A new instrument has been developed for the electrophoretic separation of large DNA molecules that can independently regulate the voltage of each of 24 electrodes and allow the magnitude, orientation, homogeneity, and duration of the electric field to be precisely controlled. Each parameter can be varied at any time during the electrophoretic process. Thus distinct sets of conditions can be combined to optimize the separation of various fragment sizes in a single run. Independent control of electrode voltage allows all of the fields to be generated with electrodes arranged in a closed contour, independent of a particular geometry. This device increases both the resolution in any size range and the speed of separation, especially for DNA molecules larger than 3 megabases.