Cell culture bioreactor
Inventors
KILPATRICK, Shane Alexander Jaques • Pundsack, Scott Raymond • Ahmed, Moin
Assignees
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Publication Number
US-12297414-B2
Publication Date
2025-05-13
Expiration Date
Abstract
A cell culture bioreactor has perfusion membranes and gas transfer membranes or a gas phase in an extra-membrane space in contact with a film on the perfusion membranes. Gas transfer membranes may travel through the perfusion membranes or through the extra-membrane space. Examples with hollow fiber and flat sheet membranes are shown. One or more of the membranes optionally has a responsive surface, for example a thermo-responsive surface. In some examples, membranes are located in X-Y planes while the length of the reactor extends in a Z-direction.
Core Innovation
The invention relates to a cell culture bioreactor having a plenum to contain growth media and growing cells, where both perfusion membranes and gas transfer membranes are disposed within the plenum. The arrangement provides gas transfer in addition to perfusion by integrating membranes for supplying nutrients and oxygen to cells within the same plenum volume. The membranes are sealed into potting blocks with open ends exposed, and the exposed ends are connected to headers and/or manifolds so the different membrane functions communicate with respective membrane layers.
The bioreactor includes potting blocks and braces that define portions of surfaces of the potting blocks, with the braces stacked in a direction perpendicular to the membranes. The perfusion membranes are arranged in layers of the perfusion membranes, and the gas transfer membranes are arranged in layers of the gas transfer membranes. Each header and/or manifold is attached to a side of the bioreactor and communicates with the open ends of membranes of either a plurality of layers of the perfusion membranes or a plurality of the layers of the gas transfer membranes, thereby organizing fluid communication across multiple stacked membrane layers.
The invention further supports optional membrane configurations using hollow fiber membranes and membrane surface features associated with responsive surfaces, including thermo-responsive surface materials such as PNIPAAm, POEGMA, and poly(2-oxazoline) to facilitate cell detachment. In the document, oxygen transfer behavior is evaluated using oxygen diffusion/convection modeling and measurements of volumetric mass transfer coefficients across configurations, and biocompatibility outcomes are demonstrated through cell-related trials and growth comparisons between perfusion-only and perfusion plus gas-transfer cartridges.
Claims Coverage
Independent claim clm-00001 covers a cell culture bioreactor that integrates a plenum containing growth media and growing cells with layered perfusion membranes and layered gas transfer membranes, each sealed in corresponding potting blocks with exposed membrane open ends, and connected to headers/manifolds that communicate with the open ends across multiple layers. The independent claim includes multiple inventive elements tied to the mechanical and fluidic integration of both membrane types within the same bioreactor.
Plenum integrating perfusion and gas transfer membranes
A cell culture bioreactor comprising a plenum to contain a growth media and growing cells, a plurality of perfusion membranes within the plenum, and a plurality of gas transfer membranes within the plenum.
Potting blocks sealing each membrane type with exposed open ends
A plurality of potting blocks having a plurality of surfaces, where the potting blocks include perfusion membrane potting blocks and gas transfer potting blocks, wherein the perfusion membranes are sealed in the perfusion membrane potting blocks with open ends of the perfusion membranes exposed and the gas transfer membranes are sealed in the gas transfer potting blocks with open ends of the gas transfer membranes exposed.
Braces stacked perpendicular to membranes defining potting surfaces
A plurality of braces, wherein the braces define portions of the surfaces of the potting blocks, wherein the braces are stacked in a direction perpendicular to the membranes.
Layered membranes with headers/manifolds communicating to open ends across layers
Membranes arranged in layers of the perfusion membranes and layers of the gas transfer membranes, and wherein the headers and/or manifolds are attached to sides of the bioreactor and each header and/or manifold communicates with the open ends of the membranes of either a plurality of the layers of the perfusion membranes or a plurality of the layers of the gas transfer membranes.
Across the independent claim, the core inventive coverage centers on integrating perfusion membranes and gas transfer membranes within a shared plenum, sealing each membrane type in dedicated potting blocks with exposed open ends, mechanically defining potting surfaces via braces, and using headers/manifolds to communicate with open ends across multiple stacked membrane layers.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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