Microcarrier bioreactor aeration device and biological reaction equipment

Abstract

The utility model relates to the field of biopharmacy, and provides a microcarrier bioreactor aeration device and biological reaction equipment, the microcarrier bioreactor aeration device comprises: a shunting mechanism, which is provided with a shunting inlet and a plurality of shunting outlets that are communicated with each other, the shunting inlet is communicated with gas storage equipment; one end of each air inlet mechanism is communicated with the corresponding flow dividing outlet through the corresponding flow meter, and the other end of each air inlet mechanism is used for being arranged at different positions in the bioreactor. According to the micro-carrier bioreactor ventilation device provided by the utility model, the flow dividing mechanism is arranged and is matched with the plurality of flow meters and the gas inlet mechanism, so that accurate flow dividing and flow adjustment of gas in the gas storage equipment are realized. According to the device, gas can be conveyed to different positions in the bioreactor at different flows according to the requirements of cells at different positions on oxygen, so that the dissolution efficiency of oxygen in the bioreactor is effectively improved.

Description

TECHNICAL FIELD

[0001] The utility model relates to the field of biopharmacy, especially to a microcarrier bioreactor ventilation device and a biological reaction equipment. BACKGROUND

[0002] Large-scale animal cell suspension culture technology is widely used in the field of biopharmacy, when the cells in the microcarrier bioreactor are expanded to a certain density, it is difficult to maintain the process setting parameters for the oxygen dissolution in the reactor. In the past, on the basis of fixed ventilation equipment, the dissolved oxygen value is maintained by increasing the oxygen ventilation amount or increasing the stirring speed. At this time, some problems will appear: increasing the stirring speed will have an impact on the mechanical shear force of the cells in the culture, which is not conducive to the growth of the cells. A large amount of oxygen enters the tank in a short time when the oxygen ventilation amount is increased, which can make the microbubbles generated by the gas distributor quickly aggregate together to form foam. The surface tension of the foam will directly cause harm to the cells in the suspension culture. At the same time, the accumulated foam may also cause the blockage of the exhaust device of the bioreactor, causing the pressure in the tank to increase, which is dangerous. SUMMARY

[0003] The utility model provides a microcarrier bioreactor ventilation device and a biological reaction equipment to solve the problem of foam aggregation caused by the increase of the ventilation amount in the prior art.

[0004] The utility model provides a microcarrier bioreactor ventilation device, which comprises:

[0005] A shunt mechanism is provided with a shunt inlet and a plurality of shunt outlets that are in communication with each other, and the shunt inlet is in communication with a gas storage device;

[0006] A plurality of flow meters and a plurality of air inlet mechanisms are provided, one end of each air inlet mechanism is in communication with a corresponding shunt outlet through a corresponding flow meter, and the other end of each air inlet mechanism is arranged at different positions in the bioreactor, so that the gas in the gas storage device is ventilated to different positions in the bioreactor after being adjusted in flow by the shunt mechanism.

[0007] According to the microcarrier bioreactor ventilation device provided by the utility model, the microcarrier bioreactor ventilation device further comprises:

[0008] A screen is arranged in the bioreactor to form a gas exchange cavity, and the other end of the air inlet mechanism is arranged in the gas exchange cavity.

[0009] According to the microcarrier bioreactor ventilation device provided by the utility model, a plurality of screens are provided, each screen is arranged at a different position in the bioreactor, and the other end of each air inlet mechanism is arranged in the gas exchange cavity of a different screen.

[0010] The micro-carrier bioreactor ventilation device further comprises:

[0011] A plurality of liquid changing mechanisms, one end of each of the liquid changing mechanisms is arranged in different air exchange cavities, and the other end of each of the liquid changing mechanisms is arranged outside the bioreactor.

[0012] The liquid changing mechanism comprises a liquid discharge pipe and a first hose which are in communication with each other.

[0013] One end of the liquid discharge pipe, which is away from the first hose, is arranged in the air exchange cavity corresponding to the screen, a pipe clamp for controlling opening and closing of the first hose is arranged on the first hose, and the other end of the first hose, which is away from the liquid discharge pipe, is arranged outside the bioreactor.

[0014] The liquid changing mechanism further comprises a first connector and a first filter element, and the other end of the first hose, which is away from the liquid discharge pipe, is connected to the first filter element through the first connector.

[0015] The shunt mechanism comprises a tee pipe, the tee pipe is provided with the shunt inlet and two shunt outlets, the air inlet mechanism comprises a first air inlet mechanism and a second air inlet mechanism, and the flow meter comprises a first flow meter and a second flow meter.

[0016] One end of the first air inlet mechanism is in communication with one of the shunt outlets through the first flow meter, and one end of the second air inlet mechanism is in communication with the other shunt outlet through the second flow meter.

[0017] The air inlet mechanism comprises:

[0018] The air inlet mechanism comprises an air inlet pipe and a gas distributor, one end of the air inlet pipe is in communication with one of the shunt outlets through the corresponding flow meter, the other end of the air inlet pipe is in communication with the gas distributor, and the gas distributor is arranged in the bioreactor.

[0019] The air inlet mechanism further comprises a second hose and a second filter element.

[0020] The second hose and the second filter element are connected between the air inlet pipe and the corresponding flow meter.

[0021] The utility model also provides a kind of biological reaction equipment, comprising:

[0022] Bioreactor and the microcarrier bioreactor ventilation device of above-mentioned, the microcarrier bioreactor ventilation device is used to ventilate to different positions in the bioreactor;

[0023] Stirring device, drive end is arranged in the bioreactor, for stirring liquid and microcarrier in the bioreactor.

[0024] The microcarrier bioreactor ventilation device and biological reaction equipment provided by the utility model realize accurate shunting and flow regulation of gas in gas storage equipment by setting shunt mechanism, cooperating with multiple flow meters and air inlet mechanism.The device can deliver gas to different positions in the bioreactor at different flow rates according to the oxygen demand of cells at different positions, thereby effectively improving the oxygen dissolution efficiency in the reactor.More importantly, by accurately controlling the ventilation amount of each air inlet mechanism, the problem of rapid aggregation of foam caused by increasing oxygen ventilation amount in traditional methods is avoided, the damage of foam to suspension culture cells is reduced, the risk of biological reactor exhaust device blockage is also reduced, and stable operation of the bioreactor is ensured. BRIEF DESCRIPTION OF DRAWINGS

[0025] In order to more clearly illustrate the technical scheme of the utility model or prior art, the following will be a brief introduction to the drawings needed to be used in embodiment or prior art description, obviously, the drawings in the following description are some embodiments of the utility model, for those skilled in the art, without creative labor, other drawings can also be obtained according to these drawings.

[0026] Figure 1 It is the structure schematic view of biological reaction equipment provided by the utility model.

[0027] Reference signs:

[0028] 10, shunt mechanism;20, flow meter;30, air inlet mechanism;310, air inlet pipe;320, gas distributor;330, second hose;340, second filter element;40, bioreactor;50, stirring device;60, screen;70, liquid replacement mechanism;710, liquid discharge pipe;720, first hose;730, first joint;740, first filter element;750, pipe clamp. DETAILED DESCRIPTION

[0029] In order to make the purpose, technical scheme and advantages of the utility model clearer, the technical scheme of the utility model will be described clearly and completely in combination with the drawings in the utility model below. Obviously, the described embodiments are part of the embodiments of the utility model, rather than all the embodiments. Based on the embodiments in the utility model, all other embodiments obtained by the ordinary skilled in the art without creative labor belong to the protection scope of the utility model.

[0030] The utility model discloses a microcarrier bioreactor ventilation device and a bioreaction equipment, which are suitable for the regulation and control of various gases such as oxygen, carbon dioxide, clean compressed air, nitrogen and mixed gas, improve the dissolved oxygen value by using oxygen, reduce the pH value by using carbon dioxide, and achieve the requirements by using clean compressed air for trace adjustment of dissolved oxygen, and use nitrogen to reduce the dissolved oxygen value. Figure 1 The microcarrier bioreactor ventilation device and the bioreaction equipment can effectively solve the problem of foam aggregation caused by the increase of ventilation volume without adjusting the stirring speed.

[0031] In an embodiment provided in the application, as shown in the drawings, Figure 1 The microcarrier bioreactor ventilation device comprises a shunt mechanism 10, a plurality of flow meters 20 and a plurality of air inlet mechanisms 30. The shunt mechanism 10 is provided with a shunt inlet and a plurality of shunt outlets that are in communication with each other, and the shunt inlet is in communication with a gas storage equipment. One end of each air inlet mechanism 30 is in communication with a corresponding shunt outlet through a corresponding flow meter 20, and the other end of each air inlet mechanism 30 is used to be arranged at different positions in a bioreactor 40, so that the gas in the gas storage equipment is ventilated to different positions in the bioreactor 40 after the flow is adjusted by the different flow meters 20.

[0032] In the embodiment, the shunt mechanism 10 serves as a preliminary distribution point of the gas, ensuring that the gas can be evenly or on-demand distributed to the plurality of shunt outlets. The shunt mechanism 10 has one shunt inlet and a plurality of shunt outlets, and the shunt outlets are connected with different flow meters 20 and air inlet mechanisms 30. The shunt inlet is directly in communication with the gas storage equipment, ensuring that the gas can smoothly enter the shunt mechanism 10. Each flow meter 20 corresponds to one shunt outlet and one air inlet mechanism 30. By adjusting the set value of the flow meter 20, the flow of the gas entering different positions in the bioreactor 40 can be accurately controlled. The air inlet mechanism 30 delivers the gas from the flow meter 20 to the specified position in the bioreactor 40. The air inlet mechanism 30 is matched with the flow meter 20 in number, ensuring that each position can be properly supplied with gas. The other end (i.e., the gas outlet) of the air inlet mechanism 30 is arranged at different positions in the bioreactor 40 to meet specific ventilation requirements.

[0033] During operation, gas from the storage device enters the distribution mechanism 10 through the distribution inlet. The distribution mechanism 10 distributes the gas to multiple distribution outlets. The gas flow at each distribution outlet is measured and controlled by a corresponding flow meter 20. The flow meter 20 adjusts the gas flow rate according to a preset flow rate value (generally, the flow rate settings for each flow meter 20 should be kept as consistent as possible). After adjustment by the flow meter 20, the gas is delivered to different locations within the bioreactor 40 through the air intake mechanism 30. The air intake mechanism 30 ensures that the gas accurately reaches the designated aeration point.

[0034] The microcarrier bioreactor aeration device provided in this embodiment of the invention, through the setting of a diversion mechanism 10, in conjunction with multiple flow meters 20 and an air inlet mechanism 30, achieves precise diversion and flow regulation of gas in the gas storage device. This device can deliver gas at different flow rates to different locations within the bioreactor 40 according to the oxygen requirements of cells at different locations, thereby effectively improving the oxygen dissolution efficiency in the reactor. More importantly, by precisely controlling the aeration rate of each air inlet mechanism 30, the rapid foam aggregation problem caused by increasing the oxygen aeration rate in traditional methods is avoided, reducing the damage of foam to suspended cultured cells, and also reducing the risk of blockage of the exhaust device of the bioreactor 40, ensuring the stable operation of the bioreactor 40.

[0035] In some embodiments, such as Figure 1 As shown, the microcarrier bioreactor aeration device also includes: a screen 60, which is set inside the bioreactor 40 to form an air exchange chamber, and the other end of the air inlet mechanism 30 is set in the air exchange chamber.

[0036] In this embodiment, a sieve 60 is disposed within the bioreactor 40. Its main function is to provide a dispersion and buffering area for the gas, while preventing bubbles from directly impacting the cells on the microcarriers. The sieve 60 typically has a porous structure, with pores that allow gas to pass through but block larger bubbles or droplets. The other end of the gas inlet mechanism 30 (i.e., the gas outlet) is disposed within the ventilation chamber formed by the sieve 60. In this way, the gas is dispersed into smaller bubbles as it passes through the sieve 60, thereby reducing the impact on the cells.

[0037] When gas enters the ventilation chamber from the inlet mechanism 30, it first encounters the obstruction of the screen 60. The porous structure of the screen 60 forces the gas to disperse into smaller bubbles, which then pass through the screen 60 into the main body of the bioreactor 40. The screen 60 not only disperses the bubbles but also provides a buffer zone, allowing the bubbles time to reduce their velocity and size before reaching the microcarriers. This reduces the direct impact and potential damage of the bubbles on the cells. Through the filtration and dispersion effect of the screen 60, the bubbles become smaller and more evenly distributed, thereby reducing the risk of damage to the cells on the microcarriers.

[0038] Generally, a plurality of screens 60 are provided, each screen 60 being arranged at different locations within the bioreactor 40 to meet the aeration requirements at different locations within the bioreactor 40 to ensure that the gas is evenly and effectively distributed throughout the reactor. The other end of each gas inlet mechanism 30 is arranged within the gas exchange chamber of a different screen 60. That is, the other end (i.e. the gas outlet) of each gas inlet mechanism 30 is arranged within the gas exchange chamber of the screen 60 associated with it. In this way, each gas inlet mechanism 30 is able to disperse and buffer the gas it carries through the screen 60. The matching design of the gas inlet mechanism 30 and the screen 60 ensures that each aeration point is provided with adequate gas supply and the gas is distributed onto the microcarriers with minimal impact and maximum uniformity.

[0039] In some embodiments, as shown in Figure 1 The microcarrier bioreactor aeration device also comprises a plurality of liquid exchange mechanisms 70. One end of each liquid exchange mechanism 70 is arranged within a different gas exchange chamber and the other end of each liquid exchange mechanism 70 is arranged outside the bioreactor 40. The liquid exchange mechanisms 70 use the pressure difference created by the aeration of the gas inlet mechanisms 30 to drain the liquid from the bioreactor 40 to the sterile liquid collection bag.

[0040] In this embodiment, a plurality of liquid exchange mechanisms 70 are provided in the aeration device to meet the liquid drainage requirements at different regions within the bioreactor 40. One end of each liquid exchange mechanism 70 is arranged within the gas exchange chamber of a different screen 60, together with the corresponding gas inlet mechanism 30 in the same gas exchange chamber. The other end of each liquid exchange mechanism 70 is arranged outside the bioreactor 40, typically connected to a sterile liquid collection bag. The liquid exchange mechanisms 70 use the pressure difference created by the aeration of the gas inlet mechanisms 30 to drain the liquid from the bioreactor 40. By controlling the aeration rate of the gas inlet mechanisms 30 and the on / off state of the liquid exchange mechanisms 70, the liquid drainage process can be precisely controlled.

[0041] When the gas inlet mechanisms 30 aerate the gas exchange chambers of the screens 60, the gas pressure within the gas exchange chambers increases. Since one end of each liquid exchange mechanism 70 is arranged within the gas exchange chamber and the other end is connected to the outside of the bioreactor 40, a pressure difference is created. Using this pressure difference, the liquid within the bioreactor 40 is pushed through the liquid exchange mechanisms 70 to the sterile liquid collection bag. By precisely controlling the aeration rate of the gas inlet mechanisms 30 and the on time of the liquid exchange mechanisms 70, the liquid drainage rate and volume can be precisely controlled. The entire liquid drainage process is carried out under sterile conditions, ensuring the sterility of the environment within the bioreactor 40. The connection of the liquid exchange mechanisms 70 to the sterile liquid collection bag typically uses sterile connection techniques, avoiding external contamination.

[0042] As shown in Figure 1As shown, the liquid exchange mechanism 70 includes: a drain pipe 710 and a first hose 720 that are interconnected; one end of the drain pipe 710 away from the first hose 720 is disposed in the air exchange chamber of the corresponding screen 60, and the first hose 720 is provided with a pipe clamp 750 for controlling its opening and closing, and the one end of the first hose 720 away from the drain pipe 710 is disposed outside the bioreactor 40.

[0043] Specifically, one end of the drain pipe 710 is positioned in the ventilation chamber of the corresponding screen 60 to ensure contact with the liquid to be drained. The other end is connected to the first flexible hose 720, forming a continuous liquid channel. The drain pipe 710 is typically made of corrosion-resistant, high-temperature-resistant, and biocompatible materials to ensure good performance even in the harsh environment inside the bioreactor 40.

[0044] The first flexible tube 720 is typically made of silicone tubing. It serves as the connection between the drain pipe 710 and the outside of the bioreactor 40, responsible for transporting the discharged liquid to an external sterile collection bag. The first flexible tube 720 is equipped with a pipe clamp 750 for controlling its opening and closing. By operating the pipe clamp 750, the flow of liquid can be precisely controlled, achieving precise control of the discharge.

[0045] When drainage is required, first ensure that the air intake mechanism 30 is venting into the corresponding air exchange chamber of the screen 60 to generate a sufficient pressure difference. Then, open the pipe clamp 750 on the first hose 720, allowing the liquid to flow through the drain pipe 710 and the first hose 720 to the sterile collection bag under the pressure difference. By adjusting the air intake mechanism 30 and the opening degree of the pipe clamp 750 on the first hose 720, the drainage speed and volume can be precisely controlled to meet different experimental and production needs.

[0046] In some embodiments, such as Figure 1 As shown, the fluid exchange mechanism 70 also includes a first connector 730 and a first filter element 740; one end of the first hose 720 facing away from the drain pipe 710 is connected to the first filter element 740 via the first connector 730. The first connector 730 is a circular plastic connector (CPC). The first filter element 740 serves as a filtration component, primarily used to prevent external air from contaminating the fluid exchange mechanism 70.

[0047] In some embodiments, such as Figure 1As shown, the shunt mechanism 10 includes a tee pipe, which is provided with a shunt inlet and two shunt outlets. The intake mechanism 30 is provided with two, namely a first intake mechanism and a second intake mechanism. The flow meter 20 is provided with two, namely a first flow meter and a second flow meter. One end of the first intake mechanism is in communication with one of the shunt outlets through the first flow meter, and one end of the second intake mechanism is in communication with the other shunt outlet through the second flow meter.

[0048] Specifically, the tee pipe has one shunt inlet and two shunt outlets. It allows the intake source to be divided into two paths, respectively supplying different areas or components. The first intake mechanism and the second intake mechanism receive intake air through the first flow meter and the second flow meter, respectively, and adjust the intake air volume as needed.

[0049] Correspondingly, the screen 60 is also provided with two, namely a first screen and a second screen, and the liquid exchange mechanism 70 is also provided with two, namely a first liquid exchange mechanism and a second liquid exchange mechanism. The first screen and the second screen correspond to the first intake mechanism and the second intake mechanism, respectively, for forming different aeration chambers in the bioreactor 40. The design of the screen 60 can be optimized according to the type of cells and experimental requirements to ensure the best aeration effect. The first liquid exchange mechanism and the second liquid exchange mechanism correspond to the first screen and the second screen, respectively, and are responsible for discharging and replacing the liquid in the bioreactor 40 with new culture medium.

[0050] In some embodiments, as Figure 1 As shown, the intake mechanism 30 includes an intake pipe 310 and a gas distributor 320. One end of the intake pipe 310 is in communication with one of the shunt outlets through the corresponding flow meter 20, and the other end of the intake pipe 310 is in communication with the gas distributor 320, which is used to be arranged in the bioreactor 40.

[0051] In this embodiment, the gas distributor 320 is responsible for uniformly and effectively distributing the gas delivered by the intake pipe 310 to the cell culture area in the bioreactor 40. The design of the gas distributor 320 can include a plurality of small gas holes or nozzles to ensure uniform distribution of gas.

[0052] In operation, the external gas source enters through the intake pipe 310 and is adjusted in flow by the flow meter 20. The adjusted gas then enters the gas distributor 320 and is uniformly distributed through the small gas holes or nozzles thereon. In this way, the cells can obtain sufficient and uniform oxygen and nutrients, thereby maintaining the best growth state.

[0053] In addition, the air intake mechanism 30 also includes a second hose 330 and a second filter 340. The second hose 330 and the second filter 340 are connected between the air intake pipe 310 and the corresponding flow meter 20. The second hose 330 is generally made of silicone tube, which has good flexibility and corrosion resistance, and can maintain stable performance in the harsh environment inside the bioreactor 40. The second filter 340 is a hydrophobic filter, which can block water and other liquid impurities from entering the air intake system while allowing gas to pass through. The pore size of the second filter 340 is 0.2 μm, which can effectively block most microorganisms and particles, ensuring that the gas entering the bioreactor 40 is sterile and pure. The main function of the second filter 340 is to filter and purify the gas entering the bioreactor 40, preventing external pollution and impurities from negatively affecting cell culture.

[0054] In an embodiment of the present application, a bioreactor apparatus is provided, as shown in Figure 1 The bioreactor apparatus includes a bioreactor 40, a microcarrier bioreactor aeration device, and a stirring device 50. The microcarrier bioreactor aeration device is used to aerate different positions inside the bioreactor 40; the stirring device 50 is arranged at the driving end inside the bioreactor 40, and is used to stir the liquid and microcarriers inside the bioreactor 40.

[0055] In this embodiment, the shunt mechanism 10 serves as the primary distribution point for gas, ensuring that the gas can be evenly or on-demand distributed to multiple shunt outlets. The shunt mechanism 10 has one shunt inlet and multiple shunt outlets, which are connected to different flow meters 20 and air intake mechanisms 30. The shunt inlet is directly connected to the gas storage device, ensuring that the gas can smoothly enter the shunt mechanism 10. Each flow meter 20 corresponds to one shunt outlet and one air intake mechanism 30. By adjusting the set value of the flow meter 20, the gas flow into different positions inside the bioreactor 40 can be accurately controlled. The air intake mechanism 30 delivers gas from the flow meter 20 to the designated position inside the bioreactor 40. The air intake mechanism 30 is matched in number with the flow meter 20, ensuring that each position can be properly supplied with gas. The other end of the air intake mechanism 30 (i.e., the gas outlet) is arranged at different positions inside the bioreactor 40 to meet specific aeration needs.

[0056] During operation, gas from the gas storage device enters the shunt mechanism 10 through the shunt inlet. The shunt mechanism 10 distributes the gas to multiple shunt outlets. The gas from each shunt outlet is measured and controlled by a corresponding flow meter 20. The flow meter 20 adjusts the flow of gas according to a preset flow value (generally, each flow meter 20 is set to maintain a consistent flow). The gas adjusted by the flow meter 20 is delivered to different locations in the bioreactor 40 by the gas inlet mechanism 30. The gas inlet mechanism 30 ensures that the gas reaches the designated aeration point accurately. The stirring device 50 rotates or vibrates in the bioreactor 40 through its driving end, thereby driving the liquid and microcarriers to move together.

[0057] The bioreactor device provided by the embodiments of the present application realizes accurate shunting and flow adjustment of the gas in the gas storage device by setting the shunt mechanism 10 in cooperation with the multiple flow meters 20 and the gas inlet mechanism 30. The device can deliver gas to different locations in the bioreactor 40 at different flow rates according to the oxygen demand of cells at different locations, thereby effectively improving the oxygen dissolution efficiency in the reactor. More importantly, by accurately controlling the aeration amount of each gas inlet mechanism 30, the problem of rapid aggregation of foam caused by increasing the oxygen aeration amount in the traditional method is avoided, the damage of foam to the suspended culture cells is reduced, and the risk of blockage of the exhaust device of the bioreactor 40 is also reduced, ensuring the stable operation of the bioreactor 40.

[0058] It should be noted that, taking oxygen as an example, when the cell density in the bioreactor 40 grows to a certain extent, the oxygen aeration amount is increased, at which time the two float flow meters 20 that are increased are adjusted to the same gas flow to evenly distribute the total aeration flow. As the contact area between oxygen and the culture medium is increased, the oxygen dissolution rate in the culture solution is accelerated. The gas flow at each gas inlet pipe 310 is relatively low, which does not cause the generation of foam. At the same time, as the oxygen is better distributed and dissolved in the bioreactor 40, a higher oxygen flow that is required when single aeration pipe culture is set is not needed. The material cost is reduced. The drain pipe 710 is designed as two, which are distributed in the two screens 60. During the liquid exchange operation, the overall liquid exchange speed can be accelerated, and the two drain pipes 710 avoid the possibility that the outer wall of the single screen 60 is blocked by microspheres due to the fast flow speed during liquid exchange.

[0059] The utility model discloses a biological reactor 40 and microcarrier biological reactor ventilation device are carried out high pressure sterilization treatment in the specific implementation, first. Close pipeline clamp 750 after sterilization, connect first joint 730 with sterile liquid receiving bag in the sterile operation platform. Connect the second hose 330 of flowmeter 20 gas outlet end with second filter core 340. The design of second filter core 340 guarantees the sterile environment in biological reactor 40. In the cultivation process stage, control the gas intake and dissolved oxygen value of biological reactor 40 through the flow value of flowmeter 20 adjustment. The flow of two flowmeters 20 setting should keep consistent as far as possible. Mixed gas enters the reactor culture solution through air inlet pipe 310, gas distributor 320. Screen 60 can avoid the harm of bubble to the cell on microcarrier. Block microcarrier to enter the liquid discharge pipe 710 when liquid exchange, avoid the loss of cell. When biological reactor 40 needs to carry out liquid exchange operation, open pipeline clamp 750, through increasing the gas intake of mixed gas, utilize the pressure difference between biological reactor 40 and sterile liquid receiving bag and carry out liquid discharge.

[0060] Table 1 comparison of oxygen flow value required to maintain dissolved oxygen before and after improvement

[0061]

[0062] The experiment can obtain that under the condition of keeping same cell density (4x10^6 / ml), dissolved oxygen value (45%-55%) and reactor culture volume (10L), the oxygen flow required by the improved ventilation device reduces from 2L / min to 1.5L / min. This change shows that the improved device can utilize oxygen more effectively while providing the same dissolved oxygen level.

[0063] Finally, it should be noted that: the above examples are used to illustrate the technical solutions of the utility model, but not to limit them; although the utility model has been described in detail with reference to the foregoing examples, those skilled in the art should understand that: it still can modify the technical solutions recorded in the foregoing examples, or make equivalent replacement to part of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the utility model embodiments.

Claims

1. A microcarrier bioreactor aeration device, characterized in that, The microcarrier bioreactor aeration device comprises: a shunt mechanism (10) provided with a shunt inlet and a plurality of shunt outlets in communication with each other, the shunt inlet being in communication with a gas storage device; a plurality of flow meters (20) and a plurality of air inlet mechanisms (30), one end of each air inlet mechanism (30) being in communication with a corresponding shunt outlet through a corresponding flow meter (20), the other end of each air inlet mechanism (30) being arranged at different positions in a bioreactor (40) so that the gas in the gas storage device is aerated to different positions in the bioreactor (40) after being adjusted in flow by the different flow meters (20) through the shunt mechanism (10).

2. The microcarrier bioreactor aeration device of claim 1, wherein, The microcarrier bioreactor aeration device further comprises: a screen (60) arranged in the bioreactor (40) and formed with a gas exchange cavity, the other end of the air inlet mechanism (30) being arranged in the gas exchange cavity.

3. The microcarrier bioreactor aeration device of claim 2, wherein, There are a plurality of screens (60), each screen (60) being arranged at a different position in the bioreactor (40), and the other end of each air inlet mechanism (30) being arranged in the gas exchange cavity of a different screen (60).

4. The microcarrier bioreactor aeration device of claim 3, wherein, The microcarrier bioreactor aeration device further comprises: a plurality of liquid exchange mechanisms (70), one end of each liquid exchange mechanism (70) being arranged in a different gas exchange cavity, and the other end of each liquid exchange mechanism (70) being arranged outside the bioreactor (40).

5. The microcarrier bioreactor aeration device of claim 4, wherein, The liquid exchange mechanism (70) comprises a drain pipe (710) and a first hose (720) in communication with each other; one end of the drain pipe (710) facing away from the first hose (720) is arranged in the gas exchange cavity of a corresponding screen (60), a pipe clamp (750) for controlling the opening and closing of the first hose (720) is arranged on the first hose (720), and the other end of the first hose (720) facing away from the drain pipe (710) is arranged outside the bioreactor (40).

6. The microcarrier bioreactor aeration device of claim 5, wherein, The liquid exchange mechanism (70) further comprises a first connector (730) and a first filter element (740); the other end of the first hose (720) facing away from the drain pipe (710) is connected to the first filter element (740) through the first connector (730).

7. The microcarrier bioreactor sparging device of claim 1, wherein, The shunt mechanism (10) comprises a tee; the tee is provided with the shunt inlet and two shunt outlets; the air inlet mechanism (30) comprises two air inlet mechanisms, namely a first air inlet mechanism and a second air inlet mechanism; the flow meter (20) comprises two flow meters, namely a first flow meter and a second flow meter; one end of the first air inlet mechanism is in communication with one of the shunt outlets through the first flow meter, and one end of the second air inlet mechanism is in communication with the other shunt outlet through the second flow meter.

8. The microcarrier bioreactor aeration device of any one of claims 1-7, wherein, The air inlet mechanism (30) comprises: an air inlet pipe (310) having one end in communication with one of the flow meters (20) through a corresponding flow meter (20) and the other end in communication with a gas distributor (320) for being disposed in the bioreactor (40).

9. The microcarrier bioreactor aeration device of claim 8, wherein, The air inlet mechanism (30) further comprises a second hose (330) and a second filter element (340). The second hose (330) and the second filter element (340) are connected between the air inlet pipe (310) and the corresponding flow meter (20).

10. A bioreactor apparatus, characterized by, Comprising: a bioreactor (40) and a microcarrier bioreactor aeration device as claimed in any one of claims 1-9 for aerating different locations within the bioreactor (40); a stirring device (50) having a driving end disposed within the bioreactor (40) for stirring liquid and microcarriers within the bioreactor (40).

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