CN100432223C - Micro cell hollow fiber reactor - Google Patents
Micro cell hollow fiber reactor Download PDFInfo
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- CN100432223C CN100432223C CNB2004100534999A CN200410053499A CN100432223C CN 100432223 C CN100432223 C CN 100432223C CN B2004100534999 A CNB2004100534999 A CN B2004100534999A CN 200410053499 A CN200410053499 A CN 200410053499A CN 100432223 C CN100432223 C CN 100432223C
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- 239000012510 hollow fiber Substances 0.000 title claims abstract description 45
- 210000004027 cell Anatomy 0.000 claims abstract description 36
- 239000000463 material Substances 0.000 claims abstract description 18
- 238000011160 research Methods 0.000 claims abstract description 17
- 102000008186 Collagen Human genes 0.000 claims abstract description 12
- 108010035532 Collagen Proteins 0.000 claims abstract description 12
- 229920001436 collagen Polymers 0.000 claims abstract description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000001301 oxygen Substances 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 239000000835 fiber Substances 0.000 claims description 39
- 229920001296 polysiloxane Polymers 0.000 claims description 32
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 24
- 239000000741 silica gel Substances 0.000 claims description 24
- 229910002027 silica gel Inorganic materials 0.000 claims description 24
- 239000003814 drug Substances 0.000 claims description 18
- 210000003494 hepatocyte Anatomy 0.000 claims description 15
- 241000581650 Ivesia Species 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 11
- 239000011259 mixed solution Substances 0.000 claims description 9
- 238000012856 packing Methods 0.000 claims description 9
- 229920002492 poly(sulfone) Polymers 0.000 claims description 9
- 230000036267 drug metabolism Effects 0.000 claims description 7
- -1 polypropylene Polymers 0.000 claims description 7
- 230000004899 motility Effects 0.000 claims description 6
- 238000012216 screening Methods 0.000 claims description 6
- 230000002440 hepatic effect Effects 0.000 claims description 5
- 231100000304 hepatotoxicity Toxicity 0.000 claims description 5
- 239000004743 Polypropylene Substances 0.000 claims description 4
- 229920002239 polyacrylonitrile Polymers 0.000 claims description 4
- 229920001155 polypropylene Polymers 0.000 claims description 4
- 206010019851 Hepatotoxicity Diseases 0.000 claims description 3
- 239000004698 Polyethylene Substances 0.000 claims description 3
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- 229920000573 polyethylene Polymers 0.000 claims description 3
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- 210000004185 liver Anatomy 0.000 abstract description 5
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- 241001465754 Metazoa Species 0.000 abstract description 4
- 210000004102 animal cell Anatomy 0.000 abstract description 3
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- 238000010874 in vitro model Methods 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 210000005229 liver cell Anatomy 0.000 abstract description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 abstract 2
- 229910052710 silicon Inorganic materials 0.000 abstract 2
- 239000010703 silicon Substances 0.000 abstract 2
- 108010010803 Gelatin Proteins 0.000 abstract 1
- 230000005540 biological transmission Effects 0.000 abstract 1
- 230000001413 cellular effect Effects 0.000 abstract 1
- 210000000805 cytoplasm Anatomy 0.000 abstract 1
- 229920001971 elastomer Polymers 0.000 abstract 1
- 239000000499 gel Substances 0.000 abstract 1
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- 235000019322 gelatine Nutrition 0.000 abstract 1
- 235000011852 gelatine desserts Nutrition 0.000 abstract 1
- 239000011664 nicotinic acid Substances 0.000 abstract 1
- 229920002379 silicone rubber Polymers 0.000 abstract 1
- 239000004945 silicone rubber Substances 0.000 abstract 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 17
- 229960005489 paracetamol Drugs 0.000 description 8
- 244000309466 calf Species 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- CPJSUEIXXCENMM-UHFFFAOYSA-N phenacetin Chemical compound CCOC1=CC=C(NC(C)=O)C=C1 CPJSUEIXXCENMM-UHFFFAOYSA-N 0.000 description 6
- 102000009027 Albumins Human genes 0.000 description 5
- 108010088751 Albumins Proteins 0.000 description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
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- 238000004043 dyeing Methods 0.000 description 3
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- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 230000007056 liver toxicity Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 2
- 229960001225 rifampicin Drugs 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- 241000196323 Marchantiophyta Species 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
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- 230000000254 damaging effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
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- 230000002588 toxic effect Effects 0.000 description 1
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- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The present invention discloses a micro-cell hollow fiber reactor which is composed of silicone rubber pipes made of the material of ventilating silicon gel, rubber plugs made of ventilating silicon and hollow fiber threads. Cells are embedded into the hollow fiber threads by collagen gelatin. The micro-cell hollow fiber reactor has the performance of oxygen and cytoplasm transmission, which is suitable for cell survival. Thus, the factions of cellular medical metabolism, etc., are kept. The present invention combines the miniaturization advantage of a hole board with the advantage of the three-dimensional bionic cultivation of an artificial liver reactor in order to keep the biological activity of animal cells. The present invention can be used as an in-vitro model of the animal liver cells to be used for the research of medical metabolism, pharmacology and toxicology, used for the laboratory research of cell cultivating conditions and product production, and used as a carrier for the research of animal cell cultivating conditions in order to provide foundation for industrial production.
Description
Technical field
The present invention relates to a kind of purposes of minicell hollow fiber reactor.
Background technology
The research of existing medicine pharmacological toxicology is based on three kinds on animal model, external primary cell model and continuous cell line model.Animal model has experimental period long, and efficient is low, and individual difference causes result error excessive greatly, and be unfavorable for shortcomings such as protection of animal, and can not eliminate species variation, be the fatal weakness of animal model.Though the continuous cell line training method is simple, efficient is expensive low, and continuous cell line and primary cultured cell still have on 26S Proteasome Structure and Function than big difference, can not embody medicine fully at human body or intravital metabolism of animal and toxic action.
At present, the investigator begins to pay attention to the application of external primary cell model on drug research both at home and abroad.Its required cell concentration is few, may fundamentally eliminate species variation and individual difference, and interfering factors is little, the good reproducibility as a result of gained.The cell in vitro model that is used for drug research mainly contains orifice plate cultivation and plate cultivation etc., though the mode of this kind two dimension is simple to operate, keep the cytoactive time short, cell function is easily lost, the good 26S Proteasome Structure and Function of analogue body inner cell, these defectives are restricted its application.And the dimensional culture mode, as tubular fibre bioartificial liver reactor, though can the long period keep cell function, the simulated liver environment, but complex structure needs the circulation of multichannel oxygen supply and substratum, and is bulky, cost is also quite high, obviously is not suitable for the drug metabolism study and the high-throughout drug screening that need miniaturization.
Simultaneously, laboratory study cell culture condition and production products of cellular metabolism need a kind of miniaturization, the device that is fit to carry out condition experiment, optimization, screening.And the large-scale hollow fiber reactor that industrial production is used obviously can't meet this requirement.If can find a kind of both simple to operately, the training method of amplifying easily again has certain meaning for the early-stage Study of zooblast suitability for industrialized production.
Summary of the invention
In order to overcome the deficiency of existing drug research model, gain enlightenment from bioartificial liver's reactor and artificial organs, the object of the present invention is to provide a kind of purposes of minicell hollow fiber reactor, required structure of general reactor and operation have been simplified greatly, mode with dimensional culture reaches the bionics effect, and can long term maintenance zooblast function.
The technical solution adopted for the present invention to solve the technical problems is:
One, one of purposes of minicell hollow fiber reactor
Be used for drug metabolism research, be used for the research of use in medicament-induced hepatotoxicity or be used for the purposes of the screening of hepatic, described hollow fiber reactor comprises silicone tube, silica gel plug, the hollow fibre filament more than 1; Hollow fibre filament is contained in the silicone tube, and seal with silica gel plug at silicone tube two, and the material of silicone tube and silica gel plug is for passing the oxygen silica gel material, and the volume of described hollow fiber reactor is 0.1ml-10ml, and the results motility rate is higher than 90% rat hepatocytes by 10
6Individual cell/ml density was inoculated in v 1: 3: in the 4 times of enrichment mediums and mouse tail collagen solution mixed solution of v, inject hollow fibre filament, place for 37 ℃ and solidified in 10 minutes, hollow fibre filament is cut short, 8cm * 12 piece, the silicone tube of packing into forms described hollow fiber reactor.
Two, two of the purposes of minicell hollow fiber reactor
Be used for the purposes that the successive cell strain is cultivated, described hollow fiber reactor comprises silicone tube, silica gel plug, the hollow fibre filament more than 1; Hollow fibre filament is contained in the silicone tube, and seal with silica gel plug at silicone tube two, and the material of silicone tube and silica gel plug is for passing the oxygen silica gel material, the volume of described hollow fiber reactor be 0.1ml-10ml with l cell L929 by 10
6Individual cell/ml density was inoculated in v 1: 3: in the 4 times of enrichment mediums and mouse tail collagen solution mixed solution of v, inject hollow fibre filament, place for 37 ℃ and solidified in 10 minutes, hollow fibre filament is cut short, 8cm * 12 piece, the silicone tube of packing into forms described hollow fiber reactor.
More than the material of hollow fibre filament in two kinds of minicell hollow fiber reactor purposes be polypropylene, polysulfones, polyacrylonitrile or the polyethylene of its molecular weight cut-off at 100KDa-1000KDa; Hollow fibre filament is the 1-100 root.
The useful effect that the present invention has is: can carry out long-term dimensional culture to zooblast, the biological activity that has kept zooblast, the one, as the animal liver cell external model of the research of drug metabolism and pharmacological toxicology, the 2nd, be used for the laboratory study that cell culture condition and product are produced.And can be used as the carrier of animal cell culture condition research, for suitability for industrialized production lays the foundation.
Description of drawings
Fig. 1 is a structural representation of the present invention;
Fig. 2 is embodiment 1 cultivates 9h and 129h in hollow fiber reactor a rat hepatocytes survival condition photo;
Fig. 3 is embodiment 1 cultivates 9h and 129h in plate a rat hepatocytes survival condition photo;
Fig. 4 is albumin and the urea production curve of embodiment 3;
Fig. 5 is the cell photo of embodiment 4.
Embodiment
The invention will be further described below in conjunction with drawings and Examples.
As shown in Figure 1, the present invention includes: silicone tube 1, the silica gel plug hollow fibre filament 3 more than 2,1; Hollow fibre filament 3 is contained in the silicone tube 1, and seal with silica gel plug 2 at silicone tube 1 two.
The comparison that specific embodiment 1:(hollow fiber reactor and plate are cultivated)
The results motility rate is higher than 90% rat hepatocytes by 10
6Cells/ml density was inoculated in 4 times of enrichment mediums and mouse tail collagen solution mixed solution (1: 3; V: v), inject 3,37 ℃ of placements of hollow fibre filament and made it to solidify in 10 minutes.Hollow fibre filament 3 is cut short, 8cm * 12 piece, the silicone tube 1 of packing into adds 5ml and contains 5% foetal calf serum Williams ' E substratum, puts into 37 ℃, 5%CO
2Incubator leaves standstill cultivation.
Will be with batch rat hepatocytes by 0.8 * 10
6Cells/ml inserts 5ml and contains 5% foetal calf serum Williams ' E substratum, cultivates at the plate that is covered with mouse tail collagen.Culture condition is same as described above.
Treat in the plate behind the cell attachment (12-18h), in hollow fiber reactor and plate, add respectively and contain medicine 10mM acetaminophen substratum to be measured and do not contain medicine substratum (as blank).Thereafter the substratum that every 60h more renews.
Each repeats three groups, measures liver function index urea and albumin, the observation of cell form.
Shown in result such as following table 1 and the accompanying drawing 2,3.
Table 1:
By accompanying drawing 2,3 and last table as seen, the existing state of rat hepatocytes in hollow fiber reactor is better than plate monolayer culture, and the hollow fiber reactor group is more remarkable than plate group to the reaction of liver toxicity medicine acetaminophen, has illustrated that hollow fiber reactor more is applicable to drug toxicity research than plate.
General porous plate often is used as the carrier of cells in vitro, and porous plate is cultivated and the plate cultivation all is the monolayer culture mode of two dimension, and a lot of common ground is arranged.Therefore, experiment finds that the hollow fiber reactor culturing cell is more superior than plate, and the difference of the present invention and porous plate also can be described.
Specific embodiment 2:(hollow fiber reactor is used for the research of drug metabolism)
The results motility rate is higher than 90% rat hepatocytes by 10
6Cells/ml density was inoculated in 4 times of enrichment mediums and mouse tail collagen solution mixed solution (1: 3; V: v), inject 3,37 ℃ of placements of hollow fibre filament and made it to solidify in 10 minutes.Hollow fibre filament 3 is cut short, 8cm * 12 piece, the silicone tube 1 of packing into adds 5ml and contains 5% foetal calf serum Williams ' E substratum, puts into 37 ℃, 5%CO
2Incubator leaves standstill cultivation.
Will be with batch rat hepatocytes by 0.8 * 10
6Cells/ml inserts 5ml and contains 5% foetal calf serum Williams ' E substratum, cultivates at the plate that is covered with mouse tail collagen.Culture condition is same as described above.
After cultivating 60h, each group adds the Phenacetin solution of about 40uM, and through the drug metabolism of 3h, the HPLC method is measured the content of Phenacetin and meta-bolites acetaminophen.The result is as shown in table 2:
Table 2:
As seen from the above table, rat hepatocytes is higher than the plate culturing cell in the ability of hollow fiber reactor intracellular metabolite Phenacetin, illustrate that Cytochrome P450 specific activity plate monolayer culture is good, so hollow fiber reactor more is applicable to drug metabolism study than plate.
Specific embodiment 3:(hollow fiber reactor is used for the research of use in medicament-induced hepatotoxicity)
The results motility rate is higher than 90% rat hepatocytes was inoculated in 4 times of enrichment mediums and mouse tail collagen solution mixed solution (1: 3 by 106cells/ml density; V: v), inject 3,37 ℃ of placements of hollow fibre filament and made it to solidify in 10 minutes.Hollow fibre filament 3 is cut short, 8cm * 12 piece, the silicone tube 1 of packing into adds 5ml and contains 5% foetal calf serum Williams ' E substratum, puts into 37 ℃, 5%CO
2Incubator leaves standstill cultivation.
After cultivating 12-18h, each group changes to respectively that to contain drug level be Rifampin 10mg/ml, the substratum of vazadrine 15mg/ml and do not contain the substratum of medicine, and every 24h takes a sample once, and every 60h changes substratum once.Triplicate, the urea of working sample and albumin output.The result as shown in Figure 4, the albumin growing amount is change curve (left side) in time, urea production is change curve (right side) in time.
As seen from the figure, the effect of the Rifampin of this concentration and vazadrine down, the output of albumin and urea all is lower than the blank group, so medicine has damaging action to rat hepatocytes, thereby causes the part forfeiture of cell liver function.Illustrated that the present invention is used for the feasibility of liver toxicity drug research.
Specific embodiment 4:(hollow fiber reactor is used for the cultivation of successive cell strain)
L cell L929 is pressed 10
6Cells/ml density was inoculated in 4 times of enrichment mediums and mouse tail collagen solution mixed solution (1: 3; V: v), inject 3,37 ℃ of placements of aforesaid two kinds of hollow fibre filaments and made it to solidify in 10 minutes.Hollow fibre filament 3 is cut short, 8cm * 12 piece, the silica gel pipe shaft 1 of packing into adds 5ml and contains 10% calf serum, 1640 substratum, puts into 37 ℃, 5%CO
2Incubator leaves standstill cultivation.
Cultivate 60h after the fluorescent microscope photo after the EB/FDA dyeing as shown in Figure 5, is the growing state of L929 behind the cultivation 60h, EB/FDA dyeing, * 100 times of fluorescent microscope photos.Molecular weight cut-off is that the polysulfone hollow fibre silk of 100KD is cultivated (left side), and molecular weight cut-off is that the polysulfone hollow fibre silk of 30KD is cultivated (right side).
As seen the growing state (cell proliferation quantity) of L929 cell in the hollow fiber reactor of molecular weight cut-off 100KD is better than the molecular weight cut-off 30KD of identical material.Thereby screening obtains 100KD polysulfone hollow fibre silk and is suitable for cell cultures.
Specific embodiment 5:(hollow fiber reactor is used for the screening of hepatic)
The results motility rate is higher than 90% rat hepatocytes by 10
6Cells/ml density was inoculated in 4 times of enrichment mediums and mouse tail collagen solution mixed solution (1: 3; V: v), inject 3,37 ℃ of placements of hollow fibre filament and made it to solidify in 10 minutes.Hollow fibre filament 3 is cut short, 8cm * 12 piece, the silicone tube 1 of packing into adds 5ml and contains 5% foetal calf serum Williams ' E substratum, puts into 37 ℃, 5%CO
2Incubator leaves standstill cultivation.
After cultivating 12-18h, each group changes to respectively that to contain drug level be 10mM acetaminophen substratum, 10mM acetaminophen+4mM gsh, 10mM acetaminophen+4mM N-acetylcystein, 10mM acetaminophen+4mM halfcystine and do not contain medicine substratum (as blank).
Observation of cell form behind the 24h finds that the cell motility rate of 10mM acetaminophen+4mM gsh group is higher.Promptly from three kinds of hepatics to be selected, screen the liver lesion induced by drugs that obtains the gsh Abensanil provide protection is arranged.This is the example that the present invention is used for the hepatic screening.
Claims (4)
1. the purposes of a minicell hollow fiber reactor is characterized in that: be used for drug metabolism research, be used for the research of use in medicament-induced hepatotoxicity or be used for the purposes of the screening of hepatic, described hollow fiber reactor comprises silicone tube (1), silica gel plug (2); Hollow fibre filament (3) is contained in the silicone tube (1), seal with silica gel plug (2) at silicone tube (1) two, the material of silicone tube (1) and silica gel plug (2) is for passing the oxygen silica gel material, and the volume of described hollow fiber reactor is 0.1ml-10ml, and the results motility rate is higher than 90% rat hepatocytes by 10
6Individual cell/ml density was inoculated in v 1: 3: in the 4 times of enrichment mediums and mouse tail collagen solution mixed solution of v, inject hollow fibre filament, place for 37 ℃ and solidified in 10 minutes, hollow fibre filament is cut short, 8cm * 12 piece, the silicone tube of packing into forms described hollow fiber reactor.
2. the purposes of a kind of minicell hollow fiber reactor according to claim 1 is characterized in that: the material of the hollow fibre filament in the minicell hollow fiber reactor purposes is polypropylene, polysulfones, polyacrylonitrile or the polyethylene of its molecular weight cut-off at 100KDa-1000KDa.
3. the purposes of a minicell hollow fiber reactor is characterized in that: be used for the purposes that the successive cell strain is cultivated, described hollow fiber reactor comprises silicone tube (1), silica gel plug (2); Hollow fibre filament (3) is contained in the silicone tube (1), seal with silica gel plug (2) at silicone tube (1) two, the material of silicone tube (1) and silica gel plug (2) is for passing the oxygen silica gel material, and the volume of described hollow fiber reactor is 0.1ml-10ml, and l cell L929 is pressed 10
6Individual cell/ml density was inoculated in v 1: 3: in the 4 times of enrichment mediums and mouse tail collagen solution mixed solution of v, inject hollow fibre filament, place for 37 ℃ and solidified in 10 minutes, hollow fibre filament is cut short, 8cm * 12 piece, the silicone tube of packing into forms described hollow fiber reactor.
4. the purposes of a kind of minicell hollow fiber reactor according to claim 4 is characterized in that: the material of the hollow fibre filament in the minicell hollow fiber reactor purposes is polypropylene, polysulfones, polyacrylonitrile or the polyethylene of its molecular weight cut-off at 100KDa-1000KDa.
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| CNB2004100534999A CN100432223C (en) | 2004-08-01 | 2004-08-01 | Micro cell hollow fiber reactor |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2006120202A1 (en) * | 2005-05-09 | 2006-11-16 | Probiogen Ag | Simultaneous parameter evaluation device for cell cultivation processes |
| CN101007999B (en) * | 2006-01-23 | 2012-04-25 | 杨炜 | Permeable and visible tri-dimensional cell culture system and its uses in tissue and newborn organ culture |
| CN102586106B (en) * | 2006-01-23 | 2014-02-05 | 杨炜 | Three-dimensional space cell culture system preparation method |
| WO2008061392A1 (en) * | 2006-11-22 | 2008-05-29 | Hua Liu | Method for preparing cell populations with anti-tumor immune response activity |
| CN105385598B (en) * | 2015-11-30 | 2017-12-29 | 赵明光 | Human cerebral arteriovenous malformations biomechanical model and its vitro construction method |
| CN109479814A (en) * | 2018-11-14 | 2019-03-19 | 苏州致诺优生物医学有限公司 | The screening model of anti-lung cancer tumour medicine |
| CN113481100A (en) * | 2021-07-14 | 2021-10-08 | 天津工业大学 | Air-permeable biological culture bottle cap and preparation method and use method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5622857A (en) * | 1995-08-08 | 1997-04-22 | Genespan Corporation | High performance cell culture bioreactor and method |
| US6001585A (en) * | 1997-11-14 | 1999-12-14 | Cellex Biosciences, Inc. | Micro hollow fiber bioreactor |
| CN2514001Y (en) * | 2001-10-26 | 2002-10-02 | 邹立军 | Biological reactor |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5622857A (en) * | 1995-08-08 | 1997-04-22 | Genespan Corporation | High performance cell culture bioreactor and method |
| US6001585A (en) * | 1997-11-14 | 1999-12-14 | Cellex Biosciences, Inc. | Micro hollow fiber bioreactor |
| CN2514001Y (en) * | 2001-10-26 | 2002-10-02 | 邹立军 | Biological reactor |
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