| AVS 63rd International Symposium & Exhibition | |
| Applied Surface Science | Thursday Sessions |
| Session AS-ThA |
| Session: | Advances for Complicated Sample Preparation Strategies and Complex Systems |
| Presenter: | Matthias Lorenz, National Physical Laboratory, UK |
| Authors: | M. Lorenz, National Physical Laboratory, UK A.G. Shard, National Physical Laboratory, UK J.-L. Vorng, National Physical Laboratory, UK I.S. Gilmore, National Physical Laboratory, UK |
| Correspondent: | Click to Email |
We report on a novel method for controlled and versatile application of matrix compound for the purpose of matrix enhanced secondary ion mass spectrometry (ME SIMS). General applicability of this approach for ion signal enhancement of drug molecules and endogenous compounds in drug dosed tissue homogenate is demonstrated.
A major problem for SIMS imaging in life-sciences is the signal-limited spatial resolution and matrix effects that suppress ion yields. In severe cases, the ion signal may be lost all together. This leads to the adage that not seeing a molecule in SIMS does not mean it is not there. One route forward is to use a molecule to enhance the signal as done in matrix assisted laser desorption/ionization (MALDI). However, it is well-known that this causes redistribution of analytes (such as drugs) over tens of microns. This circumvents the resolution benefit of SIMS over MALDI. Furthermore, methods used for MALDI are not suitable for 3D imaging, where the matrix layer would be sputtered away. We report on a novel technique for the controlled application of matrix compounds specifically for ME SIMS that overcomes these two major barriers.
The new approach provides high flexibility and precise control of the timing and amount of material applied. It is applicable for a wide range of matrix compounds. The general approach and critical instrumental parameters of the technique will be discussed, and its applicability for the enhancement of SIMS ion signals will be shown on examples of drug compounds and drug molecules embedded in tissue homogenate. We show that ion signals of clozapine could be enhanced by a factor of 3 for the protonated molecule [M+H]+ by adding 2,5-dihydroxybenzoic acid (2,5-DHB), a common matrix compound used in MALDI. The [M+H]+ ions of the drug molecules chloroquine and tamoxifen show an enhancement with 2,5-DHB matrix application. A factor of 7 enhancement of clozapine could be achieved with 3-nitrobenzonitrile (3-NBN), a species utilized for primary ion formation in the matrix assisted ionization vacuum (MAIV) technique. The abundance and intensity of lipid related signals (e.g., the phosphocholine fragment at m/z 184) in the spectra are significantly enhanced for the analysis of the tissue homogenate. The addition of formic acid shows another example for signal enhancement using the new approach, with an increase of the [M+H]+ signal of the drug molecule by a factor greater than 3 and of the phosphocholine signal (m/z 184) by a factor of 6.