In mass spectrometry imaging, spatial resolution is pushed to its limits with the use of ion microscope mass spectrometric imaging systems. An ion microscope magnifies and then projects the original spatial distribution of ions from a sample surface onto a position-sensitive detector, while retaining time-of-flight mass separation capabilities. Here, a new type of position-sensitive detector based on a chevron microchannel plate stack in combination with a 512 ϫ 512 complementary metal-oxide-semiconductor based pixel detector is coupled to an ion microscope. Spatial resolving power better than 6 m is demonstrated by secondary ion mass spectrometry and 8 -10 m spatial resolving power is achieved with laser desorption ionization. A detailed evaluation of key performance criteria such as spatial resolution, acquisition speed, and data handling is presented. (J Am Soc Mass Spectrom 2010, 21, 2023-2030 © 2010 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry M ass spectrometry imaging (MSI) [1-3] measurements allow the visualization of the spatial structure and identification of the molecular masses from complex surfaces. High spatial resolution is accomplished with ion-microscope mass spectrometers, where ions are extracted from the sample surface and projected onto a position-sensitive detector. A spatial resolution better than 4 m has been reported using UV/IR laser surface probes in matrix assisted laser desorption ionization (MALDI) [4 -8]. A pulsed primary ion beam as a surface probe can achieve higher spatial resolving powers (1 m) [9,10]. The spatial resolution can be further improved by using a more focused primary ion/laser desorption ionization surface probe. However, fragmentation of the surface molecules and long measurement times are undesired side effects of decreasing the surface probe area. For instance, at a 2 ϫ 2 m pixel size (4 m lateral resolution) and a sample size of 1 ϫ 1 mm, a typical measurement comprises 250,000 measurement points and can last several hours. An alternate approach to increase the spatial resolution is the use of microscope mode MSI. In the microscope mode, surface molecules are desorbed and ionized over a large sample area, typically 200 -300 m in diameter. An ion microscope employs ion optics to project the ionized surface compounds onto a position-sensitive detector while magnifying the image and retaining the spatial information defined by the sample surface. With a field of view of 200 ϫ 200 m and a sample size of 1 ϫ 1 mm, a microscope mode imaging experiment involves 25 measurement points and retains the 4 m lateral resolution given the corresponding ion optical magnification factor. The ion optical magnification allows high-resolution images to be obtained independent of the ionization source. Microscope mode MSI enables fast, highresolution large area imaging provided that an adequate, i.e., fast and position-sensitive, detector is used to record high quality molecular images [4].Position-sensitive detectors most commonly used for microsc...
Native mass spectrometry (native MS) has emerged as a powerful technique to study the structure and stoichiometry of large protein complexes. Traditionally, native MS has been performed on modified time-of-flight (TOF) systems combined with detectors that do not provide information on the arrival coordinates of each ion at the detector. In this study, we describe the implementation of a Timepix (TPX) pixelated detector on a modified orthogonal TOF (O-TOF) mass spectrometer for the analysis and imaging of native protein complexes. In this unique experimental setup, we have used the impact positions of the ions at the detector to visualize the effects of various ion optical parameters on the flight path of ions. We also demonstrate the ability to unambiguously detect and image individual ion events, providing the first report of single-ion imaging of protein complexes in native MS. Furthermore, the simultaneous space-and time-sensitive nature of the TPX detector was critical in the identification of the origin of an unexpected TOF signal. A signal that could easily be mistaken as a fragment of the protein complex was explicitly identified as a secondary electron signal arising from ion-surface collisions inside the TOF housing. This work significantly extends the mass range previously detected with the TPX and exemplifies the value of simultaneous space-and timeresolved detection in the study of ion optical processes and ion trajectories in TOF mass spectrometers.
We describe the construction and application of a new MALDI source for FT-ICR mass spectrometry imaging. The source includes a translational X-Y positioning stage with a 10 × 10 cm range of motion for analysis of large sample areas, a quadrupole for mass selection, and an external octopole ion trap with electrodes for the application of an axial potential gradient for controlled ion ejection. An off-line LC MALDI MS/MS run demonstrates the utility of the new source for data- and position-dependent experiments. A FT-ICR MS imaging experiment of a coronal rat brain section yields ∼200 unique peaks from m/z 400–1100 with corresponding mass-selected images. Mass spectra from every pixel are internally calibrated with respect to polymer calibrants collected from an adjacent slide.
Cardiovascular diseases are the world's number one cause of death, accounting for 17.1 million deaths a year. New high-resolution molecular and structural imaging strategies are needed to understand underlying pathophysiological mechanism. The aim of our study is (1) to provide a molecular basis of the heart animal model through the local identification of biomolecules by mass spectrometry imaging (MSI) (three-dimensional (3D) molecular reconstruction), (2) to perform a cross-species validation of secondary ion mass spectrometry (SIMS)-based cardiovascular molecular imaging, and (3) to demonstrate potential clinical relevance by the application of this innovative methodology to human heart specimens. We investigated a MSI approach using SIMS on the major areas of a rat and mouse heart: the pericardium, the myocardium, the endocardium, valves, and the great vessels. While several structures of the heart can be observed in individual two-dimensional sections analyzed by metal-assisted SIMS imaging, a full view of these structures in the total heart volume can be achieved only through the construction of the 3D heart model. The images of 3D reconstruction of the rat heart show a highly complementary localization between Na(+), K(+), and two ions at m/z 145 and 667. Principal component analysis of the MSI data clearly identified different morphology of the heart by their distinct correlated molecular signatures. The results reported here represent the first 3D molecular reconstruction of rat heart by SIMS imaging.
A new supersonic molecular beam line has been attached to an existing UHV apparatus. Three different nozzles mounted on a rotatable manipulator allow for independent gas feeds. In this way, dosing sequences with different reactive gases can be carried out within a few minutes. Due to the compact design of the beam line, the apparatus does not forfeit its original flexibility and mobility. Apart from standard techniques like thermal desorption spectroscopy, low-energy electron diffraction, reflection absorption infrared spectroscopy and x-ray photoelectron/Auger electron spectroscopy, a quadrupole mass spectrometer mounted on a linear drive and viewports allows for photochemical experiments or other laser applications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.