The use of a new class of hybrid nanomaterials as label-free optical biosensors for bacteria detection (E. coli K12 as a model system) is demonstrated. The hybrids combine a porous SiO2 (PSiO2) optical nanostructure (a Fabry–Pérot thin film) used as the optical transducer element and a hydrogel. The hydrogel, polyacrylamide, is synthesized in situ within the nanostructure inorganic host and conjugated with specific monoclonal antibodies (IgGs) to provide the active component of the biosensor. The immobilization of the IgGs onto the hydrogel via a biotin-streptavidin system is confirmed by fluorescent labeling experiments and reflective interferometric Fourier transform spectroscopy (RIFTS). Additionally, the immobilized IgGs maintain their immunoactivity and specificity when attached to the sensor surface. Exposure of these modified-hybrids to the target bacteria results in “direct cell capture” onto the biosensor surface. These specific binding events induce predictable changes in the thin-film optical interference spectrum of the hybrid. Preliminary studies demonstrate the applicability of these biosensors for the detection of low bacterial concentrations in the range of 103–105 cell mL−1 within minutes.