High-Spatial Resolution Mass Spectrometric Imaging of Peptide and Protein Distributions on a Surface

Luxembourg, S.L.; Mize, Todd H.; McDonnell, Liam A.; Heeren, Ron M. A.

doi:10.1021/ac049692q

Cited by 248 publications

(283 citation statements)

References 29 publications

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“…An alternative approach for high spatial resolution IMS is the mass microscope. Here the spatial resolution is about 4 m [34] and independent of the spot size of the ionizing beam, but solely dependent on the ion optics of the instrument and the kinetic energy distribution of the MALDI-generated ions. The desorbed molecules retain their original spatial distribution during the TOF analysis and are projected onto a position sensitive detector.…”

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confidence: 99%

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Imaging of peptides in the rat brain using MALDI-FTICR mass spectrometry

Taban

Altelaar

Burgt

et al. 2007

J. Am. Soc. Mass Spectrom.

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148

136

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Analytical methods are pursued to measure the identity and location of biomolecules down to the subcellular ( m) level. Available mass spectrometric imaging methods either compromise localization accuracy or identification accuracy in their analysis of surface biomolecules. In this study, imaging FTICR-MS is applied for the spatially resolved mass analysis of rat brain tissue with the aim to optimize protein identification by the high mass accuracy and online MS/MS capabilities of the technique. Mass accuracies up to 6 ppm were obtained in the direct MALDI-analysis of the tissue together with a spatial resolution of 200 m. The spatial distributions of biomolecules differing in mass by less than 0.1 Da could be resolved, and are shown to differ significantly. Online MS/MS analysis of selected ions was demonstrated. A comparison of the FTICR-MS imaging results with stigmatic TOF imaging on the same sample is presented. To reduce the extended measuring times involved, it is recommended to restrict the FTICR-MS analyses to areas of interest as can be preselected by other, faster imaging methods. (J Am Soc Mass Spectrom 2007, 18, 145-151)

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confidence: 99%

“…Because the mass microscope is also a TOF mass analyzer, an image is obtained for each analyte. In a microprobe experiment, this spot would constitute a single pixel for each analyte [34].…”

mentioning

confidence: 99%

Imaging of peptides in the rat brain using MALDI-FTICR mass spectrometry

Taban

Altelaar

Burgt

et al. 2007

J. Am. Soc. Mass Spectrom.

Self Cite

148

136

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“…The spatial resolution of the MS image was determined to be 8.5 μm, following the widely used metric of having the transition point of a sharp feature determined within a 20-80% intensity change of the MS signal. 18 In the case of phospholipid [PC (38:5 + Na)] + on the mouse kidney section, the feature transition between the inner medulla and the outer medulla takes place across one scan cycle in the chronogram, showing an intensity change greater than 20-80% range. Based on the sample moving speed (10.0 μm/sec) and MS data acquisition rate (0.85 sec/spectrum), the sample moving distance in one MS scan cycle (8.5 μm), i.e.…”

Section: Representative Resultsmentioning

confidence: 99%

Applications of the Single-probe: Mass Spectrometry Imaging and Single Cell Analysis under Ambient Conditions

Rao

Pan

Yang

2016

JoVE

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Mass spectrometry imaging (MSI) and in-situ single cell mass spectrometry (SCMS) analysis under ambient conditions are two emerging fields with great potential for the detailed mass spectrometry (MS) analysis of biomolecules from biological samples. The single-probe, a miniaturized device with integrated sampling and ionization capabilities, is capable of performing both ambient MSI and in-situ SCMS analysis. For ambient MSI, the single-probe uses surface micro-extraction to continually conduct MS analysis of the sample, and this technique allows the creation of MS images with high spatial resolution (8.5 μm) from biological samples such as mouse brain and kidney sections. Ambient MSI has the advantage that little to no sample preparation is needed before the analysis, which reduces the amount of potential artifacts present in data acquisition and allows a more representative analysis of the sample to be acquired. For in-situ SCMS, the single-probe tip can be directly inserted into live eukaryotic cells such as HeLa cells, due to the small sampling tip size (< 10 μm), and this technique is capable of detecting a wide range of metabolites inside individual cells at near real-time. SCMS enables a greater sensitivity and accuracy of chemical information to be acquired at the single cell level, which could improve our understanding of biological processes at a more fundamental level than previously possible. The single-probe device can be potentially coupled with a variety of mass spectrometers for broad ranges of MSI and SCMS studies.

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“…This algorithm can be adapted for all datasets of similar nature in imaging mass spectrometry, particularly the mass microscope being developed as part of our high-resolution imaging mass spectrometry research efforts [25,26].…”

Section: Discussionmentioning

confidence: 99%

Automated, feature-based image alignment for high-resolution imaging mass spectrometry of large biological samples

Broersen

Liere

Altelaar

et al. 2008

J. Am. Soc. Mass Spectrom.

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High-resolution imaging mass spectrometry of large biological samples is the goal of several research groups. In mosaic imaging, the most common method, the large sample is divided into a mosaic of small areas that are then analyzed with high resolution. Here we present an automated alignment routine that uses principal component analysis to reduce the uncorrelated noise in the imaging datasets, which previously obstructed automated image alignment. An additional signal quality metric ensures that only those regions with sufficient signal quality are considered. We demonstrate that this algorithm provides superior alignment performance than manual stitching and can be used to automatically align large imaging mass spectrometry datasets comprising many individual mosaic tiles. (J Am Soc Mass Spectrom 2008, 19, 823-832) © 2008 American Society for Mass Spectrometry I maging mass spectrometry is a rapidly developing analytical tool because it provides the ability to map the profiles of specific biomolecules, in which the intrinsic mass of the molecule differentiates between any modified forms; to record the distributions of multiple analytes in parallel; and to perform these analyses without a label and with clinical samples [1]. This combination of specificity, parallel detection, and non-targeted analysis has led to great excitement for its potential as a discovery tool.It is the goal of many research groups to be able to perform high-resolution analysis of large samples, thus combining the ability to examine distributions between organs/tumors and their surroundings as well as to investigate the subcellular/intracellular locations of the biomolecules. The central premise of this approach is that the subcellular locations will provide some of the information required to explain differences in the more global patterns.High spatial resolution measurements are a wellestablished ability of secondary ion mass spectrometry (SIMS). Recent advances in both ionization efficiency (polyatomic primary ions) and sample preparation have significantly improved the sensitivity for detecting intact, medium-sized molecular ions (Ͻ1000 Da) from tissues and cells [1][2][3][4][5][6]. High-resolution images of small peptides, lipids, cholesterol, vitamins, and pharmaceuticals have all been reported, and through the use of large polyatomic primary ions three-dimensional (3D) molecular imaging results are beginning to appear [7][8][9].The images are normally created by moving the ionization beam in a set pattern across the sample and performing mass analysis at each point of the raster (spatially correlated mass spectrometry). The raster pattern typically uses 8-or 10-bit encoding; as a result the maximum analysis field contains 256 ϫ 256 (or 1024 ϫ 1024) pixels. In a typical high spatial resolution SIMS measurement the pixel size is about 200 nm, meaning maximum analysis areas of approximately 50 or 200 m, respectively. This is much smaller than many of the biological samples of interest; for example, a tissue section of an adult rat ...

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High-Spatial Resolution Mass Spectrometric Imaging of Peptide and Protein Distributions on a Surface

Cited by 248 publications

References 29 publications

Imaging of peptides in the rat brain using MALDI-FTICR mass spectrometry

Imaging of peptides in the rat brain using MALDI-FTICR mass spectrometry

Applications of the Single-probe: Mass Spectrometry Imaging and Single Cell Analysis under Ambient Conditions

Automated, feature-based image alignment for high-resolution imaging mass spectrometry of large biological samples

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