Development of a Knudsen-type matrix coater for sample preparation for mass spectrometry imaging

Abstract

The use of time-of-flight secondary ion mass spectrometry (SIMS) is of increasing interest for biological and medical applications due to its ability to provide chemical information on a submicrometer scale. However, the detection of larger biomolecules such as phospholipids and peptides is often inhibited by high fragmentation rates and low ionization efficiencies. One way to increase the secondary ion molecular yield is to chemically modify the surface using the matrix-enhanced SIMS approach, where an organic matrix is placed upon the surface. In this study, a Knudsen cell type matrix coater was developed in order to produce well-defined thicknesses of a matrix on a sample in order to study the effect of these matrix layers on the secondary ions. Using this technique, an order of magnitude enhancement of the useful ion yield for lipids was observed and clear enhancement of image contrast for lipids in brain tissue was demonstrated. The study shows that the layer thickness has a great influence on the emission of secondary ions, and therefore, its precise control is important for optimal yield enhancement.

Influence of Matrix pKa on Molecular Ion Formation in Matrix-Enhanced Secondary-Ion Mass Spectrometry

“…As a final experiment, the best performing matrix, PFCCA, was vapor-deposited onto half of a mouse brain section. Positive ion yield for selected brain lipids was compared between the coated and uncoated portions of the brain as well as with previously published data from HCCA coated brain Figure shows selected ion images from the PFCCA-coated mouse brain.…”

“…Successful synthesis and purity of the PFCCA was confirmed by NMR and mass spectrometry. A 400 nm layer of PFCCA was vapor-deposited onto one-half of the mouse brain using a Knudsen-type vapor-deposition system that allows for control of the deposition rate and layer thickness and that has been previously described …”

Effect of cocrystallization due to bile acid on molecular‐ion sensitivity of biological phospholipids in Bi cluster time‐of‐flight secondary ion mass spectrometry measurements

“…In the future, phospholipid films coated with bile acid will be evaluated to investigate whether this method can be applied for the imaging analysis of lipids. The thickness of the MALDI matrix CHCA film affected not only the enhancement of the DPPC molecular ion but also the suppression of the fragment ions 30 . Therefore, the evaluation of the biological molecule distribution via TOF‐SIMS can be developed if the coating method includes these new aliphatic matrices to effectively enhance the sensitivity of the phospholipids.…”

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2017–2018

“…A Knudsen-type matrix coater has been developed in order to produce well-defined thicknesses of matrix in order to study the effect of these matrix layers on the production of secondary ions (Körsgen et al, 2018). The layer thickness was shown to have a great influence on the emission of secondary ions and, therefore, its precise control is important for optimal yields.…”