Gold Sputtered Fiducial Markers for Combined Secondary Ion Mass Spectrometry and MALDI Imaging of Tissue Samples

Abstract

Mass spectrometry imaging (MSI) is a label free technique capable of providing simultaneous identification and localization of biomolecules. A multimodal approach is required that allows for the study of the complexity of biological tissue samples to overcome the limitations of a single MSI technique. Secondary ion mass spectrometry (SIMS) allows for high spatial resolution imaging while matrix-assisted laser desorption (MALDI) offers a significantly wider mass range. The combination of coregistered SIMS and MALDI images results in detailed and unique biomolecular information. In this Technical Note, we describe how gold sputtered/implanted fiducial markers (FM) are created and can be used to ensure a proper overlay and coregistration of the two-dimensional images provided by the two MSI modalities.

Mass spectrometry imaging for plant biology: a review

“…Co-registration of high-resolution optical images from histochemical staining with the acquired MSI data provides more in-depth information (tissue/cell type distribution), aiding sample interpretation. Another combination is that of MALDI and SIMS, which has been used extensively in plant and animal MSI imaging (Chughtai et al 2012 ; Hanrieder et al 2014 ; Ogrinc Potočnik et al 2014 ; Seaman et al 2014 ), where the former has been used to generate lower-resolution images across a wide area, and SIMS for very-high-resolution imaging of a smaller sub-section of the tissue. The modality need not be another MSI technique or optical imaging approach; other modalities including MRI, FT-IR and XRF could be employed to examine the underlying biology.…”

3-D imaging mass spectrometry of protein distributions in mouse Neurofibromatosis 1 (NF1)-associated optic glioma

“…The use of fiducials for image registration has been incorporated into a number of imaging modalities including MRI, CT, PET and MALDI IMS. Methods for incorporating the reference points within the sample vary from one technique to another, and a number of approaches have been previously reported for MALDI IMS [7, 10, 12]. As such, some investigators have utilized printed fiducials to register optical images to images generated by signals observed through MALDI IMS analysis [7], while others have used fiducial markers to help align breast cancer explants grown in mice [10].…”

“…These fiducials were produced by injecting dyes into gelatin surrounding the sample tissue. Multimodal image alignment has also been achieved using gold sputtered fiducial markers to combine Secondary Ion Mass Spectrometry (SIMS) and MALDI IMS of tissue samples [12]. …”

Metabolite mapping by consecutive nanostructure and silver‐assisted mass spectrometry imaging on tissue sections

“…Future work should further complement the presented DIOS/Ag‐DIOS approach – first, by addressing the currently challenging co‐registration of MSI data and histology. This would be aided by the future implementation of fiducial markers in the sectioned tissue block, to allow alignment of introduced, and therefore known, spatial markers . Ultimately, the aim should be the further adaptation of DIOS/Ag‐DIOS to allow direct analysis of tissue (i.e.…”