D. Lipinsky

Changes in the molecular ion yield and fragmentation of peptides under various primary ions in ToF-SIMS and matrix-enhanced ToF-SIMS

Time of flight secondary ion mass spectrometry (ToF-SIMS) is a powerful technique for the nanoanalysis of biological samples, but improvements in sensitivity are needed in order to detect large biomolecules, such as peptides, on the individual cell level at physiological concentrations. Two promising options to improve the sensitivity of SIMS to large peptides are the use of cluster primary ions to increase desorption of intact molecules or the use of matrix-assisted laser desorption/ionization (MALDI) matrices to increase the ionization probability. In this paper, the authors have combined these two approaches in order to improve understanding of the interaction between ionization and fragmentation processes. The peptides bradykinin and melittin were prepared as neat monolayers on silicon, in a Dextran-40 matrix and in two common MALDI matrices, 2,5-dihydroxybenzoic acid (DHB) and α-cyano-4-hydroxy cinnamic acid (HCCA). ToF-SIMS spectra of these samples were collected using a range of small Bi cluster primary ions and large Ar cluster primary ions. The trends observed in the molecular ion yield and the [M+H](+)/C4H8N(+) ratio with primary ion cluster size were sample system dependent. The molecular ion yield of the bradykinin was maximized by using 30 keV Bi3 (+) primary ions in a DHB matrix but in the HCCA matrix, the maximum molecular ion yield was obtained by using 30 keV Bi7 (+) primary ions. In contrast, the molecular ion yield for melittin in both matrices was greatest using 20 keV Ar2000 (+) primary ions. Improvements in the molecular ion yield were only loosely correlated with a decrease in small fragment ions. The data indicate a complex interplay between desorption processes and ion formation processes which mean that the optimal analytical conditions depend on both the target analyte and the matrix.

ToF-SIMS investigation of tribochemical surface reaction films built up by specially added cooling lubricants

Cooling lubricants based on polyalphaolefin (PAO) are used in finishing processes for metallic components, but their influence on the formation of lifespan increasing tribochemical surface reaction films (boundary films) is poorly understood. The binding characteristics of different additives during finishing processes have been investigated using time-of-flight secondary ion mass spectrometry (ToF-SIMS). Steel substrates heated to selected temperatures between 150 and 700 °C were dipped in four different cooling lubricants based on PAO to study fundamental binding processes. The boundary films built up on the steel surfaces were analyzed using ToF-SIMS via acquiring surface spectra as well as depth profiles. The results of these studies reveal the temperatures at which additives bind to steel surfaces and provide information regarding the thickness of the boundary films formed during the finishing. They also show that the temperature at which the boundary film formation starts is at around 400 to 450 °C....

Imaging of atomic and molecular species in tissue with Laser-SNMS for pharmaceutical studies

The success of several anti-cancer therapies as well as other therapeutic and diagnostic strategies relies on the ability to selectively deliver compounds to target cells while sparing normal tissue. For many applications, however, current analytical methods lack the sensitivity and selectivity necessary to determine the distribution of pharmaceutical ultra-trace compounds within tissues with sub-cellular resolution.Laser secondary neutral mass spectrometry (Laser-SNMS) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) are capable of detecting atoms and molecules with high sensitivity and a spatial resolution of up to 100 nm. The use of such methods requires special preparation techniques which preserve the morphological and chemical integrity of the living cell.Laser-SNMS was used to verify the effectiveness of the delivery process for various pharmaceutical compounds in animal studies. After injection of the pharmaceuticals, different types of mouse tissue such as brain, kidney and tumors were extracted, then prepared on a special specimen carrier and subsequently plunged with high velocity into LN2-cooled propane for cryofixation. After trimming, the tissue block was freeze-dried. For postionization of sputtered neutrals, a laser beam with a wavelength of 193 nm was used. Ion-induced electron images showed that the structural and chemical integrity of the cells had been preserved. Cell-specific elemental and molecular signals could be used to identify individual cells and cell nuclei. The obtained data yield information about the distribution of the pharmaceutical products in different kinds of tissue.