Rocking bioreactor

Abstract

The utility model relates to a swing type bioreactor, including tray, gas adjusting device, support, the tray is placed with culture bag, is equipped with culture solution in culture bag, tray can be under the action of drive mechanism left and right tilt, relative to the fulcrum of tray swing, the bottom left and right sides of culture bag are equipped with first aeration device and second aeration device respectively, first aeration device and second aeration device are used for into the gas in culture solution, gas adjusting device is fixed on the support, is used for the gas on-off of first aeration device and second aeration device of alternation control, the support with tray or culture bag fixed connection.

Description

Technical Field

[0001] This utility model relates to a bioreactor, particularly a swing bioreactor. Background Technology

[0002] A swaying bioreactor is a biological reaction system that utilizes mechanical swaying motion to achieve mixing and mass transfer. It is widely used in cell culture, microbial fermentation, and biopharmaceuticals. It typically includes a swaying platform driven by a motor to generate a regular swaying motion. Disposable culture bags are placed on the swaying platform, and the swaying motion creates a wave-like liquid surface, promoting mixing and gas exchange. It eliminates the need for traditional agitators and regulates oxygen and carbon dioxide concentrations through a permeable membrane or direct aeration.

[0003] However, existing swing-type bioreactors are rarely used in microbial fermentation culture. This is mainly because microorganisms have rapid metabolic rates, high oxygen consumption, high culture density, rapid culture medium consumption, and high culture medium viscosity. These issues make it difficult for surface-aerated reactors / bags to meet the oxygen supply and mixing / mass transfer requirements of the culture process, resulting in low culture density or even failure to achieve the desired culture objectives. This surface aeration method is suitable for cell culture in small-volume bioreactors. When using bioreactors larger than 20L, surface gas supply is insufficient to meet the gas supply requirements for cell growth, especially for the culture of high-aerobic microorganisms. Furthermore, to regulate the temperature of the bioreactor, especially when lower temperatures are required, existing technologies typically use water baths to cool the culture bags, which is costly. Summary of the Invention

[0004] To address the aforementioned problems, this invention provides a swing-type bioreactor, comprising a tray, a gas regulating device, and a support. A culture bag containing a culture medium is placed on the tray. The tray can tilt left and right under the action of a driving mechanism. Relative to the fulcrum of the tray's swing, a first ventilation device and a second ventilation device are respectively provided on the left and right sides of the bottom of the culture bag. The first and second ventilation devices are used to introduce gas into the culture medium. The gas regulating device is fixed to the support and is used to alternately control the gas flow of the first and second ventilation devices. The support is fixedly connected to the tray or the culture bag.

[0005] Furthermore, the bioreactor also includes a gas regulating device, which has a cavity in which a sealing ball is placed. The bottom of the cavity has a structure that is low in the middle and high on both sides. The cavity is connected to an air inlet pipe and an air outlet.

[0006] Furthermore, the gas regulating device is fixedly connected to the tray or culture bag.

[0007] Furthermore, the vent includes a first vent and a second vent respectively arranged at the left and right ends of the cavity. The first vent and the second vent are located at the two ends of the cavity, respectively. The second vent on the right side is connected to the first ventilation device through a first gas pipeline, and the first vent on the left side is connected to the second ventilation device through a second gas pipeline.

[0008] Furthermore, when the tray tilts to the left at a certain angle, the sealing ball will block the first vent; when the tray tilts to the right at a certain angle, the sealing ball will block the second vent.

[0009] Furthermore, the bottom of the cavity has an arc-shaped structure.

[0010] Furthermore, the curvature of the arc structure is adjustable, and the curvature of the arc structure can be increased or decreased by tension and pressure.

[0011] Furthermore, the first ventilation device and the second ventilation device are tubular channels, and the sidewalls of the tubular channels are provided with multiple air outlet microholes.

[0012] Furthermore, the tubular channel is a straight pipe, a ring pipe, a serpentine pipe, and / or the pipe cross-section is circular, semi-circular, or square.

[0013] Furthermore, a temperature control unit is provided along the path of the first gas pipeline and the second gas pipeline. That is, after the gas flows out from the first gas outlet and the second gas outlet, it first passes through the temperature control unit for temperature adjustment, and then enters the first ventilation device and the second ventilation device.

[0014] This novel swing-type bioreactor, by incorporating a venting device at the bottom of the culture bag, allows gas to enter the bag from below the liquid surface. This effectively ensures a suitable dissolved oxygen and mass transfer environment for microbial growth, particularly beneficial for systems with high oxygen consumption rates, high culture densities, and high culture medium viscosity. It provides ample oxygen supply and mixing, facilitating the large-scale scaling and industrialization of high-oxygen-consuming microbial cultures. Simultaneously, a temperature control unit within the gas passage regulates the temperature. Since the gas ultimately flows primarily into the liquid within the culture bag, the gas exiting through the micropores causes disturbance to the liquid, significantly improving heat exchange efficiency. This design is particularly suitable for large-scale bioreactors, enabling better temperature control. Compared to water bath temperature control devices, it is smaller, lower in cost, and offers faster adjustment. Attached Figure Description

[0015] Figure 1 This is a schematic diagram of a swing-type bioreactor. Figure 2 This is a schematic diagram of a gas regulating device in a horizontal position. Figure 3This is a schematic diagram of a gas regulating device tilted to the left. Figure 4 This is a schematic diagram of a gas regulating device tilted to the right. Figure 5 This is a schematic diagram of a straight pipe structure for the ventilation device; Figure 6 This is a schematic diagram of a ring pipe structure for the ventilation device; Figure 7 This is a schematic diagram of a serpentine tube structure for the ventilation device. Detailed Implementation

[0016] See Figure 1-2 The swing-type bioreactor of this utility model includes a base 1, a support frame 2, and a tray 3. A culture bag 4 is placed on the tray 3, and the culture bag contains a culture medium. The tray 3 tilts left and right under the action of a drive mechanism (not shown), that is, it swings in a seesaw-like manner relative to the fulcrum of the tray. This drive technology belongs to the conventional swing-type bioreactor technology and will not be described in detail.

[0017] In this invention, relative to the swing center position of the tray, the bottom left and right sides of the culture bag 4 are respectively provided with a first ventilation device 7 and a second ventilation device 8. The first ventilation device 7 and the second ventilation device 8 are submerged in the culture liquid inside the culture bag 4. The first ventilation device 7 and the second ventilation device 8 are respectively connected to the first gas pipeline 9 and the second gas pipeline 10 for supplying gas (e.g., oxygen) into the culture bag 4.

[0018] The oscillating bioreactor also includes a gas regulating device 5 for alternately controlling the gas flow of the first ventilation device 7 and the second ventilation device 8. The gas regulating device 5 includes a cavity 11, within which a sealing ball 12 is placed. The bottom of the cavity 11 has an arc-shaped structure, lower in the middle and higher on both sides. A first air outlet 13 and a second air outlet 14 are respectively located at the two ends of the arc-shaped structure. An air inlet pipe 15 is connected to the upper end of the cavity 11 for supplying gas into the cavity. An exhaust pipe 16 is also connected to the culture bag 4. The gas regulating device 5 is fixed above the tray and oscillates with the left and right movement of the tray. The second air outlet 14 on the right side is connected to the first ventilation device 7 via a first gas pipe 9, and the first air outlet 13 on the left side is connected to the second ventilation device 8 via a second gas pipe 10. Those skilled in the art will understand that the gas regulating device can also be fixed to the culture bag 4, because in practical applications, the culture bag will be filled with gas and expand, or the culture bag is made of rigid material. By directly fixing the gas regulating device to the culture bag 4, it can be sold as a whole product, thereby adapting to different swing devices.

[0019] To keep the gas regulating device above the culture bag, a bracket 17 is fixedly connected to the tray 3 or the culture bag 4, and the gas regulating device is fixedly connected to the bracket 17.

[0020] Its working principle is as follows: When the tray tilts to the left at a certain angle (usually the far left) (see...) Figure 3 The culture medium in culture bag 4 flows to the left. Since the gas regulating device is fixedly connected to the tray, it also tilts to the left. The sealing ball 12 inside blocks the first vent 13. Gas from the inlet pipe 15 flows out through the cavity 11 and then through the second vent 14, passing through the first gas pipe 9 and exiting through the first ventilation device 7, thus introducing gas into the liquid inside culture bag 4. When the tray tilts to the right at a certain angle (generally the far right) (see...), Figure 4 When the culture medium in culture bag 4 flows to the right, the gas regulating device also tilts to the right. The sealing ball 12 inside cavity 11 blocks the second vent 14. The gas from the inlet pipe 15 flows out from the first vent 13 after passing through cavity 11, and then flows out from the second venting device 8 through the second gas pipe 10, thus introducing gas into the culture medium in culture bag 4. In the middle state of oscillation, gas flows out from both the first vent 13 and the second vent 14. Since the first venting device 7 and the second venting device 8 are arranged at the bottom of culture bag 4, it can also be ensured that the gas is basically introduced into the liquid.

[0021] Therefore, this invention, through the gas regulating device and related pipeline connections, ensures that during the left-right swinging of the tray, the gas is essentially introduced below the liquid surface inside the culture bag 4. Compared to traditional reactors that introduce gas above the liquid surface, this effectively guarantees the necessary dissolved oxygen and mass transfer environment for microbial growth. It is particularly beneficial for systems with high oxygen consumption rates, high culture densities, and high culture medium viscosity, providing sufficient oxygen supply and mixing. This facilitates the large-scale scaling and industrialization of high-oxygen-consuming microbial cultivation, while reducing gas costs. For microbial cultivation with lower oxygen requirements, it increases the effective culture volume of the fermentation bag, significantly reducing cultivation costs.

[0022] See Figure 1 The first ventilation device 7 and the second ventilation device 8 are elongated strips with a semi-circular cross-section, and multiple micro-holes for air outlet are opened on the side wall. The pore size of the micro-holes is selected between 200-800 micrometers, preferably 200-500 micrometers. The first ventilation device 7 and the second ventilation device 8 can also be straight pipes. Figure 5 ), ring pipe ( Figure 6 ), serpentine tube ( Figure 7 Various styles are available, and the cross-section can also be circular, square, etc., all of which can be adjusted according to the gas composition requirements of microbial culture.

[0023] Furthermore, the above Figure 1-4 The ventilation device can also be multiple pipes with micro-holes for gas outlet, thereby meeting the need for uniform gas distribution.

[0024] As a further improvement, to control the temperature during the bioreactor process, this invention incorporates a temperature control unit 6 along the paths of the first gas pipeline 9 and the second gas pipeline 10. Specifically, after the gas flows out from the first vent 13 and the second vent 14, it first passes through the temperature control unit 6 for temperature adjustment before being introduced into the arrangement 8 of the first ventilation device 7 and the second ventilation device 8. Since the gas ultimately enters the liquid inside the culture bag 4, the gas flow from the vent micropores also causes disturbance to the liquid. Compared to traditional contact heat exchange on the outside of the culture bag 4, this significantly improves heat exchange efficiency, making it particularly suitable for large bioreactors and enabling better temperature control. Compared to water bath temperature control devices, it is smaller, lower in cost, and has a faster adjustment rate.

[0025] The above embodiments are only used to illustrate the technical solutions of this utility model, and are not intended to limit it. Although this utility model has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this utility model.

Claims

1. A swing-type bioreactor, comprising a tray (3), a gas regulating device (5), and a support (17), wherein a culture bag (4) is placed on the tray (3), the culture bag (4) contains a culture medium, and the tray (3) can tilt left and right under the action of a driving mechanism, characterized in that: Relative to the fulcrum of the swaying tray, the bottom left and right sides of the culture bag (4) are respectively provided with a first ventilation device (7) and a second ventilation device (8). The first ventilation device (7) and the second ventilation device (8) are used to introduce gas into the culture medium. The gas regulating device (5) is fixed on the support (17) and is used to alternately control the gas flow of the first ventilation device (7) and the second ventilation device (8). The support (17) is fixedly connected to the tray (3) or the culture bag (4).

2. The swing-type bioreactor according to claim 1, characterized in that, The bioreactor also includes a gas regulating device (5), which has a cavity (11) in which a sealing ball (12) is placed. The bottom of the cavity (11) is low in the middle and high on both sides. The cavity (11) is connected to an air inlet pipe (15) and an air outlet.

3. The swing-type bioreactor according to claim 2, characterized in that, The gas regulating device (5) is fixedly connected to the tray (3) or the culture bag (4).

4. The swing-type bioreactor according to any one of claims 2-3, characterized in that, The air outlet includes a first air outlet (13) and a second air outlet (14) respectively arranged at the left and right ends of the cavity (11). The first air outlet (13) and the second air outlet (14) are located at the two ends of the cavity (11). The second air outlet (14) on the right side is connected to the first ventilation device (7) through the first gas pipeline (9), and the first air outlet (13) on the left side is connected to the second ventilation device (8) through the second gas pipeline (10).

5. The swing-type bioreactor according to claim 4, characterized in that, When the tray tilts to the left at a certain angle, the sealing ball (12) will block the first vent (13); when the tray tilts to the right at a certain angle, the sealing ball (12) will block the second vent (14).

6. The swing-type bioreactor according to any one of claims 2-3, characterized in that, The bottom of the cavity (11) has an arc-shaped structure.

7. The swing-type bioreactor according to claim 6, characterized in that, The curvature of the arc structure is adjustable, and the curvature can be increased or decreased by tension and pressure.

8. The swaying bioreactor according to any one of claims 1-3 and 5, characterized in that, The first ventilation device (7) and the second ventilation device (8) are tubular channels, and multiple air outlet micro-holes are provided on the side wall of the tubular channel.

9. The swing-type bioreactor according to claim 8, characterized in that, The tubular channel is a straight pipe, a ring pipe, a serpentine pipe, and / or the cross-section of the tubular channel is circular, semi-circular, or square.

10. The swing-type bioreactor according to claim 4, characterized in that, Temperature control unit (6) is provided on the path of the first gas pipeline (9) and the second gas pipeline (10). That is, after the gas flows out from the first gas outlet (13) and the second gas outlet (14), it first passes through the temperature control unit (6) for temperature adjustment, and then enters the first ventilation device (7) and the second ventilation device (8).

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