Rabies virus liquid preparation system

Abstract

The invention provides a rabies virus liquid preparation system, which belongs to the technical field of vaccine production, and comprises a mobile vehicle, a reactor, a culture basket and a controller, the reactor is arranged on the mobile vehicle, the top of the reactor is provided with a material inlet / outlet and a detection probe, and a stirring device is arranged in the reactor; the culture basket is arranged on a corresponding placing position in the reactor, a stirring channel allowing the stirring device to penetrate through is formed in the middle of the culture basket, the culture basket is of a closed structure, and an interval channel is formed between the peripheral surface of the culture basket and the side wall of the reactor; the controller is arranged on the moving trolley, and a material inlet and outlet channel is further arranged in the controller and correspondingly communicated with the material inlet and outlet. According to the rabies virus liquid preparation system provided by the invention, the damage to carriers and cells caused by impact and shearing acting force generated by stirring is effectively improved, so that the degrees of cell death and fragments generated by carrier crushing are reduced, and the adverse effects of virus culture on virus yield and subsequent purification efficiency are effectively improved.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of vaccine production, and more particularly relates to a rabies virus liquid preparation system. BACKGROUND

[0002] The main role of the rabies vaccine is to prevent rabies virus infection, which neutralizes the virus before it invades the central nervous system by stimulating the human body to produce specific antibodies against the rabies virus, thereby avoiding the disease. The production process of the rabies vaccine mainly includes virus culture, inactivation and purification, vaccine configuration and other steps. Among them, the significance of virus culture is to obtain virus antigens or gene fragments to provide key raw materials for vaccine research and development. Virus culture using carriers is an important virus culture method, which uses a micro-particle with a diameter of 60-250 um as a cell attachment carrier to realize large-scale cell expansion by combining suspension culture, and has the characteristics of high production efficiency, strong process flexibility, high safety and stability.

[0003] The existing equipment for virus culture using carriers can easily cause cell death and carrier fragments under high feed density, which directly affects the virus yield and the subsequent purification efficiency. In addition, the existing carriers are seriously stacked in the container under the action of gravity, and the flow speed of the liquid is difficult to control, making it difficult to balance the needs of full contact with the liquid and the needs of avoiding cell shedding. SUMMARY

[0004] The purpose of the present application is to provide a rabies virus liquid preparation system, which aims to solve the problems of cell death and carrier fragments caused by the existing equipment for virus culture using carriers, and the difficulty in controlling the flow speed of the liquid, making it difficult to balance the needs of full contact with the liquid and the needs of avoiding cell shedding.

[0005] To achieve the above purpose, the technical solution adopted by the present application is: A rabies virus liquid preparation system is provided, comprising: A mobile vehicle; A reactor provided on the mobile vehicle, wherein the inner cavity of the reactor is provided with at least two placement positions distributed in sequence from top to bottom, the top of the reactor is provided with a material inlet and outlet and a detection probe, and the reactor is provided with a stirring device inside; A culture basket provided on the corresponding placement position in the reactor and used for containing carriers, wherein the middle part of the culture basket is provided with a stirring channel through which the stirring device penetrates, the culture basket is of a closed structure, and through holes are formed in the top surface, the bottom surface and the peripheral surface of the culture basket, and a spacing channel is formed between the peripheral surface of the culture basket and the side wall of the reactor; A controller is arranged on the mobile vehicle, and the controller is in communication connection with the mobile vehicle, the detection probe and the stirring device respectively. The controller further has a material inlet and outlet channel, and the material inlet and outlet channel is in communication with the material inlet and outlet.

[0006] In a possible implementation, the upper part of the reactor is provided with a temperature adjusting inlet, and the bottom part is provided with a temperature adjusting outlet. The controller is provided with a temperature adjusting supply channel and a temperature adjusting discharge channel. The outlet of the temperature adjusting supply channel is in communication with the temperature adjusting inlet, and the temperature adjusting discharge channel is in communication with the inlet of the temperature adjusting outlet. The side wall of the reactor has a temperature adjusting channel, and the temperature adjusting inlet and the temperature adjusting outlet are in communication with the temperature adjusting channel respectively.

[0007] In a possible implementation, the outer contour of the culture basket is conformal to the inner cavity of the reactor. The culture basket comprises a basket body and a basket cover arranged on the top opening of the basket body. The middle part of the basket cover is provided with a cover through hole, and the middle part of the basket body is provided with a channel partition plate corresponding to the cover through hole. The top and bottom parts of the channel partition plate are both penetrated. The cover through hole and the channel partition plate cooperate to form the stirring channel.

[0008] In some embodiments, the top outer periphery of the basket body is provided with at least three circumferential limiting arms. Each of the circumferential limiting arms is uniformly distributed along the circumference of the basket body, and the outer end thereof can abut against the side wall of the inner cavity of the reactor to limit the displacement of the basket body in the circumferential direction.

[0009] In some embodiments, the bottom outer periphery of the basket body is provided with at least three supporting legs. Each of the supporting legs is uniformly distributed along the circumference of the basket body, and the supporting leg is inclined in a direction gradually away from the center line of the basket body in the direction from top to bottom. The side wall of the reactor is provided with at least three supporting bosses. Each of the supporting bosses is arranged at intervals along the circumference of the inner cavity of the reactor. An avoidance channel for the circumferential limiting arm and the supporting leg to pass through is formed between two adjacent supporting bosses.

[0010] In some embodiments, the basket cover is hinged to the basket body.

[0011] In a possible implementation, the stirring device comprises a stirring driver and a plurality of stirring units sequentially arranged from top to bottom. The stirring driver is fixed above the reactor, and each of the stirring units can penetrate the stirring channel in the corresponding culture basket. Each of the stirring units comprises a stirring shaft and a plurality of stirring paddles distributed around the stirring shaft; the upper end of the stirring shaft is provided with a first connecting piece, and the lower end is provided with a second connecting piece; the first connecting piece can be detachably connected with the output shaft of the stirring driver or the second connecting piece of the adjacent upper and lower ends of the stirring shaft.

[0012] In some embodiments, the reactor comprises a main tank body and a top cover, the top cover and the main tank body are connected through a flange structure; the material inlet and outlet and the detection probe are arranged on the top cover, the detection probe comprises a dissolved oxygen concentration detection probe, a pH value detection probe, a sugar content detection probe, a temperature detection probe and an osmotic pressure detection probe distributed around the central axis of the top cover; the material inlet and outlet comprises a plurality of steam exhaust ports, liquid inlet ports, liquid outlet ports, oxygen inlet ports, nitrogen inlet ports, carbon dioxide inlet ports, air inlet ports, pure steam inlet ports and sodium bicarbonate solution inlet ports distributed around the central axis of the top cover; the top cover is further provided with a breathing port.

[0013] In some embodiments, a sandwich cavity is arranged in the sidewall of the main tank body, and the sandwich cavity is the temperature adjusting channel.

[0014] In some embodiments, the stirring device comprises a stirring driver and a plurality of stirring units sequentially arranged from top to bottom, the stirring driver is fixed above the reactor, each of the stirring units can penetrate the stirring channel in the corresponding culture basket, and the stirring driver is arranged at the central position of the top cover.

[0015] Compared with the prior art, the rabies virus liquid preparation system provided by the application has the following beneficial effects: 1. The culture basket is a closed structure. By reasonably setting the aperture of the through holes on the top, bottom and circumferential surfaces of the culture basket, the carrier placed in the culture basket will not fall out. At the same time, the stirring device can bring disturbance to the liquid (i.e., nutrient solution), so that the liquid maintains a certain fluidity and avoids the deposition of nutrients. If the periphery of the culture basket contacts or is too close to the inner wall of the reaction chamber, it will cause the cells to adhere to the side wall of the reaction chamber, forming a "dead cavity" in this area. The liquid will not flow smoothly and cannot reach the outer peripheral wall of the culture basket. Once this happens, the cells near this area will not be able to obtain the supply of nutrients and various gases, eventually leading to the death of a large number of cells. However, by forming a spacing channel, the liquid can flow freely around the culture basket under the action of the stirring device, so that there is an adequate supply of nutrients and gases around the culture basket to ensure the activity of the cells. In addition, during the operation of the stirring device, the flow of liquid caused by stirring is blocked by the stirring channel and will not directly act on the carrier in the culture basket, which not only ensures the fluidity of the liquid, but also does not directly impact the carrier and cells inside the culture basket during the flow of the liquid. Instead, the liquid slowly enters the culture basket through the through holes on the culture basket, effectively improving the damage to the carrier and cells caused by the impact and shear force generated by stirring, thereby reducing the degree of cell death and the fragmentation of the carrier, and effectively improving the adverse effects of virus culture on virus yield and subsequent purification efficiency.

[0016] 2. In the existing culture method, the carrier is often placed in a container. After the container is placed in the reactor, the carrier accumulates at the bottom of the container under the action of gravity. If a stirring structure is used for stirring, if the stirring force is strong, although the carrier can be scattered in the liquid, the cells can be fully supplemented with basic nutrient solution, but there is also a risk that the cells are easily detached from the carrier. After a period of culture, cell fragments will accumulate and adhere to the bottom of the container, resulting in poor permeability of the container, resulting in poor liquid circulation, which will affect the problem of high cell mortality. If the stirring force is too weak, the accumulation of carriers cannot be changed, and some carriers will still not be able to fully contact the liquid, which will also lead to a high cell mortality rate. The present application adopts a method of arranging carriers in layers with multiple culture baskets, placing the carriers in different culture baskets respectively, reducing the degree of cell accumulation in the culture basket. Under the cooperation of the stirring device, the carriers in each culture basket can fully contact the liquid, greatly reducing the accuracy of the stirring device speed control, and at the same time improving the problem of liquid flow damaging the cells, ultimately improving the adverse effects of virus culture on virus yield and subsequent purification efficiency.

[0017] 3、By setting the controller, the material inlet and outlet channel of the controller can be connected with the source or the container of the material, and then the material inlet and outlet can be controlled according to the preset instructions, the detection probe can collect the reaction data inside the reactor, and the controller and the detection probe are connected to realize the collection of the reaction data inside the reactor, and then the real-time monitoring of the reaction state is realized, the control of the reaction process is more intelligent, and the reaction efficiency is significantly improved. In addition, since the material inlet and outlet channel is arranged in the controller, the material inlet and outlet channel is arranged neatly, which is more convenient for connection with each pipeline, and avoids mutual entanglement between the pipelines to affect the smoothness of the material flow.

[0018] 4、By connecting the controller with the mobile vehicle, the controller can pre-set the factory map data, and pre-plan the moving path based on the map data, the mobile vehicle can be controlled to move to the next designated position along the planned path through the controller, and the movement of the mobile vehicle can drive the reactor and the controller to move as a whole. Alternatively, the controller can interact with a mobile terminal (such as a mobile phone) to input instructions to the controller through the mobile terminal, and the controller can control the mobile vehicle to move through the input instructions, and then the mobile vehicle can be controlled to move in a remote control manner. The movement of the mobile vehicle realizes the automatic control of the system position movement, and is more convenient to use.

[0019] Overall, the rabies virus liquid preparation system of the present application optimizes the matching mode of the culture basket and the stirring device, reduces the degree of cell death and the generation of fragments caused by carrier breakage, effectively improves the adverse effects of virus culture on virus yield and subsequent purification efficiency; by setting the controller, the reaction efficiency is significantly improved, and by combining the controller with the mobile vehicle, the automatic control of the system position movement is realized, and the use is more convenient. BRIEF DESCRIPTION OF DRAWINGS

[0020] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed in the embodiments or prior art description will be briefly introduced as follows. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor.

[0021] Figure 1 The structure diagram of the rabies virus liquid preparation system provided by the first embodiment of the present application is shown in the figure; Figure 2 The internal structure diagram of the reactor used in the first embodiment of the present application is shown in the figure; Figure 3 The structure diagram of the culture basket used in the first embodiment of the present application is shown in the figure, in which the basket cover is in a closed state; Figure 4The structure diagram of the culture basket used in the first embodiment of the present application, wherein the basket cover is in the open state; Figure 5 The top view internal structure schematic diagram of the circumferential limiting support arm used in the second embodiment of the present application; Figure 6 The assembly schematic diagram of the stirring unit used in the third embodiment of the present application; Figure 7 The top view of the basket cover used in the fourth embodiment of the present application; Figure 8 The distribution schematic diagram of the support boss in the reactor used in the fifth embodiment of the present application; Figure 9 The three-dimensional structure schematic of the controller used in the sixth embodiment of the present application Figure 1 ; Figure 10 The three-dimensional structure schematic of the controller used in the sixth embodiment of the present application Figure 2 .

[0022] In the figure: 1, mobile vehicle; 2, reactor; 201, temperature-adjusting inlet; 202, temperature-adjusting outlet; 210, main tank body; 211, tank body flange; 220, top cover; 221, cover flange; 230, interlayer cavity; 240, observation window; 3, culture basket; 301, stirring channel; 302, through hole; 310, basket main body; 320, basket cover; 321, cover through hole; 330, channel partition; 340, circumferential limiting support arm; 341, guide rod; 342, support arm; 343, elastic member; 350, support leg; 4, controller; 7, stirring device; 710, stirring driver; 720, stirring unit; 721, stirring shaft; 722, stirring paddle; 723, first connecting member; 724, second connecting member; 8, spacing channel; 9, support boss; 10, avoidance channel; 11, dissolved oxygen concentration detection probe; 12, pH value detection probe; 13, sugar content detection probe; 14, temperature detection probe; 15, osmotic pressure detection probe; 16, steam outlet; 17, liquid inlet; 18, liquid outlet; 19, oxygen inlet; 20, nitrogen inlet; 21, carbon dioxide inlet; 22, air inlet; 23, pure steam inlet; 24, sodium bicarbonate solution inlet; 25, breathing port; 26, dissolved oxygen concentration detection port; 27, pH value detection port; 28, sugar content detection port; 29, temperature detection port; 30, osmotic pressure detection port; 31, oxygen outlet; 32, nitrogen outlet; 33, carbon dioxide outlet; 34, air outlet; 35, driver power supply signal port; 36, pure steam outlet; 37, hot water outlet; 38, hot water return port; 39, pure steam return port; 40, display screen; 41, power switch; 42, liquid inlet pump; 43, liquid outlet pump; 44, sodium bicarbonate solution pump; 45, standby pump; 46, oxygen inlet; 47, nitrogen inlet; 48, carbon dioxide inlet; 49, air inlet; 50, pure steam inlet; 51, hot water inlet; 52, pure steam discharge port; 53, hot water recovery port; 54, power supply interface. DETAILED DESCRIPTION

[0023] In order to make the technical problems to be solved by the present application, the technical solutions and beneficial effects clearer, the present application will be further described in detail below in combination with the drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and not used to limit the present application.

[0024] It should be noted that when an element is referred to as being "on" another element, it can be directly on the other element or indirectly on the other element with intervening elements. It should be understood that the terms "length", "width", "upper", "lower", "front", "rear", "top", "bottom", "inner", "outer", and the like, define directions or locations as viewed in the drawings and are used for convenience in describing the present application and its disclosure. None of these terms should be construed as indicating or implying necessary or essential positions, sequence or orientation of the indicated structures or elements.

[0025] The terms "first", "second", "third", "fourth", "fifth", "sixth", "seventh" and "eight" are used only to describe different instances of the same or similar elements and do not imply relative importance or a particular quantity. Thus, a feature defined with "first", "second", "third", "fourth", "fifth", "sixth", "seventh" or "eight" can include one or more of the features implicitly or explicitly.

[0026] Please refer to Figures 1 to 10 The rabies virus liquid preparation system provided by the present application will be described below. The rabies virus liquid preparation system comprises a mobile vehicle 1, a reactor 2, a culture basket 3 and a controller 4. The reactor 2 is arranged on the mobile vehicle 1. The inner cavity of the reactor 2 is provided with at least two placing positions arranged in sequence from top to bottom. The top of the reactor 2 is provided with a material inlet and outlet and a detection probe. The reactor 2 is provided with a stirring device 7. The culture basket 3 is arranged on the corresponding placing position in the reactor 2 and is used for containing a carrier. The culture basket 3 is provided with a stirring channel 301 in the middle, which is penetrated by the stirring device 7. The culture basket 3 has a closed structure, and the top surface, the bottom surface and the peripheral surface are all provided with through holes 302. The peripheral surface of the culture basket 3 and the side wall of the reactor 2 are spaced apart to form a spacing channel 8. The controller 4 is arranged on the mobile vehicle 1. The controller 4 is in communication connection with the mobile vehicle 1, the detection probe and the stirring device 7. The controller 4 is also provided with a material inlet and outlet channel, which is in communication with the material inlet and outlet.

[0027] It should be noted that the liquid can flow without order or in order under the disturbance of the stirring device 7, for example, forming a path of "stirring channel 301 → bottom of culture basket 3 → overflow channel 8 outside the culture basket 3 → top of culture basket 3 → stirring channel 301". In general, it is only required that the liquid can fully flow and fully contact each side surface of the culture basket 3, and no unique limitation is made here.

[0028] In this embodiment, the communication connection can be a limited connection or a wireless connection (such as Bluetooth), and information interaction can be realized, and no unique limitation is made here.

[0029] In this embodiment, the carrier can adopt a sheet-shaped carrier with a diameter of about 5mm-6mm. The carrier can be selected from the existing carriers according to the actual culture requirements, which will not be listed one by one here.

[0030] The rabies virus liquid preparation system provided in the application has the following beneficial effects compared with the prior art: 1. The culture basket 3 is of a closed structure. By reasonably setting the aperture of the through hole on the top surface, bottom surface and circumferential surface of the culture basket 3, the carrier placed in the culture basket 3 will not fall out. At the same time, the stirring device 7 can bring disturbance to the liquid (i.e. nutrient solution), so that the liquid maintains a certain fluidity and avoids the deposition of nutrients. If the outer periphery of the culture basket 3 contacts or is too close to the inner side wall of the reaction cavity, the cells will adhere to the side wall of the reaction cavity, and a "dead cavity" is formed in this area, the liquid flow is not smooth, and the outer periphery of the culture basket 3 cannot be reached. Once this situation occurs, the cells near this area will not be able to obtain the supply of nutrients and various gases, and eventually lead to the death of a large number of cells. However, by forming the spacing channel 8, under the action of the stirring device 7, the liquid can flow freely around the culture basket 3, so that there is sufficient supply of nutrients and gases around the culture basket 3, and the activity of the cells is ensured. In addition, during the operation of the stirring device 7, the liquid flow caused by stirring is blocked by the stirring channel 301 and will not directly act on the carrier in the culture basket 3, which not only ensures the fluidity of the liquid, but also effectively reduces the damage to the carrier and cells caused by the impact and shear force generated by stirring during the liquid flow process, thereby reducing the degree of cell death and the generation of fragments caused by the breaking of the carrier, and effectively improving the adverse effects of virus culture on virus yield and subsequent purification efficiency.

[0031] 2. In existing culture methods, the carrier is often placed in a container. After the container is placed in the reactor, the carrier accumulates at the bottom of the container under the action of gravity. If a stirring structure is used for stirring, if the stirring force is strong, although the carrier can be scattered in the liquid, which can make the cells fully absorb the basic nutrient solution, there is also a risk that the cells will easily fall off the carrier. After a period of culture, cell fragments will accumulate and adhere to the bottom of the container, resulting in poor container permeability, resulting in poor liquid circulation, and the problem of high cell mortality. If the stirring force is too weak, the carrier accumulation situation cannot be changed, and some carriers will still not be able to fully contact the liquid, which will also lead to high cell mortality. The present application adopts a method of arranging carriers in layers with multiple culture baskets 3, placing the carriers in different culture baskets 3 respectively, reducing the degree of cell accumulation in the culture baskets 3. Under the cooperation of the stirring device 7, the carriers in each culture basket 3 can fully contact the liquid without excessive liquid circulation speed, which improves the problem of liquid flow damaging the cells, and ultimately improves the adverse effects of virus culture on virus yield and subsequent purification efficiency.

[0032] 3. By setting up the controller 4, the material inlet and outlet channels of the controller 4 can be connected to the source or container of the material, and then the material inlet and outlet can be controlled according to the preset instructions through the material inlet and outlet. The detection probe can collect the reaction data inside the reactor 2. By connecting the controller 4 and the detection probe, the reaction data inside the reactor 2 can be summarized, and the reaction state can be monitored in real time. The control of the reaction process is more intelligent and the reaction efficiency is significantly improved. In addition, since the material inlet and outlet channels are set up in the controller 4, the material inlet and outlet channels are neatly arranged, which is more convenient to connect with each pipeline, avoiding the entanglement between the pipelines affecting the smoothness of material flow.

[0033] 4. By connecting controller 4 to mobile vehicle 1, controller 4 can be pre-loaded with plant map data and pre-plan a movement path based on this map data. Controller 4 can then control mobile vehicle 1 to move along the planned path to the next designated location. The movement of mobile vehicle 1 can drive the movement of reactor 2 and controller 4 as a whole. Alternatively, controller 4 can exchange data with a mobile terminal (such as a mobile phone), input commands to controller 4 through the mobile terminal, and controller 4 controls the movement of mobile vehicle 1 based on the input commands. This control can then be controlled remotely. The movement of mobile vehicle 1 enables automated control of system position movement, making it more convenient to use.

[0034] Overall, the rabies virus liquid preparation system of the present application optimizes the matching mode of the culture basket 3 and the stirring device 7, reduces the degree of cell death and the generation of fragments caused by carrier breakage, effectively improves the adverse effects of virus culture on virus yield and the subsequent purification efficiency; by setting the controller 4, the reaction efficiency is significantly improved, at the same time, by matching the controller 4 and the moving vehicle 1, the automatic control of the system position movement is realized, and the use convenience is stronger.

[0035] In some embodiments, referring to Figure 1 and Figure 2 , the upper part of the reactor 2 is provided with a temperature adjusting inlet 201, and the bottom part is provided with a temperature adjusting outlet 202, the controller 4 is provided with a temperature adjusting supply channel and a temperature adjusting discharge channel, the outlet of the temperature adjusting supply channel is communicated with the temperature adjusting inlet 201, the temperature adjusting discharge channel is communicated with the inlet of the temperature adjusting outlet 202, and the side wall of the reactor 2 has a temperature adjusting channel, and the temperature adjusting inlet 201 and the temperature adjusting outlet 202 are communicated with the temperature adjusting channel respectively. In this embodiment, the temperature adjusting channel is arranged on the side wall of the reactor 2, the temperature adjusting medium (such as water, steam, etc.) is introduced into the temperature adjusting channel through the temperature adjusting inlet 201, and the temperature adjusting medium plays a role of temperature adjustment and heat preservation during the reaction. After use, the temperature adjusting medium can be discharged through the temperature adjusting outlet 202. If the temperature adjusting medium is a liquid, it can be naturally discharged by gravity. If the temperature adjusting medium is a gas, it can be discharged by a gas pump. By arranging the temperature adjusting channel, the reaction temperature can be better adjusted to ensure the reaction efficiency.

[0036] Specifically, the temperature adjusting supply channel includes a hot water supply channel, a hot water recovery channel, a steam supply channel and a steam recovery channel, and the temperature adjusting inlet 201 is connected with the hot water supply channel and the steam supply channel through a manifold respectively, and the temperature adjusting discharge channel is connected with the hot water recovery channel and the steam recovery channel through a manifold respectively. It can be seen that the temperature adjusting medium is hot water or steam.

[0037] In some embodiments, referring to Figure 2 , the outer contour of the culture basket 3 is conformal with the inner cavity of the reactor 2, the culture basket 3 includes a basket body 310 and a basket cover 320 arranged on the top opening of the basket body 310, the middle part of the basket cover 320 is provided with a cover through hole 321, the middle part of the basket body 310 is provided with a channel partition plate 330 corresponding to the cover through hole 321, and the top and bottom of the channel partition plate 330 are penetrated, the cover through hole 321 and the channel partition plate 330 cooperate to form a stirring channel 301, wherein no opening is arranged on the partition plate, and the stirring channel 301 is isolated from the inner cavity of the basket body 310. The outer contour of the culture basket 3 is conformal with the inner cavity of the reactor 2, which can make the width of the interval channel 8 around the culture basket 3 uniform, thereby being conducive to the uniform flow of liquid; by arranging the channel partition plate 330, the blocking and guiding effects of the liquid flow caused by the stirring device 7 are achieved, and the liquid is prevented from flowing into the basket body 310 directly through the side wall of the stirring channel 301.

[0038] In some embodiments, referring to Figure 3 and Figure 4 , the top outer periphery of the basket body 310 is provided with at least three circumferential limiting arms 340, each of which is uniformly distributed along the circumference of the basket body 310 and has an outer end capable of abutting against the side wall of the inner cavity of the reactor 2 to limit the displacement of the basket body 310 in the circumferential direction. In this embodiment, each circumferential limiting arm 340 has a circumferential limiting fulcrum. By providing at least three circumferential limiting fulcrums, if the lengths of the circumferential limiting arms 340 are consistent, the basket body 310 can be positioned at the central position of the reactor 2, ensuring that the culture basket 3 is coaxially arranged with the reactor 2.

[0039] In some more specific embodiments, referring to Figure 5 , the circumferential limiting arm 340 includes a guide rod 341, a support arm 342, and an elastic member 343. The guide rod 341 is fixed to the outer periphery of the basket body 310. The support arm 342 is sleeved outside the guide rod 341 and can slide in the radial direction of the basket body 310. The elastic member 343 is arranged between the basket body 310 and the support arm 342 and is configured to have a pre-tightening force that pushes the support arm 342 away from the basket body 310. By providing the guide rod 341, the support arm 342, and the elastic member 343, the support arm 342 of some of the circumferential limiting arms 340 can be allowed to move in and out when the culture basket 3 is placed, reducing the difficulty of placement. When the culture basket 3 is placed flat, the elastic member 343 of each circumferential limiting arm 340 spontaneously expands and contracts. Ultimately, the basket body 310 is pushed to a position coaxial with the reactor 2, and the compression degree of the elastic member 343 in each circumferential limiting arm 340 is the same, i.e., the extension length of each circumferential limiting arm 340 is the same.

[0040] Optionally, the support arm 342 is conical, the guide rod 341 has an inner rod segment and an outer rod segment connected to the outer segment of the inner rod segment, the outer rod segment is a conical rod that is shaped in accordance with the support arm 342, the inner end of the inner rod segment is connected to the basket body 310, and the inner rod segment is a straight rod with a constant outer diameter; the elastic member 343 is sleeved around the outer periphery of the inner rod segment, one end of the elastic member 343 is connected to the basket body 310, and the other end is connected to the end of the support arm 342. Specifically, the implementation of the elastic member 343 includes but is not limited to a rubber sleeve, a spring, etc. Specifically, the outer end of the support arm 342 is spherical, which abuts against the inner wall of the reactor 2 to avoid scratching the inner wall of the reactor 2.

[0041] In some more specific embodiments, referring to Figure 3 , Figure 4 and Figure 8The bottom outer periphery of the basket body 310 is provided with at least three feet 350, each of which is uniformly distributed along the circumference of the basket body 310 and is inclined in a direction gradually away from the center line of the basket body 310 in the direction from top to bottom; the side wall of the reactor 2 is provided with at least three supporting bosses 9, each of which is arranged at intervals along the circumference of the inner cavity of the reactor 2, and a clearance passage 10 for the circumferential limiting arm 340 and the foot 350 to pass through is formed between two adjacent supporting bosses 9, and the supporting bosses 9 at the same level form a placement position at this height. Among them, in order to ensure uniform stress, the supporting boss 9 corresponds to the foot 350 one by one, the circumferential limiting arm 340 corresponds to the foot 350 one by one, and the circumferential limiting arm 340 and the corresponding foot 350 are vertically aligned; in addition, the supporting bosses 9 at each level are vertically aligned, and the clearance passages 10 at each level are vertically aligned. In the normal use state, each foot 350 is placed on the corresponding supporting boss 9; when the culture basket 3 needs to be taken out, the culture basket 3 on the uppermost placement position can be directly pulled up and taken out, and the culture basket 3 on the lower layer needs to be rotated by an angle so that the circumferential limiting arm 340 and the foot 350 thereof correspond to the clearance passage 10, and then pulled up and taken out; when the culture basket 3 needs to be placed, the circumferential limiting arm 340 and the foot 350 on the culture basket 3 correspond to the clearance passage 10, and then the culture basket 3 is lowered, and after the height is appropriate, the culture basket 3 is rotated and moved by an angle, so that the foot 350 contacts the corresponding supporting boss 9, and the culture basket 3 on the uppermost layer is lowered after the foot 350 corresponds to the supporting boss 9. The placement position structure of the embodiment is simple, not only can effectively support the culture basket 3, but also the placement and taking out of the culture basket 3 are relatively simple, and the use convenience is good.

[0042] On the basis of the above-mentioned embodiments, referring to Figure 4 The basket cover 320 is hinged to the basket body 310, and the basket cover 320 and the basket body 310 are not completely separated, so as to avoid the problems of loss and damage after the basket cover 320 is opened.

[0043] In some embodiments, referring to Figure 6The stirring device 7 comprises a stirring driver 710 and a plurality of stirring units 720 arranged in sequence from top to bottom, the stirring driver 710 is fixed above the reactor 2, and each stirring unit 720 can penetrate the stirring channel 301 in the corresponding culture basket 3. Each stirring unit 720 comprises a stirring shaft 721 and a plurality of stirring blades 722 distributed around the stirring shaft 721; the upper end of the stirring shaft 721 is provided with a first connecting piece 723, and the lower end is provided with a second connecting piece 724, the first connecting piece 723 is detachably connected with the output shaft of the stirring driver 710 or the second connecting piece 724 at the upper and lower ends of the adjacent stirring shaft 721. The output shaft of the stirring driver 710 is also provided with a second connecting piece 724. In the embodiment, the stirring units 720 are spliced and assembled, the number of stirring units 720 can be selected according to actual use requirements, and the use flexibility is high. For example, the height of the stirring unit 720 is substantially the same as that of the culture basket 3, the stirring unit 720 corresponds to the culture basket 3 one by one, and the number of stirring units 720 can be selectively set according to the number of culture baskets 3.

[0044] The stirring blade 722 is a guide vane, which mainly guides the liquid to flow along the expected path. According to specific application requirements, the direction in which the liquid needs to flow is determined, and the angle and shape of the vane are set to achieve the guidance of the fluid. The specific design of the guide vane can refer to the existing vane design, which can achieve the above-mentioned guide function, and will not be described in detail here.

[0045] Optionally, the stirring driver 710 can adopt a servo motor, which has the characteristics of maintenance-free, high precision, no noise, stable control, long service life and the like.

[0046] In some embodiments, the first connecting piece 723 and the second connecting piece 724 are both shaft flanges, the output shaft of the stirring driver 710 is also provided with a shaft flange, and the adjacent two stirring shafts 721 and the output shaft of the stirring driver 710 and the adjacent stirring shaft 721 are connected through the flange structure, the connection structure is simple, the connection strength is high, and the connection failure between the first connecting piece 723 and the second connecting piece 724 during stirring can be avoided.

[0047] In some embodiments, the stirring shaft 721 can also be connected with the output shaft of the stirring driver 710 through a shaft coupling, and a magnetic fluid seal is adopted between the shaft coupling and the top cover 220, so that the area is zero leakage, and the maintenance cost is also reduced.

[0048] In some embodiments, referring to Figure 1 , Figure 2 and Figure 7The reactor 2 comprises a main tank body 210 and a top cover 220, the top cover 220 and the main tank body 210 are connected through a flange structure; the material inlet and outlet and the detection probe are arranged on the top cover 220. The detection probe comprises a dissolved oxygen concentration detection probe 11, an acid-base value detection probe 12, a sugar content detection probe 13, a temperature detection probe 14 and an osmotic pressure detection probe 15 which are distributed around the central axis of the top cover 220; the material inlet and outlet comprise a plurality of steam outlets 16, liquid inlets 17, liquid outlets 18, oxygen inlets 19, nitrogen inlets 20, carbon dioxide inlets 21, air inlets 22, pure steam inlets 23 and sodium bicarbonate solution inlets 24 which are distributed around the central axis of the top cover 220; and the top cover 220 is further provided with a breathing port 25.

[0049] In the embodiment, the dissolved oxygen concentration detection is mainly used to determine whether the cell living environment is suitable, because the cell usually needs oxygen for respiration and metabolism. Different viruses have different tolerance ranges of acid-base value, so the acid-base value (pH value) detection is needed. The sugar content needs to be monitored in the virus culture process to avoid the destruction of the cell structure caused by the high sugar content. The temperature and the osmotic pressure are also parameters that need to be monitored in the virus multiplication process, and the suitable temperature and osmotic pressure can ensure the effective multiplication of the virus and avoid the destruction of the cell structure. Among them, each detection probe is inserted into the liquid to detect the acid-base value, the sugar content, the temperature and the like of the liquid.

[0050] In the embodiment, the liquid inlets 17 and the liquid outlets 18 are used to pass in and out the virus culture liquid; the pure steam inlets 23 can pass in the pure steam to clean the reactor 2, and the steam after cleaning is discharged through the steam outlets 16; the oxygen inlets 19, the nitrogen inlets 20, the carbon dioxide inlets 21, the air inlets 22 and the sodium bicarbonate solution inlets 24 respectively pass in the oxygen, the nitrogen, the carbon dioxide, the air and the sodium bicarbonate solution according to the reaction requirements.

[0051] Optionally, the edge of the upper end of the main tank body 210 is provided with a tank flange 211, the edge of the top cover 220 is provided with a cover flange 221, the tank flange 211 and the cover flange 221 are connected through a threaded connecting piece, and then the assembly of the top cover 220 and the main tank body 210 is realized.

[0052] Optionally, the dissolved oxygen concentration detection probe 11, the acid-base value detection probe 12, the sugar content detection probe 13, the temperature detection probe 14 and the osmotic pressure detection probe 15 can all adopt the existing probes, which can meet the testing requirements, and are not limited to this. For example, the dissolved oxygen concentration detection probe 11 can adopt an optical probe, the acid-base value detection probe 12 can adopt an intelligent probe, and the like.

[0053] In some embodiments, referring to Figure 9 and Figure 10The controller 4 is provided with a dissolved oxygen concentration detection port 26, a pH value detection port 27, a sugar content detection port 28, a temperature detection port 29 and an osmotic pressure detection port 30 on the side facing the reactor 2, and is also provided with an oxygen output port 31, a nitrogen output port 32, a carbon dioxide output port 33, an air output port 34, a driver power signal port 35, a pure steam outlet 36, a hot water outlet 37, a hot water return port 38, a pure steam return port 39 and a sodium bicarbonate solution inlet 24. The front side of the controller 4 is provided with a display screen 40 and a power switch 41, and is also provided with an inlet liquid pump 42, an outlet liquid pump 43, a sodium bicarbonate solution pump 44 and a standby pump 45. The side of the controller 4 facing away from the reactor 2 is provided with an oxygen input port 46, a nitrogen input port 47, a carbon dioxide input port 48, an air input port 49, a pure steam input port 50, a hot water inlet 51, a pure steam discharge port 52, a hot water recovery port 53, a sodium bicarbonate solution outlet and a power supply interface 54.

[0054] The dissolved oxygen concentration detection port 26 is electrically connected to the dissolved oxygen concentration detection probe 11, the pH value detection port 27 is electrically connected to the pH value detection probe 12, the sugar content detection port 28 is electrically connected to the sugar content detection probe 13, the temperature detection port 29 is electrically connected to the temperature detection probe 14, and the osmotic pressure detection port 30 is electrically connected to the osmotic pressure detection probe 15. The oxygen output port 31 and the oxygen input port 46 form an oxygen conveying channel, the nitrogen output port 32 and the nitrogen input port 47 form a nitrogen conveying channel, the carbon dioxide input port 48 and the carbon dioxide output port 33 form a carbon dioxide conveying channel, the air output port 34 and the air input port 49 form an air conveying channel, the pure steam outlet 36 and the pure steam input port 50 form a pure steam conveying channel, the pure steam return port 39 and the pure steam discharge port 52 form a pure steam discharge channel, and the sodium bicarbonate solution inlet 24 and the sodium bicarbonate solution outlet form a sodium bicarbonate solution conveying channel; the above-mentioned oxygen conveying channel, nitrogen conveying channel, carbon dioxide conveying channel, air conveying channel, sodium bicarbonate solution conveying channel, pure steam conveying channel and pure steam discharge channel are all material inlet and outlet channels.

[0055] In addition, the steam discharge port 16 is connected to the pure steam return port 39, the pure steam inlet 23 is connected to the pure steam outlet 36, the oxygen inlet 19 is connected to the oxygen output port 31, the nitrogen inlet 20 is connected to the nitrogen output port 32, the carbon dioxide inlet 21 is connected to the carbon dioxide output port 33, and the air inlet 22 is connected to the air output port 34.

[0056] The hot water outlet 37 and the hot water inlet 51 form a hot water supply channel, the hot water return 38 and the hot water return inlet 53 form a hot water discharge channel, and the hot water supply channel and the hot water discharge channel are both temperature adjustment supply channels. In addition, the pure steam not only plays a role in cleaning the reactor 2, but also can be used as a temperature adjustment medium, that is, the pure steam delivery channel and the pure steam discharge channel can also be used as temperature adjustment supply channels.

[0057] In addition, the hot water outlet 37 is connected with the temperature adjustment inlet 201, and the pure steam outlet 36 is also connected with the temperature adjustment inlet 201.

[0058] In some embodiments, a power pump can be integrated in the material inlet and outlet channel in the controller 4, which can provide power when supplying or discharging liquid. Specifically, the sodium bicarbonate solution pump 44 is arranged on the sodium bicarbonate solution delivery channel, the inlet pump 42 is arranged on the hot water supply channel, the outlet pump 43 is arranged on the hot water discharge channel, and the standby pump 45 is used to replace the inlet pump 42, the outlet pump 43 and the sodium bicarbonate solution pump 44 when they are damaged.

[0059] Based on the above embodiments, referring to Figure 2 , a sandwich cavity 230 is arranged in the side wall of the main tank body 210, and the sandwich cavity 230 is a temperature adjustment channel. The sandwich cavity 230 has a large inner cavity space and a large distribution area, which is conducive to uniform temperature adjustment and effective heat preservation.

[0060] In some embodiments, referring to Figure 7 , in order to fully utilize the space on the top cover 220, the stirring device 7 includes a stirring driver 710 and a plurality of stirring units 720 arranged sequentially from top to bottom, the stirring driver 710 is fixed above the reactor 2, each stirring unit 720 can penetrate the stirring channel 301 in the corresponding culture basket 3, and the stirring driver 710 is arranged at the center position of the top cover 220.

[0061] In some embodiments, the top cover 220 is provided with mounting circular platforms, the dissolved oxygen concentration detection probe 11, the pH value detection probe 12, the sugar content detection probe 13, the temperature detection probe 14 and the osmotic pressure detection probe 15 respectively penetrate the corresponding mounting circular platforms, and are connected and sealed with the corresponding mounting circular platforms by means of threaded connection or the like.

[0062] In some embodiments, referring to Figure 1 , the side wall of the main tank body 210 is provided with an observation window 240, and the observation window 240 extends vertically to facilitate observation of the reaction conditions in different height regions of the main tank body 210.

[0063] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Any modifications, equivalent replacements and improvements made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A rabies virus liquid preparation system, characterized in that: include: Mobile vehicle (1); A reactor (2) is provided on the mobile vehicle (1); the inner cavity of the reactor (2) is provided with at least two placement positions distributed sequentially from top to bottom; the top of the reactor (2) is provided with a material inlet and outlet and a detection probe; and a stirring device (7) is provided inside the reactor (2); A culture basket (3) is provided at the corresponding placement position in the reactor (2) and is used to hold the carrier. A stirring channel (301) is provided in the middle of the culture basket (3) for the stirring device (7) to pass through. The culture basket (3) is a closed structure, and through holes (302) are provided on the top, bottom and circumferential surfaces of the culture basket (3). A spacing channel (8) is formed between the outer peripheral surface of the culture basket (3) and the side wall of the reactor (2); A controller (4) is provided on the mobile vehicle (1), and the controller (4) is respectively connected to the mobile vehicle (1), the detection probe and the stirring device (7). The controller (4) also has a material inlet and outlet channel, and the material inlet and outlet channel is correspondingly connected to the material inlet and outlet.

2. The rabies virus liquid preparation system according to claim 1, characterized in that: The reactor (2) is provided with a temperature adjustment inlet (201) at the top and a temperature adjustment outlet (202) at the bottom. The controller (4) is provided with a temperature adjustment supply channel and a temperature adjustment discharge channel. The outlet of the temperature adjustment supply channel is connected to the temperature adjustment inlet (201), and the temperature adjustment discharge channel is connected to the inlet of the temperature adjustment outlet (202). The side wall of the reactor (2) has a temperature adjustment channel. The temperature adjustment inlet (201) and the temperature adjustment outlet (202) are respectively connected to the temperature adjustment channel.

3. The rabies virus liquid preparation system according to claim 1, characterized in that: The outer contour of the culture basket (3) is arranged in a conformal manner with the inner cavity of the reactor (2). The culture basket (3) comprises a basket body (310) and a basket cover (320) arranged at the top opening of the basket body (310). A cover through-hole (321) is provided in the middle of the basket cover (320). A channel partition (330) corresponding to the cover through-hole (321) is provided in the middle of the basket body (310), and the top and bottom of the channel partition (330) are both through-connected. The cover through-hole (321) and the channel partition (330) cooperate to form the stirring channel (301).

4. The rabies virus liquid preparation system according to claim 3, characterized in that: At least three circumferential limiting arms (340) are provided on the outer periphery of the top of the basket body (310), and each of the circumferential limiting arms (340) is evenly distributed along the circumference of the basket body (310), and the outer ends of the circumferential limiting arms (340) can abut against the side wall of the inner cavity of the reactor (2) to limit the displacement of the basket body (310) in the circumferential direction of the basket body (310).

5. The rabies virus liquid preparation system according to claim 4, characterized in that: At least three supporting legs (350) are provided on the outer periphery of the bottom of the basket body (310), and the supporting legs (350) are evenly distributed along the circumference of the basket body (310). From top to bottom, the supporting legs (350) are inclined in a direction gradually away from the center line of the basket body (310); The side wall of the reactor (2) is provided with at least three supporting bosses (9), each of the supporting bosses (9) is arranged at intervals along the circumference of the inner cavity of the reactor (2), and an avoidance channel (10) for the circumferential limiting support arm (340) and the support foot (350) to pass through is formed between two adjacent supporting bosses (9).

6. The rabies virus liquid preparation system according to claim 3, characterized in that: The basket cover (320) is hinged to the basket body (310).

7. The rabies virus liquid preparation system according to claim 1, characterized in that: The stirring device (7) comprises a stirring driver (710) and a plurality of stirring units (720) arranged in sequence from top to bottom, wherein the stirring driver (710) is fixed above the reactor (2), and each stirring unit (720) can pass through a stirring channel (301) in the corresponding culture basket (3); Each stirring unit (720) comprises a stirring shaft (721) and a plurality of stirring blades (722), wherein the plurality of stirring blades (722) are distributed around the stirring shaft (721); a first connecting member (723) is provided at the upper end of the stirring shaft (721), and a second connecting member (724) is provided at the lower end thereof; the first connecting member (723) can be detachably connected to the output shaft of the stirring driver (710) or the second connecting member (724) adjacent to the upper and lower ends of the stirring shaft (721).

8. The rabies virus liquid preparation system according to claim 2, characterized in that: The reactor (2) comprises a main tank body (210) and a top cover (220), wherein the top cover (220) and the main tank body (210) are connected via a flange structure; the material inlet and outlet and the detection probe are both arranged on the top cover (220), wherein the detection probe comprises a dissolved oxygen concentration detection probe (11), a pH detection probe (12), a sugar content detection probe (13), a temperature detection probe (14) and an osmotic pressure detection probe (15) distributed around the central axis of the top cover (220); the material inlet and outlet comprise a plurality of steam exhaust ports (16), liquid inlets (17), liquid outlets (18), oxygen inlets (19), nitrogen inlets (20), carbon dioxide inlets (21), air inlets (22), pure steam inlets (23) and sodium bicarbonate solution inlets (24) distributed around the central axis of the top cover (220); and the top cover (220) is further provided with a breathing port (25).

9. The rabies virus liquid preparation system according to claim 8, characterized in that: An interlayer cavity (230) is provided in the side wall of the main tank body (210), and the interlayer cavity (230) serves as the temperature adjustment channel.

10. The rabies virus liquid preparation system according to claim 8, characterized in that: The stirring device (7) includes a stirring driver (710) and a plurality of stirring units (720) arranged in sequence from top to bottom. The stirring driver (710) is fixed above the reactor (2). Each stirring unit (720) can pass through the stirring channel (301) in the corresponding culture basket (3). The stirring driver (710) is arranged at the center of the top cover (220).

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