Energy-efficient process intensification is a key aspect for a sustainable industrial production. To improve energy conversion efficiency high intensity cavitation is a promising method, especially in cases where the material to be treated is valuable and on the micro meter scale. Transient collapsing cavitation bubbles gives powerful effects on objects immersed in fluids, like cellulose fibers, mineral particles, enzymes, etc. The cavitation process needs optimization and control, since optimal conditions is multivariate challenge. This study focuses on different design principles to achieve high intensity cavitation in a specific volume in a continuous flow. This study explores some potential design principles to obtain energy efficient process intensification. The objective is to tune several different resonance phenomena to create a powerful excitation of a flowing suspension (two-phase flow and cavitation bubbles). The reactor is excited by sonotrodes, connected to two coupled resonant tube structures, at the critical frequency. Finally cavitation bubbles are initiated by a flow through a venturi nozzle. The acoustically optimised reactor geometry is modelled in Comsol Multiphysics®, and excited by dedicated ultrasound signals at three different frequencies. The effect of the high intensity cavitation is experimentally evaluated by calorimetric method, foil tests and degree of fibrillation on cellulose fibers.