A cell reactor

Abstract

The utility model discloses a cell reactor belongs to biological medicine equipment technical field. The utility model discloses to solve the problem of uneven oxygen supply, microcarrier easy settlement and low exchange efficiency of culture medium and metabolite in the existing cell culture, mainly adopt to set double -deck gas cage, air hose, stirring device, rotary filter, pressure regulating valve and pressure gauge, wherein the air hose wall is equipped with micropore and surrounds double -deck gas cage arrangement to realize bubble -free aeration, double -deck gas cage can increase the aeration, and the effect of dissolving oxygen is enhanced, the stirring shaft drives the synchronous rotation of stirring paddle and rotary filter, makes culture solution, microcarrier and oxygen even mix, and realizes microcarrier interception and culture medium and metabolite's free exchange, and pressure regulating valve and pressure gauge promote operation safety and reliability. The utility model can realize sufficient oxygen supply and even mixing in the cell culture process, and improve cell culture efficiency and product quality.

Description

Technical Field

[0001] This utility model belongs to the field of biomedical equipment technology, specifically relating to a cell reactor. Background Technology

[0002] Cell reactors have wide applications in the biopharmaceutical field and are essential equipment for producing biopharmaceuticals such as monoclonal antibodies, vaccines, and recombinant proteins. The advantages of this type of reactor lie in its ability to maintain high cell density and long culture periods, thereby increasing product yield and ensuring the consistency and stability of product quality.

[0003] During perfusion culture, the cell reactor provides a stable nutrient environment for cells by continuously adding fresh culture medium and simultaneously removing waste culture medium, and removes metabolic products, thereby extending the culture time, improving cell activity and product quality.

[0004] In cell culture, microcarriers are typically added to the culture medium as carriers for cell attachment. Cells attach and grow on the surface of the microcarriers, and continuous stirring keeps the microcarriers in suspension. Fresh culture medium is pumped or drawn into the inner side of a rotary filter. The rotary filter utilizes centrifugal force or cross-flow filtration principles to trap the microcarriers on the outside of the filter and retain them inside the reactor. Simultaneously, the culture medium can freely exchange nutrients through the filter pores, providing the cells with the necessary nutrients, while metabolic products flow through the filter pores with the culture medium into the inner side of the filter and are discharged from the reactor through the outflow pipe, thus maintaining the stability of the reactor's internal environment.

[0005] Oxygen plays a crucial role in cellular metabolism, participating in aerobic respiration and providing energy for cell growth and metabolism. In perfusion culture, oxygen supply is typically achieved by introducing oxygen or air into the culture medium, combined with agitation to promote oxygen dissolution and transfer. However, in traditional oxygen supply methods, air is directly introduced into the culture medium through tubing, inevitably generating bubbles. The shear force generated when these bubbles burst can damage the cells. Utility Model Content

[0006] The purpose of this invention is to propose a cell reactor that, by incorporating a tank body, a tank cover, a double-layered air cage, a ventilation hose, a stirring device, a rotary filter, a pressure regulating valve, and a pressure gauge, addresses the problems of uneven oxygen supply, easy sedimentation of microcarriers, and low exchange efficiency between culture medium and metabolites in existing cell cultures. This invention aims to improve oxygen supply efficiency, ensure uniform mixing of the culture medium, maintain stable suspension of microcarriers, and achieve effective exchange between culture medium and metabolites.

[0007] To achieve the above objectives, the technical solution adopted by this utility model is as follows: A cell reactor, comprising: Tank body, tank cover, double-layer air cage, ventilation hose, stirring device, rotary filter, pressure regulating valve and pressure gauge; The tank body has a cylindrical structure and an opening at the top; The can lid is sealed and installed at the opening of the can body; The double-layer air cage is located inside the tank and fixed to the tank cover. It is a coaxial nested double-layer barrel structure with a detachable connection between the two layers. Each layer of air cage includes a vent pipe, which includes an inlet pipe section and an outlet pipe section. A flexible venting hose is connected between the interfaces of the inlet pipe section and the outlet pipe section. The ventilation hose is wound in a ring around the air cage, and its two ends are connected to the air inlet section and the air outlet section of the air cage, respectively. The wall of the ventilation hose is provided with uniformly distributed micropores. The stirring device includes a stirring shaft and a stirring paddle. The stirring shaft extends from the outside of the tank through the tank cover into the inside of the tank, and the stirring paddle is fixed to the end of the stirring shaft. The rotary filter is located inside the tank and is fixedly installed on the stirring shaft; The pressure regulating valve is installed on the exhaust pipe connected to the exhaust pipe section of the double-layer air cage; The pressure gauge is installed on the pressure regulating valve.

[0008] Furthermore, the ratio of the diameter to the height of the tank is 1:(2-3).

[0009] Furthermore, the air cage also includes a screw, which, in conjunction with a locking nut, secures the air cage within a pre-drilled screw hole in the can lid.

[0010] Furthermore, the air cage includes two hoops and multiple support columns, with the two hoops fixed to the upper and lower ends of the support columns.

[0011] Furthermore, the ventilation hose includes a first ventilation hose and a second ventilation hose, both of which are wound around the air cage.

[0012] Furthermore, the ventilation hose is made of polypropylene or silicone, with a diameter of 2-5 mm, and the pore size of the micropores on the ventilation hose is 0.1-15 μm.

[0013] Furthermore, it also includes a buffer bottle, which is connected to an exhaust pipe that is connected to the exhaust pipe section of the air cage.

[0014] Furthermore, it also includes a security filter, the inlet of which is connected to the outlet of the buffer bottle, and the outlet is connected to a pressure regulating valve.

[0015] Furthermore, the two air inlet pipe sections of the double-layer air cage are connected by a Y-shaped connector, and the two air outlet pipe sections are connected by a Y-shaped connector.

[0016] The beneficial effects achieved by this utility model are as follows: 1. This invention adopts a bubble-free ventilation structure, which avoids the shear force generated by bubble rupture from damaging cells, thus ensuring the activity and growth stability of cells during the culture process.

[0017] 2. This utility model adopts a double-layer air cage design. The outer air cage can be detachably installed on the inner air cage. Single-layer or double-layer air cages can be selected as needed. The double-layer air cage has a larger air volume and better dissolved oxygen effect.

[0018] 3. The air cage of this utility model achieves full and uniform dispersion of oxygen in the culture medium through the winding structure of the upper and lower sections of ventilation hose, thereby improving the oxygen supply efficiency and maintaining the stability of dissolved oxygen level in the reactor.

[0019] 4. The ventilation hose of this utility model has micropores with a suitable aperture on its wall, which not only ensures efficient oxygen diffusion to meet the needs of cell growth, but also avoids the damage to cells caused by large air bubbles generated by traditional ventilation methods.

[0020] 5. This utility model uses a stirring shaft to drive the stirring paddle and rotary filter to rotate synchronously, which not only achieves uniform mixing of culture medium, microcarrier and gas, preventing microcarrier sedimentation, but also improves heat and gas transfer efficiency.

[0021] 6. The rotary filter of this invention can effectively trap microcarriers, keeping them stably within the reactor, while allowing free exchange of culture medium and metabolites, thereby maintaining the nutrient supply and metabolite discharge required for cell culture.

[0022] 7. This utility model can detect the exhaust pressure value in real time and monitor the operating status through a pressure regulating valve and a pressure gauge. It can control the pressure to avoid the air cage from rupture due to unstable or excessive pressure, thereby improving operational safety. It can also adjust the size of the pressure regulating valve according to the actual dissolved oxygen value in the tank, thereby regulating the dissolved oxygen, saving oxygen consumption and improving oxygen utilization.

[0023] 8. This utility model improves operational reliability by setting up a buffer bottle and a security filter to block external microbial contamination.

[0024] 9. The present invention has a compact overall structure and reasonable connections between components, which can achieve sufficient oxygen supply, uniform mixing, stable environment and safe operation during cell culture, ensuring efficient cell culture and consistent product quality. Attached Figure Description

[0025] Figure 1 This is an assembly diagram of the seed cell reactor in the embodiment.

[0026] Figure 2 This is a diagram of the internal structure of the cell reactor in the embodiment.

[0027] Figure 3 This is a structural diagram of the air cage in the embodiment.

[0028] Figure 4 This is a structural diagram of the air cage in the embodiment, where only the first ventilation hose is wrapped around it.

[0029] Figure 5 This is a structural diagram of the air cage simultaneously winding around the first and second ventilation hoses in the embodiment.

[0030] Figure 6 This is a structural diagram of the stirring device and rotary filter in the embodiment.

[0031] Explanation of reference numerals in the attached figures: 1: Tank body; 2: Tank lid; 3: Air cage; 31: Ventilation pipe; 31a: Intake pipe section; 31b: Exhaust pipe section; 32: Screw; 33: Hoop; 34: Support column; 4: Ventilation hose; 41: First ventilation hose; 42: Second ventilation hose; 5: Rotary filter; 6: Stirring device; 61: Stirring shaft; 62: Stirring paddle; 7: Buffer bottle; 8: Security filter; 9: Pressure regulating valve; 10: Pressure gauge; I1, I2, O1, O2: Interfaces. Detailed Implementation

[0032] To make the various technical features, advantages, or effects of the present invention more apparent and understandable, detailed descriptions are provided below through embodiments.

[0033] This invention provides a cell reactor, such as... Figure 1 and Figure 2 As shown, Figure 2 The middle arrow indicates the airflow direction. This cell reactor mainly includes a tank body 1, a tank cover 2, an air cage 3, a ventilation hose 4, a rotary filter 5, a stirring device 6, a buffer bottle 7, a security filter 8, a pressure regulating valve 9, and a pressure gauge 10. Among them, the stirring device 6 includes a stirring shaft 61 and a stirring paddle 62.

[0034] Tank 1 has a cylindrical structure with a diameter-to-height ratio of 1:(2-3). This ratio increases the contact area between the culture medium and air, and the cylindrical shape helps prevent cell or microcarrier deposition around the periphery. Tank 1 has an opening at the top, and a lid 2 is sealed at this opening, ensuring a tight connection between the two and guaranteeing the airtightness of the reactor's internal environment. This provides a stable reaction space for cell culture, accommodating the culture medium and cells, preventing external impurities and microorganisms from entering the reactor, and ensuring a sterile reaction environment. Simultaneously, the lid 2 provides an installation interface for components such as the air cage 3 and the stirring device 6.

[0035] Air cage 3 is a double-layer air cage, which is a coaxial nested double-layer barrel-shaped structure, and the two layers of air cage are detachably connected. Figure 3 The diagram shows a single-layer air cage. Each layer of the air cage includes a vent pipe 31, a screw 32, a clamp 33, and a support column 34. The vent pipe 31 includes an inlet section 31a and an outlet section 31b. A flexible venting hose 4 is connected between interface I of the inlet section 31a and interface O of the outlet section 31b. In a double-layer air cage, the two inlet sections are connected by a Y-shaped connector, and the two outlet sections are connected by a Y-shaped connector; these connections can be made or left unconnected as needed. In this embodiment, the air cage 3 can be connected to two flexible venting hoses via interfaces I1, I2 and O1, O2. Figure 3 The arrows indicate the airflow direction. The air cage 3 is inserted into the pre-drilled screw hole on the tank cover 2 via a screw 32 and secured with a lock nut, ensuring a stable installation of the air cage 3 on the tank cover 2. There are two hoop rings 33 and multiple support columns 34. Two hoop rings 33 are fixed to the upper and lower ends of the support columns 34 to maintain overall structural stability. The air cage 3 is used to introduce oxygen into the culture medium within the reactor. With the double-layered air cages connected, the airflow is greater, the dissolved oxygen effect is better, and the required oxygen concentration for cell growth is more effectively ensured, promoting aerobic respiration and metabolism, and increasing cell growth rate and product production.

[0036] A ventilation hose 4 is wound annularly around an air cage 3, with its inlet and outlet connected to the interfaces of the air inlet section 31a and air outlet section 31b of the air cage 3, respectively. The ventilation hose 4 is made of polypropylene or silicone, with a diameter of 2-5 mm. Micropores are evenly distributed on the hose wall, with a pore size of 0.1-15 μm, preferably 0.1-2.8 μm (e.g., 0.3 μm), to ensure uniform oxygen entry into the culture medium. The ventilation hose 4 may include a first ventilation hose 41 and a second ventilation hose 42 to enhance oxygen dispersion. Figure 4 The image shows the air cage 3 with only the first ventilation hose 41 wrapped around it; as shown Figure 5 The image shows the state in which the air cage 3 is simultaneously wrapped around the first ventilation hose 41 and the second ventilation hose 42.

[0037] like Figure 6As shown, the rotary filter 5 is fixedly installed on the stirring shaft 61 and immersed in the culture medium. The rotary filter 5 is used to trap the microcarriers required during the culture process and keep them inside the reactor, while allowing the culture medium and metabolites to exchange freely, so as to realize nutrient supply and metabolite discharge, thereby facilitating cell collection and recycling of the culture medium.

[0038] like Figure 6 As shown, the stirring shaft 61 of the stirring device 6 extends from the outside of the tank 1 through the tank cover 2 and into the inside of the tank 1. The stirring paddle 62 is fixed to the end of the stirring shaft 61 that extends into the tank 1. When the stirring shaft 61 rotates, the stirring paddle 62 rotates synchronously with the rotary filter 5. The rotation of the stirring paddle 62 generates eddies and centrifugal force, which uniformly mixes the culture medium, microcarriers, oxygen, and nutrients, preventing microcarrier sedimentation, maintaining a consistent internal environment in the reactor, thereby promoting uniform cell growth and metabolism, and improving the efficiency of heat and gas transfer.

[0039] The air outlet section 31b of the air cage 3 is connected in sequence to the buffer bottle 7, the security filter 8, and the pressure regulating valve 9 via a flexible hose. A pressure gauge 10 is connected to the pressure regulating valve 9 to monitor the pipeline pressure. The buffer bottle 7 acts as a pressure buffer, maintaining stable pipeline system pressure; the security filter 8 blocks airborne microorganisms, reducing the risk of contamination; the pressure regulating valve 9 regulates the exhaust flow rate to maintain appropriate ventilation pressure; and the pressure gauge 10 displays the system pressure in real time.

[0040] In use, the cell suspension is first inoculated into the container 1, and an external oxygen supply is connected through the air cage 3. Oxygen enters the ventilation hose 4 through the interface I of the air cage 3, and diffuses evenly into the culture medium through the micropores of the ventilation hose 4. The remaining gas is discharged through the interface O of the ventilation hose 4, and is connected in sequence to the buffer bottle 7, the security filter 8, the pressure regulating valve 9, and the pressure gauge 10.

[0041] During the culture process, the agitator 62 rotates continuously, driving the culture medium to mix thoroughly and keeping the microcarriers with attached cells suspended. The rotary filter 5 rotates with the agitator shaft 61, which can retain the microcarriers and allow the culture medium and metabolites to exchange freely. The metabolites are eventually discharged from the reactor through the discharge pipe, thereby maintaining the stability of the cell culture environment.

[0042] During the cultivation process, the exhaust pressure is gradually increased to 0.7 bar by adjusting the opening degree of the pressure regulating valve 9 to maintain the dissolved oxygen level in tank 1. Pressure gauge 10 monitors the gas pressure in tank 1 in real time to ensure the stability of the ventilation system. It is important to note that the exhaust pressure of the pressure regulating valve 9 should not exceed 0.7 bar to avoid the possibility of the ventilation hose 4 rupturing and allowing gas to directly enter tank 1, leading to abnormal termination of the cultivation.

[0043] In summary, the cell reactor of this invention achieves sufficient oxygen supply, uniform mixing, stable suspension of microcarriers, and effective exchange between culture medium and metabolites during cell culture, thus ensuring the stability and efficiency of cell growth and metabolism.

[0044] Although the present invention has been disclosed above with reference to embodiments, it is not intended to limit the present invention. Any appropriate modifications or equivalent substitutions made by those skilled in the art to the technical solutions of the present invention should be covered within the protection scope of the present invention, which is defined by the claims.

Claims

1. A cell reactor, characterized in that, include: Tank body, tank cover, double-layer air cage, ventilation hose, stirring device, rotary filter, pressure regulating valve and pressure gauge; The tank body has a cylindrical structure and an opening at the top; The can lid is sealed and installed at the opening of the can body; The double-layer air cage is located inside the tank and fixed to the tank cover. It is a coaxial nested double-layer barrel structure with a detachable connection between the two layers. Each layer of air cage includes a vent pipe, which includes an inlet pipe section and an outlet pipe section. A flexible venting hose is connected between the interfaces of the inlet pipe section and the outlet pipe section. The ventilation hose is wound in a ring around the air cage, and its two ends are connected to the air inlet section and the air outlet section of the air cage, respectively. The wall of the ventilation hose is provided with uniformly distributed micropores. The stirring device includes a stirring shaft and a stirring paddle. The stirring shaft extends from the outside of the tank through the tank cover into the inside of the tank, and the stirring paddle is fixed to the end of the stirring shaft. The rotary filter is located inside the tank and is fixedly installed on the stirring shaft; The pressure regulating valve is installed on the exhaust pipe connected to the exhaust pipe section of the double-layer air cage; The pressure gauge is installed on the pressure regulating valve.

2. The cell reactor as described in claim 1, characterized in that, The ratio of the diameter to the height of the tank is 1:(2-3).

3. The cell reactor as described in claim 1, characterized in that, The air cage also includes a screw, which, in conjunction with a locking nut, secures the air cage within a pre-drilled screw hole in the can lid.

4. The cell reactor as described in claim 1, characterized in that, The air cage includes two hoops and multiple support columns, with the two hoops fixed to the upper and lower ends of the support columns.

5. The cell reactor as described in claim 1, characterized in that, The ventilation hose includes a first ventilation hose and a second ventilation hose, both of which are wrapped around the air cage.

6. The cell reactor as described in claim 1 or 5, characterized in that, The ventilation hose is made of polypropylene or silicone, with a diameter of 2-5 mm, and the micropores on the ventilation hose have a pore size of 0.1-15 μm.

7. The cell reactor as described in claim 1, characterized in that, It also includes a buffer bottle, which is connected to an exhaust pipe that is connected to the exhaust pipe section of the air cage.

8. The cell reactor as described in claim 7, characterized in that, It also includes a security filter, the inlet of which is connected to the outlet of the buffer bottle, and the outlet is connected to a pressure regulating valve.

9. The cell reactor as described in claim 1, characterized in that, The two inlet pipe sections of the double-layer air cage are connected by a Y-shaped connector, and the two outlet pipe sections are connected by a Y-shaped connector.

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