CN111676139A - Double-layer hard plastic fluidized bed cell bioreactor of four-rocker table - Google Patents
Double-layer hard plastic fluidized bed cell bioreactor of four-rocker table Download PDFInfo
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- CN111676139A CN111676139A CN202010745650.4A CN202010745650A CN111676139A CN 111676139 A CN111676139 A CN 111676139A CN 202010745650 A CN202010745650 A CN 202010745650A CN 111676139 A CN111676139 A CN 111676139A
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- 239000004033 plastic Substances 0.000 title claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 35
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- 238000004321 preservation Methods 0.000 claims abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 49
- 229910000831 Steel Inorganic materials 0.000 claims description 38
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- 230000006978 adaptation Effects 0.000 claims description 2
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- 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
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/16—Vibrating; Shaking; Tilting
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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
- C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
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- 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
- C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
- C12M25/02—Membranes; Filters
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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
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/10—Perfusion
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Abstract
The invention relates to the technical field of cell bioreactors, in particular to a double-layer hard plastic fluidized bed cell bioreactor with a four-rocker table. The reactor comprises a polygonal heat-preservation tank body, a double-layer cell reaction tank and a four-rocker shaking table; the four-rocker shaking table adopts the upper end and the lower end of the rocker with a cross-axle structure, the load in the vertical direction is directly guided to the ground through the rocker, the overturning moment acting on the shaking table and the ground can be eliminated, the vibration and the noise generated in the whole culture process are reduced, the manufacturing cost and the self weight of the shaking table can be greatly reduced, and the shaking table can bear large load; the double-layer reaction tank and the filter screen on the double-layer reaction tank can culture cells by a perfusion process when the adherent cells are cultured by adopting a high-density microcarrier, and the cells grow in a real microgravity environment, so that the cells grow in a three-dimensional manner and the high differentiation rate amplification is kept. The reaction tank is particularly suitable for culturing mesenchymal stem cells, and is beneficial to popularization and application.
Description
Technical Field
The invention relates to the technical field of cell bioreactors, in particular to a double-layer hard plastic fluidized bed cell bioreactor with a four-rocker table.
Background
At present, the development of the world biotechnology pharmaceutical industry is rapid, and huge achievements are obtained, and the biological active proteins such as various diagnostic and therapeutic monoclonal antibodies, vaccines, growth factors and the like are produced and expressed by in vitro culture of animal cells, so that the biological active proteins have very wide market application prospects. Therefore, the disposable cell bioreactor for culturing animal cells in high density on a large scale becomes the most important equipment in the biotechnology pharmaceutical industry, and largely determines the product cost, production scale and product type of the biopharmaceutical enterprise.
When the working volume of the existing swinging cell reactor adopting circumferential oscillation is larger, such as more than 50 liters, the swinging cell reactor can generate larger overturning moment to the ground, and all the gravity of a tank body, a swinging disc and culture solution in a reaction tank of the reactor acts on the swinging disc, so that a swinging table not only needs to bear all the gravity of the tank body, but also needs to apply torque to swing the swinging cell reactor. The result is that the whole reaction process can generate large vibration and noise under the action of the overturning moment. Because of the huge gravity acting on the shaking table, the size, the strength and the weight of each part of the shaking table are inevitably increased, and the manufacturing cost and the occupied space of the shaking table are also greatly increased.
In addition, the culture bag of the existing tank external circulation reactor is made of a plastic film and a rigid plastic bracket, the centroid and the gravity center are not overlapped, the gravity center is shifted, the shaking is unstable, and the centrifugal force and the vibration are large. And only one water inlet of the flow guide pipe is arranged. When the shaking table rotates one turn, the water enters the water inlet of the flow guide pipe, so that the circulation speed of the culture solution is low, and the cells are cultured hardly to achieve high benefit.
The information disclosed in this background section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.
Disclosure of Invention
The invention aims to provide a double-layer hard plastic fluidized bed cell bioreactor of a four-rocker shaking table, which aims to solve the technical problems in the prior art.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides a double-layer hard plastic fluidized bed cell bioreactor of a four-rocker shaking table, which comprises a polygonal heat-insulating tank body and also comprises: a double-layer cell reaction tank and a four-rocker shaking table;
the double-layered cell reaction tank includes: the tank comprises a tank cover, an outer tank, an inner tank and a filter screen; the tank cover is arranged at the top of the outer tank; the inner tank is arranged inside the outer tank, and the filter screen is arranged at a position above a waist section of the inner tank; two water inlet convex parts are symmetrically arranged on two sides of the upper end of the outer tank, two water outlets are symmetrically arranged on two sides of the upper end of the inner tank, the water inlet convex parts on the upper end of the outer tank and the water outlets on the upper end of the inner tank are arranged in a one-to-one correspondence mode, a water return opening is formed in the bottom end of the inner tank, an interlayer space is formed between the outer tank and the inner tank, and the outer tank and the inner tank are kept in a communicated state through the water outlets of the inner tank, the water inlet convex parts of the outer tank, the interlayer space, the water return opening in the bottom end of the inner tank;
the polygonal heat-insulating tank body is used for bearing the double-layer cell reaction tank;
the polygonal heat-insulating tank body is arranged on the four-rocker shaking table.
As a further technical solution, the four-rocker swing bed comprises: a rocker assembly, a rocking disc assembly and a rocking bed driving box of a cross axle structure;
the shaking table driving box is connected with the shaking disc assembly;
the polygonal heat-insulation tank body is arranged on the rocking disc assembly;
the double-layer cell reaction tank is arranged on the polygonal heat-insulation tank body;
the rocking disc assembly is provided with fixed sleeves with downward openings at four corners of the rocking disc respectively, and the rocker assembly of the cross shaft structure comprises four rockers of the cross shaft structure;
the top of the rocker of the cross structure is installed at the top in the fixed sleeve through an upper supporting seat, and the bottom of the rocker of the cross structure is installed on a driving box chassis of the shaking table driving box through a lower supporting channel steel.
As a further technical solution, the rocker of the cross axle structure includes: the device comprises an upper supporting seat, a cross shaft, a sliding bearing, a lower supporting seat, a short shaft at the upper end of a rocker, a hollow sleeve of the rocker, a short shaft at the lower end of the rocker, an upper swinging channel steel, an upper limiting shaft, an upper supporting channel steel, a lower swinging channel steel, a lower supporting shaft, a lower limiting shaft and a lower supporting channel steel;
two shaft ends of the cross shaft which are oppositely arranged are respectively connected with the upper support seat through the sliding bearing, and the other two shaft ends of the cross shaft which are oppositely arranged are respectively connected with the lower support seat through the sliding bearing; the upper support seat, the cross shaft, the sliding bearing and the lower support seat form a universal joint structure at the top end of a rocker of the cross shaft structure together; the upper part of the short shaft at the upper end of the rocker is welded at the bottom of the lower supporting seat; the upper end of the rocker hollow shaft sleeve and the lower end of the short shaft at the upper end of the rocker are sleeved together and connected in a spot welding manner, so that coaxial connection is realized;
the upper end of the upper swing channel steel and the lower end of the short shaft at the lower end of the rocker are welded and connected into a whole; the bottom of the upper supporting channel steel and the upper part of the lower swinging channel steel are welded and connected into a whole, and the included angle of the two channel directions forms a 90-degree angle; the upper swing channel steel (welded with the short shaft at the lower end of the rocker into a whole) is used for installing the upper supporting channel steel (welded with the lower swing channel steel into a whole) through shafts by using two upper limiting shafts and one upper supporting shaft; the lower swing channel steel is mounted with the lower support shaft and the two lower limiting shafts through the shafts; the upper end of the short shaft at the lower end of the rocker is concentrically arranged at the lower end of the rocker hollow shaft sleeve in a penetrating way and is connected with the lower end of the rocker hollow shaft sleeve in a spot welding way.
As a further technical scheme, two upper limiting shafts are respectively and symmetrically arranged at two sides above the upper support; the two lower limiting shafts are respectively and symmetrically arranged at two sides below the lower supporting shaft.
As a further technical scheme, a driving motor is arranged in the shaking table driving box;
a power output shaft of the driving motor is provided with a small belt pulley;
the small belt pulley is connected with the large belt pulley in a tensioning manner through a belt;
the large belt pulley is arranged on the driving eccentric shaft;
the upper end of the driving eccentric shaft is connected with an upper swing disc;
the upper shaking disc is connected with four groups of driven shafts;
the upper shaking plate is connected to the shaking plate through a bolt;
the polygonal heat-insulating tank body is connected and installed on the rocking disc through the tank body bottom plate through bolts.
As a further technical scheme, the number of the polygonal sides of the polygonal heat-insulating tank body is 6-12.
As a further technical scheme, the flange plate at the top of the outer tank is connected with the flange plate of the tank cover through bolts, and the flange plate are sealed by a sealing rubber ring; the flange plate at the top of the inner tank is welded and connected with the inner ring of the flange plate of the outer tank into a whole; the top ring of filter screen with the ring flange welded connection of inner tank is in an organic whole, the foundation ring of filter screen pass through the rand with the waist festival position of inner tank is connected.
As a further technical scheme, the bottom of the outer tank is provided with four support columns; the bottom of inner tank be provided with four with the mounting hole of support column looks adaptation.
As a further technical scheme, the lower portion of the inner tank is cylindrical, the upper portion of the inner tank is conical, water outlets of the inner tank are symmetrically formed in the wall of the conical tank on the upper portion of the inner tank, a tangential flow baffle is arranged on the clockwise side of the water outlets, and a horizontal baffle is arranged at the bottom of the tangential flow baffle.
As a further technical scheme, the lower part of the outer tank is cylindrical, the upper part of the outer tank is conical, and the water inlet convex part of the outer tank is arranged on the wall of the conical cylinder in an outward expansion mode.
By adopting the technical scheme, the invention has the following beneficial effects:
the invention provides a double-layer hard plastic fluidized bed cell bioreactor of a four-rocker shaking table,
the four-rocker shaking table adopts the upper end and the lower end of the rocker with a cross-axle structure, the load in the vertical direction is directly guided to the ground through the rocker, the overturning moment acting on the shaking table and the ground can be eliminated, the vibration and the noise generated in the whole culture process are reduced, the manufacturing cost and the self weight of the shaking table can be greatly reduced, and the shaking table can bear large load;
the double-layer reaction tank and the filter screen on the double-layer reaction tank can culture cells by a perfusion process when high-density microcarrier is adopted to culture adherent cells, and the cells grow in a real microgravity environment. The cells are grown three-dimensionally, and the high differentiation rate expansion is kept. The reaction tank is particularly suitable for culturing mesenchymal stem cells, and is beneficial to popularization and application.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 is a front view of a double-layer rigid plastic fluidized bed cell bioreactor of a four-rocker rocking bed according to an embodiment of the present invention;
FIG. 2 is a side view of the double-layered hard plastic fluidized bed cell bioreactor of the four-rocker rocking bed shown in FIG. 1;
FIG. 3 is a top view of the double-layered hard plastic fluidized bed cell bioreactor of the four-rocker rocking bed shown in FIG. 1;
FIG. 4 is a schematic structural diagram of a double-layered cell reaction tank according to an embodiment of the present invention;
FIG. 5 is a top view of a double-layered cell reaction tank according to an embodiment of the present invention;
FIG. 6 is a schematic view of a can lid constructed in accordance with an embodiment of the present invention;
FIG. 7 is a top view of a can lid according to an embodiment of the present invention;
FIG. 8 is a schematic structural diagram of an outer tank according to an embodiment of the present invention;
FIG. 9 is a top view of an outer vessel provided in accordance with an embodiment of the present invention;
FIG. 10 is a schematic structural diagram of an inner vessel according to an embodiment of the present invention;
FIG. 11 is a top view of an inner vessel provided in accordance with an embodiment of the present invention;
fig. 12 is a schematic structural diagram of a filter screen according to an embodiment of the present invention;
FIG. 13 is a top view of a screen according to an embodiment of the present invention;
FIG. 14 is a top view of a collar provided by an embodiment of the present invention;
FIG. 15 is a front view of a cross-pin configuration of a rocker assembly provided in accordance with an embodiment of the present invention;
FIG. 16 is a side view of a cross-pin configuration rocker assembly according to an embodiment of the present invention.
Icon: 202-can lid; 205-inner vessel; 208-a filter screen; 209-collar; 210-a water outlet; 211-tangential flow baffles; 212-horizontal baffle; 214-an outer tank; 217-a water return port; 222-a water inlet boss; 223-sealing rubber ring; 225-support column; 300-rocker assembly of cross axle structure; 302-upper support; 305-a cross-shaft; 308-a sliding bearing; 310-lower support seat; 312-Rocker Upper short shaft; 313-rocker hollow sleeve; 314-rocker lower stub shaft; 316-upper limiting axis; 320-upper support shaft; 322-lower support shaft; 326-lower limit shaft; 330-lower supporting channel steel; 333-lower swing channel steel; 334-upper supporting channel steel; 338-up swinging channel steel; 516-polygonal heat-insulating tank body; 518-a wobble plate assembly; 520-drive box chassis; 530-shaking table drive box.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the accompanying drawings, and it should be understood that the described embodiments are some, but not all embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc., indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, and are only for convenience of description and simplicity of description, but do not indicate or imply that the device or element being referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus, should not be construed as limiting the present invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.
In the description of the present invention, it should be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral connection; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meanings of the above terms in the present invention can be understood by those skilled in the art according to specific situations.
The following detailed description of embodiments of the invention refers to the accompanying drawings. It should be understood that the detailed description and specific examples, while indicating the present invention, are given by way of illustration and explanation only, not limitation.
Referring to fig. 1 to 16, the present embodiment provides a double-layer hard plastic fluidized bed cell bioreactor with a four-rocker rocking bed, which includes a polygonal heat-preserving tank 516, and further includes: a double-layer cell reaction tank and a four-rocker shaking table; the double-layered cell reaction tank includes: tank lid 202, outer tank 214, inner tank 205, and screen 208; the tank lid 202 is mounted on top of the outer tank 214; the inner tank 205 is installed inside the outer tank 214, and the strainer 208 is installed at a position above the waist section of the inner tank 205; two water inlet convex parts 222 are symmetrically arranged on two sides of the upper end of the outer tank 214, two water outlets 210 are symmetrically arranged on two sides of the upper end of the inner tank 205, the water inlet convex parts 222 on the upper end of the outer tank 214 and the water outlets 210 on the upper end of the inner tank 205 are arranged in a one-to-one correspondence manner, a water return port 217 is arranged at the bottom end of the inner tank 205, an interlayer space is formed between the outer tank 214 and the inner tank 205, and the outer tank 214 and the inner tank 205 are kept in a communicated state through the water outlets 210 of the inner tank 205, the water inlet convex parts 222 of the outer tank 214, the interlayer space, the water return port 217 at the bottom end of the inner tank 205 and; the polygonal heat-insulating tank body 516 is used for bearing the double-layer cell reaction tank; the polygonal heat-preserving tank body 516 is installed on the four-rocker shaking table.
In this embodiment, after the device is installed, the cradle is not started, the double-layer reaction tank is filled in the polygonal heat-insulating tank 516, the culture solution is added, the heating is started, the sterilized microcarriers are put in proportion, and the device is started to shake. When the temperature reaches 35.5-37 deg.c. The seed cells are injected. Cells were allowed to adhere to the wall first at a lower rotation speed. I.e. to the surface of the microcarrier.
After the adherence is completed, the cells are cultured at a faster rotating speed, and are differentiated and amplified. Culturing by perfusion, and washing the cells from the surface of the microcarrier with enzyme after reaching the density. If the amplification culture is to be continued, the amplification culture can be performed in a reversed tank. Namely, the next reactor with larger volume is adopted, and the above operations are repeated to complete the next stage of inverted tank amplification culture.
The perfusion process is when the nutrient substances in the culture solution in the reaction tank are exhausted, but the cultured cells do not reach the required density. When the culture is continued, a fresh culture medium is added to the tank at the same flow rate while the supernatant is withdrawn from the tank, and the cells are continuously cultured and expanded to increase the cell density. The point is that the cells cannot be simultaneously extracted by extracting only the supernatant, and the cells are trapped in the tank. And continuously culturing and amplifying to meet the density requirement.
In this embodiment, preferably, the double-layer cell reaction tank may be made of a double-layer PVC material, and is suitable for culturing adherent cells with a small working volume and a high density microcarrier. The embodiment is suitable for culturing the mesenchymal stem cells, and the cell reaction tank can be made of a single-layer plastic film and a hard plastic framework when the volume is enlarged.
In this embodiment, as a further technical solution, the four-rocker swing bed includes: a rocker assembly 300, a rocking disk assembly 518 and a rocking bed driving box 530 in a cross shaft structure; the swing bed driving box 530 is connected with the swing disc assembly 518; the polygonal heat-insulating tank body 516 is arranged on the rocking disc assembly 518; the double-layer cell reaction tank is arranged on the polygonal heat-preservation tank body 516; the rocking disc assembly 518 is provided with fixing sleeves with downward openings at four corners of the rocking disc respectively, and the rocker assembly 300 of the cross shaft structure comprises four rockers of the cross shaft structure; the top of the rocker of the cross structure is mounted at the top in the fixed sleeve through an upper support base 302, and the bottom of the rocker of the cross structure is mounted on a drive box chassis 520 of the table drive box 530 through a lower support channel steel 330.
In this embodiment, specifically, the rocker of the cross axle structure includes: an upper supporting seat 302, a cross shaft 305, a sliding bearing 308, a lower supporting seat 310, a rocker upper end short shaft 312, a rocker hollow sleeve 313, a rocker lower end short shaft 314, an upper swinging channel steel 338, an upper limiting shaft 316, an upper supporting shaft 320, an upper supporting channel steel 334, a lower swinging channel steel 333, a lower supporting shaft 322, a lower limiting shaft 326 and a lower supporting channel steel 330; two shaft ends of the cross shaft which are arranged oppositely are respectively connected with the upper support base 302 through the sliding bearing 308, and the other two shaft ends of the cross shaft which are arranged oppositely are respectively connected with the lower support base 310 through the sliding bearing 308; the upper support base 302, the cross shaft, the sliding bearing 308 and the lower support base 310 together form a universal joint structure at the top end of a rocker of a cross shaft structure; the upper part of the rocker upper end short shaft 312 is welded at the bottom of the lower support seat 310; the upper end of the rocker hollow shaft sleeve and the lower end of the rocker upper end short shaft 312 are sleeved together and connected in a spot welding manner, so that coaxial connection is realized; the upper end of the upper swing channel steel 338 is welded and connected with the lower end of the rocker lower end short shaft 314 into a whole; the bottom of the upper supporting channel steel and the upper part of the lower swinging channel steel 333 are welded and connected into a whole, and the included angle of the two channels is 90 degrees; the upper swing channel 338 (welded to the rocker lower stub shaft 314) is journaled together by the upper support channels 334 (welded to the lower swing channel 333) using the two upper limiting shafts 316 and the upper support shaft 320; the lower swing channel steel 333 is formed by shaft-mounting the lower support channel steel 330 together by a lower support shaft 322 and two lower limiting shafts 326; the upper end of the rocker lower end short shaft 314 is concentrically arranged at the lower end of the rocker hollow shaft sleeve in a penetrating way and is connected with the rocker hollow shaft sleeve in a spot welding way.
The upper end and the lower end of the rocker of the universal joint cross shaft structure principle are adopted in the embodiment, and the longitudinal load of the rocker is directly guided to the ground through the rocker. The limiting shaft at the lower end of the rocker is used for limiting the rotation angle of each direction of the rocker within a preset angle, and the specific angle setting can be flexibly set according to actual needs.
In this embodiment, as a further technical solution, two upper limiting shafts 316 are respectively symmetrically disposed on two sides above the upper support; the two lower limiting shafts 326 are respectively and symmetrically arranged at two sides below the lower supporting shaft 322.
In this embodiment, as a further technical solution, a driving motor is installed in the shaking table driving box 530; a power output shaft of the driving motor is provided with a small belt pulley; the small belt pulley is connected with the large belt pulley in a tensioning manner through a belt; the large belt pulley is arranged on the driving eccentric shaft; the upper end of the driving eccentric shaft is connected with an upper swing disc; the upper shaking disc is connected with four groups of driven shafts; the upper shaking plate is connected to the shaking plate through a bolt; the polygonal heat-insulating tank body 516 is installed on the rocking disc through a tank body bottom plate by using bolts. In this embodiment, a mechanical eccentric shaft is used to output torque, so that the rocking disc performs circular oscillation motion. The shaking table does not generate overturning moment, and the supporting point of the shaking table can be higher than the gravity center of the tank body. The vertical load of the cradle is directly transmitted to the ground through the rocker.
In this embodiment, as a further technical solution, the number of the polygonal sides of the polygonal heat-insulating tank 516 is 6 to 12.
In this embodiment, as a further technical solution, the flange at the top of the outer tank 214 is connected with the flange of the tank cover 202 through bolts, and the two are sealed by a sealing rubber ring 223; the flange plate at the top of the inner tank 205 and the inner ring of the flange plate of the outer tank 214 are welded and connected into a whole; the top ring of the filter screen 208 is connected with the flange of the inner tank 205 in a welding way, and the bottom ring of the filter screen 208 is connected with the waist section of the inner tank 205 through a clamping ring 209.
In this embodiment, as a further technical solution, four support columns 225 are disposed at the bottom of the outer tank 214; the bottom of the inner tank 205 is provided with four mounting holes matched with the support columns 225.
In this embodiment, as a further technical solution, the lower portion of the inner tank 205 is cylindrical, the upper portion of the inner tank 205 is conical, the water outlets 210 of the inner tank 205 are symmetrically arranged on the conical tank wall of the upper portion of the inner tank 205, the water outlets 210 are provided with a tangential flow baffle 211 on the clockwise side, and the bottom of the tangential flow baffle 211 is provided with a horizontal baffle 212.
In this embodiment, as a further technical solution, the lower portion of the outer tank 214 is cylindrical, the upper portion of the outer tank 214 is conical, and the water inlet convex portion 222 of the outer tank 214 is extended outward from the conical cylinder.
The tank body of the embodiment is a double-layer tank, preferably made of PC material, and the working volume is below 50 liters; the tank cover and the tank body are tightened by adopting a sealing rubber ring and a bolt to finish sealing. The shape of the filter screen can be adjusted. The tank is particularly suitable for the in-vitro amplification culture of the mesenchymal stem cells; when the adherent cells are cultured by using the high-density microcarrier, the cells grow in a microgravity environment, can grow in a three-dimensional manner and keep high differentiation rate amplification; the structure of the reaction tank is designed according to the clockwise shaking design of the shaking table, and the shaking table needs to shake clockwise during working.
It should be noted that the can lid of the present embodiment can integrate the structural features of the multifunctional tray, such as: the tank cover is provided with an air inlet, an air outlet, a liquid inlet, a liquid outlet, a sampling port and the like. There are also a number of sensor assemblies including: dissolved oxygen sensors 201, PH sensors, and the like.
The working principle of the double-layer hard plastic fluidized bed cell bioreactor of the four-rocker shaking table in the embodiment is as follows:
after the whole reactor is installed, firstly, the culture solution is added into the double-layer reaction tank to reach the liquid level of a static liquid level, then the double-layer cell reaction tank is heated to the heat preservation temperature and is continuously preserved, the microcarriers are added according to the proportion, then the shaking table is started to start shaking, and then the seed cells are injected. The cells are rocked at a low speed to adhere to the wall at the beginning, and the rotating speed is increased to amplify and culture the cells after the adherence is finished; the shaking table is shaken clockwise, and after shaking, the liquid surface of the culture solution rotates at a dynamic liquid level with a high side and a low side. When the double-layer cell reaction tank rotates for one circle, the culture solution with a higher liquid level enters the two water outlets 210 first and then flows out of the inner tank 205 and enters an interlayer space between the inner tank 205 and the outer tank 214, the water inlet convex part 222 of the outer tank 214 forms a larger gas-liquid phase mixing space for the inflowing culture solution, and a large amount of water flowers and water drops are generated at the interlayer, so that the gas-liquid ratio surface area is increased, the rapid oxygen dissolution and the harmful gas dissolution are facilitated, the water drops are released from the culture solution, and the water flowers escape into the air and are discharged out of the reactor; with the shaking of the shaking table, the culture solution entering the outer tank 214 flows spirally downward in the interlayer space, reaches the bottom, flows into the inner tank 205 from the water return port 217 of the inner tank 205, then flows spirally upward until the water level of the inner tank 205 flows into the interlayer space outside the inner tank 205 from the two water outlets 210 of the inner tank 205, and circularly flows.
Meanwhile, due to the action of the filter screen 208, the high-density microcarriers with adherent cells in the culture solution are trapped in the filter screen 208, and only the culture solution flow filter screen 208 performs circular flow.
At this time, the culture liquid in the inner tank 205 flows spirally upward from the bottom to the top. The cells on the microcarriers in this space are all pushed upwards, overcoming their own weight. Therefore, the cells grow in the microgravity environment, the cells can grow in a three-dimensional manner, the differentiation rate is high, and the activity is good; the jacketed top ends of the inner 205 and outer 214 vessels of the reaction vessel are in communication with the top of the inner vessel 205. The can lid 202 flange and the outer can 214 flange are clamped tight with a bolt-on sealing ring.
Because the density of the microcarrier is high, the sedimentation rate is high, the microcarrier in the inner tank 205 is flushed by the culture solution which flows upwards spirally, but when the microcarrier reaches the round table body at the upper part of the inner tank 205, the cross sectional area is gradually increased, the flow rate of the culture solution which flows upwards is reduced, the upward thrust of the culture solution and the downward gravity of the microcarrier reach balance when the microcarrier reaches the top, the microcarrier cannot reach the water outlet 210 of the inner tank 205, and at the moment, the microcarrier can only be suspended and stopped in the inner tank 205 and float up and down. Very individual microcarriers are flushed out of the outlet 210 and are retained by the screen 208.
By adopting the technical scheme, the invention has the following beneficial effects:
the four-rocker shaking table adopts the upper end and the lower end of the rocker with a cross-axle structure, the load in the vertical direction is directly guided to the ground through the rocker, the overturning moment acting on the shaking table and the ground can be eliminated, the vibration and the noise generated in the whole culture process are reduced, the manufacturing cost and the self weight of the shaking table can be greatly reduced, and the shaking table can bear large load;
the double-layer reaction tank and the filter screen 208 on the double-layer reaction tank can culture cells by a perfusion process when high-density microcarrier is adopted to culture adherent cells, and the cells grow in a real microgravity environment. The cells are grown three-dimensionally, and the high differentiation rate expansion is kept. The reaction tank is particularly suitable for culturing mesenchymal stem cells, and is beneficial to popularization and application.
Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.
Claims (10)
1. The utility model provides a fluidized bed cell bioreactor is moulded firmly to double-deck of four rocker shaking tables, includes the polygon heat preservation jar body, its characterized in that still includes: a double-layer cell reaction tank and a four-rocker shaking table;
the double-layered cell reaction tank includes: the tank comprises a tank cover, an outer tank, an inner tank and a filter screen; the tank cover is arranged at the top of the outer tank; the inner tank is arranged inside the outer tank, and the filter screen is arranged at a position above a waist section of the inner tank; two water inlet convex parts are symmetrically arranged on two sides of the upper end of the outer tank, two water outlets are symmetrically arranged on two sides of the upper end of the inner tank, the water inlet convex parts on the upper end of the outer tank and the water outlets on the upper end of the inner tank are arranged in a one-to-one correspondence mode, a water return opening is formed in the bottom end of the inner tank, an interlayer space is formed between the outer tank and the inner tank, and the outer tank and the inner tank are kept in a communicated state through the water outlets of the inner tank, the water inlet convex parts of the outer tank, the interlayer space, the water return opening in the bottom end of the inner tank;
the polygonal heat-insulating tank body is used for bearing the double-layer cell reaction tank;
the polygonal heat-insulating tank body is arranged on the four-rocker shaking table.
2. The double-layered hard plastic fluidized bed cell bioreactor of a four-rocker rocking bed according to claim 1, wherein the four-rocker rocking bed comprises: a rocker assembly, a rocking disc assembly and a rocking bed driving box of a cross axle structure;
the shaking table driving box is connected with the shaking disc assembly;
the polygonal heat-insulation tank body is arranged on the rocking disc assembly;
the double-layer cell reaction tank is arranged on the polygonal heat-insulation tank body;
the rocking disc assembly is provided with fixed sleeves with downward openings at four corners of the rocking disc respectively,
the rocker assembly of the cross axle structure comprises four rockers of the cross axle structure;
the top of the rocker of the cross structure is installed at the top in the fixed sleeve through an upper supporting seat, and the bottom of the rocker of the cross structure is installed on a driving box chassis of the shaking table driving box through a lower supporting channel steel.
3. The double-layer hard plastic fluidized bed cell bioreactor of a four-rocker rocking bed according to claim 2, wherein the rocker of the cross-shaped structure comprises: the device comprises an upper supporting seat, a cross shaft, a sliding bearing, a lower supporting seat, a short shaft at the upper end of a rocker, a hollow sleeve of the rocker, a short shaft at the lower end of the rocker, an upper swinging channel steel, an upper limiting shaft, an upper supporting channel steel, a lower swinging channel steel, a lower supporting shaft, a lower limiting shaft and a lower supporting channel steel;
two shaft ends of the cross shaft which are oppositely arranged are respectively connected with the upper support seat through the sliding bearing, and the other two shaft ends of the cross shaft which are oppositely arranged are respectively connected with the lower support seat through the sliding bearing; the upper support seat, the cross shaft, the sliding bearing and the lower support seat form a universal joint structure at the top end of a rocker of the cross shaft structure together; the upper part of the short shaft at the upper end of the rocker is welded at the bottom of the lower supporting seat; the upper end of the rocker hollow shaft sleeve and the lower end of the short shaft at the upper end of the rocker are sleeved together and connected in a spot welding manner, so that coaxial connection is realized;
the upper end of the upper swing channel steel and the lower end of the short shaft at the lower end of the rocker are welded and connected into a whole; the bottom of the upper supporting channel steel and the upper part of the lower swinging channel steel are welded and connected into a whole, and the included angle of the two channel directions forms a 90-degree angle; the upper swing channel steel (welded with the short shaft at the lower end of the rocker into a whole) is used for installing the upper supporting channel steel (welded with the lower swing channel steel into a whole) through shafts by using two upper limiting shafts and one upper supporting shaft; the lower swing channel steel is mounted with the lower support shaft and the two lower limiting shafts through the shafts; the upper end of the short shaft at the lower end of the rocker is concentrically arranged at the lower end of the rocker hollow shaft sleeve in a penetrating way and is connected with the lower end of the rocker hollow shaft sleeve in a spot welding way.
4. The double-layer hard plastic fluidized bed cell bioreactor of the four-rocker rocking bed according to claim 3,
the two upper limiting shafts are respectively and symmetrically arranged at two sides above the upper support;
the two lower limiting shafts are respectively and symmetrically arranged at two sides below the lower supporting shaft.
5. The double-layer rigid plastic fluidized bed cell bioreactor of a four-rocker rocking bed according to claim 2, wherein a driving motor is installed in the rocking bed driving box;
a power output shaft of the driving motor is provided with a small belt pulley;
the small belt pulley is connected with the large belt pulley in a tensioning manner through a belt;
the large belt pulley is arranged on the driving eccentric shaft;
the upper end of the driving eccentric shaft is connected with an upper swing disc;
the upper shaking disc is connected with four groups of driven shafts;
the upper shaking plate is connected to the shaking plate through a bolt;
the polygonal heat-insulating tank body is connected and installed on the rocking disc through the tank body bottom plate through bolts.
6. The double-layer hard plastic fluidized bed cell bioreactor of a four-rocker rocking bed according to claim 5, wherein the number of the polygonal sides of the polygonal heat-insulating tank body is 6-12.
7. The double-layer hard plastic fluidized bed cell bioreactor of the four-rocker rocking bed according to claim 3,
the flange plate at the top of the outer tank is connected with the flange plate of the tank cover through bolts, and the flange plate are sealed by a sealing rubber ring;
the flange plate at the top of the inner tank is welded and connected with the inner ring of the flange plate of the outer tank into a whole;
the top ring of filter screen with the ring flange welded connection of inner tank is in an organic whole, the foundation ring of filter screen pass through the rand with the waist festival position of inner tank is connected.
8. The double-layer hard plastic fluidized bed cell bioreactor of the four-rocker rocking bed according to claim 3,
the bottom of the outer tank is provided with four support columns;
the bottom of inner tank be provided with four with the mounting hole of support column looks adaptation.
9. The cell bioreactor of the double-layer hard plastic fluidized bed of the four-rocker shaking table of claim 3, wherein the lower part of the inner tank is cylindrical, the upper part of the inner tank is conical, the water outlet of the inner tank is symmetrically arranged on the conical tank wall of the upper part of the inner tank, the water outlet is provided with a tangential flow baffle on the clockwise side, and the bottom of the tangential flow baffle is provided with a horizontal baffle.
10. The cell bioreactor of claim 3, wherein the lower part of the outer tank is cylindrical, the upper part of the outer tank is conical, and the water inlet convex part of the outer tank is arranged on the wall of the conical cylinder in an outward expansion manner.
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| CN202010745650.4A CN111676139A (en) | 2020-07-29 | 2020-07-29 | Double-layer hard plastic fluidized bed cell bioreactor of four-rocker table |
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| CN202010745650.4A CN111676139A (en) | 2020-07-29 | 2020-07-29 | Double-layer hard plastic fluidized bed cell bioreactor of four-rocker table |
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