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US5266476A Expired / Lapsed US ⏱️ 0.0 years remaining

Fibrous matrix for in vitro cell cultivation

Assignee: Yeda Research and Development Co Ltd
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Filing: 1992-04-14
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Granted: 1993-11-30
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Expires: 2012-04-14
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Abstract

Abstract There is provided a matrix and cultivation system for anchorage dependent cells. The matrix is characterized by a substantially increased available effective surface area for cell attachment which is attained by resorting to the use of a fiber network or open-pore foams with suitable pore size. Attachment of the cells can be enhanced by modifying the surface of the substrate. One embodiment comprises a matrix in particle or flake form.

Inventors

  • 👤 Martin Sussman
  • 👤 Zvi Bohak
  • 👤 Avinoam Kadouri

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-24 10:18
CPC Classifications
C; C12; C12N; C12N5/00; C12N5/0068; C12M; C12M23/00; C12M23/02; C12M23/08; C12M23/20; C12M25/00; C12M25/02; C12M25/14; C12N2533/00; C12N2533/30; C12N2533/32; C12N2533/50

Claims Analysis

Total Claims: 31
Claim 1
Independent Claim 94 words
A substrate in the form of a sheet for use in cell cultivation in vitro comprising a nonwoven fibrous matrix bonded to a porous support sheet, said matrix comprising a physiologically acceptable three-dimensional network of fibers in the form of a sheet having a pore volume as a percentage of total volume of from 40 to 95% and a pore size of from 10 microns to 100 microns, the overall height of the matrix being from 50 microns to 500 microns, said substrate having a surface area of from about 1 mm 2 .
Claim 2
Dependent Claim 94 words
A substrate in the form of a sheet for use in cell cultivation in vitro comprising a nonwoven fibrous matrix bonded to a porous support sheet, said matrix comprising a physiologically acceptable three-dimensional network of fibers in the form of a sheet having a pore volume as a percentage of total volume of from 40 to 95% and a pore size of from 10 microns to 100 microns, the overall height of the matrix being from 50 microns to 500 microns, said substrate having a surface area of from about 1 mm 2 .
Claim 3
Dependent Claim 41 words
A substrate according to claim 1 wherein said matrix is made of fiber selected from the group consisting of flat, non-round, and hollow fibers and mixtures thereof, said fibers being of from 0.5 microns to 50 microns in diameter or width.
Claim 4
Dependent Claim 40 words
A substrate according to claim 2 wherein said matrix is composed of ribbon formed fibers having a width of from 2 microns to 20 microns, and wherein the ratio of width to thickness of the fibers is at least 2:1.
Claim 5
Dependent Claim 21 words
A substrate according to claim 1 having a pore volume as a percentage of total volume of from 60 to 95%.
Claim 6
Dependent Claim 15 words
A substrate according to claim 1 wherein the matrix has a height of 50-250 μm.
Claim 7
Dependent Claim 34 words
A substrate according to claim 1 wherein the material of the matrix is selected from the group consisting of polyesters, polyalkylenes, polyfluorochloroethylenes, polyvinyl chloride, polystyrene, polysulfones, cellulose acetate, glass fibers, and inert metal fibers.
Claim 8
Dependent Claim 24 words
A substrate according to claim 1 wherein the matrix is in a shape selected from the group consisting of squares, rings, discs, and cruciforms.
Claim 9
Dependent Claim 16 words
A substrate according to claim 1 wherein the matrix is in the form of a disc.
Claim 10
Dependent Claim 13 words
A substrate according to claim 1 wherein the matrix is coated with poly-D-lysine.
Claim 11
Dependent Claim 36 words
A substrate according to claim 1 wherein the matrix is comprised of nonwoven polyester fabric and the support is comprised of a sheet of polypropylene mesh with substantially square mesh opening of about one square millimeter.
Claim 12
Independent Claim 82 words
A system for cell cultivation in vitro comprising a substrate in the form of a sheet comprising a nonwoven fibrous matrix bonded to a porous support sheet, said matrix comprising a physiologically acceptable three-dimensional network of fibers in the form of a sheet having a pore volume as a percentage of total volume of from 40 to 95% and a pore size of from 10 microns to 100 microns, the overall height of the matrix being from 50 microns to 500 microns.
Claim 13
Independent Claim 82 words
A system for cell cultivation in vitro comprising a substrate in the form of a sheet comprising a nonwoven fibrous matrix bonded to a porous support sheet, said matrix comprising a physiologically acceptable three-dimensional network of fibers in the form of a sheet having a pore volume as a percentage of total volume of from 40 to 95% and a pore size of from 10 microns to 100 microns, the overall height of the matrix being from 50 microns to 500 microns.
Claim 14
Dependent Claim 15 words
The system according to claim 11 wherein the substrate is pleated, folded, or spirally wound.
Claim 15
Independent Claim 99 words
The system for cell cultivation in vitro comprising a nonwoven plurality of substrates, each in the form of a sheet, each substrate comprising a fibrous matrix bonded to a porous support sheet, said matrix comprising a physiologically acceptable threedimensional network of fibers in the form of a sheet having a pore volume as a percentage of total volume of from 40 to 95% and a pore size of from 10 microns to 100 microns, the overall height of the matrix being from 50 microns to 500 microns, wherein said sheets are stacked with spacing means between adjacent matrix sheets.
Claim 16
Independent Claim 99 words
The system for cell cultivation in vitro comprising a nonwoven plurality of substrates, each in the form of a sheet, each substrate comprising a fibrous matrix bonded to a porous support sheet, said matrix comprising a physiologically acceptable threedimensional network of fibers in the form of a sheet having a pore volume as a percentage of total volume of from 40 to 95% and a pore size of from 10 microns to 100 microns, the overall height of the matrix being from 50 microns to 500 microns, wherein said sheets are stacked with spacing means between adjacent matrix sheets.
Claim 17
Dependent Claim 23 words
A system according to claim 13 wherein said spacing means are porous and have a height of from 150 microns to 1 mm.
Claim 18
Independent Claim 118 words
A system for cell cultivation in vitro comprising a plurality of substrates each in the form of a sheet, each substrate comprising a nonwoven fibrous matrix bonded to a porous support sheet, said matrix comprising a physiologically acceptable threedimensional network of fibers in the form of a sheet having a pore volume as a percentage of total volume of from 40 to 95% and a pore size of from 10 microns to 100 microns, the overall height of the matrix being from 50 microns to 500 microns, said system comprising layers of said matrix sheets between which flattened permeable or microporous tubular conduits are interleaved, said layers of interleaved structure being arranged in a stack or a spiral.
Claim 19
Independent Claim 118 words
A system for cell cultivation in vitro comprising a plurality of substrates each in the form of a sheet, each substrate comprising a nonwoven fibrous matrix bonded to a porous support sheet, said matrix comprising a physiologically acceptable threedimensional network of fibers in the form of a sheet having a pore volume as a percentage of total volume of from 40 to 95% and a pore size of from 10 microns to 100 microns, the overall height of the matrix being from 50 microns to 500 microns, said system comprising layers of said matrix sheets between which flattened permeable or microporous tubular conduits are interleaved, said layers of interleaved structure being arranged in a stack or a spiral.
Claim 20
Dependent Claim 33 words
A system according to claim 15 wherein the interleaved flattened tubular conduits are composed of films selected from the group consisting of permeable and microporous films of cellulose, polyester, polysulfone, and polyhalogenated ethylene.
Claim 21
Dependent Claim 22 words
A system according to claim 16 wherein means are provided for perfusing a fluid cell growth medium outside the interleaved flattened conduits.
Claim 22
Dependent Claim 24 words
The system according to claim 17 wherein means are provided for gentle agitation of a fluid cell growth medium outside the interleaved flattened conduits.
Claim 23
Independent Claim 115 words
A system for cell cultivation in vitro comprising a plurality of substrates each in the form of a sheet, each substrate comprising a nonwoven fibrous matrix bonded to a porous support sheet, said matrix comprising a physiologically acceptable threedimensional network of fibers in the form of a sheet having a pore volume as a percentage of total volume of from 40 to 95% and a pore size of from 10 microns to 100 microns, the overall height of the matrix being from 50 microns to 500 microns, each said matrix being in the form of a rectangle which is attached as a liner inside the surface of a container to be used for cell cultivation.
Claim 24
Independent Claim 115 words
A system for cell cultivation in vitro comprising a plurality of substrates each in the form of a sheet, each substrate comprising a nonwoven fibrous matrix bonded to a porous support sheet, said matrix comprising a physiologically acceptable threedimensional network of fibers in the form of a sheet having a pore volume as a percentage of total volume of from 40 to 95% and a pore size of from 10 microns to 100 microns, the overall height of the matrix being from 50 microns to 500 microns, each said matrix being in the form of a rectangle which is attached as a liner inside the surface of a container to be used for cell cultivation.
Claim 25
Independent Claim 86 words
A system for cell cultivation in vitro comprising a culture vessel containing a bed of randomly packed substrates, each substrate comprising a fibrous matrix bonded to a porous support sheet, each said matrix comprising a physiologically acceptable three-dimensional network of fibers in the form of a sheet having a pore volume as a percentage of total volume of from 40 to 95% and a pore size of from 10 microns to 100 microns, the overall height of the matrix being from 50 microns to 500 microns.
Claim 26
Independent Claim 86 words
A system for cell cultivation in vitro comprising a culture vessel containing a bed of randomly packed substrates, each substrate comprising a fibrous matrix bonded to a porous support sheet, each said matrix comprising a physiologically acceptable three-dimensional network of fibers in the form of a sheet having a pore volume as a percentage of total volume of from 40 to 95% and a pore size of from 10 microns to 100 microns, the overall height of the matrix being from 50 microns to 500 microns.
Claim 27
Dependent Claim 25 words
The system according to claim 20 wherein each substrate has a surface area of from about 1 mm 2 to about 700 mm 2 .
Claim 28
Dependent Claim 128 words
A substrate in the form of a sheet for use in cell cultivation in vitro comprising a nonwoven fibrous matrix bonded to a porous support sheet, said matrix comprising a physiologically acceptable three-dimensional network of fibers in the form of a sheet having a pore volume as a percentage of total volume of from 40 to 95% and a pore size of from 10 microns to 100 microns, the overall height of the matrix being from 50 microns to 500 microns, said matrix having a surface area of from about 1 mm 2 to about 700 mm 2 and a height of from about 50 microns to about 250 microns, and said substrate being in a shape selected from the group consisting of squares, rings, discs, and cruciforms.
Claim 29
Dependent Claim 128 words
A substrate in the form of a sheet for use in cell cultivation in vitro comprising a nonwoven fibrous matrix bonded to a porous support sheet, said matrix comprising a physiologically acceptable three-dimensional network of fibers in the form of a sheet having a pore volume as a percentage of total volume of from 40 to 95% and a pore size of from 10 microns to 100 microns, the overall height of the matrix being from 50 microns to 500 microns, said matrix having a surface area of from about 1 mm 2 to about 700 mm 2 and a height of from about 50 microns to about 250 microns, and said substrate being in a shape selected from the group consisting of squares, rings, discs, and cruciforms.
Claim 30
Dependent Claim 16 words
The substrate according to claim 22 wherein the substrate is in the form of a disc.
Claim 31
Dependent Claim 13 words
The substrate according to claim 22 wherein the matrix is coated with poly-D-lysine.

References Cited (Backward Citations)

US3941661A Cited
US4144126A Cited
CA1147679A Cited
US4546083A Cited
US4861714A Cited
US4789634A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1996-11-29 1997-05-31 1997-11-30 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2000-11-29 2001-05-31 2001-11-30 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2004-11-29 2005-05-31 2005-11-30 $7700.00 Window Closed / Lapsed

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