CN103131635A - Cavity-type dynamic-filling bioreaction device - Google Patents
Cavity-type dynamic-filling bioreaction device Download PDFInfo
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- CN103131635A CN103131635A CN2011103825731A CN201110382573A CN103131635A CN 103131635 A CN103131635 A CN 103131635A CN 2011103825731 A CN2011103825731 A CN 2011103825731A CN 201110382573 A CN201110382573 A CN 201110382573A CN 103131635 A CN103131635 A CN 103131635A
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- 239000000523 sample Substances 0.000 claims abstract description 46
- 235000015097 nutrients Nutrition 0.000 claims abstract description 29
- 239000012472 biological sample Substances 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims description 33
- 239000007788 liquid Substances 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- 239000000741 silica gel Substances 0.000 claims description 8
- 229910002027 silica gel Inorganic materials 0.000 claims description 8
- 230000001105 regulatory effect Effects 0.000 claims description 6
- 230000008676 import Effects 0.000 claims description 5
- 238000007789 sealing Methods 0.000 claims description 5
- 230000000295 complement effect Effects 0.000 claims description 4
- 239000000243 solution Substances 0.000 description 22
- 230000002572 peristaltic effect Effects 0.000 description 13
- 230000008859 change Effects 0.000 description 7
- 229960001866 silicon dioxide Drugs 0.000 description 7
- 239000007789 gas Substances 0.000 description 6
- 238000012258 culturing Methods 0.000 description 5
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- 238000000034 method Methods 0.000 description 4
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- 230000008569 process Effects 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 229940088623 biologically active substance Drugs 0.000 description 2
- 239000012930 cell culture fluid Substances 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
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- 230000010412 perfusion Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
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- 230000008901 benefit Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
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- 238000011161 development Methods 0.000 description 1
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- 235000003170 nutritional factors Nutrition 0.000 description 1
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Abstract
The invention provides a cavity-type dynamic-filling bioreaction device comprising a biological sample culture component, a nutrient solution flowing pipe and a power pump component. The biological sample culture component is provided with an in-out port communicated with the nutrient solution flowing pipe. The biological sample culture component comprises an upper cover body, a container body and a sample bearing frame, wherein the upper cover body is connected with the container body, a supporting ring is arranged on the inner wall of the container body, the sample bearing frame is arranged on the supporting ring, a supporting block is arranged on the inner side of the sample bearing frame, a sample bearing plate is arranged in a cavity formed by the supporting block and the sample bearing frame, and culture through holes are longitudinally formed in the sample bearing plate. The nutrient solution flowing pipe comprises an output pipe and an input pipe, wherein the output pipe and the input pipe are respectively connected with the power pump component.
Description
Technical field
The present invention relates to be applied in the device of culture sample in the field such as plant, animal and human body tissue engineering, relate in particular to a kind of reaching by the stimulation that continues dynamically to supply with nutrition and regulate mechanics and biologically active substance and promote cell and the propagation of tissue and the cavity type of differentiation dynamically to pour into biological tissue's reaction unit.
Background technology
Organizational project combines cytobiology and engineering science principle, and anatomical structure and the physiological function of research normal cell, tissue or organ are so as to producing the artificial substituting product of the structure and function that can improve, repair or rebuild damaged tissue.Its mode is to obtain a small amount of tissue from body, through separating and amplification and obtain seed cell, it is inoculated in biological support, breed and induce by vitro culture and be differentiated to form the organizational project member, then be used for repair and reconstruction, recovery organization and the organ shape and function at disease damage position.
In the organizational project development, for solving shortage and the Industrialization of tissue or the required donor material of organ transfer operation, bio-reactor arises at the historic moment.Cultivate from initial Petri dish static cultivation dynamic 3 D input type perfusion finally, the form of bio-reactor and function are in continuous variation, skewness in biological support has particular requirement to the support shape exactly but their Main Problems are not cell, and the low shortcoming of they ubiquity production capacities.
Chinese patent CN 1352240A has disclosed the device of a kind of cell with the twoport culturing bottle and organizational project cultivation.It comprises that being equipped with temperature in incubator is connected well heater and the sensor that is connected with temperature control damper with the gas flow control device.The gas inlet is arranged at incubator top, fixes an end on it and inserts the interior gas pipeline of incubator, and the other end is communicated with gas cylinder by a gas meter; Also comprise the bed that rolls, put rolling culturing bottle, its lower peace one driving mechanism of 2 above both ends opens on it, driving mechanism is connected with motor.
Chinese patent CN 1542121A has disclosed a kind of dynamic 3 D input type tissue reaction device, comprise one can be for the incubator that cell is inoculated on the biological support body with centre channel.And comprise that further at least one matches with the centre channel of biological support body and stretches into the conduit of this centre channel and a circulation infusion set that is connected with this conduit.This incubator is provided with an input aperture and a delivery port, and conduit is connected with the circulation infusion set by this input aperture.
Although existing bio-reactor can provide the dimensional culture environment to the cell on the biological support of organizational project, but cell is evenly distributed in biological support, need to again customize reactor and only can build the cell of hollow-biological support complex body when building the cell of different size-biological support complex body, these unfavorable factors all limited tissue engineering product a large amount of productions.
Summary of the invention
The present invention is according to the deficiencies in the prior art part, provide a kind of cavity type dynamically to pour into biological reaction apparatus, can be by regulating flow, stress, nutrition and the activity substance content of cell culture fluid in device, reach the propagation of promotion cell and tissue and differentiation and the formative tissue engineering component.
To achieve these goals, provide a kind of cavity type dynamically to pour into biological reaction apparatus, it is characterized in that, comprise biological sample cultivation parts, the mobile pipe fitting of nutrient solution and power-driven pump parts, described biological sample is cultivated parts and is provided with the import and export that are connected with the mobile pipe fitting of nutrient solution; Described biological sample is cultivated parts and is comprised upper cover body, container body and put the sample carrier, upper cover body is connected with container body, the container body inwall is provided with support ring, the described sample carrier of putting is arranged on support ring, the inboard of putting the sample carrier is provided with back-up block, be provided with and hold model by back-up block with in putting the formed cavity of sample carrier, the described model that holds is provided with the cultivation through hole, cultivates through hole and vertically is arranged on and holds in model.The mobile pipe fitting of described nutrient solution comprises output tube and input tube, and described output tube is connected with the power-driven pump parts respectively with input tube, and described output tube is provided with strainer.
Upper cover body connects by thread helix with container body, can guarantee good sealing property.Upper cover body, container body and put the sample carrier and can all use inorganic, the organic or metallic substance of nontoxicity to make, its shape can be rectangle, semisphere, the shape such as cylindrical.Upper cover body, container body and the shape of putting the sample carrier are mated mutually.
In the above-mentioned reaction unit that provides, wherein said biological sample is cultivated on parts and also is provided with the gaseous interchange mouth, and described gaseous interchange mouth is provided with gaseous interchange regulated valve and strainer, and described strainer is arranged on the exit of gaseous interchange regulated valve.In the above-mentioned reaction unit that provides, also have T-valve on wherein said output tube, an end of described T-valve is connected with output tube, and the other end is connected with the power-driven pump parts.Change stress and oxygen atmosphere by adjustments of gas interchange valve and peristaltic pump, equally also can change nutrition and the induced environment of nutrient solution by T-valve, affect growth and the differentiation of cell and tissue.
In the above-mentioned reaction unit that provides, the diameter of wherein said import and export and gaseous interchange mouth is 2 ~ 100 millimeters.Made by polyethylene and medical silica-gel with importing and exporting input tube and the output tube be connected, diameter is complementary with the diameter of input aperture and delivery port respectively, and its length is between 20 ~ 10000 millimeters.
In the above-mentioned reaction unit that provides, be provided with the silica gel sealing pad between wherein said upper cover body and container body.
In the above-mentioned reaction unit that provides, the wherein said sample carrier of putting is provided with draw ring, the two ends of draw ring with put the sample carrier and be connected.
In the above-mentioned reaction unit that provides, wherein said bottom of putting the sample carrier is provided with projection, and the groove that arranges on described projection and described support ring is complementary.Projection is embedded in groove, can prevent from putting the sample carrier and rotate in container body.
In the above-mentioned reaction unit that provides, the wherein said sidewall of putting the sample carrier is provided with the extension stopper, and the inwall that the sample carrier is put in the applying of extension stopper extends upward.
In the above-mentioned reaction unit that provides, the wherein said model that holds is provided with spreader plate, and separating liquid groove on spreader plate, described splitter box are provided with and lead to the flow channel for liquids that holds the model bottom.Flow channel for liquids can be arranged on the surface of splitter box, also can be arranged on the inside of holding model, can guarantee that nutrient solution evenly is diverted in each culture sample.Hold the thickness of model and spreader plate between 2 ~ 200 millimeters.
In the above-mentioned reaction unit that provides, wherein said power-driven pump parts are peristaltic pump.Forms circulation by peristaltic pump eccentric wheel extruding silicone tube power-assist nutrient solution, can be according to the flow of how much adjusting of fill orifice, direct motion that also can peristaltic pump or the flow direction of the loading change nutrient solution that drives in the wrong direction.
Cavity type provided by the invention dynamically pour into biological reaction apparatus can be under multiple environment culturing cell and tissue, and can to the organizational project member of different shape and different quantities carry out cultivate in same time and equivalent environment, can change as required nutrient environment in culturing process, add biologically active substance, and change the cultivation ambient stress and change the oxygen environment.
Description of drawings
Fig. 1 is the structural representation that cavity type of the present invention dynamically pours into biological reaction apparatus.
Fig. 2 is the sectional view that in the present invention, biological sample is cultivated parts.
Fig. 3 is the sectional view of the mid-sample carrier of the present invention.
Fig. 4 is the schematic diagram that holds model in the present invention.
Fig. 5 is the schematic diagram of spreader plate in the present invention.
Embodiment
The invention provides a kind of cavity type and dynamically pour into biological tissue's reaction unit, by regulating flow, stress and nutrition and the activity substance content of cell culture fluid in device, reach the propagation of promotion cell and tissue and differentiation and the formative tissue engineering component.
The dynamic perfused tissue reaction unit of cavity type of the present invention is the principle of utilizing blood circulation of human body, the method that adopts the dynamic liquid perfusion to cultivate, make the cell of different cells in and same chamber inner at each cell of cultivating-biological support complex body-biological support complex body inside can obtain all the time enough and balanced nutrition, make it better carry out division growth, have the tissue of good function or the surrogate of organ thereby form.
Come by the following examples the present invention is described in further details, in order to better understand the content of the invention, but embodiment does not limit the protection domain of the invention.
Cavity type provided by the invention dynamically pours into biological reaction apparatus and comprises biological sample cultivation parts, the mobile pipe fitting of nutrient solution and power-driven pump parts three parts.
Biological sample is cultivated parts and is comprised upper cover body 1, container body 13 and put sample carrier 23.Upper cover body 1 is provided with the import that is connected with the mobile pipe fitting of nutrient solution, and container body 13 is provided with the outlet that is connected with the mobile pipe fitting of nutrient solution.The diameter of import and export and gaseous interchange mouth is between 2 ~ 100 millimeters.Upper cover body 1 is connected with container body and is connected by thread helix, wherein is provided with the silica gel sealing pad 7 for sealing between upper cover body 1 and container body 13.
Be provided with support ring 10 on container body 13 inwalls, make put sample carrier 23 can frame on support ring 10.Put sample carrier upside and establish the back-up block 15 that extends internally.Hold model 22 being provided with by back-up block 15 with in putting the formed cavity of sample carrier 23.Be provided with draw ring 8 on sample carrier 23 putting, the two ends of draw ring 8 with put sample carrier 23 and be connected, be convenient to put taking of sample carrier 23.Be provided with projection 11 in the bottom of putting sample carrier 23, projection 11 is complementary with the groove that is arranged on support ring, can prevent from putting sample carrier 23 in the interior rotation of container body 13.Be provided with on the sidewall of putting sample carrier 23 and extend stopper 4, the inwall that sample carrier 4 is put in 4 applyings of extension stopper extends upward, and that extends the inner nutrient solution of the anti-locking apparatus of stopper 4 routs up reaction unit because rocking.
According to the requirement of cultivating, need the cultivation of quantity through hole 25 holding to be provided with on model 22, cultivate through hole 25 and vertically be arranged on and hold in model 22.Cultivate and place also the fixedly sample of cultivation in through hole 25, nutrient solution can be arbitrarily by cultivating through hole 25.
Be provided with spreader plate 9 on model 22 holding, the shape of spreader plate 9 is smaller holds on model 22.Separating liquid groove 213 on spreader plate 9, splitter box 213 are provided with and lead to the flow channel for liquids 214 that holds model 22 bottoms.Flow channel for liquids 214 can be arranged on the surface of splitter box 213, also can be arranged on the inside of holding model 9.These grooves and runner can guarantee that the nutrient solution after injection device evenly is diverted in each culture sample.
Cultivate on parts at biological sample and also be provided with the gaseous interchange mouth, the gaseous interchange mouth selects excellent being arranged on upper cover body 1.The gaseous interchange mouth is provided with gaseous interchange variable valve 311 and strainer 310, and strainer 310 is arranged on the exit of gaseous interchange variable valve 311, and strainer 310 can reduce in scavenging period bacterium and enter and cultivate in parts.
Upper cover body 1, container body 13 and put sample carrier 23 and can all use inorganic, the organic or metallic substance of nontoxicity to make, its shape can be rectangle, semisphere, the shape such as cylindrical.Upper cover body, container body and the shape of putting the sample carrier are mated mutually.
The mobile pipe fitting of nutrient solution comprises output tube 16 and input tube 20, and output tube 16 is connected with the power-driven pump parts respectively with input tube 20.Input tube 20 and output tube 16 are provided with the accessories such as strainer 18, T-valve 19, silica gel extruded tube 24, and it adopts telescoping to connect, and are convenient to replacing, clean filter and load nutrient solution.Select an end of T-valve 24 to be connected with output tube, the other end is connected with the power-driven pump parts, can help to load sampling observation sampling in nutritional factor or culturing process.The silica gel extruded tube has ventilation property, can complete gaseous interchange with the external world.The nutrient solution of strainer 18 filtered and recycled can stop cell and other tangible materials of being scattered to be input in the middle of the multiporous biological support.
The power-driven pump parts are selected peristaltic pump 17, make nutrient solution circulate by peristaltic pump eccentric wheel extruding silicone tube.Can be according to the flow of how much adjusting of fill orifice, its flow is controlled between 0.01 ~ 50ml/h.Nutrition supplying amount and the stress of sample be can also change by peristaltic pump, propagation and the differentiation of cell and tissue affected.But peristaltic pump extruding silicone tube direct motion or the loading nutrient solution that drives in the wrong direction make nutrient solution flow according to practical situation.
When using cavity type of the present invention dynamically to pour into biological tissue's reaction unit, need to carry out sterilization to the whole system except peristaltic pump.Be connected successively with the order of out splice going splice 14 according to input adapter 3, input tube 20, crossover sub 21, silica gel silica gel extruded tube 24, peristaltic pump 17, T-valve 19, strainer 18, output tube 16.After starting peristaltic pump 17, nutrient solution enters biological sample by peristaltic pump 17, input tube 20 and cultivates parts.Under action of gravity, nutrient solution is holding on model 9 stream with uniform distribution to the cultivation through hole 25 that holds on model 22.After flowing through the culture of cultivating in through hole 25, flow to the bottom that biological sample is cultivated parts, and flow out biological sample cultivation parts by out splice going splice 14, flowing by peristaltic pump 17 recirculation nutrient solutions.
Cavity type provided by the invention dynamically pours into the combined enclosed environment that biological reaction apparatus can be used for cells in vitro cultivation or tissue construction, and culture apparatus of the present invention can carry out common cell cultures is indoor, can carry out simultaneously the structure of the homogeneous cell of one or more, identical or different specification-biological support complex body, have the advantages such as pollution of using simple and easy, controlled, efficient, voluminous, homogeneous and effectively avoiding operating process to cause.
Above specific embodiments of the invention are described in detail, but it is just as example, the present invention is not restricted to specific embodiment described above.To those skilled in the art, any equivalent modifications that the present invention is carried out and substituting also all among category of the present invention.Therefore, not breaking away from impartial conversion and the modification of doing under the spirit and scope of the present invention, all should contain within the scope of the invention.
Claims (10)
1. a cavity type dynamically pours into biological reaction apparatus, it is characterized in that, comprises biological sample cultivation parts, the mobile pipe fitting of nutrient solution and power-driven pump parts, and described biological sample is cultivated parts and is provided with the import and export that are connected with the mobile pipe fitting of nutrient solution;
Described biological sample is cultivated parts and is comprised upper cover body, container body and put the sample carrier, upper cover body is connected with container body, the container body inwall is provided with support ring, the described sample carrier of putting is arranged on support ring, the inboard of putting the sample carrier is provided with back-up block, be provided with and hold model by back-up block with in putting the formed cavity of sample carrier, the described model that holds is provided with the cultivation through hole, cultivates through hole and vertically is arranged on and holds in model;
The mobile pipe fitting of described nutrient solution comprises output tube and input tube, and described output tube is connected with the power-driven pump parts respectively with input tube.
2. reaction unit according to claim 1, it is characterized in that, described biological sample is cultivated on parts and also is provided with the gaseous interchange mouth, and described gaseous interchange mouth is provided with gaseous interchange regulated valve and strainer, and described strainer is arranged on the exit of gaseous interchange regulated valve.
3. reaction unit according to claim 1 and 2, is characterized in that, also has strainer on described output tube.
4. reaction unit according to claim 1, is characterized in that, described upper cover body connects by thread helix with container body.
5. reaction unit according to claim 1, is characterized in that, is provided with the silica gel sealing pad between described upper cover body and container body.
6. reaction unit according to claim 1, is characterized in that, the described sample carrier of putting is provided with draw ring, the two ends of draw ring with put the sample carrier and be connected.
7. reaction unit according to claim 1, is characterized in that, described bottom of putting the sample carrier is provided with projection, and the groove that arranges on described projection and described support ring is complementary.
8. reaction unit according to claim 1, is characterized in that, the described sidewall of putting the sample carrier is provided with the extension stopper, and the inwall that the sample carrier is put in the applying of extension stopper extends upward.
9. reaction unit according to claim 1, is characterized in that, the described model that holds is provided with spreader plate, and separating liquid groove on spreader plate, described splitter box are provided with and lead to the flow channel for liquids that holds the model bottom.
10. reaction unit according to claim 1, is characterized in that, also has T-valve on described output tube, and an end of described T-valve is connected with output tube, and the other end is connected with the power-driven pump parts.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110382573.1A CN103131635B (en) | 2011-11-28 | 2011-11-28 | Cavity-type dynamic-filling bioreaction device |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110382573.1A CN103131635B (en) | 2011-11-28 | 2011-11-28 | Cavity-type dynamic-filling bioreaction device |
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| Publication Number | Publication Date |
|---|---|
| CN103131635A true CN103131635A (en) | 2013-06-05 |
| CN103131635B CN103131635B (en) | 2014-08-13 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110382573.1A Expired - Fee Related CN103131635B (en) | 2011-11-28 | 2011-11-28 | Cavity-type dynamic-filling bioreaction device |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104893973A (en) * | 2015-03-17 | 2015-09-09 | 成都军区昆明总医院 | Dynamic perfusion culture system for promoting tissue engineering products to be vascularized in vitro |
| CN104962456A (en) * | 2015-07-16 | 2015-10-07 | 中国海洋大学 | Harvesting device capable of concentrating microalgae cells in raceway pond by virtue of microbubble backflash |
| CN106010966A (en) * | 2016-06-08 | 2016-10-12 | 中山大学附属第医院 | Multidirectional tissue-engineering porous material perfusion system |
| CN108315256A (en) * | 2018-04-26 | 2018-07-24 | 上海久博生物工程有限公司 | Activity ventilation component and its active aeration type bioreactor and cell culture apparatus |
| CN109843417A (en) * | 2016-08-21 | 2019-06-04 | 艾德瓦生物技术股份有限公司 | Bioreactor and its application method |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN2356041Y (en) * | 1998-12-26 | 1999-12-29 | 王朝华 | Large scale continuous cultivating device for microorganism and animal and vegetable cell |
| CN1542121A (en) * | 2003-04-29 | 2004-11-03 | 卢建熙 | 3D dynamic input type tissue reaction device |
-
2011
- 2011-11-28 CN CN201110382573.1A patent/CN103131635B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN2356041Y (en) * | 1998-12-26 | 1999-12-29 | 王朝华 | Large scale continuous cultivating device for microorganism and animal and vegetable cell |
| CN1542121A (en) * | 2003-04-29 | 2004-11-03 | 卢建熙 | 3D dynamic input type tissue reaction device |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104893973A (en) * | 2015-03-17 | 2015-09-09 | 成都军区昆明总医院 | Dynamic perfusion culture system for promoting tissue engineering products to be vascularized in vitro |
| CN104962456A (en) * | 2015-07-16 | 2015-10-07 | 中国海洋大学 | Harvesting device capable of concentrating microalgae cells in raceway pond by virtue of microbubble backflash |
| CN106010966A (en) * | 2016-06-08 | 2016-10-12 | 中山大学附属第医院 | Multidirectional tissue-engineering porous material perfusion system |
| CN106010966B (en) * | 2016-06-08 | 2019-03-15 | 中山大学附属第一医院 | System is perfused in multi-direction organizational project porous material |
| CN109843417A (en) * | 2016-08-21 | 2019-06-04 | 艾德瓦生物技术股份有限公司 | Bioreactor and its application method |
| CN109843417B (en) * | 2016-08-21 | 2022-09-02 | 艾德瓦生物技术股份有限公司 | Bioreactor and method of use |
| CN108315256A (en) * | 2018-04-26 | 2018-07-24 | 上海久博生物工程有限公司 | Activity ventilation component and its active aeration type bioreactor and cell culture apparatus |
| WO2019206207A1 (en) * | 2018-04-26 | 2019-10-31 | 上海久博生物工程有限公司 | Active ventilation assembly, active-ventilation-type bioreactor and cell culture device |
| CN108315256B (en) * | 2018-04-26 | 2024-04-09 | 上海久博生物工程有限公司 | Active aeration component, active aeration bioreactor and cell culture device |
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| Publication number | Publication date |
|---|---|
| CN103131635B (en) | 2014-08-13 |
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