The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Richard M Caprioli - One of the best experts on this subject based on the ideXlab platform.
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combining salt doping and matrix sublimation for high spatial resolution maldi imaging mass spectrometry of neutral lipids
Analytical Chemistry, 2019Co-Authors: Martin Dufresne, Nathan Heath Patterson, Jeremy L Norris, Richard M CaprioliAbstract:The combination of sodium salt doping of a Tissue Section along with the sublimation of the matrix 2,5-dihydrobenzoic acid (DHB) was found to be an effective coating for the simultaneous detection of neutral lipids and phospholipids using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry in positive ionization mode. Lithium, sodium, and potassium acetate were initially screened for their ability to cationize difficult to analyze neutral lipids such as cholesterol esters, cerebrosides, and triglycerides directly from a Tissue Section. The combination of sodium salt and DHB sublimation was found to be an effective cation/matrix combination for detection of neutral lipids. Further experimental optimizations revealed that sodium carbonate or sodium phosphate followed by DHB sublimation increases the signal intensity of the neutral lipids studied depending on the specific lipid family and Tissue type by 10-fold to 140-fold compared with that of previously published methods. Application of sodium carbonate Tissue doping and DHB sublimation resulted in crystal sizes ≤2 μm. We were thus able to image a mouse brain cerebellum at a high spatial resolution and detected 37 cerebrosides in a single run using a MALDI-TOF instrument. The combination of sodium doping and DHB sublimation offer a targeted and sensitive approach for the detection of neutral lipids that do not typically ionize well under normal MALDI conditions.
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matrix sublimation recrystallization for imaging proteins by mass spectrometry at high spatial resolution
Analytical Chemistry, 2011Co-Authors: Junhai Yang, Richard M CaprioliAbstract:We have employed matrix deposition by sublimation for protein image analysis on Tissue Sections using a hydration/recrystallization process that produces high-quality MALDI mass spectra and high-spatial-resolution ion images. We systematically investigated different washing protocols, the effect of Tissue Section thickness, the amount of sublimated matrix per unit area, and different recrystallization conditions. The results show that an organic solvent rinse followed by ethanol/water rinses substantially increased sensitivity for the detection of proteins. Both the thickness of the Tissue Section and the amount of sinapinic acid sublimated per unit area have optimal ranges for maximal protein signal intensity. Ion images of mouse and rat brain Sections at 50, 20, and 10 μm spatial resolution are presented and are correlated with hematoxylin and eosin (H&E)-stained optical images. For targeted analysis, histology-directed imaging can be performed using this protocol where MS analysis and H&E staining are ...
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high spatial resolution imaging mass spectrometry and classical histology on a single Tissue Section
Journal of Mass Spectrometry, 2011Co-Authors: Fabian Deutskens, Junhai Yang, Richard M CaprioliAbstract:The work presented in this report describes and demonstrates a protocol for protein imaging analysis of biological Tissue using MALDI IMS where histological staining and MS analysis are performed on the same Tissue Section. Spatial image resolution is shown at 35 µm for sagittal Sections of the cerebellum from rat brain.
Tang-long Shen - One of the best experts on this subject based on the ideXlab platform.
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Precision biomarker discovery powered by microscopy image fusion-assisted high spatial resolution ambient ionization mass spectrometry imaging
Analytica chimica acta, 2019Co-Authors: Li-en Lin, Chih-lin Chen, Ying-chen Huang, Hsin-hsiang Chung, Chiao-wei Lin, Ko-chien Chen, Yu-ju Peng, Shih-torng Ding, Ming-yang Wang, Tang-long ShenAbstract:Abstract Mass spectrometry imaging (MSI) using the ambient ionization technique enables a direct chemical investigation of biological samples with minimal sample pretreatment. However, detailed morphological information of the sample is often lost due to its limited spatial resolution. In this study, predictive high-resolution molecular imaging was produced by the fusion of ambient ionization MSI with optical microscopy of routine hematoxylin and eosin (H&E) staining. Specifically, desorption electrospray ionization (DESI) and nanospray desorption electrospray ionization (nanoDESI) mass spectrometry were employed to visualize lipid and protein species on mice Tissue Sections. The resulting molecular distributions obtained by ambient ionization MSI-microscopy fusion were verified with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) MSI and immunohistochemistry (IHC) staining. Label-free molecular imaging with 5-μm spatial resolution can be acquired using DESI and nanoDESI, whereas the typical spatial resolution of ambient ionization MSI was ∼100 μm. In this regard, sharpened molecular histology of Tissue Sections was achieved, providing complementary references to the pathology. Such a multi-modal integration enables the discovery of potential tumor biomarkers. After image fusion, more than a dozen potential biomarkers on a metastatic mouse lung Tissue Section and Luminal B breast tumor Tissue Section were identified.
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High Spatial Resolution Ambient Ionization Mass Spectrometry Imaging Using Microscopy Image Fusion Determines Tumor Margins
2019Co-Authors: Li-en Lin, Chih-lin Chen, Ying-chen Huang, Hsin-hsiang Chung, Chiao-wei Lin, Ko-chien Chen, Yu-ju Peng, Shih-torng Ding, Ming-yang Wang, Tang-long ShenAbstract:Abstract Mass spectrometry imaging (MSI) using ambient ionization technique enables a direct chemical investigation of biological samples with minimal sample pretreatment. However, detailed morphological information of the sample is often lost due to its limited spatial resolution. In this study, predictive high-resolution molecular imaging was produced by the fusion of ambient ionization MSI with optical microscopy of routine hematoxylin and eosin (H&E) staining produces. Specifically, desorption electrospray ionization (DESI) and nanospray desorption electrospray ionization (nanoDESI) mass spectrometry are employed to visualize lipid and protein species on mice Tissue Sections. The resulting molecular distributions obtained by ambient ionization MSI-microscopy fusion are verified with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) MSI and immunohistochemistry (IHC) staining. Label-free molecular imaging with 5-μm spatial resolution can be acquired using DESI and nanoDESI, whereas the typical spatial resolution of ambient ionization MSI is ~100 μm. In this regard, sharpened molecular histology of Tissue Sections is achieved, providing complementary references to the pathology. Such a multimodality integration enables the discovery of potential tumor biomarkers. After image fusion, more than a dozen of potential biomarkers that could be used to determine the tumor margins on a metastatic mouse lung Tissue Section and Luminal B breast tumor Tissue Section are identified.
Andreas Rompp - One of the best experts on this subject based on the ideXlab platform.
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correlative mass spectrometry imaging applying time of flight secondary ion mass spectrometry and atmospheric pressure matrix assisted laser desorption ionization to a single Tissue Section
Rapid Communications in Mass Spectrometry, 2018Co-Authors: Nicolas Desbenoit, Alain Brunelle, Axel Walch, Bernhard Spengler, Andreas RomppAbstract:Rationale Mass spectrometry imaging (MSI) is a powerful tool for mapping the surface of a sample. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) and atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) offer complementary capabilities. Here, we present a workflow to apply both techniques to a single Tissue Section and combine the resulting data for the example of human colon cancer Tissue. Methods Following cryo-Sectioning, images were acquired using the high spatial resolution (1 μm pixel size) provided by TOF-SIMS. The same Section was then coated with a para-nitroaniline matrix and images were acquired using AP-MALDI coupled to an Orbitrap mass spectrometer, offering high mass resolution, high mass accuracy and tandem mass spectrometry (MS/MS) capabilities. Datasets provided by both mass spectrometers were converted into the open and vendor-independent imzML file format and processed with the open-source software MSiReader. Results The TOF-SIMS and AP-MALDI mass spectra show strong signals of fatty acids, cholesterol, phosphatidylcholine and sphingomyelin. We showed a high correlation between the fatty acid ions detected with TOF-SIMS in negative ion mode and the phosphatidylcholine ions detected with AP-MALDI in positive ion mode using a similar setting for visualization. Histological staining on the same Section allowed the identification of the anatomical structures and their correlation with the ion images. Conclusions This multimodal approach using two MSI platforms shows an excellent complementarity for the localization and identification of lipids. The spatial resolution of both systems is at or close to cellular dimensions, and thus spatial correlation can only be obtained if the same Tissue Section is analyzed sequentially. Data processing based on imzML allows a real correlation of the imaging datasets provided by these two technologies and opens the way for a more complete molecular view of the anatomical structures of biological Tissues.
Alain Brunelle - One of the best experts on this subject based on the ideXlab platform.
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correlative mass spectrometry imaging applying time of flight secondary ion mass spectrometry and atmospheric pressure matrix assisted laser desorption ionization to a single Tissue Section
Rapid Communications in Mass Spectrometry, 2018Co-Authors: Nicolas Desbenoit, Alain Brunelle, Axel Walch, Bernhard Spengler, Andreas RomppAbstract:Rationale Mass spectrometry imaging (MSI) is a powerful tool for mapping the surface of a sample. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) and atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) offer complementary capabilities. Here, we present a workflow to apply both techniques to a single Tissue Section and combine the resulting data for the example of human colon cancer Tissue. Methods Following cryo-Sectioning, images were acquired using the high spatial resolution (1 μm pixel size) provided by TOF-SIMS. The same Section was then coated with a para-nitroaniline matrix and images were acquired using AP-MALDI coupled to an Orbitrap mass spectrometer, offering high mass resolution, high mass accuracy and tandem mass spectrometry (MS/MS) capabilities. Datasets provided by both mass spectrometers were converted into the open and vendor-independent imzML file format and processed with the open-source software MSiReader. Results The TOF-SIMS and AP-MALDI mass spectra show strong signals of fatty acids, cholesterol, phosphatidylcholine and sphingomyelin. We showed a high correlation between the fatty acid ions detected with TOF-SIMS in negative ion mode and the phosphatidylcholine ions detected with AP-MALDI in positive ion mode using a similar setting for visualization. Histological staining on the same Section allowed the identification of the anatomical structures and their correlation with the ion images. Conclusions This multimodal approach using two MSI platforms shows an excellent complementarity for the localization and identification of lipids. The spatial resolution of both systems is at or close to cellular dimensions, and thus spatial correlation can only be obtained if the same Tissue Section is analyzed sequentially. Data processing based on imzML allows a real correlation of the imaging datasets provided by these two technologies and opens the way for a more complete molecular view of the anatomical structures of biological Tissues.
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multimodal spectroscopy combining time of flight secondary ion mass spectrometry synchrotron ft ir and synchrotron uv microspectroscopies on the same Tissue Section
Analytical Chemistry, 2010Co-Authors: Vanessa W Petit, Matthieu Refregiers, Catherine Guettier, Frederic Jamme, Kumaraparithy Sebanayakam, Alain Brunelle, Olivier Laprevote, Paul Dumas, Francois Le NaourAbstract:Mass spectrometry and spectroscopy-based approaches can provide an overview of the chemical composition of a Tissue sample. This opens up the possibility to investigate in depth the subtle biochemical changes associated with pathological Tissues. In this study, time-of-flight secondary ion mass spectrometry (TOF-SIMS) and synchrotron-FT-IR and -UV imaging were applied to the same Tissue Section by using the same sample holder. The tested sample involved liver cirrhosis, which is characterized by regeneration nodules surrounded by annular fibrosis. A Tissue Section from a cirrhotic liver was deposited on a gold coated glass slide and was initially analyzed by FT-IR microspectroscopy in order to image the distribution of lipids, proteins, sugars, and nucleic acids. This technique has identified collagen enrichment in fibrosis whereas esters were mostly distributed into the cirrhotic nodules. The exact same Section was investigated using TOF-SIMS demonstrating that some molecular lipid species were different...
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attempts for molecular depth profiling directly on a rat brain Tissue Section using fullerene and bismuth cluster ion beams
International Journal of Mass Spectrometry, 2007Co-Authors: Delphine Debois, Alain Brunelle, Olivier LaprevoteAbstract:Abstract The capabilities of time of flight secondary ion mass spectrometry (TOF-SIMS) have been recently greatly improved with the arrival in this field of polyatomic ion sources. This technique is now able to map at the micron scale intact organic molecules in a range of a thousand Daltons or more, at the surface of Tissue samples. Nevertheless, this remains a surface analysis technique, and three-dimensional information on the molecular composition of the sample could not be obtained due to the damage undergone by the organic molecules during their irradiation. The situation changed slightly with the low damage and low penetration depth of the C60 fullerene ion beams. Recent promising studies have shown the possibility of organic molecular depth profiling using this kind of beams onto model samples. This possibility has been tried out directly onto a rat brain Tissue Section, which is the most commonly used biological Tissue model in TOF-SIMS imaging method developments. The Tissue surface has been sputtered with a 10 keV energy fullerene ion beam, and surface analyses were done with a 25 keV Bi3+ ion beam at regular time intervals. The total depth which was analysed was more than two microns, with total primary ion doses of more than 1016 ions cm−2. Although not in contradiction with results previously published but with much lower doses, it is found that the molecular damage remains too large, thus making molecular imaging very difficult. In addition, most of the lipids, which are usually the main observable molecules in TOF-SIMS, are concentrated close to the sample surface in the first hundreds of nanometers.
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Lipid imaging by gold cluster time-of-flight secondary ion mass spectrometry : application to Duchenne muscular dystrophy
Journal of Lipid Research, 2005Co-Authors: David Touboul, Alain Brunelle, Frédéric Halgand, Sabine De La Porte, Olivier LaprevoteAbstract:Imaging with time-of-flight secondary ion mass spectrometry (TOF-SIMS) has expanded very rapidly with the development of gold cluster ion sources (Au(3+)). It is now possible to acquire ion density maps (ion images) on a Tissue Section without any treatment and with a lateral resolution of few micrometers. In this article, we have taken advantage of this technique to study the degeneration/regeneration process in muscles of a Duchenne muscular dystrophy model mouse. Specific distribution of different lipid classes (fatty acids, triglycerides, phospholipids, tocopherol, coenzyme Q9, and cholesterol) allows us to distinguish three different regions on a mouse leg Section: one is destroyed, another is degenerating (oxidative stress and deregulation of the phosphoinositol cycle), and the last one is stable. TOF-SIMS imaging shows the ability to localize directly on a Tissue Section a great number of lipid compounds that reflect the state of the cellular metabolism.
Olivier Laprevote - One of the best experts on this subject based on the ideXlab platform.
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multimodal spectroscopy combining time of flight secondary ion mass spectrometry synchrotron ft ir and synchrotron uv microspectroscopies on the same Tissue Section
Analytical Chemistry, 2010Co-Authors: Vanessa W Petit, Matthieu Refregiers, Catherine Guettier, Frederic Jamme, Kumaraparithy Sebanayakam, Alain Brunelle, Olivier Laprevote, Paul Dumas, Francois Le NaourAbstract:Mass spectrometry and spectroscopy-based approaches can provide an overview of the chemical composition of a Tissue sample. This opens up the possibility to investigate in depth the subtle biochemical changes associated with pathological Tissues. In this study, time-of-flight secondary ion mass spectrometry (TOF-SIMS) and synchrotron-FT-IR and -UV imaging were applied to the same Tissue Section by using the same sample holder. The tested sample involved liver cirrhosis, which is characterized by regeneration nodules surrounded by annular fibrosis. A Tissue Section from a cirrhotic liver was deposited on a gold coated glass slide and was initially analyzed by FT-IR microspectroscopy in order to image the distribution of lipids, proteins, sugars, and nucleic acids. This technique has identified collagen enrichment in fibrosis whereas esters were mostly distributed into the cirrhotic nodules. The exact same Section was investigated using TOF-SIMS demonstrating that some molecular lipid species were different...
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attempts for molecular depth profiling directly on a rat brain Tissue Section using fullerene and bismuth cluster ion beams
International Journal of Mass Spectrometry, 2007Co-Authors: Delphine Debois, Alain Brunelle, Olivier LaprevoteAbstract:Abstract The capabilities of time of flight secondary ion mass spectrometry (TOF-SIMS) have been recently greatly improved with the arrival in this field of polyatomic ion sources. This technique is now able to map at the micron scale intact organic molecules in a range of a thousand Daltons or more, at the surface of Tissue samples. Nevertheless, this remains a surface analysis technique, and three-dimensional information on the molecular composition of the sample could not be obtained due to the damage undergone by the organic molecules during their irradiation. The situation changed slightly with the low damage and low penetration depth of the C60 fullerene ion beams. Recent promising studies have shown the possibility of organic molecular depth profiling using this kind of beams onto model samples. This possibility has been tried out directly onto a rat brain Tissue Section, which is the most commonly used biological Tissue model in TOF-SIMS imaging method developments. The Tissue surface has been sputtered with a 10 keV energy fullerene ion beam, and surface analyses were done with a 25 keV Bi3+ ion beam at regular time intervals. The total depth which was analysed was more than two microns, with total primary ion doses of more than 1016 ions cm−2. Although not in contradiction with results previously published but with much lower doses, it is found that the molecular damage remains too large, thus making molecular imaging very difficult. In addition, most of the lipids, which are usually the main observable molecules in TOF-SIMS, are concentrated close to the sample surface in the first hundreds of nanometers.
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Lipid imaging by gold cluster time-of-flight secondary ion mass spectrometry : application to Duchenne muscular dystrophy
Journal of Lipid Research, 2005Co-Authors: David Touboul, Alain Brunelle, Frédéric Halgand, Sabine De La Porte, Olivier LaprevoteAbstract:Imaging with time-of-flight secondary ion mass spectrometry (TOF-SIMS) has expanded very rapidly with the development of gold cluster ion sources (Au(3+)). It is now possible to acquire ion density maps (ion images) on a Tissue Section without any treatment and with a lateral resolution of few micrometers. In this article, we have taken advantage of this technique to study the degeneration/regeneration process in muscles of a Duchenne muscular dystrophy model mouse. Specific distribution of different lipid classes (fatty acids, triglycerides, phospholipids, tocopherol, coenzyme Q9, and cholesterol) allows us to distinguish three different regions on a mouse leg Section: one is destroyed, another is degenerating (oxidative stress and deregulation of the phosphoinositol cycle), and the last one is stable. TOF-SIMS imaging shows the ability to localize directly on a Tissue Section a great number of lipid compounds that reflect the state of the cellular metabolism.
