Enhanced Peptide Molecular Imaging Using Sodium Salt Aqueous Droplets

A new method, droplet-enhanced secondary ion mass spectrometry (SIMS), was developed for the molecular imaging analysis of biological samples. To facilitate the ionization of bio-molecules, a few microliters of aqueous solution containing sodium salt was dropped onto a peptide sample before time of flight (TOF)-SIMS measurement. Using this method, we have successfully obtained strong molecular secondary ion signals from molecular weight (MW) < 1587 peptide samples while maintaining their natural distribution. On the basis of various experiments, we observed that a neutral sputtered peptide molecule (M-0) is effectively ionized by collision with a sodium ion (Na +) above the sample surface (M-0 <- Na+), and excess sodium salt doped onto the sample has effect on inhibition of the positive ion formation. This method enables to simultaneously induce the ionization of each peptide present in a multicomponent solution. We also succeeded in detecting and quantifying nanogram levels of peptides with bubble jet (BJ) printing droplets. The results obtained indicate the usefulness of TOF-SIMS for micro-meter order sized peptide/protein screening system for assessing disease and drug efficacy.