Matrix-enhanced secondary ion mass spectrometry:  a method for molecular analysis of solid surfaces

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.