title: Functionalized micro-capillary film for the rapid at-line analysis of IgG aggregates in a cell culture bioreactor.
abstract: A micro-capillary film has been developed that offers the potential for an at-line analytical tool for rapid aggregate analysis during biopharmaceutical antibody production. A non-porous walled micro-capillary film (NMCF) with cation exchange functionality was demonstrated to act as a chromatography medium that could be operated with high linear fluid velocities and was highly resistant to blockage by entrained particulates, including cells. The NMCF containing 19 parallel microcapillaries was prepared using a melt extrusion process from poly(ethylene-vinyl alcohol) copolymer (EVOH). The NMCF-EVOH was modified to have cation-exchange functionality (NMCF-EVOH-SP) and shown to differentially bind monomer and aggregated species of IgG antibody directly from a bioreactor. The use of NMCF-EVOH-SP to quantify aggregate concentrations in monoclonal antibody preparations in less than 20 minutes was demonstrated.
authors.affiliation: a Department of Chemical Engineering and Biotechnology ; University of Cambridge; New Museums Site ; Cambridge , UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Townsend
authors.forename: David E
authors.initials: DE
authors.lastname: Gruber
authors.forename: Marcel
authors.initials: M
authors.lastname: Kuiper
authors.forename: Radu A
authors.initials: RA
authors.lastname: Lazar
authors.forename: Ray P
authors.initials: RP
authors.lastname: Field
authors.forename: Richard E
authors.initials: RE
authors.lastname: Turner
authors.forename: Nigel K H
authors.initials: NK
authors.lastname: Slater
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D019149:Bioreactors; D016466:CHO Cells; D002411:Cation Exchange Resins; D018929:Cell Culture Techniques; D002852:Chromatography, Ion Exchange / Q000379:methods*; D003412:Cricetulus; D007074:Immunoglobulin G / Q000302:isolation & purification*; D066329:Protein Aggregates
chemical_list: D000911:Antibodies, Monoclonal; D002411:Cation Exchange Resins; D007074:Immunoglobulin G; D066329:Protein Aggregates
keywords: CHO; aggregate; antibody; chromatography; microcapillary film; monitoring