CN102517215A - Small bioreactor - Google Patents
Small bioreactor Download PDFInfo
- Publication number
- CN102517215A CN102517215A CN2011103935360A CN201110393536A CN102517215A CN 102517215 A CN102517215 A CN 102517215A CN 2011103935360 A CN2011103935360 A CN 2011103935360A CN 201110393536 A CN201110393536 A CN 201110393536A CN 102517215 A CN102517215 A CN 102517215A
- Authority
- CN
- China
- Prior art keywords
- cell
- tank body
- reactor
- culture
- cell cultures
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
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
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
-
- 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
- C12M23/38—Caps; Covers; Plugs; Pouring means
-
- 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
- C12M23/58—Reaction vessels connected in series or in parallel
-
- 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
- C12M27/02—Stirrer or mobile mixing elements
-
- 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
- C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
- C12M41/18—Heat exchange systems, e.g. heat jackets or outer envelopes
-
- 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
- C12M41/36—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of biomass, e.g. colony counters or by turbidity measurements
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Sustainable Development (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Analytical Chemistry (AREA)
- Clinical Laboratory Science (AREA)
- Physics & Mathematics (AREA)
- Thermal Sciences (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The invention belongs to the technical field of bioengineering, and in particular relates to a bioreactor device applied to cell culture. The bioreactor device comprises culture tank bodies, a temperature control suite, a stirring device, a liquid (gas) supplementing device, a cell optical density detection device and a heat exchange component. A plurality of small inorganic material tank bodies are used as a main body part of cell culture, and main parts meet the requirement of steam sterilization and are matched with a high-accuracy temperature control system and the cell optical density detection device to provide optimal conditions for cell culture. A cell culture main body is two or more cell culture tank bodies which are connected through the heat exchange component, so that the required temperature change or physicochemical parameter in the cell culture process can be quickly adjusted, and the aim of continuous culture is fulfilled. The whole bioreactor device has the characteristics of high integration degree, automatic control, capability of being amplified, high reliability, energy conservation and environment friendliness, and meets the requirements on medium and small scale cell culture and genetic recombination and protein expression in a bioengineering laboratory and pilot production.
Description
Technical field
The invention belongs to technical field of bioengineering, relate to a kind of pot type bio-reactor that is used for cell cultures.
Background technology
Conventional small-sized pot type bio-reactor adopts following method usually:
1) use same cell cultures tank body to carry out the whole process of cell cultures and abduction delivering;
2) when needs are kept or change temperature, adopt heating pipe built-in, sleeve pipe heating or reactor monolith put into thermostat container to keep culture temperature;
3) take the discontinuous fermentation mode of batch culture for the abduction delivering of genetically engineered cell strain;
4) method of carrying out single batch fermentation, progressively optimizing for the abduction delivering condition of cell cultures or genetically engineered cell strain;
5) the situ steam sterilization is adopted in the bio-reactor sterilization.
There is certain limitation in actual use in ordinary method.The bio-reactor of conventional single cultivation tank body can't be realized the cultured continuously of cell.Genetically engineered cell strain through abduction delivering is behind the beginning abduction delivering, and cell physiological state plays pendulum, and can't stablize to go down to posterity and sustainable high efficiency is expressed the purpose product.The cell strain of temperature-induced expression is under single jar of culture condition, and the change of cell cultures temperature is slower, is unfavorable for the timing of abduction delivering.The cell strain of chemically inducible expression can't realize that in same tank body multiple induced concentration induces the contrast of effect.For the culture condition of groping cell strain or genetically engineered cell strain, it is repeatable poor to adopt conventional single tank body to have, length consuming time, the high and inefficient limitation of cost.
Summary of the invention
The purpose of this invention is to provide a kind of bio-reactor that can realize cell cultured continuously and abduction delivering; And different abduction delivering conditions can be provided; Satisfy the demand of the abduction delivering condition of different mechanisms, thereby the rapid Optimum cell expression system prepares the condition of genetically engineered recombinant protein.The bio-reactor that the present invention relates to realize that cell breeds, makes full use of cell effectively continuously stable for the time and promote that cell high-efficient express recombinant protein product is a culturing purposes, but can be applicable to insect cell, mammalian cell and other engineering strains of suspension culture.
The scheme that the bio-reactor that the present invention proposes is taked is:
1. cell cultures tank body aspect: the cell cultures tank body of bio-reactor is divided into two portions, and promptly female tank body of initial incubation and the sub-tank body of further cultivating or abduction delivering is cultivated can be realized cultivating and carry out in different cultivation tank bodies with abduction delivering.
2. heat exchanger assembly: use inorganic heat-stable material to make heat exchanger assembly; Be used to connect different cells and cultivate tank body; Heat exchanger assembly itself has independently temperature controlling system; Can when cell culture is flowed through, change temperature rapidly, make cell culture arrive and reach desired temperature before next stage is cultivated tank body.
3. the cell optical density(OD) detects and fluid infusion system: the cell optical density(OD) detects and cooperates with fluid infusion system, is used to control cell culture density, can realize the purpose of cell high-density culture or control cell density scope.
4. cell cultures tank body and heat exchanger assembly fit system: initial cell is cultivated tank body and can be formed one to one or the fit system of one-to-many with heat exchanger assembly; Thereby insert single or a plurality of next stage and cultivate tank body, further carry out the optimization of cell cultures materialization condition.
5. cell culture flowing between initial incubation tank body and next stage tank body can be controlled through malleation or negative pressure mode.
6. cultivate the amplification of scale: adopt the method that simply increases cell cultures tank body, insulation external member in proportion and increase cell cultures tank body quantity can realize the amplification of the scale of cultivating, adapt to the needs that enlarge the cell preparation scale.
7. cell cultures tank body and heat exchanger assembly major parts all can independent steam sterilizings.
Advantage of the present invention is:
1. bio-reactor is integrated cell cultures tank body, temperature control external member and fluid infusion system height; Realize the automatic control of culturing process through system; Can realize the purpose of cell high-density culture and control cell culture density, increase substantially the stable and repeated of cell cultures effect simultaneously.
2. the cell cultures tank body cooperates with heat exchanger assembly; Can realize the multiple bind mode of female tank body of cell cultures and sub-tank body; Cell induction is expressed separate, can satisfy simultaneously and utilize different inductive condition pair cells to carry out the needs of abduction delivering with cultivation stage.
3. cell cultures tank body, heat exchanger assembly and fluid infusion system material are inorganic materials, can whole steam sterilizing, have the strong characteristics of high reliability and contamination resistance.
4. the working capacity of bio-reactor has scalable property, the needs that low scale cell cultures (1 is raised to tens of cultivation scales that rise) of centering and gene recombinant protein are expressed in suitable biotechnology laboratory, the middle trial production.
Description of drawings
Fig. 1 is the vertical face synoptic diagram of small-sized bio-reactor
[The major portion conventional letter
]
1, temperature detection probe; 11, heating muff; 12, insulation sleeve; 21, cell cultures tank body; 22, tank body top cover; 23, top seal rubber cushion and fastening piece; 24, rubber standoff; 31, light source; 32, lamp guide; 33, photovoltaic battery panel; 34, top cover sealing joint circle; 41, liquid supply device; 42, outside nutrient solution inlet opening; 43, outside nutrient solution spout; 43, air filter; 50, nutrient solution flow ipe; 51, system; 6, T-valve; 7, heat exchanger assembly.
Embodiment
Effectively working volume is the bio-reactor that 1.0-1.5 rises.
Design bio-reactor according to Fig. 1, environment for use is the 22-25oC room temperature environment.At first, make cell cultures tank body 21, about 3 liters of volume with inorganic glass materials.Use unorganic glass making can bodies top cover 22, use seal gasket and fastening piece 23 and the assembling of cell cultures tank body, at top cover central part opening with access top seal circle 34.
Use glass to add lagging material and make insulation sleeve 12, use rubber to make support 24, the socket of temperature detection probe 1 and heating sleeve pipe 11 is set on support, photovoltaic battery panel 33 and sealing-ring, line outlet are set in muff tube bottom central authorities.Cultivation tank body after the assembling is put into the insulation sleeve; System 51 is connected with the temperature detection probe with photovoltaic battery panel, heating muff; Connect light source 31 power supplys; Setting photovoltaic battery panel range of voltage values is used to activate liquid supply device and adds nutrient solution automatically, thereby cell cultures is in certain cell density scope.
Between insulation sleeve and cell cultures tank body, add pure water through temperature detection probe opening, treat homo(io)thermism after, add cell culture fluid in the cell cultures tank body to the left through nutrient solution influx 50, can begin to cultivate.Treat that cell culture enlarges when reaching certain volume, open T-valve 6,, make cell culture flow into right side cell cultures jar through heat exchanger assembly 7 via the air filter pressurization of female jar of cell cultures; After closing three-way valve, can begin to cultivate tank body and carry out abduction delivering or further cultivation, and cell cultures can be carried out cell amplification for female jar once more in the left side on the right side.
Bio-reactor after amplifying in proportion can be fit to mass cell and cultivate use.
Claims (9)
1. small-sized bio-reactor comprises: cell cultures tank body, temperature control external member, whipping appts, fluid infusion (gas) device, cell optical density(OD) proofing unit, cultivation gear and heat exchanger assembly; It is characterized in that: said cell cultures tank body connects with liquid supply device mutually; Temperature control external member, cell optical density(OD) detect external member and cooperate the growth conditions that optimization is provided for cell cultures with the cultivation gear, become a cell culture reactor unit; The cell culture reactor unit connects through heat exchanger assembly, realizes the orderly circulation of cell culture between reactor unit, reaches cell cultured continuously and the purpose of carrying out simultaneously under different physicochemical environments, cultivating.
2. according to the cell cultures tank body of claims 1 described small-sized bio-reactor, but said cell refers to insect cell, mammalian cell, yeast cell and the prokaryote of suspension culture.
3. according to claims 1 described small-sized bio-reactor, it is characterized in that: the cell cultures tank body connects via conduit between the tank body as the main body of cell cultures, realizes that through malleation or negative pressure mode culture flows in order between tank body.
4. according to claims 1 described small-sized bio-reactor, it is characterized in that: support with elastomeric material between cell cultures tank body and the temperature control external member, have support, buffering and sealing function concurrently; Cell cultures tank body material is glass or pottery, and connecting tubing is the Teflon material, uses high-temperature-resisting silicon rubber and stainless steel strip to be sealing material and fastening piece.
5. according to claims 1 described small-sized bio-reactor; It is characterized in that: the temperature controlled processes that pair cell is cultivated tank body is: open rly. when the heat-transfer medium temperature is lower than certain numerical value; Use the heating sleeve pipe to be heated to the design temperature closed relay, treat to repeat this process after medium temperature slowly reduces; Different cells is cultivated tank body can set differing temps.
6. according to claims 1 described small-sized bio-reactor, it is characterized in that: the initial cultivation tank body of cell injects next stage in order through heat exchanger assembly and cultivates tank body after reaching certain culture volume; Different cells is cultivated tank body can adopt different physical and chemical parameters.
7. according to claims 1 described small-sized bio-reactor; It is characterized by: cell optical density(OD) detection external member matches with the fluid infusion external member and realizes control automatically; Realization is kept cell density in certain culture density scope of setting, and this density range includes but not limited to the logarithmic phase density range of cell proliferation.
8. according to claims 1 described small-sized bio-reactor, it is characterized in that: the cell cultures tank body can adopt gas lift formula or stirring-type to realize suspension culture of cells.
9. according to claims 1 described small-sized bio-reactor, it is characterized in that: the initial incubation tank body of cell cultures tank body is cultivated tank body with gas can adopt different volumetric ratios.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103935360A CN102517215A (en) | 2011-12-02 | 2011-12-02 | Small bioreactor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103935360A CN102517215A (en) | 2011-12-02 | 2011-12-02 | Small bioreactor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102517215A true CN102517215A (en) | 2012-06-27 |
Family
ID=46288286
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011103935360A Pending CN102517215A (en) | 2011-12-02 | 2011-12-02 | Small bioreactor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102517215A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109517738A (en) * | 2018-12-14 | 2019-03-26 | 杭州奕安济世生物药业有限公司 | A kind of method of carbon dioxide content in regulation bioreactor |
| CN110862911A (en) * | 2019-11-27 | 2020-03-06 | 浙江省农业科学院 | Culture system and culture method for microbial culture |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009100713A (en) * | 2007-10-25 | 2009-05-14 | Jgc Corp | Device for producing bio-ethanol, and method for producing the same |
| CN101864454A (en) * | 2010-05-07 | 2010-10-20 | 胜利油田胜利动力机械集团有限公司 | External circulating fermentation technique and device thereof |
| CN102212474A (en) * | 2011-03-28 | 2011-10-12 | 北京新节点生物工程技术有限责任公司 | Small bioreactor |
-
2011
- 2011-12-02 CN CN2011103935360A patent/CN102517215A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009100713A (en) * | 2007-10-25 | 2009-05-14 | Jgc Corp | Device for producing bio-ethanol, and method for producing the same |
| CN101864454A (en) * | 2010-05-07 | 2010-10-20 | 胜利油田胜利动力机械集团有限公司 | External circulating fermentation technique and device thereof |
| CN102212474A (en) * | 2011-03-28 | 2011-10-12 | 北京新节点生物工程技术有限责任公司 | Small bioreactor |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109517738A (en) * | 2018-12-14 | 2019-03-26 | 杭州奕安济世生物药业有限公司 | A kind of method of carbon dioxide content in regulation bioreactor |
| CN110862911A (en) * | 2019-11-27 | 2020-03-06 | 浙江省农业科学院 | Culture system and culture method for microbial culture |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107904169B (en) | Modularized bioreactor suitable for culturing multiple cell types | |
| CN106467892B (en) | A kind of automatic cytological amplification system | |
| CN206783688U (en) | A kind of multilevel cell amplification system | |
| CN203096076U (en) | Pipeline reactor with built-in temperature control and microalgae culturing device with pipeline reactor | |
| CN101914431B (en) | Device and method for cultivating microalgae by utilizing all plastic modular photobioreactor system | |
| CN103897979B (en) | The duct type bioreactor of a kind of built-in circulating temperature control system | |
| CN204490886U (en) | A kind of biology cellulose fermentation system | |
| CN108004122B (en) | Fixed bed type cell bioreactor | |
| CN101613664B (en) | Air-lift photo-bioreactor | |
| CN201778022U (en) | Oil-rich microalgae culture device | |
| CN103589638A (en) | Pneumatic self-circulation animal cell culture bioreactor and application method thereof | |
| CN201442951U (en) | Airlift type photo-bioreactor | |
| CN205295351U (en) | Pipeline type microalgae photobioreactor | |
| CN102220242A (en) | Culture solution continuous filling method and system for chlamydomonas culture | |
| CN103224882B (en) | Disposable wave type bioreactor with aerating apparatus | |
| CN102517215A (en) | Small bioreactor | |
| CN201821760U (en) | Temperature control type aquatic experimental aquaculture system | |
| CN206887129U (en) | Disposable pneumo lift-type cell culture reactor | |
| CN205953993U (en) | Smooth autotrophy that little algae of continuous culture was used is established ties and is expanded major connector | |
| CN203057904U (en) | Simple fermentation device for liquid strain submerged cultivation | |
| CN201284344Y (en) | Constant temperature anaerobic reactor | |
| CN102212474A (en) | Small bioreactor | |
| CN209685742U (en) | A kind of transplantation device for batch fermentation | |
| CN204634470U (en) | A kind of culture device for liquid strain of edible fungus | |
| CN103602586B (en) | A kind of bioreactor cultivated for oil-producing microalgae |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120627 |