Video-Rate Fluorescence Lifetime Imaging System Using a Novel Switched Capacitor QVGA SPAD Sensor

A video-rate fluorescence lifetime (FLT) imaging system is presented featuring in-pixel lifetime calculation based on the center of mass of the times of arrival (ToAs) of photons received by the single-photon avalanche diode of the pixel. The ToAs of photons received during a gating window placed in the decay of the returned fluorescent emission are averaged by a switched-capacitor circuit, implementing the center-of-mass method (CMM) in a compact pixel circuit. Binning of ToAs or complex time-to-digital circuits are avoided, and instead, optimal use of all received photons is achieved on a small pixel area with low communication and computational overhead. The system is validated through analytical modeling, Monte Carlo simulations, and real-world experiments using fluorophores with known lifetimes, demonstrating agreement with the analytical model and achieving accurate FLT estimations across a large range of photon counts. A dedicated quarter video graphics array (QVGA) (320 × 240 pixel) image sensor that includes all necessary circuitry for the CMM currently reaches 10 frames per second and demonstrates the real-time FLT imaging capability of the system.