CN205434511U - Artificial liver bioreactor - Google Patents
Artificial liver bioreactor Download PDFInfo
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- CN205434511U CN205434511U CN201521130586.XU CN201521130586U CN205434511U CN 205434511 U CN205434511 U CN 205434511U CN 201521130586 U CN201521130586 U CN 201521130586U CN 205434511 U CN205434511 U CN 205434511U
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- China
- Prior art keywords
- carbon dioxide
- hollow fiber
- oxygen
- doughnut
- bioreactor
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- 210000004185 liver Anatomy 0.000 title claims abstract description 25
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims abstract description 64
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 40
- 239000001301 oxygen Substances 0.000 claims abstract description 40
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 40
- 229910002092 carbon dioxide Inorganic materials 0.000 claims abstract description 32
- 239000001569 carbon dioxide Substances 0.000 claims abstract description 32
- 239000012510 hollow fiber Substances 0.000 claims abstract description 30
- 239000007788 liquid Substances 0.000 claims abstract description 24
- 235000015097 nutrients Nutrition 0.000 claims abstract description 9
- 210000002381 plasma Anatomy 0.000 claims description 42
- 235000012489 doughnuts Nutrition 0.000 claims description 25
- 210000003494 hepatocyte Anatomy 0.000 claims description 15
- 229920002749 Bacterial cellulose Polymers 0.000 claims description 13
- 239000005016 bacterial cellulose Substances 0.000 claims description 13
- 239000000725 suspension Substances 0.000 claims description 9
- 235000016709 nutrition Nutrition 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 7
- 230000008676 import Effects 0.000 claims description 3
- 239000011229 interlayer Substances 0.000 claims description 3
- 239000010410 layer Substances 0.000 claims description 3
- 239000011148 porous material Substances 0.000 claims description 3
- 230000012010 growth Effects 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 8
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- 230000002349 favourable effect Effects 0.000 abstract description 2
- 210000005229 liver cell Anatomy 0.000 abstract 3
- 239000006285 cell suspension Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 8
- 230000010261 cell growth Effects 0.000 description 3
- 208000007788 Acute Liver Failure Diseases 0.000 description 2
- 206010000804 Acute hepatic failure Diseases 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- UBAZGMLMVVQSCD-UHFFFAOYSA-N carbon dioxide;molecular oxygen Chemical compound O=O.O=C=O UBAZGMLMVVQSCD-UHFFFAOYSA-N 0.000 description 2
- 239000012531 culture fluid Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 238000010824 Kaplan-Meier survival analysis Methods 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000002457 bidirectional effect Effects 0.000 description 1
- 239000012930 cell culture fluid Substances 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 238000013310 pig model Methods 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
Landscapes
- Materials For Medical Uses (AREA)
Abstract
The utility model discloses an artificial liver bioreactor, there is the cylindrical reactor shell of a plurality of exit and locates reactor shell many inside hollow fiber pipes including one, reactor shell one end is equipped with nutrient solution / liver cell suspension entry, plasma / in advance towards liquid entry, oxygen intake and carbon dioxide entry, and the other end is equipped with nutrient solution export, plasma / in advance towards liquid export, oxygen output and carbon dioxide export. The beneficial effects of the utility model are that: growth for the liver cell provides sufficient oxygen, has also adjusted PH simultaneously, has improved growth density and the activity of liver cell at reactor to more be favorable to exerting therapeutic action.
Description
Technical field
This utility model belongs to bioartificial liver's technical field, particularly relates to a kind of novel bioreactor of artificial liver.
Background technology
Fast development along with bioartificial liver's technology, and the core apparatus bioreactor as biological artificial liver support system seems particularly significant, the bioartificial liver of Clinical practice uses hollow fiber type mostly at present, it is to be sealed in the shell of transparent organic material by a branch of hollow fiber conduit, shell is divided into inside and outside two chambeies by this fiber pipe, general inner chamber is used for patients blood plasma of flowing, and exocoel is used for irrigating hepatocyte, this hollow fiber conduit is isolating the hepatocellular Bidirectional transporting being simultaneously achieved material, thus reaches to support the purpose of liver function.
How to ensure that in the activity of bioreactor and to maintain certain cell quantity be the key point of bioartificial liver's reactor to hepatocyte.Hepatocyte needs to consume substantial amounts of oxygen and necessary nutrient substance condition during growth metabolism, and hepatocellular quantity must reach 10 in the reactor of bioartificial liver10Below preferable effect, therefore, the requirement must being fulfilled for conditions above of suitable bioreactor can just be played.At present, in order to reach above-mentioned condition, most bioartificial liver's reactor is all to support equipment (oxygenator) in reactor external add-in, oxygen is provided indirectly, owing to oxygen effect is bad, pH can not maintain an optimum range, and therefore, the growth of final cell and activity receive and limit significantly.
Utility model content
The purpose of this utility model seeks to overcome cell in the reactor for hypoxgia, pH can not real-time monitoring and the low defect of cytoactive, a kind of oxygen that can provide abundance for hepatocellular growth is provided, PH can be regulated, improve hepatocyte stand density in reactor and the bioreactor of artificial liver of activity.
For achieving the above object, the bioreactor of artificial liver designed by this utility model, including a cylindrical reactor shell having multiple import and export and be located at many hollow fiber conduits within described shell of reactor；Described shell of reactor one end is provided with nutritional solution/hepatocyte suspension entrance, blood plasma/rush liquid entrance, oxygen intake and carbon dioxide entrance in advance, and the other end is provided with nutrient solution outlet, blood plasma/rush liquid outlet, oxygen outlet and carbon dioxide outlet in advance；Described hollow fiber conduit includes many hollow fiber plasma pipes, many doughnut oxygen hoses and Duo Gen doughnut carbon dioxide pipe；The two ends of described hollow fiber plasma pipe respectively with described blood plasma/rush in advance liquid entrance and described blood plasma/rush liquid outlet in advance；The two ends of described doughnut oxygen hose connect with described oxygen intake and described oxygen outlet respectively；The two ends of described doughnut carbon dioxide pipe connect with described carbon dioxide entrance and carbon dioxide outlet respectively.
Further, being additionally provided with the bacterial cellulose stent being curled into helical coil tubular inside described shell of reactor, described hollow fiber conduit is located in the interlayer of described bacterial cellulose stent curling.
Further, equidistant arrangement between described hollow fiber plasma pipe, doughnut oxygen hose and doughnut carbon dioxide pipe three.
Above-mentioned further scheme provides the benefit that: three's equidistant arrangement is conducive to uniformly mixing between oxygen, carbon dioxide and blood plasma culture fluid three.
Further, described bacterial cellulose stent is membranoid substance, and its thickness is 50 μm ± 10 μm, and the spacing between adjacent two layers is 10～100 microns；The pore size of described hollow fiber conduit is 0.2 μm～0.3 μm.
Above-mentioned further scheme provides the benefit that: bacterial cellulose stent is membranoid substance, has higher biocompatibility, adaptability and good biodegradability.
The beneficial effects of the utility model are: doughnut oxygen hose provides oxygen for cell, each doughnut oxygen hose is equal with hollow fiber plasma tube pitch, so oxygen can be made to be uniformly dispersed as far as possible, doughnut carbon dioxide pipe provides carbon dioxide the most as required, maintains the pH value of cell growth.Hollow fiber plasma pipe is mainly passed through cell culture fluid at phase of cell growth, is then to be passed through blood plasma in the treatment phase.Therefore, this utility model is the oxygen that hepatocellular growth provides abundance, also have adjusted PH simultaneously, improves hepatocyte stand density in reactor and activity, thus is more beneficial for playing therapeutical effect.
Accompanying drawing explanation
Fig. 1 is the structural representation of this utility model bioreactor of artificial liver.
Fig. 2 is the A A section view structure for amplifying schematic diagram of this utility model bioreactor of artificial liver.
Fig. 3 is the distributed architecture schematic diagram of hollow fiber plasma pipe, doughnut oxygen hose and doughnut carbon dioxide pipe adjacent in Fig. 2.
In figure, shell of reactor 1, nutritional solution/hepatocyte suspension entrance 2, nutrient solution outlet 3, blood plasma/rush liquid entrance 4, blood plasma/rush liquid outlet 5, oxygen intake 6, oxygen outlet 7, carbon dioxide entrance 8, carbon dioxide outlet 9, bacterial cellulose stent 10, hollow fiber plasma pipe 11, doughnut oxygen hose 12, doughnut carbon dioxide pipe 13 in advance in advance.
Detailed description of the invention
Below in conjunction with the drawings and specific embodiments, this utility model is described in further detail.
Bioreactor of artificial liver as shown in Figure 1, Figure 2, Figure 3 shows, including a cylindrical reactor shell 1 having multiple import and export and be located at many hollow fiber conduits within shell of reactor 1；Shell of reactor 1 one end is provided with nutritional solution/hepatocyte suspension entrance 2, blood plasma/rush liquid entrance 4, oxygen intake 6 and carbon dioxide entrance 8 in advance, and the other end is provided with nutrient solution outlet 3, blood plasma/rush liquid outlet 5, oxygen outlet 7 and carbon dioxide outlet 9 in advance；Hollow fiber conduit includes many hollow fiber plasma pipes 11, many doughnut oxygen hose 12 and Duo Gen doughnut carbon dioxide pipes 13；The two ends of hollow fiber plasma pipe 11 connect with blood plasma/rush in advance liquid entrance 4 and blood plasma/rush liquid outlet 5 in advance respectively；The two ends of doughnut oxygen hose 12 connect with oxygen intake 6 and oxygen outlet 7 respectively；The two ends of doughnut carbon dioxide pipe 13 connect with carbon dioxide entrance 8 and carbon dioxide outlet 9 respectively.
Shell of reactor 1 is internal is additionally provided with the bacterial cellulose stent 10 being curled into helical coil tubular, and hollow fiber conduit is located in the interlayer of bacterial cellulose stent 10 curling.
Equidistant arrangement between hollow fiber plasma pipe 11, doughnut oxygen hose 12 and doughnut carbon dioxide pipe 13 three.Three's equidistant arrangement is conducive to uniformly mixing between oxygen, carbon dioxide and blood plasma culture fluid three.
Bacterial cellulose stent 10 is membranoid substance, and its thickness is 50 μm ± 10 μm, and the spacing between adjacent two layers is 10～100 microns；The pore size of described hollow fiber conduit is 0.2 μm～0.3 μm.
The present embodiment bioreactor of artificial liver be profile be cylindrical transparent plastic shell, its a length of 290mm, a diameter of 50mm of cross-sectional area, cavity volume is 250～300mL, and exocoel volume is 150mL.
Bioreactor of artificial liver of the present utility model is not only hepatocellular growth and provides superior environment and enough nutrient substance, and bacterial cellulose stent 10 is conducive to the adherent of cell and growth, improve hepatocyte propagation density in reactor and activity, thus provide guarantee for preferably playing bioartificial liver's therapeutic effect.
The use of bioartificial liver's reactor of the present utility model is described with the example for the treatment of pig acute hepatic failure model below.
During use, it is first turned on blood plasma/rush in advance liquid entrance 4, blood plasma/rush liquid outlet 5 and nutritional solution/hepatocyte suspension entrance 2 in advance, then by blood plasma/rush in advance liquid entrance 4 to the internal saline injection of bioreactor with pre-flush bioreactor, the most aseptically will inject bioreactor exocoel with hepatocyte suspension by nutritional solution/hepatocyte suspension entrance 2, the preflush of inner chamber is by blood plasma/rush liquid outlet 5 discharge in advance simultaneously；After hepatocyte suspension is uniformly distributed in bioreactor exocoel, by blood plasma/rush in advance liquid entrance 4, blood plasma/rush liquid outlet 5 closing in advance.Subsequently by the nutritional solution of bioreactor/hepatocyte suspension entrance 2, oxygen intake 6 and carbon dioxide entrance 8 the most corresponding access nutritional solution, oxygen and carbon dioxide, and circulation circulation 3～5d under the conditions of 37 DEG C, until detection cell growth reaches requirement.In bioreactor exocoel, the bacterial cellulose stent 10 of curling has higher biocompatibility, adaptability and good biodegradability, cell can be played a supportive role, cell is enable uniformly to depend on bacteria cellulose film adherent growth, reasonably interlamellar spacing is more favorable to the growth metabolism of cell, makes cell be enriched with in a large number.
Subsequently the blood plasma of acute hepatic failure pig model is introduced hollow fiber conduit blood plasma pipe 11 from blood plasma/rush in advance liquid entrance 4, and from blood plasma/rush liquid outlet 5 discharge in advance, eventually pass back in pig body, forms one and treat closed circuit.Over the course for the treatment of, in the case of maintaining certain dissolved oxygen, pH (carbon dioxide regulation) and nutrient substance, the circulation treatment of blood plasma can be maintained up to dozens of hour, terminate treatment, Kaplan-Meier survival analysis shows that this treatment can significantly extend the time-to-live of animal subject.
Bioreactor of artificial liver of the present utility model is disposable medical apparatus and instruments.
Claims (4)
1. a bioreactor of artificial liver, it is characterised in that: include a cylindrical reactor shell (1) having multiple import and export and be located at the many hollow fiber conduits that described shell of reactor (1) is internal；Described shell of reactor (1) one end is provided with nutritional solution/hepatocyte suspension entrance (2), blood plasma/rush liquid entrance (4), oxygen intake (6) and carbon dioxide entrance (8) in advance, and the other end is provided with nutrient solution outlet (3), blood plasma/rush liquid outlet (5), oxygen outlet (7) and carbon dioxide outlet (9) in advance；Described hollow fiber conduit includes many hollow fiber plasma pipes (11), many doughnut oxygen hoses (12) and many doughnut carbon dioxide pipes (13)；The two ends of described hollow fiber plasma pipe (11) connect with described blood plasma/rush in advance liquid entrance (4) and described blood plasma/rush liquid outlet (5) in advance respectively；The two ends of described doughnut oxygen hose (12) connect with described oxygen intake (6) and described oxygen outlet (7) respectively；The two ends of described doughnut carbon dioxide pipe (13) connect with described carbon dioxide entrance (8) and carbon dioxide outlet (9) respectively.
Bioreactor of artificial liver the most according to claim 1, it is characterized in that: described shell of reactor (1) is internal is additionally provided with the bacterial cellulose stent (10) being curled into helical coil tubular, and described hollow fiber conduit is located in the interlayer that described bacterial cellulose stent (10) crimps.
Bioreactor of artificial liver the most according to claim 1 and 2, it is characterised in that: equidistant arrangement between described hollow fiber plasma pipe (11), doughnut oxygen hose (12) and doughnut carbon dioxide pipe (13) three.
Bioreactor of artificial liver the most according to claim 2, it is characterised in that: described bacterial cellulose stent (10) is membranoid substance, and its thickness is 50 μm ± 10 μm, and the spacing between adjacent two layers is 10～100 microns；The pore size of described hollow fiber conduit is 0.2 μm～0.3 μm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201521130586.XU CN205434511U (en) | 2015-12-30 | 2015-12-30 | Artificial liver bioreactor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201521130586.XU CN205434511U (en) | 2015-12-30 | 2015-12-30 | Artificial liver bioreactor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN205434511U true CN205434511U (en) | 2016-08-10 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201521130586.XU Active CN205434511U (en) | 2015-12-30 | 2015-12-30 | Artificial liver bioreactor |
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| Country | Link |
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| CN (1) | CN205434511U (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113181458A (en) * | 2021-04-22 | 2021-07-30 | 浙大宁波理工学院 | Bioreactor for artificial liver |
-
2015
- 2015-12-30 CN CN201521130586.XU patent/CN205434511U/en active Active
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113181458A (en) * | 2021-04-22 | 2021-07-30 | 浙大宁波理工学院 | Bioreactor for artificial liver |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 430206 East Lake high tech Development Zone, Hubei Province, high and new avenue, No. 818, No. Patentee after: WUHAN TOGO MEDITECH Co.,Ltd. Address before: 430206 East Lake high tech Development Zone, Hubei Province, high and new avenue, No. 818, No. Patentee before: WUHAN TOGO BIOTECHNOLOGY CO.,LTD. |
|
| CP01 | Change in the name or title of a patent holder | ||
| CP03 | Change of name, title or address |
Address after: 4th floor, podium building, Gongtou Building, No. 433-505 Chunhui Road, Lingxi Town, Cangnan County, Wenzhou City, Zhejiang Province, 325000 Patentee after: Zhejiang Tonggan Medical Technology Co.,Ltd. Country or region after: China Address before: No. 818, Gaoxin Avenue, Donghu high tech Development Zone, Wuhan, Hubei 430206 Patentee before: WUHAN TOGO MEDITECH Co.,Ltd. Country or region before: China |
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| CP03 | Change of name, title or address |