ATTOMOLE BIOMOLECULE MASS ANALYSIS BY MATRIX-ASSISTED LASER-DESORPTION IONIZATION FOURIER-TRANSFORM ION-CYCLOTRON RESONANCE

Significantly improved sensitivity for analysis of biomolecules by MALDI FT-ICR mass spectrometry is achieved by (i) microscope monitored sample deposition onto a small indentation on the probe tip and (ii) multiple remeasurement of ions from a single laser shot. A simple modification to the solids probe tip allows for microdeposition of a few amols of analyte onto small indentation spots previously aligned with the laser beam. Ion multiple remeasurement of the same ion packet enhances the signal-to-noise ratio and thus extends the achievable FT-ICR MS detection limit. We demonstrate that FT-ICR can be used to detect parent and structurally significant fragment ions of peptides and phospholipids at low amol amounts. Positive ion mass spectra for similar to 90 amol of a mixture of angiotensin II and bradykinin, similar to 40 amol of dipalmitoylglycerophosphatidylcholine, and similar to 8 amol of substance P constitute the lowest reported detection limits to date for FT-ICR mass analysis of MALDI-generated ions.