Direct modulation of the effective sensitivity of a CCD detector: a new approach to time-resolved fluorescence imaging

In this paper a novel approach to frequency-domain fluorescence lifetime imaging (FLIM) is described. In a CCD camera a single pixel is defined by a charge pattern on a group of electrodes. By modulation of the pattern of voltages defining the pixel structure it is possible to modulate the sensitivity of the CCD at radio frequency. The modulation enhances the noise performance of the CCD, in contrast to the deterioration in performance seen when an intensifier stage is similarly modulated. The new technology has potential applications to a wide range of assays as well as in conventional FLIM applications. Unlike intensifier-based systems, the directly modulated CCD is physically small, inexpensive, robust and offers superior resolution and noise performance.