary ion bombardment is investigated. The aim is to obtain a greater understanding of the ionization mechanisms that occur in secondary ion mass spectrometry (SIMS). The commonly used matrix assisted laser desorption/ionization (MALDI) matrix 2,4,6-trihydroxyacetophenone (THAP) and a range of low molecular weight biomolecules were used to investigate whether analyte/matrix suppression effects that have been observed in analogous MALDI experiments were also present in static-SIMS. The outcome of the experiments demonstrates that strong suppression of the quasi-molecular signal of one molecule in a mixture can occur due to the presence of the other, with the gas-phase basicity of the compounds being a good indicator of the secondary ions detected. It is also demonstrated that the suppression of the quasi-molecular ion signal of a compound in a two-component mixture can be minimized by the inclusion of a third compound of suitable gas-phase basicity. (J Am Soc Mass Spectrom 2007, 18, 1559 -1567

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Peer Reviewed: Organic SIMS of Biologic Tissue

Cited by 60 publications

References 14 publications

Secondary ion images of the developing rat brain

Secondary ion images of the developing rat brain

Bioimaging TOF‐SIMS: localization of cholesterol in rat kidney sections

Suppression and enhancement of secondary ion formation due to the chemical environment in static-secondary ion mass spectrometry

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