CN113073050A - Large-volume double-swing plastic bag cell bioreactor - Google Patents

Large-volume double-swing plastic bag cell bioreactor Download PDF

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CN113073050A
CN113073050A CN202110457640.5A CN202110457640A CN113073050A CN 113073050 A CN113073050 A CN 113073050A CN 202110457640 A CN202110457640 A CN 202110457640A CN 113073050 A CN113073050 A CN 113073050A
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swing
assembly
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swinging
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惠倪
惠识瑶
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/02Form or structure of the vessel
    • C12M23/14Bags
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    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/38Caps; Covers; Plugs; Pouring means
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/48Holding appliances; Racks; Supports
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    • C12M27/00Means for mixing, agitating or circulating fluids in the vessel
    • C12M27/16Vibrating; Shaking; Tilting
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/12Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
    • C12M41/18Heat exchange systems, e.g. heat jackets or outer envelopes

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Abstract

The invention relates to the technical field of cell bioreactors, in particular to a large-volume double-swing plastic bag cell bioreactor. The invention comprises the following steps: the cell culture device comprises a swing box assembly, a support frame assembly, an elastic swing rod assembly, a swing basket assembly, a multifunctional edge-covered heat preservation groove and a cell culture bag; the swing box assembly is arranged on the supporting frame assembly; the swing box assembly is connected with the upper part of the swing basket assembly through an elastic swing rod assembly; two ends of a bearing shaft of the supporting frame assembly are connected with two swinging straight handles, and the two swinging straight handles are connected through a swinging shaft at the bottom of the swinging basket assembly; the multifunctional edge-covering heat preservation groove is formed in the swing basket assembly, and the cell culture bag is arranged in the multifunctional edge-covering heat preservation groove.

Description

Large-volume double-swing plastic bag cell bioreactor
Technical Field
The invention relates to the technical field of cell bioreactors, in particular to a large-volume double-swing plastic bag cell bioreactor.
Background
At present, the development of the world biotechnology pharmaceutical industry is rapid, and more than 2020, the outbreak and the epidemic of the global new coronary epidemic situation cause a large amount of people to be infected with new coronary virus diseases, and a great number of patients die. The major epidemic situation promotes the rapid development of the biotechnology pharmaceutical industry from the opposite direction, and a large amount of funds, manpower and technologies are put into the industrialization process of the research and development of the biotechnology pharmaceutical industry and the capacity expansion aiming at the research and development and the capacity expansion of the fields of new coronary vaccines, diagnostic reagents, antibody medicines and cell therapy in the global range. Therefore, the most important bioprocess equipment in the biotechnology pharmaceutical industry, the disposable cell bioreactor for large-scale and high-density culture of animal cells, becomes a key link and bottleneck problem for expanding the productivity, and the disposable cell bioreactor largely determines the production capacity, product variety and product cost of the biopharmaceutical enterprise. When the working volume of the existing swing type cell bioreactor is larger, for example, more than 50 liters, the existing swing type cell bioreactor can generate impact force to dead points at two ends swinging left and right, and knock the ground to generate vibration and noise, when the volume is further increased, for example, more than 500 liters, the situation is more serious, the ground of a workshop is vibrated along with the vibration, and the whole environment cannot work. In addition, in case of large volume, the swing frequency of the reactor cannot be reduced to reduce impact force and vibration, because the flow speed of the culture solution in the culture bag is reduced, the dissolved oxygen level is reduced, the fluidity is reduced, the blending level is reduced, harmful gas is increased and cannot overflow, and the growth and the expansion of cells are seriously influenced when excessive accumulation occurs. The existing swing cell bioreactor has been shut down for a reactor having a volume of 50 liters or more. For the above reasons, it is now necessary to eliminate the drawbacks of impact, vibration and noise in the conventional swing-type cell bioreactor to enable large-volume and large-scale cell culture.
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 large-volume double-swing plastic bag cell bioreactor to solve the technical problem of the existing swing cell bioreactor.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides a large-volume double-swing plastic bag cell bioreactor, which comprises: the cell culture device comprises a swing box assembly, a support frame assembly, an elastic swing rod assembly, a swing basket assembly, a multifunctional edge-covered heat preservation groove and a cell culture bag;
the swing box assembly is arranged on the supporting frame assembly; the swing box assembly is connected with the upper part of the swing basket assembly through an elastic swing rod assembly; two ends of a bearing shaft of the supporting frame assembly are connected with two swinging straight handles, and the two swinging straight handles are connected through a swinging shaft at the bottom of the swinging basket assembly; the multifunctional edge-covering heat preservation groove is formed in the swing basket assembly, and the cell culture bag is arranged in the multifunctional edge-covering heat preservation groove.
Preferably, the swing case assembly includes: the device comprises a swing box cover, a swing box body, a swing rod short shaft, a thrust joint bearing combined spherical mechanism, a linear guide rail, a ball screw, a stepping motor, a box body bottom plate and a flange plate;
the swing box cover is connected with the swing box body through a flange plate; the stepping motor is arranged on a box body bottom plate of the box body of the swing box; the stepping motor is connected with a lead screw of a ball screw, a nut of the ball screw is connected with the spherical thrust joint bearing combined mechanism, the spherical thrust joint bearing combined mechanism is slidably mounted on a linear guide rail, the linear guide rail is mounted on a bottom plate of the box body, and the swing rod short shaft is mounted on the spherical thrust joint bearing combined mechanism in a penetrating manner; and a hollow part is arranged on the bottom plate of the box body of the swing box along the direction of the linear guide rail.
Preferably, the thrust spherical mechanism comprises: the thrust joint bearing comprises a shell, a shaft sleeve and a thrust joint bearing; the upper end and the lower end of the shell are respectively provided with a thrust joint bearing; the shaft sleeve is positioned between the upper thrust joint bearing and the lower thrust joint bearing; and the swing rod short shaft is sequentially arranged in the thrust knuckle bearing at the upper end, the shaft sleeve and the thrust knuckle bearing at the lower end in a penetrating manner.
Preferably, the elastic swing link assembly includes: the device comprises a swing rod, an upper disc, four tension springs, a swing rod cross shaft bearing, a tension spring fixing ring and a lower disc;
the upper part of the swing rod penetrates through a central hole of the upper disc and is connected with a swing rod short shaft of the swing box assembly; the lower part of the swing rod is connected with a swing rod cross shaft; the swing rod transverse shaft is arranged on the lower disc through a swing rod transverse shaft bearing; the upper ends of the four tension springs are respectively connected to four corners of the upper disc; the lower ends of the four tension springs are respectively connected to the periphery of the lower disc through tension spring fixing rings; the lower tray is connected with a swing frame of the swing basket assembly.
Preferably, the support frame assembly comprises: the device comprises a top frame beam, two-end supports, a swing straight shank bearing, a swing straight shank, a bearing shaft bearing, two-end inclined support plates, a swing bearing and a base bottom plate;
the top frame beam is connected with the base bottom plate through supports at two ends; the side surfaces of the brackets at the two ends are respectively provided with inclined supporting plates at the two ends; two ends of the bearing shaft are connected with the two-end brackets through bearing shaft bearings; the upper ends of the two swing straight handles are connected with the bearing shaft through swing straight handle bearings; the lower ends of the two swing straight handles are connected with the swing shaft through swing bearings.
Preferably, the bottom of the base bottom plate is provided with a rubber mat.
Preferably, the swing basket assembly includes a swing frame and a swing shaft;
the upper part of the swinging frame is connected with a lower disc of the elastic swinging rod assembly; the bottom of the swing frame is provided with a swing shaft.
Preferably, the multifunctional edge-covering heat-preserving groove is connected with a swinging frame of the swinging basket assembly through fixing platforms at two ends; the inner surface of the multifunctional edge-covered heat preservation groove is provided with a cambered surface matched with the cell culture bag; the upper part of the multifunctional edge-covering heat-insulating groove is provided with an edge-covering structure which contracts inwards; the multifunctional edge-covering heat preservation groove is fixed in the swinging basket.
Preferably, the multifunctional edge-covering heat preservation groove is heated by a rubber plate or a water jacket.
Preferably, the cross section of the cell culture bag is provided with an oval shape; the plastic film seam of the cell culture bag is arranged at the position of the upper diagonal line and the lower diagonal line of the cell culture bag.
Preferably, the upper part of the cell culture bag is provided with a plurality of liquid inlets, liquid outlets, air inlets, air outlets and interfaces for installing dissolved oxygen, pH value and temperature sensors. The cell culture bag is made by welding five or seven layers of co-extruded plastic films.
By adopting the technical scheme, the invention has the following beneficial effects:
the invention provides a large-volume double-swing plastic bag cell bioreactor.A swing basket and other parts in swing and the whole weight of culture solution act on a bearing shaft through a swing shaft and a swing straight handle, and then a load acts on the ground through a support frame assembly; in addition, the movement of the double swing mechanism is that the elastic swing rod swings the swing basket assembly left and right around the swing shaft. And the swinging shaft and the swinging straight shank swing left and right around the bearing shaft. The cell culture bag has the advantages that the culture solution in the cell culture bag flows back and forth in the left and right directions from the left and right swinging of the elastic swing rod around the swinging shaft through the left and right swinging of the swinging basket, then moves left and right at the gravity center of the swinging basket, reversely swings around the bearing shaft through the swinging shaft and the swinging straight handle, and finally the bearing shaft transmits the load to the ground through the support frame assembly. In the whole movement process, according to the law of conservation of energy, only a few places with friction have kinetic energy to be converted into heat energy to be consumed, and the rotating parts are the rotation of the shaft and the bearing, so that the lubrication is good, the friction coefficient is extremely small, and the energy consumption is extremely small. The rest energy is changed into potential energy from kinetic energy, then changed into swing kinetic energy, and finally changed into positive pressure to act on the ground. Basically, no impact force exists, shaking occurs, and vibration is generated. The problem that the existing mainstream swing type cell reactor in the world generates large impact force, vibration, shaking and noise when swinging to the left end point and the right end point when the volume is large (more than 50 liters), and is particularly serious when the volume is large (more than 500 liters) is solved completely. However, the large-volume double-swing plastic bag cell reactor can stably culture cells under the conditions of no impact force, small shaking, vibration and small noise, the working volume can reach 10000 liters, and simultaneously, no large impact force or vibration exists.
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 large-volume double-swing plastic bag cell bioreactor according to an embodiment of the present invention;
FIG. 2 is a side view of a large volume double oscillating plastic bag cell bioreactor according to an embodiment of the present invention;
FIG. 3 is a top view of a large-volume double-swing plastic bag cell bioreactor according to an embodiment of the present invention;
FIG. 4 is a front view of a swing basket assembly provided by an embodiment of the present invention;
FIG. 5 is a side view of a swing basket assembly provided by an embodiment of the present invention;
FIG. 6 is a top view of a swing basket assembly provided by an embodiment of the present invention;
FIG. 7 is a front view of a swing box assembly provided by an embodiment of the present invention;
FIG. 8 is a top view of a swing box assembly provided by an embodiment of the present invention;
FIG. 9 is a front view of a resilient rocker assembly provided in accordance with an embodiment of the present invention;
FIG. 10 is a top view of a resilient rocker assembly according to an embodiment of the present invention;
FIG. 11 is a front view of a multifunctional covered edge heat-preserving groove provided by the embodiment of the invention;
FIG. 12 is a top view of the multifunctional covered edge heat-preserving groove provided by the embodiment of the invention;
FIG. 13 is a schematic structural diagram of a spherical mechanism of a thrust knuckle bearing assembly according to an embodiment of the present invention;
FIG. 14 is a front view of a cell culture bag according to an embodiment of the present invention;
FIG. 15 is a top view of a cell culture bag according to an embodiment of the present invention;
FIG. 16 is a front view of a support frame assembly provided by an embodiment of the present invention;
FIG. 17 is a side view of a support frame assembly provided in accordance with an embodiment of the present invention;
FIG. 18 is a top view of a support frame assembly provided in accordance with an embodiment of the present invention;
FIG. 19 is a schematic diagram illustrating a state that a large-volume double-swing plastic bag cell bioreactor provided in an embodiment of the present invention swings to the leftmost end;
FIG. 20 is a schematic diagram of the large-volume double-swing plastic bag cell bioreactor provided in the embodiment of the present invention swinging to the rightmost end.
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 20, the present embodiment provides a large-volume double-swing plastic bag cell bioreactor, which includes: the cell culture device comprises a swing box assembly 100, a support frame assembly 200, an elastic swing rod assembly 300, a swing basket assembly 400, a multifunctional edge-covered heat preservation groove 500 and a cell culture bag 600; the swing box assembly 100 is mounted on the support frame assembly 200; the swing box assembly 100 is connected with the upper part of the swing basket assembly 400 through an elastic swing rod assembly 300; two ends of the bearing shaft 800 of the support frame assembly 200 are connected with two swing straight handles 210, and the two swing straight handles 210 are connected through a swing shaft 900 at the bottom of the swing basket assembly 400; the multifunctional covered edge heat preservation groove 500 is arranged in the swing basket assembly 400, and the cell culture bag 600 is arranged in the multifunctional covered edge heat preservation groove 500.
In this embodiment, preferably, the swing box assembly 100 includes: the device comprises a swing box cover 101, a swing box body 102, a swing rod short shaft 112, a thrust joint bearing combined spherical mechanism 110, a linear guide rail 104, a ball screw 106, a stepping motor 107, a box body bottom plate 108 and a flange plate 109; the swing box cover 101 is connected with the swing box body 102 through a flange plate 109; the stepping motor 107 is arranged on a box body bottom plate 108 of the swinging box body 102; the stepping motor 107 is connected with a lead screw of a ball screw 106, a nut of the ball screw 106 is connected with the spherical thrust joint bearing combination mechanism 110, the spherical thrust joint bearing combination mechanism 110 is slidably mounted on a linear guide rail 104, the linear guide rail 104 is mounted on a box body bottom plate 108, and the pendulum rod short shaft 112 is mounted on the spherical thrust joint bearing combination mechanism 110 in a penetrating manner; the bottom plate of the swing box body 102 is provided with a hollow part along the direction of the linear guide rail 104. In the embodiment, the swing box adopts a spherical mechanism formed by combining a swing rod short shaft and a thrust joint bearing and is matched with an outer frame of the spherical mechanism to realize linear reciprocating motion, vertical linear movement in the axial direction of the short shaft and three-dimensional rotation.
In this embodiment, preferably, the spherical thrust knuckle bearing assembly 110 is slidably mounted on the two linear guide rails 104 through a sliding seat. Because the minor axis of the swing rod is the tail end of the rocker, the arm of force is very long and the stress is very small, so the stress is very small when the swing box swings, and the application range of the swing box is very large; of course, the swing box adopts a ball screw mechanism to push and pull the swing rod in a reciprocating manner, and hydraulic and pneumatic mechanisms can be adopted to replace the function. The selection is mainly determined by the factors such as reliability, noise size, cost and the like. The spherical thrust joint bearing combined mechanism only needs to adopt a domestic bearing, and has low requirement on precision due to low rotating speed; conditions allow the use of imported parts and components where the drive components and linear guides are the primary procurement items.
In this embodiment, preferably, the spherical thrust joint bearing assembly 110 includes: a housing 118, a bushing 116, and a thrust knuckle bearing 114; the upper end and the lower end of the shell 118 are respectively provided with a thrust joint bearing 114; the shaft sleeve 116 is positioned between the upper thrust knuckle bearing 112 and the lower thrust knuckle bearing 112; the swing rod short shaft 112 is sequentially arranged in the thrust knuckle bearing 112 at the upper end, the shaft sleeve 116 and the thrust knuckle bearing 112 at the lower end in a penetrating manner.
In this embodiment, preferably, the elastic swing link assembly 300 includes: a swing rod 302, an upper disc 304, four tension springs 306, a swing rod cross shaft 308, a swing rod cross shaft bearing 309, a tension spring fixing ring 320 and a lower disc 310; the upper part of the swing rod 302 passes through the central hole of the upper disc 304 and is connected with the swing rod short shaft 112 of the swing box assembly 100; the lower part of the swing rod 302 is connected with a swing rod transverse shaft 308; the swing rod cross shaft 308 is mounted on the lower disc 310 through a swing rod cross shaft bearing 309; the upper ends of the four tension springs 306 are respectively connected to four corners of the upper disc 304; the lower ends of the four tension springs 306 are respectively connected to the periphery of the lower disc 310 through tension spring fixing rings 320; the lower plate 310 is connected to the swing frame 402 of the swing basket assembly 400.
In this embodiment, preferably, the support frame assembly 200 includes: the top frame beam 202, the two-end bracket 204, the swing straight shank bearing 206, the swing straight shank 210, the bearing shaft 800, the bearing shaft bearing 806, the two-end inclined support plate 222, the swing bearing 902 and the base bottom plate 208; the top frame beam 202 is connected to a base plate 208 by two end brackets 204; two end inclined support plates 222 are respectively arranged on the side surfaces of the two end brackets 204; two ends of the bearing shaft 800 are connected with the brackets 204 at two ends through bearing shaft bearings 806; the upper ends of the two swing straight handles 210 are connected with the bearing shaft 800 through swing straight handle bearings 206; the lower ends of the two swing straight shanks 210 are connected to the swing shaft 900 through swing bearings 902.
In this embodiment, preferably, a rubber pad is disposed at the bottom of the base bottom plate 208.
In this embodiment, preferably, the swing basket assembly 400 includes a swing frame 402 and a swing shaft 406; the upper part of the swing frame 402 is connected with the lower disc 310 of the elastic swing rod assembly 300; the bottom of the swing frame 402 is provided with a swing shaft 406.
In this embodiment, preferably, the inner surface of the multifunctional covered edge heat preservation groove 500 is configured as an arc surface matched with the cell culture bag; the upper part of the multifunctional edge-covering heat-insulating groove 500 is provided with an edge-covering structure which contracts inwards; the multifunctional edge-covered heat preservation groove 500 is fixed in the swing frame 402 of the swing basket assembly 400. The multifunctional edge-covering heat-preserving groove 500 is connected with the swinging frame 402 of the swinging basket assembly 400 through fixed platforms 508 at two ends; the upper part of the multifunctional edge-covering heat-preserving groove 500 is provided with an edge-covering structure which shrinks inwards.
In this embodiment, preferably, the multifunctional edge-covering heat-preserving groove 500 is heated by a rubber plate or a water jacket.
In this embodiment, it is preferable that the cross section of the welding seals 606 at both ends of the cell culture bag 600 is set to be elliptical; the plastic film seam 602 of the cell culture bag 600 is positioned diagonally above and below it. The upper part of the cell culture bag 600 is provided with a plurality of liquid inlets, liquid outlets, air inlets, air outlets and interfaces for installing dissolved oxygen, PH value and temperature sensors. The cell culture bag 600 is made by welding five or seven co-extruded plastic films.
The principle of the movement analysis of the large-volume double-swing plastic bag cell bioreactor of the embodiment is as follows:
1. the reactor motion principle is as follows: the power source is a stepping motor and a ball screw in a swing box, and a spherical mechanism combined with a thrust joint shaft arranged on the sliding table is pushed on the linear guide rail to do reciprocating linear motion. The short shaft at the center of the spherical mechanism drives the elastic swing rod to swing left and right around the swing shaft center, and the swing basket and the multifunctional heat preservation tank are driven by the swing frame to swing left and right together with the cell culture bag and the culture solution in the cell culture bag, so that the culture solution in the cell culture bag flows back and forth in left and right directions, and the main motion of culturing cells is completed. Next, since the swinging basket assembly is mounted on the swinging shaft through a bearing, and the swinging basket and the swinging shaft are relatively rotated.
2. When the swinging rod swings the swinging basket leftwards, the culture solution in the culture bag in the swinging basket flows leftwards, the gravity center of the swinging basket assembly also moves leftwards, and the swinging shaft swings rightwards around the axial direction of the bearing shaft under the action of the force, so that a swinging angle, namely a rightward swinging angle is generated between the swinging shaft and the vertical line. Along with the rightward swing of the swing shaft, the horizontal height of the swing shaft center is also increased, namely the horizontal height h of the whole swing basket assembly is also increased (for example, when the swing straight handle is in a vertical position), so that the swing kinetic energy on the swing straight handle is converted into potential energy (the height is increased). When the swing rod swings to the left end point, the swing shaft swings rightwards to the highest position, and at the moment, the kinetic energy of the whole swing basket assembly is completely converted into potential energy, and the potential energy reaches the maximum. When the swinging rod swings back, namely swings right, the culture solution in the culture bag flows to the right, the gravity center of the swinging basket assembly moves right, and meanwhile, the potential energy drives the swinging shaft to swing back to the left, namely the potential energy is converted into swinging kinetic energy swinging to the left. Then the swinging shaft and the swinging straight shank swing together leftwards around the bearing shaft. When swinging to the highest point on the left, namely the point with the largest potential energy. At the moment, the potential energy also drives the swinging shaft to swing back to the right, namely the potential energy is converted into the swinging kinetic energy of the swinging shaft swinging to the right. Meanwhile, the swinging rod starts to swing leftwards, the swinging shaft swings to the right end point in the same way as the swinging shaft, then the swinging rod starts to swing backwards leftwards, the potential energy on the swinging shaft starts to be converted into kinetic energy swinging leftwards, the whole mechanism is circulated repeatedly, and the next cycle of swinging leftwards and rightwards starts;
3. in the whole movement process of the double-swing mechanism, according to the law of conservation of energy, only the friction between a plurality of positions of the shaft and the rotation position of the bearing has the consumption of kinetic energy converted into heat energy. And because the shaft and the bearing rotate, the lubrication is good, the friction coefficient is extremely small, and the energy consumption is extremely small. Similarly, the motion of the simple pendulum mechanism is converted back and forth from the swing kinetic energy and the potential energy, so that the energy consumption is low, and finally, the energy is converted into positive pressure to act on the ground. The double swing mechanism is substantially free from the generation of impact force, shaking and vibration. The problem that the existing mainstream swinging type plastic bag cell reactor in the world generates impact force, vibration, shaking and noise when swinging to the left end point and the right end point when the volume is large (more than 50 liters), is particularly serious when the volume is large (more than 500 liters), and as a result, the swinging type plastic bag cell reactor with the volume of more than 50 liters is not produced any more is solved completely. However, the large-volume double-swing plastic bag cell reactor has no problems in terms of impact force, shaking, vibration, noise and the like when the reactor with the volume of 10000 liters is estimated to have no impact force, small shaking, vibration and small noise.
In conclusion, the invention adopts the swing box with a spherical structure, and adopts the spherical mechanism combining the swing rod short shaft and the thrust knuckle bearing to be matched with the outer frame thereof, so as to realize the linear reciprocating motion, the up-and-down linear movement and the three-dimensional rotation in the axial direction of the short shaft; because the oscillating bar and the oscillating frame are longer, namely the arm of force is very long, the oscillating box bears very little force during oscillation, so the reaction force borne by the oscillating box and the upper part of the supporting frame is very little, and the vibration and the noise are also very little; the elastic oscillating bar has the characteristics of absorbing and storing energy and releasing energy, so that when the weight of an object to be oscillated is large and the elastic oscillating bar is subjected to a large reaction force, the energy can be well absorbed, stored and released, and the impact and the vibration are small;
the invention adopts the principle of double swinging: the first swing of the double-swing refers to the swing of the swing rod for swinging the swing basket assembly around the swing shaft; the weight of the swinging basket assembly acts on the swinging shaft, and the swinging basket and the swinging shaft rotate relatively through a bearing; the second swing of the double-swing refers to the swing of a single-swing system formed by all loads on the swing shaft, the two swing straight handles and the bearing shaft around the bearing shaft. Just this second single swing system through the interconversion of pendulum motion energy and potential energy, eliminated the impact force, rock, vibrations and the noise that produce at the left and right swing endpoint that produce in the first swing, made whole double pendulum motion reactor only finally the effort of support frame to ground, namely positive pressure. Other factors such as shaking, vibration and noise are very small and can be almost ignored. Therefore, the double-swing plastic bag cell bioreactor can stably culture cells in a large scale under the conditions of no impact force, no vibration and no noise; as for the structure and the movement principle of the reactor, the working volume of the reactor reaches 1 kiloliter, the reactor can also work stably, and impact force, vibration and the like can not be generated;
the multifunctional edge-covering heat-insulating groove is provided with the edge-covering structure at the upper part, so that when the culture solution flows to the left end point and the right end point, namely when the impact force is maximum, the stainless steel edge-covering structure bears the impact force, so that the cell culture bag can be protected, and meanwhile, the edge-covering structure also increases the heat-insulating area of the cell culture bag;
the two ends of the cell culture bag with the oval cross section are oval cross sections, so that the cross section area is large and the volume is large when the culture bag is the same in width. Secondly, when the culture solution swings to one end, the culture bag is evenly stressed by the oval section, and the damage of stress concentration can not be caused. Moreover, the two welding seams of the culture bag are changed from the left end and the right end to be in vertical oblique symmetry, and the welding seams are kept away from the place with the largest impact force, so that the use reliability of the culture bag is improved.
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. A large-volume double-swing plastic bag cell bioreactor, comprising: the cell culture device comprises a swing box assembly (100), a support frame assembly (200), an elastic swing rod assembly (300), a swing basket assembly (400), a multifunctional edge-covered heat preservation groove (500) and a cell culture bag (600);
the swing box assembly (100) is mounted on the support frame assembly (200); the swing box assembly (100) is connected with the upper part of the swing basket assembly (400) through an elastic swing rod assembly (300); two ends of a bearing shaft (800) of the supporting frame assembly (200) are connected with two swinging straight handles (210), and the two swinging straight handles (210) are connected through a swinging shaft (900) at the bottom of the swinging basket assembly (400); the multifunctional edge-covering heat preservation groove (500) is arranged in the swing basket assembly (400), and the cell culture bag (600) is arranged in the multifunctional edge-covering heat preservation groove (500).
2. The large-volume double-oscillating plastic bag cell bioreactor according to claim 1, wherein the oscillating box assembly (100) comprises: the device comprises a swing box cover (101), a swing box body (102), a swing rod short shaft (112), a thrust joint bearing combined spherical mechanism (110), a linear guide rail (104), a ball screw (106), a stepping motor (107), a box body bottom plate (108) and a flange plate (109);
the swing box cover (101) is connected with the swing box body (102) through a flange plate (109); the stepping motor (107) is arranged on a box body bottom plate (108) of the swinging box body (102); the stepping motor (107) is connected with a screw rod of a ball screw (106), a nut of the ball screw (106) is connected with the thrust joint bearing combined spherical mechanism (110), the thrust joint bearing combined spherical mechanism (110) is slidably mounted on a linear guide rail (104), the linear guide rail (104) is mounted on a box body bottom plate (108), and the swing rod short shaft (112) is mounted in the thrust joint bearing combined spherical mechanism (110) in a penetrating manner; the bottom plate of the swing box body (102) is provided with a hollow part along the direction of the linear guide rail (104).
3. The large-volume double-oscillating plastic bag cell bioreactor according to claim 2, wherein the spherical thrust joint bearing assembly mechanism (110) comprises: a shell (118), a shaft sleeve (116) and a thrust knuckle bearing (114); the upper end and the lower end of the shell (118) are respectively provided with a thrust joint bearing (114); the shaft sleeve (116) is positioned between the upper thrust joint bearing and the lower thrust joint bearing (112); the swing rod short shaft (112) is sequentially arranged in the thrust knuckle bearing (112) at the upper end, the shaft sleeve (116) and the thrust knuckle bearing (112) at the lower end in a penetrating mode.
4. The large-volume double-oscillating plastic bag cell bioreactor according to claim 1, wherein the elastic oscillating bar assembly (300) comprises: the device comprises a swing rod (302), an upper disc (304), four tension springs (306), a swing rod transverse shaft (308), a swing rod transverse shaft bearing (309), a tension spring fixing ring (320) and a lower disc (310);
the upper part of the swing rod (302) penetrates through a central hole of the upper disc (304) to be connected with a swing rod short shaft (112) of the swing box assembly (100); the lower part of the swing rod (302) is connected with a swing rod transverse shaft (308); the swing rod transverse shaft (308) is mounted on the lower disc (310) through a swing rod transverse shaft bearing (309); the upper ends of the four tension springs (306) are respectively connected to four corners of the upper disc (304); the lower ends of the four tension springs (306) are respectively connected to the periphery of the lower disc (310) through tension spring fixing rings (320); the lower plate (310) is connected with a swing frame (402) of the swing basket assembly (400).
5. The large-volume double-oscillating plastic bag cell bioreactor according to claim 1, wherein the support frame assembly (200) comprises: the device comprises a top frame beam (202), two-end supports (204), a swing straight shank bearing (206), a swing straight shank (210), a bearing shaft (800), a bearing shaft bearing (806), two-end inclined support plates (222), a swing bearing (902) and a base bottom plate (208);
the top frame beam (202) is connected with a base bottom plate (208) through two end brackets (204); two inclined support plates (222) are respectively arranged on the side surfaces of the two end brackets (204); two ends of the bearing shaft (800) are connected with the brackets (204) at the two ends through bearing shaft bearings (806); the upper ends of the two swing straight handles (210) are connected with the bearing shaft (800) through swing straight handle bearings (206); the lower ends of the two swing straight handles (210) are connected with a swing shaft (900) through swing bearings (902).
6. The large-volume double-oscillating plastic bag cell bioreactor as claimed in claim 5, wherein the bottom of the base bottom plate (208) is provided with a rubber pad.
7. The large-volume double-swing plastic bag cell bioreactor according to claim 1, wherein the swing basket assembly (400) comprises a swing frame (402) and a swing shaft (406);
the upper part of the swinging frame (402) is connected with a lower disc (310) of the elastic swinging rod assembly (300); the bottom of the swing frame (402) is provided with a swing shaft (406).
8. The large-volume double-swing plastic bag cell bioreactor as claimed in claim 1, wherein the multifunctional covered edge heat preservation tank (500) is connected with the swing frame (402) of the swing basket assembly (400) through two end fixing platforms (508); the upper part of the multifunctional edge-covering heat-preserving groove (500) is provided with an edge-covering structure which shrinks inwards.
9. The large-volume double-swing plastic bag cell bioreactor as claimed in claim 8, wherein the multifunctional covered edge heat preservation tank (500) is heated by a rubber plate or a water jacket.
10. The large-volume double-swing plastic bag cell bioreactor as claimed in claim 1, wherein the cross-section of the welded seals (606) at both ends of the cell culture bag (600) is configured to be elliptical; the plastic film seam (602) of the cell culture bag (600) is arranged at the position of the upper diagonal line and the lower diagonal line.
CN202110457640.5A 2021-04-27 2021-04-27 Large-volume double-swing plastic bag cell bioreactor Pending CN113073050A (en)

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CN202110457640.5A CN113073050A (en) 2021-04-27 2021-04-27 Large-volume double-swing plastic bag cell bioreactor

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Application Number Priority Date Filing Date Title
CN202110457640.5A CN113073050A (en) 2021-04-27 2021-04-27 Large-volume double-swing plastic bag cell bioreactor

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114874879A (en) * 2022-07-11 2022-08-09 浙江金仪盛世生物工程有限公司 Support frame with clamping function and biological reaction device

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114874879A (en) * 2022-07-11 2022-08-09 浙江金仪盛世生物工程有限公司 Support frame with clamping function and biological reaction device
CN114874879B (en) * 2022-07-11 2022-09-16 浙江金仪盛世生物工程有限公司 Support frame with clamping function and biological reaction device

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