WO2001023520A1 - Method and apparatus for culturing cells - Google Patents
Method and apparatus for culturing cells Download PDFInfo
- Publication number
- WO2001023520A1 WO2001023520A1 PCT/AU2000/001197 AU0001197W WO0123520A1 WO 2001023520 A1 WO2001023520 A1 WO 2001023520A1 AU 0001197 W AU0001197 W AU 0001197W WO 0123520 A1 WO0123520 A1 WO 0123520A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cells
- media
- bioreactor
- cell
- acellular
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/10—Perfusion
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
- C12M25/10—Hollow fibers or tubes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
- C12M25/10—Hollow fibers or tubes
- C12M25/12—Hollow fibers or tubes the culture medium flowing outside the fiber or tube
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
- C12M35/08—Chemical, biochemical or biological means, e.g. plasma jet, co-culture
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
- C12M41/34—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas
Definitions
- the cell type is genetically modified to secrete biological molecules that have biotechnological or pharmaceutical applications.
- a cellular expression system is used to produce a protein, peptide or viral vector that is encoded by genes isolated from another organism.
- proteins that have been expressed in cell lines include monoclonal antibodies or their fragments, specific binding domains, enzymes, cytokines, growth factors, cell surface receptors and so on. More than one domain may be combined to form a chimaeric protein which is expressed by the genetically modified cell line.
- replication-deficient retroviruses used for human gene therapy have been produced by modified mouse fibroblast cells.
- Mammalian or yeast cell lines may be used to express proteins that require synthesis of additional carbohydrate side-chains for full biological activity.
- Figure 4 is a graph showing the influence of insulin, BSA and dextran in extracapillary media (mean ⁇ SEM) *p ⁇ 0.05, **p ⁇ 0.01;
- Figure 5 is a schematic drawing one embodiment of a bioreactor in accordance with the invention.
- FIG 6 is a schematic drawing of a further embodiment of a bioreactor in accordance with the invention.
- Figure 7 is a graph showing glucose and lactate levels in EC media during a bioreactor run described in Example 4.
- FIG. 4 shows the growth curves for this series of experiments.
- StemPro media supplement was the best extracapillary media, however BSA on its own could be substituted for StemPro media supplement with only a marginal (not statistically significant) decrease in growth.
- Surprisingly insulin in the extracapillary media appeared to reduce cell growth (p ⁇ 0.05). There was poor growth and cell necrosis when dextran was substituted in the extracapillary media.
- albumin An important function of albumin is to bind calcium and small molecules such as insulin. Dextran does not bind these molecules, and it may be necessary to adjust calcium so that intracapillary free calcium levels are in the physiological range.
- Enriched cells were left in situ, and the extracapillary space was perfused with acellular culture media from reservoir 127 via acellular inlet port 89 . There may be intracapillary flow of media from intracapillary media reservoir 91 via intracapillary inlet 83 as well. Cells were harvested after 1-3 weeks of growth using fluid shear and cell releasing agents if necessary.
- Solenoid pinch valves (1-8) control fluid paths.
- Two peristaltic pumps 42, 44 control extracapillary and intracapillary flow respectively.
- Table 5 shows the typical valve and pump states of the bioreactor of this embodiment.
- valve 8 There is communication between the extracapillary and intracapillary circuits via valve 8 so that higher flow rate may be supplied to the intracapillary circuit for cell harvesting. This communication also facilitates the removal of degraded extracapillary media to waste 82 and its replenishment with fresh media without interruption of the flow of conditioned-media during the culture process.
- the fibre diameter is 200 ⁇ m, and the module length is 30 cm. able 5 Typical valve and pump states
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Sustainable Development (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Physiology (AREA)
- Cell Biology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP00969061A EP1222249A4 (en) | 1999-09-30 | 2000-09-29 | Method and apparatus for culturing cells |
AU78889/00A AU781265B2 (en) | 1999-09-30 | 2000-09-29 | Method and apparatus for culturing cells |
CA002386001A CA2386001A1 (en) | 1999-09-30 | 2000-09-29 | Method and apparatus for culturing cells |
JP2001526904A JP2003510068A (en) | 1999-09-30 | 2000-09-29 | Method and apparatus for culturing cells |
US11/646,256 US20070122904A1 (en) | 2000-09-29 | 2006-12-28 | Method and apparatus for culturing cells |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AUPQ3191 | 1999-09-30 | ||
AUPQ3191A AUPQ319199A0 (en) | 1999-09-30 | 1999-09-30 | Method and apparatus for culturing cells |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/646,256 Continuation US20070122904A1 (en) | 2000-09-29 | 2006-12-28 | Method and apparatus for culturing cells |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2001023520A1 true WO2001023520A1 (en) | 2001-04-05 |
Family
ID=3817354
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/AU2000/001197 WO2001023520A1 (en) | 1999-09-30 | 2000-09-29 | Method and apparatus for culturing cells |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1222249A4 (en) |
JP (1) | JP2003510068A (en) |
AU (1) | AUPQ319199A0 (en) |
CA (1) | CA2386001A1 (en) |
WO (1) | WO2001023520A1 (en) |
Cited By (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1005233A (en) * | 1961-04-14 | 1965-09-22 | Sandoz Ltd | New monoazo dyestuffs |
EP1786894A1 (en) * | 2004-09-10 | 2007-05-23 | Unisearch Limited | Device and method to prevent culture media degradation |
US20080220522A1 (en) * | 2007-03-05 | 2008-09-11 | Gambro Bct, Inc. | Methods to Control Cell Movement in Hollow Fiber Bioreactors |
US8309347B2 (en) | 2007-03-05 | 2012-11-13 | Terumo Bct, Inc. | Cell expansion system and methods of use |
WO2012168295A1 (en) | 2011-06-06 | 2012-12-13 | ReGenesys BVBA | Expansion of stem cells in hollow fiber bioreactors |
WO2016012249A1 (en) * | 2014-07-25 | 2016-01-28 | Ge Healthcare Bio-Sciences Ab | Method and system for suspension culture |
US9617506B2 (en) | 2013-11-16 | 2017-04-11 | Terumo Bct, Inc. | Expanding cells in a bioreactor |
US9677042B2 (en) | 2010-10-08 | 2017-06-13 | Terumo Bct, Inc. | Customizable methods and systems of growing and harvesting cells in a hollow fiber bioreactor system |
US10077421B2 (en) | 2014-04-24 | 2018-09-18 | Terumo Bct, Inc. | Measuring flow rate |
US10577576B2 (en) | 2012-08-20 | 2020-03-03 | Terumo Bct, Inc. | System for expanding cells |
US11008547B2 (en) | 2014-03-25 | 2021-05-18 | Terumo Bct, Inc. | Passive replacement of media |
US11104874B2 (en) | 2016-06-07 | 2021-08-31 | Terumo Bct, Inc. | Coating a bioreactor |
EP3794104A4 (en) * | 2018-05-18 | 2022-06-08 | Children's Research Institute, Children's National Medical Center | System of cell expansion and methods of using the same |
US11608486B2 (en) | 2015-07-02 | 2023-03-21 | Terumo Bct, Inc. | Cell growth with mechanical stimuli |
US11624046B2 (en) | 2017-03-31 | 2023-04-11 | Terumo Bct, Inc. | Cell expansion |
US11629332B2 (en) | 2017-03-31 | 2023-04-18 | Terumo Bct, Inc. | Cell expansion |
WO2023064187A1 (en) * | 2021-10-13 | 2023-04-20 | Life Technologies Corporation | Scalable systems and methods for continuous transfection of cells |
US11667881B2 (en) | 2014-09-26 | 2023-06-06 | Terumo Bct, Inc. | Scheduled feed |
US11685883B2 (en) | 2016-06-07 | 2023-06-27 | Terumo Bct, Inc. | Methods and systems for coating a cell growth surface |
US11965175B2 (en) | 2016-05-25 | 2024-04-23 | Terumo Bct, Inc. | Cell expansion |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2676323A1 (en) * | 2007-01-18 | 2008-07-24 | Suomen Punainen Risti, Veripalvelu | Novel methods and reagents directed to production of cells |
JP2015519922A (en) * | 2012-06-21 | 2015-07-16 | ネオステム オンコロジー リミテッド ライビリティ カンパニー | Bioreactor cartridge and system |
JP6696206B2 (en) * | 2016-02-17 | 2020-05-20 | 東洋紡株式会社 | Cell culture device using gas impermeable tube and cell culture method |
Citations (2)
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WO1991010425A1 (en) * | 1990-01-08 | 1991-07-25 | Brown University Research Foundation | Cell capsule extrusion systems |
WO1995027041A1 (en) * | 1994-04-01 | 1995-10-12 | Unisyn Technologies, Inc. | Culture media additives for bioreactors |
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JPS63188386A (en) * | 1987-01-29 | 1988-08-03 | Shimadzu Corp | Bioreactor |
JPH01235578A (en) * | 1988-03-14 | 1989-09-20 | Terumo Corp | Bioreactor |
JP2750581B2 (en) * | 1988-08-12 | 1998-05-13 | 川澄化学工業株式会社 | Culture device |
JP2835629B2 (en) * | 1989-05-18 | 1998-12-14 | ザ リージェンツ オブ ザ ユニヴァーシティ オブ ミネソタ | Bioreactor equipment |
JPH0315382A (en) * | 1989-06-14 | 1991-01-23 | Terumo Corp | Base material and base material unit for culturing cell, bioreactor and external circulation type therapeutic device |
JP2675408B2 (en) * | 1989-09-14 | 1997-11-12 | 宇部興産株式会社 | Hollow fiber membrane bioreactor |
ATE238410T1 (en) * | 1993-10-29 | 2003-05-15 | Unisearch Ltd | CELL SEPARATION DEVICE |
JP4003982B2 (en) * | 1995-06-30 | 2007-11-07 | 東レ株式会社 | Polysulfone-based selectively permeable separation membrane |
JP3651121B2 (en) * | 1995-06-30 | 2005-05-25 | 東レ株式会社 | Permselective separation membrane |
JP3617194B2 (en) * | 1995-06-30 | 2005-02-02 | 東レ株式会社 | Permselective separation membrane and method for producing the same |
-
1999
- 1999-09-30 AU AUPQ3191A patent/AUPQ319199A0/en not_active Abandoned
-
2000
- 2000-09-29 WO PCT/AU2000/001197 patent/WO2001023520A1/en active IP Right Grant
- 2000-09-29 EP EP00969061A patent/EP1222249A4/en not_active Withdrawn
- 2000-09-29 JP JP2001526904A patent/JP2003510068A/en active Pending
- 2000-09-29 CA CA002386001A patent/CA2386001A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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WO1991010425A1 (en) * | 1990-01-08 | 1991-07-25 | Brown University Research Foundation | Cell capsule extrusion systems |
WO1995027041A1 (en) * | 1994-04-01 | 1995-10-12 | Unisyn Technologies, Inc. | Culture media additives for bioreactors |
Non-Patent Citations (3)
Title |
---|
GERLACH J. C. ET AL.: "Comparison of hollow fiber membranes for hepatocyte immobilisation in bioreactors", THE INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS, vol. 19, no. 10, 1996, pages 610 - 616 * |
LLOYD J. R. ET AL.: "Hollow-fibre bioreactors compared to batch and chemostat culture for the production of a recombinant toxoid by a marine Vibrio", APPLIED MICROBIOLOGY BIOTECHNOLOGY, vol. 48, 1997, pages 155 - 161 * |
See also references of EP1222249A4 * |
Cited By (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1005233A (en) * | 1961-04-14 | 1965-09-22 | Sandoz Ltd | New monoazo dyestuffs |
EP1786894A1 (en) * | 2004-09-10 | 2007-05-23 | Unisearch Limited | Device and method to prevent culture media degradation |
EP1786894A4 (en) * | 2004-09-10 | 2007-12-12 | Unisearch Ltd | Device and method to prevent culture media degradation |
US9260698B2 (en) | 2007-03-05 | 2016-02-16 | Terumo Bct, Inc. | Cell expansion system and methods of use |
US8309347B2 (en) | 2007-03-05 | 2012-11-13 | Terumo Bct, Inc. | Cell expansion system and methods of use |
US20080220522A1 (en) * | 2007-03-05 | 2008-09-11 | Gambro Bct, Inc. | Methods to Control Cell Movement in Hollow Fiber Bioreactors |
US8785181B2 (en) | 2007-03-05 | 2014-07-22 | Terumo Bct, Inc. | Cell expansion system and methods of use |
US11773363B2 (en) | 2010-10-08 | 2023-10-03 | Terumo Bct, Inc. | Configurable methods and systems of growing and harvesting cells in a hollow fiber bioreactor system |
US11746319B2 (en) | 2010-10-08 | 2023-09-05 | Terumo Bct, Inc. | Customizable methods and systems of growing and harvesting cells in a hollow fiber bioreactor system |
US9677042B2 (en) | 2010-10-08 | 2017-06-13 | Terumo Bct, Inc. | Customizable methods and systems of growing and harvesting cells in a hollow fiber bioreactor system |
US11613727B2 (en) | 2010-10-08 | 2023-03-28 | Terumo Bct, Inc. | Configurable methods and systems of growing and harvesting cells in a hollow fiber bioreactor system |
US9725689B2 (en) | 2010-10-08 | 2017-08-08 | Terumo Bct, Inc. | Configurable methods and systems of growing and harvesting cells in a hollow fiber bioreactor system |
US10870827B2 (en) | 2010-10-08 | 2020-12-22 | Terumo Bct, Inc. | Configurable methods and systems of growing and harvesting cells in a hollow fiber bioreactor system |
US10669519B2 (en) | 2010-10-08 | 2020-06-02 | Terumo Bct, Inc. | Customizable methods and systems of growing and harvesting cells in a hollow fiber bioreactor system |
WO2012168295A1 (en) | 2011-06-06 | 2012-12-13 | ReGenesys BVBA | Expansion of stem cells in hollow fiber bioreactors |
EP3572497A1 (en) | 2011-06-06 | 2019-11-27 | Regenesys bvba | Expansion of stem cells in hollow fiber bioreactors |
US10577576B2 (en) | 2012-08-20 | 2020-03-03 | Terumo Bct, Inc. | System for expanding cells |
US9617506B2 (en) | 2013-11-16 | 2017-04-11 | Terumo Bct, Inc. | Expanding cells in a bioreactor |
US11667876B2 (en) | 2013-11-16 | 2023-06-06 | Terumo Bct, Inc. | Expanding cells in a bioreactor |
US10557112B2 (en) | 2013-11-16 | 2020-02-11 | Terumo Bct, Inc. | Expanding cells in a bioreactor |
US10633625B2 (en) | 2013-11-16 | 2020-04-28 | Terumo Bct, Inc. | Expanding cells in a bioreactor |
US11708554B2 (en) | 2013-11-16 | 2023-07-25 | Terumo Bct, Inc. | Expanding cells in a bioreactor |
US11795432B2 (en) | 2014-03-25 | 2023-10-24 | Terumo Bct, Inc. | Passive replacement of media |
US11008547B2 (en) | 2014-03-25 | 2021-05-18 | Terumo Bct, Inc. | Passive replacement of media |
US10077421B2 (en) | 2014-04-24 | 2018-09-18 | Terumo Bct, Inc. | Measuring flow rate |
US11254903B2 (en) | 2014-07-25 | 2022-02-22 | Cytiva Sweden Ab | Method and system for suspension culture |
JP2017521080A (en) * | 2014-07-25 | 2017-08-03 | ジーイー・ヘルスケア・バイオサイエンス・アクチボラグ | Suspension culture method and system |
WO2016012249A1 (en) * | 2014-07-25 | 2016-01-28 | Ge Healthcare Bio-Sciences Ab | Method and system for suspension culture |
CN106536712A (en) * | 2014-07-25 | 2017-03-22 | 通用电气健康护理生物科学股份公司 | Method and system for suspension culture |
US11667881B2 (en) | 2014-09-26 | 2023-06-06 | Terumo Bct, Inc. | Scheduled feed |
US11608486B2 (en) | 2015-07-02 | 2023-03-21 | Terumo Bct, Inc. | Cell growth with mechanical stimuli |
US11965175B2 (en) | 2016-05-25 | 2024-04-23 | Terumo Bct, Inc. | Cell expansion |
US11685883B2 (en) | 2016-06-07 | 2023-06-27 | Terumo Bct, Inc. | Methods and systems for coating a cell growth surface |
US11634677B2 (en) | 2016-06-07 | 2023-04-25 | Terumo Bct, Inc. | Coating a bioreactor in a cell expansion system |
US11104874B2 (en) | 2016-06-07 | 2021-08-31 | Terumo Bct, Inc. | Coating a bioreactor |
US11999929B2 (en) | 2016-06-07 | 2024-06-04 | Terumo Bct, Inc. | Methods and systems for coating a cell growth surface |
US11702634B2 (en) | 2017-03-31 | 2023-07-18 | Terumo Bct, Inc. | Expanding cells in a bioreactor |
US11629332B2 (en) | 2017-03-31 | 2023-04-18 | Terumo Bct, Inc. | Cell expansion |
US11624046B2 (en) | 2017-03-31 | 2023-04-11 | Terumo Bct, Inc. | Cell expansion |
EP3794104A4 (en) * | 2018-05-18 | 2022-06-08 | Children's Research Institute, Children's National Medical Center | System of cell expansion and methods of using the same |
WO2023064187A1 (en) * | 2021-10-13 | 2023-04-20 | Life Technologies Corporation | Scalable systems and methods for continuous transfection of cells |
Also Published As
Publication number | Publication date |
---|---|
EP1222249A1 (en) | 2002-07-17 |
CA2386001A1 (en) | 2001-04-05 |
AUPQ319199A0 (en) | 1999-10-28 |
JP2003510068A (en) | 2003-03-18 |
EP1222249A4 (en) | 2006-06-07 |
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