Aim: Preliminary experiments confirm the possibility to load Red Blood Cells (RBCs) with probing molecules (PM) by applying mechanical shear stresses (τ) on RBCs stroma. This work is aimed at studying the optimal fluid dynamic conditions allowing the encapsulation of PM into RBCs flowing in a microchannel (MC). Methods: A computational model was developed by using COMSOL Multiphysics 4.2a (Stockholm, Sweden). A 50 x 50 μm cross-section and 58.5 mm length MC was considered. The Mixture Model was used to evaluate velocity (v), volume fraction of dispersed phase (Id) and τ for a suspension of RBCs and PM (FITC-Dextran) in a Phosphate Buffer. When the pair of τ values and duration lays in the sub-haemolytic portion of the Tillman Dia...