In this contribution highly sensitive and quantitative analytical methodologies based on femtosecond Laser Ablation IonizationMass Spectrometry (fs-LIMS) for the analysis of model systems and state-of-the-art Cu interconnects are reviewed and discussed. The method development introduces in a first stage a 1D chemical depth profiling approach on electrodeposited Cu films containing periodically confined organic layers. Optimization of measurement conditions on these test platforms enabled depth profiling investigations with vertical resolution at the nm level. In a second stage, a matrix-free laser desorption methodology was developed that allowed for preliminary molecular identification of the embedded organic contaminants beyond elementary composition. These studies provided specific fragmentation markers in the lower mass range, which support a previously proposed reaction mechanism responsible for successful leveling employing a new class of plating additives for Damascene processes. Further combined LIMS and Scanning Auger Microscopy (SAM) studies on through-silicon-vias (TSV) interconnects confirmed the embedment upon plating of the organic additives at the upper side-walls of the TSV channel in the boundary between the Cu seed layer and the electrodeposited Cu. (C) The Author(s) 2018. Published by ECS.