title: A scale-down cross-flow filtration technology for biopharmaceuticals and the associated theory.
abstract: Use of microfiltration (MF) and ultrafiltration (UF) in cross-flow mode has been intensifying in downstream processing for expensive biopharmaceuticals. A scale-down cross-flow module with ring channel was constructed for reducing costs and increasing throughput. Commensurate with its validation, a new scale down (or scale up) theoretical framework has been further developed to 3 operational parities: (1) ratio of initial sample volume to membrane area, (2) shear force adjacent to membrane surface, and (3) initial permeate flux. By keeping identical initial physicochemical properties, we show that these 3 operational parities are equivalent to 2 further time-dependent theoretical parities for flux and transmission respectively. Importantly, transmission sensitively reflects membrane conditions for partially transmissible molecules or particles. Computational fluid dynamics simulation was conducted to confirm nearly identical shear forces for the mini and its reference filters. Permeate fluxes in suspension containing Escherichia coli phage T7, a monoclonal antibody (MAb) or other proteins, and transmission (with phage T7) were measured. For application demonstration, diafiltration and concentration modes were applied to the MAb, and separation mode to a mixture of bovine serum albumin and lysozyme. In conclusion, the developed scale-down filter has been shown to behave identically or similarly to its reference filter.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, & The College of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China.
authors.forename: Shuyin
authors.initials: S
authors.lastname: Guo
authors.affiliation: Institute of Applied Biotechnology, Biberach University of Applied Sciences, Karlstrasse 11, 88400 Biberach, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Kiefer
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, & The College of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China.
authors.forename: Dansheng
authors.initials: D
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, & The College of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China. Electronic address: y.h.guan@ecust.edu.cn.
authors.forename: Yue Hugh
authors.initials: YH
authors.lastname: Guan
authors.affiliation: Shanghai Sunny Hengping Scientific Instrument Co. Ltd., 456 Hong Cao Rd., Shanghai 200233, PR China.
authors.forename: Shili
authors.initials: S
authors.lastname: Wang
authors.affiliation: Shanghai Sunny Hengping Scientific Instrument Co. Ltd., 456 Hong Cao Rd., Shanghai 200233, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, & The College of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China; Institute of Applied Biotechnology, Biberach University of Applied Sciences, Karlstrasse 11, 88400 Biberach, Germany.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, & The College of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China.
authors.forename: Yingping
authors.initials: Y
authors.lastname: Zhuang
mesh_terms: D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D017123:Bacteriophage T7 / Q000302:isolation & purification; D001702:Biopharmaceutics / Q000295:instrumentation / Q000379:methods*; D003198:Computer Simulation; D005374:Filtration / Q000295:instrumentation* / Q000379:methods; D057446:Hydrodynamics; D011506:Proteins / Q000302:isolation & purification
chemical_list: D000911:Antibodies, Monoclonal; D011506:Proteins
keywords: Acetonitrile (PubChem CID:6342); Bioprocessing scale-down; Cross-flow filtration; IgG (PubChem CID:190955); Lysozyme (PubChem CID:24839946); Microfiltration; Monoclonal antibody; Polymethyl methacrylate (PubChem CID:6658); Tangential flow filtration; Trifluoroacetic acid (PubChem CID:6422); Ultrafiltration