The new physics associated with cluster SIMS, i.e. reduced chemical damage enabling 3D dynamic imaging, and increased ion yields from organics samples, suggests that cluster sources may be suitable for use on commercial MALDI/electrospray (ESI) instruments. In efforts to investigate this approach to secondary ion analysis, a 20 keV C-60(+) primary ion source by Ionoptika Ltd. was fitted to a commercial LC/MS/MS instrument; the QSTAR (R) XL system by Applied Biosystems/MDS Sciex. This instrument is capable of MS/MS, ion trapping, chemical imaging, and utilizes an orthogonal ToF, enabling use of a DC primary ion beam for imaging and data collection. The system employs high nitrogen pressure, typically several millitorr, in the sample region, as opposed to large extraction voltages, to facilitate the transmission of the secondary ions to the ToF region. In these initial experiments, it was demonstrated that ion signal generated by C-60(+) bombardment can be enhanced by trapping in the collision cell and that secondary ions can fragment via collision induced dissociation ( CID) to yield MS/MS information. In ToF-MS mode, efficiencies are comparable with pulsed primary beam ToF-SIMS instruments. Mass resolution of over 12,000 is routinely observed with mass accuracy in the 2 ppm range, which has important implications in accurate ion mapping in imaging mode. (C) 2008 Elsevier B. V. All rights reserved.