Self-referencing substrates for optical interferometric biosensors

Optical interference is a powerful technique for monitoring surface topography or refractive index changes in a thin film layer. Reflectance spectroscopy provides label-free biosensing capability by monitoring small variations in interference signature resulting from optical path length changes from surface-adsorbed biomolecules. Spectral reflectance data can be acquired either by broad wavelength illumination and spectroscopy at a single point, thus necessitating scanning, or by varying the wavelength of illumination and imaging the reflected intensity allowing for acquisition of a spectral image of a large field of view simultaneously. In imaging modalities, intensity fluctuations of the illuminating light source couple into the detected signal, increasing the noise in measured surface profiles. This article introduces a simple technique for eliminating the effects of illumination light power fluctuations by fabricating on-substrate self-reference regions to measure and normalize for the incident intensity, simplifying the overall platform for reflection or transmission-based imaging biosensors. Experimental results demonstrate that the sensitivity performance using self-referencing is equivalent or better than an optimized system with an external reference.