CN110106085A - A kind of integrated bioreactor for attached cell culture - Google Patents
A kind of integrated bioreactor for attached cell culture Download PDFInfo
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- CN110106085A CN110106085A CN201910441574.5A CN201910441574A CN110106085A CN 110106085 A CN110106085 A CN 110106085A CN 201910441574 A CN201910441574 A CN 201910441574A CN 110106085 A CN110106085 A CN 110106085A
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- 238000004113 cell culture Methods 0.000 title claims abstract description 57
- 239000007788 liquid Substances 0.000 claims abstract description 34
- 230000033228 biological regulation Effects 0.000 claims abstract description 21
- 238000010008 shearing Methods 0.000 claims abstract description 21
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000001301 oxygen Substances 0.000 claims abstract description 19
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 14
- 238000012544 monitoring process Methods 0.000 claims abstract description 11
- 239000007789 gas Substances 0.000 claims abstract description 8
- 239000006285 cell suspension Substances 0.000 claims abstract description 6
- 230000002572 peristaltic effect Effects 0.000 claims description 20
- 241001672694 Citrus reticulata Species 0.000 claims description 11
- 230000001105 regulatory effect Effects 0.000 claims description 11
- 230000001276 controlling effect Effects 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 229920001296 polysiloxane Polymers 0.000 claims description 7
- 238000005303 weighing Methods 0.000 claims description 2
- 239000001963 growth medium Substances 0.000 abstract description 10
- 239000002609 medium Substances 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 18
- 238000011049 filling Methods 0.000 description 6
- 230000008859 change Effects 0.000 description 5
- 238000009826 distribution Methods 0.000 description 5
- 230000010261 cell growth Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000005056 cell body Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
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- 230000005540 biological transmission Effects 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000000249 desinfective effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 230000009969 flowable effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
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- 238000012986 modification Methods 0.000 description 1
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- 230000029219 regulation of pH Effects 0.000 description 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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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
- C12M23/08—Flask, bottle or test tube
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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
- C12M23/48—Holding appliances; Racks; Supports
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- 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
- C12M29/06—Nozzles; Sprayers; Spargers; Diffusers
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- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
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- 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
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- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
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- 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
- C12M41/32—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of substances in solution
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- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/44—Means for regulation, monitoring, measurement or control, e.g. flow regulation of volume or liquid level
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Abstract
The present invention provides a kind of integrated bioreactor for attached cell culture, and the bioreactor includes sequentially connected regulator control system, reaction kettle body and cell culture unit, and the regulator control system, reaction kettle body are connected with the inside of cell culture unit；Gas pressure balancing hole and dripping hole are provided on the regulator control system, center deflector hole and liquid level monitoring hole are provided on the cell culture unit, the gas pressure balancing hole, which is connected with liquid level monitoring hole by pipeline, constitutes liquid level sensor, the bioreactor further includes cell suspension bottle, center deflector hole one end is connected by pipeline with dripping hole, and the other end is connected by pipeline with cell suspension bottle.The culture medium of cell culture unit and regulator control system is successfully swapped and is recycled by the present invention, is successfully realized the unified regulation of each unit Medium's PH Value and oxygen dissolving value；Also achieve the regulation to laminar flow shearing force and liquid level in cell culture unit.
Description
Technical field
The present invention relates to bioreactor technology fields, more particularly, to a kind of one for attached cell culture
Change bioreactor.
Background technique
Bioreactor be can environment in mimic biology well, thus required for the growth for different cells provides
The cultured and amplified in vitro device of nutriment, physical environment and chemical environment.Therefore in the production of drug, organizational project and again
In raw medicine, bioreactor possesses great development prospect and potentiality.
In the bioreactor, the distribution that the culture solution of flowable formula makes the nutriment in culture solution more uniform,
So that cell can draw nourishment from well, substance grow and excretes metabolic waste immediately.Biological respinse at present
Device can be divided into many types according to different training methods.With the culture solution type of flow can be divided into filling type bioreactor with
And hybrid bioreactor, the transmission efficiency of filling type bioreactor is high in the middle, flow field is stable, therefore is more studied
The concern of personnel.Filling type bioreactor can equally be divided by structure fluidized-bed reactor, multi-layer planar reactor and in
Hollow fibre reacotr etc..In multi-layer planar filling type bioreactor, using multi-layer planar arranged in parallel as the load of cell
Body is flooded with culture solution in plate and plate, is gathered in fluid hole by center deflector hole or flows into different layers culture plate, at present
It has been successfully applied in the clinical tests such as Stem cells cultured in vitro, bioartificial liver.
Chinese patent ZL 201310197609.8 discloses a kind of filling type bioreactor, contains the double-deck cyclic system
System, including outer loop system, the culture tank, gas loading system and internal layer inside culture tank being set to outside culture tank
The circulatory system, it is intended to solve cell in experiment incubation for the demand contradictory of the culture solution circulated, and can be with
The problem of promoting the solubility of oxygen in culture solution and being uniformly distributed, the discharge of more convenient waste, and greatly subtract
The bubble generated in cell culture area is lacked.But the patent does not solve the controllable technical problem of pH, dissolved oxygen, shearing force.
In the bioreactor, the growth of cell and the size and distribution relation of flow field shearing force are close.Suitable flow field
Shearing force can be effectively facilitated the activity of cell differentiation and cell growth, on the contrary, excessive flow field shearing force will lead to
The reduction of cell activity even results in Apoptosis.Filling type bioreactor there are the problem of as culture solution inlet stream
Field shearing force is larger, and suitable growing environment can not be provided for cell.In addition, cell will receive shearing force at bubbles burst
It influences, the activity of cell is caused to reduce.Culture solution is directly filled into multilayer and put down by current multi-layer planar bioreactor use
In hardened structure, shearing force environment in flow field unevenly distributed is caused, the growth of cell is inhibited.Therefore, it is necessary to research and develop one kind
PH, dissolved oxygen and the controllable bioreactor of shearing force.
Summary of the invention
It is an object of the invention to overcome the shortcomings of that prior art pH, dissolved oxygen and shearing force can not regulate and control, one kind is provided
The integrated bioreactor controllable for the pH, dissolved oxygen, shearing force of attached cell culture, integral biological provided by the invention
Reactor can be realized the study on microenvironment regulation of pH value, dissolved oxygen, laminar shear power and temperature of attached cell culture environment etc..
In order to solve the above technical problems, the technical solution adopted by the present invention is that:
A kind of integrated bioreactor controllable for the pH, dissolved oxygen, shearing force of attached cell culture, the biology are anti-
Answering device includes sequentially connected regulator control system, reaction kettle body and cell culture unit, the regulator control system, reaction kettle body and cell
The inside of culture unit is connected；Gas pressure balancing hole and dripping hole, the cell culture are provided on the regulator control system
Center deflector hole and liquid level monitoring hole are provided on unit, the gas pressure balancing hole is connected with liquid level monitoring hole by pipeline
Logical to constitute liquid level sensor, the bioreactor further includes cell suspension bottle, center deflector hole one end by pipeline with
Dripping hole is connected, and the other end is connected by pipeline with cell suspension bottle；The minim pipette is connected with center deflector hole
It is provided with out on pipeline and flows peristaltic pump, be provided with the wriggling that becomes a mandarin on the pipeline that the center deflector hole is connected with cell suspension bottle
Pump.
The present invention connects the center deflector hole of cell culture unit and the dripping hole of regulator control system by pipeline, and by compacted
Dynamic pump realizes the culture medium exchange of cell culture unit and regulator control system, to realize the unified regulation of each unit pH value and dissolved oxygen.
Laminar flow shearing force size in rotation speed regulating and controlling cell culture unit of the present invention by going out stream peristaltic pump, passes through the letter of liquid level sensor
The liquid level of breath feedback cell culture unit, and the liquid level of the rotational speed regulation cell culture unit by regulating and controlling the peristaltic pump that becomes a mandarin
Highly.In addition, concentration regulation can be used in temperature regulation, can also need to regulate and control respectively using each culture unit according to different.
In the present invention, the cell culture unit is the perfusion column plate type bioreactor kettle cultivated for attached cell
Body.The regulator control system is the upper regulation autoclave body regulated and controled for realizing dissolved oxygen, pH value.
Preferably, further include bracket for carrying the bioreactor.
Preferably, the air inlet for regulating and controlling pH and dissolved oxygen is additionally provided on the cell culture unit.
Preferably, the pipeline is transparent medical high temperature high voltage resistant silicone tube.
The present invention goes back while protecting the concentration regulation of above-mentioned integrated bioreactor and the regulation of individuation regulation synthesis
Method, the regulation method are as follows:
Laminar flow shearing force size in rotation speed regulating and controlling cell culture unit by going out stream peristaltic pump, passes through liquid level sensor
Information feeds back the liquid level of cell culture unit, and the liquid of the rotational speed regulation cell culture unit by regulating and controlling the peristaltic pump that becomes a mandarin
Face height.
Compared with prior art, the invention has the following beneficial effects:
Provided by the present invention for the controllable integrated bioreactor of the pH of attached cell culture, dissolved oxygen, shearing force, at
Function the culture medium of cell culture unit and regulator control system is swapped and recycled, is successfully realized each unit culture medium pH value
And the unified regulation of oxygen dissolving value；By adjusting out the revolving speed of stream peristaltic pump, cell culture unit and reaction kettle are successfully changed
The size and distribution of laminar flow shearing force in body, the influence deeper into ground research laminar shear power to cell proliferation and growthform；
Successfully pass through the culture medium liquid level of the information monitoring cell culture unit of liquid level sensor；Change turning for the peristaltic pump that becomes a mandarin
Speed successfully has adjusted the liquid level of cell culture unit, to greatly optimize the function and performance of system.
Detailed description of the invention
Fig. 1 is the front view for the integrated bioreactor that embodiment 1 provides.
Fig. 2 is the schematic diagram of the regulator control system for the integrated bioreactor that embodiment 1 provides.
Fig. 3 is the side view of the reaction kettle body for the integrated bioreactor that embodiment 1 provides.
Fig. 4 is the bottom view of the cell culture unit for the integrated bioreactor that embodiment 1 provides.
Fig. 5 be become a mandarin peristaltic pump with go out flow peristaltic pump structural schematic diagram.
Specific embodiment
Further illustrate the present invention below in conjunction with specific embodiments and the drawings, but embodiment the present invention is not done it is any
The restriction of form.Unless stated otherwise, the present invention uses reagent, method and apparatus is the art conventional reagents, method
And equipment.
Unless stated otherwise, agents useful for same and material of the present invention are commercially available.
Embodiment 1
Fig. 1 is the front view of integrated bioreactor provided in this embodiment, as shown in Figure 1, bioreactor includes
For realizing dissolved oxygen, pH value regulate and control regulator control system 1, reaction kettle body 2, for attached cell culture cell culture unit 3 with
And bracket 4.
The schematic diagram of Fig. 2,4 respectively regulator control system and cell culture unit, Fig. 3 is the side view of reaction kettle body, and Fig. 5 is
Become a mandarin peristaltic pump with go out flow peristaltic pump structural schematic diagram.As shown in Fig. 2,3,4,5, during the experiment, with transparent medical resistance to
The dripping hole 6 of regulator control system 1 is connected by high temperature and pressure silicone tube with the center deflector hole 7 of cell culture unit 3, and it is compacted to match stream
Dynamic pump 11 realizes the exchange of culture medium, to realize the pH value and oxygen dissolving value of culture medium in cell culture unit 3 and regulator control system 1
Unified regulation exchange with recycling, the system for constituting self-loopa.Change and flows the revolving speed of peristaltic pump 11 out to regulating cell culture
The size and distribution of laminar flow shearing force in unit 3 and reaction kettle body 2, research stratification shearing force is to cell proliferation quantity and growth shape
The influence of state.
In monitoring regulation process, liquid level monitoring hole 8 is put down with gas pressure with transparent medical high temperature high voltage resistant silicone tube
Weighing apparatus hole 5 is connected, and constitutes the liquid level sensor that can transmit liquid level information in cell culture unit 3 and reaction kettle body 2.With transparent
Medical high temperature high voltage resistant silicone tube connection center deflector hole 7 and cell suspending liquid bottle, and the peristaltic pump that becomes a mandarin is set on silicone tube
10.Cell suspending liquid is squeezed into cell culture unit 3 and reaction kettle body from center deflector hole 7 by the use for the flow pumps 10 that become a mandarin
In 2, to realize the actual liquid level height of culture medium in monitoring cell culture unit 3 and reaction kettle body 2.
Fig. 4 is the bottom view of cell culture unit, as shown in figure 4, being additionally provided on cell culture unit 3 for regulating and controlling pH
With the air inlet 9 of dissolved oxygen.
The operating procedure of integrated bioreactor provided in this embodiment is as follows:
(1) bioreactor bracket is put into 75% alcoholic solution and is placed in super-clean bench UV environment after soaking and washing
Lower irradiation simultaneously air-dries；
(2) integrated bioreactor is soaked in after bromogeramine 2 hours and is cleaned with clear water, be subsequently placed into 60 DEG C of air blast
It is dried in drying box；
(3) it is taken out after integrated bioreactor is dry, bioreactor bracket is installed on bioreactor bottom
Cell culture unit is constituted, integrated bioreactor is put into 120 DEG C of disinfecting actions of progress in high-pressure sterilizing pot, then by one
Body bioreactor is placed in 5%CO2, in 37 DEG C of cell incubator environment；
(4) human marrow mesenchymal stem cell is cultivated in Tissue Culture Flask to proliferation to 10,000,000 cells, and uses tryptose
Cell suspending liquid is made after enzymic digestion cell, is afterwards squeezed into cell suspending liquid in bioreactor by peristaltic pump.It is quiet to cell
After adhering to bracket after setting 24 hours, bioreactor is connected by silicone tube with BioBundles fermentor and carries out parameter tune
Section and circumfusion；
(5) cell growth is observed after cell culture 10 days and breeding state, cell reach 85% fusion.On the super-clean bench
Bioreactor flat bracket is taken out, reaches 120,000,000 by counting discovery cell quantity, that is, realizes the external expansion of stem cell
Increase.
The integrated bioreactor controllable for the pH, dissolved oxygen, shearing force of attached cell culture provided in this embodiment,
Successfully the culture medium of cell culture unit and regulator control system is swapped and recycled, is successfully realized each unit medium pH
The unified regulation of value and oxygen dissolving value；By adjust out stream peristaltic pump revolving speed, successfully change cell culture unit with react
The size and distribution of laminar flow shearing force in autoclave body, deeper into ground research laminar shear power to the shadow of cell proliferation and growthform
It rings；Successfully pass through the culture medium liquid level of the information monitoring cell culture unit of liquid level sensor；Change the peristaltic pump that becomes a mandarin
Revolving speed, the liquid level of cell culture unit is successfully had adjusted, to greatly optimize the function and performance of system.
Obviously, the above embodiment of the present invention be only to clearly illustrate example of the present invention, and not be pair
The restriction of embodiments of the present invention.For those of ordinary skill in the art, may be used also on the basis of the above description
To make other variations or changes in different ways.There is no necessity and possibility to exhaust all the enbodiments.It is all this
Made any modifications, equivalent replacements, and improvements etc., should be included in the claims in the present invention within the spirit and principle of invention
Protection scope within.
Claims (5)
1. it is a kind of for attached cell culture integrated bioreactor, which is characterized in that the bioreactor include according to
Regulator control system (1), reaction kettle body (2) and the cell culture unit (3) of secondary connection, the regulator control system (1), reaction kettle body (2)
It is connected with the inside of cell culture unit (3)；Gas pressure balancing hole (5) and dropping liquid are provided on the regulator control system (1)
Hole (6), center deflector hole (7) and liquid level monitoring hole (8) are provided on the cell culture unit (3), and the gas pressure is flat
Weighing apparatus hole (5), which is connected with liquid level monitoring hole (8) by pipeline, constitutes liquid level sensor, and the bioreactor further includes that cell is outstanding
Floating bottle, described center deflector hole (7) one end are connected by pipeline with dripping hole (6), and the other end is suspended by pipeline and cell
Bottle is connected；Stream peristaltic pump (11) is provided with out on the pipeline that the minim pipette (6) is connected with center deflector hole (7), it is described
The peristaltic pump that becomes a mandarin (10) are provided on the pipeline that center deflector hole (7) is connected with cell suspension bottle.
2. integrated bioreactor according to claim 1, which is characterized in that further include for carrying the biological respinse
The bracket (4) of device.
3. integrated bioreactor according to claim 1, which is characterized in that also set on the cell culture unit (3)
It is equipped with the air inlet (9) for regulating and controlling pH and dissolved oxygen.
4. integrated bioreactor according to claim 1, which is characterized in that the pipeline is that transparent medical high temperature resistant is high
Press silicone tube.
5. the comprehensive regulation side of the concentration regulation and individuation regulation of any integrated bioreactor of Claims 1 to 4
Method, which is characterized in that the regulation method is as follows:
Laminar flow shearing force size in rotation speed regulating and controlling cell culture unit by going out stream peristaltic pump, passes through the information of liquid level sensor
The liquid level of cell culture unit is fed back, and the liquid level of the rotational speed regulation cell culture unit by regulating and controlling the peristaltic pump that becomes a mandarin is high
Degree.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201910441574.5A CN110106085B (en) | 2019-05-24 | 2019-05-24 | Integrated bioreactor for adherent cell culture |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201910441574.5A CN110106085B (en) | 2019-05-24 | 2019-05-24 | Integrated bioreactor for adherent cell culture |
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| CN110106085B CN110106085B (en) | 2022-06-28 |
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6080581A (en) * | 1998-07-02 | 2000-06-27 | Charles Daniel Anderson | Culture vessel for growing or culturing cells, cellular aggregates, tissues and organoids and methods for using same |
| CN101899394A (en) * | 2010-07-29 | 2010-12-01 | 罗火生 | External circulation animal cell culture bioreactor |
| CN203582875U (en) * | 2013-11-12 | 2014-05-07 | 罗火生 | Pneumatic self-circulation animal cell culture bioreactor |
| CN203801564U (en) * | 2014-05-20 | 2014-09-03 | 齐齐哈尔医学院 | Human body specimen filling device |
| CN105586249A (en) * | 2016-03-07 | 2016-05-18 | 浙江大学 | Circulating perfusion biological reactor device capable of achieving circulating perfusion of three-dimensional support |
| US20170204358A1 (en) * | 2014-04-04 | 2017-07-20 | Synthecon, Inc. | Bioreactor system for stem cell expansion |
| CN108060081A (en) * | 2018-02-05 | 2018-05-22 | 中山大学 | A kind of multi-layer planar filling type bioreactor |
| CN208584926U (en) * | 2018-07-10 | 2019-03-08 | 青岛乐喜力科技发展有限公司 | A kind of pressure inductive glue liquid level regulation device |
| CN109576157A (en) * | 2019-01-14 | 2019-04-05 | 南京鼓楼医院 | Circumfusion formula biology artificial hepatocyte reactor and its application method |
-
2019
- 2019-05-24 CN CN201910441574.5A patent/CN110106085B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6080581A (en) * | 1998-07-02 | 2000-06-27 | Charles Daniel Anderson | Culture vessel for growing or culturing cells, cellular aggregates, tissues and organoids and methods for using same |
| CN101899394A (en) * | 2010-07-29 | 2010-12-01 | 罗火生 | External circulation animal cell culture bioreactor |
| CN203582875U (en) * | 2013-11-12 | 2014-05-07 | 罗火生 | Pneumatic self-circulation animal cell culture bioreactor |
| US20170204358A1 (en) * | 2014-04-04 | 2017-07-20 | Synthecon, Inc. | Bioreactor system for stem cell expansion |
| CN203801564U (en) * | 2014-05-20 | 2014-09-03 | 齐齐哈尔医学院 | Human body specimen filling device |
| CN105586249A (en) * | 2016-03-07 | 2016-05-18 | 浙江大学 | Circulating perfusion biological reactor device capable of achieving circulating perfusion of three-dimensional support |
| CN108060081A (en) * | 2018-02-05 | 2018-05-22 | 中山大学 | A kind of multi-layer planar filling type bioreactor |
| CN208584926U (en) * | 2018-07-10 | 2019-03-08 | 青岛乐喜力科技发展有限公司 | A kind of pressure inductive glue liquid level regulation device |
| CN109576157A (en) * | 2019-01-14 | 2019-04-05 | 南京鼓楼医院 | Circumfusion formula biology artificial hepatocyte reactor and its application method |
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