Affinity-based fluorescence sensing has been one of the key enabling technologies in biomolecular sensing, used for detection of proteins, DNAs, toxins, bacteria, etc, and remains one of the most sensitive, specific, robust, and widely used diagnostics methodology [1-4]. In absence of high-performance integrated optical filters, miniaturization of a fluorescence sensing system in CMOS has relied on time-resolved techniques with synchronized sources or externally grown optical filters and/or collimators. This paper presents a nanophotonic-electronic co-design approach towards fully-integrated fluorescence biosensor with on-chip copper-interconnect based nanoplasmonic filters. The filters demonstrate a measured extinction ratio of greater than 51dB in the excitation/emission bands for a class of quantum-dot based fluorescence tags. Integrated with these filters, the sensor platform is a correlated double sampling architecture which achieves femtowatt photon sensitivity. Detection sensitivity of 47 zeptomoles of quantum-dots was experimentally demonstrated, making the chip a low-cost, fully integrated, high-performance, and fully scalable biosensor for point-of-care applications.