In this work, quartz crystal microbalance (QCM) crystal surfaces were analyzed in order to study the behavior of protein attachment on fouling substrates. In this context, covalent and noncovalent immobilization of different proteins [bovine serum albumin (BSA), collagen] has been investigated. For the noncovalent immobilization, silicon dioxide-coated QCM crystals were used, while the covalent immobilization was obtained via plasma-polymerized acrylic acid film (ppAA) deposited onto the QCM substrates. Two different activation processes, namely, reaction with trifluoroacetic anhydride (TFAA) and 1-ethyl-3,3-dimethyl carbodiimide (EDC) and N-hydroxysuccinimide (NHS), were studied.After the QCM experiments, all samples were analyzed with X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry to gain information on the surface chemistry and composition. The results indicate that the protein adsorption process depends on protein concentration, whereas the complement activation effectiveness depends on protein type. In particular, for BSA, XPS and QCM data show a greater immobilization in the case of EDC/NHS activation compared to the TFAA, whereas in the case of collagen, only the EDC/NHS activation was able to yield covalent coupling. Copyright © 2010 John Wiley & Sons, Ltd.