Ultra-miniaturized CMOS fluorescence microarray system. a, Overview of the system including the CMOS IC with the integrated 96-sensor array, the UV LED as the excitation light source, removable glass slip as the bio-interface, and silicon fixtures enabling automatic alignment with a disposable bio interface for multiplexed detection. b, Fluorescence reader system. c, Perspective and cross-sectional view of the sensing pixels. The strong UV light excites the immobilized fluorophores to emit a weak signal in NIR. Integrated nanoplasmonic filter rejects the UV light and allows the local fluorescence to be detected and process by the photon-detection circuity and integrated electronics underneath. The nanoplasmonic filter is realized using the 4th to 7th copper interconnect layers in the 65-nm CMOS process and spreads across all the sensor sites. The 1st–3rd interconnect layers are used for circuit routing and optical blocking. The multiplexed fluorescence signals are read out in a time-multiplexed fashion and are further processed by CDS circuits to eliminate random offsets and suppress low-frequency noise.