Nucleic acid preparation compositions and methods

A method for enriching relatively short nucleic acid from cell-free nucleic acid, 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 nucleic acid of the biological composition comprises relatively short nucleic acid and relatively long nucleic acid,
• (ii) the relatively short nucleic acid is 300 base pairs or less,
• (iii) the relatively long nucleic acid is larger than 300 base pairs, and
• (iv) the association conditions do not include polyethylene glycol;
• 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 acid, 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 in the cell-free nucleic acid from the substantially cell-free biological composition.