Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8951784-B2
Publication Date
2015-02-10
Expiration Date
Abstract
A cell culture bioreactor having a culture chamber for cell growth, a culture medium reservoir mounted externally to the culture chamber, a fluid circulation mechanism for moving culture medium from the reservoir through the culture chamber, and an aerating mechanism for introducing air into and removing air from the culture chamber is provided. The cell culture bioreactor comprises a manifold mechanism mounted at the top end of the culture chamber, a fluid circulation mechanism fluidly connected to the culture medium reservoir, for receiving culture medium from the culture medium reservoir and distributing culture medium into the culture chamber. A support matrix is mounted within the culture chamber in fluid communication with the fluid circulation mechanism with at least a portion of the support matrix contacting the culture medium wherein the culture medium flows from the manifold means in a thin film over substantially the entire surface of the support matrix allowing the biological cells to grow on the support matrix.
Core Innovation
The invention provides a cell culture bioreactor device having a culture chamber and a support matrix for biological cell growth thereupon, with the support matrix mounted within the culture chamber and having a top end and at least one bottom end. An external culture medium reservoir is operationally connected to the culture chamber to supply culture medium to the culture environment, and a manifold receives and distributes culture medium and is supported within the culture chamber directly above the top end of the support matrix.
Fluid circulation means move the culture medium from the culture medium reservoir through the manifold positioned above the top end of the support matrix. The culture medium flows from the manifold as a thin film over substantially an entire surface of the support matrix that supports biological cell growth, where the thin film is sufficient to supply nutrients and is thin enough to allow oxygen from the air to permeate or otherwise reach, from any surface of the support matrix, all biological cells grown on the support matrix.
The device further includes aerating means for introducing air into and removing air from the culture chamber. In embodiments, the support matrix is elastic porous, hydrophilic fibrous material with continuous interconnected open pores that provide substantially equivalent communication between the support surface and the interior of the culture chamber, including configurations such as spongy mesh.
Additional embodiments include regeneration means that receive culture medium from an outlet, optionally remove waste and/or extract materials, optionally replenish nutrients, and return resulting culture medium to the fluid circulation means.
Claims Coverage
The independent claim set defines a cell culture bioreactor device with 7 inventive features. It combines a top-positioned manifold delivering a thin film of culture medium across substantially an entire surface of a porous support matrix with aeration, and it specifies how the thin film simultaneously supports nutrient supply and enables oxygen reaching substantially all cells. The provided claim set also adds specific support-matrix structure, operational constraints on delivery to avoid turbulence/foam and avoid back pressure, and optional regeneration/recirculation with waste removal and nutrient replenishment.
Top-positioned manifold delivering thin-film culture medium
A manifold in fluid communication with an external culture medium reservoir is configured for receiving and distributing a culture medium and is positioned directly above the top end of the support matrix within the culture chamber.
Thin-film over substantially entire support surface for nutrients and oxygen permeation
Fluid circulation means move culture medium from the reservoir through the manifold so that the culture medium flows as a thin film over substantially an entire surface of the support matrix, where the thin film is sufficient to supply nutrients and is thin enough to allow oxygen from air to permeate or otherwise reach, from any surface of the support matrix, all biological cells grown on the support matrix.
Aerating means introducing and removing air from the culture chamber
Aerating means introduce air into and remove air from the culture chamber.
Elastic porous hydrophilic fibrous support matrix with continuous interconnected open pores
The support matrix is elastic porous, hydrophilic fibrous material with continuous interconnected open pores providing substantially equivalent communication between the support surface and the interior of the culture chamber.
Non-turbulent, non-foam culture medium delivery via fluid delivery rate
Fluid circulation means deliver a culture medium at a specified fluid delivery rate so the medium is delivered non-turbulently to the support matrix while avoiding turbulence and foam-causing agitation.
Avoiding back pressure while supporting wicking/permeation through sides and center
Fluid circulation means deliver culture medium at a rate that avoids back pressure obstructing atmosphere flow, with biological cells growing on a spongy mesh support matrix that is fully wicked and permeated as the culture medium flows through both the sides and the center.
Regeneration means with optional waste removal/extraction and nutrient replenishment
Regeneration means connected to the fluid circulation means receive culture medium from an outlet, optionally remove waste and/or extract materials, optionally replenish nutrients, and return the resulting culture medium to the fluid circulation means.
The core inventive coverage is a cell culture bioreactor device that delivers culture medium as a thin film from a manifold positioned above a porous support matrix, where the film is sufficient for nutrients and thin enough for oxygen to permeate or otherwise reach cells from any support surface, while aerating means introduce and remove air. The dependent refinements further specify porous support-matrix structure, operational constraints for non-turbulent, non-foam delivery and avoiding back pressure, wicking/permeation behavior through a spongy mesh, and optional regeneration with waste removal and nutrient replenishment.
Stated Advantages
Simultaneous oxygenation and nutrient delivery by using a culture medium thin film that is sufficient to supply nutrients and thin enough to allow oxygen from air to permeate or otherwise reach the biological cells.
Non-turbulent delivery that avoids foam-causing agitation.
Fluid delivery at a rate that avoids back pressure obstructing atmosphere flow.
Porous support matrix communication that provides substantially equivalent communication between the support surface and the interior of the culture chamber.
Optional regeneration capability to remove waste and/or extract materials and optionally replenish nutrients and return culture medium for continued use.
Documented Applications
Culturing biological cells on a porous support matrix within a cell culture bioreactor, including embodiments for monoclonal antibody producing hybridoma cells and CHO and other mammalian cells, using culture medium.
Regeneration/recirculation operation in which spent culture medium is processed to optionally remove waste and/or extract materials and optionally replenish nutrients before returning to fluid circulation means.
Interested in licensing this patent?