CN102154100B - Potential difference circulating bioreactor - Google Patents
Potential difference circulating bioreactor Download PDFInfo
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- CN102154100B CN102154100B CN 201110002842 CN201110002842A CN102154100B CN 102154100 B CN102154100 B CN 102154100B CN 201110002842 CN201110002842 CN 201110002842 CN 201110002842 A CN201110002842 A CN 201110002842A CN 102154100 B CN102154100 B CN 102154100B
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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
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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
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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
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
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Abstract
The invention relates to a potential difference circulating bioreactor which comprises a container, wherein the inner cavity of the container is divided into an upper gas-containing chamber and a lower liquid-containing chamber; a lateral wing channel structure extending towards a lateral wing is arranged at the joint between the gas-containing chamber and the liquid-containing chamber on the side wall of the container; the inner port of the lateral wing channel structure is communicated with the inner cavity of the container; the outer port of the lateral wing channel structure is provided with a circulating pipe in a communication mode; the lower port of the circulating pipe is communicated with the bottom of the inner cavity of the container; and a one-way venting valve is arranged in the pipeline of the circulating pipe or at the lower port of the circulating pipe. When the bioreactor is driven to transversely swing or the lateral wing channel structure is driven to vertically swing by certain power, an altitude difference can be formed between the liquid level in the upper section of the circulating pipe and the liquid level in the liquid-containing chamber under the action of the one-way venting valve, so that the potential difference can drive the culture solution to flow to the bottom of the container through the lower circulating pipeline and realize the circulation of the culture solution between the liquid-containing chamber and the circulating pipeline, thereby finishing sufficient gas-liquid exchange and efficient culture solution mixing.
Description
Technical field
The present invention relates to a kind of potential difference circulatory bio-reactor that utilizes gravitional force to promote the nutrient solution circulation, this bio-reactor is mainly used in animal cell culture and utilizes zooblast to carry out the production of biological technology products, also can be used for the cultivation of insect cell and vegetable cell and microorganism and the production of biological technology products thereof.
Background technology
Utilize the zooblast (comprising the human cell) of cultivating to carry out life science; cellular transplantation therapy clinical disease and production biological technology products are (such as protein; the polypeptide class; nucleic acid; antibody class; virus vector and virus vaccines class) production, often need to carry out efficiently and the animal cell culture of mass-producing, therefore need research and development and production can satisfy the zooblast reactor of high-level efficiency and large-scale production.So-called animal bioreactor is exactly to carry out large-scale animal cell culture and utilize the zooblast of these large scale culturing to carry out the device that biological technology products is produced under the artificial conditions such as temperature, PH and dissolved oxygen of setting.Because zooblast poor growth and acellular wall, poor and responsive to the shearing force of ventilating and stirring causes to environmental change adaptive facultys such as temperature and PH, therefore, when carrying out animal cell culture, will be under suitable temperature and Ph environment, the most sufficient oxygen of cell (O2) and nutritive substance are provided, and avoid to greatest extent stirring the shearing damage that causes with gas-filled bubbles.This also is zooblast reactor and other reactors (such as microorganism fermentation tank) difference.Scientists is being devoted to research and development and the production of desirable animal bioreactor always in recent decades, come into the market from being amplified to step by step the existing dissimilar bio-reactor of suitability for industrialized production at present, multi-ply wood reactor for example, spinner bottle incubator, the plastics bag multiplier (-icator), the spiral membrane reactor, the tubular type helical reactors, the cellular reactor of ceramic rectangular channel, fluidized-bed reactor, hollow fiber reactor, film reactor, stirred reactor, airlift reactor and perfusion type reactor etc., its principle all is to improve as far as possible the dissolved oxygen that gas-to-liquid contact and gas-liquid exchange to increase nutrient solution, realizes fully mixing to satisfy cell to the demand of oxygen and nutritive substance with as far as possible little shearing force.Assign to from the growth forms of culturing cell, above-mentioned bio-reactor can be suspension culture formula and adherent culture formula two large classes.Suspension culture formula bio-reactor is mainly used in the suspension culture of non-adherent cell and the suspension culture of attached cell-microcarrier, so-called non-adherent type cell, namely be to need not to be attached to support surface can grow, comprise blood, lymphocyte, many tumour cells and some transformant.This class cell need to carry out suspension culture.The serum-free suspension culture is a kind of cell cultures mode that replaces animal serum with the known albumen of the people source of purifying or animal-origin or hormone, and it can reduce later stage purifying work, improves the quality of products, and becomes just gradually the trend that animal cell large-scale is cultivated.So-called adherent type cell then is to be attached to the cell that could grow with the support surface of an amount of electric charge, the most animals cell, and non-lymphocyte and many heteroploid cells all belong to this class.
Although various bio-reactors are in structure, the culturing cell type, transmission of power, scale, efficient, shearing force, Operating Complexity, have nothing in common with each other in the aspect such as crossed contamination and price, but can form mainly including of main product at home and abroad: the rolling bottle bio-reactor, magnetic agitation bio-reactor, NBS are the cage type bioreactor of representative, WAVE wave bio-reactor and AP rip current type bio-reactor etc.Wherein the rolling bottle reactor can carry out the attached cell cultivation, has advantages of that shearing force is little; The magnetic agitation reactor all can carry out suspension culture to non-adherent cell and attached cell-microcarrier, but the magnetic agitation shearing force is larger; No matter rolling bottle reactor or magnetic agitation reactor; all can only carry out the small-scale cell cultures or cultivate for mass-producing providing seed to amplify; labour intensity is large; efficient is low; can not mass-producing or perhaps mass production; just be difficult to quality control, there is cross-contamination issue in addition non-once use.The representative main flow bio-reactor that can carry out large-scale industrial production on the market mainly contains three kinds, the static Perfusion bioreactor of the one, NBS, and the 2nd, WAVE shakes the pocket type bio-reactor, and the 3rd, pacify general rip current type reactor.The static Perfusion bioreactor of NBS is to utilize the oxygenation of nutrient solution bubbling, the stirring arm agitation cycle, cell on the static diaphragm carrier that is grown in the cage is carried out perfusion type to be cultivated, has shearing force little and be suitable for extensive attached cell and cultivate, shortcoming is to be unsuitable for suspension culture, because the shearing force that stirs is crossed conference to the cell composition damage of suspension culture, and this device structure is complicated, also exist the operative technique difficulty large, expensive, the non-once use exists wasting time and energy of cleaning and sterilizing and cross-contamination issue.It is that cell cultures is cultivated in the soft bag of disposable plastic that WAVE shakes the pocket type bio-reactor, produces wave by shaking bag, makes cell suspension, nutrient solution mixes, gaseous interchange, its shearing force less is suitable for the suspension culture of non-adherent cell and microcarrier-attached cell.Its main drawback is: this product can not highdensityly be cultivated attached cell, it is reported, at least 10 times to 100 times are lower than the static perfusion type of picture and cultivate.To the cell of suspension culture, when small volume is cultivated, can not produce enough waves and make cell suspension, cell deposition at the bottom of bag, phase mutual friction in the process of shaking and damaging, when therefore amplifying on a small scale, often need to be by rolling bottle or magnetic agitation culturing bottle.Secondly, the WAVE culture bag of different model will be with the rocker that matches, and pouch section can use large rocker, and sack can not use little rocker, need to buy from the small-scale cultivation equipment of a series of costlinesses through being amplified to step by step large-scale industrial production.In addition, it is plastic soft bag that WAVE shakes bag, adds continuous a series of pipelines, operates also more complicated.Pacifying general rip current type reactor, to have a dissolved oxygen high; little and the disposable rip current type reaction bag of shearing force is without the advantage of crossed contamination; but only can be used for the static cultivation of mass-producing attached cell; the nutrient solution circulation that utilizes peristaltic pump to produce can not be used for the suspension culture of non-adherent cell, because can be pushed the cell of suspension culture repeatedly.This equipment is also expensive, and operation is also complicated.
Summary of the invention
The object of the present invention is to provide a kind of simple in structurely, easy to use, shearing force is little, it is good to mix ventilation effect, not only has been suitable on a small scale preparation but also can have realized the potential difference circulatory bio-reactor of suitability for industrialized production.
For achieving the above object, the present invention adopts following technical scheme: a kind of potential difference circulatory bio-reactor, this reactor comprises that the top of inner chamber is for holding air chamber, the bottom is the container body of liquid storage chamber, has the flank cavity structure of extending to the side in the adjoiner that holds air chamber and liquid storage chamber on the sidewall of this container body, the inner port of flank cavity structure is communicated with the inner chamber of container body, be communicated with on the external port of flank cavity structure and be provided with circulation tube, the lower port of circulation tube is communicated with the bottom of the inner chamber of container body, and in the pipeline of circulation tube or lower port place is provided with unidirectional venting valve.
The below that the epimere of described circulation tube extends to the external port place of flank cavity structure by the outer side wall place of container body and is close to flank cavity structure arranges.
Described unidirectional venting valve structure is plural bag-shaped flexible valve, and the sack of bag-shaped flexible valve is towards the inner chamber of container body, and the outer side correspondence of bag-shaped flexible valve is arranged on the inwall of circulation tube.
Described unidirectional venting valve structure is positioned at the lower port place of circulation tube, unidirectional venting valve structure is the limit diaphragm of the paddle type of coincideing with the lower port shape of circulation tube, the limit diaphragm folding is sticked on the lower port of circulation tube, and the lower port place of circulation tube has the diameter that is embedded limit diaphragm greater than the counterbore of the interior caliber of circulation tube.
String is provided with inside and is mounted with perfusion post for the diaphragm carrier that attaches cell on the described circulation tube.
The top of the inner chamber of described container body is that oval column, bottom are the semielliptical shape, and described flank cavity structure is two, lays respectively at the two ends of the major axis of container body.
Be provided with container cover on the upper end open of described appearance air chamber, the sidewall that holds air chamber is provided with ventilative window, is provided with the bacteriological filtration film on the ventilative window.
Sealing is provided with container cover on the upper end open of described appearance air chamber, hold be communicated with on the sidewall of air chamber be provided with the air inlet mouth of pipe, the mouth of pipe of giving vent to anger, the liquid in-out mouth of pipe and sampling nozzle, PH susceptor interface and DO susceptor interface.
Described flank cavity structure and circulation tube epimere can swing up and down with respect to container body.
The sidewall of described appearance air chamber has the elastic laminates section that can stretch up and down, and the sidewall that holds air chamber is provided with the swing arm that the other end is connected with the external end head of flank cavity structure in the top of telescopic section.
Has the flank cavity structure of extending to the side at appearance air chamber and liquid storage chamber's adjoiner on the sidewall of container body of the present invention, the inner port of flank cavity structure is communicated with the inner chamber of container body, the external port of flank cavity structure is connected with circulation tube, the lower port of circulating line is communicated with the bottom of the inner chamber of container body, and in the pipeline of circulation tube or the lower port place of circulation tube is provided with unidirectional venting valve.When any power wheel drive the present invention vacillates now to the left, now to the right, when perhaps driving flank cavity structure and swinging up and down, under the effect of unidirectional venting valve, can cause the liquid level height of formation in circulation tube epimere and the liquid storage chamber poor, namely the formation gravitional force of nutrient solution is poor in the nutrient solution in the circulation tube epimere and the liquid storage chamber, the poor gravitional force of saving of this gravitional force can promote nutrient solution and flow to container bottom through the bottom circulating line, and the nutrient solution that is in the liquid storage chamber bottom originally can upwards turn over from the bottom, cause nutrient solution iterative cycles between liquid storage chamber and circulating line, thereby realize sufficient gas-liquid exchange and efficiently nutrient solution mixing, this circulation is simply effective, mix ventilation effect good, circulation shear power is minimum, and it is good to mix ventilation effect, can suspension culture can staticly cultivate again, not only can be suitable on a small scale preparation but also can realize suitability for industrialized production.Hold air chamber and facing of liquid storage chamber meet the place because flank cavity structure of the present invention is positioned at, when practicality, the liquid level of nutrient solution can be in the middle part of flank cavity structure inner chamber, like this top aerification of flank cavity, and the bottom is full of nutrient solution, can increase the exchange area of gas.Further strengthen ventilation effect.
Unidirectional venting valve structure of the present invention is plural bag-shaped flexible valve, the sack of bag-shaped flexible valve is towards the port of lower opening, bag-shaped flexible valve is arranged on the inwall of circulating line by a side, drive reactor side rocking of the present invention in external force, perhaps drive in the process that flank cavity structure swings up and down, when flank cavity locations of structures reduces, nutrient solution can enter from the inner chamber of container body the inner chamber of flank cavity structure, then enter in the circulating line, and the nutrient solution that is positioned at the lower port inboard of the circulating line bottom the liquid storage chamber this moment is full of the flexible valve bag, bag-shaped flexible valve expands lower port is shut, when flank cavity locations of structures raise, nutrient solution pushed bag-shaped flexible valve in circulating line, and the liquid in the bag-shaped flexible valve is extruded, bag-shaped flexible valve smaller volume, nutrient solution will be discharged by lower opening, and this valve is biomimetic features, and unidirectional through-flow reliability is high, bag-shaped flexible flaps film body is flexible, and shearing force is minimum.
Be provided with container cover on the upper end open of container body of the present invention, the interval connection is provided with inlet mouth and air outlet on the sidewall of appearance air chamber, when the volume of culture vessel is larger, when the oxygen that nutrient solution only dissolves by gaseous interchange in culture vessel upper end ventilation mouth and the incubator can't be satisfied the demand, can be by inlet mouth oxygenation in the culture vessel, discharge the waste gas that organism produces by the air outlet simultaneously, can well guarantee the vegetative activity of organism.
String is provided with the perfusion post on the circulation tube of the present invention, attaches attached cell in the perfusion post, just can carry out static perfusion and cultivate, when carrying out suspension culture, the perfusion post removed and get final product, therefore the present invention both can carry out suspension culture, can carry out again static perfusion and cultivate, and subject range is extensive.
Description of drawings
Fig. 1 is the structural representation of the front view of the embodiment of the invention 1;
Fig. 2 is the left view of Fig. 1;
Fig. 3 is the vertical view of Fig. 1;
Fig. 4 is the structural representation behind the base of adding of the embodiment of the invention 1;
Fig. 5 is the stereographic map at a visual angle of bag-shaped flexible valve among Fig. 1;
Fig. 6 is the structural representation of bag-shaped flexible valve among Fig. 1;
Fig. 7 is the fundamental diagram of bag-shaped flexible valve among Fig. 1;
Fig. 8 is the another kind of form of the unidirectional venting valve structure of the embodiment of the invention 1;
Fig. 9 is the fundamental diagram of another kind of form of the unidirectional venting valve structure of the embodiment of the invention 1;
Figure 10 is the structural representation of the front view of the embodiment of the invention 2;
Figure 11 is the structural representation of the front view of the embodiment of the invention 3;
Figure 12 is the structural representation of the front view of the embodiment of the invention 4.
Embodiment
A kind of embodiment 1 of potential difference circulatory bio-reactor, in Fig. 1 ~ 7, this reactor comprises container body, and the inner chamber of container body is divided into up and down two portions, and top is liquid storage chamber 2 for appearance air chamber 1, bottom.Have two flank cavity structures 4 of extending to both sides on the sidewall of container body, flank cavity structure 4 is positioned at the adjoiner that holds air chamber and liquid storage chamber, flank cavity structure 4 has inside and outside two ports, the inner port of flank cavity structure 4 is communicated with the inner chamber of container body, the external port of flank cavity structure 4 is communicated with the upper port of circulation tube 5, the below that the epimere of circulation tube 5 is close to flank cavity structure 4 arranges, the upper end of circulation tube 5 is extended to the external port place of flank cavity structure 4 by the side-walls of container body, the external port of flank cavity structure 4 is divided a word with a hyphen at the end of a line with the upper port of circulation tube 5 and is communicated with.The interlude of circulation tube 5 and hypomere move down along the outer side wall of container body, and the lower port of circulation tube 5 is communicated with the bottom of the inner chamber of container body.The inboard that the lower port place of circulation tube 5 is provided with is provided with bag-shaped flexible valve 7, bag-shaped flexible flaps is three, the sack of bag-shaped flexible valve 7 is towards the inner chamber of container body, the bag top is towards the inside of circulation tube 5, three bag-shaped flexible valve 7 are distributed on the lower port place of circulation tube 5 and with the lower port of circulation tube 5 obturages, the outer side that bag-shaped flexible valve 7 is adjacent with the tube wall of circulation tube 5 is fixedly installed on the tube wall of circulation tube 5, bag-shaped flexible valve is biomimetic features, copy the endovascular valve designs of organism, bag-shaped flexible valve can be semi-moon shaped pocket-like, also can be the pocket-like of semielliptical shape.Fig. 7 is the one-way flow schematic diagram of bag-shaped flexible valve, when liquid stream flows to sack by the bag top, liquid in the bag-shaped flexible valve will be extruded, each bag-shaped flexible valve is pressed against the tube wall place of circulation tube 5, and liquid stream is flow through by the center of circulation tube, when liquid stream is backflowed when pushing up to bag by sack, to be full of liquid in the bag-shaped flexible valve, liquid is large with bag-shaped flexible valve support, and each bag-shaped flexible valve 7 is sealed up the lower port of circulation tube 5, thereby realizes the purpose of one-way flow.
The below of container body is provided with base 17, base 17 is flat, the length direction of base 17 is consistent with the direction of extension of flank cavity structure 4, both sides at the width of base 17 are provided with support 16, the lower end of support 16 is fixed on the base 17, the upper end of support 16 is hinged on by rotational pin 15 on the sidewall of container body, and like this, container body can rotate with respect to base.When the needs container body swings with base 17, rotational pin 15 can be fixed on the support 16, also rotational pin and container body are fixed simultaneously, stop container body to rotate with respect to base.
Unidirectional venting valve structure in the present embodiment is bag-shaped flexible valve, unidirectional venting valve also can adopt structure as shown in Figure 8, in Fig. 8, the be sticked limit diaphragm 13 of paddle type of the outside of the lower port of circulation tube 5, the outer rim of limit diaphragm 13 is greater than the internal diameter of the lower port of circulation tube 5, the lower port place of circulation tube 5 has diameter greater than the counterbore of the interior caliber of circulation tube 5, limit diaphragm 13 is embedded in this counterbore, this counterbore can be arranged on the end face of lower port of circulation tube 5, also can be arranged on the chamber wall of inner chamber of container body.Fig. 9 is limit diaphragm 13 one-way flow schematic diagrams, when in liquid flows by the lateral of circulation tube, flowing, the pressure of liquid stream can be pressed on limit diaphragm 13 on the bottom surface of counterbore at lower port place of circulation tube 5, closing of the lower port of realization circulation tube, when liquid stream is outwards flowed by the inboard of circulation tube, liquid fails to be convened for lack of a quorum and presses off the limit diaphragm 13 that is sticked on the lower port of circulation tube 5, the opening of the lower port of circulation tube, and liquid stream passes through smoothly.
Hold as the improvement of the present embodiment that sealing is provided with container cover 6 on the upper end open of air chamber 1, hold be communicated with on the sidewall of air chamber 1 be provided with the air inlet mouth of pipe 9, the mouth of pipe 10 of giving vent to anger, the feed liquor mouth of pipe 8 and the fluid mouth of pipe 3, PH susceptor interface 11 and DO susceptor interface 12, and sampling nozzle 14.The air inlet mouth of pipe 9, the mouth of pipe 10 of giving vent to anger, the feed liquor mouth of pipe 8 and the fluid mouth of pipe 3, PH susceptor interface 11 and DO susceptor interface 12 and and sampling nozzle 14 all with hold air chamber 1 and be communicated with.
A kind of embodiment 2 of potential difference circulatory bio-reactor, in Figure 10, the difference of the present embodiment and embodiment 1 is: the pars intermedia bit string of the circulation tube 5 in the present embodiment is provided with perfusion post 20, perfusion post 20 is stylostome, the inside of perfusion post 20 is mounted with the diaphragm carrier, and the diaphragm carrier is used for attaching for cell.The perfusion post is existing a kind of structure of cultivating attached cell.Other structure of potential difference circulatory bio-reactor in the present embodiment is the same with embodiment 1 corresponding construction.
A kind of embodiment 3 of potential difference circulatory bio-reactor, in Figure 11, the difference of the present embodiment and embodiment 1 is: be installed with perfusion post 19 in the present embodiment in the inner chamber of container body, the cavity that perfusion post 19 coincide for the inner chamber for profile and container body, reprint the inside of perfusion post 19 the diaphragm carrier, and the diaphragm carrier is used for attaching for cell.The perfusion post is existing a kind of structure of cultivating attached cell.Other structures of potential difference circulatory bio-reactor in the present embodiment are the same with embodiment 1 corresponding construction.
A kind of embodiment 4 of potential difference circulatory bio-reactor, in Figure 12, the difference of the present embodiment and embodiment 1 is: have the elastic laminates section 23 that an end can stretch up and down on the sidewall of the appearance air chamber 1 of the present embodiment, one end of swing arm 22 is hinged to be arranged on the sidewall that holds air chamber 1, swing arm 22 is positioned at the top of elastic laminates section 23 at appearance air chamber 1 sidewall upper link point, the other end of swing arm 22 is hinged to be arranged on the external end head of flank cavity structure 4, flank cavity structure 4 is flexible materials with the junction of container body, and flank cavity structure 4 can swing with respect to container body.Other structures of potential difference circulatory bio-reactor in the present embodiment are the same with embodiment 1 corresponding construction.Be hinged setting between the swing arm of the present embodiment and container body and the flank cavity configuration, when container body and flank cavity configuration are softer silica gel, when latex glue material or plastics were made, swing arm and container chamber and flank cavity structure also can directly be fixed.Swing arm in the present embodiment also can replace with lifting silk.
Flank cavity configuration and circulation tube among the above embodiment are integrated setting, turn back at the external port place of flank cavity configuration, and the section of turning back is the epimere of circulation tube.
The top of the inner chamber of container body is that oval column, bottom are the semielliptical shape among the above embodiment, and two flank cavity structures lay respectively at the two ends of the major axis of container body.
Be provided with the air inlet mouth of pipe on the appearance gas chamber sidewall among the above embodiment, the mouth of pipe of giving vent to anger, the feed liquor mouth of pipe, the fluid mouth of pipe and sampling nozzle, PH susceptor interface and DO(oxygen dissolved) the susceptor interface, when the small volume of container body, need to these mouthfuls be set at the sidewall that holds air chamber.At this moment only at the sidewall that holds air chamber ventilative window is set, now takes a breath by the transom cause for gossip, in order to prevent the nutrient solution in the extraneous bacterial contamination container body inner chamber, can the bacteriological filtration film be set at ventilative window.
Packed flexible valve among the above embodiment is arranged on the lower port place of circulation tube, also packed flexible valve can be arranged in the tube chamber of circulation tube.
Packed flexible valve among the above embodiment can be wholely set on circulation tube.
Flank cavity structure among the above embodiment can be arranged to oblate shape, and the epimere of corresponding circulation tube is positioned at the oblate shape that flank cavity structural shape adapts to.
The bag-shaped flexible valve of above embodiment is two, also can be for more.
The below that the epimere of the circulation tube among the above embodiment is close to flank cavity structure arranges, and the below that also can not be close to flank cavity structure arranges, and circulation tube has the external port place of flank cavity structure directly to hang down.
The chamber face of the liquid storage chamber of the container body of above embodiment and circulating line is smooth arc line shaped and smooth surface, when flowing, nutrient solution produces as far as possible little shearing force, the unidirectional venting valve of bag-shaped flexibility of bionical thing cardiovascular valve has been proved to be the shearing force that the blood circulation cell is had minimum; The shearing force that the circulation that promotes by gravitional force produces stirs more than mechanicalness, and wave mixes, and the shearing force that the peristaltic pump circulation produces is little.
Be a kind of potential difference circulatory bio-reactor that utilizes gravitional force to promote the nutrient solution circulation among the above embodiment, this reactor is from bionic angle design.
During the work of potential difference circulatory bio-reactor in above embodiment, the flank cavity structure that can swing or drive reactor by various power wheel drive reactors swings with respect to container body together with the epimere of circulation tube.When the epimere that drives flank cavity structure and circulation tube swings, can adopt the outer end of the piston head pressure flank cavity structure of hydro-cylinder, make it upwards put and make its bottom under action of gravitation, with flank cavity structure outer section of living directly is fixed on the piston rod of hydro-cylinder, allow piston rod in the process that moves up and down, drive flank cavity structure and swing up and down together with the epimere of circulation tube, form the potential difference that drives the circulation of liquid stream.Also can arrange at container body and fix driving gear, driving gear and transmitting gear engagement, transmitting gear is by electric motor driving, and motor drives container body by rotating and swings.Can also be on container body the fixing horizontal lever, drive horizontal lever and swing, realize the swing of container body.
Life science is told us, from the lower animal to the mankind, from animalcule to huge elephant, the terricole dinosaur that body weight is 130 tons, the whale that surpasses 200 tons of weights, none does not provide oxygen and nutritive substance by circulation for body, and therefore, circulation provides the exchange efficiency of oxygen and nutritive substance to want high more than mixing.Animal is realized circulation, and by the power-driven pump of this shearing force minimum of heart, and the most critical structure of formation way flow is the minimum cardiovascular valve of shearing force.The activity of animal hearts and cardiovascular valve to all the time all not have to damage in circulation and to the highstrung red corpuscle of shearing force, show that its shearing force is minimum, and the artificial mechanical valve prosthesis's of heart (wear-resisting reach 100 years) successful clinical application, it is feasible that enlightenment utilizes the artificial mechanical valve prosthesis to research and develop recycling trioreactor as the way flow valve of bio-reactor, utilize run by gravity for impellent also more than the stirring arm of using with present bio-reactor, the shearing force that wave and peristaltic pump produce is much smaller.
Claims (10)
1. potential difference circulatory bio-reactor, it is characterized in that: this reactor comprises that the top of inner chamber is the container body of liquid storage chamber for appearance air chamber, bottom, has the flank cavity structure of extending to the side in the adjoiner that holds air chamber and liquid storage chamber on the sidewall of this container body, the inner port of flank cavity structure is communicated with the inner chamber of container body, be communicated with on the external port of flank cavity structure and be provided with circulation tube, the lower port of circulation tube is communicated with the bottom of the inner chamber of container body, and in the pipeline of circulation tube or lower port place is provided with unidirectional venting valve.
2. potential difference circulatory bio-reactor according to claim 1 is characterized in that: the below that the epimere of described circulation tube extends to the external port place of flank cavity structure by the outer side wall place of container body and is close to flank cavity structure arranges.
3. potential difference circulatory bio-reactor according to claim 1, it is characterized in that: described unidirectional venting valve structure is plural bag-shaped flexible valve, the sack of bag-shaped flexible valve is towards the inner chamber of container body, and the outer side correspondence of bag-shaped flexible valve is arranged on the inwall of circulation tube.
4. potential difference circulatory bio-reactor according to claim 1, it is characterized in that: described unidirectional venting valve structure is positioned at the lower port place of circulation tube, unidirectional venting valve structure is the limit diaphragm of the paddle type of coincideing with the lower port shape of circulation tube, the limit diaphragm folding is sticked on the lower port of circulation tube, and the lower port place of circulation tube has the diameter that is embedded limit diaphragm greater than the counterbore of the interior caliber of circulation tube.
5. the described potential difference circulatory bio-reactor of any one claim according to claim 1-4 is characterized in that: string is provided with inside and is mounted with perfusion post for the diaphragm carrier that attaches cell on the described circulation tube.
6. potential difference circulatory bio-reactor according to claim 1, it is characterized in that: the top of the inner chamber of described container body is that oval column, bottom are the semielliptical shape, and described flank cavity structure is two, lays respectively at the two ends of the major axis of container body.
7. potential difference circulatory bio-reactor according to claim 1 is characterized in that: be provided with container cover on the upper end open of described appearance air chamber, the sidewall that holds air chamber is provided with ventilative window, is provided with the bacteriological filtration film on the ventilative window.
8. potential difference circulatory bio-reactor according to claim 1, it is characterized in that: sealing is provided with container cover on the upper end open of described appearance air chamber, hold be communicated with on the sidewall of air chamber be provided with the air inlet mouth of pipe, the mouth of pipe of giving vent to anger, the liquid in-out mouth of pipe and sampling nozzle, PH susceptor interface and DO susceptor interface.
9. potential difference circulatory bio-reactor according to claim 1, it is characterized in that: described flank cavity structure and circulation tube epimere can swing up and down with respect to container body.
10. potential difference circulatory bio-reactor according to claim 9, it is characterized in that: the sidewall of described appearance air chamber has the elastic laminates section that can stretch up and down, and the sidewall that holds air chamber is provided with the swing arm that the other end is connected with the external end head of flank cavity structure in the top of telescopic section.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110002842 CN102154100B (en) | 2011-01-07 | 2011-01-07 | Potential difference circulating bioreactor |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110002842 CN102154100B (en) | 2011-01-07 | 2011-01-07 | Potential difference circulating bioreactor |
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| Publication Number | Publication Date |
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| CN102154100A CN102154100A (en) | 2011-08-17 |
| CN102154100B true CN102154100B (en) | 2013-04-10 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110002842 Expired - Fee Related CN102154100B (en) | 2011-01-07 | 2011-01-07 | Potential difference circulating bioreactor |
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| CN (1) | CN102154100B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102787072B (en) * | 2012-04-28 | 2014-05-21 | 郑州威瑞生物技术有限公司 | Soft membrane bioreactor |
| CN103911285B (en) * | 2014-03-08 | 2017-03-22 | 郑州威瑞生物技术有限公司 | Disposable bioreactor |
| CN109270282A (en) * | 2018-09-27 | 2019-01-25 | 重庆微浪生物科技有限公司 | Miniflow liquid changing device and change liquid method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63202371A (en) * | 1987-02-18 | 1988-08-22 | Mitsui Petrochem Ind Ltd | Spin culture apparatus |
| CN101831385B (en) * | 2010-04-27 | 2013-08-28 | 惠识瑶 | Jar external circulatory packed bed type cell reactor and method for cultivating animal cell |
| CN101812405B (en) * | 2010-04-30 | 2013-05-22 | 惠倪 | Polygonal plastic bag swing cell reactor and method for culturing animal cells |
| CN201971839U (en) * | 2011-01-07 | 2011-09-14 | 郑州威瑞生物技术有限公司 | Potential difference circulatory bioreactor |
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| CN102154100A (en) | 2011-08-17 |
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