A method for observing and determining the size of individual molecules and for determining the
weight distribution of a sample containing molecules of varying size, which involves placing a deformable or nondeformable molecule in a medium, subjecting the molecule to an external force, thereby causing conformational and / or positional changes, and then measuring these changes. Preferred ways to measure conformational and positional changes include: (1) determining the rate at which a deformable molecule returns to a relaxed state after termination of the external force, (2) determining the rate at which a molecule becomes oriented in a new direction when the direction of the perturbing force is changed, (3) determining the rate at which a molecule rotates, (4) measuring the length of a molecule, particularly when it is at least partially stretched, or (5) measuring at least one
diameter of a spherical or ellipsoidal molecule. Measurements of relaxation, reorientation, and rotation rates, as well as length and
diameter can be made using a light
microscope connected to an
image processor. Molecule relaxation, reorientation and rotation also can be determined using a
microscope combined with a spectroscopic device. The invention is particularly useful for measuring
polymer molecules, such as nucleic acids, and can be used to determine the size and
map location of restriction digests. Breakage of large
polymer molecules mounted on a
microscope slide is prevented by condensing the molecules before mounting and unfolding the molecules after they have been placed in a matrix.