Automated parallel DNA sequencing on multiple channel microchips

We report automated DNA sequencing in 16-channel microchips. A microchip pr efilled with sieving matrix is aligned on a heating plate affixed to a mova ble platform. Samples are loaded into sample reservoirs by using an eight-t ip pipetting device, and the chip is docked with an array of electrodes in the focal plane of a four-color scanning detection system. Under computer c ontrol, high voltage is applied to the appropriate reservoirs in a programm ed sequence that injects and separates the DNA samples. An integrated four- color confocal fluorescent detector automatically scans all 16 channels. Th e system routinely yields more than 450 bases in 15 min in all 16 channels. In the best case using an automated base-calling program, 543 bases have b een called at an accuracy of >99%. Separations, including automated chip lo ading and sample injection, normally are completed in less than 18 min. The advantages of DNA sequencing on capillary electrophoresis chips include un iform signal intensity and tolerance of high DNA template concentration. To understand the fundamentals of these unique features we developed a theore tical treatment of cross-channel chip injection that we call the differenti al concentration effect We present experimental evidence consistent with th e predictions of the theory.