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For larger macromolecules, however, there are variations in the phase of the scattered light from different parts in the macromolecule. This can lead to the destructive or constructive interference of the scattered light. The net result is that the intensity of scattered light away from the direction of the laser beam is changed and, for molecules small compared to the wavelength of the incident light, is reduced. This case generally describes the so-called RGD theory mentioned earlier. Each macromolecule is assumed to be made up of very small elements, each of which scatters independently of any other. However, during the time of passage of the incident light wavefront over the macromolecule, each element scatters in phase with the scattering of adjacent elements. Thus the scattered waves will add destructively or constructively producing constructive or destructive interference in certain directions.

If the angular dependence of the scattered light is measured, it is possible to determine the size of the molecule. Here, the size measurement is known as the root mean square (rms) radius, or sometimes the "radius of gyration". The latter term is a misnomer since it describes a kinematic measure of a molecule rotating about a particular axis in space. The rms radius, on the other hand is a measure of its size weighted by the mass distribution about its center of mass. Once the molecule's conformation is determined, (e.g., random coil, sphere, or rod), the rms radius can be related to its geometrical dimensions. For a sample containing a broad distribution of molecular masses, following separation by chromatographic means, the measured rms radius may be plotted against the correspondingly measured molar mass to determine the sample's conformation.