CN209162090U - Bioreactor and its cover assembly - Google Patents

Abstract

The utility model relates to a kind of bioreactor and its cover assemblies.Wherein the cover assembly includes lid ontology；And intake section and exhaust portion；The intake section and exhaust portion are respectively arranged at the lid ontology, and the intake section is greater than the exhaust portion in the length perpendicular to lid ontology bottom surface direction.The above cover assembly and bioreactor at least have many advantages, such as that conveying gas is rapid, are convenient for clean and maintenance.

Description

Bioreactor and its cover assembly

Technical field

The utility model relates to bioreactor and its cover assemblies.

Background technique

Cellular immunotherapy therapy, principle be acquisition human autoimmune's cell, by vitro culture, make its quantity at Thousand times are increased, the enhancing of targeting killing ability, and it is thin to kill pathogen, cancer in blood and tissue then to feed back to human body again Born of the same parents.

For treatment of cancer universal at present, tumour cell is killed over the course for the treatment of and lacks selectivity, is being killed While tumour cell, large quantities of normal cells are also killed.Therefore, targeted therapy is always the hot research class for the treatment of of cancer Topic.

And the method for cellular immunity, such as CAR-T (Chimeric Antigen Receptor T-Cell Immunotherapy, Chimeric antigen receptor T cell immunotherapy) it is to obtain to carry identification tumour antigen spy by gene modification The treatment method of specific receptor T lymphocyte.Its chimeric antigen receptor can specifically bind the antigen of tumor cell surface, To avoid CAR-T cellular damage to the normal cell of human body, targeted therapy is realized.On August 10th, 2017, Novartis announce FDA Its breakthrough CAR-T therapy Kymriah (tisagenlecleucel) listing of official approval, former name CTL019.For treating 25 years old refractory B cell acute lymphoblastic leukemia (ALL) patients below fix a price 47.5 ten thousand dollars.2017 10 The moon 18, FDA ratify another money CAR-T therapy Yescarta (axicabtagene ciloleucel) listing, former name KTE- C19.For treating Diffuse Large B-Cell Lymphoma (DLBCL), Primary mediastinal B-cell lymthoma (PMBCL) and transformant filter Bubble property lymthoma (TFL) is fixed a price 37.3 ten thousand dollars.The step of obtaining CAR-T cell is usually to carry out gene to the T cell of culture It transduces (CAR transduction), the cell after transduction is expanded later, obtains a large amount of CAR-T cell；CAR-T cell is difficult to height Large-scale culture is imitated, is cellular immunotherapy one of reason with high costs.Zooblast is not due to having cell wall, for outside Environment is very sensitive, such as the indexs such as gas concentration lwevel, being mixed into etc. for the pollutant in cultivating system, can be thin to animal The large-scale culture yield of born of the same parents, especially T cell significantly affects.

The animal cell culture tank of many technical grades is described in the prior art, such as in publication number CN107904169A A kind of modularized bioreactor of cell culture, air inlet pipe disclosed in state's utility model patent application protrude into culture solution With in the hybrid system of cell with to system provide oxygen.Inventors have found that during scale evaluation T cell, if will be into Tracheae protrudes into liquid level or less and conveys oxygen to cultivating system, then the bubble generated will destroy T cell, and influence cell yield.

In another example a kind of cell culture disclosed in the Chinese utility model patent application documents of publication number CN 108410734A Bioreactor, rabbling mechanism are set to tank base center, include the agitating shaft positioned at the tank interior, agitating shaft Top be equipped with upper blade, similarly with it, the life of the Chinese utility model patent application documents of publication number CN107904169A Object reactor, rabbling mechanism are similarly provided at tank base.

In practice, the magnetic agitation mechanism of above-mentioned culture tank and gas piping are difficult to dismantle taking-up, clear after culture It is clean to be cleaned in tank, if need to clean up completely, multiple repeated flushing is needed, and due to space in tank body Limitation is easy the presence of cleaning dead angle, pollutes subsequent cell culture environment.Meanwhile pipe-line system protrudes into the bottom of culture systems, The bubble of its air inlet can damaging cells.In addition, the component of rabbling mechanism is needed through tank body to connect driving motor, such as above-mentioned Rabbling mechanism in culture tank is needed through tank body bottom surface to connect driving motor, when such setting, to guarantee tank body leakproofness, Corresponding sealing element will be increased, so that structure is complicated for bioreactor, maintenance cost is increased.

In conclusion this field needs a kind of bioreactor and cover assembly, in order to realize the rule of CAR-T cell Mould culture.

Utility model content

One purpose of the utility model is to provide a kind of cover assembly.

One purpose of the utility model is to provide a kind of bioreactor.

According to a kind of cover assembly of the utility model one aspect, including lid ontology；And intake section and exhaust portion； The intake section and exhaust portion are respectively arranged at the lid ontology, and the intake section is perpendicular to lid ontology bottom surface direction Length be greater than the exhaust portion.

In the embodiment of the cover assembly, the intake section includes air inlet pipe, and the exhaust portion includes exhaust pipe, institute It states air inlet pipe and is greater than the exhaust pipe in the length perpendicular to lid ontology bottom surface direction.

In the embodiment of the cover assembly, the air inlet pipe and exhaust pipe are respectively from the plane perpendicular of the lid ontology Extend.

In the embodiment of the cover assembly, the intake section, exhaust portion respectively further comprise protrusion and are set to the lid Air inlet, the exhaust outlet of ontology are respectively used to extraneous gas source importing air inlet pipe and export the gas in exhaust pipe.

According to a kind of bioreactor of the utility model another aspect, including lid group described in any of the above one Part, the cover assembly are openably connect with the tank body；The tank body includes that highest allows liquid level；The intake section goes out Port is higher than the air inlet of the exhaust portion in the intracorporal vertical position of the tank, and the gas outlet of the intake section is higher than The highest allows liquid level.

It further include the blender for being set to the tank interior space in the embodiment of the bioreactor, it is described Blender is removably connect with the cover assembly.

In the embodiment of the bioreactor, the cover assembly further includes hollow cylindricality engaging body, the column The bottom surface one of the bottom surface of shape engaging body and the lid ontology has including one group of opposite side with connecting hole and one group The opposite side of wedge-shaped card slot；The hollow region of the one end of the axis of the blender far from the blade and a cylindricality fixture block Prop hole match, the cylindricality fixture block includes one group of opposite outside having with the wedge-shaped fixture block of the wedge-shaped card slot cooperation Wall and one group of opposite lateral wall with the snap hook cooperated with the connecting hole, the blender and the cover assembly are logical It crosses the cylindricality fixture block and cylindricality engaging body is detachably connected.

In the embodiment of the bioreactor, the gas outlet of the intake section, which is higher than the highest, allows liquid level 30- 50mm。

According to a kind of bioreactor of the another aspect of the utility model, including tank body, intake section and exhaust portion；It is described Tank body includes that highest allows liquid level；The gas outlet of the intake section is higher than the exhaust in the intracorporal vertical position of the tank The air inlet in portion, and the gas outlet of the intake section is higher than highest permission liquid level.

In the embodiment of the bioreactor, the gas outlet of the intake section, which is higher than the highest, allows liquid level at least 30-50mm。

The progress effect of the utility model includes at least, the design of cover assembly, so that cultivating system and extraneous energy are sufficiently Rapidly carry out gas exchanges, at the same be also easy to tank body, blender installing and dismounting, facilitate carry out clean and maintenance.

Detailed description of the invention

The above and other feature, property and advantage of the utility model will be by with reference to the accompanying drawings and examples Description and become readily apparent from, in which:

Fig. 1 is the structural schematic diagram of the embodiment of cell culture system.

Fig. 2 is the structural schematic diagram of the embodiment of bioreactor.

Fig. 3 is the schematic cross-sectional view of the embodiment of bioreactor.

Fig. 4 is the external structure schematic diagram of the embodiment of the tank body of bioreactor.

Fig. 5 is the structural schematic diagram of the embodiment of the cover component of bioreactor.

Fig. 6 is the schematic cross-sectional view of the cover component of Fig. 5.

Fig. 7 is the structural schematic diagram of the embodiment of cylindricality fixture block.

Fig. 8 is the structural schematic diagram of the embodiment of the blender of bioreactor.

Fig. 9 is the structural schematic diagram of another angle of the blender of Fig. 8.

Figure 10 is the structural schematic diagram of the depression angle of the blender of Fig. 8

Figure 11 is the blender whipping process schematic diagram of bioreactor.

Figure 12 is the structural schematic diagram of the embodiment of bioreactor.

Specific embodiment

It is following to disclose the embodiment or embodiment of subject technology scheme described in a variety of different implementations.For simplification The specific example of each element and arrangement is described below in disclosure, and certainly, these are only example, is not to this The protection scope of utility model is limited.Such as the fisrt feature then recorded in the description above second feature or It is formed above, may include the embodiment that the first and second features are formed by way of directly contacting, also be included in The embodiment that supplementary features are formed between one and second feature, to can not directly be contacted between the first and second features. In addition, in these disclosures may in different examples repeat reference numerals and/or letter.The repetition is in order to brief With it is clear, itself do not indicate each embodiment being discussed and/or interstructural relationship.Further, when first element is It is described with the mode for being connected with second element or combining, which includes that the first and second elements are connected directly or are bonded to each other Embodiment, also include made using one or more other intervening elements additions the first and second interelements ground connection be connected or that This is combined.

In addition, it is necessary to understand, the noun of locality such as " front, rear, top, and bottom, left and right ", " laterally, vertical, vertical, horizontal " and Orientation or positional relationship indicated by " top, bottom " etc. is normally based on orientation or positional relationship shown in the drawings, merely to just In description the utility model and simplify description, in the absence of explanation to the contrary, these nouns of locality do not indicate that and imply institute The device or element of finger must have a particular orientation or be constructed and operated in a specific orientation, therefore should not be understood as to this The limitation of utility model protection range；The noun of locality " inside and outside " refers to inside and outside the profile relative to each component itself, use " the One ", the words such as " second " limit components, it is only for convenient for distinguishing to corresponding components, such as without separately sound Bright, there is no particular meanings for above-mentioned word, therefore can not be interpreted as the limitation to scope of protection of the utility model.

Meanwhile the application has used particular words to describe embodiments herein.Such as " one embodiment ", " one implements Example ", and/or " some embodiments " mean a certain feature relevant at least one embodiment of the application, structure or feature.Cause This, it should be highlighted that and it is noted that " embodiment " or " an implementation referred to twice or repeatedly in this specification in different location Example " or " some embodiments " are not necessarily meant to refer to the same embodiment.In addition, certain in one or more embodiments of the application Feature, structure or feature can carry out combination appropriate.

As shown in Figure 1 to Figure 3, T cell culture systems include bioreactor 1, the circulatory system 2 and and bioreactor The connected and pipeline 41,42,43,44,45 with external connection.Bioreactor 1 includes tank body 11, the setting of 11 upper end of tank body Cover assembly 12 and tank interior space 11 is set to for stirring the blender 13 of T cell and culture solution.Tank body 11 There are four mouth, first entrances 110, for inputting liquid or the initial T by transduction to 11 inner space of tank body for side wall setting Cell, in the cell amplification cultivation stage, the liquid inputted toward first entrance 110 is culture solution, after amplification cultivation, toward first The liquid that entrance 110 inputs is the physiological saline for washing T cell；First outlet 111 is for being output to the outside cell culture Product, in the present embodiment, output be T cell and physiological saline that washing finishes mixture；Second entrance 112, second go out Mouth 113 is connected with the circulatory system 2, in cell cultivation process, under the driving of the peristaltic pump (not shown) of the circulatory system 2, carefully The mixture of born of the same parents' culture solution and cell is discharged into the filtering film component 21 of the circulatory system 2, filtering film component from second outlet 113 21 can be hollow filter membrane component, and filtering film component 21 has semi-permeable membrane, and membrane aperture can be 0.2 micron, can through water with And the ingredient for the metabolic waste that cell culture generates in culture solution, and cell itself can not then penetrate, therefore, part culture solution and Metabolic waste is filtered, and remaining part culture solution and cell are entered the inner space of tank body 11 by second entrance 112 again.The One outlet 111, second outlet 113 are all set in the bottom position of tank wall, sufficiently to pump out the cell inside tank body 11 And liquid.Specifically, as shown in Figure 1 and Figure 2, first entrance 110, first outlet 111 are identical in the circumferential position of side wall, First entrance 110 is higher by at least 30mm of first outlet 111 in the axial direction, to facilitate the operation of grafting pipeline, but art technology The speed that falls to cultivating system of the personnel it should be understood that the height of first entrance can not be excessively high, when otherwise culture solution imports It spends fastly, is directly impinging liquid level from top to down, it is likely that damage T cell, first entrance 110 are higher by first outlet in the axial direction 111 distance can be 30-50mm.Second entrance 112, the position of second outlet 113 and first entrance 110, first outlet 111 Position with the axis of tank body 11 axisymmetricly, to facilitate draft process when processing.

As shown in Fig. 2, Fig. 3, Figure 11 and Figure 12, driving tank body 11 inside blender 13 rotation structure can be as Magnetic agitation structure shown in Figure 12.The pallet 3 of magnetic agitation structure includes the disk for the bottom supporting tank body in tank body 11 Body 31 and magnetic agitation driver 32, as shown in figure 3, magnetite 14 is set in the magnetite accommodating chamber 131 of blender 13.Continue With reference to Figure 11, under the driving of magnetic driver 31, the magneticaction of magnetite 14 and driver 32 that blender 13 accommodates, driving Blender 13 inside tank body 11 rotates, to stir cell and culture solution, so that cell, culture solution and oxygen sufficiently connect Touching.The principle that magneticaction drives blender 13 to rotate is the working principle of the magnetic stirring apparatus of chemical-biological field routine, i.e., The motor of driver 32 drives the magnet rotation of driver after energization, and then drives magnetite 14, drives blender 13 to rotate, this is Skilled addressee readily understands that content, therefore narration is no longer developed in details.Inner fovea part can be set in the bottom of tank body 11 115, tank body 11 is cooperated with the corresponding male part 311 of external disk body 31, to fix tank body 11, so but also tank body 11 assembling on pallet 3 is more convenient.It is stirred in above-described embodiment using the contactless driving of magnetic agitation principle Device 13, the mode for generalling use the shaft of motor direct-drive blender compared with the prior art are compared, and most important advantage exists In can guarantee the clean and easy to maintain of the cell culture environment inside tank body 11.The reason is that direct using motor The shaft of blender is driven, motor usually requires to be placed in except tank body 11, then the shaft of blender must extend tank body 11, Therefore it needs to guarantee stringent sealing under culture environment for a long time between the shaft and tank body 11 of blender, so increases and be The complexity of system is difficult to safeguard, and the abrasion of sealing element itself may also pollute cultivating system.In addition, tank body 11 What side wall can be at least partly transparent, it so can be convenient the culture situation in operator's observation tank body 11, such as liquid level height It is low, culture solution and the mixing uniformity of cell etc., it is preferable that as shown in Figure 2, Figure 4 shows, phase can be set in the side wall of tank body 11 The fluid level scale answered, to facilitate operation person's quantitative observation, record liquid level variation.Fluid level scale includes that highest allows liquid level 117, i.e., The extreme higher position of the cultivating system of addition cell and culture solution, which must not exceed highest, allows liquid level, and position can be used as culture The air inlet of the intake section of tank 1 protrude into depth inside tank body 11, blender 13 blade height reference.In Fig. 2, Fig. 4 The diameter of the tank body 11 of embodiment is 80mm, and highest allows liquid level 117 to be at 300mL scale.For different culture scales Demand can increase accordingly the diameter of tank body 11, and height is constant, therefore its highest allows the height of liquid level also constant, example It such as can be 100mm, 120mm by the enlarged-diameter of tank body 11, highest allows liquid level to be 450mL, 650mL scale, but its tank The height of body 11 is constant, therefore highest allows liquid level 117 constant in the position of tank body 11.

With reference to shown in Fig. 3, Fig. 4, the open end 118 of tank body 11, i.e., the top of the tank body 11 of embodiment in figure, be provided with from The threaded joints 119 that open end 118 extends to the other end of tank body, the screw thread of the inner wall of the lid ontology of corresponding cover assembly 12 Interconnecting piece 120, as shown in Figure 5, Figure 6, the threaded joints 120 of Gai Benti are internal screw thread, and the threaded joints 119 of tank body 11 are External screw thread, it should be readily apparent to one skilled in the art that threaded joints 120 or external screw thread, threaded joints 119 can also be with For internal screw thread, tank body 11 is connected with cover assembly 12 using screw connection structure, facilitates operator that cover assembly 12 is installed Tighten and remove cleaning.As shown in Figures 2 to 4, tank body 11 is provided in the end side of threaded joints 119 from 11 side wall of tank body The retention bead 1110 of radial projection, plays position-limiting action during tightening cover assembly 12, i.e. prompt operator is screwed to It can stop herein.It is of course also possible to cover this body sidewall accordingly open up groove (not shown), after tightening with retention bead 1110 cooperations, to prevent cover assembly 12 caused by due to maloperation etc. from even being opened by random loosen, it is ensured that cultivated Gnotobasis in journey inside tank body 11.

As shown in Fig. 1, Fig. 3 and Fig. 5 to Fig. 7, the cover assembly 12 of bioreactor 1 include lid ontology 121 and It is set to being used for the intake section 122 of the conveying of 11 inner space of tank body and discharge gas, exhaust portion 123 for the lid ontology 121, Such as Fig. 3 and shown in fig. 5, length of the intake section 122 in the bottom surface direction perpendicular to lid ontology 121 is greater than exhaust portion 123；? When cell culture, intake section 122 is for conveying gas into the tank body 11 of bioreactor 1, when carrying out cell culture, air inlet Portion 122 conveys gas by the way of non-contact conveying, i.e. structure of intake section 122 itself and the liquid level of culture solution is contactless, Such setting is beneficial in that, protrudes into liquid level with the air inlet pipe of the prior art, causes to generate bubble in cultivating system and damage Hurt T cell, contactless conveying can prevent the generation of bubble, improve the yield of T cell.Meanwhile intake section 122 perpendicular to The length in the bottom surface direction of lid ontology 121 is greater than exhaust portion 123, the beneficial effect is that, compared to the length of intake and exhaust Equal or shorter setting can adjust oxygen and gas concentration lwevel in cultivating system more quickly.The gas of air inlet Ingredient is deployed with the different phase of culture, and the ratio of the carbon dioxide of initial stage air inlet properly increases, and with culture Progress, cellular respiration also generates a certain amount of carbon dioxide, so that the ratio of carbon dioxide can reduce in air inlet.Specifically Ground, as shown in Fig. 3 and Fig. 5 to Fig. 6, intake section 122, exhaust portion 123 specific structure example can be it is as shown in the figure Intake section 122 includes air inlet pipe, and exhaust portion 123 includes exhaust pipe, and the air inlet pipe is perpendicular to 121 bottom surface direction of lid ontology Length is greater than the exhaust pipe.Although exhaust outlet can also be only provided with using other structure types, such as exhaust portion 123 Structure, without exhaust pipe.Intake section 122, exhaust portion 123 are all made of the structure of exhaust pipe, so that cultivating system and the external world Gas exchanges are more rapid, also can more efficiently adjust the gas componant in culture gas.Further, air inlet pipe and exhaust pipe Specific structure can be as Fig. 3 and Fig. 5 to it is shown in fig. 6 from the plane perpendicular of lid ontology 121 extend.Although there is also it Its set-up mode, such as radially extended in the side wall of lid ontology 121, it bends later, then along the bottom surface perpendicular to lid ontology 121 Direction extend.The structure extended using the plane perpendicular of direct lid ontology 121 as shown in the figure, easy to process and installation, Convenient for cleaning air inlet pipe and escape pipe.In addition, intake section 122, exhaust portion 123 are also distinguished with reference to Fig. 1, Fig. 3 and Fig. 5 to Fig. 6 Be set to air inlet 124, the exhaust outlet 125 of lid ontology 121 including protrusion, be respectively used to import extraneous gas source air inlet pipe and By the gas export in exhaust pipe.Although there is also others importing and derived type structures, such as directly in lid ontology 121 itself Mouth is opened up, directly contacts and is connected with air inlet pipe, exhaust pipe.It, can using the setting of the air inlet 124, exhaust outlet 125 of protrusion setting In order to the grafting and disassembly of pipeline and air inlet pipe, exhaust pipe, the sealing of bioreactor 1 is also ensured.Protrusion setting into Port 124, exhaust outlet 125 specific structure not with illustrate in pagoda-shaped interface be limited, be also possible to hickey, fast grafting The common interface structures such as mouth.

With continued reference to Fig. 3, Fig. 5 to Fig. 7, in bioreactor 1, the connection structure of blender 13 and cover assembly 12 can be with It is that removably, so can be convenient operator and carry out clean and maintenance.When being cleaned, operator first tears cover assembly 12 open Under, blender 13 is removed from lid later, so fully cover assembly 12 and blender 13 can be carried out clearly It washes, guarantees the clean level of cultivating system.The specific structure being detachably connected can be Fig. 3, Fig. 5 to cylindricality card shown in Fig. 7 Structure is closed, cover assembly 12 further includes hollow cylindricality engaging body 126, the bottom surface one of bottom surface and lid ontology 121, cylindricality card Zoarium 126 includes one group of opposite side with the opposite side of connecting hole 127 and one group with wedge-shaped card slot 1261.Phase Accordingly, the formation of prop hole 129 of one end of the axis 132 of blender 13 and the hollow region 1200 for being set to cylindricality fixture block 128 Shaft hole matching, as shown in figure 3, in the lower end of prop hole 129, i.e., close to one end of blade, axis 132, which is additionally provided with, to be radially extended Step surface 136, the beneficial effect is that, axis when rotated, may rub with the prop hole 129 of cooperation and generate clast, platform The setting of terrace 136 can prevent above-mentioned clast from falling into cultivating system out of prop hole 129, to keep culture environment It is clean.Cylindricality fixture block 128 further includes one group of opposite lateral wall with the wedge-shaped fixture block 1200 cooperated with wedge-shaped card slot 1261 There is the opposite lateral wall of the snap hook 1201 cooperated with connecting hole 127 with one group, blender 13 passes through with cover assembly 12 Cylindricality fixture block 128 and the snap-in structure of cylindricality engaging body 126 are detachably connected.

In addition, the concrete form that cover assembly 12 and tank body 11 cooperate can be cover assembly 12 and tank body 11 openably Connection, such as Fig. 2 are also possible to other common openable formula connection structures to screw thread Detachable connection structure shown in fig. 6, Such as cover assembly is connect with tank body by movable hinge.With continued reference to Fig. 2 and Fig. 3, the gas outlet 1221 of intake section 122 Vertical position in tank body 11 is higher than the air inlet 1231 of exhaust portion 123, and the gas outlet 1231 of intake section 122 is higher than The highest of tank body 11 allows liquid level 117, generates bubble damage T cell to prevent intake section 122 from directly contacting with liquid level.It is preferred that Ground, intake section gas outlet are higher than highest liquid level 30-50mm, to guarantee that distance of the gas outlet 1221 away from liquid level is guaranteeing not damage T While cell, quickly, gas is sufficiently conveyed into cultivating system, so that T cell comes into full contact with fresh oxygen.It can manage Xie Di, cover assembly 12 are also possible to, the i.e. cover assembly 12 closed top that is a kind of tank body 11 not openable with tank body 11 The form in face, the relative position of the air inlet 1231 of 1221 exhaust portion 123 of gas outlet of intake section 122 and intake section 122 The highest of gas outlet 1221 and tank body 11 allows the relative position of liquid level 117, can beat with above-mentioned cover assembly 12 with tank body 11 The embodiment opened is consistent.So also can achieve prevents from generating bubble in cultivating system, and guarantees in cultivating system sufficiently quickly Gaseous matter exchange effect, certainly, the not openable structure of use, i.e. tank body 11 and intake section 122, exhaust portion 123 1 The structure of body reduces the number of part, reduces cost, but may may cause inconvenience to the cleaning of the two.

With reference to Fig. 3, Fig. 8 to Figure 11, the structure of the blender 13 of bioreactor 1 includes axis 132 and with axis 132 Axis is in rotational symmetry and the blade 133 for connecting axis 132, and the quantity of blade can be two panels as shown in Figure 3, be also possible to It is more than two panels.Every blade 133 includes blade body, and such as Fig. 9 and shown in Fig. 10, blade body extends in the shape of a spiral, leaf The dimensional parameters of piece ontology include 20% to 35% that its axial length accounts for the height of tank body 11, and the axis 132 of blender is basic Height along tank body 11 is arranged, i.e. the axial length of blade body accounts for the 20% to 35% of 132 length of axis；The spiral shell of blade body Rotation rotation angle is 15 ° to 50 °, is in the illustrated embodiment 18 °, and maximum radial length is the radical length of tank body 11 50% to 90%, the corresponding diameter of tank body 11 of illustrated embodiment can be 80mm, 100mm, 120mm, corresponding blade respectively The range of the maximum radial length of ontology is 20-36mm or 25-45mm or 30-54mm respectively, and blade body is from bottom to top Radical length gradually become smaller.Using the blade 133 of above-mentioned shape, the shearing force for T cell can be reduced while making T Cell and cultivating system stir evenly.Its concrete reason is, as shown in figure 11, under the driving of magnetic driver 31, stirs The magnetite 14 of the receiving of device 13 and the magneticaction of driver 32 are mixed, driving is located at the blender 13 inside tank body 11 and rotates.It compares In the configuration of the plane formula blade of the prior art, spiral blade is smaller for the shearing force of fluid, more leniently " holds up " Cell and culture solution, and the axial direction of blade body, radial dimension design, so that blade is larger with respect to the size of tank body, so Reduce in the radial space between blade body and tank body and form the space being tangentially vortexed, further protects T cell；Together When, the radical length of blade body from bottom to top reduces, and allows and is swimmingly flowed by the cell of " picking-up " with culture solution Dynamic circulation, make cell and culture solution stirring body axial sufficiently agitation mixedly it is also possible to quickly, fully with Input the gas contact of cultivating system.Especially for intake section 122 shown in Fig. 3 embodiment to the tank body of bioreactor 1 For the structure for non-contactly conveying gas in 11, axial rolling up and down be more advantageous to cell, culture solution sufficiently with input Oxygen contact.Culture blender 13 using the above structure in bioreactor 1, turns during T cell amplification cultivation T cell after leading can continue to stir during the cultivation process with culture liquid mixture, amplification cultivation immunocyte, it is preferable that stirring The mixing speed of device is about 20-60 revs/min, and more slow mixing speed is combined with the blade 133 of above-mentioned shape, favorably In further decreasing the shearing force in stirring system, the yield of T cell is improved.

Further, as shown in Fig. 8 to Figure 10, the radical length of blade body is gradually smaller specific from bottom to top Structure, which can be, to be gradually become smaller with axial height with linear relationship, such as is cut on the basis of a right helicoid by circular conical surface It is retained in the part within the circular conical surface after removing to be formed, the semi-cone angle of circular conical surface is 20-45 degree；Straight edge line and axis can also be used The angle of line be 20-45 degree oblique helicoid or the corresponding conical surface semi-cone angle be 20-45 degree cone helicoid based on, by The spiral-shaped of blade is obtained after circular conical surface excision.The beneficial effect so obtained is reaching thin conducive to axial rolling up and down While the technical effect of born of the same parents and culture solution, reduces blade 133 and 11 side wall of tank body forms the space of radial whirl, stirred with reducing The shearing force for mixing process generation improves its yield to protect T cell.Inner fovea part can be set for the bottom of tank body 11 115, tank body 11 is cooperated with the corresponding male part 311 of external disk body 31, for fixing the embodiment of tank body 11, is stirred 133 bottom for mixing the blade of device 13 also corresponds to the notch 134 that the inner fovea part 115 of tank body 11 is arranged, it is readily appreciated that ground, notch Also need between 134 and inner fovea part 115 there are certain interval, when preventing the blade 133 of blender 13 from rotating with inner fovea part 115 It interferes.Axial gap between notch 134 and inner fovea part 115 is at least 2mm.Using the structure of notch 134, beneficial to effect The installation that fruit is convenient for blender 13.Specifically, first that tank body 11 is fast by the setting of inner fovea part 115 in assembling process The speed cooperation of male part 311 corresponding with disk body 31 is fixedly mounted, and blender 13 is passed through blade notch 134 and inner fovea part later 115 are coupled to the inside of tank body 11.

Further, the specific structure being detachably connected for realizing blender 13 and cover assembly 12 may include specification The cylindricality of cover assembly above-mentioned 12 and blender 13 is connected together structure, is also possible to other connection structures, such as by axis 132 one end is processed as external screw thread or internal thread structure and connect with cover assembly 12 etc..

To sum up, using the cell culture system of above-described embodiment, bioreactor 1, cover assembly 12 and blender 13 Beneficial effect include at least:

1. the blade of blender uses helicoid and specific axial dimension, radial dimension of design, in cultivating system In reach and axially stir cell and culture solution in tank body 11, minimize radial shearing force, to protect cell, improve cell The effect of yield；

2. the design of cover assembly 12 enables cultivating system and the external world sufficiently and quickly to carry out gas exchanges, while Be easy to tank body 11,13 installing and dismounting of blender, facilitate carry out clean and maintenance.

3. the cooperation of the entrance and cell culture system of tank body 11, so that can be recycled in cell cultivation process constantly Ground persistently carries out the supplement of fresh medium and the discharge of waste liquid, improves the efficiency of cell culture.

Although the utility model is disclosed as above with above-described embodiment, its be not for limiting the utility model, it is any Those skilled in the art without departing from the spirit and scope of the utility model, can make possible variation and modification, example The T cell culture of above-described embodiment is such as applied to the culture of other types of immunocyte, even other types of lactation The culture of zooblast.Therefore, all contents without departing from technical solutions of the utility model, the technology according to the utility model are real Matter any modification, equivalent variations and modification to the above embodiments, each fall within what the utility model claims were defined Within protection scope.

Claims (10)

1. a kind of cover assembly is used for cell culture system characterized by comprising

Lid ontology；And

Intake section and exhaust portion；

The intake section and exhaust portion are respectively arranged at the lid ontology, and the intake section is perpendicular to lid ontology bottom surface The length in direction is greater than the exhaust portion.

2. cover assembly as described in claim 1, which is characterized in that the intake section includes air inlet pipe, the exhaust portion packet Exhaust pipe is included, the air inlet pipe is greater than the exhaust pipe in the length perpendicular to lid ontology bottom surface direction.

3. cover assembly as claimed in claim 2, which is characterized in that the air inlet pipe and exhaust pipe are respectively from the lid ontology Plane perpendicular extend.

4. cover assembly as claimed in claim 2, which is characterized in that the intake section, exhaust portion respectively further comprise protrusion and set It is placed in air inlet, the exhaust outlet of the lid ontology, is respectively used to extraneous gas source be imported to air inlet pipe and by the gas in exhaust pipe Body export.

5. a kind of bioreactor, including tank body, which is characterized in that the cover assembly as described in claim 1-4 any one, The cover assembly is openably connect with the tank body；The tank body includes that highest allows liquid level；The outlet of the intake section Mouth is higher than the air inlet of the exhaust portion in the intracorporal vertical position of the tank, and the gas outlet of the intake section is higher than institute Stating highest allows liquid level.

6. bioreactor as claimed in claim 5, which is characterized in that further include being set to stirring for the tank interior space Device is mixed, the blender is removably connect with the cover assembly.

7. bioreactor as claimed in claim 6, which is characterized in that

The cover assembly further includes hollow cylindricality engaging body, the bottom surface of the bottom surface of the cylindricality engaging body and the lid ontology One, opposite side and one group of opposite side with wedge-shaped card slot including one group with connecting hole；

The one end of the axis of the blender far from stirring blade is matched with the prop hole of the hollow region of a cylindricality fixture block, described Cylindricality fixture block includes one group to be had and institute with the opposite lateral wall of the wedge-shaped fixture block with the wedge-shaped card slot cooperation and one group State the opposite lateral wall of the snap hook of connecting hole cooperation, the blender and the cover assembly by the cylindricality fixture block with And cylindricality engaging body is detachably connected.

8. bioreactor as claimed in claim 5, which is characterized in that the gas outlet of the intake section permits higher than the highest Perhaps liquid level 30-50mm.

9. a kind of bioreactor, which is characterized in that including tank body, intake section and exhaust portion；

The tank body includes that highest allows liquid level；

The gas outlet of the intake section is higher than the air inlet of the exhaust portion in the intracorporal vertical position of the tank, and described The gas outlet of intake section, which is higher than the highest, allows liquid level.

10. bioreactor as claimed in claim 9, which is characterized in that the gas outlet of the intake section is higher than the highest Allow liquid level at least 30-50mm.