This paper presents a system-on-chip solution based on an array of programmable, current-mode integrated circuits for computing refractive index detected using a variable wavelength interrogation scheme in an SPR-based sensing system. The system-on-chip solution is tested in the context of a highly portable sensing configuration consisting of a fiber-based optical path and LED-based light source using a non-functionalized SPR probe. The results are applicable to both functionalized (analyte-specific) and non-functionalized (bulk refractive index) sensing systems. The effect of interferents (pH, temperature, and other background fluctuations) is minimized using a current-mode compensation scheme that accounts for both systematic environmental influences and dark current/fixed pattern noise in the photodetection stage. The output of the chip is an optimized single voltage that represents the refractive index of the sensing environment. The single chip solution contains photodiodes, a photodiode biasing scheme, current-mode dark current/fixed pattern noise compensation, programmable current-mode background (reference) compensation, and an integration stage for weighting signals from multiple wavelengths to compute a single voltage output. Experimental results, including the effects of electronic noise, batch mismatch, and quantization error demonstrate a 6.8 X 10-4 resolution in refractive index units. This resolution is comparable to that demonstrated in previous efforts for SPR-based signal processing using purely software-based techniques (5 X 10-4 resolution), and fully integrated, pulse-weighted multiplication approaches (3 X 10-3 resolution).