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We demonstrate that the deviation in the reflectivity signal is reduced to ∼8 × 10-6 for a solution change from phosphate-buffered saline (PBS) (n = 1.335) to 1% dimethyl sulfoxide (DMSO) in PBS (n = 1.336). As a proof of concept, we applied the method to a biotin-streptavidin interaction, where biotin (MW = 244.3 Da) was dissolved at a final concentration of 1 μM in a 1% solution of DMSO in PBS and flowed over immobilized streptavidin. Clear binding results were obtained without a reference channel or any computational correction.NiCo2S4