Surface-based sensing assays based on fluorescence-based detection have become commonplace for both environmental and biomedical diagnostics. Traditional array scanners are expensive, large, and complex instruments. This paper describes the design of an active CMOS biosensor substrate for fluorescence-based assays that enables time-gated, time-resolved fluorescence spectroscopy without the need for an external reader. The array is sensitive to photon densities as low as 1 15 108 cm2, has a dynamic range of over 74 dB, and has subnanosecond timing resolution. Sensitivity is achieved through subsampling and averaging.