An upper-swinging annular tubular plastic bag cell bioreactor

Abstract

The present invention relates to the technical field of cell bioreactors, and particularly to an up-swinging annular tubular plastic bag cell bioreactor. The present invention includes: a down-dip shaker, a swinging box, an elastic rocker, a swinging frame, a swinging basket, a heat preservation tank body, an annular tubular plastic bag, a base and a support frame; the down-dip shaker is mounted on the support frame; the swinging box is connected to the bottom plate of the down-dip shaker and performs circular swinging under the action of the down-dip shaker; the swinging box is connected to a double-thrust joint bearing combined spherical mechanism through a linear motion mechanism; a short shaft is penetrated in the double-thrust joint bearing combined spherical mechanism; the lower end of the short shaft is connected to the elastic rocker; the lower end of the elastic rocker is connected to the swinging frame; the lower end of the swinging frame is connected to the swinging basket; the heat preservation tank body is installed in the swinging basket; the annular tubular plastic bag is installed in the heat preservation tank body. The present invention has remarkable effects and is conducive to popularization and application.

Description

Technical Field

[0001] The invention relates to the technical field of cell bioreactors, in particular to an upper swinging annular tubular plastic bag cell bioreactor. Background Art

[0002] In order to expand the production capacity of COVID-19 vaccines, diagnostic reagents, antibody drugs and cell therapy, a large amount of funds, manpower and technology have been invested in the industrialization process of biopharmaceutical R&D and capacity expansion worldwide. Therefore, the disposable cell bioreactor, which is the most important bioprocess equipment in the biotechnology pharmaceutical industry for large-scale and high-density animal cell culture, has become a key link and bottleneck problem in expanding production capacity. Disposable cell bioreactors largely determine the production capacity, product variety and product cost of biopharmaceutical companies. At present, the existing swinging cell bioreactors and circular oscillating cell bioreactors of biopharmaceutical companies have many defects and shortcomings. For example, when the volume of the swinging cell bioreactor increases, the impact force on the end points of the swing in the left and right directions is very large, causing serious vibration and noise. Therefore, it can only achieve a volume of 50 liters, and it will not work if it is larger. The circular shaking cell bioreactor also has such defects. When the volume is large, the shaking speed is high and the eccentricity is large, which generates a large centrifugal force. Then it generates a tipping torque and shaking to the ground. When the volume is large, even the ground shakes. Moreover, the cell bioreactor itself must have a large mass to stabilize the large shaking and vibration of the reactor bed caused by the shaking of the reactor. If the rotation speed is reduced and the eccentricity is reduced for this purpose, the dissolved oxygen level and flow rate of the mixed culture solution in the culture bag will be reduced, which will seriously affect the growth and expansion of cells. The poor fluidity of the culture solution will also cause the cells to settle and adhere to each other, causing the cell membrane to rupture and die.

[0003] The information disclosed in this background technology section is only intended to deepen the understanding of the overall background technology of the present invention, and should not be regarded as acknowledging or suggesting in any form that the information constitutes the prior art already known to those skilled in the art. Summary of the invention

[0004] The purpose of the present invention is to provide an upper swinging annular tubular plastic bag cell bioreactor to solve the technical problems existing in the existing shaking and swinging cell bioreactors.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions:

[0006] The present invention provides an up-swinging annular tubular plastic bag cell bioreactor, which comprises: a down-probing shaker, a swinging box, an elastic rocker, a swinging frame, a swinging basket, a heat preservation tank body, an annular tubular plastic bag, a base and a support frame; the down-probing shaker is mounted on the support frame; the swinging box is connected with the down-probing shaker and performs circular shaking under the action of the down-probing shaker; the swinging box is connected with a double-thrust joint bearing combined spherical mechanism through a linear motion mechanism; a short shaft is inserted into the double-thrust joint bearing combined spherical mechanism; the lower end of the short shaft is connected with the elastic rocker; the lower end of the elastic rocker is connected with the swinging frame; the lower end of the swinging frame is connected with the swinging basket; the heat preservation tank body is installed in the swinging basket; the annular tubular plastic bag is installed in the heat preservation tank body; the bottom of the swinging basket contacts the ground through the base.

[0007] Preferably, the down-probing shaker comprises: a shaker body, a shaking disc, an upper fixing plate, four down-probing columns and a down-probing cradle bottom plate; the shaker body is fixed on the steel beam of the support frame through a fixing clamp at the bottom; the shaker body is connected with the shaking disc; the shaking disc is connected with the upper fixing plate through bolts; the four corners of the upper fixing plate are connected with the upper ends of the four down-probing columns through nuts; the lower ends of the four down-probing columns are connected with the four corners of the down-probing cradle bottom plate through nuts; the swinging box is installed on the down-probing cradle bottom plate.

[0008] In this embodiment, the specific form of the shaker body is not limited and can refer to the prior art.

[0009] For example: the shaker body comprises: a shaker drive box; a drive motor is installed in the shaker drive box; a small pulley is installed on the power output shaft of the drive motor; the small pulley and the large pulley are tightly connected through a belt; the large pulley is installed on the active eccentric shaft; the upper end of the active eccentric shaft is connected with the upper shaking disc; the upper shaking disc is connected with four groups of driven shafts; the upper shaking disc is connected with the shaking disc through bolts, and the shaking disc is connected with the upper fixing plate through bolts.

[0010] Preferably, the swinging box comprises: a swinging box body, a short shaft, a double-thrust joint bearing combined spherical mechanism, a support plate, a sliding guide rail, a sliding seat, a ball screw, a stepping motor and a swinging box bottom plate;

[0011] The double-thrust spherical joint bearing assembly is fixed on the support plate by bolt connection; the support plate is connected to the sliding seat; the sliding seat is connected to the sliding guide rail; the sliding guide rail is fixed on the swing box bottom plate by bolts; the nut of the ball screw is connected to the outer shell of the double-thrust spherical joint bearing assembly; the stepping motor is concentrically connected to the screw rod of the ball screw at the front end, and the bottom of the stepping motor is fixed on the swing box bottom plate by bolts; the short shaft is inserted through the double-thrust spherical joint bearing assembly; the swing box bottom plate and the lower-probing cradle bottom plate are both provided with hollowed parts along the direction of the sliding guide rail to allow the short shaft to extend and move.

[0012] Preferably, the double-thrust spherical joint bearing assembly includes: a double-thrust spherical joint bearing, a housing, a bushing and a short shaft; the inner rings of the double-thrust spherical joint bearings are symmetrically installed on the bushing up and down, and the outer rings of the double-thrust spherical joint bearings are symmetrically externally connected to the inside of the housing up and down; the inner hole on the bushing is sleeved on the short shaft, and the outer circumferential surface of the short shaft slides relative to the inner hole surface of the bushing, so that the short shaft can move linearly up and down along its axis in the bushing hole.

[0013] Preferably, the elastic rocker includes a swing rod, an upper disc, four tension springs, tension spring rings, a lower disc and a swing frame;

[0014] The upper part of the swing rod passes through the central hole of the upper disc and is concentrically connected to the short shaft in the swing box, and the lower part of the swing rod is connected to the cross-axis universal joint; the cross-axis universal joint is connected to the center of the lower disc by bolts; the upper ends of the four tension springs are connected to the tension spring rings at the four corners of the upper disc, and the lower ends of the four tension springs are connected to the tension spring rings at the four corners of the lower disc; the lower disc is connected to the upper part of the swing frame; the lower part of the swing frame is connected to the upper border of the swing basket.

[0015] Preferably, the upper and lower parts of the swing frame are supported by three columns; the upper part of the swing frame is connected to the lower disc of the elastic rocker by a circular ring border; the lower part of the swing frame is connected to the upper border of the swing basket by a dodecagon border by bolts.

[0016] Preferably, the upper outer border of the swing basket is connected to the lower part of the swing frame; a raised central fixing disc is provided at the center of the swing basket; the swing basket forms an annular space for accommodating the heat preservation tank body; the central fixing disc is connected to the stepped shaft chassis of the base.

[0017] In this embodiment, the swing basket includes: a first group of polygon frames, a second group of polygon frames, a third group of polygon frames and a central fixing disc that are concentrically arranged in sequence and have decreasing sizes;

[0018] The first group of polygon frames includes three polygon frames of the same size divided vertically into upper, middle, and lower parts, which together form the side structure of the swing basket. The upper part of the upper polygon frame of the first group is connected to the lower part of the swing frame; the second group of polygon frames consists of only one polygon frame and the only one polygon frame in the third group, which together form the bottom structure of the swing basket; the central fixed disk protrudes upward from the center of the swing basket; a circular positioning frame is arranged around the central fixed disk.

[0019] Preferably, the heat preservation tank body includes: a tank body polygon outer shell; a heating rubber plate system or a heating water jacket system is installed in the side wall sandwich of the tank body polygon outer shell; an annular groove for installing an annular tubular plastic bag is formed inside the tank body polygon outer shell; a wrapping structure is arranged at the upper open edge of the annular groove; a heat preservation tank body installation position is arranged at the midline position of the tank body polygon outer shell; the heat preservation tank body installation position is adapted to the positioning frame of the central fixed disk to achieve positioning installation.

[0020] In this embodiment, the heat preservation tank body installation position includes: a concentrically arranged cylindrical installation position and a conical cylindrical installation position. The cylindrical installation position is correspondingly connected to the heat preservation tank body installation position; the conical cylindrical installation position is sleeved at the central position of the swing basket.

[0021] Preferably, the annular tubular plastic bag is welded into an annular tubular bag by a five-layer or seven-layer co-extruded plastic film. Preferably, a plurality of liquid inlets, liquid outlets, air inlets, air outlets, and interfaces for installing dissolved oxygen, pH value, and temperature sensors are arranged at the upper part of the annular tubular plastic bag.

[0022] Preferably, the base includes: a stepped shaft chassis, a stepped shaft, a thrust joint bearing, a bearing support, a limit shaft head, and a shock-absorbing rubber pad;

[0023] The stepped shaft chassis is concentrically connected to the stepped shaft by bolts; the stepped shaft is concentrically linked to the inner ring hole of the thrust joint bearing; the limit shaft head and the stepped shaft are integrally arranged; the outer ring and the inner ring of the thrust joint bearing cooperate with each other, and the outer surface of the outer ring of the thrust joint bearing is connected to the bearing support in a matching manner; the shock-absorbing rubber pad is connected to the bearing support.

[0024] Preferably, the support frame includes: a shaker platform, four inclined struts, a support frame bottom plate, and shock-absorbing rubber pads; the shaker platform is located at the top of the support frame; the shaker platform is fixedly connected to the shaker body at the bottom through bolts; the upper parts of the four inclined struts are welded to the shaker platform, and the lower parts of the four inclined struts are welded to the support frame bottom plate; the upper parts of the shock-absorbing rubber pads are connected to the four corners of the support frame bottom plate.

[0025] With the above technical solution, the present invention has the following beneficial effects:

[0026] The structure and principle of the present invention are as follows: The circular shaking of the lower-probing shaker drives the short shaft in the swing box to make a circular motion. The short shaft can move up and down along the axis on the inner hole surface of the spherical mechanism. Through the elastic rocker, the swing frame rocks the swing basket to make a circular motion around the axis of the thrust joint bearing in the base, that is, to rock the mixed culture solution in the annular tubular plastic bag in the heat preservation tank body. In such a shaking, the mixed culture solution (the culture solution containing live cells) makes an inclined rolling flow and makes a circular flow in the annular tubular plastic bag. At a very low rotation speed (below 10 revolutions per minute), many waves, water droplets and water splashes can be formed in the flowing and rolling of the mixed culture solution, which greatly increases the gas-liquid specific surface area of the mixed culture solution. At the same time, the dissolved oxygen is also greatly increased. When the gas-liquid specific surface area is greatly increased, it is very conducive to the harmful gases such as ammonia and carbon dioxide to escape from the mixed culture solution into the gas above the culture bag and then be discharged outside the annular tubular plastic bag through the air outlet on the annular tubular plastic bag, thereby purifying the mixed culture solution in the plastic bag. The above is the result under the condition of the simple circular shaking of the shaker. If we start the stepping motor in the swing box at the same time, drive the ball screw to drive the short shaft in the spherical mechanism, and add a linear reciprocating motion with a fixed stroke to the short shaft while the shaker rotates one week, the result is the combined trajectory formed by the rocking of the rocking disc and the linear reciprocating motion of the short shaft as shown in the analysis diagram. In fact, after adding this linear motion, the swing angle of the swing basket is increased. The gas-liquid specific surface area is larger, the dissolved oxygen level is higher, the fluidity and the effect of purifying the mixed culture solution are better than those in the case of simple circular shaking. At the same time, the rotation speed of the shaker can be reduced, that is, the shaking and vibration caused by the rocking of the swing basket are reduced;

[0027] The present invention adopts a thrust joint bearing on the base, so that the total weight of the swing basket assembly, the heat preservation tank body and the culture solution in the plastic bag acts on the ground through the thrust joint bearing itself and the base. The shaking is a three-dimensional circular shaking of the swing rocker around the center of the thrust joint bearing, that is, the spherical center. During the shaking, there is only the spherical sliding friction between the inner ring and the outer ring of the thrust joint bearing, and the lubrication of the bearing is very good, and the friction coefficient is very small. Moreover, the self-weights of the lower-probing shaker and the support frame also act on the ground through the support frame itself. Therefore, the present invention has no drawbacks and defects such as tipping moment, shaking and vibration. Even if the working volume of the present invention is enlarged to 10,000 liters, it can still work stably without the above-mentioned drawbacks and defects. Compared with the current reactors with simple planar circular shaking and the reactors with simple left-right swing: The present invention eliminates the tipping moment on the ground, the inertial force caused by the centrifugal force, the impact force on the ground, the vibration and the noise, etc. This is particularly obvious when the reactor has a large volume and a large load;

[0028] The present invention uses a relatively long elastic rocker, taking advantage of the property of the elastic rocker to store and release energy again, effectively eliminating the impact force generated during the swinging process of the swinging basket assembly on the top end of the rocker, i.e., the impact force when the short shaft part swings to the end point. At the same time, the lever action of the relatively long rocker also greatly reduces the intensity of the impact force at the end point, thus greatly reducing the impact force and vibration on the upper part of the reactor support frame;

[0029] The present invention uses an annular tubular plastic bag, and the mixed culture solution is restricted to flow within the annular container. The fluidity is very good even at low rotational speeds. Such a flow eliminates the cell sedimentation and aggregation, mutual adhesion, and further destruction of the cell membrane and massive cell death caused by the flow velocity approaching zero when the radius of the flow center approaches zero. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required for use in the description of the specific embodiments or the prior art. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0031] Figure 1 The first state diagram of the upper-swinging annular tubular plastic bag cell bioreactor provided by the embodiment of the present invention;

[0032] Figure 2 The second state diagram of the upper-swinging annular tubular plastic bag cell bioreactor provided by the embodiment of the present invention;

[0033] Figure 3 The front view of the swinging basket provided by the embodiment of the present invention;

[0034] Figure 4 The top view of the swinging basket provided by the embodiment of the present invention;

[0035] Figure 5 The front view of the swinging box provided by the embodiment of the present invention;

[0036] Figure 6 The top view of the swinging box provided by the embodiment of the present invention;

[0037] Figure 7 The front view of the elastic rocker provided by the embodiment of the present invention;

[0038] Figure 8 The top view of the elastic rocker provided by the embodiment of the present invention;

[0039] Figure 9The front view of the heat preservation tank body provided by the embodiment of the present invention;

[0040] Figure 10 The top view of the heat preservation tank body provided by the embodiment of the present invention;

[0041] Figure 11 The structural schematic diagram of the thrust joint bearing combined spherical mechanism provided by the embodiment of the present invention;

[0042] Figure 12 The structural schematic diagram of the base provided by the embodiment of the present invention;

[0043] Figure 13 The side view of the support frame provided by the embodiment of the present invention;

[0044] Figure 14 The top view of the support frame provided by the embodiment of the present invention. Detailed implementation manners

[0045] Next, the technical solutions of the present invention will be described clearly and completely with reference to the accompanying drawings. Obviously, the described embodiments are some but not all of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0046] In the description of the present invention, it should be noted that the orientation or positional relationship indicated by the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. is based on the orientation or positional relationship shown in the accompanying drawings. It is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of the present invention. In addition, the terms "first", "second", "third" are only used for descriptive purposes and cannot be construed as indicating or implying relative importance.

[0047] In the description of the present invention, it should be noted that unless otherwise clearly defined and limited, the terms "installation", "connection", "connection" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the communication inside two elements. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific situations.

[0048] The following will describe the detailed implementation manners of the present invention with reference to the accompanying drawings. It should be understood that the detailed implementation manners described herein are only used to illustrate and explain the present invention and are not used to limit the present invention.

[0049] Combined with Figures 1 to 14 As shown in the figure, the present invention provides an upper-swinging annular tubular plastic bag cell bioreactor, which includes: a lower-probing shaker 100, a swinging box 200, an elastic rocker 400, a swinging frame 500, a swinging basket 600, a heat preservation tank body 700, an annular tubular plastic bag 800, a base 900 and a support frame 990; the lower-probing shaker 100 is mounted on the support frame 990; the swinging box 200 is connected to the lower-probing shaker 100 and performs circular shaking under the action of the lower-probing shaker 100; the swinging box 200 is connected to a double-thrust joint bearing combined spherical mechanism 204 through a linear motion mechanism; a short shaft 203 is installed inside the double-thrust joint bearing combined spherical mechanism 204; the lower end of the short shaft 203 is suspended with an elastic rocker 400; the lower end of the elastic rocker 400 is connected to the swinging frame 500; the lower end of the swinging frame 500 is connected to the swinging basket 600; the heat preservation tank body 700 is installed in the swinging basket 600; the annular tubular plastic bag 800 is installed in the heat preservation tank body 700; the bottom of the swinging basket 600 is in contact with the ground through the base 900.

[0050] Preferably, the lower-probing shaker 100 includes: a shaker body, a shaking disk, an upper fixing plate, lower-probing four columns and a lower-probing cradle bottom plate; the shaker body is fixed on the steel beam of the support frame 990 through a fixing clip 102 at the bottom; the shaker body is connected to the shaking disk; the shaking disk is connected to the upper fixing plate through bolts; the four corners of the upper fixing plate are connected to the upper ends of the lower-probing four columns through nuts; the lower ends of the lower-probing four columns are connected to the four corners of the lower-probing cradle bottom plate through nuts; the swinging box 200 is installed on the lower-probing cradle bottom plate.

[0051] In this embodiment, the specific form of the shaker body is not limited and can refer to the prior art.

[0052] For example: the shaker body includes: a shaker drive box; a drive motor is installed inside the shaker drive box; a small pulley is installed on the power output shaft of the drive motor; the small pulley and the large pulley are tightly connected through a belt; the large pulley is installed on the active eccentric shaft; the upper end of the active eccentric shaft is connected to the upper shaking disk; the upper shaking disk is connected to four groups of driven shafts; the upper shaking disk is connected to the shaking disk through bolts, and the shaking disk is connected to the upper fixing plate through bolts.

[0053] Preferably, the swing box 200 includes: a swing box body 226, a short shaft 203, a double-thrust spherical plain bearing combination spherical mechanism 204, a support plate 206, a sliding guide rail 208, a sliding seat 210, a ball screw 216, a stepping motor 220, and a swing box bottom plate 224; the double-thrust spherical plain bearing combination spherical mechanism 204 is fixedly connected to the support plate 206 by bolts; the support plate 206 is connected to the sliding seat 210; the sliding seat 210 is connected to the sliding guide rail 208; the sliding guide rail 208 is fixed to the swing box bottom plate 224 by bolts; the nut of the ball screw 216 is connected to the outer shell of the double-thrust spherical plain bearing combination spherical mechanism 204; the stepping motor 220 is concentrically connected to the screw rod of the ball screw 216 at the front end, and the bottom of the stepping motor 220 is fixed to the swing box bottom plate 224 by bolts; the short shaft 203 is inserted through the double-thrust spherical plain bearing combination spherical mechanism 204; the swing box bottom plate 224 and the lower-probing cradle bottom plate are both provided with hollow parts 230 that allow the short shaft 203 to extend and move along the direction of the sliding guide rail 208.

[0054] Preferably, the double-thrust spherical plain bearing combination spherical mechanism 204 includes: a double-thrust spherical plain bearing 234, a housing 232, a bushing 236, and a short shaft 203; the inner rings of the double-thrust spherical plain bearings 234 are symmetrically mounted on the bushing 236 up and down, and the outer rings of the double-thrust spherical plain bearings 234 are symmetrically externally connected to the inside of the housing 232 up and down; the inner hole on the bushing 236 is sleeved on the short shaft 203, and the outer circumferential surface of the short shaft 203 slides relative to the inner hole surface of the bushing 236, so that the short shaft 203 can move linearly up and down along its axis in the hole of the bushing 236.

[0055] Preferably, the elastic rocker 400 includes a rocker arm 422, an upper disc 404, four tension springs 408, tension spring rings 428, a lower disc 410, and a swing frame 500; the upper part of the rocker arm 422 passes through the central hole of the upper disc 404 and is concentrically connected to the short shaft 203 in the swing box 200, and the lower part of the rocker arm 422 is connected to a cross universal joint 426; the cross universal joint 426 is connected to the center of the lower disc 410 by bolts; the upper ends of the four tension springs 408 are connected to the tension spring rings 428 at the four corners of the upper disc 404, and the lower ends of the four tension springs 408 are connected to the tension spring rings 428 at the four corners of the lower disc 410; the lower disc 410 is connected to the upper part of the swing frame 500; the lower part of the swing frame 500 is connected to the upper frame of the swing basket 600.

[0056] Preferably, the upper and lower parts of the swing frame 500 are supported by three columns; the upper part of the swing frame 500 is connected to the lower disc 410 of the elastic rocker 400 by a circular ring frame; the lower part of the swing frame 500 is connected to the upper frame of the swing basket 600 by a dodecagon frame.

[0057] Preferably, the upper outer frame of the swing basket 600 is connected to the lower part of the swing frame 500; a convex central fixing disc 620 is provided at the center of the swing basket 600; the swing basket 600 forms an annular space for accommodating the heat preservation tank body 700; the central fixing disc 620 is connected to the stepped shaft chassis 902 of the base 900.

[0058] In this embodiment, the swing basket 600 includes: upper, middle, and lower three polygon frames of the same size in the vertical direction, which jointly constitute the side structure of the swing basket. The upper part of the upper polygon frame of the first group is connected to the lower part of the swing frame; the second group of polygon frames consists of only one polygon frame and the only one polygon frame in the third group jointly constitute the bottom structure of the swing basket; the central fixing disc protrudes upward from the center of the swing basket; a circular positioning frame is provided around the central fixing disc.

[0059] Preferably, the heat preservation tank body includes: a tank body polygon outer shell; a heating rubber plate system or a heating water jacket system is installed in the side wall sandwich of the tank body polygon outer shell; an annular groove 706 for installing the annular tubular plastic bag 800 is formed inside the tank body polygon outer shell; a wrapping structure is provided at the upper open edge of the annular groove 706; a heat preservation tank body installation position is provided at the middle line position of the tank body polygon outer shell; the heat preservation tank body installation position is adapted to the positioning frame of the central fixing disc to achieve positioning installation.

[0060] In this embodiment, the heat preservation tank body installation position includes: a concentrically arranged cylindrical installation position and a conical cylindrical installation position. The cylindrical installation position is correspondingly connected to the heat preservation tank body installation position; the conical cylindrical installation position is sleeved at the central position of the swing basket 600.

[0061] Preferably, the annular tubular plastic bag 800 is welded into an annular tubular bag by a five-layer or seven-layer co-extruded plastic film.

[0062] In this embodiment, the annular tubular plastic is equipped with dissolved oxygen, PH, temperature sensors and various interfaces and pipelines for liquid inlet and outlet, gas inlet and outlet, and standby.

[0063] Preferably, the base 900 includes: a stepped shaft chassis 902, a stepped shaft 904, a thrust joint bearing 906, a bearing support 908, a limit shaft head 920, and a shock-absorbing rubber pad 910;

[0064] The stepped shaft chassis 902 and the stepped shaft 904 are concentrically connected by bolts; the stepped shaft 904 is concentrically linked to the inner ring hole of the thrust joint bearing 906; the limit shaft head 920 and the stepped shaft 904 are integrally provided; the outer ring and the inner ring of the thrust joint bearing 906 cooperate with each other, and the outer surface of the outer ring of the thrust joint bearing 906 is connected to the bearing support 908 in a mating manner; the shock-absorbing rubber pad 910 is connected to the bearing support 908.

[0065] Preferably, the support frame 990 includes: a rocking bed platform 992, four inclined struts 994, a support frame bottom plate 996, and shock-absorbing rubber pads 998; the rocking bed platform 992 is located at the top of the support frame 990; the rocking bed platform 992 is connected to the fixed clamp 102 at the bottom of the rocking bed body through a steel beam; the upper parts of the four inclined struts 994 are welded to the rocking bed platform 992, and the lower parts of the four inclined struts 994 are welded to the support frame bottom plate 996; the upper parts of the shock-absorbing rubber pads 998 are connected to the four corners of the support frame bottom plate 996.

[0066] In summary, the structure and principle of the present invention are as follows: the circumferential shaking of the lower-probing rocking bed drives the short shaft in the swing box to perform circumferential shaking. The short shaft can move up and down along the axis on the inner hole surface of the spherical mechanism. Also, through the elastic rocker, the swing frame rocks the swing basket to perform circumferential shaking around the axis of the thrust joint bearing in the base, that is, to shake the mixed culture solution in the annular tubular plastic bag in the heat preservation tank body. In such shaking, the mixed culture solution (the culture solution containing live cells) performs inclined rolling flow and annular flow in the annular tubular plastic bag. At a very low rotation speed (below 10 revolutions per minute), waves, water droplets, and water splashes can be formed in the flowing and rolling of the mixed culture solution, which greatly increases the gas-liquid specific surface area of the mixed culture solution. At the same time, the dissolved oxygen is also greatly increased. The large increase in the gas-liquid specific surface area is very conducive to the escape of harmful gases such as ammonia and carbon dioxide from the mixed culture solution, and then discharged outside the annular tubular plastic bag through the air outlet on the annular tubular plastic bag, thereby purifying the mixed culture solution in the plastic bag. The above is the result under the condition of pure circumferential shaking. If we start the stepping motor in the swing box, drive the ball screw to drive the short shaft in the spherical mechanism, and add a linear reciprocating motion with a fixed stroke to the short shaft while the rocking bed rotates one week, the result is the combined trajectory formed by the rocking of the rocking disc and the linear reciprocating motion of the short shaft as shown in the analysis diagram. In fact, after adding this linear motion, the swing angle of the swing basket is increased. The gas-liquid specific surface area is larger, the dissolved oxygen level is higher, and the fluidity and the effect of purifying the mixed culture solution are better than those in the case of pure circumferential shaking. At the same time, the rotation speed of the rocking bed can be reduced, that is, the shaking and vibration caused by the shaking of the swing basket are reduced;

[0067] The present invention adopts a thrust joint bearing on the base. In this way, the total weight of the swing basket assembly, the insulation tank body, the culture solution in the plastic bag, etc. acts on the ground through the thrust joint bearing itself and the base. The shaking is a three-dimensional circular shaking of the swing rod around the center of the thrust joint bearing, i.e., the spherical center. During shaking, there is only spherical sliding friction between the inner ring and the outer ring of the thrust joint bearing, and the lubrication of the bearing is very good, with a very small friction coefficient. Moreover, the self-weight of the down-dip shaker and the support frame, etc. also acts on the ground through the support frame itself. Therefore, the present invention has no drawbacks and defects such as tipping moment, shaking, and vibration. Even if the working volume of the present invention is enlarged to 10,000 liters, it can still work stably without the above-mentioned drawbacks and defects. Compared with the current reactors with simple planar circular shaking and the swing reactors with simple left-right swing: the present invention eliminates drawbacks such as the tipping moment on the ground, the inertial force caused by the centrifugal force, the impact force on the ground, vibration, and noise. This is especially obvious when the reactor has a large volume and large load;

[0068] The present invention adopts a longer elastic swing rod and utilizes the performance of the elastic swing rod to store and release energy again, effectively eliminating the impact force generated when the swing basket assembly swings to the end point at the top of the swing rod, i.e., the short axis part. At the same time, the lever action of the longer swing rod also greatly reduces the intensity of the end point impact force, thus greatly reducing the impact force and vibration on the upper part of the reactor support frame;

[0069] The present invention adopts an annular tubular plastic bag, and the mixed culture solution is restricted to flow in the annular container. Its fluidity is very good even at low rotation speeds. Such a flow eliminates the cell sedimentation and aggregation, mutual adhesion, and further the destruction of the cell membrane and a large number of cell deaths caused by the flow velocity approaching zero when the flow center radius approaches zero.

[0070] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements for some or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. An upper-swinging annular tubular plastic bag cell bioreactor, characterized in that, it includes: a down-dropping shaker, a swinging box, an elastic rocker, a swinging frame, a swinging basket, a heat preservation tank body, an annular tubular plastic bag, a base and a support frame; The down-dropping shaker is installed on the support frame; the swinging box is connected to the down-dropping shaker and performs circular swinging under the action of the down-dropping shaker; the swinging box is connected to a double-thrust joint bearing combined spherical mechanism through a linear motion mechanism; a short shaft is installed inside the double-thrust joint bearing combined spherical mechanism; the lower end of the short shaft is connected to the elastic rocker; the lower end of the elastic rocker is connected to the swinging frame; the lower end of the swinging frame is connected to the swinging basket; the heat preservation tank body is installed in the swinging basket; The annular tubular plastic bag is installed in the heat preservation tank body; The bottom of the swinging basket contacts the ground through the base; The down-dropping shaker includes: a shaker body, a shaking disc, an upper fixing plate, down-dropping four columns and a down-dropping cradle bottom plate; the shaker body is fixed on the steel beam of the support frame through a fixed clamp at the bottom; the shaker body is connected to the shaking disc; the shaking disc is connected to the upper fixing plate through bolts; the four corners of the upper fixing plate are connected to the upper ends of the down-dropping four columns through nuts; the lower ends of the down-dropping four columns are connected to the four corners of the down-dropping cradle bottom plate through nuts; the swinging box is installed on the down-dropping cradle bottom plate; the swinging box includes: a swinging box body, a short shaft, a double-thrust joint bearing combined spherical mechanism, a support plate, a sliding guide rail, a sliding seat, a ball screw, a stepping motor and a swinging box bottom plate; the double-thrust joint bearing combined spherical mechanism is fixedly connected to the support plate through bolts; the support plate is connected to the sliding seat; the sliding seat is connected to the sliding guide rail; the sliding guide rail is fixed on the swinging box bottom plate through bolts; the nut of the ball screw is connected to the outer shell of the double-thrust joint bearing combined spherical mechanism; the stepping motor is concentrically connected to the screw rod of the ball screw at the front end, and the bottom of the stepping motor is fixed on the swinging box bottom plate through bolts; the double-thrust joint bearing combined spherical mechanism is provided with the short shaft; the swinging box bottom plate and the down-dropping cradle bottom plate are both provided with hollow parts along the direction of the sliding guide rail to allow the short shaft to extend and move.

2. The upper-swinging annular tubular plastic bag cell bioreactor according to claim 1, characterized in that, The double-thrust joint bearing combined spherical mechanism includes: a double-thrust joint bearing, a housing, a bushing and a short shaft; the inner rings of the double-thrust joint bearings are symmetrically installed on the bushing up and down, and the outer rings of the double-thrust joint bearings are symmetrically externally connected to the inside of the housing up and down; the inner hole on the bushing is sleeved on the short shaft, and the outer surface of the short shaft slides relative to the inner hole surface of the bushing, so that the short shaft can move up and down linearly along its axis in the hole of the bushing.

3. The upper-swinging annular tubular plastic bag cell bioreactor according to claim 2, characterized in that, The elastic rocker includes a swinging rod, an upper disc, four tension springs, a tension spring ring, a lower disc and a swinging frame; The upper part of the swing rod passes through the central hole of the upper disc and is concentrically connected to the short shaft in the swing box. The lower part of the swing rod is connected to a cross universal joint. The cross universal joint is connected to the center of the lower disc by bolts. The upper ends of the four tension springs are connected to the tension spring rings at the four corners of the upper disc, and the lower ends of the four tension springs are connected to the tension spring rings at the four corners of the lower disc. The lower disc is connected to the upper part of the swing frame. The lower part of the swing frame is connected to the upper frame of the swing basket by bolts.

4. The upper swing annular tubular plastic bag cell bioreactor according to claim 3, characterized in that between the upper and lower parts of the swing frame are supported by three columns; the upper part of the swing frame is connected to the lower disc of the elastic rocker by a circular ring frame; the lower part of the swing frame is connected to the upper frame of the swing basket by a dodecagon frame.

5. The upper swing annular tubular plastic bag cell bioreactor according to claim 4, characterized in that the upper outer frame of the swing basket is connected to the lower part of the swing frame; a convex central fixing disc is provided at the center of the swing basket; the swing basket forms an annular space for accommodating a heat preservation tank body; the central fixing disc is connected to the stepped shaft chassis of the base.

6. The upper swing annular tubular plastic bag cell bioreactor according to claim 5, characterized in that the heat preservation tank body includes: a tank body polygon outer shell; a heating rubber plate system or a heating water jacket system is installed in the side wall sandwich of the tank body polygon outer shell; the inner side of the tank body polygon outer shell encloses an annular groove for installing an annular tubular plastic bag; a wrapping structure is provided at the upper open edge of the annular groove; a heat preservation tank body installation position is provided at the middle line position of the tank body polygon outer shell; the heat preservation tank body installation position is adapted to the positioning frame of the central fixing disc to achieve positioning installation.

7. The upper swing annular tubular plastic bag cell bioreactor according to claim 6, characterized in that the base includes: a stepped shaft chassis, a stepped shaft, a thrust joint bearing, a bearing support, a limit shaft head and a shock-absorbing rubber pad; the stepped shaft chassis is concentrically connected to the stepped shaft by bolts; the stepped shaft is concentrically linked to the inner ring hole of the thrust joint bearing; the limit shaft head and the stepped shaft are integrally provided; the outer ring and the inner ring of the thrust joint bearing cooperate with each other, and the outer surface of the outer ring of the thrust joint bearing is connected to the bearing support in a matching manner; the shock-absorbing rubber pad is connected to the bearing support.

8. The upper swing annular tubular plastic bag cell bioreactor according to claim 7, characterized in that the support frame includes: a shaking table platform, four inclined struts, a support frame bottom plate, and shock-absorbing rubber pads; the shaking table platform is located at the top of the support frame; the shaking table platform is connected to the fixed clamp at the bottom of the shaking table body through a steel beam; the upper parts of the four inclined struts are welded to the shaking table platform, and the lower parts of the four inclined struts are welded to the support frame bottom plate; the upper parts of the shock-absorbing rubber pads are connected to the four corners of the support frame bottom plate.

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