CN113214989A - Upper swing annular tubular plastic bag cell bioreactor - Google Patents
Upper swing annular tubular plastic bag cell bioreactor Download PDFInfo
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- CN113214989A CN113214989A CN202110472143.2A CN202110472143A CN113214989A CN 113214989 A CN113214989 A CN 113214989A CN 202110472143 A CN202110472143 A CN 202110472143A CN 113214989 A CN113214989 A CN 113214989A
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- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
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- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
- C12M41/18—Heat 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 an upward swinging annular tubular plastic bag cell bioreactor. The invention comprises the following steps: the device comprises a downward-probing type shaking table, a shaking box, an elastic rocking bar, a shaking frame, a shaking basket, a heat-preservation groove body, an annular tubular plastic bag, a base and a supporting frame; the downward-probing type shaking table is erected on the supporting frame; the shaking box is connected with the bottom plate of the downward probing shaking table and is used for carrying out circumferential shaking under the action of the downward probing shaking table; the swinging box is connected with the double-thrust joint bearing combined spherical mechanism through a linear motion mechanism; a short shaft penetrates through 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 groove body is arranged in the swinging basket; the annular tubular plastic bag is arranged in the heat preservation groove body. The invention has obvious effect and is beneficial to popularization and application.
Description
Technical Field
The invention relates to the technical field of cell bioreactors, in particular to an upward swinging annular tubular plastic bag cell bioreactor.
Background
Aiming at the research and development and capacity expansion of the fields of new coronary vaccines, diagnostic reagents, antibody drugs and cell therapy, a large amount of funds, manpower and technologies are all put into the research and development of the biopharmaceutical industry and the industrial process of capacity expansion in the global range. Therefore, the disposable cell bioreactor for culturing animal cells in large scale and high density is the most important biological process equipment in the biotechnology pharmaceutical industry, and becomes a key link and bottleneck problem for expanding the productivity. The disposable cell bioreactor determines the production capacity, product variety and product cost of the biopharmaceutical enterprise to a large extent. The existing swing cell bioreactor and the cell bioreactor shaking in a circumferential oscillation mode in the current biopharmaceutical enterprises have a plurality of defects and shortcomings. For example, when the volume of the rocking cell bioreactor increases, the end points of the rocking in the left and right directions receive a large impact force, and the resulting vibration and noise are severe. Therefore, the volume of the product can only be 50 liters, and the product cannot be used after the volume is increased. The cell bioreactor with circular shaking also has the defects of large volume, high eccentric distance due to high rotating speed of shaking and great centrifugal force. And then the ground overturning moment and the shaking are generated, and when the volume is larger, the ground is shaken along with the shaking. But the cell bioreactor itself must have a large mass to stabilize the shaking and vibration of the bed of the reactor caused by the shaking of the reactor. If the eccentricity is reduced by reducing the rotation speed, the dissolved oxygen level and the flow speed of the mixed culture solution in the culture bag are reduced, and the cell growth and the cell amplification are seriously influenced. The cells are deposited and adhered to each other due to poor fluidity of the culture medium, and the cell membrane is ruptured and died.
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 an upward-swinging annular plastic bag cell bioreactor, which aims to solve the technical problems of the existing swinging and swinging cell bioreactors.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides an up-swinging annular tubular plastic bag cell bioreactor, which comprises: the device comprises a downward-probing type shaking table, a shaking box, an elastic rocking bar, a shaking frame, a shaking basket, a heat-preservation groove body, an annular tubular plastic bag, a base and a supporting frame; the downward-probing type shaking table is erected on the supporting frame; the shaking box is connected with the downward probing shaking table and is used for carrying out circumferential shaking under the action of the downward probing shaking table; the swing box is connected with the double-thrust joint bearing combined spherical mechanism through the linear motion mechanism; a short shaft penetrates through 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 groove body is arranged in the swinging basket; the annular tubular plastic bag is arranged in the heat preservation groove body; the bottom of the swinging basket is in contact with the ground through the base.
Preferably, the downward rocking device comprises: the rocking bed comprises a rocking bed body, a rocking disc, an upper fixing plate, four downward-probing upright posts and a downward-probing cradle bottom plate; the bottom of the shaking table body is fixed on the steel beam of the supporting frame through a fixing clip; the shaking table body is connected with the shaking disc; the rocking disc is connected with the upper fixing plate through a bolt; four corners of the upper fixing plate are connected with the upper ends of the four downward-extending stand columns through nuts; the lower ends of the downward-exploring four upright posts are connected with four corners of the bottom plate of the downward-exploring cradle through nuts; the swinging box is arranged on the bottom plate of the downward-exploring cradle.
In this embodiment, the specific form of the rocking bed body is not limited, and reference can be made to the prior art.
For example: the shaking table body includes: a shaking table driving box; a driving motor is arranged in the shaking table driving box; a power output shaft of the driving motor is provided with a small belt pulley; the small belt pulley is connected with the large belt pulley in a tensioning manner through a belt; the large belt pulley is arranged on the driving eccentric shaft; the upper end of the driving eccentric shaft is connected with an upper swing disc; the upper shaking disc is connected with four groups of driven shafts; the upper shaking plate is connected to the shaking plate through a bolt, and the shaking plate is connected to the upper fixing plate through a bolt.
Preferably, the swing box comprises: the device comprises a swinging box body, a short shaft, a double-thrust joint bearing combined spherical mechanism, a supporting plate, a sliding guide rail, a sliding seat, a ball screw, a stepping motor and a swinging box bottom plate;
the double-thrust spherical joint bearing combined mechanism is fixedly connected to the supporting plate through a bolt; the supporting 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 bottom plate of the swinging box through a bolt; the nut of the ball screw is connected with the shell of the double-thrust joint bearing combined spherical mechanism; the front end of the stepping motor is concentrically connected with a lead screw of the ball screw, and the bottom of the stepping motor is fixed on a bottom plate of the swing box through a bolt; the short shaft is arranged in the thrust joint bearing combined spherical mechanism in a penetrating manner; the bottom plate of the swinging box and the bottom plate of the downward-exploring cradle are provided with hollowed-out parts allowing the short shaft to extend out and move along the direction of the sliding guide rail.
Preferably, the double thrust spherical plain bearing combined mechanism comprises: the double-thrust joint bearing comprises a double-thrust joint bearing body, a shell body, a shaft sleeve and a short shaft; the inner ring of the double-thrust joint bearing is vertically symmetrically arranged on the shaft sleeve, and the outer ring of the double-thrust joint bearing is vertically symmetrically externally connected in the shell; the inner hole of the shaft sleeve is sleeved on the short shaft, and the outer circle surface of the short shaft slides relative to the surface of the inner hole of the shaft sleeve, so that the short shaft can linearly reciprocate up and down in the shaft sleeve hole along the axis of the shaft sleeve.
Preferably, the elastic rocker comprises a rocking rod, an upper disc, four tension springs, a tension spring ring, a lower disc and a rocking frame;
the upper part of the swing rod penetrates through a central hole of the upper disc and is concentrically connected with a short shaft in the swing box, and the lower part of the swing rod is connected with a cross universal joint; the cross shaft universal joint is connected with the center of the lower disc through a bolt; the upper ends of the four tension springs are connected with the tension spring rings at the four corners of the upper disc, and the lower ends of the four tension springs are connected with the tension spring rings at the four corners of the lower disc; the lower disc is connected with the upper part of the swinging frame; the lower part of the swinging frame is connected with the upper frame of the swinging basket.
Preferably, the upper part and the lower part of the swinging frame are supported by three upright posts; the upper part of the swinging frame is connected with the lower disc of the elastic rocker through a circular ring frame; the lower part of the swinging frame adopts a dodecagon frame to be connected with the upper frame of the swinging basket through bolts.
Preferably, the outer upper frame of the swinging basket is connected with the lower part of the swinging frame; a raised central fixed disc is arranged in the center of the swinging basket; the swinging basket forms an annular space for accommodating the heat preservation groove body; the central fixed disk is connected with the step shaft chassis of the base.
In this embodiment, the swinging basket comprises: the first group of polygonal frames, the second group of polygonal frames, the third group of polygonal frames and the central fixed disk are concentrically arranged in sequence and have progressively reduced sizes;
the first group of polygonal frames comprise upper, middle and lower polygonal frames which are divided in the vertical direction and have the same size, and the upper parts of the first group of upper polygonal frames are connected with the lower parts of the swinging frames; only one polygonal frame in the second group of polygonal frames and only one polygonal frame in the third group of polygonal frames jointly form the bottom structure of the swinging basket; the central fixed disc is upwards protruded from the center of the swinging basket; and a circular positioning frame is arranged around the central fixed disk.
Preferably, the insulation tank body comprises: a polygonal shell of the tank body; a heating rubber plate system or a heating water jacket system is arranged in an interlayer of the side wall of the polygonal shell of the tank body; an annular groove for mounting an annular tubular plastic bag is formed by the inner side of the polygonal outer shell of the groove body in a surrounding manner; an edge covering structure is arranged at the edge of an upper opening of the annular groove; a heat-preservation tank body installation position is arranged at the central line position of the polygonal shell of the tank body; the heat preservation groove body installation position and the positioning frame of the central fixed disk are matched to realize positioning installation.
In this embodiment, the installation position of the heat preservation groove body comprises: the mounting device comprises a cylindrical mounting position and a conical mounting position which are concentrically arranged. The cylindrical mounting position is correspondingly connected with the mounting position of the heat preservation groove body; the conical cylinder-shaped mounting position is sleeved at the central position of the swinging basket.
Preferably, the annular tubular plastic bag is formed by welding five or seven layers of co-extruded plastic films into an annular tubular bag. Preferably, the upper part of the annular tubular plastic 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.
Preferably, the base includes: the device comprises a step shaft chassis, a step shaft, a thrust joint bearing, a bearing support, a limiting shaft head and a damping rubber pad;
the step shaft chassis is concentrically connected with the step shaft through bolts; the step shaft is concentrically linked with an inner ring hole of the thrust knuckle bearing; the limiting shaft head and the step shaft are integrally arranged; the outer ring and the inner ring of the thrust joint bearing are matched with each other, and the outer surface of the outer ring of the thrust joint bearing is connected with the bearing support in a matched manner; the shock-absorbing rubber pad is connected with the bearing support.
Preferably, the support frame comprises: the device comprises a shaking table platform, four inclined struts, a supporting frame bottom plate and a damping rubber pad; the rocking bed platform is positioned at the top of the supporting frame; the shaking table mounting platform is connected with a fixing clamp at the bottom of the shaking table body through a bolt; the upper parts of the four oblique struts are welded on the rocking bed platform, and the lower parts of the four oblique struts are welded on the supporting frame bottom plate; the upper part of the shock absorption rubber cushion is connected with four corners of the supporting frame bottom plate.
By adopting the technical scheme, the invention has the following beneficial effects:
the structure and principle of the invention are that the minor axis in the rocking box is driven to do circumferential rocking through the circumferential rocking of the downward-probing rocking bed, the minor axis can move up and down along the axis on the surface of the inner hole of the spherical mechanism, and the rocking basket is rocked by the elastic rocking bar to do circumferential rocking around the axis of the thrust knuckle bearing in the base, namely, the mixed culture solution in the annular tubular plastic bag in the rocking heat-preservation tank body. In such shaking, the mixed culture solution (culture solution containing living cells) is caused to flow in a tilted tumbling manner and is caused to flow in a circular tubular plastic bag in a circular manner. At a very low rotation speed (less than 10 rpm), the mixed culture solution can form a plurality of waves, water drops and water flowers in the flowing and rolling process, so that the gas-liquid ratio surface area of the mixed culture solution is greatly increased. Meanwhile, the dissolved oxygen is greatly increased, the gas-liquid ratio surface area is greatly increased, and the harmful gases such as ammonia gas, carbon dioxide and the like are greatly facilitated to escape from the mixed culture solution to the gas on the upper part of the culture bag and then are discharged outside the annular tubular plastic bag through the gas outlet on the annular tubular plastic bag, so that the mixed culture solution in the plastic bag is purified. If we start the stepping motor in the rocking box at the same time to drive the ball screw and then drive the short shaft in the spherical mechanism, and when the rocking bed rotates for a circle, a linear reciprocating motion with a fixed stroke is added to the short shaft, and the result is the comprehensive track formed by the rocking of the rocking disc and the linear reciprocating motion of the short shaft as shown in the analysis chart. In fact, this linear movement, in addition, increases the angle of oscillation of the swinging basket. Compared with gas-liquid phase generated by simple circular shaking, the surface area is larger, the dissolved oxygen level is higher, and the fluidity and the effect of purifying the mixed culture solution are better. Meanwhile, the rotating speed of the rocking platforms can be reduced, namely, the shaking and the vibration caused by the shaking of the rocking basket are reduced;
the invention adopts the thrust knuckle bearing on the base, so that all the weight of the swinging basket assembly, the heat preservation groove body, the culture solution in the plastic bag and the like acts on the ground through the thrust knuckle bearing and the base, and the swinging is realized by the swinging rod doing three-dimensional circumference swinging around the center of the thrust knuckle bearing, namely the spherical center. Only the spherical sliding friction between the inner ring and the outer ring of the thrust knuckle bearing is generated during the rocking process, the lubrication of the bearing is very good, and the friction coefficient is very small. Furthermore, the self weight of the downward swinging bed, the supporting frame and the like is acted on the ground through the supporting frame. Therefore, the invention has no defects and defects of overturning moment, shaking, vibration and the like, can stably work even if the working volume of the invention is enlarged to 10000 liters, and does not have the defects and the defects. Compared with the existing reactor which is purely in plane circumference shaking and the existing swinging reactor which is purely in left-right swinging: the invention eliminates the defects of inertia force caused by overturning moment and centrifugal force on the ground, impact force, vibration, noise and the like on the ground. Particularly, the reaction is more obvious when the reactor has large volume and large load;
the invention adopts the longer elastic rocking bar, and utilizes the performance of the elastic rocking bar in storing and releasing energy, thereby effectively eliminating the impact force generated by the rocking basket assembly in the rocking process when the top end of the rocking bar, namely the short shaft part, swings to the end point. Meanwhile, the force of the end point impact force is greatly reduced due to the lever action of the longer rocker, and the impact force and the vibration on the upper part of the reactor supporting frame are also greatly reduced;
the invention adopts the annular tubular plastic bag, the mixed culture solution is limited to flow in the annular container, the fluidity is very good at low rotating speed, and the flowing speed is close to zero when the radius of the flowing center is close to zero, so that the cell sedimentation, accumulation and mutual adhesion are avoided, and further the cell membrane is damaged to cause cell death.
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 embodiments or the prior art descriptions 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 first state view of an up-swing tubular plastic bag-shaped cell bioreactor in a circular shape according to an embodiment of the present invention;
FIG. 2 is a second state diagram of the upper swing tubular plastic bag-shaped cell bioreactor according to the embodiment of the present invention;
FIG. 3 is a front view of a swing basket provided by an embodiment of the present invention;
FIG. 4 is a top view of a swing basket provided by an embodiment of the present invention;
FIG. 5 is a front view of a swing case provided in an embodiment of the present invention;
FIG. 6 is a top view of a swing box provided in accordance with an embodiment of the present invention;
FIG. 7 is a front view of the resilient rocker according to the embodiment of the present invention;
FIG. 8 is a top view of the resilient rocker provided in accordance with an embodiment of the present invention;
FIG. 9 is a front view of the heat-insulating tank according to the embodiment of the present invention;
FIG. 10 is a top view of an insulating tank provided in an embodiment of the present invention;
FIG. 11 is a schematic structural diagram of a spherical mechanism of a thrust knuckle bearing assembly according to an embodiment of the present invention;
FIG. 12 is a schematic structural diagram of a base according to an embodiment of the present invention;
FIG. 13 is a side view of a support frame provided by an embodiment of the present invention;
fig. 14 is a top view of a support frame provided in an embodiment of the present invention.
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 obtained by a person skilled in the art without any inventive step based on the embodiments of the present invention, are within the 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", and the like 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 referred to must have a specific orientation, be constructed in a specific orientation, and be operated, 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 stated 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 invention, are intended for purposes of illustration and explanation only and are not intended to limit the scope of the invention.
Referring to fig. 1 to 14, the present invention provides an up-swing tubular plastic bag cell bioreactor, comprising: the downward-probing type shaking table 100, the shaking box 200, the elastic rocking bar 400, the shaking frame 500, the shaking basket 600, the heat-insulating groove body 700, the annular tubular plastic bag 800, the base 900 and the supporting frame 990; the downward swinging bed 100 is mounted on a supporting frame 990; the shaking box 200 is connected with the downward probing shaking table 100 and is shaken circumferentially under the action of the downward probing shaking table 100; the swinging box 200 is connected with a double-thrust joint bearing combined spherical mechanism 204 through a linear motion mechanism; a short shaft 203 penetrates through the double-thrust joint bearing combined spherical mechanism 204; the lower end of the short shaft 203 is hung with an elastic rocker 400; the lower end of the elastic rocker 400 is connected with the swing frame 500; the lower end of the swing frame 500 is connected with a swing basket 600; the heat preservation groove body 700 is arranged in the swinging basket 600; the annular tubular plastic bag 800 is mounted in the heat-insulating tank body 700; the bottom of the swing basket 600 is in contact with the ground through the base 900.
Preferably, the rocking device 100 comprises: a rocking bed body 110, a rocking disk 108, an upper fixing plate 106, four downward-extending upright posts 116 and a downward-extending cradle bottom plate 104; the cradle body 110 is fixed to the steel beam 114 of the support frame 990 at the bottom by a fixing clip 102; the shaking table body 110 is connected with the shaking disc 108; the rocking disc 108 is connected with the upper fixing plate 106 through bolts; four corners of the upper fixing plate 106 are connected with the upper ends of the lower four upright posts 116 through nuts 118; the lower ends of the downward-exploring four upright posts 116 are connected with four corners of the downward-exploring cradle bottom plate 104 through nuts 118; the swing box 200 is mounted to the lower deck 104 of the lower swing cradle.
In this embodiment, the specific form of the rocking bed body 110 is not limited, and reference can be made to the prior art.
For example: the rocking bed body 110 includes: a shaking table driving box; a driving motor is arranged in the shaking table driving box; a power output shaft of the driving motor is provided with a small belt pulley; the small belt pulley is connected with the large belt pulley in a tensioning manner through a belt; the large belt pulley is arranged on the driving eccentric shaft; the upper end of the driving eccentric shaft is connected with an upper swing disc; the upper shaking disc is connected with four groups of driven shafts; the upper rocking disc is bolted to the rocking disc 108, and the rocking disc 108 is bolted to the upper fixing plate 106.
Preferably, the swing box 200 includes: the device comprises a swing box 226, a short shaft 203, a double-thrust joint bearing combined spherical mechanism 204, a supporting 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 joint bearing combined mechanism 204 is fixedly connected to the supporting plate 206 through bolts; the support plate 206 is connected to the sliding seat 210; the slide mount 210 is connected to the slide rail 208; the sliding guide rail 208 is fixed on the bottom plate 224 of the swinging box through bolts; the nut of the ball screw 216 is connected to the shell of the double-thrust spherical joint bearing combination mechanism 204; the front end of the stepping motor 220 is concentrically connected with the screw rod of the ball screw 216, and the bottom of the stepping motor 220 is fixed on the bottom plate 224 of the swinging box through a bolt; the short shaft 203 is arranged on the thrust joint bearing combined spherical mechanism 204 in a penetrating manner; the bottom plate 224 of the swinging box and the bottom plate 104 of the downward-exploring cradle are provided with hollowed-out parts 230 which allow the short shaft 203 to extend and move along the direction of the sliding guide rail 208.
Preferably, the double thrust knuckle bearing combined spherical mechanism 204 includes: double thrust joint bearing 234, housing 232, bushing 236 and stub shaft 203; the inner ring of the double-thrust knuckle bearing 234 is vertically and symmetrically mounted on the shaft sleeve 236, and the outer ring of the double-thrust knuckle bearing 234 is vertically and symmetrically circumscribed in the shell 232; the inner hole of the shaft sleeve 236 is sleeved on the short shaft 203, and the outer circle surface of the short shaft 203 and the inner hole surface of the shaft sleeve 236 slide relatively, so that the short shaft 203 can linearly reciprocate up and down along the axis of the shaft sleeve 236 in the hole.
Preferably, the elastic rocker 400 includes a rocking bar 422, an upper disc 404, four tension springs 408, a tension spring ring 428, a lower disc 410 and a rocking frame 500; the upper part of the swing rod 422 passes through the central hole of the upper disc 404 and is concentrically connected with the stub shaft 203 in the swing box 200, and the lower part of the swing rod 422 is connected with a cross universal joint 426; the cross universal joint 426 is connected with the center of the lower disc 410 through a bolt; the upper ends of the four tension springs 408 are connected with tension spring rings 428 at four corners of the upper disc 404, and the lower ends of the four tension springs 408 are connected with tension spring rings 428 at four corners of the lower disc 410; the lower plate 410 is connected with the upper portion of the swing frame 500; the lower portion of the swing frame 500 is connected to the upper rim of the swing basket 600.
Preferably, the upper part and the lower part of the swing frame 500 are supported by a three-column 502; the upper part of the swing frame 500 is connected with the lower disc 410 of the elastic rocker 400 by a circular ring frame; the lower portion of the swing frame 500 is connected to the upper portion of the swing basket 600 by a dodecagon frame 504.
Preferably, the outer upper rim of the swing basket 600 is connected with the lower portion of the swing frame 500; a raised central fixed disc 620 is arranged at the center of the swinging basket 600; the swing basket 600 forms an annular space for accommodating the insulation tank body 700; the central fixed disk 620 is connected with the stepped shaft chassis 902 of the base 900.
In this embodiment, the swinging basket 600 includes: in the vertical direction, the lower three polygonal frames with the same size form the side structure of the swinging basket together, and the upper parts of the upper polygonal frames of the first group are connected with the lower parts of the swinging frames; only one polygonal frame in the second group of polygonal frames and only one polygonal frame in the third group of polygonal frames jointly form a bottom structure of the swinging basket; the central fixed disc is upwards protruded from the center of the swinging basket; and a circular positioning frame is arranged around the central fixed disk.
Preferably, the insulation tank body comprises: a tank body polygonal housing 708; a heating rubber plate system or a heating water jacket system is arranged in the interlayer of the side wall of the polygonal shell 708 of the tank body; the inner side of the groove body polygonal shell 708 is enclosed to form an annular groove 706 for installing the annular tubular plastic bag 800; the edge of the upper opening of the annular groove 706 is provided with a covered edge structure; a heat preservation groove body installation position is arranged at the central line position of the groove body polygonal shell 708; the heat preservation groove body installation position is matched with the positioning frame of the central fixing disc to realize positioning installation.
In this embodiment, the installation position of the heat preservation groove body comprises: the mounting device comprises a cylindrical mounting position and a conical mounting position which are concentrically arranged. The cylindrical mounting position is correspondingly connected with the mounting position of the heat preservation groove body; the conical cylindrical mounting position is sleeved at the central position of the swinging basket 600.
Preferably, the annular tubular plastic bag 800 is formed by welding five or seven layers of co-extruded plastic films into an annular tubular bag.
In this embodiment, the annular tubular plastic is provided with dissolved oxygen, PH, temperature sensors, liquid inlet and outlet, gas inlet and outlet, and various spare connectors and pipelines.
Preferably, the base 900 includes: the step shaft chassis 902, the step shaft 904, the thrust knuckle bearing 906, the bearing support 908, the limiting shaft head 920 and the shock-absorbing rubber pad 910;
the step shaft chassis 902 and the step shaft 904 are concentrically connected by bolts; the step shaft 904 is concentrically linked with an inner ring hole of the thrust knuckle bearing 906; the limiting shaft head 920 and the step shaft 904 are arranged integrally; the outer ring and the inner ring of the thrust joint bearing 906 are matched with each other, and the outer ring of the thrust joint bearing 906 is connected with the bearing support 908 in a matched manner; the cushion rubber 910 is coupled to the bearing support 908.
Preferably, the support frame 990 includes: a cradle platform 992, four oblique struts 994, a support frame bottom plate 996 and a shock-absorbing rubber pad 998; the cradle platform 992 is positioned at the top of the support frame 990; the swing bed platform 992 is connected with the fixing clip 102 at the bottom of the swing bed body 110 through a steel beam 114; the upper parts of the four diagonal braces 994 are welded on the rocking bed platform 992, and the lower parts of the four diagonal braces 994 are welded on the supporting frame bottom plate 996; the upper part of the shock-absorbing rubber pad 998 is connected with four corners of the support frame base plate 996.
In conclusion, the structure and the principle of the invention are that the minor axis in the rocking box is driven to do circumferential rocking through the circumferential rocking of the downward-probing rocking bed, the minor axis can move up and down along the axis on the surface of the inner hole of the spherical mechanism, and the rocking basket of the rocking frame does circumferential rocking around the axis of the thrust knuckle bearing in the base through the elastic rocking rod, namely the mixed culture solution in the annular tubular plastic bag in the rocking heat-preservation tank body. In such shaking, the mixed culture solution (culture solution containing living cells) is caused to flow in a tilted tumbling manner and is caused to flow in a circular shape in a circular tube-shaped plastic bag. At a very low rotation speed (less than 10 rpm), the mixed culture solution can form a plurality of waves, water drops and water flowers in the flowing and rolling process, so that the gas-liquid ratio surface area of the mixed culture solution is greatly increased. Meanwhile, the dissolved oxygen is greatly increased, the gas-liquid specific surface area is greatly increased, and the harmful gases such as ammonia gas and carbon dioxide are greatly facilitated to escape from the mixed culture solution and then are discharged outside the annular tubular plastic bag through the air outlet on the annular tubular plastic bag, so that the mixed culture solution in the plastic bag is purified. If we start the stepping motor in the rocking box to drive the ball screw and then 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 for one circle, the result is the comprehensive track formed by the rocking of the rocking disk and the linear reciprocating motion of the short shaft as shown in the analysis chart. In fact, this linear movement, in addition, increases the angle of oscillation of the swinging basket. Compared with gas-liquid phase generated by simple circular shaking, the surface area is larger, the dissolved oxygen level is higher, and the fluidity and the effect of purifying the mixed culture solution are better. Meanwhile, the rotating speed of the rocking platforms can be reduced, namely, the shaking and the vibration caused by the shaking of the rocking basket are reduced;
the invention adopts the thrust knuckle bearing on the base, so that all the weight of the swinging basket assembly, the heat preservation groove body, the culture solution in the plastic bag and the like acts on the ground through the thrust knuckle bearing and the base, and the swinging is performed by the swinging rod to perform three-dimensional circular swinging around the center of the thrust knuckle bearing, namely the spherical center. Only the spherical sliding friction between the inner ring and the outer ring of the thrust knuckle bearing exists during the shaking, the lubrication of the bearing is very good, and the friction coefficient is very small. Furthermore, the self weight of the downward-probing shaking table, the supporting frame and the like acts on the ground through the supporting frame. Therefore, the invention has no defects and defects of overturning moment, shaking, vibration and the like, can stably work even if the working volume of the invention is enlarged to 10000 liters, and does not have the defects and the defects. Compared with the existing reactor which is purely in plane circumference shaking and the existing swinging reactor which is purely in left-right swinging: the invention eliminates the defects of inertia force caused by overturning moment and centrifugal force on the ground, impact force, vibration, noise and the like on the ground. Particularly, the reaction is more obvious when the reactor has large volume and large load;
the invention adopts the longer elastic rocking bar, and utilizes the performance of the elastic rocking bar in storing and releasing energy, thereby effectively eliminating the impact force generated in the swinging process of the swinging basket assembly when the top end of the rocking bar, namely the short shaft part swings to the end point. Meanwhile, the force of the end point impact force is greatly reduced due to the lever action of the longer rocker, and the impact force and the vibration on the upper part of the reactor supporting frame are also greatly reduced;
the invention adopts the annular tubular plastic bag, the mixed culture solution is limited to flow in the annular container, the fluidity is very good at low rotating speed, and the flowing speed is close to zero when the radius of the flowing center is close to zero, so that the cell sedimentation, accumulation and mutual adhesion are avoided, and further the cell membrane is damaged to cause cell death.
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 such modifications and substitutions do not depart from the spirit and scope of the present invention as defined by the appended claims.
Claims (10)
1. An up-swinging annular tubular plastic bag cell bioreactor, comprising: a downward-probing type shaking table (100), a swinging box (200), an elastic rocker (400), a swinging frame (500), a swinging basket (600), a heat-preservation groove body (700), an annular tubular plastic bag (800), a base (900) and a supporting frame (990); the downward-probing shaking table (100) is erected on the supporting frame (990); the shaking box (200) is connected with the downward probing shaking bed (100) and is shaken circumferentially under the action of the downward probing shaking bed (100); the swing box (200) is connected with a double-thrust joint bearing combined spherical mechanism (204) through a linear motion mechanism; a short shaft (203) penetrates through the double-thrust joint bearing combined spherical mechanism (204); the lower end of the short shaft (203) is connected with an elastic rocker (400); the lower end of the elastic rocker (400) is connected with the swinging frame (500); the lower end of the swinging frame (500) is connected with the swinging basket (600); the heat preservation groove body (700) is arranged in the swinging basket (600); the annular tubular plastic bag (800) is arranged in the heat preservation groove body (700); the bottom of the swinging basket (600) is contacted with the ground through the base (900).
2. The upward swinging annular plastic bag cell bioreactor according to claim 1, wherein the downward probing rocking bed (100) comprises: a shaking table body (110), a shaking disc (108), an upper fixing plate (106), a downward-probing four-upright post (116) and a downward-probing cradle bottom plate (104);
the bottom of the shaking table body (110) is fixed on a steel beam (114) of the supporting frame (990) through a fixing clip (102); the shaking table body (110) is connected with the shaking disc (108); the rocking disc (108) is connected with the upper fixing plate (106) through bolts; four corners of the upper fixing plate (106) are connected with the upper ends of the four downward-extending upright posts (116) through nuts (118); the lower ends of the downward-probing four upright posts (116) are connected with four corners of the downward-probing cradle bottom plate (104) through nuts (118); the swinging box (200) is arranged on the bottom plate (104) of the downward-exploring swinging cradle.
3. The upward-rocking annular plastic bag tubular cell bioreactor according to claim 1, wherein the rocking box (200) comprises: the device comprises a swing box body (226), a short shaft (203), a double-thrust joint bearing combined spherical mechanism (204), a supporting 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 joint bearing combined spherical mechanism (204) is fixedly connected to the supporting plate (206) through bolts; the supporting 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 on the swinging box bottom plate (224) through bolts; the nut of the ball screw (216) is connected with the shell of the double-thrust joint bearing combined spherical mechanism (204); the front end of the stepping motor (220) is concentrically connected with a screw rod of the ball screw (216), and the bottom of the stepping motor (220) is fixed on the bottom plate (224) of the swinging box through a bolt; the short shaft (203) is arranged on the thrust joint bearing combination spherical mechanism (204) in a penetrating manner; the bottom plate (224) of the swinging box and the bottom plate (104) of the downward-exploring cradle are respectively provided with a hollowed-out part (230) allowing the short shaft (203) to extend and move along the direction of the sliding guide rail (208).
4. The upward swinging annular plastic bag cell bioreactor according to claim 3, wherein the double thrust knuckle bearing combined spherical mechanism (204) comprises: a double thrust knuckle bearing (234), a housing (232), a shaft sleeve (236) and a stub shaft (203); the inner ring of the double-thrust joint bearing (234) is vertically and symmetrically arranged on the shaft sleeve (236), and the outer ring of the double-thrust joint bearing (234) is vertically and symmetrically externally connected in the shell (232); the inner hole of the shaft sleeve (236) is sleeved on the short shaft (203), the outer circle surface of the short shaft (203) and the inner hole surface of the shaft sleeve (236) slide relatively, and the short shaft (203) can linearly reciprocate up and down along the axis of the short shaft in the shaft sleeve (236) hole.
5. The upward-rocking annular plastic bag cell bioreactor as claimed in claim 4, wherein the elastic rocking bar (400) comprises a rocking bar (422), an upper disc (404), four tension springs (408), a tension spring ring (428), a lower disc (410) and a rocking frame (500);
the upper part of the swing rod (422) penetrates through the central hole of the upper disc (404) to be concentrically connected with a short shaft (203) in a swing box (200), and the lower part of the swing rod (422) is connected with a cross-axle universal joint (426); the cross shaft universal joint (426) is connected with the center of the lower disc (410) through a bolt; the upper ends of the four tension springs (408) are connected with tension spring rings (428) at four corners of the upper disc (404), and the lower ends of the four tension springs (408) are connected with tension spring rings (428) at four corners of the lower disc (410); the lower plate (410) is connected with the upper part of the swinging frame (500); the lower part of the swinging frame (500) is connected with the upper frame of the swinging basket (600) by bolts.
6. The upward-rocking tubular plastic bag cell bioreactor as claimed in claim 5, wherein the upper and lower parts of the rocking frame (500) are supported by three pillars (502); the upper part of the swinging frame (500) is connected with a lower disc (410) of the elastic rocker (400) by a circular ring frame; the lower part of the swinging frame (500) is connected with the upper part of the swinging basket (600) by a dodecagon frame (504).
7. The upward-rocking annular tubular plastic bag cell bioreactor according to claim 5, wherein the outer upper rim of the rocking basket (600) is connected with the lower part of the rocking frame (500); a raised central fixed disc (620) is arranged at the center of the swinging basket (600); the swinging basket (600) forms an annular space for accommodating the heat-preservation tank body (700); the central fixed disc (620) is connected with a step shaft chassis (902) of the base (900).
8. The upward swinging annular plastic bag cell bioreactor according to claim 7, wherein the incubation well comprises: a trough body polygonal shell (708); a heating rubber plate system or a heating water jacket system is arranged in an interlayer of the side wall of the polygonal shell (708) of the tank body; an annular groove (706) for mounting an annular tubular plastic bag (800) is formed by the inner side of the polygonal shell (708) of the groove body in a surrounding manner; an edge covering structure is arranged at the edge of an upper opening of the annular groove (706); a heat preservation groove body installation position is arranged at the central line position of the groove body polygonal shell (708); the heat preservation groove body installation position and the positioning frame of the central fixed disk are matched to realize positioning installation.
9. The upward swinging annular plastic bag cell bioreactor according to claim 8, wherein the base (900) comprises: the device comprises a step shaft chassis (902), a step shaft (904), a thrust knuckle bearing (906), a bearing support (908), a limiting shaft head (920) and a shock-absorbing rubber pad (910);
the step shaft chassis (902) and the step shaft (904) are concentrically connected by bolts; the step shaft (904) is concentrically linked with an inner annular bore of the thrust knuckle bearing (906); the limiting shaft head (920) and the step shaft (904) are arranged in an integrated manner; the outer ring and the inner ring of the thrust joint bearing (906) are matched with each other, and the outer surface of the outer ring of the thrust joint bearing (906) is matched and connected with the bearing support (908); the shock-absorbing rubber pad (910) is connected with the bearing support (908).
10. The upward-rocking annular plastic bag cell bioreactor according to claim 9, wherein the support frame (990) comprises: a cradle platform (992), four inclined struts (994), a supporting frame bottom plate (996) and a shock-absorbing rubber pad (998); the cradle platform (992) is positioned at the top of the support frame (990); the shaking table platform (992) is connected with a fixing clip (102) at the bottom of the shaking table body (110) through a steel beam (114); the upper parts of the four oblique struts (994) are welded on the shaker platform (992), and the lower parts of the four oblique struts (994) are welded on the supporting frame bottom plate (996); the upper part of the shock absorption rubber cushion (998) is connected with four corners of the supporting frame bottom plate (996).
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN114517156A (en) * | 2022-02-14 | 2022-05-20 | 飞鼎智造(上海)生物科技有限公司 | Swing device of swing type bioreactor |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN114517156A (en) * | 2022-02-14 | 2022-05-20 | 飞鼎智造(上海)生物科技有限公司 | Swing device of swing type bioreactor |
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