The invention is a high sensitivity and high throughput capillary multiwavelength fluorescence detection system. The fluorescent detection system is configured to illuminate a relatively large volume of a single capillary or a plurality of capillaries, with a pixelated detection system capable of imaging an area of each capillary that differentiates the capillary walls, the space between the capillaries, and the internal liquid volume within the capillary. Only the desired pixels or image area are used for processing and generating an output signal.