We present a new size-selective detection method for integrated optical interferometric biosensors that can strongly enhance their performance. We demonstrate that by launching multiple wavelengths into a Young interferometer waveguide sensor it is feasible to derive refractive index changes from different regions above the waveguide surface, enabling one to distinguish between bound particles (e.g. proteins, viruses, bacteria) based on their differences in size and simultaneously eliminating interference from bulk refractive index changes. Therefore it is anticipated that this new method will be ideally suited for the detection of viruses in complex media. Numerical calculations are used to optimize sensor design and the detection method. Furthermore the specific case of virus detection is analyzed theoretically showing a minimum detectable virus mass coverage of 4 × 102 fg/mm2 (typically corresponding to 5 × 101 particles/ml).