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.