Antibiotic resistance constitutes a serious threat in healthcare. Across the world, antibiotic resistance has reached an unsafe level and, if the situation doesn’t change, even benign infections will reveal dangerous. The increase and spread of antibiotic resistance need to be urgently solved. The WHO provides a priority list for bacteria antibiotic resistance, divided into three groups according to the urgent need for new treatments. Pseudomonas aeruginosais part of the group 1: « critical » level. P. aeruginosa, a gram negative, opportunistic pathogenic bacteria, is a major cause of various infections because of its ability to form biofilms in several environments. In this context, the aim of this work is to discover new natural antimicrobial agents with original modes of action. The strategy we propose relies on the disruption of the biofilm architecture to improve the penetration of antimicrobial agents. Thanks to a CDC bioreactor system, we generated biofilms imitating in vivoconditions and characterized their architecture using electron microscopy. The effects of antimicrobial agents have been studied (i) on biofilm architecture using microfluidic cells and (ii) on biofilm formation using Nunc TSP plates. From these data, we intend to develop a new, easier and faster method to measure the disruption of biofilm architecture based on electrical potentials measurements. The use of selected mutant strains and known modulators of QS systems will allow to elucidate the mechanism and targets of discovered natural molecules active towards the biofilms.