Contents I. Introduction
Nowadays, the whole-body and intravital optical imaging [1], [2] has become a very popular technique in medical research dealing with spatial-temporal behaviour of infectious processes. This approach is based on monitoring the luminance of green fluorescent protein (GFP)-expressing bacteria from outside intact infected animals, where no substrate injection, radioactivity, contrast agent, or anaesthesia is required [1]. The latter is normally achieved through an optical excitation induced using lasers, mercury lamps, or LEDs [3]. On the other hand, the multiple single-molecule fluorescence microscopy [4] is currently used in the DNA analysis, where nanometer-localized multiple single-molecules (NALMS) can be properly localized by use of centroid localization and photobleaching (degradation of the emitted radiation intensity) of the single fluorophores [4]. In both applications, solid-state imagers are required to acquire the emitted fluorescence light, which should operate with extremely long photogenerated charge collection times ranging from several milliseconds to several seconds in extreme cases, and very low radiant fluxes. For example, for the multiple single-molecule fluorescence microscopy application reported in [4], each “count” detected by a CCD imager operated in frame transfer mode and cooled to , using 1s charge collection times for each frame, corresponds to roughly two collected photons. In both applications described, the emitting radiation corresponds to visible part of the spectra (with wavelengths ).
