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CN102787072A - Soft membrane bioreactor - Google Patents

Soft membrane bioreactor Download PDF

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Publication number
CN102787072A
CN102787072A CN2012102496534A CN201210249653A CN102787072A CN 102787072 A CN102787072 A CN 102787072A CN 2012102496534 A CN2012102496534 A CN 2012102496534A CN 201210249653 A CN201210249653 A CN 201210249653A CN 102787072 A CN102787072 A CN 102787072A
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mantle
container
bio
reactor
mantle container
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CN2012102496534A
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CN102787072B (en
Inventor
韩志强
刘慧涛
童胜
孙向东
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ZHENGZHOU VIRI BIOTECHNOLOGY CO Ltd
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ZHENGZHOU VIRI BIOTECHNOLOGY CO Ltd
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/02Form or structure of the vessel
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/26Constructional details, e.g. recesses, hinges flexible
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/38Caps; Covers; Plugs; Pouring means
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M29/00Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/20Degassing; Venting; Bubble traps

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  • Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Sustainable Development (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Clinical Laboratory Science (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

The invention relates to the bioreactor field, and especially relates to a soft membrane bioreactor. The reactor comprises a closed soft membrane container; the soft membrane container comprises a base and above three side walls; the base is a flat base; there is an angle of 5-90DEG C between the internal wall surface of each of the side walls and the base; a corner is formed at the connection position of two adjacent side walls; the soft membrane container is provided with at least one internally-and-externally-permeable communication port; and the lower opening edge of the communication port is positioned on the surface of a culture solution injected to the soft membrane container in use. The soft membrane container of the soft membrane bioreactor self-maintains an internal three-dimensional space structure like a hard container without blasting, the soft membrane bioreactor can be arranged in a present culture case and/or a mixed drive device, such as a track shaking bed, an incline rotation device or a swing drive device, during use to carry out mixed drive, and the solution in the reactor generates a solution flow in a wave or vortex manner, so the full mixing and the efficient gas exchange are realized.

Description

A kind of mantle bio-reactor
Technical field
The present invention relates to the bio-reactor field; Particularly a kind of mantle bio-reactor; 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 mikrobe, insect cell and vegetable cell and the production of biological technology products thereof.
Background technology
Bio-reactor (Bioreactor) is to be used to realize biochemical reaction process, particularly can control culture condition to produce the container of best biologics, comprises enzyme reactor, fixed cell reactor drum, various cell culture apparatus and fermentor tank etc.Bio-reactor can be used for the vitro culture of bacterium, fungi, insect cell, mammalian cell and vegetable cell and other viable cell; With the cellular transplantation therapy that carries out life science, clinical disease and the production of biological technology products; The meta-bolites that organism produced, antibody, albumen, virus, polysaccharide, the DNA that comprise cultivation; Cellular component, and cell derivative etc.Whether needs are attached to biological cell is divided into two types on the upholder according to its vitro culture growth pattern, need be attached to the attached cell (for example most of zooblasts of vitro culture) that grows on the upholder and need not be attached to the non-adherent cell of growing on the upholder (for example mikrobe with come autoblood, spleen and marrow cultured cells and some cancer cells).From the training method of cell, comprise two kinds of state type cultivation and floated cultivations.State type cultured cells incubator comprises the Tissue Culture Flask and the perfusions cultivation formula bio-reactors such as tubular fibre and packed bed of the static cultivation usefulness in common plane.Comprise various biological cell vitro culture at present with in the culture vessel, most widely used is static cultured cells culturing bottle in plane and suspension culture formula bio-reactor.Suspension culture formula bio-reactor is widely used in the suspension culture of mikrobe and non-adherent cell and attached cell is carried out microcarrier suspension culture.Because the effect of gravity; Biological cell; The zooblast that particularly volume is bigger has and under static state is tending towards sedimentary characteristic, and suspension culture formula bio-reactor need keep the biological cell suspended state growth down of cultivating, and just must mix fully.Therefore, the major function of suspension culture formula bio-reactor be exactly under the condition of alap shearing force, produce mix fully so that cultured cells keep suspended state and obtain abundant nutrition and suitable oxygen divides and the gas exchange efficiency that improves liquid-vapo(u)r interface to increase dissolved oxygen.
The static cultured cells culturing bottle in existing plane and most of suspension culture formula bio-reactor are the container of mechanically resistant material; Comprise the animal cell culture bottle that generally uses in the laboratory, Erlenmeyer flask that microorganism culturing and animal cell culture are used and industrially scalable biological products are produced employed stirring type bioreactor and airlift bioreactor etc.The common defective that the bio-reactor of mechanically resistant material exists is high with production requirement to the structure design of reactor drum, and transportation and preservation take up space greatly, disposable use cost height or be inappropriate for disposable use etc.Because the bio-reactor of mechanically resistant material does not have resiliency to liquid flow impact; Flow knock-on reaction device interior wall construction or interior arrangement that the suspendible nutrient solution is produced all can produce shearing force; Thereby cause the cell responsive to shearing force, the for example damage of zooblast even cause necrocytosis is therefore to the reactor wall structure; The stirring rake of stirring type bioreactor, the design of aspects such as the gas tip of airlift reactor and drainage tube and defoaming device and production requirement are high.In addition, the bioreactor construction of mechanically resistant material is also complicated, and price is more expensive, reuses also to exist and cleans, the problem that aspect time and effort consumings such as steam sterilizing and checking are high with cost.
Compare with the bio-reactor of mechanically resistant material, the bio-reactor of plastics soft film material has with low cost, and preparation easily possesses unreactiveness and nutrient solution does not react; Good sealing property and barrier property, waterproof and airtight, physical strength stretch-proof and resistance to bend(ing); After giving sterilization and checking and reaching GMP and require, the program that can remove user's authentication from can be saved manpower; Time, cost of investment and operation cost reduce advantages such as environmental pollution and discharging.Therefore engender the bio-reactor of soft film material in recent years, what for example U.S. WAVE produced waves-the soft bag of wave bio-reactor (USP 6,544,788).Existing soft bag bio-reactor is mainly the two-dimentional soft bag bio-reactor of the pillow-like that two-layer mantle forms through peripheral fusion, and two dimension soft bag bio-reactor is not owing to self have supporting structure, and needing inflation just can make soft bag expansion and keep its top is the spatiality of liquid for the gas bottom; The soft bag of two dimension bio-reactor is prone to form gauffer after injecting nutrient solution; Thereby produce bigger shearing force and damaging cells, therefore need appropriate support and tractive, yet; Support and tractive also can cause soft bag distortion and gauffer improperly; And tractive is tight more, and soft bag elasticity is low more, and the volume of receiving fluids is more little; The volume of the soft bag of two dimension bio-reactor is low with the ratio of mantle area far beyond having three-dimensional three-dimensional mantle bio-reactor, take up space during use greatly and service efficiency low.In addition; The soft bag of pillow shape of two dimension is not had a space structure of three dimensional container; Be inconvenient to operate, add that the turnover feed channel of band filter membrane well heater and special gas-liquid perfusion equipment are inappropriate for small-scale cell cultures, also are difficult to utilize existing incubator and culture device to cultivate.
Based on above-mentioned existing plane static cultivation formula culturing bottle and suspension culture formula bio-reactor respectively at structural complexity; The accessibility of operation; Cost cost and disposable use; Therefore the different shortcoming and defect that aspects such as mixing process generation shearing force exist respectively needs research and development and produces the new-type bioreactor of the shortcoming and defect that can overcome above-mentioned existing bio-reactor existence.
Summary of the invention
The object of the present invention is to provide a kind of easy to use, with low cost, non-invasi to mix, shearing force is low, both be suitable for adherent static cultivation, is suitable for the disposable mantle bio-reactor of suspension culture and existing culture device capable of using again.
In order to address the above problem; Mantle bio-reactor of the present invention adopts following technical scheme: the mantle bio-reactor; Comprise airtight mantle container, said mantle container comprises the end and the sidewall more than three, and the said end is flat; The inner-wall surface of each sidewall and have 5 ~ 90 ° angle at the end; Form the turning in the junction of the two between the adjacent two side, the mantle container is provided with penetrating connected entrance inside and outside at least one, and the end opening of said connected entrance is along on the liquid level that is arranged in the nutrient solution that injects the mantle container when using.
Said mantle container is connected with pipe through its connected entrance, said pipe and mantle container be fixed together and the two between be sealed and matched, pipe is equipped with the spiral cover of mechanical seal or the spiral cover of the ventilative filter membrane of end face band away from the threaded one end of mantle container.
The end of said mantle container and sidewall are made up of a mantle, and the inner-wall surface of the sidewall of mantle container and the angle at the end are folded to form by mantle, and the junction of adjacent two side between the two merged by hot pressing and be sealed and matched.
Said mantle container is fixed with the escape pipe that at least one inlet pipe and the inner chamber through the mantle container are communicated with said inlet pipe, saidly all is communicated with the inner chamber of mantle container with mantle container sealing cooperation and the corresponding connected entrance that passes through on the mantle container respectively into and out of tracheae.
The PH transmitter and being used for that the mantle container is provided with the normally closed catheter that injects for liquid or emit, be used for monitoring the potential of hydrogen of the nutrient solution that injects the mantle container when using is monitored the DO transmitter of the oxygen dissolved of the nutrient solution that injects the mantle container when using; It is different that said catheter, PH transmitter and DO transmitter lay respectively at common intersection and three's the position at adjacent two side and the end, and catheter, PH transmitter and DO transmitter all cooperate with the mantle container sealing.
Merged and form the fusion edge that extends to the mantle external container by hot pressing between the adjacent two side of mantle container and/or between the end and the sidewall, said fusion edge is for being merged the nexus that the back forms by two-layer mantle by hot pressing.
Said mantle container is pyramid or frusta-pyramidal, and the end of mantle container forms the end of pyramid or truncated pyramid, and the sidewall of mantle container forms the side of pyramid or truncated pyramid.Said mantle bio-reactor also comprises being used to cover and is located on the said mantle container isolating cap that receives outside contamination with the nutrient solution that prevents the mantle internal tank; Said isolating cap covers the connected entrance of mantle container when covering the mantle container; When said isolating cap when covering the mantle container, inner wall surface thereof has ventilative gap with being communicated with between the mouth of pipe.
One of them sidewall of said isolating cap is provided with the ventilation window, and sealing is merged on the ventilation window has ventilative bacteriological filtration film, and when isolating cap covered the mantle container, ventilative bacteriological filtration film covered the connected entrance of mantle container.
Said mantle container is the triangular prism shaped of body of one who has dropped dead by the roadside placement.
Because what mantle bio-reactor of the present invention adopted is the mantle container, therefore with low cost, and soft film material; Particularly the plastics mantle has good elasticity; Can cushion the impact of flow front to the sidewall of mantle container, the elastical retraction power that the elasticity of mantle produces can make flow produce wave and strengthen dissolved oxygen and mixed effect, in conjunction with the existence at the turning between the inner-wall surface of sidewall and the angle at the end and the adjacent sidewall; When the sidewall of liquid flow impact mantle container; Angle and turning provide the expansion space and produce surge capability and the elastical retraction power to liquid, thereby under its elastical retraction power effect, make liquid produce wave, during use; The nutrient solution that injects the mantle container produces liquid-flow in mixing process; When flow rushed at said angle and corner location, it is big that the angle at the turning between sidewall and the angle at the end and sidewall and the sidewall becomes automatically under the effect of flow, thereby to the mobile buffering that compensates of flow; And then reduced shearing force and impact that Object of Development receives at this place, prevent because of receiving shearing force or impact damages; In addition; The mantle container has the end and the sidewall more than three, the inner-wall surface of each sidewall and have 5 ~ 90 ° angle at the end, and the adjoiner at the two between the adjacent two side forms the turning; Principle according to trilateral stability; The turning that forms between the adjacent two side constitutes the three-dimensional basis of mantle internal tank, can prevent collapsing of sidewall effectively, and its principle is as building a wall; When two adjacent between the walls have a turning; Just can form mutual support between the two, be not easy to collapse, the adjacent two side of the mantle container of mantle bio-reactor of the present invention just is equivalent to two walls that the process of building a wall forms the turning; Thereby make the mantle container not need air-blowing just can lean on and self keep inner three-D space structure as rigid container; Use the time image rigid container equally convenient, can mantle bio-reactor of the present invention be contained in existing incubator and/or hybrid drive, for example track shaking table, plane revolving gear, space revolving gear, inclination swivel arrangement or yaw drive etc. are carried out combination drive; The interior liquid of reactor drum produces the liquid-flow of wave or eddy current form, thereby realizes mixing and gaseous interchange fully efficiently.Certainly, when using large-scale mantle bio-reactor of the present invention to surpass existing commercialization incubator big or small, can through with supporting large-scale thermostat container or thermostatic chamber and with it the hybrid drive that adapts to of size cooperate and realize.
Further; Be connected with the pipe that is communicated with connected entrance on the said mantle container; Be installed with spiral cover through screw thread on pipe, pipe is the door that injects the biologics of nutrient solution and culturing cell and results cultivation, also is the passage of realizing the inside and outside gaseous interchange of mantle container chamber.Spiral cover can prevent the pollution of bacterium and the dust in the external environment etc., and in the working process, the available mode that unscrews spiral cover realizes mantle container and extraneous gaseous interchange through the gap of spiral cover and the combination section between pipe; When use side is worn the spiral cover of ventilative filter membrane, can spiral cover be screwed, gas is realized mantle container and extraneous gaseous interchange through the ventilative filter membrane of spiral cover end face; Said fusion edge is set between the adjacent two side of mantle container; Except that having supporting role; Also, can cooperate tractive mantle container, even be contained in during very big or use at the mantle volume of a container under the very big situation of the impact of the nutrient solution oppose side wall in the mantle container through the tractive fixed sturcture corresponding with merging edge as the fixing tractive structure of mantle container of external force tractive; Also can guarantee to maintain in the mantle container three-dimensional space always, can not collapse because of reactor drum is excessive; Because merging edge is to be positioned at the three-dimensional outside that the mantle container surrounds; Be its cavity that does not directly surround the mantle container, so the fusion edge of each wall both sides of straight line tractive mantle container, neither can cause the mantle container to produce fold; The volume that also can be as the soft bag of two dimension dwindle the mantle container because of tractive; When at the sidewall of mantle container with when said fusion edge is set at the end, can the mantle container be fixed on corresponding position through fixing said fusion edge, to guarantee its steady operation; The end of mantle container and sidewall are made up of a mantle; And sidewall and the transition structure at the end are for turning down structure but not other fit structure; Utilized the slipperiness of mantle nature to form the corner of smooth transition, the slickness that mode such as reduced further that mantle hot pressing is merged or bonding causes reduces the shearing force of being brought; When the volume of mantle bio-reactor of the present invention is big; Can be through said inlet pipe artificial initiatively air feed in the mantle container; To satisfy the demand of the required oxygen of reaction; Through the gas after air outlet discharge and the nutrient solution gaseous interchange; Owing to all cooperate with the mantle container sealing and is communicated with the inner chamber of mantle container through the corresponding connected entrance on the mantle container respectively into and out of tracheae, and on the liquid level of the end opening of connected entrance nutrient solution of injection mantle container when being arranged in use, one side prevents nutrient solution inflow pipe and spills; Can prevent on the other hand that the gas that charges into is contained in the nutrient solution in the mantle container in use forms bubble, avoids producing the death that shearing force causes culturing cell because of bubble breaks; When using mantle bio-reactor of the present invention to carry out large scale culturing, can in the mantle container, add nutrient solution through catheter, or obtain appearance through catheter in the mantle container and analyze and gather in the crops cultured cells and biologics.Certainly this catheter is normally closed pipe, has only when needed and just opens, and PH transmitter and DO transmitter can be used for monitoring in real time the state of reaction solution, so that adjustment in time guarantees the optimum response state; Small-sized bio-reactor is suitable for cultivating on a small scale and process exploitation; When cell cultures; Often need carry out microscopically observation of cell growth conditions; Therefore the present invention all links together the upper end of each sidewall of mantle container and is sealed and matched with roof with a roof, parallel to each other at the end of roof and mantle container, observes thereby make mantle bio-reactor of the present invention to be convenient to microscopically as the Tissue Culture Flask of hard; At the end of mantle container and the intersection of sidewall described fusion edge is set; Just can the mantle container be securely fixed on the permanent seat with transparent seat board through merging edge during use; Can use as traditional Tissue Culture Flask is convenient; Attached cell is taked static cultivation, cell directly adherent growth on the mantle of mantle container bottoms; The end of mantle container and sidewall constitute pyramid jointly or frusta-pyramidal then makes the end of mantle container and the intersection of sidewall all form along linearly extended transition interface; Owing to very easily cause the gauffer of mantle along the transition interface of curve form; Therefore adopt along linearly extended transition interface and reduced the formation of gauffer to greatest extent, thereby further reduced the structure that can form shearing force; The mantle container adopts and is the triangular prism shaped space that makes full use of in the mantle container that body of one who has dropped dead by the roadside is placed; More convenient and the further cost that reduced is made and used to isolating cap with respect to pipe and spiral cover.
When using mantle bio-reactor of the present invention that non-adherent cell or mikrobe are cultivated, very simple, directly non-adherent cell or mikrobe are put into the mantle container and carry out suspension culture and get final product; When using mantle bio-reactor of the present invention that attached cell is cultivated; Both can be as common Tissue Culture Flask; Attached cell directly is attached on the mantle of bottom surface and carries out static cultivation, also can attached cell be attached to and carry out suspension culture on the microcarrier, attached cell directly is attached to carries out static cultivation on the mantle of bottom surface and be mostly small-scale cultivation; Make things convenient for microscopically to observe, be mostly large-scale cultivation and attached cell is attached to the suspension culture of carrying out on the microcarrier.Microcarrier is small bead; Under admixture, can be suspended among the nutrient solution; Cell is attached to the surface growth of bead; So just become the stereo suspending that is attached on the microballoon to the attached cell subsides by the static cultivation in the plane that is attached to the Tissue Culture Flask bottom interior surface and cultivated, improved culture efficiency greatly, very be fit to when the cultivation of attached cell being carried out extensive or suitability for industrialized production.
Description of drawings
Fig. 1 is the structural representation of the embodiment 1 of mantle bio-reactor of the present invention;
Fig. 2 is the stretch-out view of the embodiment 1 of mantle bio-reactor of the present invention;
Fig. 3 is the structural representation (the band annular heat merges circle) of the pipe among Fig. 1;
Fig. 4 is the structural representation of the spiral cover among Fig. 1;
Fig. 5 is the user mode synoptic diagram that the embodiment 1 of mantle bio-reactor of the present invention injects nutrient solution;
Fig. 6 is the structural representation of support cages of the embodiment 1 of mantle bio-reactor of the present invention;
Fig. 7 be the embodiment 1 of mantle bio-reactor of the present invention in when work the mixing principle synoptic diagram to nutrient solution;
Fig. 8 is the structural representation of the embodiment 2 of mantle bio-reactor of the present invention;
Fig. 9 is the structural representation of the air-permeable spiral cover of the ventilative filter membrane of band among Fig. 8;
Figure 10 is the structural representation of the embodiment 3 of mantle bio-reactor of the present invention;
Figure 11 is the exploded view of the embodiment 3 of mantle bio-reactor of the present invention;
Figure 12 is the structural representation of the embodiment 4 of mantle bio-reactor of the present invention;
Figure 13 is the structural representation of the embodiment 5 of mantle bio-reactor of the present invention;
Figure 14 is the exploded view of the embodiment 5 of mantle bio-reactor of the present invention;
Figure 15 is the structural representation of the embodiment 6 of mantle bio-reactor of the present invention;
Figure 16 is the structural representation of the embodiment 7 of mantle bio-reactor of the present invention;
Figure 17 is the stretch-out view of the embodiment 7 of mantle bio-reactor of the present invention;
Figure 18 is the structural representation of the embodiment 8 of mantle bio-reactor of the present invention;
Figure 19 is the structural representation of the embodiment 9 of mantle bio-reactor of the present invention;
Figure 20 is the structural representation of the embodiment 10 of mantle bio-reactor of the present invention;
Figure 21 is the structural representation of the embodiment 11 of mantle bio-reactor of the present invention;
Figure 22 is the structural representation of the embodiment 12 of mantle bio-reactor of the present invention;
Figure 23 is the fusion synoptic diagram of the embodiment 13 of mantle bio-reactor of the present invention;
Figure 24 is the structural representation of the embodiment 14 of mantle bio-reactor of the present invention;
Figure 25 is the exploded view of the embodiment 14 of mantle bio-reactor of the present invention;
Figure 26 is the structural representation of mantle container of the embodiment 15 of mantle bio-reactor of the present invention;
Figure 27 is the structural representation of permanent seat of the embodiment 15 of mantle bio-reactor of the present invention;
Figure 28 is the synoptic diagram that cooperates of mantle container and permanent seat of the embodiment 15 of mantle bio-reactor of the present invention;
Figure 29 is the structural representation of the embodiment 16 of mantle bio-reactor of the present invention;
Figure 30 is the structural representation of the embodiment 17 of mantle bio-reactor of the present invention;
Figure 31 is the structural representation of the embodiment 18 of mantle bio-reactor of the present invention;
Figure 32 is the structural representation of the embodiment 19 of mantle bio-reactor of the present invention;
Figure 33 is the structural representation of mantle container of the embodiment 19 of mantle bio-reactor of the present invention;
Figure 34 is the structural representation of isolating cap of the embodiment 19 of mantle bio-reactor of the present invention;
Figure 35 is the expansion synoptic diagram of isolating cap of the embodiment 19 of mantle bio-reactor of the present invention;
Figure 36 is the isolating cap structural representation of the embodiment 20 of mantle bio-reactor of the present invention;
Figure 37 is the structural representation of the embodiment 21 of mantle bio-reactor of the present invention;
Figure 38 is the mantle unrolling of container synoptic diagram of the embodiment 21 of mantle bio-reactor of the present invention.
Embodiment
The embodiment 1 of mantle bio-reactor of the present invention shown in Fig. 1-7, comprises by the formed airtight mantle container that is triangular taper of 1 and three sidewall at the bottom of 2 and one being used to support the support cages of mantle container to prevent that its sidewall 2 from collapsing.Mantle container in the present embodiment is processed by a mantle, and this mantle is non-PVC cartridge bag plastics mantle, like multi-layer co-extruded by a certain percentage films that forms such as Vestolen PP 7052 (PP), Vilaterm (PE, PPE), polyamide (PA) and polyesters copolymers; It is unaffected to have the sterilization of good transparency and 121 ℃ of high-temperature steams, and extremely low to gas-premeable and water vapor transmission, inertia is fabulous; Do not produce chemical reaction with any medicine, flexible and good springiness is prone to reply, and physical strength is high; Can anti-low temperature, be difficult for breaking, be easy to transportation, store; After the burning disposal; Picture burning natural materials such as blockishness only produce water, titanium dioxide carbon oxides, environmental sound and advantage with low cost.The angle 3 that passes through to turn back and be connected to form smooth transition between the end 1 of mantle container and three sidewalls 2; Adjacent sidewall is in the intersection of the two; The rib place that is said triangular taper forms turning 4 and is connected to form three fusion edge 5 in this position by the hot pressing fusion; Merging edge 5 all extends to the outside of mantle container; Merge and to be laid with 6, three sidewalls of hanging hole back that crosses on top on the edge 5 respectively and to be merged and constitute the top 7 of the airtight mantle container of the triprismo bodily form, penetrating connected entrance and the pipe 8 that is communicated with connected entrance inside and outside a sidewall of mantle container is provided with by hot pressing; Pipe 8 merges circle 9 (like Fig. 3) through the annular that is provided with on its end near the mantle container and merges mutually with connected entrance mantle on every side; Thereby make its with the corresponding sidewall of mantle container between be sealed and matched, in addition, the external port of pipe 8 is provided with the spiral cover 10 (like Fig. 4) that cooperates with the threaded one end away from the mantle container of pipe 8.That shown in Figure 2 is the mantle unrolling of container figure of this mantle bio-reactor.Fig. 5 is the view of injecting in the mantle container of this mantle bio-reactor behind the nutrient solution, and nutrient solution is in the bottom of mantle container, and the top of mantle container is the space that holds gas.The structure of support cages is as shown in Figure 6; It is up-small and down-big tubaeform that its integral body is; Comprise on fixed ring 11, superposed annular under the annular of bottom fixed ring 12 and be connected the sway brace 13 between the upper and lower fixed ring; The diameter of last fixed ring 12 down fixed ring 11 for little and the two on be equipped with chute 14, be respectively arranged with elasticity tractive hook 15 in the chute on last fixed ring 12 and following fixed ring 11; This support cages is only in violent mixed culture; The occasion of cultivating on a large scale like shaken culturing micro-organisms and large-scale reactor drum just can be activated; When being activated, support cages is through the company of extension that matches of the hanging hole 6 on the fusion edge of its elasticity tractive hook 15 and mantle container.The quantity of the fusion edge of the need tractive of the quantity of tractive hook 15 and mantle container is complementary on chute 14 and the chute, such as present embodiment is triprismo, and tractive hook 15 on three chutes 14 and three chutes is arranged respectively; Can be at the bottom of mantle container and the top multi-faceted tractive of support cages with guarantee that fixedly reactor drum can not produce mobile or collapses because of various blended motions; This support cages is suitable for violent mixed culture, cultivates and large-scale reactor drum carries out large-scale cell cultures like the jolting of mikrobe.Among other embodiment of mantle bio-reactor of the present invention; Particularly small-sized mantle bio-reactor; The tractive that does not need any external force with fixing promptly can be as the container of hard; Keep its three-D space structure, therefore can carry out static cultivation and the gentle nutrient solution blended suspension culture that drives, therefore also hanging hole need be set without any need for the tractive stationary installation.When using large-scale mantle bio-reactor, or when needing violent suspendible to cultivate, can carry out tractive with fixing, in case the collapsing or displacement of mantle container through support cages or permanent seat.
When using this mantle bio-reactor; At first an amount of nutrient solution and biological cell are passed through to inject pipe in this mantle container; The amount of the nutrient solution that injects should guarantee that liquid level is positioned at below the end opening edge of connected entrance all the time when reactor drum is worked; Then the mantle container is placed on track shaking table, plane revolving gear, space revolving gear or the yaw drive, when the liquid in the mantle container when a direction flows and impact sidewall, the sidewall mantle is outwards bulging owing to have elasticity; Thereby generation can cushion the impact of flow and reduce shearing force; When flow flowed round about, the mantle of sidewall was through elastical retraction and utilize its elastical retraction wave that power produces, and mixed and the gas-liquid exchange thereby produce.Because the mantle container is triangular taper; Therefore the corner between its end and the sidewall is an acute angle, and sidewall has the outside bulging of very big elasticity, thereby the surge capability that produces is bigger; Elastical retraction power is also bigger, and the wave that utilizes its elastical retraction power to be produced produces and mixes fully and the gas-liquid exchange.Because reactor drum is the little pyramidal structure with the bottom in top, center of gravity is leaned on down, under the jolting situation of gentleness, can keep its stability without any need for fixing; When jolting speed increases to simply the mantle reactor drum is placed on when being not enough to stablize on the hybrid drive, thereby can stably is seated on the drive unit with the frictional force maintenance mantle reactor drum that increases film pad and mantle reactor drum fixedly installing film pad that pellosil pad or any has viscosity on the drive unit; When the needs shaken is cultivated or is cultivated on a large scale, can the mantle bio-reactor be fixed on the support cages through hanging hole, again support cages is fixedly cultivated on the suspendible drive unit.
The embodiment 2 of mantle bio-reactor of the present invention; Shown in Fig. 8-9, the difference of present embodiment and embodiment 1 is: the end face of the spiral cover 10 of present embodiment has the ventilation fenestra, the ventilative filter membrane 16 that the ventilation fenestra is sealed up; In such cases; Can spiral cover 10 be tightened in use, realize mantle container intracavity and extraneous gaseous interchange through the ventilative filter membrane of ventilation fenestra, ventilative filter membrane has ventilative; The function of dustproof and bacteriological filtration, the mantle container in the present embodiment has omitted the hanging hole described in the embodiment 1.
The embodiment 3 of mantle bio-reactor of the present invention; Shown in Figure 10-11; The difference of present embodiment and embodiment 1 is: the seam that connected entrance is reserved when hot pressing is merged by adjacent two side constitutes, and is located at the adjoiner of corresponding two side pipe 8, and the outline of heat fusion circle 9 assumes diamond in shape and merges with corresponding two side hot pressing through its periphery; Because connected entrance is to be made up of the seam between the two side, employing rhombohedral heat merges circle and can reduce the fold that combines generation to greatest extent.
The embodiment 4 of mantle bio-reactor of the present invention, shown in figure 12, the difference of present embodiment and embodiment 3 only is: the end face of the spiral cover 10 of present embodiment has the ventilation fenestra; The ventilative filter membrane 16 that the ventilation fenestra is sealed up; In such cases, can spiral cover 10 be tightened in use, realize mantle container intracavity and extraneous gaseous interchange through the ventilative filter membrane on the ventilation fenestra; Ventilative filter membrane has ventilative, the function of dustproof and bacteriological filtration.
The embodiment 5 of mantle bio-reactor of the present invention; Shown in Figure 13-14; The difference of present embodiment and embodiment 1 only is: said mantle container is frusta-pyramidal; Connected entrance is located at the intersection of three sidewalls at the top, and heat merges that fusion faces that the periphery of circle 9 connects by three head and the tail that are triangularly arranged constitute and the top through its periphery and three sidewalls merges.
The embodiment 6 of mantle bio-reactor of the present invention, shown in figure 15, the difference of present embodiment and embodiment 5 only is: the end face of the spiral cover 10 of present embodiment has the ventilation fenestra; The ventilative filter membrane 16 that the ventilation fenestra is sealed up; In such cases, can spiral cover 10 be tightened in use, realize mantle container intracavity and extraneous gaseous interchange through the ventilative filter membrane on the ventilation fenestra; Ventilative filter membrane has ventilative, the function of dustproof and bacteriological filtration.
The embodiment 7 of mantle bio-reactor of the present invention, shown in Figure 16-17, the difference of present embodiment and embodiment 1 only is: said mantle container is positive rectangular pyramid shape, and it has four sidewalls 2, and in such cases, the end 1 of mantle container, be square.
The embodiment 8 of mantle bio-reactor of the present invention; Shown in figure 18, the difference of present embodiment and embodiment 1 is: the mantle container is provided with two other (three altogether) connected entrance, and these two connected entrances are located at respectively on pyramidal two ribs of mantle container formation; The seam of when hot pressing is merged, being reserved by the two side of correspondence constitutes; The mantle container is connected with inlet pipe 17 through one in this connected entrance, is connected with escape pipe 18 through another, into and out of the inner chamber of tracheae through the mantle container be communicated with and the two on all be serially connected with strainer 19; In addition; The upper reaches in corresponding strainer on the inlet pipe 17 also are provided with air pump 20, when only depending on gap air inlet between spiral cover 10 and the connected entrance can't satisfy the needs of reaction, can realize in the mantle container inflation and spiral cover 10 is screwed through air pump 20 and inlet pipe 17; Discharge through escape pipe 18, thereby realize mantle container and outside gaseous interchange; Wherein said strainer and air pump all can be established as required in use in addition.
The embodiment 9 of mantle bio-reactor of the present invention; Shown in figure 19; The difference of present embodiment and embodiment 3 is: the mantle container is provided with two other (three altogether) connected entrance, and these two connected entrances are located at respectively on pyramidal two ribs of mantle container formation, and the seam of when hot pressing is merged, being reserved by the two side of correspondence constitutes; The mantle container is connected with inlet pipe 17 through one in this connected entrance; Be connected with escape pipe 18 through another, into and out of the inner chamber of tracheae through the mantle container be communicated with and the two on all be serially connected with strainer 19, the upper reaches in corresponding strainer also are provided with air pump 20 on the inlet pipe 17 in addition; When the transom gas inlet hole on only depending on spiral cover 10 can't satisfy the needs of reaction; Can come in the mantle container, to inflate and spiral cover 10 is screwed through air pump 20 and inlet pipe 17 realizations,, thereby realize the gaseous interchange of mantle container and outside through escape pipe 18 exhausts; Wherein said strainer and air pump all can be established as required in use in addition.
The embodiment 10 of mantle bio-reactor of the present invention; Shown in figure 20; The difference of present embodiment and embodiment 5 is: the mantle container is provided with two other (three altogether) connected entrance, and these two connected entrances are located at respectively on pyramidal two ribs of mantle container formation, and the seam of when hot pressing is merged, being reserved by the two side of correspondence constitutes; The mantle container is connected with inlet pipe 17 through one in this connected entrance; Be connected with escape pipe 18 through another, into and out of the inner chamber of tracheae through the mantle container be communicated with and the two on all be serially connected with strainer 19, the upper reaches in corresponding strainer also are provided with air pump 20 on the inlet pipe 17 in addition; When only depending on gap air inlet between spiral cover 10 and the connected entrance can't satisfy the needs of reaction; Can realize in the mantle container inflation and spiral cover 10 is screwed through inlet pipe,, thereby realize mantle container and outside gaseous interchange through the escape pipe exhaust; Wherein said strainer and air pump all can be established as required in use in addition.
The embodiment 11 of mantle bio-reactor of the present invention, shown in figure 21, the difference of present embodiment and embodiment 8 is: mantle container bottom also is connected with catheter 21, PH transmitter 22 and DO transmitter 23; The three is respectively at the place, three summits at the end 1 of mantle container; Be that the rib that forms between the adjacent two side is communicated with the inner chamber of mantle container with the intersection at the end, can reduce the appearance of fold so to greatest extent, PH transmitter 22 is used to respond to the potential of hydrogen of nutrient solution; DO transmitter 23 is used to respond to the oxygen dissolved of nutrient solution; Mantle bio-reactor in the present embodiment is applicable to the occasion that needs big volume, production in enormous quantities, adopts the artificial initiatively mode of air feed can satisfy the needs of big volume reaction, and PH transmitter 22 and DO transmitter 23 can be used for monitoring in real time the state of reaction solution; So that adjustment in time; Guarantee optimum reaction condition, certainly, should guarantee that above-mentioned two sensors contacts with nutrient solution when reactor drum is worked always; When needs are taked biologics that sample and final results cultivate, 21 of catheters can reactor drum excessive suitable topple over realize the tapping function when getting liquid, convenient for taking liquid, this catheter 21 is normally closed pipe certainly, has only when needed and just opens.
The embodiment 12 of mantle bio-reactor of the present invention, shown in figure 22, the difference of present embodiment and embodiment 9 is: mantle container bottom also is connected with catheter 21, PH transmitter 22 and DO transmitter 23; The three is respectively at the place, three summits at the end 1 of mantle container; Be that the rib that forms between the adjacent two side is communicated with the inner chamber of mantle container with the intersection at the end, can reduce the appearance of fold so to greatest extent, PH transmitter 22 is used to respond to the potential of hydrogen of nutrient solution; DO transmitter 23 is used to respond to the oxygen dissolved of nutrient solution; Mantle bio-reactor in the present embodiment is applicable to the occasion that needs big volume, production in enormous quantities, adopts the artificial initiatively mode of air feed can satisfy the needs of big volume reaction, and PH transmitter 22 and DO transmitter 23 can be used for monitoring in real time the state of reaction solution; So that adjustment in time; Guarantee optimum reaction condition, certainly, should guarantee that above-mentioned two sensors contacts with nutrient solution when reactor drum is worked always; When needs are taked biologics that sample and final results cultivate, 21 of catheters can reactor drum excessive suitable topple over realize the tapping function when getting liquid, convenient for taking liquid, this catheter 21 is normally closed pipe certainly, has only when needed and just opens.
The embodiment 13 of mantle bio-reactor of the present invention, shown in figure 23, the difference of present embodiment and embodiment 10 is: mantle container bottom also is connected with catheter 21, PH transmitter 22 and DO transmitter 23; The three is respectively at the place, three summits at the end 1 of mantle container; Be that the rib that forms between the adjacent two side is communicated with the inner chamber of mantle container with the intersection at the end, can reduce the appearance of fold so to greatest extent, PH transmitter 22 is used to respond to the potential of hydrogen of nutrient solution; DO transmitter 23 is used to respond to the oxygen dissolved of nutrient solution; Mantle bio-reactor in the present embodiment is applicable to the occasion that needs big volume, production in enormous quantities, adopts the artificial initiatively mode of air feed can satisfy the needs of big volume reaction, and PH transmitter 22 and DO transmitter 23 can be used for monitoring in real time the state of reaction solution; So that adjustment in time; Guarantee optimum reaction condition, certainly, should guarantee that above-mentioned two sensors contacts with nutrient solution when reactor drum is worked always; When needs are taked biologics that sample and final results cultivate, 21 of catheters can reactor drum excessive suitable topple over realize the tapping function when getting liquid, convenient for taking liquid, this catheter 21 is normally closed pipe certainly, has only when needed and just opens.
The embodiment 14 of mantle bio-reactor of the present invention; Shown in Figure 24-25; The difference of present embodiment and embodiment 11 is: omitted the connected entrance, pipe 8 and the spiral cover 10 that have spiral cover 10 among the embodiment 11 on the mantle container, the mantle bio-reactor in the present embodiment is applicable to large scale culturing, when large scale culturing; Need not carry out the conveying of nutrient solution and culturing cell through above-mentioned connected entrance; Only there are inlet pipe 17, escape pipe 18 and catheter 21 to get final product, it is pointed out that and in the foregoing description 12,13, also can omit connected entrance, pipe and the spiral cover that has spiral cover.
The embodiment 15 of mantle bio-reactor of the present invention; Shown in Figure 26-28; The difference of present embodiment and embodiment 7 is: comprise that also a permanent seat and mantle container are frusta-pyramidal, the mantle container can by a mantle through shear, folding and hot pressing is any forms, also can be assembled by many mantles; It has a roof 24 parallel with the end 1; Be wholely set between roof 24 and the sidewall 2 and the intersection of the two has the angle that is folded to form, thereby make smooth transition between sidewall 2 and the roof 24, be convenient to the cell growth state in the microscopically observing response device; The intersection at intersection between the adjacent two side and sidewall and the end is equipped with to the outside fusion edge 5 that extends of reactor drum, merges edge 5 for two-layer mantle (sidewall and the end or sidewall and sidewall) hot pressing being merged the nexus that the back forms; Permanent seat comprises transparent seat board 25, and transparent seat board 25 is provided with the fixed sturcture of the fusion edge of the sidewall that is used for fixing the mantle container and the intersection at the end, in the present embodiment; This fixed sturcture adopts retaining clip 26; Retaining clip 26 is provided with the elasticity arm 27 that upwards overhangs, and arm 27 is provided with suspension hook 28, suspension hook 28 be used for and adjacent two side between the fusion edge that forms articulate; Thereby the sidewall that further guarantees the mantle container does not collapse; It is pointed out that said permanent seat can also establish in use in addition, fixed sturcture also can adopt parts such as adhesive tape, hook; When using bio-reactor of the present invention to carry out the static cultivation of attached cell; On the mantle of the bottom surface of cell attachment growth; Take for ease and possibly make when preventing to take the bottom surface mantle produce distortion, can use permanent seat that the mantle container is fixed on the permanent seat, just as the culturing bottle of a hard with transparent seat board; Both conveniently taken and microscopic examination, and also can prevent the distortion of bottom surface mantle and cause attaching the coming off of cell of growth above that.
The embodiment 16 of mantle bio-reactor of the present invention; Shown in figure 29, the difference of present embodiment and embodiment 15 only is: the end face of the spiral cover of present embodiment has the ventilation fenestra, the ventilative filter membrane 16 that the ventilation fenestra is sealed up; In such cases; Can spiral cover 10 be tightened in use, realize mantle container intracavity and extraneous gaseous interchange, the function of ventilative filter membrane has ventilative, dustproof and bacteriological filtration through the ventilative filter membrane of ventilation on the fenestra.
The embodiment 17 of mantle bio-reactor of the present invention, shown in figure 30, the difference of present embodiment and embodiment 15 only is: the mantle container in the present embodiment is that the inner-wall surface of sidewall and the angle at the end are the hexahedron at right angle.
The embodiment 18 of mantle bio-reactor of the present invention; Shown in figure 31, the difference of present embodiment and embodiment 17 only is: the end face of the spiral cover 10 of present embodiment has the ventilation fenestra, the ventilative filter membrane 16 that the ventilation fenestra is sealed up; In such cases; Can spiral cover 10 be tightened in use, realize mantle container intracavity and extraneous gaseous interchange, the function of ventilative filter membrane has ventilative, dustproof and bacteriological filtration through the ventilative filter membrane of ventilation on the fenestra.
The embodiment 19 of mantle bio-reactor of the present invention; Shown in Figure 32-35, the difference of present embodiment and embodiment 1 only is: the connected entrance place on the mantle container in the present embodiment is not provided with pipe and spiral cover, in the present embodiment; Connected entrance on the mantle container covers through an isolating cap 30; Isolating cap 30 prevents to be contained in the nutrient solution the mantle container when pollutent such as dust, bacterium pollutes use from connected entrance entering mantle container in the external environment, and isolating cap 30 is processed by mantle equally, and the method for manufacture of the isolating cap 30 in the present embodiment and the method for manufacture of mantle container are similar; Also be to process through cutting, hot pressing fusion treatment to one whole film; It is shaped as pyramid, and wherein isolating cap installs additional and seals for ease, and the fusion edge between the corresponding sidewall of the mantle container in the present embodiment is cut by part; Merge the edge rest parts and just can also play the effect of supporting isolating cap; In such cases, isolating cap similarly is a cap of mantle container, after " wearing " gone up mantle container, can cover between connected entrance and inner wall surface thereof and the connected entrance on the mantle container to be provided with ventilative gap; Ventilative gap is in order to realize the circulation of the air between mantle internal tank and mantle container and the isolating cap, to satisfy reaction needed.
The embodiment 20 of mantle bio-reactor of the present invention; Shown in figure 36; The difference of present embodiment and embodiment 19 only is: one of them sidewall of isolating cap is provided with a ventilation window; Sealing is merged on the ventilation window has ventilative bacteriological filtration film 31, and during the mantle container, ventilative bacteriological filtration film 31 covers the connected entrance of mantle container on isolating cap 31.
The embodiment 21 of mantle bio-reactor of the present invention; Shown in Figure 37-38, the difference of present embodiment and embodiment 1 only is: said mantle container is the triangular prism shaped of body of one who has dropped dead by the roadside placement, adopts this kind shape can make full use of the space in the mantle container; The making method of the mantle container among the mantle container in the present embodiment and the embodiment 1 is identical; Also be to merge by one whole mantle cutting, hot pressing to form, all be located at connected entrance and pipe at the triangular prism shaped end of mantle container formation that connected entrance and pipe all only have one in the present embodiment; In other embodiments; The quantity of connected entrance and pipe also can suitably be provided with as required, when connected entrance has two when above, can also divide the triangular prism shaped top that is located at the mantle container and forms, at the end; Certainly, can also be located at connected entrance and pipe on the two sides of correspondence of the triangular prism that the mantle container forms; In addition, in other embodiments, also can be as required be provided with in the present embodiment the mantle container described like embodiment 8 into and out of tracheae and strainer and the catheter described in embodiment 11, PH transmitter and transmitter.
The embodiment 1-7 of mantle bio-reactor of the present invention, the bio-reactor of 19-20 are particularly suitable for that the laboratory is cultivated on a small scale and the small-scale of process exploitation is cultivated; Place track shaking table, plane to circle round on shaking table, space revolving gear or the yaw drive said mantle bio-reactor during use, the taper culturing bottle of the hard that it is used as common mikrobe and zooblast suspension culture is cultivated and is utilized connected entrance to carry out the gas-dispersion exchange just can to react.
The bio-reactor of the embodiment 8-14 of mantle bio-reactor of the present invention is applicable to the cell cultures of comparatively large vol.When using said mantle bio-reactor to carry out comparatively large vol when cultivating, when only carrying out the gas-dispersion exchange and can not meet the demands, can inflate cultivation through connected entrance.When utilizing incubator to cultivate, miniature aerator pump or peristaltic pump are connected in inlet pipe, gas is taken from incubator, pumps in the reactor drum, realizes being discharged by escape pipe after the gaseous interchange, therefore saves gas mixed traffic meter; When reactor drum size surpasses the scale of existing commercialization incubator, the thermostat container or the thermostatic chamber that also need be complementary with the reactor drum size.
The embodiment 21 of mantle bio-reactor of the present invention is the triangular prism shaped of body of one who has dropped dead by the roadside placement; Connected entrance both capable of using carries out gaseous interchange; Be fit to cultivate on a small scale as embodiment 1-7, also capable of using as the described inlet pipe of embodiment 8-14 and escape pipe and utilize catheter PH transmitter and mass-producing cultivation that the DO transmitter is inflated and monitored.
The bio-reactor of the embodiment 15-18 of mantle bio-reactor of the present invention is small-sized reactor drum; Be mainly used in cell cultures and process exploitation on a small scale; When using small-sized end face to carry out small-scale cell cultures or process exploitation as the mantle bio-reactor of horizontal plane, attached cell can directly be attached on the mantle of bottom surface and grow, and the reactor drum of present embodiment is similar to Tissue Culture Flask; Both can staticly cultivate; Can when needing microscopically to observe the growth conditions of culturing cell, can the reactor drum of present embodiment be placed and carry out the microscopically direct viewing through driving the mobile mixed culture of nutrient solution again.This bio-reactor has the transparent seat board of a hard can printing opacity, and therefore the cell in can the direct viewing reactor drum need not take out cell and observe, and conveniently uses and saves time.Transparent seat board is provided with fixed sturcture, can with the mantle biopack securely tractive be fixed on the transparent seat board.
In sum; Mantle bio-reactor of the present invention is mainly used in from breadboard small-scale; Amplify to series; Again to the animal cell culture of industrially scalable and utilize zooblast to carry out the production of biological technology products, also can be used for cultivation and the production of biological technology products thereof of mikrobe, insect cell and the vegetable cell of corresponding scale.When being used for microorganism culturing, the triangle of cultivating usefulness on a small scale be can replace and bottle and large scale culturing fermentor tank shaken, mainly solve the disposable use problem of microorganism culturing container, provide and use the mantle formula culture vessel more convenient, that cost is lower.The mantle bio-reactor that adopts the present invention to have planar top can replace existing Tissue Culture Flask, but cheaper than existing Tissue Culture Flask cost.
This shows; That mantle bio-reactor of the present invention has is simple in structure, easy to use, non-invasi mixes, disposable characteristic, and existing thermostat container capable of using, incubator and hybrid drive apparatus are particularly suitable for cultivating on a small scale; The scale of also can carrying out is amplified and is produced; Mainly be suitable for the suspension culture of zooblast, comprise the suspension culture of non-adherent cell and the microcarrier suspension culture of attached cell, also can be used for the cultivation of mikrobe or other biological cell.When using mantle bio-reactor of the present invention that non-adherent cell or mikrobe are cultivated, very simple, directly non-adherent cell or mikrobe are put into the mantle container and carry out suspension culture and get final product; And when attached cell is cultivated, both can be as common Tissue Culture Flask, attached cell directly is attached on the mantle of bottom surface and carries out static cultivation, also can attached cell be attached to and carry out suspension culture on the microcarrier.Microcarrier is small bead; Cell is grown in the surface of bead; So just paste attached cell by the static cultivation in the plane that is attached to the Tissue Culture Flask bottom interior surface and become the stereo suspending cultivation that is attached on the microballoon; Improve culture efficiency greatly, very be fit to when the cultivation of attached cell being carried out extensive or suitability for industrialized production.In addition; In other embodiment of mantle bio-reactor of the present invention; Mantle container described in the foregoing description 1-14 can also be wedge shape, and the top of embodiment 5,6, the mantle container that is frusta-pyramidal described in 15 can also be not parallel the end of with, promptly can be obliquely installed; The quantity of the sidewall of mantle container is all can more than two; Inlet pipe described in the embodiment 8-14 also can be as required and corresponding source of the gas, connects like devices such as gas tanks, in such cases, then can omit said air pump; Among each embodiment, sidewall and the angle at the end between 5-90 ° (comprising 5 ° and 90 °) all can, be the best wherein with 30-90 °; Because too little angle; The volume of mantle container is too little, and service efficiency is too low, and is big less than the buffering and the elastical retraction ability of 90 ° acute angle sidewall mantles; Effective, it is also more stable to form support each other between each sidewall; The quantity of sidewall is best with the odd number; Because inject wave that the nutrient solution of mantle container forms in the time of can guaranteeing to use like this and when to-and-fro movement at a side place be at least and impinge upon on the inner-wall surface of a sidewall (always have a sidewall relative) with a rib; Thereby the generation of having avoided reciprocating situation between the corner that wave that nutrient solution forms forms at two rib places is to reduce the shearing force that might produce as far as possible; Between the liquid of edges and corners and each wall of converging in edges and corners because the tensile effect makes flow slow, even have also can be very little for the shearing force that is produced.
The employed mantle of mantle bio-reactor of the present invention is non-PVC cartridge bag plastics mantle, the infusion bag and the used plastics mantle of transfusion bags that for example generally use; For Vestolen PP 7052 (PP), Vilaterm (PE, PPE), the polymeric amide multi-layer co-extruded films of material such as (nylon PA), be generally three layers of film to the 100-200 micron thickness of five-layer co-squeezing, internal layer is the inert polymer of totally nontoxic; Usually adopt Vestolen PP 7052 (PP), Vilaterm (PE) etc.; Have extremely strong chemicalstability (inertia), do not come off or the foreign matter of degrading out, reactionless with nutrient solution and soup; Heat seal strength is high; The middle layer is the dense material layer, like Vestolen PP 7052 (PP), polyamide (PA), has solid gas and liquid barrier performance, elasticity, snappiness, high thermal resistance; Skin is Vestolen PP 7052 (PP), Vilaterm (PE) or multi-ester copolymer, mainly is the physical strength that improves soft bag.Non-PVC cartridge bag plastics mantle has good transparency and 121 ℃ of high-temperature steam sterilizations are unaffected, and extremely low to gas-premeable and water vapor transmission, inertia is fabulous, does not produce chemical reaction with any medicine; Flexible be prone to reply with good springiness, the physical strength height can anti-low temperature, is difficult for breaking; Be easy to transportation, store, after the burning disposal, as burning natural materials such as blockishness; Only produce water, titanium dioxide carbon oxides, environmental sound and advantage with low cost are as present optimal cartridge bag material; Infusion bag for example, transfusion bags and liquid storing bag, widespread use worldwide.Though PVC SE mantle also can be made mantle bio-reactor of the present invention; But, PVC SE mantle destroys atmospheric layer because producing organochlorine in burning the destruction process; Contaminate environment; Softening agent in the PVC material (DEHP) but seepage have side effects among being dissolved in nutrient solution or soup, in addition, the PVC material is to the barriering effect difference of gas and liquid infiltration and have shortcomings such as particulate comes off; Not ideal medical drugs packet materials, neither make the preferred material of mantle reactor drum of the present invention.

Claims (10)

1. the mantle bio-reactor is characterized in that, comprises airtight mantle container; Said mantle container comprises the end and the sidewall more than three; The said end is flat, the inner-wall surface of each sidewall and have 5 ~ 90 ° angle at the end, and the junction at the two between the adjacent two side forms the turning; The mantle container is provided with penetrating connected entrance inside and outside at least one, and the end opening of said connected entrance is along on the liquid level that is arranged in the nutrient solution that injects the mantle container when using.
2. mantle bio-reactor according to claim 1; It is characterized in that; Said mantle container is connected with pipe through its connected entrance; Said pipe and mantle container be fixed together and the two between be sealed and matched, pipe is equipped with the spiral cover of mechanical seal or the spiral cover of the ventilative filter membrane of end face band away from the threaded one end of mantle container.
3. mantle bio-reactor according to claim 1; It is characterized in that; The end of said mantle container and sidewall are made up of a mantle; The inner-wall surface of the sidewall of mantle container and the angle at the end are folded to form by mantle, and the junction of adjacent two side between the two merged by hot pressing and be sealed and matched.
4. mantle bio-reactor according to claim 1; It is characterized in that; Said mantle container is fixed with the escape pipe that at least one inlet pipe and the inner chamber through the mantle container are communicated with said inlet pipe, saidly all is communicated with the inner chamber of mantle container with mantle container sealing cooperation and the corresponding connected entrance that passes through on the mantle container respectively into and out of tracheae.
5. mantle bio-reactor according to claim 1; It is characterized in that; The PH transmitter and being used for that the mantle container is provided with the normally closed catheter that injects for liquid or emit, be used for monitoring the potential of hydrogen of the nutrient solution that injects the mantle container when using is monitored the DO transmitter of the oxygen dissolved of the nutrient solution that injects the mantle container when using; It is different that said catheter, PH transmitter and DO transmitter lay respectively at common intersection and three's the position at adjacent two side and the end, and catheter, PH transmitter and DO transmitter all cooperate with the mantle container sealing.
6. mantle bio-reactor according to claim 1; It is characterized in that; Merged and form the fusion edge that extends to the mantle external container by hot pressing between the adjacent two side of mantle container and/or between the end and the sidewall, said fusion edge is for being merged the nexus that the back forms by two-layer mantle by hot pressing.
7. according to each described mantle bio-reactor of claim 1-6; It is characterized in that; Said mantle container is pyramid or frusta-pyramidal, and the end of mantle container forms the end of pyramid or truncated pyramid, and the sidewall of mantle container forms the side of pyramid or truncated pyramid.
8. according to claim 1 or each described mantle bio-reactor of 3-6; It is characterized in that; Also comprise being used to cover and be located on the said mantle container isolating cap that receives outside contamination with the nutrient solution that prevents the mantle internal tank; Said isolating cap covers the connected entrance of mantle container when covering the mantle container, when said isolating cap when covering the mantle container, inner wall surface thereof has ventilative gap with being communicated with between the mouth of pipe.
9. mantle bio-reactor according to claim 8; It is characterized in that one of them sidewall of said isolating cap is provided with the ventilation window, sealing is merged on the ventilation window has ventilative bacteriological filtration film; When isolating cap covered the mantle container, ventilative bacteriological filtration film covered the connected entrance of mantle container.
10. according to each described mantle bio-reactor of claim 1-6, it is characterized in that said mantle container is the triangular prism shaped of body of one who has dropped dead by the roadside placement.
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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105886398A (en) * 2016-06-24 2016-08-24 郑州威瑞生物技术有限公司 Soft-film bioreactor with three-dimensional inner cavity and supporting frame of soft-film bioreactor
CN106834117A (en) * 2015-10-27 2017-06-13 苏州迪欧益生物科技有限公司 Enzyme reactor and intelligent enzyme reaction work station for releasing zooblast attaching
CN108430633A (en) * 2015-12-23 2018-08-21 赛多利斯斯泰迪姆埃赛普蒂克斯公司 The method for manufacturing sealing container
US20200339931A1 (en) * 2019-04-24 2020-10-29 Sartorius Stedim Biotech Gmbh Bioreactor for use on a moving platform, bioreactor motion system, and method of performing a bioprocess using a bioreactor motion system
WO2020221789A1 (en) * 2019-05-02 2020-11-05 Global Life Sciences Solutions Usa Llc Single-use, flexible bioprocessing bag and method of manufacturing a single-use, flexible bioprocessing bag
CN113073050A (en) * 2021-04-27 2021-07-06 惠倪 Large-volume double-swing plastic bag cell bioreactor
CN114907977A (en) * 2022-07-11 2022-08-16 浙江金仪盛世生物工程有限公司 Support frame and biological reaction device
EP3931298A4 (en) * 2019-02-25 2022-12-21 University of Maryland, Baltimore County Adjustable fermentation and cell culture flasks
WO2025000315A1 (en) * 2023-06-29 2025-01-02 韩世杰 Polyhedral cell culture bag, assistance device thereof and preparation method therefor

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1132460A2 (en) * 2000-03-06 2001-09-12 Sefar AG Bioreactor and process for the growth of dentritic cells
CN101255395A (en) * 2006-11-15 2008-09-03 米利波尔公司 Self-standing bioreactor structure
CN101812405A (en) * 2010-04-30 2010-08-25 惠倪 Polygonal plastic bag swing cell reactor and method for culturing animal cells
CN201713522U (en) * 2010-04-30 2011-01-19 惠倪 Swinging cell reactor with polygonal plastic bag
CN201737946U (en) * 2010-04-30 2011-02-09 惠倪 Polygonal plastic culturing bag for animal cell culture
CN102154100A (en) * 2011-01-07 2011-08-17 郑州威瑞生物技术有限公司 Potential difference circulating bioreactor
CN202688333U (en) * 2012-04-28 2013-01-23 郑州威瑞生物技术有限公司 Soft membrane bioreactor

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1132460A2 (en) * 2000-03-06 2001-09-12 Sefar AG Bioreactor and process for the growth of dentritic cells
CN101255395A (en) * 2006-11-15 2008-09-03 米利波尔公司 Self-standing bioreactor structure
CN101812405A (en) * 2010-04-30 2010-08-25 惠倪 Polygonal plastic bag swing cell reactor and method for culturing animal cells
CN201713522U (en) * 2010-04-30 2011-01-19 惠倪 Swinging cell reactor with polygonal plastic bag
CN201737946U (en) * 2010-04-30 2011-02-09 惠倪 Polygonal plastic culturing bag for animal cell culture
CN102154100A (en) * 2011-01-07 2011-08-17 郑州威瑞生物技术有限公司 Potential difference circulating bioreactor
CN202688333U (en) * 2012-04-28 2013-01-23 郑州威瑞生物技术有限公司 Soft membrane bioreactor

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106834117A (en) * 2015-10-27 2017-06-13 苏州迪欧益生物科技有限公司 Enzyme reactor and intelligent enzyme reaction work station for releasing zooblast attaching
CN108430633B (en) * 2015-12-23 2021-06-01 赛多利斯斯泰迪姆埃赛普蒂克斯公司 Method for manufacturing sealed container
CN108430633A (en) * 2015-12-23 2018-08-21 赛多利斯斯泰迪姆埃赛普蒂克斯公司 The method for manufacturing sealing container
CN105886398B (en) * 2016-06-24 2019-04-09 郑州威瑞生物技术有限公司 The mantle bioreactor and its support frame of three-dimensional endoluminal
CN105886398A (en) * 2016-06-24 2016-08-24 郑州威瑞生物技术有限公司 Soft-film bioreactor with three-dimensional inner cavity and supporting frame of soft-film bioreactor
EP3931298A4 (en) * 2019-02-25 2022-12-21 University of Maryland, Baltimore County Adjustable fermentation and cell culture flasks
US20200339931A1 (en) * 2019-04-24 2020-10-29 Sartorius Stedim Biotech Gmbh Bioreactor for use on a moving platform, bioreactor motion system, and method of performing a bioprocess using a bioreactor motion system
US11999935B2 (en) * 2019-04-24 2024-06-04 Sartorius Stedim Biotech Gmbh Bioreactor for use on a moving platform, bioreactor motion system, and method of performing a bioprocess using a bioreactor motion system
WO2020221789A1 (en) * 2019-05-02 2020-11-05 Global Life Sciences Solutions Usa Llc Single-use, flexible bioprocessing bag and method of manufacturing a single-use, flexible bioprocessing bag
CN113785043A (en) * 2019-05-02 2021-12-10 环球生命科技咨询美国有限责任公司 Single-use flexible bioprocessing packs and methods of making single-use flexible bioprocessing packs
JP7536380B2 (en) 2019-05-02 2024-08-20 グローバル・ライフ・サイエンシズ・ソリューションズ・ユーエスエー・エルエルシー Disposable flexible bioprocessing bag and method for manufacturing a disposable flexible bioprocessing bag
CN113785043B (en) * 2019-05-02 2024-11-12 环球生命科技咨询美国有限责任公司 Single-use flexible bioprocessing package and method of making a single-use flexible bioprocessing package
CN113073050A (en) * 2021-04-27 2021-07-06 惠倪 Large-volume double-swing plastic bag cell bioreactor
CN114907977A (en) * 2022-07-11 2022-08-16 浙江金仪盛世生物工程有限公司 Support frame and biological reaction device
WO2025000315A1 (en) * 2023-06-29 2025-01-02 韩世杰 Polyhedral cell culture bag, assistance device thereof and preparation method therefor

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