NUCLEIC ACID PREPARATION COMPOSITIONS AND METHODS

The invention relates to a method for enriching relatively short nucleic acid from a nucleic acid composition, which comprises: (a) contacting cell-free nucleic acid from a substantially cell-free biological composition with a solid phase under association conditions, wherein: (i) the cell-free nucleic acid of the biological composition comprises relatively short nucleic acid and relatively long nucleic acid, (ii) the relatively short nucleic acid is about 200 base pairs or less, and (iii) the relatively long nucleic acid is larger than about 200 base pairs; whereby the relatively short nucleic acid and the relatively long nucleic acid are associated with the solid phase; (b) introducing the solid phase after (a) to dissociation conditions that comprise a volume exclusion agent and a salt, wherein: (i) the salt is not a chaotropic salt, and (ii) the relatively short nucleic acid preferentially dissociates from the solid phase under the dissociation conditions as compared to the relatively long nucleic, thereby yielding dissociated nucleic acid; and (c) separating the dissociated nucleic acid from the solid phase, whereby the relatively short nucleic acid is enriched in the dissociated nucleic acid relative to the cell-free nucleic from the substantially cell-free biological composition.