CN101549181A - Nanometer fiber net sheet superposed type biological reactor - Google Patents
Nanometer fiber net sheet superposed type biological reactor Download PDFInfo
- Publication number
- CN101549181A CN101549181A CNA2009100984067A CN200910098406A CN101549181A CN 101549181 A CN101549181 A CN 101549181A CN A2009100984067 A CNA2009100984067 A CN A2009100984067A CN 200910098406 A CN200910098406 A CN 200910098406A CN 101549181 A CN101549181 A CN 101549181A
- Authority
- CN
- China
- Prior art keywords
- doughnut
- fiber net
- reactor
- nanometer fiber
- type biological
- 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.)
- Granted
Links
Images
Abstract
The invention relates to a medical equipment, aims to provide a nanometer fiber net sheet superposed type biological reactor. A plurality of longitudinally superposed nanometer fiber net sheets in the casing of the reactor; the nanometer fiber net sheet is woven by nanometer fibers and hollow fibers; a plurality of vertically disposed hollow fibers are passed through the grid centers of the nanometer fiber net sheets; the hollow fiber is polyether sulfone hollow fiber or polysulfones hollow fiber; a cell suspension inlet and a liquid inlet are formed on the bottom of the reactor casing, a cell suspension outlet and a liquid outlet are formed on the top, while a gas inlet and a gas outlet are formed side walls oppositely. The invention realizes three dimensional cultivation, is easy for systematization; is beneficial to the obtaining and long time cultivation for liver cell with high density and high activity, and has stem cell Induction differentiation promoting function; has smaller liquid flow resistance which causes the cell to subject to smaller shearing force and to be amplified easily; achieves higher substance exchanging efficiency and has oxygenation and immunization separating function.
Description
Technical field
The present invention relates to a kind of armarium, specifically, is the core apparatus of a kind of biotype or hybrid artificial liver treatment, and the device of differentiation, i.e. nanometer fiber net sheet superposed type biological reactor are cultivated and induced to perhaps a kind of stem cell.
Background technology
Bioreactor (being reactor) is the core apparatus of biotype and hybrid artificial liver treatment, and the place of mass exchange both is provided for exogenous hepatocyte and blood samples of patients or blood plasma, for hepatocyte provides suitable growing environment, has a extensive future again.Ideal bioreactor for artificial liver should meet following basic demand: 1, competent hepatic cell growth space, and support a liver failure patient to need 10% normal liver quality approximately, amount to hepatocyte number about 15,000,000,000.2, excellent biological compatibility can guarantee hepatocellular activity and function.3, medium and small material transmitted in both directions, the macromolecular substances immunity intercepts.
Bioreactor mainly contains four types so far: hollow fiber type, dull and stereotyped monolayer culture type, filling fluidized-bed type/support rack type and cell parcel/floating type.At present, what clinical practice was maximum is the hollow fiber type reactor, and it has oxygenate and immune iris action, and cell is subjected to advantages such as shearing force is little.But there is following shortcoming: 1, in the traditional hollow fiber reactor, the parallel tight arrangement of fiber, hepatic cell growth insufficient space; 2, can only cultivate for hepatocyte provides two dimension, the 3 D stereo culture environment can not be provided, cytoactive and function are not good, are difficult to systematism; 3, cell easily is deposited in reactor bottom, skewness; 4, cell easily stops up semipermeable membrane, influences mass exchange.Using also more another kind of reactor aspect zoopery and the cell culture is to irritate fluidized-bed type/support rack type reactor, and it has and can amplify the advantage that mass exchange is good easily for hepatocyte provides the dimensional culture environment.But there is following problem: 1, lack immune isolated potential safety hazard; 2, mostly the internal stent hole is irregular uneven, easily produce the perfusion inequality, the center of support integral body and edge zone easily produce dead space, dead space: 3, the resistance by a large amount of supports is big, and required perfusion intensity is big, cause cell and be subjected to shearing force big, be difficult to amplify.How comprehensively the advantage of variety classes reactor is maximized favourable factors and minimized unfavourable ones, and overcomes one's shortcomings, and becomes recently the focus of research both at home and abroad.
In recent years, the research of biologic bracket material has had considerable progress, and the macromolecule polymer material emerge in multitude of modification such as natural material such as emerging nano-fiber material, alginic acid-chitosan and galactose, heparin also is widely used in cell culture.Especially emerging nano-fiber material is proved more and can promotes hepatocellular growth and breeding, helps the generation of hepatocyte spheroplast, and the active performance of cell function and keeping for a long time, and has and promote stem cell to induce the function of differentiation.Nanofiber can also be woven into micron order or millimetre-sized fibre bundle according to certain rule, and the fibre bundle after the braiding has good intensity.The fast development of biomaterial, especially nano-fiber material is the development of new-type bioreactor, has created huge opportunity.
Summary of the invention
The objective of the invention is to provides a kind of nanometer fiber net sheet superposed type biological reactor in order to overcome deficiency of the prior art.
Nanometer fiber net sheet superposed type biological reactor among the present invention comprises shell of reactor; Arrange some vertical synergetic nano fibre sheets in the shell of reactor, nano fibre sheet is formed by nanofiber mixing woven hollow fiber; The doughnut of some vertical layouts passes the center of the grid of aforementioned nano fibre sheet, and described doughnut is polyether sulfone doughnut or polysulfone hollow fibre; Cell suspension inlet and liquid inlet are established in the bottom of shell of reactor, and cell suspension outlet and liquid outlet are established in the top, and the sidewall subtend is provided with gas access and gas outlet;
The described inside that is used for the doughnut of mixed weaving nano fibre sheet is gas passage, and the one end connects the gas access, and the other end connects gas outlet; The inside of the doughnut of described vertical layout is fluid passage, and the one end connects the liquid inlet, and the other end connects liquid outlet; The hepatocellular three dimensional growth of the common formation of the outer wall of all fibres and the inwall of shell of reactor space is communicated with cell suspension inlet and cell suspension outlet.
As a kind of improvement, bacteria filter is equipped with in described cell suspension inlet and cell suspension exit respectively, is fixed on the shell of reactor with spiral cover.
As a kind of improvement, described nano fibre sheet is formed by interlacing about the nanofiber mixing doughnut of both direction, the micron order fibre bundle that is woven into for nanofiber is arranged in parallel in one direction, and micron order fibre bundle that is woven into for nanofiber on another direction and doughnut parallel interval are arranged.
As a kind of improvement, the described nanofiber that is used for weaving nano fibre sheet is at least a of following nanofiber: chitosan nano fiber, polycaprolactone nanofiber or polyvinyl alcohol nano.
As a kind of improvement, polyether sulfone doughnut or polysulfone hollow fibre that the fibronectin that the described doughnut that is used for the mixed weaving fiber mat is a permeable watertight is modified.
As a kind of improvement, the doughnut of described vertical layout is aperture 0.2 μ m, molecular retention amount 50～100kD, and not modified polyether sulfone doughnut or polysulfone hollow fibre.
As a kind of improvement, the grid length of side of described nano fibre sheet is 1mm.
As a kind of improvement, nano fibre sheet is according to the vertical bonding stack of the spacing of 300 μ m.
As a kind of improvement, described shell of reactor is cuboid or cylindrical transparent lucite shell.
The invention has the beneficial effects as follows:
The present invention utilizes the micron order fibre bundle that nanofiber is woven into and the spatial organization of doughnut, does not introduce three-dimensional biological support, has but realized the 3 D stereo cultivation, and hepatocellular activity and function all are better than traditional two dimension cultivates, and is easy to systematism; Micro-nanometer ordered structure in the fibre bundle more can promote hepatocellular growth and breeding, promotes the generation of hepatocyte spheroplast, more helps high density, the hepatocellular acquisition of high activity and permanent the cultivation, and has the promotion stem cell to induce the function of differentiation; The three-dimensional hole that fiber combinations constitutes is small, helps fixed cell, makes cell distribution even; The three-dimensional hole rule that fiber combinations constitutes is even, and liquid flowing resistance is little, makes the suffered shearing force of cell little, is easy to amplify; Utilize the different qualities fiber (can promote the nanofiber of hepatic cell growth breeding, the modified doughnut that is easy to hepatic cell growth and energy oxygen supply, and doughnut) combination with immune iris action, improved the defective that cell easily stops up semipermeable membrane, mass exchange efficient height, and have oxygenate and immune barriers function concurrently.The reactor of this invention is powerful, can be used for biotype or hybrid artificial liver, also can be used for the cultivation of stem cell and induce differentiation.
Description of drawings
Fig. 1 is a reactor longitudinal profile structural representation of the present invention;
Fig. 2 is a reactor horizontal section structural representation of the present invention;
Fig. 3 uses sketch map for the biotype artificial liver support system.
Reference numeral: nano fibre sheet 1, the vertical doughnut of arranging 2, hepatocellular three dimensional growth space 3, micron order fibre bundle 4, the doughnut 5 in the nano fibre sheet, shell of reactor 6, liquid inlet 7, liquid outlet 8, gas access 9, gas outlet 10, cell suspension inlet 11, cell suspension outlet 12, bacteria filter 13, spiral cover 14, patient or laboratory animal 15, plasma separator 16, extracorporeal circulation pool 17 that nanofiber is woven into.
The specific embodiment
Nanometer fiber net sheet superposed type biological reactor of the present invention, the spacing of nano fibre sheet, sizing grid and reactor scale can or be dwindled according to the practical application amplification.
Below in conjunction with embodiment the present invention is described in further detail:
Nanometer fiber net sheet superposed type biological reactor in the present embodiment comprises a cuboid transparent organic glass shell of reactor 6.Cell suspension inlet 11 and liquid inlet 7 are established in the bottom of shell of reactor 6, and cell suspension outlet 12 and liquid outlet 8 are established in the top, and the sidewall subtend is provided with gas access 9 and gas outlet 10.Cell suspension inlet 11 and cell suspension export 12 places bacteria filter 13 all are housed, and are fixed on the shell of reactor 6 with spiral cover 14.
Arrange some vertical synergetic nano fibre sheets 1 in the shell of reactor 6, polyether sulfone doughnut 5 braidings that the micron order fibre bundle 4 that nano fibre sheet 1 is woven into according to certain rule by nanofiber, blending surface are fit to fibronectin modification hepatic cell growth, permeable watertight form.Being arranged in parallel for micron order fibre bundle 4 on 1 one directions of nano fibre sheet, is that micron order fibre bundle 4 is arranged with doughnut 5 parallel interval on another direction.Be thick with the grid that the length of side is 1mm on the nano fibre sheet 1, each layer nano fibre sheet is according to the bonding stack of the spacing of 300 μ m.The material of the nanofiber in the net sheet can be a natural material, and as chitosan etc., the perhaps excellent macromolecular compound of biocompatibility is as in polycaprolactone, the polyvinyl alcohol etc. one or more.The inside of the doughnut 5 in the net sheet is passages of oxygen and carbon dioxide gas mixture, and the one end connects gas access 9, and the other end connects gas outlet 10.
The doughnut 2 of some vertical layouts passes the center of the grid of nano fibre sheet 1, the vertical doughnut of arranging 2 is aperture 0.2 μ m, molecular retention amount 50～100kD and not modified polyether sulfone doughnut, possess good biocompatibility and immune isolation effect, the not modified risk that reduces hepatocyte at the quick growth obstruction in its surface fiber holes in vertical doughnut 2 surfaces.The inside of the vertical doughnut of arranging 2 is passages of blood plasma or culture fluid, and the one end connects the liquid inlet, and the other end connects liquid outlet.
The characteristics of the doughnut 5 in the net sheet are: permeable watertight, and the surface is easy to hepatic cell growth; The characteristics of the vertical doughnut of arranging 2 are: air-and water-permeable, have immune iris action, have good biocompatibility, the surface needn't be easy to hepatic cell growth very much, and is too fast and stop up the risk of fiber holes in its superficial growth to reduce cell.According to this standard, also can select for use polysulfones etc. to possess the material of same characteristic as doughnut.
The hepatocellular three dimensional growth of the common formation of the inwall of the outer wall of all fibers and shell of reactor 6 space 3, this space is communicated with cell suspension inlet 11 and cell suspension outlet 12.Hepatocyte mainly attaches to the surface of nano fibre sheet 1, and part attaches to the surface of the doughnut 2 of vertical layout, is the 3 D stereo growth, is easy to systematism.
Interlacing part fiber in reactor can remove with cell suspension inlet 11 and cell suspension outlet 12, so that the inflow of hepatocyte suspension and outflow.
Present embodiment is used for stem cell and induces the use of differentiation as follows:
1, the inoculation of stem cell.Stem cell can be selected mesenchymal stem cells MSCs etc. for use.
(1) is mixed with the stem cell suspension of suitable concn with culture fluid.
(2) open the spiral cover 14 of cell suspension inlet 11, in the cell suspension injecting reactor, till being full of reactor and overflowing to cell suspension from the cell suspension outlet 12 at top.Stem cell attaches to the fiber outer wall, through attaching firmly behind the certain hour.
(3) pour into fresh culture from cell suspension inlet 11, flow out from cell suspension outlet 12, wash away not adherent stem cell through reactor.
2, shown in pressing this reactor and extracorporeal circulation pool 17 etc. in Fig. 3 frame of broken lines, be linked to be the cell culture peripheral passage, fresh culture medium respectively from the liquid inlet 7 and liquid outlet 8 flow into and outflow reactors, for cell provides nutrient and takes away metabolite.
3, utilizing this cell culture peripheral passage to carry out stem cell cultivates and induces.
Present embodiment is used for the Biotype artificial rami hepatici, and to hold the use of system as follows:
After the blood lead body of patient or laboratory animal 15 is outer, at first be separated into cell composition and blood plasma components through blood plasma separator 16, wherein blood plasma components enters extracorporeal circulation pool 17,7 enter in the reactor from the liquid inlet then, inner chamber by vertical doughnut 2 flows out, after hepatocyte in the hepatocellular three dimensional growth space 3 (hepatocyte for inoculate in advance and cultivate) fully contacts, flow back to the inner chamber of vertical doughnut 2, liquid outlet 8 to reactor head flows out from bottom to top, returns circulatory pool 17.After repeatedly circulating, the cell composition in blood feeds back in the body again.
Hepatocyte can be selected former generation people, porcine hepatocyte or hepatic cell line etc. for use, and summary inoculation and incubation step are as follows:
1, is mixed with the hepatocyte suspension of suitable concn with culture fluid.
2, open the spiral cover 14 of cell suspension inlet 11, in the hepatocyte suspension injecting reactor, till being full of reactor and overflowing to cell suspension from the cell suspension outlet 12 at top.Hepatocyte attaches to the fiber outer wall, attaches firmly after about 24 hours.
3, pour into fresh culture from cell suspension inlet 11, flow out from cell suspension outlet 12, wash away not adherent hepatocyte through reactor.
4, shown in pressing this reactor and extracorporeal circulation pool 17 etc. in Fig. 3 frame of broken lines, be linked to be the liver cell culture peripheral passage, fresh culture medium respectively from the liquid inlet 7 and liquid outlet 8 flow into and outflow reactors, for hepatocyte provides nutrient and takes away metabolite.
5, after the suitable time of cultivation, can be combined into the Biotype artificial rami hepatici by Fig. 3 connection and hold system.
At last, it is also to be noted that what more than announce only is specific embodiments of the invention.All distortion that those of ordinary skill in the art can directly derive or associate from content disclosed by the invention all should be thought protection scope of the present invention.
Claims (9)
1, a kind of nanometer fiber net sheet superposed type biological reactor comprises shell of reactor, it is characterized in that, arranges some vertical synergetic nano fibre sheets in the shell of reactor, and nano fibre sheet is formed by nanofiber mixing woven hollow fiber; The doughnut of some vertical layouts passes the center of the grid of aforementioned nano fibre sheet, and described doughnut is polyether sulfone doughnut or polysulfone hollow fibre; Cell suspension inlet and liquid inlet are established in the bottom of shell of reactor, and cell suspension outlet and liquid outlet are established in the top, and the sidewall subtend is provided with gas access and gas outlet;
The described inside that is used for the doughnut of mixed weaving nano fibre sheet is gas passage, and the one end connects the gas access, and the other end connects gas outlet; The inside of the doughnut of described vertical layout is fluid passage, and the one end connects the liquid inlet, and the other end connects liquid outlet; The hepatocellular three dimensional growth of the common formation of the outer wall of all fibres and the inwall of shell of reactor space is communicated with cell suspension inlet and cell suspension outlet.
2, nanometer fiber net sheet superposed type biological reactor according to claim 1 is characterized in that, bacteria filter is equipped with in described cell suspension inlet and cell suspension exit respectively, is fixed on the shell of reactor with spiral cover.
3, nanometer fiber net sheet superposed type biological reactor according to claim 1, it is characterized in that, described nano fibre sheet is formed by interlacing about the nanofiber mixing doughnut of both direction, the micron order fibre bundle that is woven into for nanofiber is arranged in parallel in one direction, and micron order fibre bundle that is woven into for nanofiber on another direction and doughnut parallel interval are arranged.
4, nanometer fiber net sheet superposed type biological reactor according to claim 1, it is characterized in that the described nanofiber that is used for weaving nano fibre sheet is at least a of following nanofiber: chitosan nano fiber, polycaprolactone nanofiber or polyvinyl alcohol nano.
5, nanometer fiber net sheet superposed type biological reactor according to claim 1 is characterized in that, polyether sulfone doughnut or polysulfone hollow fibre that the fibronectin that the described doughnut that is used for the mixed weaving fiber mat is a permeable watertight is modified.
6, nanometer fiber net sheet superposed type biological reactor according to claim 1, it is characterized in that, the doughnut of described vertical layout is aperture 0.2 μ m, molecular retention amount 50～100kD, and not modified polyether sulfone doughnut or polysulfone hollow fibre.
7, nanometer fiber net sheet superposed type biological reactor according to claim 1 is characterized in that, the grid length of side of described nano fibre sheet is 1mm.
8, nanometer fiber net sheet superposed type biological reactor according to claim 1 is characterized in that, nano fibre sheet is according to the vertical bonding stack of the spacing of 300 μ m.
9, nanometer fiber net sheet superposed type biological reactor according to claim 1 is characterized in that, described shell of reactor is cuboid or cylindrical transparent lucite shell.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100984067A CN101549181B (en) | 2009-05-07 | 2009-05-07 | Nanometer fiber net sheet superposed type biological reactor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100984067A CN101549181B (en) | 2009-05-07 | 2009-05-07 | Nanometer fiber net sheet superposed type biological reactor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101549181A true CN101549181A (en) | 2009-10-07 |
| CN101549181B CN101549181B (en) | 2011-11-02 |
Family
ID=41153817
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009100984067A Active CN101549181B (en) | 2009-05-07 | 2009-05-07 | Nanometer fiber net sheet superposed type biological reactor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101549181B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012122719A1 (en) * | 2011-03-17 | 2012-09-20 | 浙江大学 | Hepatic lobule-like bioreactor |
| 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 |
| CN105754846A (en) * | 2014-12-16 | 2016-07-13 | 国家开发投资公司 | Hollow microculture film plate and microculture system |
| CN111249554A (en) * | 2020-03-16 | 2020-06-09 | 中南大学湘雅二医院 | Biological artificial liver purification circulation unit and artificial liver support system |
| CN111254078A (en) * | 2020-03-16 | 2020-06-09 | 中南大学湘雅二医院 | Honeycomb support plate for in-vitro culture of hepatic cells and bioreactor for artificial liver |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE1009306A5 (en) * | 1995-04-28 | 1997-02-04 | Baxter Int | Bioreactor. |
| CN101050418A (en) * | 2007-03-20 | 2007-10-10 | 东南大学 | Bioreactor of artificial liver |
| CN101081182A (en) * | 2007-07-05 | 2007-12-05 | 南京大学医学院附属鼓楼医院 | Novel biology artificial hepatocyte reactor |
| CN100556381C (en) * | 2007-08-17 | 2009-11-04 | 浙江大学 | Filling bracket perfusion type bioreactor for artificial liver |
| CN101199436A (en) * | 2007-11-28 | 2008-06-18 | 中国人民解放军第三军医大学第一附属医院 | Three-dimensional liver cell culture bioreactor |
-
2009
- 2009-05-07 CN CN2009100984067A patent/CN101549181B/en active Active
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012122719A1 (en) * | 2011-03-17 | 2012-09-20 | 浙江大学 | Hepatic lobule-like bioreactor |
| US8735143B2 (en) | 2011-03-17 | 2014-05-27 | Zhejiang University | Hepatic lobule-like bioreactor |
| CN105754846A (en) * | 2014-12-16 | 2016-07-13 | 国家开发投资公司 | Hollow microculture film plate and microculture system |
| 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 |
| CN111249554A (en) * | 2020-03-16 | 2020-06-09 | 中南大学湘雅二医院 | Biological artificial liver purification circulation unit and artificial liver support system |
| CN111254078A (en) * | 2020-03-16 | 2020-06-09 | 中南大学湘雅二医院 | Honeycomb support plate for in-vitro culture of hepatic cells and bioreactor for artificial liver |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101549181B (en) | 2011-11-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN201418905Y (en) | Fiber mesh stacked bioreactor for artificial liver | |
| CN101549179B (en) | Perforated brick type filling support type reactor used in artificial liver | |
| CN101559246B (en) | Hybrid artificial liver support system equipped with nano fibre sheet stacked reactor | |
| Kim et al. | Dynamic seeding and in vitro culture of hepatocytes in a flow perfusion system | |
| CN101549181B (en) | Nanometer fiber net sheet superposed type biological reactor | |
| US8778330B2 (en) | En vivo generated tissue system | |
| CN101199436A (en) | Three-dimensional liver cell culture bioreactor | |
| CN103194390B (en) | Double-loop oscillation perfusion-type biological reaction system | |
| CN104353142B (en) | Biological artificial liver reactor | |
| CN100556381C (en) | Filling bracket perfusion type bioreactor for artificial liver | |
| CN101381678B (en) | Multi-layer diaphragm structure perfusion bioreactor and application | |
| CN103614296A (en) | Double-chamber three-dimensional pouring bioreactor system | |
| WO2012122719A1 (en) | Hepatic lobule-like bioreactor | |
| CN103100119A (en) | Artificial liver bioreactor | |
| JP2012044908A (en) | Hollow fiber module for cell culture and method for cell culture | |
| CN101096639B (en) | Multi-group fiber pipes even distributed multifunctional hollow fiber film pipe bioreactor | |
| CN204072913U (en) | Zhu Shi bioartificial liver reactor | |
| CN101569767B (en) | Hybrid artificial liver supporting system equipped with perforated brick type filling bracket type reactor | |
| CN101751696B (en) | Method for constructing bionic three-dimensional vessel network of human parenchymal viscera | |
| CN201418901Y (en) | Perforated brick-type packed scaffold reactor for artificial liver | |
| CN101294136A (en) | Biological artificial liver cell growth component, artificial liver reactor and preparation method thereof | |
| CN111254078B (en) | Honeycomb support plate for in-vitro culture of hepatic cells and bioreactor for artificial liver | |
| CN202027968U (en) | Perfusion type biological artificial liver reactor based on dual-layer nitrocellulose membrane | |
| CN107814958A (en) | A kind of preparation method of cellulose sponge and its mixed solution | |
| CN201286882Y (en) | Perfusion-type bioreactor of multi-layer membrane structure |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Weihai Weigao Life Science & Technology Co., Ltd. Assignor: Zhejiang University Contract record no.: 2012330000164 Denomination of invention: Nanometer fiber net sheet superposed type biological reactor Granted publication date: 20111102 License type: Exclusive License Open date: 20091007 Record date: 20120411 |