Differential phase-contrast BioCD biosensor.

Common-path differential phase-contrast interferometry measures the spatial gradient of surface dipole density on a bio-optical compact disk (BioCD) and is sensitive to small changes in dipole density following molecular binding of target molecules out of solution. The recognition molecules are antibody IgG proteins that are deposited in periodic patterns on the BioCD using soft lithography or photolithography on the silanized silica surfaces of dielectric mirrors. Spatial carrier-wave sideband demodulation extracts the slowly varying protein envelope that modulates the protein carrier frequency. The experimental interferometric profilometry has surface height sensitivity down to 20 pm averaged over a lateral scale of 70 microm with a corresponding scaling mass sensitivity limit of 1.5 pg/mm. Under the conditions of an IgG immunoassay with background changes caused during incubation, the scaling mass sensitivity is approximately 7 pg/mm. A saturated reverse immunoassay performed with IgG at 100 ng/ml showed false positive and false negative rates of 0.2%.