A Processing Technique for Cell Surfaces Using Gas Cluster Ions for Imaging Mass Spectrometry (original) (raw)
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Molecular imaging of biological tissue using gas cluster ions
2014
An Ar n + (n = 1-6000) gas cluster ion source has been utilized to map the chemical distribution of lipids in a mouse brain tissue section. We also show that the signal from high mass species can be further enhanced by doping a small amount of CH 4 into the Ar cluster to enhance the ionization of several biologically important molecules. Coupled with secondary ion mass spectrometry instrumentation which utilizes a continuous Ar cluster ion projectile, maximum spatial resolution and maximum mass resolution can be achieved at the same time. With this arrangement, it is possible to achieve chemically resolved molecular ion images at the 4-µm resolution level. The focused Ar n + /[Ar x (CH 4) y ] + beams (4-10 µm) have been applied to the study of untreated mouse brain tissue. A high signal level of molecular ions and salt adducts, mainly from various phosphocholine lipids, has been seen and directly used to map the chemical distribution. The signal intensity obtained using the pure Ar cluster source, the CH 4-doped cluster source and C 60 is also presented.
Journal of Mass Spectrometry, 2005
Time-of-flight secondary ion mass spectrometry (TOF-SIMS) using liquid metal ion guns (LMIGs) is now sensitive enough to produce molecular-ion images directly from biological tissue samples. Primary cluster ions strike a spot on the sample to produce a mass spectrum. An image of this sample is achieved by rastering the irradiated point over the sample surface. The use of secondary ion mass spectrometry for mapping biological tissue surfaces provides unique analytical capabilities; in particular, it enables in a single acquisition a large variety of biological compounds to be localised on a micrometer scale and scrutinised for colocalisations. Without any treatment of the sample, this method is fully compatible with subsequent and complementary analyses like fluorescence microscopy, histochemical staining, or even matrix-assisted laser desorption/ionisation imaging. Basic physical concepts, required instrumentation (ion source and mass analyzer), sample preparation methods, image acquisition, image processing, and emerging biological applications will be described and discussed.
Tissue Molecular Ion Imaging by Gold Cluster Ion Bombardment
Analytical Chemistry, 2004
The use of gold cluster focused ion beams produced by a liquid metal ion gun in a TOF-SIMS mass spectrometer is shown to dramatically enhance secondary ion emission of phospholipids and peptides. The method has been successfully tested with cells grown onto plastic slips and with mouse brain slices, without any treatment of the samples. Very reliable time-of-flight mass spectra are acquired with a low primary ion dose of a few 10 7 ions, and high lateral resolution molecular ion images are obtained for heavy ions of great biological interest. This approach offers new opportunities in pharmacological and biological research fields by localizing compounds of interest such as drugs or metabolites in tissues.
Imaging mass spectrometry on the nanoscale with cluster ion beams
Analytical chemistry, 2015
Imaging with cluster secondary ion mass spectrometry (SIMS) is reaching a mature level of development. Using a variety of molecular ion projectiles to stimulate desorption, 3-dimensional imaging with the selectivity of mass spectrometry can now be achieved with submicrometer spatial resolution and <10 nm depth resolution. In this Perspective, stock is taken regarding what it will require to routinely achieve these remarkable properties. Issues include the chemical nature of the projectile, topography formation, differential erosion rates, and perhaps most importantly, ionization efficiency. Shortcomings of existing instrumentation are also noted. Speculation about how to successfully resolve these issues is a key part of the discussion.
Biological Cluster Mass Spectrometry
Annual Review of Physical Chemistry, 2010
This article reviews the new physics and new applications of secondary ion mass spectrometry using cluster ion probes. These probes, particularly C60, exhibit enhanced molecular desorption with improved sensitivity owing to the unique nature of the energy-deposition process. In addition, these projectiles are capable of eroding molecular solids while retaining the molecular specificity of mass spectrometry. When the beams are microfocused to a spot on the sample, bioimaging experiments in two and three dimensions are feasible. We describe emerging theoretical models that allow the energy-deposition process to be understood on an atomic and molecular basis. Moreover, experiments on model systems are described that allow protocols for imaging on biological materials to be implemented. Finally, we present recent applications of imaging to biological tissue and single cells to illustrate the future directions of this methodology.
Cluster Secondary Ion Mass Spectrometry
Surface Analysis and Techniques in Biology, 2014
In principle, secondary ion mass spectrometry (SIMS) molecule-specific imaging has vast implications in biological research where submicrometer spatial resolution, uppermost surface layer sensitivity, and chemically unmodified sample preparation are essential. Yet SIMS imaging using atomic projectiles has been rather ineffective when applied to biological materials. The common pitfalls experienced during these analyses include low secondary ion yields, extensive fragmentation, restricted mass ranges, and the accumulation of significant physical and chemical damage after sample erosion beyond 1 % of the surface molecules. Collectively, these limitations considerably reduce the amount of material available for detection and result in inadequate sensitivity for most applications. In response, polyatomic (cluster) ions have been introduced as an alternate imaging projectile. Cluster ion bombardment has been observed to enhance secondary ion yields, extend the spectral mass range, and decrease the incidence of physical and chemical damage during sample erosion. The projectiles are expected to considerably increase the number of molecules available for analysis and to significantly improve the overall sensitivity. Hence, the objectives of this chapter are to describe the unique physical basis for the improvements observed during polyatomic bombardment and to identify the emerging biological applications made practical by the introduction of cluster projectiles to SIMS.
Journal of the American Society for Mass Spectrometry, 2010
A C 60 ϩ cluster ion projectile is employed for sputter cleaning biological surfaces to reveal spatio-chemical information obscured by contamination overlayers. This protocol is used as a supplemental sample preparation method for time of flight secondary ion mass spectrometry (ToF-SIMS) imaging of frozen and freeze-dried biological materials. Following the removal of nanometers of material from the surface using sputter cleaning, a frozen-patterned cholesterol film and a freeze-dried tissue sample were analyzed using ToF-SIMS imaging. In both experiments, the chemical information was maintained after the sputter dose, due to the minimal chemical damage caused by C 60 ϩ bombardment. The damage to the surface produced by freeze-drying the tissue sample was found to have a greater effect on the loss of cholesterol signal than the sputter-induced damage. In addition to maintaining the chemical information, sputtering is not found to alter the spatial distribution of molecules on the surface. This approach removes artifacts that might obscure the surface chemistry of the sample and are common to many biological sample preparation schemes for ToF-SIMS imaging.
Journal of The American Society for Mass Spectrometry, 2005
A new liquid metal ion gun (LMIG) filled with bismuth has been fitted to a time-of-flight—secondary ion mass spectrometer (TOF-SIMS). This source provides beams of Bi n q+ clusters with n = 1–7 and q = 1 and 2. The appropriate clusters have much better intensities and efficiencies than the Au 3+ gold clusters recently used in TOF-SIMS imaging, and allow better lateral and mass resolution. The different beams delivered by this ion source have been tested for biological imaging of rat brain sections. The results show a great improvement of the imaging capabilities in terms of accessible mass range and useful lateral resolution. Secondary ion yields Y, disappearance cross sections σ, efficiencies E = Y/σ;, and useful lateral resolutions ΔL have been compared using the different bismuth clusters, directly onto the surface of rat brain sections and for several positive and negative secondary ions with m/z ranging from 23 up to more than 750. The efficiency and the imaging capabilities of the different primary ions are compared by taking into account the primary ion current for reasonable acquisition times. The two best primary ions are Bi 3+ and Bi 52+. The Bi 3+ ion beam has a current at least five times larger than Au 3+ and therefore is an excellent beam for large-area imaging. Bi 52+ ions exhibit large secondary ions yields and a reasonable intensity making them suitable for small-area images with an excellent sensitivity and a possible useful lateral resolution <400 nm.
Secondary ion mass spectrometry with gas cluster ion beams
Applied Surface Science, 2003
Secondary ion mass spectrometry (SIMS) with gas cluster ion beams was studied with experiments and molecular dynamics (MD) simulations to achieve a high-resolution depth profiling. For this purpose, it is important to prevent both ion mixing and the surface roughening due to energetic ions. As the Ar cluster ion beams shows high secondary ion yield and surface smoothing effects in the low-energy regime, it is suitable for the primary ion beam of SIMS. From MD simulations of Ar cluster ion impact on Si, ion mixing is heavier than than those for Ar monomer ions at the same energy per atom, because the energy density at the impact point is extremely high. However, the sputtering yields with Ar cluster ions are one or two orders of magnitude higher than that with Ar monomer ions at the same energy per atom. Comparing at the ion energy where the ion-mixing depths are the same by both Ar cluster and Ar monomer ions, cluster ions show almost 10 times higher sputtering yield than by Ar monomer ions. A preliminary experiment of SIMS with Ar cluster ion was performed and a mass resolution of several nm was achieved for a Ta film. Ó 2002 Published by Elsevier Science B.V.