A new and simple strategy based on nanostructured CaCO3-PEI MPs for phenol sensing using PDMS/glass fluidic microchip is developed. This fluidic microsystem including integrated screen-printed-electrodes (SPE) modified with CaCO3-PEI MPs and tyrosinase (Tyr) through cross-linking with glutaraldehyde, represents a low cost platform for phenol detection. The designed fluidic microsystem improves the sensitivity of the biosensor allowing the detection of very low concentrations of phenol (up to 10 nM). This device shows high repeatability and low detection limit, is easy to be fabricated, inexpensive, disposable and amenable to mass production.