CN101199436A - Three-dimensional liver cell culture bioreactor - Google Patents
Three-dimensional liver cell culture bioreactor Download PDFInfo
- Publication number
- CN101199436A CN101199436A CNA2007100930693A CN200710093069A CN101199436A CN 101199436 A CN101199436 A CN 101199436A CN A2007100930693 A CNA2007100930693 A CN A2007100930693A CN 200710093069 A CN200710093069 A CN 200710093069A CN 101199436 A CN101199436 A CN 101199436A
- Authority
- CN
- China
- Prior art keywords
- chamber
- cell culture
- culture
- dimensional
- bioreactor
- 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
Landscapes
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Disclosed is a 3-D bioreactor to culture hepatic cells, comprising a culture cavity provided with a cell feeding port and a vent, an inflow cavity with a culture fluid inlet and an outflow cavity with a culture fluid outlet which are arranged next to the culture cavity. A plurality of hollow fibers are arranged inside the culture cavity, each with one end communicated with the inflow cavity and the other end communicated with the outflow cavity, forming a culture fluid flow passage which is communicated with the culture cavity through the tiny holes on the hollow fibers. The invention is characterized in that a 3-d bracket with a plurality of holes is arranged inside the culture cavity. The invention can provide a growth and culture condition that accords better with the physiological environment for the hepatic cells, which is good for culturing dense hepatic cells with high activity so as to ensure the therapeutic effect of a bio-artificial liver with the hepatic cells as the core.
Description
Technical field
Patent of the present invention relates to a kind of armarium, particularly a kind of core apparatus that both can be used as the external biological artificial liver support system, also can be used as a kind of experimental provision or biological preparation device, the small-sized process units that can also be used to cultivate hepatocellular experimentation and extract cell products.
Background technology
The existing bioreactor that is used for clinically is the hollow fiber type reactor, its structure and hemodialyzer are identical, be material, aperture and the molecular retention amount difference of used semipermeable membrane, this hollow fiber type reactor is that a branch of (50～100) doughnut is sealed in the transparent organic material shell, by doughnut it is divided into inside and outside two chambeies, be respectively applied for and place hepatocyte and mobile blood samples of patients, by this hollowfibre semi-permeable membrance, carry out two-way mass transfer and immune iris action, thereby realize that the bioartificial liver supports and therapeutical effect.
There are many defectives in actual applications in the reactor of this pattern: 1. structurally, the parallel dense arrangement of doughnut of tradition common response device, be the pencil cylindricality, the hepatocellular culture environment of less consideration, liver cell culture and substance transportation, the exchange inharmonious; 2. aspect cell culture, can only cultivate, the dimensional culture microenvironment can not be provided, be unfavorable for that hepatocyte is at external systematism cultivation and functional rehabilitation for hepatocyte provides two dimension; 3. aspect cell distribution, be subjected to the effect of gravity often to be deposited on reactor bottom, can't be uniformly distributed between the doughnut, even cell also can supply the deficiency inactivation because of oxygen in the middle of can arriving fibre bundle when adding cell; 4. in clinical rami hepatici is held, this traditional reactor is low because of cell concentration few (adult hepatocyte's amount of 1%～5% is generally only arranged), vigor, the function difference is difficult to bring into play due biological function and effect.
At present, also has a kind of perfusion bed cribbing type reactor, it is bio-artificial liver cell culture or bioartificial liver's research and the more reactor of zoopery use, its structure is that the three-dimensional stent material with different materials or different apertures is sealed in the shell, utilizes three-dimensional rack to provide the dimensional culture microenvironment for hepatocyte.When carrying out liver cell culture, constantly feed culture fluid from shell circularly, the slit of culture fluid between three-dimensional rack and hepatocyte circulates, for hepatocyte provides abundant oxygen and nutrient substance; Be used as for the bioartificial liver studies or during clinical use, patient's blood or blood plasma is constantly fed from shell, blood or the blood plasma slit between three-dimensional rack and hepatocyte circulates, and normal liver cell detoxifies to blood plasma or blood.
The following shortcoming that this bioreactor exists: 1. from structure of reactor, when being used as for bioartificial liver's research or clinical use, hepatocyte direct and in the three-dimensional rack contacts for blood samples of patients or blood plasma, there is not any immune iris action, be unfavorable for protecting patient's immune safety, be difficult to use at clinical expansion; 2. when carrying out liver cell culture, aspect nutrition supply, nutritional solution is by the slit flow mistake between three-dimensional rack and the hepatocyte, along with hepatocellular growth, the slit diminishes gradually, makes the nutritional solution that circulates be subject to block, cause circulation not smooth, the perfusion inequality, nutrition supply is limited; 3. blood, blood plasma or nutritional solution are subjected to circulating under the effect of pump, make cell be subjected to directly to be subjected to bigger shearing force, cause hepatocellular damage easily.
So above-mentioned defective is that present bioartificial liver treats the liver failure curative effect and is difficult to one of key factor that further improves.
Summary of the invention
The purpose of patent of the present invention just provides a kind of three-dimensional bioreactor simple in structure and easy to use, it can provide growth and the condition of culture that more meets physiological environment for hepatocyte, help turning out have high activity, highdensity hepatocyte, bring into play biological action to greatest extent, realize liver specificity function of detoxification, biosynthesis and conversion metabolic function, realize that liver cell culture, immunity intercept, the perfect adaptation of mass transfer, guarantee is held and therapeutical effect as the bioartificial liver's of core rami hepatici.
The objective of the invention is to realize by such technical scheme, it includes the cell culture chamber that the band cell adds inlet and air vent, what be in close proximity to that the cell culture chamber place is provided with the influent stream chamber of band culture fluid inlet and the outlet of band culture fluid goes out to flow the chamber, an end that is positioned at many doughnuts of cell culture intracavity all communicates with the influent stream chamber, the other end all with go out to flow the chamber and communicate, the influent stream chamber, go out to flow the chamber and constitute the culture fluid flow channels with many doughnuts, communicate with each other by the micropore on the doughnut between culture fluid flow channels and the cell culture chamber, it is characterized in that: the cell culture intracavity is provided with three-dimensional porous rack material.
In the present invention, described three-dimensional porous rack material is the biomaterial of indication in the biomedical sector organizational project, it is the three-dimensional rack that the seed cell formative tissue is depended on for existence and depended on before, it can be with cell fixation in certain position, for physiological activities such as its growth, breeding, metabolism and extracellular matrix secretion provide the place, and guiding regenerating tissues basic configuration.Therefore, it had both had good biocompatibility, the timbering material that has given shape and three-dimensional connected porous structure again, being mainly the cell growth provides support and the three dimensional growth space, comprise degradable and non-degradable three-dimensional stent material, as chitosan, collagen, fibrin, polylactic acid, polylactic acid-polyglycolic acid ester, polyurethane etc.
Three-dimensional porous rack material can riddle whole cell culture intracavity, also can be to be arranged in the cell culture intracavity like this: the apart segment distance of multi-layer three-dimension porous support materials be distributed in the cell culture intracavity successively, and every layer of three-dimensional porous rack material all is full of on the pairing transverse section of cell culture chamber.Certainly, user or Producer can optionally be arranged at the cell culture intracavity with three-dimensional porous rack material according to actual needs.
The present invention can be used for hepatocellular cultivation, also can be used for the external biological artificial liver, can also be used for experimentation and be used to prepare biological preparation.
The method of cultivating liver cell culture with the present invention is:
1, patent of the present invention is placed in the cell culture incubator, gives 95% oxygen, 5% carbon dioxide and 100% damp condition.
2, will be through the isolating hepatocyte of external digestion technology, use centrifugal inocalation method and circulation perfusion inocalation method to be inoculated in the three-dimensional porous rack material in the cell culture chamber of the present invention, concrete steps are as follows:
(1), centrifugal inocalation method: hepatocyte suspension is added inlet through hepatocyte join the cell culture intracavity, each addition is 30～100 grams, and carries out centrifugal treating 3 minutes, with reversed order about the present invention, centrifugal repeatedly 5 times.
(2), circulation perfusion inocalation method: hepatocyte adds inlet and is communicated with air vent by peristaltic pump and silica gel tube, to constitute a circulation canal, under the effect of peristaltic pump, make the hepatocyte suspension in the liver cell culture mobile at the circulation canal internal recycle with 1ml/ minute speed, after 30 minutes, hepatocyte is uniformly distributed in the three-dimensional porous rack material in the liver cell culture chamber.
(3), remove peristaltic pump and silica gel tube, the sealing hepatocyte adds inlet and air vent.
3, the present invention is carried out following connection: cultivate liquid pool and be communicated with culture fluid inlet of the present invention by silica gel tube, peristaltic pump, oxygenator, culture fluid outlet of the present invention passes to the cultivation liquid pool by silica gel tube, thereby makes culture fluid flow channels of the present invention constitute a culture fluid circulation canal with oxygenator, peristaltic pump, cultivation liquid pool.
4, under the effect of peristaltic pump, culture fluid carries out following circulating: flow into culture fluid inlet of the present invention by cultivating liquid pool through oxygenator, flow through the culture fluid flow channels then, be back in the storage pond from culture fluid outlet of the present invention; The speed controlling that culture fluid circulates is about 30ml/min.Culture fluid is in the process of circulating, provide abundant oxygen and nutrient substance by the micropore on the doughnut equably to the hepatocyte of cell culture intracavity, make hepatocyte in three-dimensional porous rack material, be the 3 D stereo growth, thereby turn out a large amount of, high activity, highdensity hepatocyte, hepatocyte possesses good biological function.
After utilizing the present invention to turn out a large amount of hepatocyte by above-mentioned method, just the present invention can be used for the external biological artificial liver, at this moment, what cycle through in the culture fluid flow channels is not culture fluid, but blood samples of patients or blood plasma, the micropore of normal liver cell in the cell culture chamber by doughnut detoxifies to patient's blood or blood plasma, simultaneously, having intercepted blood or blood plasma directly directly contacts with hepatocyte, play immune iris action, thereby brought into play better artificial liver support and therapeutical effect.Certainly, also can be with this bright experimentation that is used for, it can satisfy hepatocellular physiological requirement; When the present invention is used to prepare biological preparation, can extract more cellular products.
Owing to adopted technique scheme, patent of the present invention has following advantage:
1. rational in infrastructure, three-dimensional porous rack material and doughnut are combined and be applied in the bioreactor, more effectively satisfy the requirement that bioreactor of artificial liver intercepts liver cell culture, mass transfer, immunity.
2. use doughnut can carry out the mass transfer of culture fluid or patient blood effectively, plays the effect that immunity intercepts simultaneously, and the shearing force that alleviates culture fluid significantly is to hepatocellular influence.
3. utilize three-dimensional porous rack material for hepatocyte provides three-dimensional support effect, make hepatocyte in three-dimensional porous rack material, be 3 D stereo growth, easy systematism, hepatocyte density height, quantity is big, function is strong.
4. the small-bore micropore in the three-dimensional porous rack material can make hepatocyte be evenly distributed in the three-dimensional porous rack material, has avoided hepatocyte to be deposited on the cell culture chamber bottom, effectively overcomes original hollow fiber reactor and is difficult to the hepatocellular deficiency of high-efficient culture.
5. culture fluid is that hepatocyte provides oxygen and nutrient substance equably with spoke stream and disperse dual mode simultaneously, improve the supply distance of nutrient substance and oxygen significantly, break through the distance limit of dispersion 100 μ m～200 μ m, oxygen and nutrient substance that hepatocyte is obtained are abundanter.
6. the hepatocyte metabolite flow to spoke stream intracavity by the micropore spoke on the cellulose isolating membrane, can effectively reduce toxicant in the metabolite to hepatocellular toxic action.
Description of drawings
Description of drawings of the present invention is as follows:
Fig. 1 is the structural representation of first kind of embodiment of the present invention;
Fig. 2 is the structural representation of second kind of embodiment of the present invention;
Fig. 3 is an A-A cutaway view among Fig. 2;
Fig. 4 is the structural representation of the third embodiment of the present invention;
Fig. 5 is a B-B cutaway view among Fig. 4;
Fig. 6 is the annexation figure of the third embodiment user mode of the present invention.
Among the figure: 1. housing; 2. influent stream chamber; 3. go out to flow the chamber; 4. cellulose isolating membrane; 5. cell culture chamber; 6. spoke flows the chamber; 7. three-dimensional porous rack material; 8. doughnut; 9. culture fluid flow channels; 10. culture fluid enters the mouth; 11. culture fluid outlet; 12. spoke flow liquid outlet; 13. cell adds inlet; 14. air vent; 15. filter screen; 16. filter screen; 17. cultivation liquid pool; 18. silica gel tube; 19. peristaltic pump; 20. oxygenator; 21. peristaltic pump; 22. silica gel tube; 23. waste liquid pool.
The specific embodiment
The invention will be further described below in conjunction with drawings and Examples:
As Fig. 1,2, shown in 3, the present invention includes and be with cell to add the cell culture chamber 5 of inlet 13 and air vent 14, what be in close proximity to that cell culture chamber 5 places are provided with the influent stream chamber 2 of band culture fluid inlet 10 and band culture fluid outlet 12 goes out to flow chamber 3, an end that is positioned at the many doughnuts 8 of cell culture chamber 5 all communicates with influent stream chamber 2, the other end all with go out to flow chamber 3 and communicate, influent stream chamber 2, go out to flow chamber 3 and constitute culture fluid flow channels 9 with many doughnuts 8, communicate with each other by the micropore on the doughnut 8 between culture fluid flow channels 9 and the cell culture chamber 5, it is characterized in that: be provided with three-dimensional porous rack material 7 in the cell culture chamber 5.
Embodiment 1: as shown in Figure 1, three-dimensional porous rack material 7 can riddle in the whole cell culture chamber 5.Embodiment 2: shown in Fig. 2,3, three-dimensional porous rack material 7 also can be to be arranged in like this in the cell culture chamber 5: multi-layer three-dimension porous support materials 7 apart segment distances are distributed in the cell culture chamber 5 successively, and every layer of three-dimensional porous rack material 7 all is full of on the cell culture chamber 5 pairing transverse section.
The present invention can be used for hepatocellular cultivation, also can be used for the external biological artificial liver, can also be used for experimentation and be used to prepare biological preparation.
The method of cultivating liver cell culture with the present invention is:
1, patent of the present invention is placed in the cell culture incubator, gives 95% oxygen, 5% carbon dioxide and 100% damp condition.
2, will be through the external digestion technical point from the hepatocyte that crosses, use centrifugal inocalation method and circulation perfusion inocalation method to be inoculated in the three-dimensional porous rack material 7 in the cell culture chamber 5 of the present invention, concrete steps are as follows:
(1), centrifugal inocalation method: hepatocyte suspension is added inlet through hepatocyte join in the cell culture chamber 5, each addition is 30～100 grams, and carries out centrifugal treating 3 minutes, with reversed order about the present invention, centrifugal repeatedly 5 times.
(2), circulation perfusion inocalation method: hepatocyte adds inlet 13 and is communicated with air vent 14 by peristaltic pump and silica gel tube, to constitute a circulation canal, under the effect of peristaltic pump, make the hepatocyte suspension in the liver cell culture mobile at the circulation canal internal recycle with 1ml/ minute speed, after 30 minutes, hepatocyte is uniformly distributed in the three-dimensional porous rack material 7 in the liver cell culture chamber.
(3), remove peristaltic pump and silica gel tube, the sealing hepatocyte adds inlet 13 and air vent 14.
3, the present invention is carried out following connection: cultivate liquid pool 17 and be communicated with culture fluid inlet 10 of the present invention by silica gel tube 18, peristaltic pump 19, oxygenator 20, culture fluid outlet 11 of the present invention passes to by silica gel tube 18 and cultivates liquid pool 17, thereby make culture fluid flow channels 9 of the present invention constitute a culture fluid circulation canal with oxygenator 20, peristaltic pump 19, cultivation liquid pool 17, can be as can be known with reference to Fig. 6.
4, under the effect of peristaltic pump 19, culture fluid carries out following circulating: flow into culture fluid inlet 10 of the present invention by cultivating liquid pool 17 through oxygenator 20, flow through culture fluid flow channels 9 then, be back to from culture fluid outlet 11 of the present invention again and cultivate in the liquid pool 17; The speed controlling that culture fluid circulates is about 30ml/min.Culture fluid is in the process of circulating, provide abundant oxygen and nutrient substance equably by the hepatocyte of the micropore on the doughnut 8 in cell culture chamber 5, make hepatocyte in three-dimensional porous rack material 7, be the 3 D stereo growth, thereby turn out a large amount of, high activity, highdensity hepatocyte, hepatocyte possesses good biological function.
After utilizing the present invention to turn out a large amount of hepatocyte by above-mentioned method, just the present invention can be used for the external biological artificial liver, at this moment, what cycle through in the culture fluid flow channels 9 is not culture fluid, but blood samples of patients or blood plasma, the micropore of normal liver cell in the cell culture chamber 5 by doughnut 8 detoxifies to patient's blood or blood plasma, simultaneously, having intercepted blood or blood plasma directly directly contacts with hepatocyte, play immune iris action, thereby brought into play better artificial liver support and therapeutical effect.Certainly, also can be with this bright experimentation that is used for, it can satisfy hepatocellular physiological requirement; When the present invention is used to prepare biological preparation, can extract more cellular products.
Embodiment 3: outside cell culture chamber 5, be provided with the spoke stream chamber 6 that coats cell culture chamber 5, the chamber wall of cell culture chamber 5 is all made with cellulose isolating membrane 4, communicate with each other by the micropore on the cellulose isolating membrane 4 between cell culture chamber 5 and the spoke stream chamber 6, the cavity in spoke stream chamber 6 is provided with the spoke flow liquid outlet 12 that communicates with spoke stream chamber 6.Realize this embodiment concrete structure such as Fig. 4, shown in 5, it be in housing 1 about relatively both sides be respectively arranged with influent stream chamber 2 and go out to flow chamber 3, in influent stream chamber 1 and go out to flow between the chamber 3, inwall and influent stream chamber 2 outer walls by the cellulose isolating membrane 4 of tubbiness, go out to flow chamber 3 outer walls and surround a cell culture chamber 5 together, the outer wall of cellulose isolating membrane 4 and housing 1 inwall, influent stream chamber 2 outer walls, go out to flow chamber 3 outer walls and surround a spoke stream chamber 6 together, be full of three-dimensional porous rack material 7 in the cell culture chamber 5, an end that is positioned at the many doughnuts 8 of cell culture chamber 5 all communicates with influent stream chamber 2, the other end all with go out to flow chamber 3 and communicate, influent stream chamber 2, go out to flow chamber 3 and constitute culture fluid flow channels 9 with many doughnuts 8, communicate with each other by the micropore on the doughnut 8 between culture fluid flow channels 9 and the cell culture chamber 5, communicate with each other by the micropore on the cellulose isolating membrane 4 between cell culture chamber 5 and the spoke stream chamber 6, housing 1 is provided with the culture fluid inlet 10 that communicates with influent stream chamber 2, also be provided with and go out to flow the culture fluid outlet 11 that chamber 3 communicates, housing 1 is provided with the spoke flow liquid outlet 12 that communicates with spoke stream chamber 6, and housing 1 is provided with the cell that communicates with cell culture chamber 5 and adds inlet 13 and air vent 14.
As shown in Figure 6, be the annexation figure of the user mode of the embodiment of the invention 3, among the figure, the spoke flow liquid outlet 12 in spoke stream chamber 6 passes to by peristaltic pump 21, silica gel tube 22 and cultivates liquid pool 17 and waste liquid pool 23.The annexation of other parts is identical with aforesaid embodiment 1,2.
The present invention is placed in the cell culture incubator, give 95% oxygen, 5% carbon dioxide and 100% damp condition, it is that cultivation is hepatocellular like this: will be through the isolating hepatocyte of external digestion technology, use centrifugal inocalation method and circulation perfusion inocalation method to be inoculated in the three-dimensional porous rack material 7 in the cell culture chamber 5 of patent of the present invention, utilize suitable centrifugal force and the effect of circulation perfusion that hepatocyte is evenly distributed in the three-dimensional porous rack material 7; In culture fluid flow channels 9, cycle through culture fluid then, and impose certain pressure, make between culture fluid flow channels 9 and the spoke stream chamber 6 and form pressure differential, under this action of pressure, the doughnut 8 of part culture fluid from culture fluid flow channels 9 flow to spoke stream chamber 6 through cell culture chamber 5 spokes, the spoke of culture fluid flows through in the journey, provide abundant oxygen and nutrient substance equably for hepatocyte on the one hand, also take away the hepatocyte metabolite on the other hand to spoke stream chamber 6, discharge through spoke flow liquid outlet 12.This process meets the hepatocyte physiological environment and the blood environment of normal liver, therefore, can turn out a large amount of, high activity, highdensity hepatocyte, and hepatocyte possesses good biological function.
In order to prevent that the impurity in the nutritional solution from flowing in the cell culture chamber 5, as shown in Figure 1, can be provided with and the corresponding filter screen 15 of the port of many doughnuts 8 in the influent stream chamber 2.Equally, as shown in Figure 2, go out to flow chamber 3 interior can being provided with and the corresponding filter screen 16 of the port of many doughnuts 8.As shown in Figure 4, influent stream chamber 2, go out to flow in the chamber 3 and can be provided with and the corresponding filter screen 15,16 of the port of many doughnuts 8.
Claims (7)
1. the bioreactor of a three-dimensional liver cell culture, include the cell culture chamber (5) that the band cell adds inlet (13) and air vent (14), be in close proximity to cell culture chamber (5) and locate to be provided with that the influent stream chamber (2) of band culture fluid inlet (10) and band culture fluid export (11) goes out to flow chamber (3), an end that is positioned at the many doughnuts (8) of cell culture chamber (5) all communicates with influent stream chamber (2), the other end all with go out to flow chamber (3) and communicate, influent stream chamber (2), go out to flow chamber (3) and constitute culture fluid flow channels (9) with many doughnuts (8), communicate with each other by the micropore on the doughnut (8) between culture fluid flow channels (9) and the cell culture chamber (5), it is characterized in that: be provided with three-dimensional porous rack material (7) in the cell culture chamber (5).
2. the bioreactor of three-dimensional liver cell culture as claimed in claim 1, it is characterized in that: three-dimensional porous rack material (7) riddles whole cell culture intracavity (5).
3. the bioreactor of three-dimensional liver cell culture as claimed in claim 1, it is characterized in that: three-dimensional porous rack material (7) is to be arranged in like this in the cell culture chamber (5): the apart segment distance of multi-layer three-dimension porous support materials (7) is distributed in the cell culture chamber (5) successively, and every layer of three-dimensional porous rack material (7) all is full of on the pairing transverse section of cell culture chamber (5).
4. as the bioreactor of claim 1,2 or 3 described three-dimensional liver cell cultures, it is characterized in that: outside cell culture chamber (5), be provided with the spoke stream chamber (6) that coats cell culture chamber (5), the chamber wall of cell culture chamber (5) all uses cellulose isolating membrane (4) to make, communicate with each other by the micropore on the cellulose isolating membrane (4) between cell culture chamber (5) and the spoke stream chamber (6), the cavity in spoke stream chamber (6) is provided with the spoke flow liquid outlet (12) that communicates with spoke stream chamber (6).
5. the bioreactor of three-dimensional liver cell culture as claimed in claim 4 is characterized in that: be provided with the corresponding filter screen of port (15) with many doughnuts (8) in influent stream chamber (2).
6. the bioreactor of three-dimensional liver cell culture as claimed in claim 4 is characterized in that: go out to flow the corresponding filter screen of port (16) that is provided with in the chamber (3) with many doughnuts (8).
7. the bioreactor of three-dimensional liver cell culture as claimed in claim 4 is characterized in that: influent stream chamber (2), go out to flow the corresponding filter screen of port (15,16) that is provided with in the chamber (3) with many doughnuts (8).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100930693A CN101199436A (en) | 2007-11-28 | 2007-11-28 | Three-dimensional liver cell culture bioreactor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100930693A CN101199436A (en) | 2007-11-28 | 2007-11-28 | Three-dimensional liver cell culture bioreactor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101199436A true CN101199436A (en) | 2008-06-18 |
Family
ID=39514929
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007100930693A Pending CN101199436A (en) | 2007-11-28 | 2007-11-28 | Three-dimensional liver cell culture bioreactor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101199436A (en) |
Cited By (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101864361A (en) * | 2009-04-16 | 2010-10-20 | 赛宇细胞科技股份有限公司 | Scalable packed-bed cell culture device |
| CN101549181B (en) * | 2009-05-07 | 2011-11-02 | 浙江大学 | Nanometer fiber net sheet superposed type biological reactor |
| CN101559246B (en) * | 2009-05-26 | 2011-11-02 | 浙江大学 | Hybrid artificial liver support system equipped with nano fibre sheet stacked reactor |
| CN101486968B (en) * | 2009-02-13 | 2011-11-09 | 中国人民解放军第三军医大学第一附属医院 | Intellectualized bionic cultivation apparatus for tissue engineering tissue |
| CN102304476A (en) * | 2011-08-22 | 2012-01-04 | 陕西师范大学 | Three-dimensional cell dynamic culture reactor |
| CN101732770B (en) * | 2009-12-14 | 2012-04-25 | 浙江大学 | Dual-cavity liquid storage tank for biological artificial liver support system |
| CN101724557B (en) * | 2009-12-11 | 2012-05-30 | 南开大学 | Polysaccharide composite stent perfusion type liver cell reactor system for use in medicament-induced hepatotoxicity evaluation |
| CN102517247A (en) * | 2011-12-23 | 2012-06-27 | 武汉介观生物科技有限责任公司 | Lattice-type three-dimensional cell culture support and its manufacturing method and use method |
| CN102834503A (en) * | 2009-12-16 | 2012-12-19 | 维瓦生物细胞股份公司 | A Continuous Culturing Device |
| CN101428154B (en) * | 2008-12-04 | 2013-10-30 | 浙江大学 | Implantation type artificial hepar |
| CN104353142A (en) * | 2014-09-30 | 2015-02-18 | 南京比瑞生物科技有限公司 | Biological artificial liver reactor |
| CN105154332A (en) * | 2015-09-23 | 2015-12-16 | 中国科学院力学研究所 | Orthogonal flow and sandwich hepatic cell bioreactor |
| CN105170205A (en) * | 2015-09-19 | 2015-12-23 | 大连理工大学 | Bionic chip constructed based on micro-fluidic chip technology |
| CN105498005A (en) * | 2016-01-22 | 2016-04-20 | 浙江省人民医院 | Acellularized scaffold type bioreactor for artificial liver and utilization method of acellularized scaffold type bioreactor for artificial liver |
| CN106222086A (en) * | 2016-07-29 | 2016-12-14 | 武汉仝干医疗科技股份有限公司 | Lint wire type bioartificial liver's reactor |
| US9718029B2 (en) | 2012-06-15 | 2017-08-01 | United Arab Emirates University | Serviceable bioreactor |
| CN107904170A (en) * | 2017-12-18 | 2018-04-13 | 上海白泽医疗器械有限公司 | Media to cell culture modules and cell culture system |
| CN108379661A (en) * | 2018-05-25 | 2018-08-10 | 中国人民解放军总医院 | The method for planting structure Bladder Tissue Engineering using centrifugation |
| CN108421106A (en) * | 2018-03-21 | 2018-08-21 | 中国人民解放军陆军军医大学第附属医院 | Bioartificial liver system based on people iHep cells and membrane type panel-shaped reactor |
| CN108485964A (en) * | 2018-03-14 | 2018-09-04 | 苏杰 | A kind of medical human erythrocyte culture instrument |
| CN108588006A (en) * | 2018-05-10 | 2018-09-28 | 华东理工大学 | A kind of biological support and its preparation method and application for liver cell dimensional culture |
| CN108641952A (en) * | 2018-05-07 | 2018-10-12 | 宁波华仪宁创智能科技有限公司 | The bionical culture apparatus of cell and method |
| CN109136090A (en) * | 2018-02-06 | 2019-01-04 | 上海微知卓生物科技有限公司 | A kind of bioreactor |
| CN110055174A (en) * | 2019-02-27 | 2019-07-26 | 中国医学科学院生物医学工程研究所 | A kind of classification inoculation apparatus and its application method for three-dimensional cell cultivation |
| CN110117527A (en) * | 2019-05-15 | 2019-08-13 | 刘宝全 | A kind of reinforcing discharge method of stem cell metabolic waste |
| CN111704998A (en) * | 2020-07-14 | 2020-09-25 | 兰州大学第一医院 | Vertical plate constant-flow type biological artificial liver reactor |
| CN112608843A (en) * | 2020-12-21 | 2021-04-06 | 山东壹瑞特生物科技有限公司 | Method for culturing cells in pulsating flow mode and cell reaction apparatus thereof |
| CN113174331A (en) * | 2021-05-20 | 2021-07-27 | 郑路瑶 | Self-adjusting cell culture ware for biological medicine |
| WO2022115033A1 (en) * | 2020-11-24 | 2022-06-02 | Turtletree Labs Pte. Ltd. | Bioreactor systems and methods for culturing cells |
| US11518971B2 (en) | 2018-11-27 | 2022-12-06 | Research Triangle Institute | Method and apparatus for spatial control of cellular growth |
-
2007
- 2007-11-28 CN CNA2007100930693A patent/CN101199436A/en active Pending
Cited By (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101428154B (en) * | 2008-12-04 | 2013-10-30 | 浙江大学 | Implantation type artificial hepar |
| CN101486968B (en) * | 2009-02-13 | 2011-11-09 | 中国人民解放军第三军医大学第一附属医院 | Intellectualized bionic cultivation apparatus for tissue engineering tissue |
| CN101864361B (en) * | 2009-04-16 | 2013-02-06 | 赛宇细胞科技股份有限公司 | Scalable cell culture device |
| CN101864361A (en) * | 2009-04-16 | 2010-10-20 | 赛宇细胞科技股份有限公司 | Scalable packed-bed cell culture device |
| CN101549181B (en) * | 2009-05-07 | 2011-11-02 | 浙江大学 | Nanometer fiber net sheet superposed type biological reactor |
| CN101559246B (en) * | 2009-05-26 | 2011-11-02 | 浙江大学 | Hybrid artificial liver support system equipped with nano fibre sheet stacked reactor |
| CN101724557B (en) * | 2009-12-11 | 2012-05-30 | 南开大学 | Polysaccharide composite stent perfusion type liver cell reactor system for use in medicament-induced hepatotoxicity evaluation |
| CN101732770B (en) * | 2009-12-14 | 2012-04-25 | 浙江大学 | Dual-cavity liquid storage tank for biological artificial liver support system |
| CN102834503A (en) * | 2009-12-16 | 2012-12-19 | 维瓦生物细胞股份公司 | A Continuous Culturing Device |
| CN102304476A (en) * | 2011-08-22 | 2012-01-04 | 陕西师范大学 | Three-dimensional cell dynamic culture reactor |
| CN102304476B (en) * | 2011-08-22 | 2013-10-09 | 陕西师范大学 | Three-dimensional cell dynamic culture reactor |
| CN102517247A (en) * | 2011-12-23 | 2012-06-27 | 武汉介观生物科技有限责任公司 | Lattice-type three-dimensional cell culture support and its manufacturing method and use method |
| CN102517247B (en) * | 2011-12-23 | 2014-02-19 | 武汉介观生物科技有限责任公司 | Lattice-type three-dimensional cell culture support and its manufacturing method and use method |
| US9718029B2 (en) | 2012-06-15 | 2017-08-01 | United Arab Emirates University | Serviceable bioreactor |
| CN104353142A (en) * | 2014-09-30 | 2015-02-18 | 南京比瑞生物科技有限公司 | Biological artificial liver reactor |
| CN105170205A (en) * | 2015-09-19 | 2015-12-23 | 大连理工大学 | Bionic chip constructed based on micro-fluidic chip technology |
| CN105154332A (en) * | 2015-09-23 | 2015-12-16 | 中国科学院力学研究所 | Orthogonal flow and sandwich hepatic cell bioreactor |
| CN105498005A (en) * | 2016-01-22 | 2016-04-20 | 浙江省人民医院 | Acellularized scaffold type bioreactor for artificial liver and utilization method of acellularized scaffold type bioreactor for artificial liver |
| CN106222086A (en) * | 2016-07-29 | 2016-12-14 | 武汉仝干医疗科技股份有限公司 | Lint wire type bioartificial liver's reactor |
| CN107904170A (en) * | 2017-12-18 | 2018-04-13 | 上海白泽医疗器械有限公司 | Media to cell culture modules and cell culture system |
| CN109136090A (en) * | 2018-02-06 | 2019-01-04 | 上海微知卓生物科技有限公司 | A kind of bioreactor |
| CN108485964B (en) * | 2018-03-14 | 2021-10-22 | 北京轻盈医院管理有限公司 | Medical human red blood cell culture instrument |
| CN108485964A (en) * | 2018-03-14 | 2018-09-04 | 苏杰 | A kind of medical human erythrocyte culture instrument |
| CN108421106A (en) * | 2018-03-21 | 2018-08-21 | 中国人民解放军陆军军医大学第附属医院 | Bioartificial liver system based on people iHep cells and membrane type panel-shaped reactor |
| CN108641952A (en) * | 2018-05-07 | 2018-10-12 | 宁波华仪宁创智能科技有限公司 | The bionical culture apparatus of cell and method |
| CN108588006A (en) * | 2018-05-10 | 2018-09-28 | 华东理工大学 | A kind of biological support and its preparation method and application for liver cell dimensional culture |
| CN108379661A (en) * | 2018-05-25 | 2018-08-10 | 中国人民解放军总医院 | The method for planting structure Bladder Tissue Engineering using centrifugation |
| CN108379661B (en) * | 2018-05-25 | 2024-01-23 | 中国人民解放军总医院 | Method for constructing tissue engineering bladder by utilizing centrifugal planting |
| US11518971B2 (en) | 2018-11-27 | 2022-12-06 | Research Triangle Institute | Method and apparatus for spatial control of cellular growth |
| CN110055174A (en) * | 2019-02-27 | 2019-07-26 | 中国医学科学院生物医学工程研究所 | A kind of classification inoculation apparatus and its application method for three-dimensional cell cultivation |
| CN110117527A (en) * | 2019-05-15 | 2019-08-13 | 刘宝全 | A kind of reinforcing discharge method of stem cell metabolic waste |
| CN111704998A (en) * | 2020-07-14 | 2020-09-25 | 兰州大学第一医院 | Vertical plate constant-flow type biological artificial liver reactor |
| WO2022115033A1 (en) * | 2020-11-24 | 2022-06-02 | Turtletree Labs Pte. Ltd. | Bioreactor systems and methods for culturing cells |
| CN112608843A (en) * | 2020-12-21 | 2021-04-06 | 山东壹瑞特生物科技有限公司 | Method for culturing cells in pulsating flow mode and cell reaction apparatus thereof |
| CN112608843B (en) * | 2020-12-21 | 2022-05-03 | 山东壹瑞特生物科技有限公司 | Method for culturing cells in pulsating flow mode and cell reaction apparatus thereof |
| CN113174331A (en) * | 2021-05-20 | 2021-07-27 | 郑路瑶 | Self-adjusting cell culture ware for biological medicine |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101199436A (en) | Three-dimensional liver cell culture bioreactor | |
| EP0866849B1 (en) | Solid support for use in cell cultivation, especially for the cultivation of liver cells, biological reactor containing said solid support and the use thereof in a bio-artificial liver system | |
| JP3692147B2 (en) | Filter device | |
| US5605835A (en) | Bioreactor device with application as a bioartificial liver | |
| Gerlach | Long-term liver cell cultures in bioreactors and possible application for liver support | |
| CN101081182A (en) | Novel biology artificial hepatocyte reactor | |
| CN101549179B (en) | Perforated brick type filling support type reactor used in artificial liver | |
| WO1992007615A1 (en) | A bioartificial liver | |
| CN105505775A (en) | Extracorporeal liver support system | |
| WO2021230669A1 (en) | Bioreactor using nanosheet composite made of hollow fibers and nanofibers | |
| WO2018018792A1 (en) | Four-in-one on-line monitoring and constant-temperature heating integrated system of plush type for bioartificial liver | |
| Morelli et al. | Hollow fiber and nanofiber membranes in bioartificial liver and neuronal tissue engineering | |
| CN101559246B (en) | Hybrid artificial liver support system equipped with nano fibre sheet stacked reactor | |
| CN201418905Y (en) | Fiber mesh stacked bioreactor for artificial liver | |
| CN101381678B (en) | Multi-layer diaphragm structure perfusion bioreactor and application | |
| CN101549181B (en) | Nanometer fiber net sheet superposed type biological reactor | |
| CN103100119A (en) | Artificial liver bioreactor | |
| US20050003524A1 (en) | Module for the culture and/or preservation of microorganisms and the utilization of its metabolic performance | |
| CN101569767B (en) | Hybrid artificial liver supporting system equipped with perforated brick type filling bracket type reactor | |
| CN106267400B (en) | Four-in-one formula bioartificial liver monitors on-line and heated at constant temperature integrated system | |
| CA2372219A1 (en) | Modular cell support systems for the three-dimensional cell growth | |
| CN101357084B (en) | Biology artificial kidney tubule bioreactor and use thereof | |
| CN1633950A (en) | Bioreactor for artificial liver | |
| CN201286882Y (en) | Perfusion-type bioreactor of multi-layer membrane structure | |
| CN2803310Y (en) | Biological Reactor for artificial liver |
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 |
Open date: 20080618 |