Method for membrane gas transfer in high density bioreactor culture
AssigneeBoehringer Ingelheim International GmbH
InventorsJonathan Coffman, Scott Godfrey, Lisa Sawicki
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Abstract
The present invention provides improved bioprocessing systems and methods for cell culture using the improved bioreactors, e.g., batch-fed or perfusion bioreactor cell culture systems for production of monoclonal or bi-specific antibodies, which are modified to include one or more membrane gas transfer modules in place of a sparger- or microsparger-based aeration systems to better regulate the levels of critical gases in a bioreactor cell culture, e.g., the dissolved levels of O2 and CO2, even at high cell densities, without subjecting the cells to bubble-burst associated cell death.
Claims15
A method of culturing Chinese Hamster Ovary (CHO) cells in a bioreactor comprising providing a mass transfer of a gas to/from the bioreactor without generating bubbles inside the bioreactor, wherein the mass transfer of gas to/from the bioreactor is provided by two or more gas transfer modules comprising a plurality of hollow fibers, wherein at least one gas transfer module comprises an oxygen flow path through the hollow fibers and a cell culture medium flow path around the hollow fibers separated by a non-porous membrane comprising PDMS and wherein at least one gas transfer module comprises an air/carbon dioxide flow path through the hollow fibers and a cell culture medium flow path around the hollow fibers separated by a non-porous membrane comprising PDMS;
- wherein the bioreactor is a perfusion bioreactor, and wherein the bioreactor comprises a CHO cell density of at least 20×106 cells/ml.
Dependencies are inferred from the claim text.