WO2007142664A1 - A method to increase dissolved oxygen in a culture vessel - Google Patents
A method to increase dissolved oxygen in a culture vessel Download PDFInfo
- Publication number
- WO2007142664A1 WO2007142664A1 PCT/US2006/037468 US2006037468W WO2007142664A1 WO 2007142664 A1 WO2007142664 A1 WO 2007142664A1 US 2006037468 W US2006037468 W US 2006037468W WO 2007142664 A1 WO2007142664 A1 WO 2007142664A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- culture
- vessel
- culture medium
- medium
- rolling
- Prior art date
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- 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
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/02—Form or structure of the vessel
-
- 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
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/10—Rotating vessel
-
- 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
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/16—Vibrating; Shaking; Tilting
Definitions
- the present invention describes a method to make effective bioreactors.
- This invention describes mechanism of action of previously described suspension culture vessels with an inversed frusto-conical or inverted frustum bottom (patent application PCT/US06/22312).
- This invention discloses a method to increase dissolved oxygen (DO) in culture medium, which forms a foundation to design and make effective mammalian cell culture bioreactors.
- DO dissolved oxygen
- Figure 1 A wide-body vessel with inverted frusto-conical bottom for suspension mammalian cell culture.
- FIG. 1 Illustration of Flurometrix DO/pH patch sensor detection technology.
- Figure 2b Fluorometrix DO/pH patch sensor detection system.
- Figure 3 150 ml work volume culture vessel with inverted frusto-conical bottom on shaker platform.
- Figure 4 Use of air pump to bubble the culture medium at static status to increase DO level.
- Figure 5a, b, c, d, e Nikon digital camera captured instant medium surface characteristics. At an instant moment, all pictures showed titled medium surface level mostly on one side of vessel wall. This characteristics of the medium movement increases DO in the culture medium by repetitively "sweeping" or washing air-exposed smooth vessel surface.
- Figure 7 Use of plastic tubes with inverted frusto-conical bottom (diameter 3 cm), suspension cultured CHOK cells easily reached 2.2% pcv in 4-days of culture on adjustable shaker platform with constant DO 100%. This created an effective mini- bioreactor system for cell clone robustness screening.
- Figure 8a A ball-shaped self-rolling bioreactor with back and forth movement for culture medium mixing.
- Figure 8b A ball-shaped self-rolling bioreactor on orbital shaker platform for culture medium mixing.
- Figure 8c A cone-shaped self-rolling bioreactor vessel with inside projected orbital rails.
- Figure 9b 10-liter vessel base with inverted frusto-conical bottom.
- Figure 10 a current Flurometrix cell clone robustness screening and process optimization high-throughput mini-bioreactor system.
- Figure 1 Ob Shaker-based multiple wells with frusto-conical bottom for cell line robustness screening.
- This invention is based, at least in part, on the previous discovery that, without using sophisticated control tower and related DO and pH probes, suspension adapted mammalian cells grew significantly better in culture vessels with an inversed frusto- conical or inverted frustum bottom on a shaker platform with certain motion length than classical Applikon bioreactor as well as flat-bottom shaker bottles ( Figure 1).
- DO sensor In order to study its mechanism of action, we have employed DO sensor, pH sensor and their detection system (www.flurometrix .com)( Figure 2a, b). We have also employed digital camera (Nikon) to catch and study detailed culture medium movement during shaking motion in the frusto-conical bottom vessels.
- Table 3 Simultaneously monitoring DO. pH, glucose. Mixing speed and temperature in a batch culture process in 150ml work volume vessel with inverted frusto-conical bottom.
- Bioreactor vessel bases with inverted frusto-conical bottom and soft plastic bags were designed and constructed. These bases and bags were designed to use in shaker platforms with adjustable motion length. The designed frusto-conical bottom together with adjustable shaker platform were intended to make the culture medium climbing as high as possible and as easier as possible (use of minimum shaking energy) to increase DO level in the medium and meet the challenge of high level use of 02 at high cell density culture condition. 3, 10, 20, 40, 100, 500 and 1000-liter size vessel bases and plastic bags have been designed for prototype construction and testing. Our goal is to construct cost-effective shear-force-less single-used mammalian culture bioreactors for R&D and industrial uses.
- Robustness of a production cell line is important for stability of scale-up process and ultimate expression yield of a give protein drug.
- the high expression cell lines screened from thousands of cell clones some of them are robust cell lines who meet industrial production cell standard.
- the selected robust cell lines are able to grow in high density for longer time and thus generate >10 fold higher expression titer than original screened cell clone expression titer.
- Current mini-bioreactor system www.flurometrix.com
- Figure 10a is not optimized for high cell density cell growth and does not have optimal DO level to support of high density cell population. Thus it does not have screening of robust cell clones. Without sufficient medium DO, there is no way to optimize fed-batch process at high cell density.
- the designed multiple well plate on shaker platform (Figure 10b) will provide sufficient DO in the medium due to shaking motion and frusto-conical bottom of the culture wells to support high cell density growth, thus being able to screen a given cell line's ultimate capacity to grow in highest density and be distinguished from non-robust cell clones.
- This system is easy to handle and very cost-effective in addition.
- Figure 8a shows a ball-shaped self-rolling bioreactor vessel by repetitively washing the air exposed vessel inner surface. This rolling movement increases DO in the culture medium to support high cell density growth. While a back and forth movement at ground level makes the culture medium well mixed during rolling movement ( Figure 8a). Together they support optimal suspension cell culture.
- Figure 8b shows an ball-shaped self-rolling bioreactor vessel. This rolling movement increases DO in the culture medium by repetitively washing the air exposed vessel inner surface to support high cell density growth. While an orbital shaker-platform at ground level makes the culture medium well mixed during rolling movement. Together they support optimal suspension cell culture.
- Figure 8c shows a cone-shaped self-rolling bioreactor vessel. This rolling movement increases DO in the culture medium by repetitively washing the air exposed vessel inner surface to support high cell density growth. While inside projected orbital rails make the culture medium move up to upper one end while rolling and fall back to the lower end. This additional movement helps culture medium mixing during rolling movement. Together they support optimal suspension cell culture.
Abstract
Description
Claims
Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK06815465.7T DK2021459T3 (en) | 2006-06-08 | 2006-09-27 | A PROCEDURE TO INCREASE DISSOLVED OXYGEN IN A CULTURE CONTAINER |
CN2006800555460A CN101506349B (en) | 2006-06-08 | 2006-09-27 | A method to manufacture effective bioreactor |
CA002654577A CA2654577A1 (en) | 2006-06-08 | 2006-09-27 | A method to increase dissolved oxygen in a culture vessel |
MX2008015671A MX2008015671A (en) | 2006-06-08 | 2006-09-27 | A method to increase dissolved oxygen in a culture vessel. |
ES06815465.7T ES2663202T3 (en) | 2006-06-08 | 2006-09-27 | A method to increase dissolved oxygen in a culture vessel |
US12/303,837 US9512392B2 (en) | 2006-06-08 | 2006-09-27 | Method to increase dissolved oxygen in a culture vessel |
BRPI0621678-1A BRPI0621678A2 (en) | 2006-06-08 | 2006-09-27 | method for increasing dissolved oxygen in a culture vessel and a mammalian cell suspension culture vessel |
AU2006344392A AU2006344392A1 (en) | 2006-06-08 | 2006-09-27 | A method to increase dissolved oxygen in a culture vessel |
JP2009514250A JP2009539373A (en) | 2006-06-08 | 2006-09-27 | Method for increasing dissolved oxygen in culture vessels |
EP06815465.7A EP2021459B8 (en) | 2006-06-08 | 2006-09-27 | A method to increase dissolved oxygen in a culture vessel |
IL195568A IL195568A0 (en) | 2006-06-08 | 2008-11-27 | A method to increase dissolved oxygen in a culture vessel |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
USPCT/US06/22512 | 2006-06-08 | ||
PCT/US2006/022512 WO2007015722A2 (en) | 2005-06-16 | 2006-06-08 | Addressing, command protocol, and electrical interface for non-volatile memories utilized in recording usage counts |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2007142664A1 true WO2007142664A1 (en) | 2007-12-13 |
Family
ID=38801767
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2006/037468 WO2007142664A1 (en) | 2006-06-08 | 2006-09-27 | A method to increase dissolved oxygen in a culture vessel |
Country Status (1)
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WO (1) | WO2007142664A1 (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2010005746A1 (en) * | 2008-06-16 | 2010-01-14 | Amprotein Corporation | Bioreactors |
WO2010069319A2 (en) | 2008-12-19 | 2010-06-24 | Stobbe Tech A/S | Method and device for industrial biolayer cultivation |
WO2011161086A2 (en) | 2010-06-23 | 2011-12-29 | Stobbe Tech. A/S | Device and method for industrial cultivation of cells |
WO2014044612A1 (en) * | 2012-09-18 | 2014-03-27 | Bayer Technology Services Gmbh | Disposable bottle reactor tank |
US20150211027A1 (en) * | 2010-03-10 | 2015-07-30 | Eino Elias Hakalehto | Method and apparatus for accelerating biotechnical reaction and production |
WO2018082552A1 (en) | 2016-11-03 | 2018-05-11 | Zhejiang Jinyishengshi Bioengineering Co., Ltd. | Parallel bioreactor system |
WO2022115319A1 (en) * | 2020-11-30 | 2022-06-02 | Corning Incorporated | Cell culture media conditioning vessels and perfusion bioreactor system |
WO2022203513A1 (en) * | 2021-03-25 | 2022-09-29 | Meatable B.V. | Apparatus and process for culturing tissue |
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Cited By (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101821378A (en) * | 2008-06-16 | 2010-09-01 | 美国安普公司 | Bio-reactor |
CN101821378B (en) * | 2008-06-16 | 2015-07-08 | 浙江金仪盛世生物工程有限公司 | Bioreactors |
WO2010005746A1 (en) * | 2008-06-16 | 2010-01-14 | Amprotein Corporation | Bioreactors |
US9228579B2 (en) | 2008-12-19 | 2016-01-05 | Stobbe Tech A/S | Method and device for industrial biolayer cultivation |
WO2010069319A2 (en) | 2008-12-19 | 2010-06-24 | Stobbe Tech A/S | Method and device for industrial biolayer cultivation |
US10508647B2 (en) | 2008-12-19 | 2019-12-17 | Stobbe Pharma Tech Gmbh | Electronically controlled diaphragm pump |
US10288060B2 (en) | 2008-12-19 | 2019-05-14 | Stobbe Pharma Tech Gmbh | Electronically controlled diaphragm pump |
US9493797B2 (en) * | 2010-03-10 | 2016-11-15 | Eino Elias Hakalehto | Method and apparatus for accelerating biotechnical reaction and production |
US20150211027A1 (en) * | 2010-03-10 | 2015-07-30 | Eino Elias Hakalehto | Method and apparatus for accelerating biotechnical reaction and production |
US9677038B2 (en) | 2010-06-23 | 2017-06-13 | Strobbe Pharma Tech Gmbh | Device and method for industrial cultivation of cells |
WO2011161086A2 (en) | 2010-06-23 | 2011-12-29 | Stobbe Tech. A/S | Device and method for industrial cultivation of cells |
WO2014044612A1 (en) * | 2012-09-18 | 2014-03-27 | Bayer Technology Services Gmbh | Disposable bottle reactor tank |
WO2018082552A1 (en) | 2016-11-03 | 2018-05-11 | Zhejiang Jinyishengshi Bioengineering Co., Ltd. | Parallel bioreactor system |
EP3532601A4 (en) * | 2016-11-03 | 2020-06-03 | Zhejiang Jinyishengshi Bioengineering Co., Ltd. | Parallel bioreactor system |
WO2022115319A1 (en) * | 2020-11-30 | 2022-06-02 | Corning Incorporated | Cell culture media conditioning vessels and perfusion bioreactor system |
WO2022203513A1 (en) * | 2021-03-25 | 2022-09-29 | Meatable B.V. | Apparatus and process for culturing tissue |
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