The present contribution aims at illustrating and demonstrating how micro-machining technology can give a boost to High Performance Liquid Chromato-graphy (HPLC).Currently, HPLC is routinely used in nearly every chemical analysis lab.Despite its high degree of maturity, the technique however suffers from serious performance limitations when faced to the complex samples that need to be separated to solve the current state-of-the-art problems in the biological and pharmaceutical research (e.g., proteomics and metabolomics), thefood and environmental analysis, etc The currently used packed bed HPLC columns are clearly underachieving because of the packing disorder and the concomitant large degree of band broadening.To solve this packing disorder problem, the present contributionwill focus on the possibilities of advanced photolithographic etching techniques such as the Bosch-process to produce perfectly ordered porous support columns with optimized hydrodynamic shape and optimized external porosity.