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Publication Number
US-10988725-B2
Publication Date
2021-04-27
Expiration Date
Abstract
Provided herein are tubular membrane filter elements, tangential flow filtration systems comprising such filter elements and methods of using such filter elements and filtration systems.
Core Innovation
The invention relates to tubular porous membrane filter elements comprising macroporous plastic tubular porous membranes enclosed within a casing, where the porous membranes retain mammalian cells while allowing virus to pass into a permeate. In the described filtration, a cell culture media comprising mammalian cells and a virus is passed through a plurality of tubular porous membranes of the filter element enclosed within a casing, and the permeate comprising the virus flows through the pores of the tubular porous membranes into the casing.
The described approach is positioned for use in tangential flow filtration (TFF) and alternating tangential flow (ATF) perfusion systems to support closed-system viral harvest. The invention addresses limitations of standard hollow-fiber ATF filters by using a pore size range intended to reduce viral retention/aggregation concerns while still retaining mammalian cells in the tubular porous membranes.
The disclosed configuration is scalable by varying the number and geometry of tubular porous membranes and corresponding casing dimensions to adjust the filtration capacity. The document frames the filtration around mammalian suspension culture, using a viable cell density of at least 10^6 cells per mL, and mentions membrane materials such as UHMWPE for forming the porous plastic tubular membranes.
Claims Coverage
The partial content provides one independent claim covering a casing-enclosed tubular porous membrane filtration method that retains mammalian cells while passing virus into a permeate. The inventive features include specific membrane pore sizing, tubular internal diameters, and the retention/permeate flow relationship under a defined viable cell density condition.
Casing-enclosed plurality of tubular porous membranes for cell retention and virus permeation
A method of filtering a cell culture media by passing a cell culture media comprising mammalian cells and a virus through a plurality of tubular porous membranes of a filter element enclosed within a casing, wherein the mammalian cells are retained within the tubular porous membranes and a permeate comprising the virus flows through the pores of the tubular porous membranes into the casing.
Macroporous pore size distribution and tubular internal diameter ranges
Each tubular porous membrane filter element comprises a plurality of tubular porous membranes, wherein at least 95% of the pores in each of the plurality of tubular porous membranes are between 5 μm and 15 μm in size and wherein the internal diameter of each of the plurality of tubular porous membranes is between about 1 mm to about 10 mm.
Filtration of virus with mammalian cells at defined viable cell density
The method passes a cell culture media comprising mammalian cells at a viable cell density of at least 10×10^6 cells per mL and a virus through the plurality of tubular porous membranes of the filter element enclosed within a casing, generating a permeate comprising the virus.
Across the provided independent claim, the coverage centers on a casing-enclosed filter element with multiple tubular porous membranes using a defined macroporous pore-size distribution and tubular internal-diameter range to retain mammalian cells while directing a virus-containing permeate through the membrane pores into the casing.
Stated Advantages
Supports retaining mammalian cells while allowing virus to pass into a permeate for subsequent downstream purification.
Provides a basis for closed-system viral harvest in tangential flow filtration (TFF) and alternating tangential flow (ATF) perfusion contexts.
Enables scalability by varying the number and geometry of tubular porous membranes and casing dimensions.
Documented Applications
Closed-system viral harvest using tangential flow filtration (TFF) and alternating tangential flow (ATF) perfusion systems to produce a viral permeate while retaining mammalian cells.
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