Molecule-Specific Imaging with Mass Spectrometry and a Buckminsterfullerene Probe: Application to Characterizing Solid-Phase Synthesized Combinatorial Libraries

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Abstract
We employ a newly developed buckminsterfullerene (C60) primary ion beam with time-of-flight secondary ion mass spectrometry to create molecule-specific images of resin particles employed in the solid-phase synthesis of peptide combinatorial libraries. This new cluster ion source, when operated at an incident energy of 20 keV, is remarkably effective at desorbing small peptides directly from a polymer surface and opens new possibilities for characterizing large arrays of diverse sets of molecules. In addition, the C60 ion beam may be focused to a spot of 1.5 μm in diameter, enabling molecule-specific images of single 100 μm resin particles to be acquired. We report three significant aspects associated with utilizing the C60 projectile that show how this technology can be taken to a more advanced level, especially when compared to results obtained with more conventional atomic primary ions. First, the useful yield of molecular ions is generally observed to be enhanced by at least 3 orders of magnitude over those previously possible. Second, the energy dissipation process associated with the C60 impact is most efficient at desorbing molecules on soft substrates such as polymer surfaces rather than harder substrates such as metals or semiconductors. Third, there is a greatly reduced tendency for insulating surfaces to build up excess charge, obviating the need for charge compensation. Using a small five-member peptide library as a model, we show that by utilizing the focusing properties of the C60 beam, it is possible to assay the surface composition of 100-μm polymer beads at a rate of up to 10 particles/s. Moreover, even at the picomole level, there are enough sequence ions in the mass spectrum to determine a unique composition. The results illustrate the ability to quickly assay large libraries without the use of tags and suggest the strategy may be applicable to a range of high-throughput experiments.