title: DNA hydrodynamic degradation controlled by Kolomogorov length scales in pipe flow.
abstract: Strict US Food and Drug Administration regulations on contamination levels for DNA therapeutics acceptable for human use complicate the manufacturing process. This study aims to improve therapeutic production through the investigation of the molecular effects of hydrodynamic forces encountered during processing. Results suggest that the strain rate and residence time were not solely responsible for degradation within the system. Instead, turbulent flows at the entrance or developing flow regions dominate especially when the Kolmogorov length scale approaches the stretched molecular length scale. We specifically suggest this for linear genomic DNA and supercoiled plasmid DNA when the ratio of the molecular length to the Kolmogorov length scale must remain smaller than unity to minimize loss of the desired structure. These findings suggest that bioprocessing systems should design expansions and contractions to minimize recirculation and turbulent mixing zones, although, not always possible, careful attention should be paid to pipe surface roughness to ensure that turbulent eddies are not generated in low Reynolds number flows.
authors.affiliation: Department of Mechanical and Materials Engineering, University of Denver, Denver, Colorado 80208. Electronic address: Corinne.Lengsfeld@du.edu.
authors.forename: Corinne S
authors.initials: CS
authors.lastname: Lengsfeld
authors.affiliation: Department of Mechanical and Materials Engineering, University of Denver, Denver, Colorado 80208.
authors.forename: Leslie
authors.initials: L
authors.lastname: Munson
authors.affiliation: School of Pharmacy, University of Colorado Denver, Aurora, Colorado 80045.
authors.forename: Yvonne K
authors.initials: YK
authors.lastname: Lentz
authors.affiliation: School of Pharmacy, University of Colorado Denver, Aurora, Colorado 80045.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Anchordoquy
mesh_terms: D003198:Computer Simulation; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004278:DNA, Superhelical / Q000737:chemistry* / Q000235:genetics; D004355:Drug Stability; D004926:Escherichia coli / Q000235:genetics; D057446:Hydrodynamics; D008956:Models, Chemical; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D013314:Stress, Mechanical
chemical_list: D004269:DNA, Bacterial; D004278:DNA, Superhelical