A very-long-chain (C22) organosilicon self-assembled monolayer (SAM) with terminal glycidyl groups was used to immobilize antibodies on the silica waveguide of a Love mode surface acoustic wave (SAW) immunosensor. This route enabled us to specifically detect, in real time, living Escherichia coli bacteria by using monoclonal anti-E. coli antibodies, leading to a marked sensor response in liquid aqueous medium. Conversely, no bacteria detection could be observed by this direct method upon functionalization of the waveguide surface by a (3-glycidoxypropyl) trimethoxysilane (GPTS) monolayer. This improvement was attributed to a surface smoothing effect resulting from the very-long-chain SAM and a better accessibility of the surface epoxide groups.