The objective of this research is to determine if an integrated circuit sensor can combine the benefits of fluorescence intensity imagers and fluorescence lifetime sensors. The approach is to compare three competing technologies for high-speed photon detection (traditional pixels, photomixing pixels, and single photon avalanche diodes) at the pixel, imager, and application level. Intellectual Merit The inclusion of fluorescence lifetime data in fluorescence intensity measurements can improve the signal-to-noise ratio, increase the number of imaging channels, and even allow the development of low-cost fluorescence imagers that do not require filters. This fluorescence lifetime data is only rarely collected because existing sensors are expensive and slow. The work proposed here will either demonstrate that integrated circuit detectors can overcome these hurdles or point the way to research on integrated circuit detectors to reach that goal. Broader Impacts Fluorescence instruments are critical in medical diagnosis, drug discovery, and pathogen detection. This project will enable creation of new instruments that are more sensitive, more portable, faster, and cheaper. The development of these sensors is also an opportunity to train students in the classic area of circuit design and the emerging area of bioelectronics. In particular, a graduate student will be prepared for a career in mixed-signal circuit design and a team of undergraduates will gain experience in interdisciplinary engineering developing the systems for testing these integrated circuits with realistic fluorescence assays.