Imaging and differentiation of mouse embryo tissues by ToF-SIMS

Wu, Ligang; Lü, Xing; Kulp, Kristen S.; Knize, Mark G.; Berman, Elena S. F.; Nelson, Erik J.; Felton, James S.; Wu, Kuang Jen

doi:10.1016/j.ijms.2006.09.029

Cited by 41 publications

(29 citation statements)

References 34 publications

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“…TOF-SIMS generates comprehensive spectral data and is therefore attracting increasing interest as a tool for classifying biological samples [5][6][7]. However, since the method is only semiquantitative and visual interpretation of spectra is difficult, multivariate analysis of the acquired data is often very useful [7][8][9]. Thus, multivariate analysis was applied here, using principal component analysis followed by orthogonal partial least squares (OPLS), to screen TOF-SIMS spectra.…”

mentioning

confidence: 99%

TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls

Almstrand

Josefson²,

Bredberg³

et al. 2011

European Respiratory Journal

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Particles in exhaled air (PEx) may reflect the composition of respiratory tract lining fluid (RTLF); thus, there is a need to assess their potential as sources of biomarkers for respiratory diseases. In the present study, we compared PEx from patients with asthma and controls using time-of-flight-secondary ion mass spectrometry (TOF-SIMS) and multivariate analysis.Particles were collected using an instrument developed in-house. 15 nonsmoking subjects with physician-diagnosed asthma and 11 nonsmoking healthy controls performed 10 consecutive forced exhalations into the instrument. Particle concentrations were recorded and samples of particles collected on silicon plates were analysed by TOF-SIMS.Subjects with asthma exhaled significantly lower numbers of particles than controls (p50.03) and the ratio of unsaturated to saturated phospholipids was significantly lower in samples from subjects with asthma (0.25 versus 0.35; p50.036). Orthogonal partial least squares-discriminant analysis models showed good separation between both positive and negative spectra. Molecular ions from phosphatidylcholine and phosphatidylglycerol, and protein fragments were found to discriminate the groups.We conclude that analysis of PEx is a promising method to examine the composition of RTLF. In the present explorative study, we could discriminate between subjects with asthma and healthy controls based on TOF-SIMS spectra from PEx.

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mentioning

confidence: 99%

TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls

Almstrand

Josefson²,

Bredberg³

et al. 2011

European Respiratory Journal

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“…Molecular and elemental information is obtained for organic and inorganic materials providing a powerful technique to image organic compounds associated with inorganic substrates or vice versa [9,10]. This has been demonstrated by imaging solid-state pharmaceutical formulations [11][12][13][14], however, to date this has not been extended to porous silicon substrates.…”

mentioning

confidence: 99%

Use of TOF-SIMS to study adsorption and loading behavior of methylene blue and papain in a nano-porous silicon layer

Kempson

Barnes

Prestidge

2010

J. Am. Soc. Mass Spectrom.

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TOF-SIMS was applied to study the cross-sectional distribution of methylene blue and papain in porous silicon layers. Elemental and molecular information were used to study their distributions in the porous region and the chemistry of their adsorption. Methylene blue (MW ϭ 284 Da) [4], and the delivery of active pharmaceutical ingredients [5,6]. The ongoing interest in pSi for use as a therapeutic delivery system is due to the large internal surface area available, the readily modified surface chemistry [7] and, in particular, the excellent in vivo biodegradation and biocompatibility (low toxicity) of the silicon substrate, hydrolysing to form orthosilicic acid, which is readily excreted [8]. The loading dynamics of molecules into a pSi matrix is dependent on wetting and the size of the pores. Likewise, the interaction between a loaded molecule and the pSi substrate is of interest, particularly in the case of protein based therapeutics, whose bioactivity is dependent on remaining in a specific 3D conformation.TOF-SIMS analysis provides information regarding elemental and molecular species present in a sample surface (i.e., within 1-1.5 nm) with high mass resolution (up to ϳ10,000 m/⌬m) and spatial resolution for imaging (ϳ1 micron). Molecular and elemental information is obtained for organic and inorganic materials providing a powerful technique to image organic compounds associated with inorganic substrates or vice versa [9,10]. This has been demonstrated by imaging solid-state pharmaceutical formulations [11][12][13][14], however, to date this has not been extended to porous silicon substrates.In this study, TOF-SIMS was used to map the distribution of methylene blue and papain across porous silicon layers after loading from aqueous solution. Methylene blue (C 16 H 18 N 3 S ϩ , MW ϭ 284.12 g/mol) is a relatively small organic dye molecule commonly used in adsorption studies and can be considered analogous to therapeutic molecules. A molecular mass of 284 g/mol is within a reasonable mass range for a TOF-SIMS' Ga ϩ primary ion beam and can be easily and uniquely identified without interference or confusion from spectral peaks originating from the silicon substrate or in the instance of organic contamination. This molecule was chosen for its convenience, and to assess the ability to use smaller organic fragments to reflect the distribution of the molecule of interest. This is important to be able to extend this work to studying larger molecules, such as proteins and enzymes of pharmaceutical interest, which will not provide a molecular ion in TOF-SIMS. In contrast to methylene blue, papain is a much larger molecule, detailed elsewhere [15], comprising 212 residue units in two domains, giving a molecular weight of 23,406 g/mol. Papain is a cysteine protease hydrolase enzyme present in papaya. This molecular weight is far greater than can be detected with TOF-SIMS, however, fragmentation products can be detected. Smaller organic fragments can be compared with the distribution of methylene blue to investigate si...

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“…As shown by some researchers, it is also possible to acquire ToF-SIMS images of lipids from the same or serial section where an H&E stained image is acquired. 21,44 The typical image field of view for ToF-SIMS is in the submillimeter range. However, tissue sample sizes are often many millimeters and even centimeters in size.…”

Section: B Mice: Image Data Acquisition and Analysismentioning

confidence: 99%

ToF-SIMS of tissues: “Lessons learned” from mice and women

et al. 2015

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The ability to image cells and tissues with chemical and molecular specificity could greatly expand our understanding of biological processes. The subcellular resolution mass spectral imaging capability of time of flight secondary ion mass spectrometry (ToF-SIMS) has the potential to acquire chemically detailed images. However, the complexities of biological systems combined with the sensitivity of ToF-SIMS require careful planning of experimental methods. Tissue sample preparation methods of formalin fixation followed by paraffin embedding (FFPE) and OCT embedding are compared. Results show that the FFPE can potentially be used as a tissue sample preparation protocol for ToF-SIMS analysis if a cluster ion presputter is used prior to analysis and if nonlipid related tissue features are the features of interest. In contrast, embedding tissue in OCT minimizes contamination and maintains lipid signals. Various data acquisition methodologies and analysis options are discussed and compared using mouse breast and diaphragm muscle tissue. Methodologies for acquiring ToF-SIMS 2D images are highlighted along with applications of multivariate analysis to better identify specific features in a tissue sections when compared to H&E images of serial sections. Identification of tissue features is necessary for researchers to visualize a molecular map that correlates with specific biological features or functions. Finally, lessons learned from sample preparation, data acquisition, and data analysis methods developed using mouse models are applied to a preliminary analysis of human breast tumor tissue sections.

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Imaging and differentiation of mouse embryo tissues by ToF-SIMS

Cited by 41 publications

References 34 publications

TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls

TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls

Use of TOF-SIMS to study adsorption and loading behavior of methylene blue and papain in a nano-porous silicon layer

ToF-SIMS of tissues: “Lessons learned” from mice and women

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