Interferometric Biosensors

Abstract

Every chemical reaction or interaction causes a change in refractive index, including such bioconjugate interactions as antibody/antigen, DNA hybridization and enzyme/substrate interactions. Interferometry is an optical method for measuring refractive index changes. With the proper choice of sensing film, an interferometer can identify and quantify the presence of a biological moiety. An interferometer compares optically two almost equivalent light paths – one that interrogates the refractive index change caused by a bioconjugate interaction, and the other that serves as a reference that cancels out any nonspecific interactions. Interferometers have the capability of detecting refractive index changes of 10−7, which corresponds to ppb concentrations of small molecules, pg/mL concentrations of toxins and proteins, and 100s–1000s of whole cells, viruses and spores. Several optical interferometric designs are described. Most configurations combine a bioconjugate reaction isolated on a rigid support with a long interaction length of mm to cm to achieve high sensitivity. The most common interferometric configuration utilizes a planar optical waveguide. The evanescent field associated with a wave-guided beam extends above the waveguide surface where the bioreceptor is immobilized. The bioconjugate interaction perturbs the propagating beam and the extent of this perturbation is measured by comparing the phase of the light traveling along the sensing channel with that traveling along a reference channel that is not functionalized with the bioreceptor. The phase change is measured by optically combining the two beams at the output of the interferometer to create an interference pattern, a series of dark and light fringes that is caused by constructive and destructive interference. By proper choice of receptor molecule and calibration, both the identity and the quantity of a specific bioentity can be measured with the interferometric biosensor.