In the present contribution Angle Resolved X-ray Photoelectron Spectroscopy (AR-XPS) was proposed as useful tool to address the challenge of probing the near-surface region of bio-active sensors surface. A model bio-functionalized surface was characterized by Parallel AR-XPS and commercially available Thermo Avantage-ARProcess software was used to generate non-destructive concentration depth profiles of protein functionalized silicon oxide substrates. At each step of the functionalization procedure, the surface composition, the overlayer thickness, the in-depth organization and the in-plane homogeneity were evaluated. The critical discussion of the generated profiles highlighted the relevance of the information provided by PAR-XPS technique.