We report a general procedure to prepare functional organic thin films for biological assays on oxide surfaces. Silica surfaces were functionalized by self-assembly of an amine-terminated silane film using both vapor- and solution-phase deposition of 3'-aminopropylmethyldiethoxysilane (APMDES). We found that vapor-phase deposition of APMDES under reduced pressure produced the highest quality monolayer films with uniform surface coverage, as determined by atomic force microscopy (AFM), ellipsometry, and contact angle measurements. The amine-terminated films were chemically modified with a mixture of carboxylic acid-terminated poly(ethylene glycol) (PEG) chains of varying functionality. A fraction of the PEG chains (0.1-10 mol %) terminated in biotin, which produced a surface with an affinity toward streptavidin. When used in pseudo-sandwich assays on waveguide platforms for the detection of Bacillus anthracis protective antigen (PA), these functional PEG surfaces significantly reduced nonspecific binding to the waveguide surface while allowing for highly specific binding. Detection of PA was used to validate these films for sensing applications in both buffer and complex media. Ultimately, these results represent a step toward the realization of a robust, reusable, and autonomous biosensor.