Bioreactor

Abstract

This bioreactor is provided with: a fixed cylindrical surface; a rotary cylindrical surface which partitions and forms a pool between the fixed cylindrical surface and the rotary cylindrical surface; a bottom plate part; a top plate part; a liquid supply part; an air supply part; a first rib which projects in a radial direction from at least one of the fixed cylindrical surface and the rotary cylindrical surface toward the other one, wherein a tip end faces the other one via a clearance; an air discharge part which is disposed above the first rib and discharges air from the pool; and a liquid level adjustment part which adjusts the liquid level of a liquid in the pool so as to be positioned above the first rib and below the air discharge part.

Description

Bioreactor

[0001] This application claims priority to Japanese Patent Application No. 2024-105521, filed on June 28, 2024, the contents of which are incorporated herein by reference.

[0002] For example, Patent Document 1 discloses a bioreactor for culturing cells. This bioreactor has a double-cylinder structure with a rotating inner cylinder and a fixed outer cylinder. A pool for containing a culture solution is defined between the inner and outer cylinders. When the inner cylinder rotates, Taylor vortices are formed in the culture solution contained in the pool. The Taylor vortices agitate the culture solution, promoting cell culture.

[0003] In order to stably form these Taylor vortices, it is preferable to have a flow with the bottom and top of the pool as fixed ends, that is, to fill the entire pool with liquid so that the liquid comes into contact with the bottom and top.

[0004] Japanese Patent Application Publication No. 8-308560

[0005] However, for cell culture, air must be introduced into the pool to allow cells to breathe. In this case, an interface between the gas and liquid phases (liquid surface) is formed. This creates the problem of the Taylor vortex collapse as the upper surface of the pool becomes a free edge.

[0006] The present disclosure provides a bioreactor that allows for the supply and discharge of air while forming Taylor vortices more stably.

[0007] a rotating cylindrical surface that extends in the axial direction around an axis and that is radially opposed to the axis and defines a pool between the fixed cylindrical surface and the rotating cylindrical surface, the rotating cylindrical surface being rotatable about the axis; a bottom plate that forms the bottom surface of the pool; a top plate that forms the top surface of the pool; a liquid supply unit that can supply liquid to the pool; an air supply unit that supplies air into the pool from the bottom surface; a first rib that extends radially from at least one of the fixed cylindrical surface and the rotating cylindrical surface to the other and has a tip that faces the other via a clearance; an air discharge unit that is provided above the first rib and that discharges the air from the pool; and a liquid level adjustment unit that adjusts the liquid level in the pool so that it is above the first rib and below the air discharge unit.

[0008] According to the present disclosure, it is possible to provide a bioreactor that is capable of forming Taylor vortices more stably while allowing the supply and discharge of air.

[0009] FIG. 1 is a cross-sectional view showing the configuration of a bioreactor according to a first embodiment of the present disclosure. FIG. 2 is an enlarged cross-sectional view of a main portion of a bioreactor according to a first embodiment of the present disclosure. FIG. 3 is an enlarged cross-sectional view of a main portion of a modified example of a bioreactor according to the first embodiment of the present disclosure. FIG. 4 is an enlarged cross-sectional view of a main portion of a bioreactor according to a second embodiment of the present disclosure. FIG. 5 is an enlarged cross-sectional view of a main portion of a bioreactor according to a third embodiment of the present disclosure. FIG. 6 is an enlarged cross-sectional view of a main portion of a bioreactor according to a fourth embodiment of the present disclosure. FIG. 7 is a cross-sectional view showing the configuration of a bioreactor according to a fifth embodiment of the present disclosure. FIG. 8 is an enlarged cross-sectional view of a main portion of a bioreactor according to a sixth embodiment of the present disclosure. FIG. 9 is an enlarged cross-sectional view of a main portion of a bioreactor according to a seventh embodiment of the present disclosure. FIG. 10 is a cross-sectional view showing the configuration of a bioreactor according to an eighth embodiment of the present disclosure. FIG. 11 is a view showing a modified example of a bioreactor according to the first embodiment of the present disclosure.

[0010] First Embodiment (Configuration of Bioreactor 1) A bioreactor 1 according to a first embodiment of the present disclosure will be described below with reference to Figures 1 and 2. The bioreactor 1 shown in Figure 1 is an apparatus for growing cells, producing viral vectors, or generating antibodies, and is also applicable to animal cell culture in general. The bioreactor 1 includes an inner cylinder 10, a drive unit 20, an outer cylinder 30, a top plate 40, a bottom plate 50, an air supply unit 60, a cell supply unit 70, a liquid supply unit 80, and a fixed end forming rib 90.

[0011] (Inner cylinder 10) The inner cylinder 10 has a cylindrical shape centered on an axis X extending in the vertical direction. The diameter of the inner cylinder 10 is constant throughout the vertical direction. The outer circumferential surface of the inner cylinder 10 is a rotational cylindrical surface 11. The inner cylinder 10 is driven to rotate about the axis X by an electric motor serving as a drive unit 20 arranged on the axis X.

[0012] (Outer cylinder 30) The outer cylinder 30 has a cylindrical shape centered on the axis X, and faces the inner cylinder 10 from the outer peripheral side with a radial gap therebetween. The inner diameter dimension of the outer cylinder 30 is constant over the entire area in the direction of the axis X. The inner peripheral surface of the outer cylinder 30 is a fixed cylindrical surface 31. The space defined between the fixed cylindrical surface 31 and the rotating cylindrical surface 11 is a pool P to which the culture solution is supplied.

[0013] A hole (liquid level adjusting unit 100) is provided at a portion of the circumference of the outer cylinder 30 to discharge the liquid (culture solution) in the pool P and appropriately adjust the liquid level. The position of this liquid level adjusting unit 100 in the direction of the axis X is desirably determined appropriately according to the design and specifications. More specifically, the liquid level adjusting unit 100 adjusts the liquid level in the pool P so that it is above a fixed end forming rib 90 (described later) and below an air discharge unit 110 (described later).

[0014] (Top plate portion 40) An opening on one side of the outer cylinder 30 in the direction of the axis X (i.e., the upper side in the vertical direction) is closed by the top plate portion 40. The top plate portion 40 is disk-shaped and centered on the axis X. An opening through which the output shaft of the drive unit 20 is inserted is formed in the center of the top plate portion 40. In addition, a hole (air discharge portion 110) is formed in part of the circumferential direction of the top plate portion 40 for discharging part of the air supplied into the pool P to the outside. The surface of the top plate portion 40 facing downward is defined as the top surface 41. A space in which air is stored is formed between the top surface 41 and the liquid surface.

[0015] (Bottom plate portion 50) The opening on the other side of the outer cylinder 30 in the direction of the axis X (i.e., the lower side in the vertical direction) is closed by the bottom plate portion 50. The bottom plate portion 50 is disk-shaped and centered on the axis X. The surface of the bottom plate portion 50 facing upward is the bottom surface 51. In other words, the pool P described above is formed by the bottom surface 51, the fixed cylindrical surface 31, the rotating cylindrical surface 11, and the top surface 41.

[0016] The lower end face of the inner cylinder 10 faces the bottom surface 51 with a small clearance between them. The size of this clearance is small compared to the overall size of the bioreactor 1. The vertical dimension of the clearance is set to, for example, 1 / 1000 to 1 / 100 of the vertical length of the outer cylinder 30. The dimension of the clearance is set to, for example, 1 mm to 10 mm.

[0017] In addition, air supply units 60 (sparger) for supplying air to the liquid in the pool P are provided on the bottom surface 51. As an example, a plurality of air supply units 60 are arranged at intervals in the circumferential direction about the axis X.

[0018] Furthermore, a tube serving as a cell supply unit 70 for supplying cells into pool P and a tube serving as a liquid supply unit 80 for supplying liquid (culture medium) into pool P are inserted into bottom plate 50. These tubes pass vertically through bottom plate 50, with their downstream ends opening inside pool P. Various tanks and the like are connected to the upstream ends. It is also desirable to provide a pump or the like at a midpoint on these tubes for pressure-feeding liquid and cells.

[0019] (Fixed-End Forming Rib 90) A fixed-end forming rib 90 (first rib) is provided on the inner peripheral surface of the outer cylinder 30, i.e., the fixed-cylindrical surface 31. The fixed-end forming rib 90 has an annular shape centered on the axis X. The fixed-end forming rib 90 is positioned slightly below the hole serving as the liquid level adjusting unit 100. The surface facing downward of the fixed-end forming rib 90 is designated as the fixed-end surface 91. In a cross-sectional view including the axis X, the fixed-end surface 91 extends radially relative to the axis X. In other words, the fixed-end surface 91 extends within a horizontal plane perpendicular to the axis X. The surface facing the opposite side from the fixed-end surface 91 (the upper surface) is designated as an inclined surface 92. In a cross-sectional view including the axis X, the inclined surface 92 extends downward from the outer peripheral end, which is the base end, to the inner peripheral end, which is the tip end. The space above the inclined surface 92 is designated as a surplus region V, which does not contribute to cell culture, even within the pool P.

[0020] Furthermore, a clearance is formed between the inner peripheral edge (tip) of the fixed end forming rib 90 and the inner cylinder 10. In other words, the tip faces the inner cylinder 10 via this clearance. As shown in FIG. 2 , the radial dimension of this clearance is defined as C. Furthermore, the distance between the rotating cylindrical surface 11 and the fixed cylindrical surface 31 is defined as R, the liquid level in the pool P is defined as D1, and the vertical dimension from the liquid level to the tip of the fixed end forming rib 90 is defined as D2. In this case, C is preferably 50% to 99% of R. More preferably, C is 70% to 99% of R. Most preferably, C is 85% to 99% of R. Furthermore, D2 is preferably 1% to 50% of D1. Even more preferably, D2 is 1% to 30% of D1. Most preferably, D2 is 1% to 10% of D1.

[0021] (Effects) The bioreactor 1 described above has a double-cylinder structure including a rotating inner cylinder 10 and a fixed outer cylinder 30. A pool P containing a culture solution is defined between the inner cylinder 10 and the outer cylinder 30. As the inner cylinder 10 rotates, Taylor vortices are formed in the culture solution contained in the pool P. The Taylor vortices stir the culture solution, promoting cell culture. To stably form these Taylor vortices, it is preferable to fill the entire pool P with liquid so that the bottom surface 51 and the top plate of the pool P are fixed ends, i.e., the liquid comes into contact with the bottom surface 51 and the top plate.

[0022] However, when the purpose is cell culture, it is necessary to introduce air into the pool P to allow the cells to breathe. In this case, an interface between the gas phase and the liquid phase (liquid surface) is formed. This causes the upper surface of the pool P to become a free end, and bubbles are generated on the liquid surface, which can lead to the collapse of the Taylor vortices. To solve this problem, the present embodiment employs the above-described configurations.

[0023] According to the above configuration, the fixed-end forming rib 90 is provided, and the region between the fixed-end forming rib 90 and the bottom surface 51 can be used as a culture region with the fixed end. This allows stable Taylor vortices to form within the culture region. Meanwhile, the supplied air passes through the clearance at the tip of the fixed-end forming rib 90 toward the excess region V above, and is then discharged through the air exhaust hole located further above. Furthermore, because bubbles form on the liquid surface in the excess region V, they do not affect the Taylor vortices. This allows cells to be cultured more stably.

[0024] Here, for example, if the liquid level drops, cells may remain above the fixed-end forming rib 90 and die. These dead cells are thought to become a breeding ground for microbial growth and ultimately cause contamination. On the other hand, with the above configuration, the upper surface of the fixed-end forming rib 90 extends downward from the base end to the tip. In other words, because the upper surface of the fixed-end forming rib 90 slopes downward toward the clearance, the liquid containing cells flows downward. This minimizes the possibility of liquid stagnation on the upper surface of the fixed-end forming rib 90, preventing contamination in this area. As a result, the freshness and cleanliness of the culture liquid can be maintained at a high level.

[0025] The first embodiment of the present disclosure has been described above. Note that various changes and modifications can be made to the above configuration without departing from the gist of the present disclosure.

[0026] <Modifications of the First Embodiment> For example, as a modification, as shown in Figure 3, the fixed end forming rib 90 may be provided on the rotating cylindrical surface 11 of the inner cylinder 10. Even in this case, the same effects as those described above can be obtained. In other words, the fixed end forming rib 90 only needs to be provided on at least one of the fixed cylindrical surface 31 and the rotating cylindrical surface 11. That is, the fixed end forming rib 90 may be provided on both the fixed cylindrical surface 31 and the rotating cylindrical surface 11 (see Figure 11). Furthermore, the shape of the fixed end forming rib 90 does not necessarily have to be annular when viewed in the direction of the axis X, and it may also be a shape with a portion cut out or a shape divided into multiple parts in the circumferential direction.

[0027] Second Embodiment Next, a second embodiment of the present disclosure will be described with reference to Fig. 4. Note that the same components as those in the first embodiment are denoted by the same reference numerals, and detailed description thereof will be omitted.

[0028] 4, in this embodiment, the shape of the fixed end forming rib 190 is different from that in the first embodiment. Furthermore, a dead water area blocking member 120 (blocking member) is provided to fill the corner between the fixed cylindrical surface 31 and the bottom surface 51.

[0029] In the fixed end forming rib 190, the fixed end surface 91 facing downward extends vertically upward from the outer periphery, which is the base end, to the inner periphery, which is the tip end. In other words, in a cross section including the axis X, the fixed end forming rib 190 has, for example, an isosceles triangle shape. Alternatively, the fixed end forming rib 190 may have a curved surface shape or a polygonal cross section with multiple inclination angles.

[0030] The dead water area blocking member 120 fills the corner (dead water area) between the lower part of the fixed cylindrical surface 31 and the outer peripheral portion of the bottom surface 51. The dead water area blocking member 120 has a curved surface that is concave toward the outer peripheral side in a cross section including the axis X. It is desirable that the radius of curvature of this curved surface be determined appropriately based on the radius of the desired Taylor vortex. Furthermore, the dead water area blocking member 120 is formed over the entire circumferential area. The dead water area blocking member 120 may be solid or hollow.

[0031] (Effects) According to the above configuration, the lower surface of the fixed end forming rib 190 extends upward from the base end to the tip end. As a result, bubbles generated below the lower surface are guided toward the clearance on the tip side of the lower surface as they move upward due to buoyancy. This allows the bubbles to be efficiently discharged without stagnation. As a result, it is possible to reduce the possibility of Taylor vortex breakdown due to the inclusion of bubbles.

[0032] According to the above configuration, the dead water area blocking member 120 is provided to fill the dead water area. This prevents the separation and dissipation of Taylor vortices between the bottom surface 51 and at least one of the fixed cylindrical surface 31 and the rotating cylindrical surface 11. As a result, the Taylor vortices can grow more stably. This allows cells to be cultured more stably.

[0033] The second embodiment of the present disclosure has been described above. Note that various changes and modifications can be made to the above configuration without departing from the gist of the present disclosure.

[0034] Third Embodiment Next, a third embodiment of the present disclosure will be described with reference to Fig. 5. Note that the same components as those in the above-described embodiments are denoted by the same reference numerals, and detailed description thereof will be omitted.

[0035] 5, the bioreactor 1 according to this embodiment further includes a defoaming mechanism 130 in addition to the components of the first embodiment. The defoaming mechanism 130 is provided above the fixed end forming rib 90 in the pool P, and above the liquid level adjusting unit 100. In other words, the defoaming mechanism 130 is located above the liquid surface.

[0036] The defoaming mechanism 130 extends over the entire area of ​​the pool P in plan view. More specifically, the defoaming mechanism 130 covers from above the annular area defined by the inner cylinder 10 and the outer cylinder 30. That is, the defoaming mechanism 130 forms an annular shape centered on the axis X. In other words, the defoaming mechanism 130 extends radially from at least one of the fixed cylindrical surface 31 and the rotating cylindrical surface 11 to the other. The defoaming mechanism 130 is integrally formed, for example, from a mesh-like or porous metal or resin member, and has numerous small pores formed in its surface.

[0037] (Effects) According to the above configuration, a mesh-like defoaming mechanism 130 is provided above the fixed end forming rib 90. As a result, bubbles generated on the liquid surface are captured in the holes of the defoaming mechanism 130 as the culture liquid is stirred, and eventually disappear. This reduces the possibility of bubbles entering the air discharge part 110, preventing the air discharge part 110 from becoming a breeding ground for microbial growth due to the intrusion of bubbles. As a result, contamination can be prevented.

[0038] The third embodiment of the present disclosure has been described above. Note that various changes and modifications can be made to the above configuration without departing from the gist of the present disclosure.

[0039] Fourth Embodiment Next, a fourth embodiment of the present disclosure will be described with reference to Fig. 6. Note that the same components as those in the above-described embodiments are denoted by the same reference numerals, and detailed description thereof will be omitted.

[0040] As shown in Figure 6, in this embodiment, the shape of the fixed end forming rib 290 is different from that of the first embodiment. That is, the fixed end forming rib 290 has a plate-like shape with its upper and lower surfaces parallel to each other. In addition, a plurality of partitioning ribs 140 (second ribs) are provided below the fixed end forming rib 290. These partitioning ribs 140 protrude in opposing directions from the fixed cylindrical surface 31 and the rotating cylindrical surface 11, and are arranged at intervals so that their positions in the direction of the axis X are alternated. Taylor vortices are formed in the regions between these partitioning ribs 140.

[0041] The tip of the partitioning rib 140 faces the fixed cylindrical surface 31 or the rotating cylindrical surface 11 with a gap in the radial direction. This gap serves as a flow path for air or liquid to pass through, similar to the clearance described in the first embodiment.

[0042] (Effects) According to the above configuration, the separator further includes partitioning ribs 140 that alternately protrude from the fixed cylindrical surface 31 and the rotating cylindrical surface 11. This allows Taylor vortices to continue to grow stably between the partitioning ribs 140. In addition, because the partitioning ribs 140 are alternately arranged, the flow of cells contained in the culture solution is not impeded. This allows cell culture to proceed more stably and quickly.

[0043] The fourth embodiment of the present disclosure has been described above. Various changes and modifications can be made to the above-described configurations without departing from the spirit and scope of the present disclosure. For example, the number of dividing ribs 140 and their arrangement intervals can be determined appropriately depending on the design and specifications.

[0044] Fifth Embodiment Next, a fifth embodiment of the present disclosure will be described with reference to Fig. 7. Note that the same components as those in the above-described embodiments are denoted by the same reference numerals, and detailed description thereof will be omitted.

[0045] 7, in this embodiment, the fixed end forming rib 390 is detachably attached to the outer cylinder 30. Specifically, the fixed end forming rib 390 has a locking portion 391, a support portion 392, and a rib main body 393. The locking portion 391 is arranged so as to overlap the upward-facing end surface of the outer cylinder 30 in the direction of the axis X. For example, a plurality of locking portions 391 may be provided at intervals in the circumferential direction, or may have an annular shape centered on the axis X.

[0046] The support portion 392 has a cylindrical shape that extends downward from the inner peripheral edge of the locking portion 391. The support portion 392 is preferably formed integrally with the locking portion 391. The surface of the support portion 392 facing the outer peripheral side abuts against the inner peripheral surface of the outer cylinder 30, i.e., the fixed cylindrical surface 31, from the inner peripheral side.

[0047] The rib main body 393 has an annular shape that projects inward from the lower edge of the support portion 392. The upper surface of the rib main body 393 forms an inclined surface 92, as in the first embodiment. That is, the inclined surface 92 extends downward from the base end to the tip end in a cross section including the axis X. The lower surface of the rib main body 393 forms a fixed end surface 91, as in the first embodiment. That is, the fixed end surface 91 extends radially in a cross section including the axis X. The same standards as those described in the first embodiment apply to the clearance between the rib main body 393 and the rotating cylindrical surface 11.

[0048] It is desirable to prepare in advance a plurality of types of fixed end forming ribs 390 with different lengths in the axial direction X of the support portion 392. That is, by changing the fixed end forming rib 390 each time to change the length of the support portion 392, it is possible to adjust the distance (vertical position) of the rib main body 393 from the liquid surface.

[0049] (Effects) According to the above configuration, the fixed end forming rib 390 is detachable and positionally adjustable. This makes it possible to easily add the fixed end forming rib 390 to, for example, an existing bioreactor 1. Furthermore, because the vertical position is adjustable, Taylor vortices of an appropriate size can be formed depending on the properties of the culture medium. This allows cell culture to proceed more efficiently and stably.

[0050] The fifth embodiment of the present disclosure has been described above. Note that various changes and modifications can be made to the above configurations without departing from the spirit and scope of the present disclosure.

[0051] Sixth Embodiment Next, a sixth embodiment of the present disclosure will be described with reference to Fig. 8. Note that the same components as those in the above-described embodiments are denoted by the same reference numerals, and detailed description thereof will be omitted.

[0052] As shown in Figure 8, the fixed end forming rib 490 according to this embodiment is detachably attached to the inner cylinder 10 so as to be fitted from the direction of the axis X. That is, the fixed end forming rib 490 has an annular shape centered on the axis X. An opening having an inner diameter equal to the outer diameter of the inner cylinder 10 is formed in the center of the fixed end forming rib 490. The fixed end forming rib 490 is preferably fixed to the inner cylinder 10 by interference fit or intermediate fit. This is to allow the vertical height position of the fixed end forming rib 490 to be adjusted. Therefore, by applying a slight force, the fixed end forming rib 490 can be moved in the direction of the axis X.

[0053] (Effects) According to the above configuration, the fixed end forming rib 490 is detachable and positionally adjustable. This makes it possible to easily add the fixed end forming rib 490 to, for example, an existing bioreactor 1. Furthermore, because the vertical position is adjustable, Taylor vortices of an appropriate size can be formed depending on the properties of the culture medium. This allows cell culture to proceed more efficiently and stably.

[0054] The sixth embodiment of the present disclosure has been described above. Note that various changes and modifications can be made to the above configurations without departing from the gist of the present disclosure.

[0055] Seventh Embodiment Next, a seventh embodiment of the present disclosure will be described with reference to Fig. 9. Note that the same components as those in the above-described embodiments are denoted by the same reference numerals, and detailed description thereof will be omitted.

[0056] 9, the fixed end forming rib 590 according to this embodiment has an upper ring 591, a rib main body 592, and a lower ring 593. The upper ring 591, the rib main body 592, and the lower ring 593 are all annular in shape, centered on the axis X, and have holes formed on their inner peripheries through which the shaft portion of the inner cylinder 10 is inserted. The shape of the rib main body 592 can be any of the various shapes described in the above embodiments.

[0057] The lower ring 593 is fitted onto the shaft portion of the inner cylinder 10, and the rib main body 592 and upper ring 591 are attached in this order so as to overlap the upper portion of the lower ring 593. It is desirable to prepare a plurality of types of upper rings 591 and lower rings 593 with different dimensions in the direction of the axis X. This is to make it possible to adjust the height position of the rib main body 592. It is also possible to insert shims between these components to fine-tune the height position.

[0058] (Effects) According to the above configuration, the fixed end forming rib 590 is detachable and positionally adjustable. This makes it possible to easily add the fixed end forming rib 590 to, for example, an existing bioreactor 1. Furthermore, because the vertical position is adjustable, Taylor vortices of an appropriate size can be formed depending on the properties of the culture medium. This allows cell culture to proceed more efficiently and stably.

[0059] The seventh embodiment of the present disclosure has been described above. Note that various changes and modifications can be made to the above configurations without departing from the spirit and scope of the present disclosure.

[0060] Eighth Embodiment Next, an eighth embodiment of the present disclosure will be described with reference to Fig. 10. Note that the same components as those in the above-described embodiments are denoted by the same reference numerals, and detailed description thereof will be omitted.

[0061] As shown in Figure 10, the bioreactor 201 of this embodiment comprises an inner cylinder 10, an outer cylinder 30, an intermediate cylinder 150, an air supply section 60, a cell supply section 70, a liquid supply section 80, a fixed end forming rib 90, an air discharge section 110, and a liquid level adjustment section 101.

[0062] Unlike the inner cylinder 10 described in the first embodiment, the inner cylinder 10 is a stationary member fixed to the bottom surface 51. An intermediate cylinder 150 is arranged on the outer periphery of the inner cylinder 10 so as to surround the inner cylinder 10. The intermediate cylinder 150 has a cylindrical main body 151 centered on the axis X, a lid 152 that closes the upper opening of the cylindrical main body 151, and a shaft 153 that extends upward from the axis X position of the lid 152. The upper end of the shaft 153 is connected to the drive unit 20. In other words, the intermediate cylinder 150 can be driven to rotate around the axis X by the drive unit 20. The space between the inner cylinder 10 and the intermediate cylinder 150 is a first pool P1 that is filled with culture medium.

[0063] The outer cylinder 30 is disposed further outward from the intermediate cylinder 150. The space between the intermediate cylinder 150 and the outer cylinder 30 serves as a second pool P2 to be filled with culture medium.

[0064] The outer peripheral surface of the inner cylinder 10 and the inner peripheral surface of the outer cylinder 30 form a fixed cylindrical surface 31. The inner peripheral surface and outer peripheral surface of the intermediate cylinder 150 form a rotating cylindrical surface 11. Of these surfaces, each fixed cylindrical surface 31 is provided with the fixed end forming rib 90 described in each of the above embodiments. The shape and clearance dimensions are the same as those described above.

[0065] As in the first embodiment, the bottom surface 51 is provided with a liquid supply unit 80 and an air supply unit 60. A tube serving as a liquid level adjustment unit 101 is inserted into the space (surplus area V) above the second pool P2. It is desirable that the end of this tube be positioned slightly below the liquid level. In addition, holes serving as an air exhaust unit 110 for exhausting air to the outside are formed in the lid 152 of the intermediate cylinder 150 and the top plate 40 of the outer cylinder 30.

[0066] (Effects) With the above configuration, when the intermediate cylinder 150 is rotated, Taylor vortices are formed in each of the first pool P1 and the second pool P2, allowing the culture medium to be stirred. Furthermore, since the fixed end forming ribs 90 are provided on each of the fixed cylindrical surfaces 31, the formation of the fixed ends prevents the collapse of the Taylor vortices while allowing the air in the first pool P1 and the second pool P2 to be discharged to the outside. Therefore, cell culture can be carried out stably.

[0067] The eighth embodiment of the present disclosure has been described above. Various changes and modifications can be made to the above configuration without departing from the spirit and scope of the present disclosure. For example, the configurations described in the second to seventh embodiments can be combined and applied to the bioreactor 201 including the intermediate cylinder 150 described in the eighth embodiment. This configuration allows the combined effects described in each embodiment to be achieved.

[0068] <Additional Notes> The bioreactor 1 described in each embodiment can be understood, for example, as follows.

[0069] (1) The bioreactor 1 according to the first aspect includes a fixed cylindrical surface 31 extending in the direction of the axis X about the axis X, a rotating cylindrical surface 11 extending in the direction of the axis X about the axis X and radially opposing the fixed cylindrical surface 31 to define a pool P between the fixed cylindrical surface 31 and rotatable about the axis X, a bottom plate portion 50 forming a bottom surface 51 of the pool P, a top plate portion 40 forming a top surface 41 of the pool P, a liquid supply portion 80 capable of supplying a liquid to the pool P, and a liquid supply portion 80 configured to supply a liquid from the bottom surface 51 into the pool P. The device is equipped with an air supply unit (60) that supplies air, a first rib (90) that extends radially from at least one of the fixed cylindrical surface (31) and the rotating cylindrical surface (11) toward the other and whose tip faces the other via a clearance, an air discharge unit (110) that is provided above the first rib (90) and discharges the air from within the pool (P), and a liquid level adjustment unit (100) that adjusts the liquid level of the liquid in the pool (P) so that it is above the first rib (90) and below the air discharge unit (110).

[0070] According to the above configuration, it becomes possible to continue culturing cells more stably.

[0071] (2) The bioreactor 1 according to the second aspect is the bioreactor 1 of (1), in which the upper surface of the first rib 90 extends downward from the base end to the tip end.

[0072] According to the above configuration, the freshness and cleanliness of the culture solution can be maintained at a high level.

[0073] (3) The bioreactor 1 according to the third aspect is the bioreactor 1 according to (1) or (2), in which the lower surface of the first rib 90 extends upward from the base end to the tip end.

[0074] According to the above configuration, it is possible to reduce the possibility of the breakdown of Taylor vortices due to the inclusion of bubbles.

[0075] (4) The bioreactor 1 according to the fourth aspect is a bioreactor 1 according to any one of aspects (1) to (3), further comprising a blocking member 120 that fills the corner between at least one of the fixed cylindrical surface 31 and the rotating cylindrical surface 11 and the bottom surface 51.

[0076] According to the above configuration, it is possible to grow the Taylor vortex more stably.

[0077] (5) The bioreactor 1 according to the fifth aspect is the bioreactor 1 according to any one of the aspects (1) to (4), and further includes a defoaming mechanism 130 provided above the first rib 90 in the pool P and extending radially from at least one of the fixed cylindrical surface 31 and the rotating cylindrical surface 11 to the other.

[0078] According to the above configuration, it is possible to prevent contamination caused by the presence of bubbles.

[0079] (6) The bioreactor 1 according to the sixth aspect is the bioreactor 1 according to any one of the aspects (1) to (5), further comprising second ribs 140 arranged below the first ribs 90 in the pool P and protruding alternately from the fixed cylindrical surface 31 and the rotating cylindrical surface 11 along the axis X.

[0080] According to the above configuration, cell culture can be carried out more stably and quickly.

[0081] (7) The bioreactor 1 according to the seventh aspect is a bioreactor 1 according to any one of aspects (1) to (6), in which the first rib 90 is detachably attached to one of the fixed cylindrical surface 31 and the rotating cylindrical surface 11.

[0082] According to the above configuration, cell culture can be carried out more efficiently and stably.

[0083] (8) The bioreactor 1 according to the eighth aspect is the bioreactor 1 of (7), wherein the first rib 90 is detachable from one of the fixed cylindrical surface 31 and the rotating cylindrical surface 11 by being fitted from the direction of the axis X.

[0084] According to the above configuration, cell culture can be carried out efficiently and stably.

[0085] (9) The bioreactor 1 according to the ninth aspect is the bioreactor 1 according to any one of aspects (1) to (8), in which the fixed end forming rib 90 is arranged so that its position in the vertical direction can be adjusted.

[0086] According to the above configuration, cell culture can be carried out more efficiently and stably.

[0087] (10) The bioreactor 1 according to the tenth aspect is the bioreactor 1 of (9), wherein the first rib 90 has an upper ring 591 and a lower ring 593 for position adjustment, and a rib body 592 arranged between the upper ring 591 and the lower ring 593.

[0088] According to the above configuration, the height position of the rib main body 592 can be adjusted more easily.

[0089] (11) The bioreactor 1 according to the eleventh aspect is the bioreactor 1 of (1) or (2), wherein the first rib 90 has a locking portion 391, a support portion 392, and a rib main body 393, the locking portion 391 is arranged so as to overlap the upward-facing end face of the fixed cylindrical surface 31 in the direction of the axis X, the support portion 392 is cylindrical and extends downward from the inner edge of the locking portion 391, and the rib main body 393 protrudes from the lower edge of the support portion 392 toward the inner edge.

[0090] According to the above configuration, the height position of the rib main body 393 can be adjusted more easily.

[0091] (12) The bioreactor 201 according to the twelfth aspect is the bioreactor 201 of (1) or (2), and includes an inner cylinder 10 having the fixed cylindrical surface 31, an outer cylinder 30 that covers the inner cylinder 10 from the outer periphery and whose inner circumferential surface forms the fixed cylindrical surface 31, and an intermediate cylinder 150 that is disposed between the inner cylinder 10 and the outer cylinder 30 and is supported rotatably around the axis X, so that the inner circumferential surface and the outer circumferential surface form the rotating cylindrical surface 11.

[0092] According to the above configuration, cell culture can be carried out more efficiently and stably.

[0093] According to the present disclosure, it is possible to provide a bioreactor that is capable of forming Taylor vortices more stably while allowing the supply and discharge of air.

[0094] DESCRIPTION OF SYMBOLS 1... Bioreactor 10... Inner cylinder 11... Rotating cylindrical surface 20... Drive unit 30... Outer cylinder 31... Fixed cylindrical surface 40... Top plate portion 41... Top surface 50... Bottom plate portion 51... Bottom surface 60... Air supply portion 70... Cell supply portion 80... Liquid supply portion 90... Fixed end forming rib 91... Fixed end surface 92... Inclined surface 100... Liquid level adjustment portion 101... Liquid level adjustment portion 110... Air discharge portion 120... Dead water area blocking member 130... Defoaming mechanism 140... Partitioning rib 150... Intermediate cylinder 151... Cylinder main body 152... Lid portion 153... Shaft 190... Fixed end forming rib 201... Bioreactor 290... Fixed end forming rib 390... Fixed end forming rib 391... Locking portion 392... Support portion 393... Rib main body 490: Fixed end forming rib 590: Fixed end forming rib 591: Upper ring 592: Rib body 593: Lower ring P: Pool P1: First pool P2: Second pool V: Surplus area X: Axis

Claims

a rotating cylindrical surface that extends in the axial direction about an axis, the rotating cylindrical surface extending in the axial direction about the axis and radially opposing the axis to define a pool between the rotating cylindrical surface and the fixed cylindrical surface, the rotating cylindrical surface being rotatable about the axis, a bottom plate portion that forms the bottom surface of the pool, a top plate portion that forms the top surface of the pool, a liquid supply portion that can supply liquid to the pool, an air supply portion that supplies air into the pool from the bottom surface, a first rib that extends radially from at least one of the fixed cylindrical surface and the rotating cylindrical surface to the other, with its tip facing the other via a clearance, an air discharge portion that is provided above the first rib and discharges the air from within the pool, and a liquid level adjustment portion that adjusts the liquid level of the liquid in the pool so that it is above the first rib and below the air discharge portion.

2. A bioreactor according to claim 1, wherein the upper surface of the first rib extends downward from the base end to the tip end.

3. A bioreactor according to claim 1 or 2, wherein the lower surface of the first rib extends upward from the base end to the tip end.

4. A bioreactor according to claim 1 or 2, further comprising a closing member for filling a corner between at least one of the fixed cylindrical surface and the rotating cylindrical surface and the bottom surface.

5. A bioreactor as described in claim 1 or 2, further comprising a foam-busting mechanism provided above the first rib in the pool and extending radially from at least one of the fixed cylindrical surface and the rotating cylindrical surface to the other.

6. A bioreactor as described in claim 1 or 2, further comprising second ribs arranged below the first rib in the pool and protruding alternately from the fixed cylindrical surface and the rotating cylindrical surface along the axial direction.

7. A bioreactor according to claim 1 or 2, wherein the first rib is detachably attached to one of the fixed cylindrical surface and the rotating cylindrical surface.

8. A bioreactor according to claim 7, wherein the first rib is detachable from at least one of the fixed cylindrical surface and the rotating cylindrical surface by being fitted from the axial direction.

9. A bioreactor according to claim 1 or 2, wherein the first rib is provided so that its position in the vertical direction can be adjusted.

10. The bioreactor of claim 9, wherein the first rib comprises an upper ring and a lower ring for position adjustment, and a rib body disposed between the upper ring and the lower ring.

11. A bioreactor as described in claim 1 or 2, wherein the first rib has a locking portion, a support portion, and a rib body, the locking portion is arranged so as to overlap the upward-facing end face of the fixed cylindrical surface in the axial direction, the support portion is cylindrical and extends downward from the inner peripheral edge of the locking portion, and the rib body protrudes from the lower edge of the support portion toward the inner peripheral side.

12. A bioreactor as described in claim 1 or 2, comprising: an inner cylinder having the fixed cylindrical surface; an outer cylinder that covers the inner cylinder from the outer side and whose inner peripheral surface forms the fixed cylindrical surface; and an intermediate cylinder that is disposed between the inner cylinder and the outer cylinder and is supported rotatably about the axis, thereby forming the rotating cylindrical surface on its inner and outer peripheral surfaces.

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