A sensitive photon detection system generates an electronic photon sensor signal as a K factor times a number N photons per unit time. The system is configured by combining a separate optical amplifier with a gain factor K1 with a photo detector with a gain factor K2 such that K may be realized as the product of K1 and K2. The values of K1 and K2 are chosen to meet a predetermined K while optimizing a signal quality of the photon sensor signal. The optical amplifier may be preceded by a photon gathering device and/or a light chopping device to further optimize system performance. Further, the photon sensor signal may be further processed analog circuitry or may be digitized and processed using digital signal processing to generate an enhanced photon sensor signal with enhanced signal quality by adding gain and/or bandwidth limiting.