The relatively new electrospray droplet impact method is based on electrospray at atmospheric pressure and has been successful in achieving efficient desorption/ionization of biological molecules, soft etching of polymers, and nonselective etching of metal oxides. However, the beam current and brightness of this method are not practical for surface analyses. To improve the performance of this method, the authors have developed a new droplet ion beam gun using an electrospray of aqueous solutions in a vacuum. This technique could be expected to be a high-intensity massive cluster ion beam and they evaluate the performance of the vacuum-type electrospray droplet ion (V-EDI) gun. In this study, V-EDI and gas cluster ion beam guns were installed in a time-of-flight analyzer to directly compare the relative secondary ion yields of several biomolecules produced by several cluster ion beams.