Focused acoustic treatment of samples including a target biomolecule, such as cfDNA, may aid in the recovery of the biomolecule from a sample. cfDNA in a sample, whether chemically stabilized or not, may be linked or otherwise bound to histones or other proteins, e.g., by hydrogen bonds of histones or chaperone proteins to DNA and/or covalent crosslinks of such proteins to the DNA. Focused acoustic energy may remove or disrupt such links, aiding in isolation of the cfDNA from the sample.