title: Microspectroscopic investigation of the membrane clogging during the sterile filtration of the growth media for mammalian cell culture.
abstract: Growth media for mammalian cell culture are very complex mixtures of several dozens of ingredients, and thus the preparation of qualified media is critical to viable cell density and final product titers. For liquid media prepared from powdered ingredients, sterile filtration is required prior to use to safeguard the cell culture process. Recently one batch of our prepared media failed to pass through the sterile filtration due to the membrane clogging. In this study, we report the root cause analysis of the failed sterile filtration based on the investigations of both the fouling media and the clogged membranes with multiple microspectroscopic techniques. Cellular particles or fragments were identified in the fouling media and on the surfaces of the clogged membranes, which were presumably introduced to the media from the bacterial contamination. This study demonstrated that microspectroscopic techniques may be used to rapidly identify both microbial particles and inorganic precipitates in the cell culture media.
authors.affiliation: Attribute Sciences, Process Development, Amgen Inc., Thousand Oaks, CA, United States. Electronic address: xiaolinc@amgen.com.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Cao
authors.affiliation: Attribute Sciences, Process Development, Amgen Inc., Thousand Oaks, CA, United States.
authors.forename: James A
authors.initials: JA
authors.lastname: Loussaert
authors.affiliation: Attribute Sciences, Process Development, Amgen Inc., Thousand Oaks, CA, United States.
authors.forename: Zai-qing
authors.initials: ZQ
authors.lastname: Wen
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry*; D005374:Filtration / Q000295:instrumentation / Q000379:methods*; D006046:Gold / Q000737:chemistry; D008567:Membranes, Artificial; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D010316:Particle Size; D013052:Spectrometry, X-Ray Emission; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D003470:Culture Media; D008567:Membranes, Artificial; D006046:Gold
keywords: Cell culture media; Cellular particles; Membrane clogging; Microspectroscopy; Particle identification; Sterile filtration