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

Abstract

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is one of the most important techniques for chemical imaging of nanomaterials and biological samples with high lateral resolution. However, low ionization efficiency limits the detection of many molecules at low concentrations or in very small volumes. One promising approach to increasing the sensitivity of the technique is by the addition of a matrix that promotes ionization and desorption of important analyte molecules. This approach is known as matrix-enhanced secondary-ion mass spectrometry (ME-SIMS). We have investigated the effect of matrix acidity on molecular ion formation in three different biomolecules. A series of cinnamic acid based matrixes that vary in acidity was employed to systematically investigate the influence of matrix acidity on analyte ion formation. The positive ion signal for all three biomolecules showed a strong increase for more acidic matrixes. The most acidic matrix was then vapor-deposited onto mouse brain sections. This led to significant enhancement of lipid signals from the brain. This work indicates that proton donation plays an important role in the formation of molecular ions in ME-SIMS.

Enhancing Ion Signals and Improving Matrix Selection in Time-of-Flight Secondary Ion Mass Spectrometry with Microvolume Expansion Using Large Argon Clusters

“…This can be related to the increase in the ion signal of the fragment but also to the fragmentation induced during the transfer with the Ar cluster beam. However, the [PC(34:1) + H] + /PC HG secondary ion yield ratio is greatly increased upon transfer on CHCA (SI, Figure S6B), showing that, in agreement with other studies, 16,48,49 the matrix enhances the formation of [M + H] + ions through at least two mechanisms, by reducing the fragmentation and donating protons.…”

“…This result was anticipated since CHCA is a cinnamic acid of p K a of 1.17 and proton donation plays a major role in the formation of molecular ions for those kinds of matrices. Previous studies have demonstrated a correlation between decreasing p K a and increasing protonated positive ion, especially for halogen-substituted cinnamic acid derivatives …”

“…Previous studies have demonstrated a correlation between decreasing pK a and increasing protonated positive ion, especially for halogensubstituted cinnamic acid derivatives. 49 The microvolume expansion technique may benefit from the increase in the ion signal at the interface between the organic layer and a hard substrate, which could explain the observed increase in signal despite the reduction in available molecules per unit area after expansion. To verify this hypothesis, mouse brain gray matter was also transferred onto another hard surface (Au-coated silicon) and compared to a soft surface (PE foil).…”

“…Additionally, a comprehensive matrix optimization can be conducted by evaluating the sputtering yield, the ionization yield, and the damage cross section for a wider range of matrices. With this aim in mind, potential new matrix candidates, including halogen-substituted cinnamic acid derivatives 49 or acid molecules without aromatic cycles, should be explored.…”

Matrix-Enhanced SIMS: The Influence of Primary Ion Species and Cluster Size on Ion Yield and Ion Yield Enhancement of Lipids

“…This approach mimics what has been done in matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). A variety of matrix compounds have been demonstrated to improve ion yield in SIMS, including both compounds used in MALDI-MS as well as compounds that are unsuitable for MALDI-MS. − …”