WO2015135376A1 - 一次性生物反应器 - Google Patents

一次性生物反应器 Download PDF

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Publication number
WO2015135376A1
WO2015135376A1 PCT/CN2015/000132 CN2015000132W WO2015135376A1 WO 2015135376 A1 WO2015135376 A1 WO 2015135376A1 CN 2015000132 W CN2015000132 W CN 2015000132W WO 2015135376 A1 WO2015135376 A1 WO 2015135376A1
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WO
WIPO (PCT)
Prior art keywords
chamber
reactor
disposable bioreactor
wall
chamber wall
Prior art date
Application number
PCT/CN2015/000132
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English (en)
French (fr)
Inventor
韩志强
童胜
刘慧涛
Original Assignee
郑州威瑞生物技术有限公司
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Application filed by 郑州威瑞生物技术有限公司 filed Critical 郑州威瑞生物技术有限公司
Publication of WO2015135376A1 publication Critical patent/WO2015135376A1/zh
Priority to US15/154,869 priority Critical patent/US20160257919A1/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/28—Constructional details, e.g. recesses, hinges disposable or single use
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/34—Internal compartments or partitions
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/38—Caps; Covers; Plugs; Pouring means
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/06—Nozzles; Sprayers; Spargers; Diffusers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/26—Means for regulation, monitoring, measurement or control, e.g. flow regulation of pH
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/34—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas

Definitions

  • the present invention relates to the field of bioreactor technology, and in particular to a disposable bioreactor.
  • Shaker-driven non-intrusive hybrid bioreactors include small culture tubes, rotary bottles, conical flasks, inverted cone bottom bottles, flat cone bottom bottles and flat cone bottom tanks, and agitated bioreactors of different sizes driven by paddles. It is the most widely used bioreactor for fermentation and cell suspension culture.
  • a common feature of a shaker driven non-intrusive hybrid bioreactor is that the opening is located at one end of the reactor and coaxial with the long axis of the reactor chamber, except that the rotating bottle is placed horizontally at the upper end and is driven by rotation or swirling. The liquid in the device generates eddy currents.
  • Increasing the oxygen transfer of the liquid by generating eddy currents mainly utilizes the principle of increasing the surface area of the liquid, and the oxygen transfer mode which increases the surface area of the liquid still has the problem of low mixing efficiency. Since the opening is located at one end of the long axis of the reactor and coaxial with the long axis of the reactor chamber, in order to prevent liquid spillage, it is necessary to increase the length of the upper gas passage, that is, to increase the ineffective passage of gas exchange through the reactor opening. , thus reducing the efficiency of gas exchange.
  • the agitated bioreactor has an efficient mixing, it is one of the main drawbacks of the agitated reactor because the shearing force of the agitating paddle causes cell damage and death and limits it to gentle agitation.
  • the existing rotary bottles, conical flasks, inverted cone bottom bottles, flat cone bottom bottles and flat cone bottom tanks, and different sizes of stirred tank reactors are made of hard materials such as glass, hard plastic and stainless steel, due to Reactors for glass and stainless steel need to be reused, not only for cleaning, disinfection and certification, but also for the risk of cross-contamination.
  • the hard plastic injection molding reactor can be used at one time, due to the limitation of production process efficiency and the use of relatively large raw materials, the shape is fixed and cannot be stretched and deformed, and cannot be nested with each other, occupying a large space, not only transportation, irradiation and storage costs.
  • the disposable bioreactor of the present invention adopts the following technical scheme: a disposable bioreactor including a reactor chamber and a communication tube, the communication tube is located at the top of the reactor chamber, and the reactor chamber is composed of two The cavity wall above the sheet is fused or adhesively joined and has a junction and at least one hollow arm that communicates with the communication tube through the junction, the end of the hollow arm being closed.
  • the hollow arms are horizontally disposed.
  • the reactor chamber has one of the hollow arms, the communication tube being located at the top of the reactor chamber and forming an L-shaped structure with the hollow arms.
  • the reactor chamber has two of said hollow arms, and the communication tube is disposed at the top of the reactor chamber and forms an inverted T-shaped structure with the hollow arms.
  • the reactor chamber has two pieces of the chamber wall, and the two chamber walls are arranged one above the other, the upper part is the upper chamber wall, the other is the lower chamber wall, and at least one of the upper and lower chamber walls has the curved chamber wall. .
  • One of the upper and lower chamber walls is a solid support chamber wall that retains its inherent shape, and the other is a soft membrane chamber wall.
  • the solid support cavity wall is injection molded from a plastic material or molded or blow molded from a plastic sheet.
  • the soft membrane cavity wall is composed of a flat plastic film or a deformable soft bubble formed by a plastic film of a flat plastic film.
  • the upper and lower chamber walls are all the curved chamber walls, and the solid support chamber wall is a stackable cavity wall which can be inserted into the sleeve, and the soft membrane chamber wall can be folded into the solid support chamber wall to make the reactor The cavity can be inserted into the wall of the cavity.
  • One of the upper and lower chamber walls is the curved chamber wall and the other is a planar chamber wall.
  • the connecting pipe and the upper cavity wall are integrated structures.
  • the outer port of the connecting pipe is punched out after the plastic forming, and the outer port of the communicating pipe has a reinforcing ring around the outer port which is punched and left.
  • the lower chamber wall is the curved chamber wall
  • the bioreactor further comprises a supporting fixing seat, wherein the supporting fixing seat is provided with a retaining groove for giving way to the lower chamber wall, and the groove for the recess is provided
  • a fixed structure for fixing or pulling the reactor cavity is provided around the mouth.
  • junction of the upper and lower chamber walls has a joint edge extending toward the periphery for supporting and pulling the fixed reactor cavity.
  • the reactor further includes a cover for covering the upper chamber wall of the reactor chamber, and the cover is provided with a sealing portion for sealing the nozzle of the communication tube.
  • the cover forms a flip structure of the reactor cavity, one of the opposite sides of the cover is joined to the joint edge, and a fixed snap is provided between the other side and the joint edge.
  • the chamber wall of the reactor chamber is provided with a conduit connecting the reactor chamber for liquid and gas to enter and exit, and dissolved oxygen, carbon dioxide, and PH sensor electrodes, and the conduit connecting the inner chamber of the reactor is integrated with the connected chamber wall. Molded structure.
  • the reactor cavity is formed by melting or bonding two chamber walls, one of the two chamber walls is a front chamber wall, and the other is a rear chamber wall, and a joint edge is provided at a joint portion of the front and rear chamber walls.
  • the hollow arms of the reactor chamber are formed by corresponding portions of the front and rear chamber walls.
  • the reactor chamber has a junction portion and at least one hollow arm portion that communicates with the communication tube through the intersection portion, the end of the hollow arm portion is sealed and the communication tube is located in the reactor The top of the cavity.
  • the bioreactor of the present invention is capable of flowing liquid in a narrow space at least at the hollow arm, since the communication tube is disposed at the top of the reactor chamber, the liquid is along the horizontal direction of the reactor
  • the long axis flow, the shaft of the connecting tube shaft liquid flow is a vertical axis, whether placed in a rocking shaker, a plane swing shaker, or a three-dimensional swing shaker, the liquid can flow in the hollow arm of the reactor Without causing splattering, when reaching the closed end of the hollow arm, the flow turbulates, folds back and turns under the action of turbulence, eddy currents and waves generated at the sealing end of the hollow arm.
  • the oxygen in the upper space is entangled into the liquid flow, that is, the liquid in the hollow arm can be alternately tumbling up and down during the flow, so that the oxygen is in full contact with the present
  • the method of increasing the surface area of the liquid flow is used to greatly improve the mixing and mass transfer efficiency as compared with the manner in which the liquid stream is mixed with oxygen.
  • the curved cavity wall can reduce the wrinkle of the reactor cavity when pulling the reactor cavity; the solid support cavity wall is more favorable for maintaining the three-dimensional space in the reactor cavity and is convenient to use; After the cavity wall is set as a stackable cavity wall, the space occupied by the reactor can be further reduced, the transportation, irradiation and storage of the reactor are facilitated, and the cost is reduced; the reinforcing ring at the outer port of the connecting pipe is connected. It has the function of strengthening the strength of the connecting nozzle and preventing the cap from slipping off; supporting the fixing seat can assist the fixing of the reactor cavity, which brings convenience for the large-scale development of the reactor; the joint edge can not only support the reactor cavity The role, but also provides a focus for the pulling of the reactor cavity.
  • the cover can cover and close the upper cavity wall together with the communication tube, and the sealing portion of the cover can be used for sealing the nozzle of the communication pipe.
  • the chamber wall of the reactor chamber includes a conduit connected to the reactor chamber for the liquid and gas to enter and exit, and a conduit for the dissolved oxygen, carbon dioxide, and PH sensor electrodes to be integrally formed with the reactor chamber wall.
  • Figure 1 is a schematic view showing the structure of Embodiment 1 of a disposable bioreactor
  • FIG. 2 is an exploded view of Embodiment 1 of the disposable bioreactor
  • FIG. 3 is a first working principle diagram of Embodiment 1 of the disposable bioreactor
  • FIG. 4 is a second working principle diagram of Embodiment 1 of the disposable bioreactor
  • Figure 5 is a schematic view showing the cooperation of the connecting pipe and the pipe cap of Figure 1;
  • Figure 6 is a schematic structural view of Embodiment 2 of a disposable bioreactor
  • Figure 7 is a schematic structural view of Embodiment 3 of a disposable bioreactor
  • Figure 8 is an exploded view of Example 3 of the disposable bioreactor
  • Figure 9 is a schematic structural view of Embodiment 4 of a disposable bioreactor
  • Figure 10 is a schematic structural view of Embodiment 5 of a disposable bioreactor
  • Figure 11 is an exploded view of Example 5 of the disposable bioreactor
  • Figure 12 is a side view of a side-by-side placement of Example 5 of a disposable bioreactor
  • Figure 13 is a schematic view showing the structure of Embodiment 6 of the disposable bioreactor
  • Figure 14 is a schematic view showing the structure of Embodiment 7 of the disposable bioreactor
  • Figure 15 is a schematic view showing the structure of the disposable bioreactor after the liquid is charged into the liquid;
  • Figure 16 is a schematic view of the insert stack of the embodiment 7 of the disposable bioreactor
  • Figure 17 is a schematic view showing the structure of Embodiment 8 of the disposable bioreactor
  • Figure 18 is a schematic view showing the structure of the disposable bioreactor after the liquid is charged into the liquid;
  • Figure 19 is a schematic view of the insert stack of the eighth embodiment of the disposable bioreactor.
  • Figure 20 is a schematic view showing the structure of Embodiment 9 of the disposable bioreactor.
  • Figure 21 is a schematic view showing the structure of the disposable bioreactor after the liquid is charged into the liquid;
  • Figure 22 is a schematic view of the insert stack of the embodiment 9 of the disposable bioreactor
  • Figure 23 is a schematic view showing the structure of Embodiment 10 of the disposable bioreactor.
  • Figure 24 is a schematic view showing the structure of the disposable bioreactor of Example 10 after being filled with liquid;
  • Figure 25 is a stacked schematic view of Example 10 of a disposable bioreactor
  • Figure 26 is a schematic view showing the structure of the embodiment 11 of the disposable bioreactor
  • Figure 27 is a schematic view showing the structure of Embodiment 12 of the disposable bioreactor
  • Figure 28 is a schematic view showing the structure of Embodiment 13 of the disposable bioreactor
  • Figure 29 is a schematic structural view of Embodiment 14 of a disposable bioreactor
  • Figure 30 is a schematic view showing the structure of Embodiment 15 of the disposable bioreactor
  • Figure 31 is a schematic view showing the structure of the embodiment 16 of the disposable bioreactor
  • Figure 32 is a schematic view showing the structure of Embodiment 17 of the disposable bioreactor
  • Figure 33 is a schematic view showing the structure of Embodiment 18 of the disposable bioreactor
  • Figure 34 is a schematic view showing the structure of Embodiment 19 of the disposable bioreactor
  • Figure 35 is a schematic view showing the structure of Embodiment 20 of the disposable bioreactor
  • Figure 36 is a schematic view showing the structure of the embodiment 21 of the disposable bioreactor
  • Figure 37 is a schematic illustration of the structure of Example 22 of a disposable bioreactor.
  • Example 1 of the disposable bioreactor as shown in Figures 1-5, the disposable bioreactor comprises a reactor chamber and a communication tube 11, and the reactor chamber is made of a non-toxic and harmless plastic material.
  • the requirements for use can be seen from Figures 1 and 2.
  • the reactor cavity is formed by the fusion of two chamber walls, and the two chamber walls are arranged one above the other, wherein one of the upper portions is the upper chamber wall 12 and is located at the lower portion.
  • One of the lower chamber walls 13, the fusion of the upper and lower chamber walls forms a joint edge 14, which can be supported and pulled by the joint edge 14 when needed; the communication tube 11 is located on the upper chamber wall 12 and It is integral with the upper chamber wall 12.
  • both the upper and lower chamber walls are solid support chamber walls, that is, the chamber walls that maintain their intrinsic shape, which are all formed by plastic sheeting (in other embodiments, upper and lower chambers).
  • the wall may also be a bulb structure formed by blow molding of a plastic sheet material or a solid support cavity wall formed by injection molding of a plastic material, wherein the specific material of the plastic sheet may be polypropylene PP, polyethylene PE, polyparaphenylene Ethylene glycolate PET (including APET and PETG), polyvinyl chloride PVC, ABS, PC, PS GAG and acrylic, such as injection-molded or blister-formed raw materials or sheets or coils, and composite blister-formable Plastic sheets and coils include PVC/PE, PET/PE, HIPS and other thermoplastic coils, PVC, PET, PP and PS.
  • the upper and lower chamber walls are all curved.
  • the cavity wall that is, the upper and lower cavity walls are non-planar cavity walls, which makes the upper and lower cavity walls naturally
  • the reactor chamber in this embodiment includes a junction portion 1001 and two hollow arm portions 1002.
  • the end of the hollow arm portion 1002 is closed, the blind end of the hollow arm portion is hemispherical, and the hollow arm portion 1002 is disposed.
  • the hollow arms are
  • the cross section of the 1002 is circular (in other embodiments, the cross-sectional shape of the hollow arm may also be elliptical, polygonal, rectangular, triangular, semi-circular, semi-elliptical, trapezoidal or the above geometrical figures are combined into one same
  • the different combinations of the cavities are formed by the corresponding portions of the upper and lower chamber walls. Due to the arrangement of the hollow arms 1002, the length-to-diameter ratio of the reactor chamber in the direction in which the hollow arms 1002 extend is greater than or equal to 1.5. .
  • the center lines of the two hollow arms 1002 are collinear and communicate with the communication tube 11 through the intersection 1001 of the cavity at the intersection 1001 of the cavity, thereby also causing the communication tube 11 and the hollow arm 1002 of the reactor cavity Together Formed an inverted T-shaped structure.
  • the communication tube 11 and the upper chamber wall 12 are of a unitary structure, and the upper chamber wall 12 is formed by suction molding, so that the communication tube 11 is also formed by blistering, after the plastic forming, the communication tube 11 is The outer end is initially impervious, and a hard shell structure having a certain thickness is formed at the position, and the outer port of the communication tube 11 is punched out on the hard shell structure, after the punching is completed, the The hard shell structure forms a reinforcing ring 15 at the outer port of the connecting tube, and the reinforcing ring 15 can be directly used for snap-fitting with the cap 16 (cover) of the communicating tube 11, which is a common passage for the reaction material and the gas exchange. .
  • the disposable bioreactor can be used to move the liquid along the long axis in the reactor chamber whether it is placed on a rocking shaker, a plane-rotating shaker or a three-dimensional swing shaker, and is driven by the potential energy of one end and the kinetic energy of the liquid.
  • the liquid flows to the lower end of the potential energy and the kinetic energy of the liquid to form a wave mixing and turbulent mixing.
  • the curved tangent of the wall portion forms a turbulent mixing; when using the rocking shaker, the center of the hollow arm is required The line is consistent with the direction of the sway; when the disposable bioreactor is placed on the plane gyroscopic motion platform, the liquid is actually thrown up the slope, and then the gravity of the liquid slides down the tangential line to form a wave in the hollow arm or Turbulent mixing and gas exchange at both ends.
  • Embodiment 2 of the disposable bioreactor as shown in FIG. 6, the difference between this embodiment and Embodiment 1 is that, in the present embodiment, the upper chamber wall 21 is a flat top structure, and the top portion thereof is other than the communication tube 22.
  • a gas exchange tube 23 is also provided, and the gas exchange tube 23 is also integrally formed with the upper chamber wall 21, and a gas exchange tube cap 24 is provided at the outer end thereof.
  • Embodiment 3 of the disposable bioreactor differs from Embodiment 1 in that, in this embodiment, the upper chamber wall 31 of the reactor chamber is a planar chamber wall.
  • Embodiment 4 of the disposable bioreactor as shown in FIG. 9, the difference between this embodiment and Embodiment 3 is that in the present embodiment, the upper chamber wall 41 is a flat top structure, and the top portion thereof is in addition to the communication tube 42.
  • a gas exchange tube 43 is provided, and the gas exchange tube 43 is also integrally formed with the upper chamber wall 41, and a gas exchange tube cap 44 is provided at the outer end thereof.
  • Embodiment 5 of the disposable bioreactor as shown in FIGS. 10-12, the difference between this embodiment and Embodiment 1 is that in the present embodiment, the lower chamber wall 51 of the reactor cavity is a planar cavity wall, After the lower chamber wall of such a structure, the reactor chamber can be automatically held in a standing position as a small reactor tube of the tube-free frame, and is convenient to use.
  • Embodiment 6 of the disposable bioreactor as shown in FIG. 13, the difference between this embodiment and Embodiment 5 is that, in the present embodiment, the upper chamber wall 61 is a flat-top bulb structure, and the top portion thereof except the communication tube 62 In addition to the gas exchange tube 63, the gas exchange tube 63 is also integrally formed with the upper chamber wall 61, and a gas exchange tube cap 64 is provided at the outer end.
  • Embodiment 7 of the disposable bioreactor as shown in FIGS. 14-16, the difference between this embodiment and Embodiment 1 is that in the present embodiment, the upper chamber wall 71 of the reactor chamber has a small top and a large bottom.
  • the sleeve wall can be inserted into the stack, the lower chamber wall 72 is a soft membrane chamber wall, and the shape of the lower chamber wall 72 (except for the non-connected tube structure) is adapted to the shape of the upper chamber wall 71, specifically by plastic forming.
  • the soft bubble is composed of a soft film which is a flat soft film and then stretched and formed into a flexible film having a curved structure.
  • the flat soft film may be a polyethylene PE film, a low density polyethylene LDPE film, and an ultra low density poly Ethylene LLDPE film, polypropylene PP film, polyvinyl chloride (PVC) film, polyethylene terephthalate (PET) film, polystyrene (PS) film, ethylene/vinyl acetate (EVA) film, polyamide (PA) film, etc., multilayer composite film of the above different resin film combinations, multi-layer co-extruded film of the above-mentioned different resin layers, and PP/SEBS/PP co-extruded film containing SEBS and EVOH, PA/EVOH/ PE coextruded film and multilayer coextruded film such as PA/EVOH/PP.
  • PVC polyvinyl chloride
  • PET polyethylene terephthalate
  • PS polystyrene
  • EVA ethylene/vinyl acetate
  • PA polyamide
  • the lower chamber wall 72 is flipped up into the upper chamber wall 71, so that the reactor chambers can be placed in a nested manner (Fig. 16), thereby reducing the transportation to the reactor. Irradiation and storage costs.
  • the upper chamber wall 71 is a solid support chamber wall, it can function to support the reactor chamber.
  • the lower chamber wall 72 will automatically be under the action of liquid drooping gravity. It is removed from the upper chamber wall 71 and automatically maintains a three-dimensional shape under the action of liquid gravity (Fig. 15).
  • the design side is a rigid supporting blister structure, and the other side is a soft film, which not only utilizes the structure of the rigid supporting blister structure, but also has a simple operation and convenient characteristics, and avoids the full soft film.
  • the reactor needs a gassing system to maintain the shortcomings of the three-dimensional internal space, and the advantage of the soft membrane cushioning shear force is utilized.
  • the buffer flow impact causes shear damage to the cells, by utilizing the deformability of the soft membrane and the hard foam.
  • the advantages of the stacking of the shells are that the shape-matched soft bubbles are embedded in the rigid bulbs when not in use to save space.
  • Embodiment 8 of the disposable bioreactor is different from Embodiment 7 in that, in the present embodiment, the top of the upper chamber wall 81 is provided with gas exchange in addition to the communication tube 82.
  • the tube 83, the gas exchange tube 83 is also integrally formed with the upper chamber wall 81, and has a gas exchange tube cap 84 at its outer end.
  • Embodiment 9 of the disposable bioreactor as shown in Figures 20-22, the difference between this embodiment and Embodiment 2 is that in the present embodiment, the lower chamber wall 91 of the reactor chamber is small and large.
  • the upper cavity wall 92 is a soft-membrane cavity wall, and the shape of the upper cavity wall 92 is adapted to the shape of the lower cavity wall 91 except for the non-connected pipe and the inlet and outlet pipes, thereby being During transport and irradiation, the upper chamber wall 92 is folded into the lower chamber wall 91, and the reactor chamber is placed in a stack (Fig. 19) to reduce the transportation and irradiation costs to the reactor.
  • Embodiment 10 of the disposable bioreactor differs from Example 8 in that the upper chamber wall 101 of the reactor chamber is a planar chamber wall.
  • Embodiment 11 of the disposable bioreactor as shown in FIG. 26, the difference between this embodiment and the embodiment 1 is that the disposable bioreactor of the embodiment further includes a support fixing base 111 for supporting the fixing base 111. There is a relief groove 113 for giving way to the lower chamber wall 112.
  • Embodiment 12 of the disposable bioreactor is different from the embodiment 11 in that the upper chamber wall 121 in this embodiment is a flat-top bulb structure, and the top portion thereof is other than the communication tube 122.
  • a gas exchange tube 123, a liquid inlet tube 124, a liquid take-up tube 125, an oxygen and carbon dioxide sensor electrode sleeve 126, and a pH sensor electrode sleeve 127 are also provided.
  • the gas exchange tube 123 is also integrally formed with the upper chamber wall 121.
  • the outer end is provided with a gas filter (not shown), the gas exchange tube, the inlet tube, the oxygen tube and the carbon dioxide sensor electrode sleeve, and the PH sensor electrode sleeve are also integrally formed with the upper chamber wall 121.
  • the joint flange 128 of the reactor cavity is provided with a pulling fixing hole 129
  • the fixed supporting seat 1210 is provided with a ball head 1211 corresponding to the pulling fixing hole, which can be used through the ball head 1211 and the joint edge 128.
  • the pulling fixing hole 129 cooperates to fix the reactor cavity.
  • Embodiment 13 of the disposable bioreactor as shown in FIG. 28, the difference between this embodiment and the embodiment 11 is that, in this embodiment, the bottom portion of the lower chamber wall 131 is further provided with a bottom intake pipe 132; A heating member (not shown) is further disposed in the recess of the support base 133.
  • the heating member may be specifically a heating device such as an electric blanket or a heat exchanger whose temperature is automatically adjusted.
  • Embodiment 14 of the disposable bioreactor as shown in FIG. 29, the difference between this embodiment and Embodiment 12 is that in the present embodiment, the upper chamber wall 141 of the reactor chamber is a planar chamber wall, and In this embodiment, the upper cavity wall 141 is a solid support cavity wall. In other embodiments, the upper cavity wall 141 may also be a planar soft film cavity wall. For the selection of the planar soft film material, refer to Embodiment 7.
  • Embodiment 15 of the disposable bioreactor as shown in Fig. 30, the difference between this embodiment and the embodiment 1 is that in the present embodiment, the reactor chamber has only one hollow arm portion 151, so that the communication tube 152 With the middle of the reactor cavity The empty arm portion 151 forms an L-shaped structure.
  • the lower chamber wall 153 of the reactor chamber is a planar chamber wall, and FIG. 30 shows a situation in which six reactors are juxtaposed, and can be sucked once on the same piece of material during production.
  • a plurality of upper chamber walls 154 are molded or injection molded and then bonded or fused to a sheet to obtain a plurality of reactor chambers at a time.
  • Embodiment 16 of the disposable bioreactor as shown in Fig. 31, the difference between this embodiment and the embodiment 15 is that, in the present embodiment, the intersection portion 161 of the reactor cavity forms an bulging structure, and the convergence of the bulging structures The portion 161 can further facilitate communication between the communication tube 162 and the hollow arm portion 163 of the reactor chamber and prevent excessive liquid in the hollow arm portion 163 from overflowing into the communication tube 162.
  • Embodiment 17 of the disposable bioreactor as shown in FIG. 32, the difference between this embodiment and Embodiment 1 is that in the present embodiment, the two chamber walls of the reactor chamber are disposed one after the other, two pieces. One of the front walls of the cavity wall is the front cavity wall, and the other is the posterior cavity wall. The front and back cavity walls are joined together by fusion, and their fusion forms a joint edge 171. Further, as can be seen from Fig. 32, in the present embodiment, the communication tube 172 and the hollow arm portion 173 of the reactor chamber are formed by splicing the front and rear chamber walls.
  • Embodiment 18 of the disposable bioreactor as shown in FIG. 33, the difference between this embodiment and the embodiment 17 is that the communication tube 181 is located on the front cavity wall 182, and the front and rear cavity walls are respectively provided separately.
  • Embodiment 19 of the disposable bioreactor is different from the embodiment 18 in that, in the present embodiment, the bottom of the reactor chamber is further provided with an intake pipe 191.
  • Embodiment 20 of the disposable bioreactor as shown in FIG. 35, the difference between this embodiment and the embodiment 15 is that in the embodiment, the two chamber walls of the reactor chamber are disposed one after the other, two pieces. One of the front walls of the cavity wall is the front cavity wall, and the other is the posterior cavity wall. The front and back cavity walls are joined together by fusion, and their fusion forms a joint edge 201. Further, as can be seen from Fig. 32, in the present embodiment, the communication tube 202 and the hollow arm portion 203 of the reactor chamber are formed by splicing the front and rear chamber walls.
  • the difference between this embodiment and the embodiment 2 is that the gas exchange tube and the gas exchange are omitted on the upper chamber wall 211 of the reactor chamber in this embodiment.
  • the reactor in this embodiment further has a cover 213 which is actually an extension structure of the cap of the communication tube 212 for integrally shielding the upper chamber wall 211 and the communication tube 212 while passing through the upper portion thereof.
  • the sealing portion 214 is provided to close the nozzle of the communication tube 212.
  • the cover 213 has the same shape as the upper chamber wall 211 and forms a flip structure of the reactor cavity, one of the opposite sides of which is joined to the joint edge 215, and the other side A buckle 216 is disposed between the joint edge 215 and a joint crease 217 is provided at the joint between the two, and the positioning fold 217 is used to bend the cover 213 from the same position when the cover 213 is turned.
  • the cover 213 loosely covers the upper chamber wall 211 and the communication tube 212 of the reactor, the reactor aeration culture can be maintained.
  • the cover 213 When the cover 213 tightly closes the upper chamber wall 211 and the communication tube 212 of the reactor, the cover 213 is additionally While the buckle 216 of the joint edge is fastened, the cover 213 and the upper cavity wall 211 are closed close to the gap, and the sealing portion 214 blocks the nozzle of the communication pipe 212, and the anaerobic culture or the storage of the reactant after the culture can be performed. Prevent liquid evaporation.
  • Embodiment 22 of the disposable bioreactor is different from the embodiment 5 in that the reactor in this embodiment further has a cover 223 which is actually a communication tube 222.
  • An extension structure of the cap for integrally shielding the upper chamber wall 221 and the communication tube 222 while blocking the nozzle of the communication tube 222 through the sealing portion 224 provided thereon.
  • the cover 223 has the same shape as the upper chamber wall 221 and forms a flip structure of the reactor cavity, one of the opposite sides of which is joined to the joint edge 225, and the other side Between the joint edge 225
  • the buckle 226 has a positioning crease 227 at the junction of the two, and the positioning crease 227 is used to bend the cover 223 from the same position when the cover 223 is turned.
  • the cover 223 When the cover 223 is tightly fastened to the upper chamber wall 221 and the communication tube 222 of the reactor, the cover 223 is additionally When the buckle 226 is fastened to the joint edge, the cover 223 and the upper cavity wall 221 are closed to close the gap, and the sealing portion 224 blocks the nozzle of the communication tube 222, and the anaerobic culture or the storage of the reactant after the culture can be performed. Prevent liquid evaporation.
  • the disposable bioreactor of the present invention is pre-irradiated and sterilized, and can be used in one time, thereby avoiding the trouble of cleaning, disinfection and cross-contamination.
  • the reactor cavity may also be formed by fusion or bonding of three or more cavity walls.
  • each cavity wall does not have to be
  • the hollow arm portion of the reactor chamber can be formed by splicing a plurality of chamber walls; in addition, in other embodiments, the upper and lower chamber walls of the reactor can also be soft membrane walls because The existence of the hollow arm, even if the upper and lower chamber walls are made of soft film, in the process of use, without the need for air blowing, the three-dimensional space in the reactor cavity can be maintained only by means of pulling and fixing;
  • the right wall can also be used as a solid support cavity wall, and the other is a soft membrane cavity wall or a soft membrane cavity wall; the reactor cavity can be made of medical latex film, silicone mold and other materials.
  • the upper cavity wall can also adopt a planar soft membrane cavity wall.
  • the upper cavity wall due to the supporting action of the joint edge and the lower cavity wall, the upper cavity wall can automatically maintain the unfolded state without falling.
  • the three-dimensional space in the reactor chamber can be maintained without blowing and pulling.

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Abstract

提供了一种一次性生物反应器，包括反应器腔体和连通管，连通管位于反应器腔体顶部，所述反应器腔体由两片以上的腔壁经融合连接或粘合连接而成并且具有交汇部和至少一个通过交汇部与连通管交汇连通的中空臂部，所述中空臂部的末端封闭。利用摇床驱动反应器腔内液体沿其长轴流动，产生波浪和湍流混合，提高了混合和传质效率。

Description

一次性生物反应器 技术领域
本发明涉及生物反应器技术领域，特别是涉及到了一种一次性生物反应器。
背景技术
摇床驱动的非介入混合式生物反应器包括小型的培养管，转瓶，锥形瓶，倒置锥底瓶，平锥底瓶和平锥底罐以及搅拌桨驱动的不同规模的搅拌式生物反应器，是目前最广泛使用的用于发酵和细胞悬浮培养的生物反应器。摇床驱动的非介入式混合生物反应器的共同特点是开口位于反应器的一端且与反应器腔体长轴同轴，除转瓶水平放置外均开口在上端并通过旋转或回旋方式驱动反应器内液体产生涡流而实现。而通过产生涡流来提高液体的氧传递主要是利用增大液体表面积的原理，这种靠增大液体表面积的氧传递方式仍然存在混合效率低的问题。由于开口位于反应器长轴的一端且与反应器腔体长轴同轴，为了防止液体溅出，需要加大上部气体通道的长度，也就是加大了通过反应器开口进行气体交换的无效通道，因而降低了气体交换的效率。虽然搅拌式生物反应器具有高效的混合，但由于搅拌桨的剪切力会造成细胞损伤和死亡而限制其只能采取温和的搅拌，这也是搅拌式反应器的主要缺陷之一。
另外，现有的转瓶，锥形瓶，倒置锥底瓶，平锥底瓶和平锥底罐以及不同大小的搅拌罐反应器均由硬质材料如玻璃，硬塑料和不锈钢等制成，由于玻璃和不锈钢材料的反应器需要重复使用，不仅带来清洗，消毒和认证的麻烦，而且还存在交叉污染的风险。虽然硬塑料注塑成型的反应器可以一次性使用，但由于生产工艺效率限制和使用原料相对多，形状固定不能伸缩变形以及相互间不能相互套叠，占空间大，不仅运输，辐照和存放成本高，同时也产生的较多废物带来更多的环境问题，虽然对全硬质的微型反应器一次性使用是可行的，但对转瓶及以上规模的反应器，特别是大型生产规模的反应器来说，全硬质材料注塑成型的反应器一次性使用将会带来生产成本，辐照成本，运输成本和存放成本的大幅提高并产生大量废物，从节约成本和环保的角度考虑是不可取的。因此研发以工艺开发和系列放大为目的的小型反应器和以规模生产为目的的大型反应器并实现一次性使用是未来生物反应器的发展趋势，需要进一步研发更节省材料，更高生产效率，更少占空间和产生环境废物的新型生物反应器。
发明内容
本发明的目的在于提供一种一次性生物反应器，以解决现有的摇床驱动的非介入混合现有的摇床驱动式生物反应器的存在混合和传质效率低的问题。
为了解决上述问题，本发明的一次性生物反应器采用以下技术方案：一次性生物反应器，包括反应器腔体和连通管，连通管位于反应器腔体顶部，所述反应器腔体由两片以上的腔壁经融合连接或粘合连接而成并且具有交汇部和至少一个通过交汇部与连通管交汇连通的中空臂部，所述中空臂部的末端封闭。
所述中空臂部水平设置。
反应器腔体有一个所述中空臂部，连通管位于反应器腔体顶部并且与中空臂部一起形成L形结构。
反应器腔体有两个所述中空臂部，连通管设于反应器腔体顶部并且与中空臂部一起形成倒T字形结构。
反应器腔体有两片所述腔壁，两片腔壁一上一下设置，位于上部的一个为上腔壁，另一个为下腔壁，上、下腔壁中至少一片为有曲面腔壁。
所述上、下腔壁中的一个为可保持其固有形状的固形支持腔壁，另一个为软膜腔壁。
所述固形支持腔壁由塑料原料经注塑成型或由塑料片材经吸塑或吹塑成型。
软膜腔壁由平面塑料膜构成或者是由平面塑料膜经吸塑成型的可形变的软膜泡构成。
上、下腔壁均为所述有曲面腔壁，所述固形支持腔壁为可插套叠置的叠摞式腔壁，软膜腔壁为可折入固形支持腔壁内以使反应器腔体能够插套叠置的腔壁。
上、下腔壁中的一个为所述有曲面腔壁，另一个为平面腔壁。
连通管与上腔壁为一体式结构。
连通管的外端口是在吸塑成型后冲切而成，连通管的外端口处具有冲切留下的环绕外端口的加强环。
所述下腔壁为所述有曲面腔壁，该生物反应器还包括支持固定座，所述支持固定座上设有用于为下腔壁让位的让位凹槽，让位凹槽的槽口周边设置有用于固定或牵拉反应器腔体的固定结构。
所述上、下腔壁的结合处具有向外围延伸的用于支持和牵拉固定反应器腔体的联合缘。
该反应器还包括罩盖用于封盖反应器腔体的上腔壁的罩盖，罩盖上设有用于封堵连通管的管口的封管部。
所述罩盖形成反应器腔体的翻盖结构，罩盖的相对的两侧中的一侧与联合缘连接在一起，另一侧与联合缘之间设有固定卡扣。
反应器腔体的腔壁上设置有连通反应器内腔供液体和气体进出以及溶氧，二氧化碳，PH传感器电极通过的管道，所述连通反应器内腔的管道与所连接的腔壁为一体成型结构。
反应器腔体由两个所述腔壁融接或粘接而成，两腔壁中的一个为前腔壁，另一个为后腔壁，前、后腔壁的配合处设有联合缘，反应器腔体的中空臂部由前、后腔壁的相应部位构成。
本发明的有益效果：在该一次性生物反应器中，反应器腔体具有交汇部和至少一个通过交汇部与连通管交汇连通的中空臂部，中空臂部的末端密闭并且连通管位于反应器腔体顶部。由于所述中空臂部的存在，本发明的生物反应器能够至少在中空臂部处使液体在一个狭长的空间内流动，由于连通管设于反应器腔体顶部，液体沿反应器的水平方向的长轴流动，连通管的轴反应器液体流动的轴为垂直轴向，无论置于摇摆的摇床，平面回旋摇床，还是三维回旋摇床，均可使液体在反应器中空臂部内流动而不会造成溅出，当到达中空臂部的封闭端时，液流在中空臂部封口端产生的湍流、涡流和波浪的作用下翻腾、折返并且 上下交替，在翻腾和上下交替的过程中将上部空间的氧气卷入液流，即中空臂部中的液体能够在流动的过程中不停的上下翻滚交替，从而充分的与氧气接触，与现有技术中依靠增大液流表面积的方式来使液流与氧气混合的方式相比，大大提高了混合和传质效率。
更进一步的，带曲面腔壁可在牵拉反应器腔体时起到减少反应器腔体褶皱的作用；固形支持腔壁更加有利于保持反应器腔体内的三维空间且使用方便；将固形支持腔壁设为可插套叠置的叠摞式腔壁以后，能够进一步减小反应器所占的空间，方便反应器的运输、辐照和存放，降低成本；连通管外端口处的加强环具有加强连通管口强度和防止管帽滑脱掉得作用；支持固定座可协助反应器腔体的固定，为反应器的大型化发展带来方便；联合缘不仅可以起到支撑反应器腔体的作用，而且为对反应器腔体的牵拉提供了着力点。罩盖可以将上腔壁连同连通管整体遮住封闭，罩盖的封管部可用于封堵连通管的管口，在打开罩盖的时候，可不必与连通管口周围直接接触，从而避免对液体的污染；翻盖式的罩盖可避免丢失，卡扣是为了方便对罩盖的固定。反应器腔体的腔壁上包括软膜腔壁上设置的连通反应器内腔供液体和气体进出以及溶氧，二氧化碳，PH传感器电极通过的管道，均与反应器腔壁一体成型，免去了管道与反应器腔壁，特别是软膜腔壁间的连接需要打孔和融台圈热合焊接的麻烦工艺。
附图说明
图1是一次性生物反应器的实施例1的结构示意图；
图2是一次性生物反应器的实施例1的分解图；
图3是一次性生物反应器的实施例1的第一工作原理图；
图4是一次性生物反应器的实施例1的第二工作原理图；
图5是图1中的连通管与管帽的配合示意图；
图6是一次性生物反应器的实施例2的结构示意图；
图7是一次性生物反应器的实施例3的结构示意图；
图8是一次性生物反应器的实施例3的分解图；
图9是一次性生物反应器的实施例4的结构示意图；
图10是一次性生物反应器的实施例5的结构示意图；
图11是一次性生物反应器的实施例5的分解图；
图12是一次性生物反应器的实施例5的并排放置示意图；
图13是一次性生物反应器的实施例6的结构示意图；
图14是一次性生物反应器的实施例7的结构示意图；
图15是一次性生物反应器的实施例7装入液体后的结构示意图；
图16是一次性生物反应器的实施例7的插套叠摞示意图；
图17是一次性生物反应器的实施例8的结构示意图；
图18是一次性生物反应器的实施例8装入液体后的结构示意图；
图19是一次性生物反应器的实施例8的插套叠摞示意图；
图20是一次性生物反应器的实施例9的结构示意图；
图21是一次性生物反应器的实施例9装入液体后的结构示意图；
图22是一次性生物反应器的实施例9的插套叠摞示意图；
图23是一次性生物反应器的实施例10的结构示意图；
图24是一次性生物反应器的实施例10装入液体后的结构示意图；
图25是一次性生物反应器的实施例10的叠摞示意图；
图26是一次性生物反应器的实施例11的结构示意图；
图27是一次性生物反应器的实施例12的结构示意图；
图28是一次性生物反应器的实施例13的结构示意图；
图29是一次性生物反应器的实施例14的结构示意图；
图30是一次性生物反应器的实施例15的结构示意图；
图31是一次性生物反应器的实施例16的结构示意图；
图32是一次性生物反应器的实施例17的结构示意图；
图33是一次性生物反应器的实施例18的结构示意图；
图34是一次性生物反应器的实施例19的结构示意图；
图35是一次性生物反应器的实施例20的结构示意图；
图36是一次性生物反应器的实施例21的结构示意图；
图37是一次性生物反应器的实施例22的结构示意图。
具体实施方式
一次性生物反应器的实施例1，如图1-5所示，该一次性生物反应器包括反应器腔体和连通管11，反应器腔体采用无毒无害的塑料材质，可达到一次性利用要求，从图1、2中可以看出，反应器腔体是由两片腔壁融合而成，两片腔壁一上一下设置，其中位于上部的一个为上腔壁12，位于下部的一个为下腔壁13，上、下腔壁的融合处形成了联合缘14，在需要时，可通过联合缘14支撑和牵拉反应器腔体；连通管11位于上腔壁12上并且与上腔壁12为一体式结构。在本实施例中，上、下腔壁均为固形支持腔壁，即可保持其固有形状的腔壁，它们均是由塑料片材经吸塑成型(在其它实施例中，上、下腔壁还可以是通过塑料片材料吹塑成型或者由塑料原料经注塑成型的固形支持腔壁)的泡壳结构，其中塑料片材的具体材料可以是聚丙烯PP，聚乙烯PE，聚对苯二甲酸乙二醇酯PET(包括APET和PETG)，聚氯乙烯PVC，ABS，PC，PS GAG和亚克力等可注塑成型或吸塑成型的原料或片材或卷材以及复合的可吸塑成型的塑料片材和卷材包括有PVC/PE，PET/PE，HIPS等热塑性塑料卷材，PVC，PET，PP和PS，另外，从2中还可以看出，上、下腔壁均为带曲面腔壁，即上、下腔壁均为非平面腔壁，这使得上、下腔壁在融合以后，二者之间自然形成一个三维的空间。
从整体上来看，该实施例中的反应器腔体包含有一个交汇部1001和两个中空臂部1002，中空臂部1002的末端封闭，其盲端呈半球面形，中空臂部1002的设置使得反应器腔体内形成了一个细长腔道，从而可便于液体在反应器腔体内沿反应器长轴(即相应中空臂部的延伸方向)的往复流动，在本实施例中，中空臂部1002的横截面呈圆形(在其它实施例中，中空臂部的横截面形状还可以为椭圆形，多边形，矩形，三角形，半圆形，半椭圆形，梯形或上述几何图形组合成同一内腔的不同组合形状)并且是由上、下腔壁的相应部位拼合而成，由于中空臂部1002的设置，使得反应器腔体在中空臂部1002延伸方向上的长径比大于或等于1.5。两个中空臂部1002的中心线共线并且在腔体的交汇部1001处通过腔体的交汇部1001与连通管11连通，由此也使得连通管11和反应器腔体的中空臂部1002一起 构成了倒T字形结构。
上文已经提到，连通管11与上腔壁12为一体式结构，而上腔壁12是吸塑成型的，因此连通管11也是吸塑而成，在吸塑成型以后，连通管11的外端最初是不通透的，并且该位置处形成了具有一定厚度的硬壳结构，而连通管11的外端口正是在该硬壳结构上冲切而成，冲切完成后，所述硬壳结构在连通管的外端口处形成了加强环15，该加强环15可直接用于与连通管11的管帽16(盖子)卡接配合，连通管为反应物料和气体交换的共同通道。
该一次性生物反应器无论置于摇摆的摇床，平面回旋摇床，还是三维回旋摇床，均可使液体在反应器腔内沿长轴流动，通过一端的势能和液体动能的提高，驱动液体向势能和液体动能的低端流动，形成波浪混合和湍流混合，在中空臂部盲端处，管壁部的弧形切线形成湍流混合；使用摇摆摇床时，要使中空臂部的中心线与摇摆方向保持一致；当一次性生物反应器倾斜放置在平面回旋运动平台上回旋运动时，实际上是将液体沿斜面抛向上，然后液体的重力沿切线下滑，形成中空臂部内波浪式或两端湍流式混合和气体交换。
一次性生物反应器的实施例2，如图6所示，本实施例与实施例1的区别在于：在本实施例中，上腔壁21为平顶结构，其的顶部除了连通管22以外还设置有气体交换管23，气体交换管23同样与上腔壁21为一体式结构，其外端设有气体交换管帽24。
一次性生物反应器的实施例3，如图7-8所示，本实施例与实施例1的区别在于：在本实施例中，反应器腔体的上腔壁31为平面腔壁。
一次性生物反应器的实施例4，如图9所示，本实施例与实施例3的区别在于：在本实施例中，上腔壁41为平顶结构，其顶部除了连通管42以外还设置有气体交换管43，气体交换管43同样与上腔壁41为一体式结构，其外端设有气体交换管帽44。
一次性生物反应器的实施例5，如图10-12所示，本实施例与实施例1的区别在于：在本实施例中，反应器腔体的下腔壁51为平面腔壁，采用此种结构的下腔壁以后，反应器腔体可以作为免管架的小型的反应器管自动保持立姿，使用方便。
一次性生物反应器的实施例6，如图13所示，本实施例与实施例5的区别在于：在本实施例中，上腔壁61为平顶泡壳结构，其顶部除了连通管62以外还设置有气体交换管63，气体交换管63同样与上腔壁61为一体式结构，其外端设有气体交换管帽64。
一次性生物反应器的实施例7，如图14-16所示，本实施例与实施例1的区别在于：在本实施例中，反应器腔体的上腔壁71为顶小底大的、可插套叠摞式腔壁，下腔壁72为软膜腔壁，下腔壁72的形状(除无连通管结构外)与上腔壁71的形状适配，具体是由吸塑成型的软膜泡构成，软膜泡为平面软膜再经吸塑拉伸成型具有曲面结构的柔性薄膜，所述平面软膜可以为聚乙烯PE薄膜，低密度聚乙烯LDPE薄膜，超低密度聚乙烯LLDPE薄膜，聚丙烯PP薄膜，聚氯乙烯(PVC)薄膜、聚对苯二甲酸乙二醇酯(PET)薄膜、聚苯乙烯(PS)薄膜、乙烯/乙酸乙烯(EVA)薄膜、聚酰胺(PA)薄膜等，上述不同树脂薄膜组合的多层复合膜，上述不同树脂多层共挤的多层共挤薄膜，以及含SEBS和EVOH的PP/SEBS/PP共挤膜，PA/EVOH/PE共挤膜和PA/EVOH/PP等多层共挤膜。在运输、辐照和存放的过程中将下腔壁72向上翻嵌入上腔壁71中，可使反应器腔体相互间插套叠摞放置(如图16)，降低对反应器的运输，辐照和存放成本。在使用的过程中，由于上腔壁71为固形支持腔壁，因此其可起到支持反应器腔体的作用，充入液体以后，在液体下垂重力的作用下，下腔壁72将会自动从上腔壁71中脱出并在液体重力的作用下自动保持三维形状(如图15)。
由于软膜具有弹性和剪切力低的特点，设计一面为刚性的支撑泡壳结构，另一面为软膜，既利用了刚性的支撑泡壳结构的结构简单操作方便特性，避免了全软膜反应器需要鼓气系统才能维持三维内部空间的缺点，又利用了软膜缓冲剪切力的优点缓冲液流冲击造成对细胞的剪切损伤，通过利用了软膜的可变形特性以及硬质泡壳的套摞叠置优点，在非使用时将形状吻合的软膜泡嵌入硬质泡壳内以节省空间。事实上，从经济方面和节能环保方面考虑，大型全硬质的反应器作为一次性使用是不可接受的，但本发明的软硬嵌合反应器不仅大大节约了生产，运输，辐照和存放的成本，而且降低了废物的产生，因此可以实现一次性使用。
一次性生物反应器的实施例8，如图17-19所示，本实施例与实施例7的区别在于：在本实施例中，上腔壁81顶部除了连通管82以外还设置有气体交换管83，气体交换管83同样与上腔壁81为一体式结构，其外端设有气体交换管帽84。
一次性生物反应器的实施例9，如图20-22所示，本实施例与实施例2的区别在于：在本实施例中，反应器腔体的下腔壁91为顶大底小的、可插套叠摞式腔壁，上腔壁92为软膜泡腔壁，上腔壁92的形状除无连通管处和进出气管外与下腔壁91的形状适配，由此可在运输、辐照的过程中将上腔壁92折入下腔壁91中，将反应器腔体插套叠摞放置(如图19)，降低对反应器的运输和辐照成本。
一次性生物反应器的实施例10，如图23-25所示，本实施例与实施例8的区别在于：反应器腔体的上腔壁101为平面腔壁。
一次性生物反应器的实施例11，如图26所示，本实施例与实施例1的区别在于：该实施例的一次性生物反应器还包括一个支持固定座111，支持固定座111上设有用于为下腔壁112让位的让位凹槽113。
一次性生物反应器的实施例12，如图27所示，本实施例与实施例11的区别在于：该实施例中的上腔壁121为平顶泡壳结构，其顶部除了连通管122以外还设置有气体交换管123、进液管124、取液管125、氧气和二氧化碳传感器电极套管126、PH传感器电极套管127，气体交换管123同样与上腔壁121为一体式结构，其外端设有气体滤菌器(图中未示出)，气体交换管、进液管、取液管氧气和二氧化碳传感器电极套管、PH传感器电极套管也是与上腔壁121一体吸塑成型；另外，反应器腔体的联合缘128上设有牵拉固定孔129，固定支持座1210上设有与牵拉固定孔对应的球头1211，使用时可通过球头1211与联合缘128上的牵拉固定孔129配合固定反应器腔体。
一次性生物反应器的实施例13，如图28所示，本实施例与实施例11的区别在于：在该实施例中，下腔壁131的底部还设有底部进气管132；另外，固定支持座133的凹槽中还设有加热部件(图中未示出)，加热部件具体可采用温度自动调控的电热毯、热交换器等加热装置。
一次性生物反应器的实施例14，如图29所示，本实施例与实施例12的区别在于：在本实施例中，反应器腔体的上腔壁141为平面腔壁，另外，在本实施例中，上腔壁141为固形支持腔壁，在其它实施例中，上腔壁141还可以为平面软膜腔壁，平面软膜材料的选取可参照实施例7。
一次性生物反应器的实施例15，如图30所示，本实施例与实施例1的区别在于：在本实施例中，反应器腔体仅有一个中空臂部151，从而使得连通管152与反应器腔体的中 空臂部151形成了L形结构。另外，在本实施例中，反应器腔体的下腔壁153为平面腔壁，图30所示的是六个反应器并列放置的情形，在生产的时候，可在同一片材料上一次吸塑或注塑成型多个上腔壁154，然后将它们与一张片材粘合或融合便可一次得到多个反应器腔体。
一次性生物反应器的实施例16，如图31所示，本实施例与实施例15的区别在于：在本实施例中，反应器腔体的交汇部161形成了鼓胀结构，鼓胀结构的交汇部161可进一步方便连通管162与反应器腔体的中空臂部163之间的连通并防止中空臂部163内过多液体向连通管162内溢出。
一次性生物反应器的实施例17，如图32所示，本实施例与实施例1的区别在于：在本实施例中，反应器腔体的两片腔壁一前一后设置，两片腔壁中位于前部的一个为前腔壁，另一个为后腔壁，前、后腔壁经融合连接在一起，它们的融合处形成了联合缘171。另外，从图32中还可以看到，在本实施例中，连通管172和反应器腔体的中空臂部173均是由前、后腔壁拼合而成的。
一次性生物反应器的实施例18，如图33所示，本实施例与实施例17的区别在于：连通管181是位于前腔壁182上，另外，前、后腔壁上还分别设有用于与外界相应部件(进液管、O2，CO2和PH传感器等)连接的连接管183。
一次性生物反应器的实施例19，如图34所示，本实施例与实施例18的区别在于：在本实施例中，反应器腔体的底部还设有进气管191。
一次性生物反应器的实施例20，如图35所示，本实施例与实施例15的区别在于：在本实施例中，反应器腔体的两片腔壁一前一后设置，两片腔壁中位于前部的一个为前腔壁，另一个为后腔壁，前、后腔壁经融合连接在一起，它们的融合处形成了联合缘201。另外，从图32中还可以看到，在本实施例中，连通管202和反应器腔体的中空臂部203均是由前、后腔壁拼合而成的。
一次性生物反应器的实施例21，如图36所示，本实施例与实施例2的区别在于：本实施例中的反应器腔体的上腔壁211上省略了气体交换管、气体交换管帽和连通管212的管帽。另外，该实施例中的反应器还具有一个罩盖213，罩盖213其实是连通管212的管帽的延伸结构，其用于整体遮蔽上腔壁211和连通管212，同时通过其上所设的封管部214封堵连通管212的管口。在本实施例中，罩盖213的形状与上腔壁211的形状相同并且形成了反应器腔体的翻盖结构，其相对的两侧中的一侧与联合缘215连接在一起，另一侧与联合缘215之间设有卡扣216，二者的连接处设有定位折痕217，定位折痕217用于使罩盖213翻动时均从同一位置处弯折。当罩盖213松松遮盖反应器上腔壁211和连通管212时，可保持反应器通气培养，当罩盖213紧紧扣盖反应器上腔壁211和连通管212时，罩盖213另一边与联合缘的卡扣216紧扣，罩盖213与上腔壁211紧贴间隙闭合，封管部214封堵连通管212的管口，可进行厌氧培养或培养后反应物的保存以防液体蒸发。
一次性生物反应器的实施例22，如图37所示，本实施例与实施例5的区别在于：该实施例中的反应器还具有一个罩盖223，罩盖223其实是连通管222的管帽的延伸结构，其用于整体遮蔽上腔壁221和连通管222，同时通过其上所设的封管部224封堵连通管222的管口。在本实施例中，罩盖223的形状与上腔壁221的形状相同并且形成了反应器腔体的翻盖结构，其相对的两侧中的一侧与联合缘225连接在一起，另一侧与联合缘225之间设有 卡扣226，二者的连接处设有定位折痕227，定位折痕227用于使罩盖223翻动时均从同一位置处弯折。当罩盖223松松遮盖反应器上腔壁221和连通管222时，可保持反应器通气培养，当罩盖223紧紧扣盖反应器上腔壁221和连通管222时，罩盖223另一边与联合缘的卡扣226紧扣，罩盖223与上腔壁221紧贴间隙闭合，封管部224封堵连通管222的管口，可进行厌氧培养或培养后反应物的保存以防液体蒸发。
上述各实施例中，本发明的一次性生物反应器采用预先辐照灭菌，可即时一次性使用，避免了清洗，消毒的麻烦和交叉污染的风险。
在一次性生物反应器的其它实施例中，反应器腔体还可以是由三片以上的腔壁经融合连接或粘合连接而成，当四片以上腔壁时，每一片腔壁都不必为有曲面腔壁，反应器腔体的中空臂部可由多片腔壁拼接而成；另外，在其它的实施例中，反应器的上、下腔壁还均可以为软膜腔壁，因为中空臂部的存在，即使是上、下腔壁均采用软膜，在使用的过程中，不需鼓气，仅通过牵拉固定等手段也可以保持反应器腔体内的三维空间；另外，左、右腔壁也可以采用一个为固形支持腔壁，另一个为软膜腔壁或者都采用软膜腔壁的形式；反应器腔体可以采用医用乳胶膜，硅胶模等其它材质。在上述实施例3、4中，上腔壁还可以采用平面软膜腔壁，此种情况下，由于联合缘和下腔壁的支撑作用，上腔壁可自动保持展开的状态而不会下坠，无需鼓气和牵拉便可保持反应器腔体内的三维空间。

Claims (18)

  1. 一次性生物反应器，包括反应器腔体和连通管，连通管位于反应器腔体顶部，其特征在于，所述反应器腔体由两片以上的腔壁经融合连接或粘合连接而成并且具有交汇部和至少一个通过交汇部与连通管交汇连通的中空臂部，所述中空臂部的末端封闭。
  2. 根据权利要求1所述的一次性生物反应器，其特征在于，所述中空臂部水平设置。
  3. 根据权利要求1所述的一次性生物反应器，其特征在于，反应器腔体有一个所述中空臂部，连通管位于反应器腔体顶部并且与中空臂部一起形成L形结构。
  4. 根据权利要求1所述的一次性生物反应器，其特征在于，反应器腔体有两个所述中空臂部，连通管设于反应器腔体顶部并且与中空臂部一起形成倒T字形结构。
  5. 根据权利要求1所述的一次性生物反应器，其特征在于，反应器腔体有两片所述腔壁，两片腔壁一上一下设置，位于上部的一个为上腔壁，另一个为下腔壁，上、下腔壁中至少一片为有曲面腔壁。
  6. 根据权利要求5所述的一次性生物反应器，其特征在于，所述上、下腔壁中的一个为可保持其固有形状的固形支持腔壁，另一个为软膜腔壁。
  7. 根据权利要求6所述的一次性生物反应器，其特征在于，所述固形支持腔壁由塑料原料经注塑成型或由塑料片材经吸塑或吹塑成型。
  8. 根据权利要求6所述的一次性生物反应器，其特征在于，软膜腔壁由平面塑料膜构成或者是由平面塑料膜经吸塑成型的可形变的软膜泡构成。
  9. 根据权利要求6所述的一次性生物反应器，其特征在于，上、下腔壁均为所述有曲面腔壁，所述固形支持腔壁为可插套叠置的叠摞式腔壁，软膜腔壁为可折入固形支持腔壁内以使反应器腔体能够插套叠置的腔壁。
  10. 根据权利要求5所述的一次性生物反应器，其特征在于，上、下腔壁中的一个为所述有曲面腔壁，另一个为平面腔壁。
  11. 根据权利要求5所述的一次性生物反应器，其特征在于，连通管与上腔壁为一体式结构。
  12. 根据权利要求11所述的一次性生物反应器，其特征在于，连通管的外端口是在吸塑成型后冲切而成，连通管的外端口处具有冲切留下的环绕外端口的加强环。
  13. 根据权利要求5所述的一次性生物反应器，其特征在于，所述下腔壁为所述有曲面腔壁，该生物反应器还包括支持固定座，所述支持固定座上设有用于为下腔壁让位的让位凹槽，让位凹槽的槽口周边设置有用于固定或牵拉反应器腔体的固定结构。
  14. 根据权利要求5-13任一项所述的一次性生物反应器，其特征在于，所述上、下腔壁的结合处具有向外围延伸的用于支持和牵拉固定反应器腔体的联合缘。
  15. 根据权利要求14所述的一次性生物反应器，其特征在于，该反应器还包括罩盖用于封盖反应器腔体的上腔壁的罩盖，罩盖上设有用于封堵连通管的管口的封管部。
  16. 根据权利要求15所述的一次性生物反应器，其特征在于，所述罩盖形成反应器腔体的翻盖结构，罩盖的相对的两侧中的一侧与联合缘连接在一起，另一侧与联合缘之间设有固定卡扣。
  17. 根据权利要求1所述的一次性生物反应器，其特征在于，反应器腔体的腔壁上设置有连通反应器内腔供液体和气体进出以及溶氧，二氧化碳，PH传感器电极通过的管道，所述连通反应器内腔的管道与所连接的腔壁为一体成型结构。
  18. 根据权利要求1或2或3或4或17所述的一次性生物反应器，其特征在于，反应器腔体由两个所述腔壁融接或粘接而成，两腔壁中的一个为前腔壁，另一个为后腔壁，前、后腔壁的配合处设有联合缘，反应器腔体的中空臂部由前、后腔壁的相应部位构成。
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