Matrix-Enhanced Secondary Ion Mass Spectrometry:  A Method for Molecular Analysis of Solid Surfaces

Abstract

A new methodology, matrix-enhanced secondary ion mass spectrometry (ME-SIMS), is reported for the molecular analysis of biomaterials. The technique applies static secondary ion mass spectrometry (SSIMS) techniques to samples prepared in a solid organic matrix similar to sample preparations used in matrix-assisted laser desorption/ionization (MALDI). Molecular ions are observed in this ion beam sputtering of organic mixtures for peptides and oligonucleotides up to masses on the order of 10 000 Da. This matrix-enhanced SIMS exhibits substantial increases in the ionization efficiency of selected analyte molecules compared to conventional SSIMS processes. Thus, higher mass peptides, proteins, and nucleic acids become accessible to near-surface analysis by ion beam techniques, and subpicomole sensitivity has been demonstrated. A number of matrices were examined for their efficiency in ME-SIMS applications, and these initial matrix studies focused on common MALDI matrices and their isomers. The results of this survey indicate that 2,5-dihydroxybenzoic acid provides the best general enhancement of molecular secondary ions emitted from analyte/matrix mixtures.

Gold-Enhanced Biomolecular Surface Imaging of Cells and Tissue by SIMS and MALDI Mass Spectrometry

“…29 Another way of modifying the bioorganic surface is deposition of a MALDI matrix. In 1996, Wu and Odom 21 showed that MALDI sample preparation protocols can be used in SIMS to enhance the desorption/ionization yield of "large" molecular species. This technique is named matrix-enhanced (ME)-SIMS.…”

Higher sensitivity secondary ion mass spectrometry of biological molecules for high resolution, chemically specific imaging

“…The central role of the sample surface has led to the development of several sample preparation techniques that have demonstrated increased molecular ion yields of high mass molecules. These are: (1) matrix-enhanced SIMS (ME-SIMS) [13][14][15][16][17][18][19][20]-uses the sample preparation protocols of MALDI to benefit from the detanglement [21] and chemical ionization aspects of MALDI [22][23][24]. Molecular ions of analytes as large as ubiquitin and lysozyme have been detected, and for lower mass analytes, Ͻ2 kDa, the ME-SIMS spectra frequently resemble those obtained using MALDI [17,19].…”

Proteome imaging: A closer look at life's organization

“…Yet, the real promise of high-resolution imaging of larger biomolecules (peptides and proteins) has yet to be shown with SIMS imaging without surface modifications. After the successful introduction of organic matrices in MALDI, it became clear that a similar beneficial effect was found when a MALDI preparation was examined with SIMS [44]. Protein ions up to 12 kDa were found using a standard MALDI sample preparation protocol, indicating that similar gas- phase ion molecule reactions must play a role during matrix enhanced SIMS (ME-SIMS).…”