Abstract: Apparatus and methods are described for pharmaceutical grade manufacture extrachromosomal nucleic acids from cell lysates using flotation to separate and eliminate undesired insoluble cellular debris including chromosomal DNA from the lysates. A gas is introduced to controllably generate bubbles that reduce the density of the cell debris and create a buoyant flocculent phase that can be readily separated from, and thus provide, a substantially clarified fluid lysate phase that is enriched in extrachromosomal DNA but substantially depleted of cellular proteins and chromosomal DNA.