Tandem mass spectrometry is a widely used tool for molecular structure determination of biomolecules. Advances in
proteome analysis depend on the development of improved methods for ion activation that yield greater sequence
information, with selective control over the fragmentation chemistry. A novel activation method, femtosecond laser-induced
ionization/dissociation, is described here, and compared to collision induced dissociation through the analysis of three peptides.
We present a novel imaging mass spectrometry technique that uses femtosecond laser pulses to directly ionize the
sample. The method offers significant advantages over current techniques by eliminating the need of a laser-absorbing
sample matrix, being suitable for atmospheric pressure sampling, and by providing 10μm resolution, as demonstrated
here with a chemical image of vegetable cell walls.
Controlled molecular photofragmentation and ionization achieved with shaped femtosecond laser pulses is coupled with
mass spectrometry to achieve a powerful multidimensional tool for fast, accurate, reproducible and quantitative
molecular identification. Specific pulse shaping functions are introduced to enhance structure-dependent differences in
fragmentation fingerprints. Identification of geometric and structural isomer mixtures is demonstrated. Receiver
operational (ROC) curves from our experimental data demonstrate the enhanced reliability that can be achieved by
femtosecond laser control mass spectrometry. The potential use of this method for identification of chemicals and
explosives with no false alarms is discussed.