Theory for the separation of very large DNA molecules by radial migration

Abstract

The separation of very large biological macromolecules is not presently possible with conventional techniques such as sedimentation and gel electrophoresis. For molecules larger than about 5 x 10(8) daltons, such as chromosomal DNA, it is necessary to develop new separation methods. Herein we describe the principle for a new device which shows promise for separating molecules in this size range, as a function of molecular weight. It is based on the deformability of random coil molecules, and the normal stresses which they generate in a certain class of rheological flows. In particular, when a solution of large DNA molecules (we have used the intact chromosome from phage T2) is contained between two concentric cones, one of which rotates relative to the other, there will be a "radial migration" of the DNA toward the center of the cones. The velocity with which the macromolecules migrate is highly dependent on the molecular weight, and therefore the potential exists for separating these large molecules.