Capillary electrophoresis provides powerful separations of biomolecules, including DNA, proteins, lipids, and carbohydrates. to improve the analytical throughput, we have developed a number of multiple capillary laser-induced fluorescence detectors. These instruments all detect fluorescence from analyte that are flowing in a fluid filled chamber, a few micrometers downstream from the outlet of the capillaries. We have developed four versions of the multiple capillary detectors, with different design features and goals.

       These instruments were originally designed for use in DNA sequencers, where it is necessary to resolve fluorescence in four spectral channels. two lasers were used for excitation in the earliest instruments; improved dye chemistry eliminated the need for the second laser.

       Modest-scale instruments are based on 5-, 16-, and 32-capillary designs, in which the capillaries are arranged in a linear configuration, like the teeth of a comb, in a rectangular sheath-flow cuvette. Sheath fluid is pumped through the interstitial space between the capillaries, drawing sample as a discrete stream beneath each capillary. fluorescence is excited by a single laser beam, that is focused about 50-micrometers down-stream from the capillary exit. Fluorescence is collected with an lens and imaged onto a set of GRIN-lens coupled fiber optics, which direct the fluorescence to a set of photodetectors.

      This design offers several important properties. Because the laser beam traverses a fluid filled chamber with excellent optical properties, there is no scattered laser light that would be observed if the beam illuminates the capillaries directly. The instrument is extremely efficient in its use of excitation light; a single 5-mW laser beam excites all the samples simultaneously and with 100% duty cycle. In contrast, scanning systems must move the beam and collection optics between capillaries, allowing most analyte to pass through the system undetected.
       Rather then using PMT's as photodetectors, the 5 and the 16 capillary instruments use avalanche photodiodes. They are smaller and more robust then PMT's but equally sensitive. A rotating filter wheel was employed in these early generation instruments.
       The 32-capillary instrument uses a prism to disperse fluorescence across the face of a CCD camera, which eliminates all moving parts from the instrument. It also allows us to monitor all emission wavelengths simultaneously.
       The sheath flow cuvette in the 5-capillary instrument is a piece of quartz with a rectangular hole that holds 5 capillaries in a row. We construct 16- capillary cuvettes using microlithography technology so that microstructures within the cuvette hold the capillaries in a precise alignment. This patented design greatly simplifies the optical alignment of the sample streams with the laser beam and the detector optics.
       The use of larger numbers of capillaries in a linear array is undesirable because it is difficult to collect fluorescence across the long, linear array with high efficiency. To provide a high detection efficiency, we have packed the capillaries in a two-dimensional array. Fluorescence from this array is dispersed by a prism and imaged onto a CCD camera. Far more than 96 capillaries can be packed into a 2-D array. It is theoretically possible to detect fluorescence from over 2000 capillaries in a 2-D array format, for extremely high throughput analysis.