Time‐of‐flight secondary ion mass spectrometry imaging of biological samples with delayed extraction for high mass and high spatial resolutions

Vanbellingen, Quentin; Elie, Nicolas; Eller, Michael J.; Della‐Negra, S.; Touboul, David; Brunelle, Alain

doi:10.1002/rcm.7210

Cited by 88 publications

(91 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A second setting mode of the primary ion column was then used to record an image over an area of 100 Φm × 100 Φm with a spatial resolution of 400 nm, but with only a nominal mass resolution. In that case, the primary ion dose was 1.0 × 10 12 ions·cm −2 (a more recent method using a delayed extraction of the secondary ions enables this spatial resolution of 400 nm while keeping a mass resolution of several thousand) [19]. In all cases, a low energy electron flood gun (20 eV) was activated between two pulses of the primary ion beam to neutralize any charge on the surface of the samples.…”

Section: Tof-sims (Time-of-flight Secondary Ion Mass Spectrometry)mentioning

confidence: 99%

The Prismatic Layer of Pinna: A Showcase of Methodological Problems and Preconceived Hypotheses

et al. 2018

Self Cite

View full text Add to dashboard Cite

Abstract:The prismatic layer of Pinna (Mollusca) is one of the most studied models for the understanding of the biomineralization mechanisms, but our knowledge of the organic components of this layer is limited to the proteins of the soluble organic matrices. The interplay of the mineral and organic matrices is studied using scanning electron and atomic force microscopy, infra-red spectrometry, thermogravimetric analyses, aminoacids analyses, thin layer chromatography (TLC), X-ray fluorescence, X-ray Absorption near Edge Structure (XANES) and time-of-flight secondary ion mass spectrometry (TOF-SIMS). Proteins, polysaccharides and lipids are detected within the prisms and their envelopes. The role of the technical choices to study calcareous biominerals is evidenced, showing that a single analysis is not enough to decipher complex biominerals.

show abstract

Section: Tof-sims (Time-of-flight Secondary Ion Mass Spectrometry)mentioning

confidence: 99%

The Prismatic Layer of Pinna: A Showcase of Methodological Problems and Preconceived Hypotheses

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…One attempt to improve mass resolution in TOF-SIMS using Ar-GCIB involves applying delayed extraction, an essential technique in TOF mass spectrometry. [17][18][19][20][21][22][23][24][25][26][27][28] In the conventional static extraction mode (standard mode) of TOF-SIMS analysis, the width of the primary ion pulse directly affects the start accuracy of the TOF measurement, regardless of whether the analysis is performed with Ar-GCIB or with a liquid metal ion gun. This is because the pulsed primary ions desorb the secondary ions while the extraction field is already switched on, as shown in Scheme 1(a).…”

Section: Resultsmentioning

confidence: 99%

Improved mass resolution and mass accuracy in TOF-SIMS spectra and images using argon gas cluster ion beams

Shon¹,

Yoon²,

Moon³

et al. 2016

Biointerphases

View full text Add to dashboard Cite

The popularity of argon gas cluster ion beams (Ar-GCIB) as primary ion beams in time-of-flight secondary ion mass spectrometry (TOF-SIMS) has increased because the molecular ions of large organic- and biomolecules can be detected with less damage to the sample surfaces. However, Ar-GCIB is limited by poor mass resolution as well as poor mass accuracy. The inferior quality of the mass resolution in a TOF-SIMS spectrum obtained by using Ar-GCIB compared to the one obtained by a bismuth liquid metal cluster ion beam and others makes it difficult to identify unknown peaks because of the mass interference from the neighboring peaks. However, in this study, the authors demonstrate improved mass resolution in TOF-SIMS using Ar-GCIB through the delayed extraction of secondary ions, a method typically used in TOF mass spectrometry to increase mass resolution. As for poor mass accuracy, although mass calibration using internal peaks with low mass such as hydrogen and carbon is a common approach in TOF-SIMS, it is unsuited to the present study because of the disappearance of the low-mass peaks in the delayed extraction mode. To resolve this issue, external mass calibration, another regularly used method in TOF-MS, was adapted to enhance mass accuracy in the spectrum and image generated by TOF-SIMS using Ar-GCIB in the delayed extraction mode. By producing spectra analyses of a peptide mixture and bovine serum albumin protein digested with trypsin, along with image analyses of rat brain samples, the authors demonstrate for the first time the enhancement of mass resolution and mass accuracy for the purpose of analyzing large biomolecules in TOF-SIMS using Ar-GCIB through the use of delayed extraction and external mass calibration.

show abstract

“…Another mode of operation could be used, which combines a higher spatial resolution of ca 400 nm and a mass resolution of M/ΔM = 8 × 10 3 , thanks to a delayed extraction of the secondary ions. 43 However in the present case the "high-current bunched mode" was preferred because it ensures the fastest acquisition time. Under these conditions, the fluence (also called the primary ion dose density) was maintained at 5.0 × 10 11 ions cm −2 , which is below the so-called static SIMS limit.…”

Section: Tof-sims Imagingmentioning

confidence: 92%

“…Consequently, in this mode the pixel stepsize was smaller than the beam diameter (2 μm), leading to oversampling. Another mode of operation could be used, which combines a higher spatial resolution of ca 400 nm and a mass resolution of M /Δ M = 8 × 10 3 , thanks to a delayed extraction of the secondary ions . However in the present case the “high‐current bunched mode” was preferred because it ensures the fastest acquisition time.…”

Section: Methodsmentioning

confidence: 99%

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

Desbenoît

Walch

Spengler

et al. 2017

Rapid Comm Mass Spectrometry

View full text Add to dashboard Cite

RationaleMass 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.MethodsFollowing 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.ResultsThe 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.ConclusionsThis 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.

show abstract

Time‐of‐flight secondary ion mass spectrometry imaging of biological samples with delayed extraction for high mass and high spatial resolutions

Cited by 88 publications

References 56 publications

The Prismatic Layer of Pinna: A Showcase of Methodological Problems and Preconceived Hypotheses

The Prismatic Layer of Pinna: A Showcase of Methodological Problems and Preconceived Hypotheses

Improved mass resolution and mass accuracy in TOF-SIMS spectra and images using argon gas cluster ion beams

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

Contact Info

Product

Resources

About