CN107858285A - Split type bioreactor - Google Patents

Split type bioreactor Download PDF

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Publication number
CN107858285A
CN107858285A CN201711328770.9A CN201711328770A CN107858285A CN 107858285 A CN107858285 A CN 107858285A CN 201711328770 A CN201711328770 A CN 201711328770A CN 107858285 A CN107858285 A CN 107858285A
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culture
compression chamber
tank body
cabin
pressurization
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CN201711328770.9A
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周广东
刘延群
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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
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/40Means for regulation, monitoring, measurement or control, e.g. flow regulation of pressure
    • 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
    • C12M37/00Means for sterilizing, maintaining sterile conditions or avoiding chemical or biological contamination
    • C12M37/04Seals

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

Abstract

The present invention relates to a kind of split type bioreactor, is made up of compression chamber, culture cabin, pressure seal, and several can be placed in the compression chamber has the culture cabin of independent sealed structure, cultivates cabin by changing, can improve the service efficiency of compression chamber;Built with gas-pressurized into and out of pipe, pressurization hatchcover is tightly connected compression chamber casing with compression chamber casing contact position by sealing gasket, and pressurization hatchcover is fixed on compression chamber casing with Quick connection part;The pressure seal in corresponding culture cabin is separately mounted to compression chamber and covered, the annular handgrip of machinery is connected by drive link thereon with the pilot hole in pressurization hatchcover, it is tightly connected between pilot hole in drive link and pressurization hatchcover by seal, when being pressurizeed in compression chamber, the annular handgrip of machinery is pressed under the driving of pressure seal on the gel silica membrane in culture cabin, make to be formed between gel silica membrane and culture tank body upper surface and seal, it will not be overflowed with reaching the liquid when being pressurizeed to compression chamber, accomplish that safety asepsis operates.

Description

Split type bioreactor
Technical field
The present invention relates to a kind of bioreactor, especially a kind of split type bioreactor, belong to bioreactor skill Art field.
Background technology
Bioreactor is the experiment instrument for cultivating tissue of biological cells, is that cell tissue provides 1 hour daily High pressure culture environment, it is necessary to meet the strict aseptic condition of cell and tissue structrue needs (once contamination of cells tissue will be by To irremediable a mortal blow, sterile this is cell culture basis), sufficient nutrient environment (including (various types of cells must for nutrition Must biotic factor degradation rate it is fast) supply and waste removing), for meet the needs of biological tissue routinely change every other day Liquid.
The integrated bioreactor of the existing circulatory system and compression system.Such as patent publication No. CN103589638B, A kind of pneumatic self-loopa animal cell culture bioreactor and its application method, magnetic agitation system positioned at big pot bottom, Heating system and control system, big tank upper end are provided with closure, and big tank both sides are provided with the chuck being connected with heating system, small Tank upper end is provided with end socket and its lower end is provided with opening, and end socket is sealedly and fixedly connected with closure by breather pipe, breather pipe Upper end passes closure and is connected to vacuum air pump and air pressure pump, and its lower end passes end socket and entered in canister.Such as Patent publication No. CN102899250B, disclose a kind of controlled hydraulic bioreactor for organizational project, the upper end of top cover Portion is provided with controlled hydraulic system, and the bottom of tank body is provided with circumfusion system;Be provided with flexible partition in tank body, it is flexible every The cavity that tank body and top cover are formed is separated into culture chamber and pressurizing chamber by film;Using hydraulic pressurization mode and controllable unloading technology, Real-time, the precision control to key parameters such as Pressure stimulation intensity, frequency, action times can be achieved, realize a variety of stimulus modalities Conversion;Nutrient solution import and export is introduced in culture systems to realize circumfusion culture.
The circulatory system of the integrated bioreactor of the existing circulatory system and compression system, culture tank body and the bottle that reloads Linked by silicone tube, peristaltic pump provides circulation power.Cause and change liquid and (change liquid within 2 weeks) not in time, culture environment is unfavorable for cell Tissue cultures.It is high that the circulatory system of multicompartment causes cell tissue pollution rate when changing liquid.The complicated link of the link of various pipes Add pollution risk.The existing circulatory system and pressure system combining together bioreactor so that compression chamber is long-term One group of experiment takes for a long time, and reactor service efficiency is low.The design of integration, is not easy to the observation on Growth to sample, integration The tissue of design is placed on to be placed in sealed shell of tank for a long time, it is impossible to accomplishes the Real Time Observation to tissue.Integrated design, cause every time Pressurized operation include manual-lock disengaging fluid valve, open compression system;Pressurization, which finishes, every time will also close compression system, beat Drive liquid valve door into.Complex operation, human error is easily produced, cause fluid leakage, once there is fluid leakage to will result in dirt Dye.The design of integration, it is impossible to carry out routine and change liquid every other day, it is impossible to meet cell and tissue structrue environmental nutrient condition.Integration Design, having resulted in bulky compression chamber will be with the long-term cultivation in incubator that is organized in of culture, damp and hot ring in incubator Border is caused each component aging fast, is reduced the stability of equipment, is added the risk of pollution.The design of integration causes groups of cells The complex operation such as knit and be put into reactor, go out from reactor, and being the high operation of pollution risk.The design of integration, in order to Reach safety condition of the internal pressurization cabin in high-pressure environment, reactor design weight is very big, is practical operation, carries very tired Difficulty, operate suffering.The design of integration, to reach sterile requirement, it is necessary to uniformly be disappeared to whole reactor all parts Poison, assembling, complicated assembling link need rigorous aseptic, and a link occurs polluting and will cause the failure of cell tissue, one It is exactly to pollute amplifier to change design.
The content of the invention
The present invention is to provide for a kind of split type bioreactor, and the bioreactor eliminates the circulatory system, whole training It is independent sealed structure in compression chamber to support tank body, eliminates relevant connection component, obtains relatively reliable gnotobasis, maximum Limit reduces the pollution for carrying out autoreactor.
To achieve the above object, the technical scheme is that:A kind of split type bioreactor, by compression chamber, culture Cabin, pressure seal form, and can place several in the compression chamber has the culture cabin of independent sealed structure, passes through replacing Cabin is cultivated, the service efficiency of compression chamber can be improved;The compression chamber is made up of compression chamber casing and pressurization hatchcover, compartment-box of pressurizeing It is higher than the height of liquid level in compression chamber casing into and out of pipe, the import and export of gas-pressurized into and out of pipe equipped with gas-pressurized in vivo, adds Ballasting lid is tightly connected with compression chamber casing contact position by sealing gasket, and pressurization hatchcover is fixed on pressurization with Quick connection part On compartment-box body;Several independent pressure seals are separately mounted to compression chamber and covered, and corresponding culture cabin, the pressurization are close The mechanical annular handgrip of seal apparatus is connected by drive link thereon with the pilot hole in pressurization hatchcover, and the annular handgrip of machinery passes through Drive link can move up and down along pilot hole, and be tightly connected between the pilot hole in drive link and pressurization hatchcover by seal, When being pressurizeed in compression chamber, the annular handgrip of machinery is sealed in compression chamber, and the annular handgrip of machinery is under the driving of pressure seal Be pressed on the gel silica membrane in culture cabin, make to be formed between gel silica membrane and culture tank body upper surface and seal, with reach pair plus Liquid will not overflow when ballasting is pressurizeed, and accomplish that safety asepsis operates.
The culture cabin is made up of culture tank body, culture cover and gel silica membrane, and the culture cover leads to culture tank body Threaded connection is crossed, and cultivates and gel silica membrane is set between tank body and culture cover, training is pressed in by gel silica membrane by culture cover Support the preliminary sealing formed on tank body between culture cover and culture tank body.
Concavo-convex mating structures are additionally provided between the culture cover and culture tank body, culture cover passes through groove ring thereon Labyrinth type mechanical seal is cooperatively formed with the culture convex ring of tank body.Semicircle is respectively equipped with culture cover and gel silica membrane contact position Scrobicular ring and semicircle bulge loop, cultivate and close connection is coordinated by semicircle scrobicular ring and semicircle bulge loop between cover and gel silica membrane, make silicon Glue film can be removed with culture cover from culture tank body, convenient sterilizing.
When cultivating cabin pressurization, liquid is filled in the culture tank body, in silica gel thin slice of its liquid side with cultivating Cap for tin body Flat face touches.So that liquid need to only reach culture tank body mouth, liquid can be reduced and overflow compression chamber.
The pressure seal is by pressing mechanism with machinery pressure ring group into mechanical pressure ring is by the annular handgrip of machinery and transmission Bar forms, drive link upper end connection pressing mechanism, the annular handgrip of lower end connection machinery.
Each culture cabin is corresponding with a pressing mechanism, and pressing mechanism includes pressurizer, support, and pressurizer passes through support Covered installed in compression chamber.The output axis connection drive link and the annular handgrip of machinery of pressurizer.
Pressurizer is cylinder, oil cylinder, watched with one kind in motor or linear electric motors;The pressurizer passes for adjustable mechanical Lead the pressurizer of power.
The beneficial effects of the invention are as follows:
The split type reactor of the present invention, first whole removing remove the circulatory system, and whole tank body of cultivating is only in compression chamber Vertical sealing structure, eliminates relevant connection component, obtains relatively reliable gnotobasis, reduces carry out autoreactor to greatest extent Pollution.Split-type design, culture cabin stand alone type design so that we routinely change liquid operation and are possibly realized every other day, independent training Supporting cabin can be with cellar culture in the non-pressurised time.Split-type design so that the miniaturization of culture cabin, it is in light weight, pick and place conveniently.Point Bodyization designs, and can improve the service efficiency of compression chamber, cultivates cabin by changing, can improve the service efficiency of compression chamber.Add Ballasting can carry out 24 hours pressurized operations in theory.Splitization designs, convenient to cell tissue progress Real Time Observation, timely Solve cell growth status.Splitization design, disinfectant component only cultivate cabin, cultivate cabin pressurization lid can with autoclave sterilization, Disposable sterilized consumptive material can also be used as, sterilization is convenient, comprehensive guarantee gnotobasis.Splitization designs, and is set inside compression chamber There is constant temperature water bath system.Ensure the temperature requirement being organized in pressurized environment.
The split type reactor of the present invention, key design has been done to culture cabin, and the details of design is provided to reduce culture Pollution inside cabin.Culture cabin is needed to fill liquid when being pressurizeed so that liquid side can be thin with the silica gel of culture cabin top cover Face is in contact.So that liquid need to only reach platform, reduce liquid and overflow compression chamber, culture cabin uses double-layer sealing structure, led to Cross culture cover and cultivate the threaded connection of tank body, accomplish tentatively to seal.Pellosil is given by compression chamber top annular handgrip The pressurization of piece, 2 sealings are carried out, will not be overflowed with reaching the liquid when being pressurizeed to compression chamber.Accomplish that safety asepsis operates.
The bioreactor of novel separatedization design, key design has been done to compression chamber, using the annular handgrip of machinery, is passed through The conduction of mechanical force, the enough pressure of diaphragm is given, act on culture cabin edge inner ring.Pressure of the novel reactor to culture cabin From mechanical force, the size to cultivating cabin applying power can be precisely controlled, it is the duration, safer, effectively.
Brief description of the drawings
Fig. 1 is the split type bioreactor use state structural upright schematic diagram of the present invention;
Fig. 2 is the split type bioreactor use state structural front view of the present invention;
Fig. 3 is Fig. 2 top view;
Fig. 4 is Fig. 2 left view;
Fig. 5 is along A-A sectional view in Fig. 3;
Fig. 6 is along B-B sectional view in Fig. 3;
Fig. 7 is that the split type bioreactor of the present invention opens the structural upright schematic diagram of pressurization hatchcover;
Fig. 8 is the structure decomposition figure of the split type bioreactor of the present invention;
Fig. 9 is culture cabin structure stereogram;
Figure 10 is culture cabin structure sectional view;
Figure 11 is the partial enlarged drawing at B in Figure 10;
Figure 12 is culture cabin structure exploded view.
Embodiment
The invention will be further described with embodiment below in conjunction with the accompanying drawings.
As shown in Figures 1 to 12, a kind of split type bioreactor, by compression chamber 1, culture cabin 4, pressure seal 2 Composition.Several can be placed in compression chamber 1 has the culture cabin 4 of independent sealed structure, eliminates relevant connection component, obtains more Add reliable gnotobasis, reduce the pollution for carrying out autoreactor to greatest extent.Cultivate the stand alone type design of cabin 4 so that Wo Menchang Rule are changed liquid operation and are possibly realized every other day, and independent culture cabin can be with cellar culture in the non-pressurised time.Cabin is cultivated by changing, The service efficiency of compression chamber can be improved.
Compression chamber 1 is made up of compression chamber casing 1-1 and pressurization hatchcover 1-2.Compression chamber casing 1-1 is built with gas-pressurized Into and out of pipe 1-3,1-4, the import and export of gas-pressurized into and out of pipe is higher than the height of liquid level in compression chamber casing 1-1, and pressurize hatchcover 1-2 is connected by hinge with compression chamber casing 1-1, during pressurization, pressurization hatchcover 1-2 and the sealing of compression chamber casing 1-1 contact positions Pad 1-5 is sealed, and pressurization hatchcover 1-2 is fixed on compression chamber casing 1-1 with Quick connection part 3.
As shown in Fig. 9 to Figure 12, culture cabin 4 is made up of culture tank body 4-1, culture cover 4-2 and gel silica membrane 4-3.Training Support cover 4-2 and culture tank body 4-1 to be connected through a screw thread, and cultivate and gel silica membrane is set between tank body 4-1 and culture cover 4-2 4-3, it is pressed in by culture cover 4-2 by gel silica membrane 4-3 on culture tank body 4-1 and forms culture cover 4-2 and culture tank body 4-1 Between preliminary sealing.
In addition, being additionally provided with concavo-convex mating structures between culture cover 4-1 and culture tank body 4-1, culture cover 4-2 passes through it On groove ring cooperatively form labyrinth type mechanical seal with bulge loop on culture tank body 4-1.Cultivate cover 4-2 and gel silica membrane 4-3 Be respectively equipped with semicircle scrobicular ring and semicircle bulge loop on contact position, cultivate between cover 4-2 and gel silica membrane 4-3 by semicircle scrobicular ring and Semicircle bulge loop coordinates close connection, gel silica membrane 4-3 is removed with culture cover 4-2 from culture tank body 4-1, convenient Sterilization.
When cultivating the pressurization of cabin 1, culture tank body 4-1 fills liquid so that liquid side can be with the silica gel of culture tank body 4-1 lids Thin slice 4-3 inner face is in contact.So that liquid need to only reach culture tank body 4-1 mouths, reduce liquid and overflow compression chamber.
Several independent pressure seals 2 are separately mounted to pressurize on hatchcover 1-2, and corresponding culture cabin 4.Pressurize close Seal apparatus 2 is by pressing mechanism with machinery pressure ring group into mechanical pressure ring is made up of the annular handgrip 2-3 of machinery and drive link, mechanical ring Shape handgrip 2-3 is connected by drive link thereon with the pilot hole in pressurization hatchcover 1-2, and the annular handgrip 2-3 of machinery passes through transmission Bar can move up and down along pilot hole, and be tightly connected between the pilot hole in drive link and pressurization hatchcover 1-2 with seal, be driven Bar upper end connects pressing mechanism, the annular handgrip 2-3 of lower end connection machinery.When being pressurizeed in compression chamber 1, make the annular handgrip 2-3 of machinery It is sealed in compression chamber 1, the annular handgrip 2-3 of machinery is pressed on the gel silica membrane 4-3 in culture cabin 4 under the driving of pressing mechanism On, make to form second of sealing between gel silica membrane 4-3 and culture tank body 4-1 upper surfaces, to reach when pressurizeing to compression chamber Liquid will not overflow, and accomplish that safety asepsis operates.
Each culture cabin 4 is corresponding with a pressing mechanism.Pressing mechanism includes pressurizer 2-1, support 2-2, pressurizer 2-1 is arranged on pressurization hatchcover 1-2 by support 2-2.Pressurizer 2-1 output axis connection drive link and the annular handgrip 2- of machinery 3.Pressurizer 2-1 is cylinder, oil cylinder, watched with motor or linear electric motors etc..
The present invention, by adjusting pressurizer 2-1 mechanical conductive power, gives gel silica membrane using the annular handgrip 2-3 of machinery Pressure enough 4-3, act on the culture edge inner ring of cabin 4.And the size to cultivating the applying power of cabin 4 can be precisely controlled, continue It is time, safer, effectively.
In use, first the culture tank body in culture cabin fills liquid, and allow liquid side with cultivating the silica gel of Cap for tin body Sake is in contact, and screws culture cover, then culture cabin is put into the compression chamber casing for filling liquid, covers pressurization hatchcover, and Pressurization hatchcover is locked with Quick connection part, starts pressure seal, is made under the annular handgrip of machinery to mobile and be pressed on culture On the gel silica membrane in cabin, then, pressed gas is sent into by compression chamber by gas-pressurized inlet pipe, the pressed gas warp in compression chamber Space in the annular handgrip of machinery is acted on gel silica membrane applies pressure to the liquid in culture tank body.

Claims (7)

1. a kind of split type bioreactor, it is made up of compression chamber, culture cabin, pressure seal, it is characterised in that:It is described to add Several can be placed in ballasting has the culture cabin of independent sealed structure, cultivates cabin by changing, can improve making for compression chamber Use efficiency;The compression chamber is made up of compression chamber casing and pressurization hatchcover, compression chamber casing built with gas-pressurized into and out of pipe, The import and export of gas-pressurized into and out of pipe is higher than the height of liquid level in compression chamber casing, pressurization hatchcover and compression chamber casing contact position It is tightly connected by sealing gasket, and pressurization hatchcover is fixed on compression chamber casing with Quick connection part;Several it is independent plus Pressure sealing device is separately mounted to compression chamber and covered, and corresponding culture cabin, the mechanical annular handgrip of the pressure seal lead to The drive link crossed thereon is connected with the pilot hole in pressurization hatchcover, and the annular handgrip of machinery can be moved down by drive link along pilot hole It is dynamic, and be tightly connected between the pilot hole in drive link and pressurization hatchcover by seal, when being pressurizeed in compression chamber, machinery annular Handgrip is sealed in compression chamber, and the annular handgrip of machinery is pressed on the gel silica membrane in culture cabin under the driving of pressure seal On, make to form sealing between gel silica membrane and culture tank body upper surface, to reach when being pressurizeed to compression chamber, prevent liquid from overflowing Go out, accomplish that safety asepsis operates.
2. split type bioreactor according to claim 1, it is characterised in that:The culture cabin is by culture tank body, training Cover and gel silica membrane composition are supported, the culture cover is connected through a screw thread with culture tank body, and cultivates tank body and culture cover Between gel silica membrane is set, by culture cover by gel silica membrane be pressed in culture tank body on is formed culture cover with cultivate tank body it Between preliminary sealing.
3. split type bioreactor according to claim 2, it is characterised in that:It is described culture cover and culture tank body it Between be additionally provided with concavo-convex mating structures, culture cover cooperatively forms labyrinth type machine by groove ring thereon and the culture convex ring of tank body Tool seals;Semicircle scrobicular ring and semicircle bulge loop are respectively equipped with the culture cover and gel silica membrane contact position, cultivates cover and silicon Close connection is coordinated by semicircle scrobicular ring and semicircle bulge loop between glue film, makes gel silica membrane can be with culture cover from culture Removed on tank body, convenient sterilizing.
4. the split type bioreactor according to Claims 2 or 3, it is characterised in that:When cultivating cabin pressurization, the culture Liquid is filled in tank body, its liquid side is in contact with cultivating the silica gel thin slice inner plane of Cap for tin body so that liquid need to only reach training Tank body mouth is supported, liquid can be reduced and overflow compression chamber.
5. split type bioreactor according to claim 1, it is characterised in that:The pressure seal is by pressuring machine Structure and machinery pressure ring group are made up of into, mechanical pressure ring the annular handgrip of machinery and drive link, drive link upper end connection pressing mechanism, under The annular handgrip of end connection machinery.
6. split type bioreactor according to claim 5, it is characterised in that:The pressing mechanism include pressurizer, Support, pressurizer are covered by support installed in compression chamber.
7. split type bioreactor according to claim 6, it is characterised in that:The pressurizer is cylinder, oil cylinder, watched With one kind in motor or linear electric motors;The pressurizer is the pressurizer of adjustable mechanical conductance.
CN201711328770.9A 2017-12-13 2017-12-13 Split type bioreactor Pending CN107858285A (en)

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CN109280623A (en) * 2018-11-01 2019-01-29 刘延群 Biological respinse experiment instrument
CN109370893A (en) * 2018-11-01 2019-02-22 刘延群 Biological culture reaction unit

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Publication number Priority date Publication date Assignee Title
CN109280623A (en) * 2018-11-01 2019-01-29 刘延群 Biological respinse experiment instrument
CN109370893A (en) * 2018-11-01 2019-02-22 刘延群 Biological culture reaction unit

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