CN1290743A - Three-dimensional discal rotary hollow on-line cell cultivator with air and liquid supply - Google Patents
Three-dimensional discal rotary hollow on-line cell cultivator with air and liquid supply Download PDFInfo
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- CN1290743A CN1290743A CN 99123884 CN99123884A CN1290743A CN 1290743 A CN1290743 A CN 1290743A CN 99123884 CN99123884 CN 99123884 CN 99123884 A CN99123884 A CN 99123884A CN 1290743 A CN1290743 A CN 1290743A
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- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/10—Perfusion
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/10—Rotating vessel
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Abstract
The three-dimensional cultivator has a main body comprising a hollow discal cell culturing chamber, a culture liquid flowing chammber, an air chamber and a culture liquid returning chamber. The cell culturing chamber has liquid to liquid exchange film and air-liquid exchange film separately on its two side walls, and the main body is connected via a main shaft to a driving mechanism driven by a motor, and is rotated by the driving mechanism. The main body together with an air supplying and liquid supplying system realizes in-situ air supply while replacing culture liquid continuously.
Description
The present invention relates to the incubator in biomedical engineering, organizational project (Tissue Engineering) technology, particularly relate in the biomedical engineering cell/tissue and cultivate employed online air feed, the hollow rotational circle disc type of feed flow cell three-dimensional incubator.
NASA (NASA) Johnson center is on the basis of containers for culturing organisms RWV system, develop two classes and be suitable for the cell culture apparatus that clinical experiment is used, wherein there is a class to be called for short HARV (High Aspect Ratio Vessel) system, as: document [1] Culturing a Future, shown in the Fall 1998.MicroGravity NEWS. (as Fig. 1).The cell culture apparatus of this system adopts double-disc structure; promptly mainly comprise open circles disc type air chamber 2 and open circles disc type cell culture chamber 1; clamp the gas/liquid exchange membrane between air chamber 2 and the cell culture chamber 1; the external fixation wall of cell culture chamber 1 is provided with liquid-inlet pipe A and the drain pipe B that communicates with cell culture chamber 1; C among Fig. 1 is a stopple coupon; the external fixation wall of air chamber 2 is provided with air inlet port and production well (not shown); air pump feeds air chamber by air inlet port with live gas; gas after the exchange is discharged by production well; the injection of the fresh medium of cell culture chamber 1; must under stopped status, carry out; after promptly shutting down; open the valve on liquid-inlet pipe and the drain pipe, discharge used nutrient solution, inject fresh medium by liquid-inlet pipe by drain pipe.This cell culture apparatus characteristics are that diameter/length is bigger than very, and it is significant for development individuation cell therapy and gene therapy, and clinical and experimental study is being carried out in some medical centers of the U.S..So-called high, wide, long than (HAR), the ratio of meaning culturing room's axial dimension (h) and radial dimension (D) is much smaller than 1 (h/D<<1).From fluid mechanics principle, two disk incubators begin to rotate after after a while the viscous fluid between the disk will move together as solid and disk, so cell (coupling that depends on rotating speed and nutrient solution viscosity) under certain condition can overcome gravity settling, cell suspension obtains the condition of three dimensional growth between rotating-disk.Be not difficult to find out that by Fig. 1 the HARV system of NASA is by as the online air feed of gas/liquid exchange membrane of open circles dish type culturing room sidewall, that is to say can only online air feed and can not online feed flow.The renewal of its nutrient solution is undertaken by injection orifice on the disk opposite side, and, before changing, nutrient solution must shut down earlier; can not move continuously, and make institute's cultured cells be deposited in certain zone, under static state, upgrade nutrient solution; and then restart, this must cause two problems:
1, in intermittent process, gravity settling makes the cell calmness form the contact supression in the cell culture chamber wall, thereby disturbs and even destroyed the three dimensional growth of cell;
2, the viscous fluid between Xuan Zhuan two disks moves together as solid and disk after setting up stable flow field, does not have relative movement between the fluid infinitesimal, thereby mobile shearing stress goes to zero.But in starting (flow field foundation) and (flow field disappearance) process of shutdown, fluidised form changes the dynamic stress that causes and can not ignore.And in this process, fluid not only has axially and radial motion, also has axial motion (can consult document 2:Schilichting " boundary layer theory " p.114-121), this axial flow might drive cell collision culturing room's sidewall or adhesion, spread in sidewall, because h/D<<1, this possibility is very important, and is especially true during high-density culture.Incubation time is long more, intermittently---and the number of starts is many more, and the problem that is unfavorable for the cell growth that causes is big more.
The objective of the invention is to: the incubator that overcomes prior art must be shut down earlier when upgrading nutrient solution, can not move continuously, when shutting down in culturing process, the defective that the cell calmness is restrained the cell growth in culturing room's wall formation contact occurs; In order to solve real realization cell dimensional culture and improve culture effect in incubator, thereby provide a kind of in dynamic air feed, also the hollow rotational circle disc type of online air feed, the feed flow cell three-dimensional incubator of online feed flow.
The object of the present invention is achieved like this:
Online air feed provided by the present invention, the hollow rotational circle disc type of feed flow cell three-dimensional incubator, comprise the incubator main body, motor, base, support and air feed-exhaust and feed flow-drainage system, it is characterized in that: the incubator main body is an open circles disk body, its inner shaft is to air chamber is set successively abreast, cell culture chamber, nutrient solution flow chamber and nutrient solution return passage, clamp the gas/liquid exchange membrane between air chamber and the cell culture chamber, clamp liquid/liquid exchange membrane between cell culture chamber and the nutrient solution flow chamber, the circular wall of another of nutrient solution flow chamber is a fixation wall, same radial position place in its upper edge is provided with some return ports, this return port communicates with the nutrient solution return passage, the external fixation wall of air chamber is provided with the residual air outlet with incubator main body exterior, be horizontally disposed with a pair of hollow axle on the base on the two stands of parallel placement with the unsettled support of incubator main body, wherein, the circular external fixation wall of the end of a hollow axle and air chamber is fixed, its internal cavity communicates with the air chamber gas circuit for the gas passage of carrying fresh air, the circular fixation wall of another root hollow axle end and nutrient solution flow chamber is fixed, one nutrient solution flow duct is set in it with one heart, nutrient solution flow duct inner chamber communicates with nutrient solution flow chamber liquid road, the axial wall that is positioned at the hollow axle of nutrient solution return passage is provided with some nutrient solution return ports, this nutrient solution return port communicates with the nutrient solution return passage, this hollow axle exposes the solid shield retaining of cover on the outer rotating shaft section of support, shield retaining is one to be fixed on the hollow cylinder on the support, its inner radial is provided with and vertical nutrient solution import of its medullary ray and metabolite outlet, liquid-inlet pipe is installed in the nutrient solution import to communicate with the nutrient solution flow duct that is arranged in hollow axle, the interior circular channel of metabolite outlet pipe and hollow axle is installed in the metabolite outlet to communicate, between the outlet of nutrient solution import in the shield retaining and metabolite and the opposite side of nutrient solution import the sealing-ring that its sealing is separated respectively is set, motor drives above-mentioned two hollow axles by speed change mechanism and rotates synchronously, its air feed-exhaust system comprises source of the gas, air pump and gas pipe line, gas pipe line that links to each other with air pump and the intracavity inter-connection that is fixed on the hollow axle on the air chamber fixation wall, feed flow-drainage system comprises reservoir, liquid pump and liquid-transport pipe-line, the liquid-transport pipe-line that links to each other with liquid pump is connected with nutrient solution liquid-inlet pipe in the shield retaining.
The exit end of above-mentioned metabolite outlet pipe is communicated with deoscillator by liquid-transport pipe-line, deoscillator is communicated with the nutrient solution dialyzer, dialyzer outlet is communicated with metabolite collector and gas/liquid interchanger respectively, and the gas/liquid interchanger is communicated with reservoir, and the reservoir outlet is connected with liquid-inlet pipe on the shield retaining.
The liquid-transport pipe-line that the source of the gas of described air feed-exhaust system links to each other with air chamber is provided with voltage stabilizing, relief valve, and the residual air outlet of air chamber is connected on the residual air collector by gas exhaust duct.
Online air feed provided by the invention, the hollow rotational circle disc type of feed flow cell three-dimensional incubator principle of work is: liquid pump enters the nutrient solution flow chamber with the fresh medium in the reservoir from the liquid-inlet pipe on the shield retaining, in the incubator rotation process, nutrient solution is the online supply nutrition of cell culture chamber and takes metabolite out of by the centrifugal force uniform distribution and by liquid/liquid exchange membrane, the nutrient solution of finishing exchange is that metabolite flows into the nutrient solution return passage through return port, return port flows into annular return flow line in the hollow axle on hollow axle again, metabolite outlet pipe from shield retaining flows out, at this moment, finished the exchange of new and old nutrient solution.Owing to contain the part fresh medium in the effusive metabolite liquid, in order to economize in raw materials, reduce cost, effusive metabolite fluid is sent into the nutrient solution dialyzer through dialysis through deoscillator, its metabolite is sent into the metabolite collector afterwards, after the nutrient solution process gas/liquid interchanger of dialysis, regulate the oxygen level and the pH value of nutrient solution, and flow back to the nutrient solution reservoir for recycling after adding nutrition and somatomedin; Simultaneously, opposite side at incubator, the gas passage that the high oxygen rich gas of certain proportioning is equipped with from entrance end in the hollow axle of air inlet filter membrane enters air chamber, carry out oxygen and carbon dioxide exchange by the gas/liquid exchange membrane that is installed between cell culture chamber and the air chamber, for cell culture chamber provides new fresh oxygen, and take waste gas out of, waste gas is recovered in the residual air collector by the residual air outlet, finishes gaseous interchange.The liquid-transport pipe-line that source of the gas links to each other with air chamber is provided with voltage stabilizing, relief valve.In this incubator, the cell that cell cultures is indoor, carry out nutritional supplementation by liquid/liquid exchange membrane pair cell on the one hand, the metabolite that excretes, carry out the discharge of replenishing of oxygen and waste gas on the other hand by the cell in the gas/liquid exchange membrane pair cell culturing room, thereby the cell three-dimensional of having realized online air feed, feed flow is cultivated.
Effect of the present invention: overcome that prior art shuts down in culturing cell is crossed that liquid feeding causes cell settlement and the shortcoming damaged; in order to realize dynamic online feed flow, air feed; the device continuously-running; avoid intermittent disadvantageous effect of shutting down to institute's culturing cell; thereby eliminate the hidden danger that the HARV system may cause individual therapy and gene therapy; reach real cell three-dimensional and cultivate, thereby a kind of online air feed, feed flow rotational circle disc type lamella cell three-dimensional incubator are provided.
The present invention is described in detail below in conjunction with drawings and Examples:
Fig. 1 is known cell culture apparatus (HARV) structural representation;
Fig. 2 is online air feed of the present invention, the hollow rotational circle disc type of feed flow cell three-dimensional incubator structural representation;
Fig. 3 is the structure and the structural representation that is connected with axle of Fig. 2 hollow core garden disk body shape incubator main body;
Fig. 4 is the structural representation of shield retaining.
Wherein: cell culture chamber 1 air chamber 2 nutrient solution flow chambers 3
Gas/liquid exchange membrane 4 liquid/liquid exchange membrane 5 nutrient solution return passages 6
The 15 nutrient solution imports 16 of liquid-inlet pipe 14 metabolite outlet pipes
Metabolite exports 17 sealing-rings, 18 speed change mechanisms 19
Hollow axle W, Q shield retaining S
Online air feed provided by the present invention, the hollow rotational circle disc type of feed flow cell three-dimensional incubator, comprise incubator main body 8, motor 20, base 22, support 21 and air feed-exhaust and feed flow-drainage system, it is characterized in that: incubator main body 8 is an open circles disk body, its inner shaft is to air chamber 2 is set successively abreast, cell culture chamber 1, nutrient solution flow chamber 3 and nutrient solution return passage 6, clamp gas/liquid exchange membrane 4 between air chamber 2 and the cell culture chamber 1, clamp liquid/liquid exchange membrane 5 between cell culture chamber 1 and the nutrient solution flow chamber 3, the circular wall of another of nutrient solution flow chamber 3 is a fixation wall, same radial position place in its upper edge is provided with some return ports 10, this return port 10 communicates with nutrient solution return passage 6, the external fixation wall of air chamber 2 is provided with the residual air outlet 9 with incubator main body 8 exterior, be horizontally disposed with a pair of hollow axle W and Q on the two stands 21 of parallel placement on the base 22 with the 8 unsettled supports of incubator main body, wherein, the circular external fixation wall of the end of a hollow axle W and air chamber 2 is fixed, its internal cavity communicates with air chamber 2 gas circuits for the gas passage 7 of carrying fresh air, the end of another root hollow axle Q and the circular fixation wall of nutrient solution flow chamber 3 are fixed, one nutrient solution flow duct 12 is set in it with one heart, nutrient solution flow duct 12 inner chambers communicate with nutrient solution flow chamber 3, the axial wall that is positioned at the hollow axle Q of nutrient solution return passage 6 is provided with some nutrient solution return ports 11, nutrient solution return port 11 and nutrient solution return passage 6 communicate, this hollow axle Q exposes the solid shield retaining S of cover on the support 21 rotating shaft section outward, shield retaining S one is fixed on the hollow cylinder on the support 21, its inner radial is provided with and vertical nutrient solution import 16 of its medullary ray and metabolite outlet 17, liquid-inlet pipe 14 is installed in the nutrient solution import 16 to communicate with the nutrient solution import 16 of the nutrient solution flow duct 12 that is arranged in hollow axle Q, metabolite on the annular return flow line 13 in the metabolite outlet pipe of installing in the metabolite outlet 17 15 and the hollow axle Q exports 17 and communicates, among the shield retaining S between fluid inlet 16 and the metabolite outlet 17 and the opposite side of fluid inlet 16 sealing-ring 18 that its sealing is separated respectively is set, motor 20 drives above-mentioned two hollow axle W by speed change mechanism 19, Q rotates synchronously, air feed-exhaust system of the present invention comprises source of the gas, air pump and gas pipe line, the gas pipe line that links to each other with air pump is connected with hollow axle W on being fixed on air chamber 2 fixation wall, promptly the gas pipe line that links to each other with air pump and the inner chamber of hollow axle W are that the inlet mouth of gas passage 7 communicates, the gas pipe line that source of the gas links to each other with air chamber is provided with voltage stabilizing, relief valve, enter the gaseous tension of air chamber with control, the residual air outlet of air chamber 29 is connected on the residual air collector by gas pipe line; Feed flow-drainage system comprises nutrient solution reservoir, liquid pump and liquid-transport pipe-line, and the liquid-transport pipe-line that links to each other with liquid pump is connected with the nutrient solution inlet pipe 14 of shield retaining S; The exit end of metabolite drain pipe 15 is communicated with deoscillator by liquid-transport pipe-line, the deoscillator outlet is communicated with the nutrient solution dialyzer, the outlet of nutrient solution dialyzer is communicated with metabolite collector and gas/liquid interchanger respectively, the gas/liquid interchanger is communicated with reservoir, and the reservoir outlet is connected with liquid-inlet pipe 14 on the shield retaining S.
Among the figure, the diameter of open circles dish type cell culture chamber 1 is 150mm, and thickness is 120mm, and capacity is 200ml; BGC-823 human stomach cancer cell line of packing in it, cell culture chamber 1 is connected with air chamber 2 by gas/liquid exchange membrane 4; Be connected with nutrient solution flow chamber 3 by liquid/liquid exchange membrane 5.Make of medical polycarbonate or tetrafluoroethylene by the incubator main body that cell culture chamber 1, nutrient solution flow chamber 3, air chamber 2 and nutrient solution return passage 6 are formed.
Clamp gas/liquid exchange membrane 4 between open circles dish type air chamber 2 and the cell culture chamber 1, another wall is a fixation wall, fixation wall is provided with residual air outlet 9, and live gas enters air chamber 2 by air pump through the gas passage 7 of hollow axle W inner chamber and the air inlet filter membrane that is positioned at gas passage 7.
Clamp liquid/liquid exchange membrane 5 between nutrient solution flow chamber 3 and the cell culture chamber 1, dress DMEM nutrient solution in it, the microballon carrier adopts Gtodex-3, another sidewall is fixation wall and nutrient solution return passage 6 adjacency, same diameter place is provided with some nutrient solution return ports 10 on the fixation wall, fresh medium is by the nutrient solution flow duct 12 of nutrient solution inlet pipe 14 in hollow axle Q, enter nutrient solution flow chamber 3, under pressure and centrifugal action, upgrade the nutrient solution in the nutrient solution flow chamber 3, the metabolite that metabolism goes out enters nutrient solution return passage 6 through return port 10, annular return flow line 13 in return port 11 flows into hollow axle Q again, afterwards, the metabolite outlet pipe 15 by isolation mechanism S flows out;
The gas/liquid exchange membrane that gas/liquid exchange membrane 4 is made for the ordinary silicon rubber diaphragm;
Liquid/liquid exchange membrane 5 is commercially available Miripor film;
The end of two concentric hollow axle W, Q is separately fixed in the centre hole of pair of brackets 21, the other end of hollow axle W penetrates air chamber 2 and is fixed on the fixation wall of air chamber 2, the inner chamber of hollow axle W is a gas passage 7, and gas passage 7 communicates with open circles dish type air chamber 2; The other end of hollow axle Q passes nutrient solution return passage 6 and is fixed on the fixation wall of nutrient solution flow chamber 3, the middle placement nutrient solution flow duct 12 of this root hollow axle Q, inner chamber in the hollow axle Q outside the nutrient solution flow duct 12 is annular return flow line 13, be positioned on the axial wall of hollow axle of nutrient solution return passage 6 some return ports 11 are arranged, return port 11 communicates with nutrient solution return passage 6 liquid roads by return port 10, exposing has metabolite outlet 17 on the support 21 outer hollow axle Q sections, and at the solid isolation mechanism S of the hollow axle Q of this section cover;
Fresh medium inlet pipe 14 joins with the liquid-transport pipe-line of feed flow-drainage system;
Sealing-ring 18 among the shield retaining S separates nutrient solution import and export 16 and metabolite outlet 17 sealings;
At shield retaining S inner seal ring 18 nutrient solution import 16 and metabolite outlet 17 sealings are separated, nutrient solution liquid-inlet pipe 12 communicates with nutrient solution flow chamber 3 in the hollow axle Q chamber, belt return flow line 13 internal reflux of metabolite phegma between axle inwall and nutrient solution liquid-inlet pipe 12 flow out by metabolite outlet 17.Two supports 21 that are used for back shaft and incubator main body are fixed on base 22, and motor 20 is fixed on the support 21, and motor 20 drives two concentric hollow rotating shaft W, Q by speed change mechanism 19 and rotates synchronously; The inner chamber of gas transmission pipeline in air feed-exhaust system and hollow axle W communicates as the inlet mouth of gas passage 7; The liquid pump of present embodiment is imported nutrient solution liquid-inlet pipes 12 from reservoir through liquid-transport pipe-line and nutrient solution inlet pipe 14 with fresh medium, enter nutrient solution flow chamber 3 again: metabolite flows out from metabolite outlet pipe 15 through nutrient solution return passage 6, annular return flow line 13.Its effluent flows into dialyzer 22 through deoscillator, flow into meta-bolites collector and gas/liquid interchanger respectively again, after regulating, and flow to reservoir for recycling after adding nutrition and somatomedin etc. through the oxygen level of the nutrient solution of gas/liquid interchanger and pH value.
Claims (3)
1. online air feed, the hollow rotational circle disc type of feed flow cell three-dimensional incubator, comprise the incubator main body, motor, base, support and air feed and liquid-supplying system, it is characterized in that: the incubator main body is an open circles disk body, its inner shaft is to air chamber is set successively abreast, cell culture chamber, nutrient solution flow chamber and nutrient solution return passage, clamp the gas/liquid exchange membrane between air chamber and the cell culture chamber, clamp liquid/liquid exchange membrane between cell culture chamber and the nutrient solution flow chamber, the circular wall of another of nutrient solution flow chamber is a fixation wall, same radial position place in its upper edge is provided with some return ports, this return port communicates with the nutrient solution return passage, the external fixation wall of air chamber is provided with the residual air outlet with incubator main body exterior, be horizontally disposed with a pair of hollow axle on the base on the two stands of parallel placement with the unsettled support of incubator main body, wherein, the circular external fixation wall of the end of a hollow axle and air chamber is fixed, its inner chamber communicates with the air chamber gas circuit for the gas passage of carrying fresh air, the circular fixation wall of the end of another root hollow axle and nutrient solution flow chamber is fixed, one nutrient solution flow duct is set in it with one heart, nutrient solution flow duct inner chamber communicates with the nutrient solution flow chamber, the axial wall that is positioned at the hollow axle of nutrient solution return passage is provided with some nutrient solution return ports, this nutrient solution return port communicates with the nutrient solution return passage, this hollow axle exposes the solid shield retaining of cover on the outer rotating shaft section of support, shield retaining is one to be fixed on the hollow cylinder on the support, its inner radial is provided with and vertical nutrient solution import of its medullary ray and metabolite outlet, liquid-inlet pipe is installed in the nutrient solution import to communicate with the nutrient solution flow duct that is arranged in hollow axle, the interior circular channel of metabolite outlet pipe and hollow axle is installed in the metabolite outlet to communicate, between the outlet of nutrient solution import in the shield retaining and metabolite and the opposite side of nutrient solution import the sealing-ring that its sealing is separated respectively is set, motor drives above-mentioned two hollow axles by speed change mechanism and rotates synchronously, its air feed-exhaust system comprises source of the gas, air pump and gas pipe line, gas pipe line that links to each other with air pump and the intracavity inter-connection that is fixed on the hollow axle on the air chamber fixation wall, feed flow-drainage system comprises reservoir, liquid pump and liquid-transport pipe-line, the liquid-transport pipe-line that links to each other with liquid pump is connected with nutrient solution liquid-inlet pipe in the shield retaining.
2. by the described online air feed of claim 1, the hollow rotational circle disc type of feed flow cell three-dimensional incubator, it is characterized in that: the exit end of described metabolite outlet pipe is communicated with deoscillator by liquid-transport pipe-line, the deoscillator outlet is communicated with the nutrient solution dialyzer, the dialyzer outlet is communicated with metabolite collector and gas/liquid interchanger respectively, the gas/liquid interchanger is communicated with reservoir, and the reservoir outlet is connected with liquid-inlet pipe on the shield retaining.
3. by the described online air feed of claim 1, the hollow rotational circle disc type of feed flow cell three-dimensional incubator, it is characterized in that: the liquid-transport pipe-line that the source of the gas of described air feed-exhaust system links to each other with air chamber is provided with voltage stabilizing, relief valve, and the residual air outlet of air chamber is connected on the residual air collector by gas exhaust duct.
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CN 99123884 CN1131303C (en) | 1999-11-16 | 1999-11-16 | Three-dimensional discal rotary hollow on-line cell cultivator with air and liquid supply |
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CN 99123884 CN1131303C (en) | 1999-11-16 | 1999-11-16 | Three-dimensional discal rotary hollow on-line cell cultivator with air and liquid supply |
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CN1290743A true CN1290743A (en) | 2001-04-11 |
CN1131303C CN1131303C (en) | 2003-12-17 |
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
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CN101838610A (en) * | 2010-03-19 | 2010-09-22 | 南方医科大学珠江医院 | Bioreactor and control system and method thereof |
CN101914438A (en) * | 2010-08-12 | 2010-12-15 | 中山大学 | Low-intensity pulse ultrasound-assisted rotary tubular cell/tissue culture system |
CN102234612A (en) * | 2010-05-06 | 2011-11-09 | 同济大学 | Biological engineering extracorporeal circulatory system |
CN102329729A (en) * | 2011-10-08 | 2012-01-25 | 中国科学院力学研究所 | Culture system for simulating microgravity effect of suspension cells |
CN102961998A (en) * | 2012-11-23 | 2013-03-13 | 西安医学院第二附属医院 | Rotary shaker for microorganism and molecular biological experiments |
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 |
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1999
- 1999-11-16 CN CN 99123884 patent/CN1131303C/en not_active Expired - Fee Related
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101838610A (en) * | 2010-03-19 | 2010-09-22 | 南方医科大学珠江医院 | Bioreactor and control system and method thereof |
CN102234612A (en) * | 2010-05-06 | 2011-11-09 | 同济大学 | Biological engineering extracorporeal circulatory system |
CN102234612B (en) * | 2010-05-06 | 2014-01-29 | 同济大学 | Biological engineering extracorporeal circulatory system |
CN101914438A (en) * | 2010-08-12 | 2010-12-15 | 中山大学 | Low-intensity pulse ultrasound-assisted rotary tubular cell/tissue culture system |
CN101914438B (en) * | 2010-08-12 | 2013-07-10 | 中山大学 | Low-intensity pulse ultrasound-assisted rotary tubular cell/tissue culture system |
CN102329729A (en) * | 2011-10-08 | 2012-01-25 | 中国科学院力学研究所 | Culture system for simulating microgravity effect of suspension cells |
CN102329729B (en) * | 2011-10-08 | 2013-05-29 | 中国科学院力学研究所 | Culture system for simulating microgravity effect of suspension cells |
CN102961998A (en) * | 2012-11-23 | 2013-03-13 | 西安医学院第二附属医院 | Rotary shaker for microorganism and molecular biological experiments |
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 |
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PB01 | Publication | ||
AR01 | Abandonment of patent right to avoid double patenting |
According to article 9 of the patent law and article 13 of the detailed rules for the implementation of the patent law: 99123884.2 of the invention patents in this issue as a notice of authorization, and at the same time corresponding to the 99254071.2 utility model patent to be given up, and in the 19 volume of the 51 issue of the new type of communique on the patent right to abandon the announcement. |
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C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C19 | Lapse of patent right due to non-payment of the annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |