The BioCD is a class of self-referencing interferometric optical biosensor that measures phase modulation from proteins on a spinning disk. The optical detection of the patterns at high speed yields low noise floors far from 1/f noise. Two scans of a disk before and after a 20 hour buffer wash are differenced yielding an rms surface height measurement error of 45 pm corresponding to 5 femtograms of protein within a focal spot diameter. Simple area scaling relations are derived that predict the performance of immunoassays as a function of well area. The scaling mass sensitivity of the BioCD is determined to be 0.25 pg/mm under the conditions of an assay, with a metrology limit of the technique between 0.05 to 0.1 pg/mm. The BioCD sensitivity is equivalent to the best reported surface mass sensitivity of surface plasmon resonance sensors, and is achieved without resonant structures and hence is easy to fabricate and operate.© (2006) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.