JP2020080694A - Flexible culture device - Google Patents

Abstract

To provide a flexible culture device capable of suppressing ill effects caused by an extension room part of a culture bag when a volume of a space for culture in the culture bag is varied, in a culture tank comprising the culture bag and a housing, and dissolving problems in which cleaning between a lid and the culture tank cannot be cleaned, and preventing entry of a foreign matter caused by slide between the lid and the culture tank when the lid is vertically moved, into a culture fluid.SOLUTION: A flexible culture device 1 comprises: a flexible culture bag 2 capable of forming therein, a culture space S for culturing; and a housing 3 for storing the culture bag 2. A volume of the culture space S can be set and can be varied up to a maximum volume of the culture bag 2. When the volume of the culture space S is set to less than the maximum volume of the culture bag 2, the culture bag 2 has a lower use part 2a forming the culture space S and an upper extension room part 2b. The flexible culture device comprises: a first seal mechanism Ms1 for sealing a boundary 2c between the user part 2a and the extension room part 2b and releasing a sealing; and a first vertical move mechanism Mm1 capable of vertically moving the first seal mechanism Ms1 following change of the volume of the culture space S.SELECTED DRAWING: Figure 1

Description

The present invention relates to a flexible culture device used for manufacturing biopharmaceuticals and the like, for example.

For example, when producing biopharmaceuticals, mammalian cells, bacteria, viruses and the like (hereinafter referred to as cells and the like) are cultured in a culture tank. As such a culture tank, a culture tank having a flexible culture bag and a housing for accommodating the culture bag may be used (see, for example, Patent Documents 1 to 3). This type of culture tank does not transfer the culture solution containing cells etc. in the culture bag, the installation area does not change, the culture tank does not need to be transferred, and the foreign matter is not mixed into the culture solution from the outside of the culture bag. There is an advantage that contamination can be prevented.

Special table 2014-501537 gazette Japanese Patent Publication No. 2014-530094 JP, 2018-19615, A Japanese Patent Publication No. 2005-502306

By the way, when culturing cells or the like in a culture tank, for example, the density (concentration) of cells or the like may be kept constant, and the culture solution may be proliferated as the number of cells or the like increases (see, for example, Patent Document 4).

When the amount of the culture solution changes in this way, when the culture tank equipped with the above-mentioned culture bag and housing is used, the culture tank for containing the culture solution and the culture gas can be used for culture. Since the volume of space changes, the following problems are possible.

The capacity of the culture bag used is determined in consideration of the maximum value of the volume of the space for culture. Therefore, in a state where the volume of the space for culturing is small, there is an expansion room where the culture solution does not exist inside the culture bag. The lower part of the culture bag has a stable shape due to the weight of the culture solution, but the expansion room where the culture solution does not exist has an irregular shape. If the culture solution enters and accumulates inside the irregular expansion room, it becomes a problem in quality control. In addition, when the culture solution evaporates inside the expansion room and the culture solution decreases, the culture solution is expensive and the cost loss increases. Further, if the expansion room itself enters the culture solution, it may interfere with stirring of the culture solution.

On the other hand, as a culture tank, one that is not equipped with the above-mentioned culture bag and has a lid that closes the upper opening of the culture tank to form a space for accommodating (containing a culture solution or a culture gas) It is possible to adopt it. In such a culture tank, it is conceivable that the lid is moved up and down with a change in the volume of the space for culturing with respect to a change in the amount of the culture solution.

However, in this case, the peripheral edge of the lid and the inner surface of the culture tank are in close contact with each other, and cleaning of these parts is impossible. Further, if the lid is moved up and down while the peripheral edge of the lid is in close contact with the inner surface of the culture tank, foreign matter may be generated due to sliding, and this foreign matter may be mixed in the culture solution.

In view of the above circumstances, the present invention, in a culture tank including a culture bag and a housing, suppresses the harmful effects caused by the expansion room of the culture bag when the volume of the space for culture in the culture bag changes. Also, it is a technical problem to solve the problem that cleaning is not possible between the lid and the culture tank, and to prevent contamination of the culture solution with foreign matter generated by sliding the lid on the culture tank when the lid moves up and down. And

A flexible culture device according to the present invention, which was devised to solve the above-mentioned problems, comprises a flexible culture bag capable of forming a culture space for performing culture therein, and a housing for housing the culture bag. In the flexible culture device, the volume of the culture space can be variably set at a maximum volume of the culture bag or less, and the volume of the culture space is less than the maximum volume of the culture bag, The culture bag has a lower use portion that forms the culture space and an upper expansion room portion thereof, and a seal mechanism capable of sealing and releasing the boundary between the use area and the expansion room portion. And a vertical movement mechanism capable of moving the sealing mechanism up and down in accordance with a change in the volume of the culture space. Here, the culture space includes a space for containing a culture solution (medium) containing cells to be cultured, and a space for containing a gas for culture.

According to this configuration, the boundary between the used portion and the expansion room portion of the culture bag can be sealed by the sealing mechanism. Therefore, it is possible to prevent the culture solution from accumulating inside the expansion room. It is also possible to prevent the culture solution from evaporating inside the expansion room. It is also possible to prevent the expansion room from entering the culture solution. Therefore, it is possible to suppress the adverse effect caused by the expansion room of the culture bag. The sealing mechanism can move up and down as the volume of the culture space changes due to the vertical movement mechanism, so that the volume of the culture space changes and the boundary between the used portion and the expansion room in the culture bag moves up and down. Even if it moves, it is possible to seal this boundary. That is, according to the flexible culture device of the present invention, in the culture tank including the culture bag and the housing, when the volume of the space for culture in the culture bag changes, an adverse effect caused by the expansion room of the culture bag Can be suppressed.

Further, in the above configuration, since the culture space is formed inside the culture bag, it is not necessary to provide a lid having a peripheral edge that is in close contact with the inner surface of the culture tank in order to form the space for culture. Therefore, according to the flexible culture device of the present invention, the problem of inability to clean between the lid and the culture tank is solved, and foreign matter generated in the culture solution by the sliding of the lid with the culture tank during vertical movement It is possible to prevent contamination.

In the above configuration, the sealing mechanism may be arranged in a plurality of stages vertically, and the sealing mechanisms in a plurality of stages may seal and release the boundary portion independently of each other.

In this structure, a plurality of stages of the sealing mechanisms may be vertically movable independently of each other.

In the above configuration, the sealing mechanism may include a pressing member that seals the boundary portion by pressing the boundary portion against the housing.

In this configuration, the sealing mechanism may include a support member arranged above the culture bag, and the pressing member may be arranged on the outer periphery of the support member.

In the above structure, the pressing member may be an expansion seal capable of expanding and contracting.

Here, the expansion seal is a hollow gasket formed of an elastic member such as rubber, and expands by supplying a fluid such as air to the hollow portion to come into contact with other members and exert a sealing function, By discharging the fluid from the hollow portion, the fluid contracts and separates from the other member, and the sealing function is released (hereinafter the same).

In the above configuration, the sealing mechanism may include a pair of sandwiching members that sandwich the boundary portion to seal the boundary portion.

According to the present invention, in the culture tank including the culture bag and the housing, when the volume of the space for culture in the culture bag is changed, the adverse effect caused by the expansion room of the culture bag is suppressed, and It is possible to solve the problem that cleaning is not possible between the lid and the culture tank, and it is possible to prevent the inclusion of foreign matter into the culture solution that occurs due to sliding of the lid on the culture tank when the lid moves up and down.

It is sectional drawing which shows notionally the flexible culture apparatus which concerns on 1st Embodiment of this invention. It is sectional drawing which shows notionally the flexible culture apparatus in the state where the culture solution increased. It is an enlarged view of the A section of FIG. It is sectional drawing which shows notionally the flexible culture apparatus which concerns on 2nd Embodiment of this invention. It is an enlarged view of the B section of FIG. It is a figure for demonstrating operation|movement of a sealing mechanism. It is sectional drawing which shows notionally the flexible culture apparatus which concerns on 3rd Embodiment of this invention. FIG. 8 is a sectional view taken along the line xx of FIG. 7. It is sectional drawing which shows notionally the flexible culture apparatus in the state where the culture solution increased. It is sectional drawing which shows notionally the modification of the flexible culture apparatus which concerns on 3rd Embodiment. FIG. 11 is a sectional view taken along the line yy of FIG. 10. It is sectional drawing which shows notionally the flexible culture apparatus which concerns on 4th Embodiment of this invention. It is a figure for demonstrating operation|movement of a sealing mechanism.

Embodiments of the present invention will be described below with reference to the drawings.

FIG. 1 is a sectional view conceptually showing a flexible culture device according to a first embodiment of the present invention. The flexible culture device 1 according to this embodiment is used for manufacturing biopharmaceuticals and the like, but is not limited to this, and may be used for manufacturing other foods, fuels and the like.

The flexible culture device 1 includes a culture bag 2 and a housing 3 that accommodates and supports the culture bag 2. Further, the flexible culture device 1 includes a first lid member 4 (support member) disposed above the culture bag 2, a first wire rope 5 that suspends and supports the first lid member 4, and a first wire rope. And a first winch 6 capable of winding and delivering 5.

The culture bag 2 is made of a resin film or the like and has flexibility. In the present embodiment, it is for so-called single-use (single-use) that is sterilized and supplied and then discarded after one-time use. It may be reused later.

The culture bag 2 can form a culture space S for culturing in its internal space. In the culture space S, cells to be cultured (not shown), a culture solution L (medium) for culture, and a gas G for culture are put. In the present embodiment, the culture bag 2 is in a substantially inflated state (a state of maximum volume) and has a substantially cylindrical shape in which the side surface is cylindrical and the upper and lower surfaces are substantially flat. The shape of is not limited to this.

The volume of the culture space S can be variably set below the maximum volume of the culture bag 2. As shown in FIG. 1, when the volume of the culture space S is set to be less than the maximum volume of the culture bag 2, the culture bag 2 has a lower use portion 2a forming the culture space S and an upper side thereof. And an expansion room 2b. The expansion room 2b is provided on the outer peripheral side of the upper part of the culture bag 2 and is folded back at the upper end.

Inside the culture solution L in the culture bag 2, stirring blades 7 for stirring the culture solution L are arranged. The stirring blade 7 is driven and rotated by a drive mechanism (not shown) arranged outside the housing 3. In addition to the blade stirring, other stirring methods such as rocking stirring may be used for stirring.

Further, inside the culture solution L in the culture bag 2, there is provided a sparger 8 which releases gas supplied from a liquid phase gas supply pipe (not shown) into the culture solution L as bubbles Gb. The gas G is formed by mixing the gas of the bubbles Gb with the gas from the vapor-phase gas supply pipe described later.

Although not shown, the culture bag 2 has a gas-phase gas supply pipe for supplying gas to the culture space S above the liquid level of the culture liquid L, and a culture space above the liquid level of the culture liquid L. A gas discharge pipe for discharging the gas G from S, a culture liquid supply pipe for supplying the culture liquid L into the culture space S, a culture liquid discharge pipe for discharging the culture liquid L together with the cells and the like from the culture space S, and the like are provided. Has been done.

The housing 3 has a bottomed cylindrical shape with an open top, and has a bottom wall portion 3a and a cylindrical side wall portion 3b, but is not limited to this as long as the culture bag 2 can be accommodated and supported. The material of the housing 3 is, for example, a metal such as stainless steel, but is not limited to this as long as the culture bag 2 can be accommodated and supported, and may be, for example, resin or ceramics. In the illustrated example, the side wall 3b of the housing 3 is provided with a viewing window 3c with LED illumination.

The first lid member 4 has a disc shape and is made of a metal such as stainless steel or a resin such as silicone, but is not limited to this. The first lid member 4 has a plurality of cushion members 4a on the lower side thereof. The first lid member 4 is integrated with the upper surface of the culture bag 2 by fixing the upper portion of the culture bag 2 (or fixing the upper portion of the culture bag 2) via the cushioning material 4a, and the shape of the upper portion of the culture bag 2 is integrated. Has the effect of stabilizing.

The first lid member 4 is provided with a first expansion seal 9 (pressing member) that can expand and contract over the entire circumference of the first lid member 4. In the present embodiment, the first expansion seal 9 operates by air pressure.

In the expanded state, the first expansion seal 9 presses the boundary portion 2c between the used portion 2a of the culture bag 2 and the expansion room 2b against the housing 3 from the outside of the culture bag 2. As a result, the first expansion seal 9 seals the boundary portion 2c and fixes it at a predetermined position. When the first expansion seal 9 is contracted from the state where the boundary portion 2c is sealed with the first expansion seal 9, the seal of the boundary portion 2c with respect to the housing 3 is released (seal release), and the boundary portion 2c is at a predetermined position. Is released from. In this way, the first lid member 4 and the first expansion seal 9 constitute a first sealing mechanism Ms1 capable of sealing and releasing the boundary 2c.

The first wire rope 5 is attached to a winch via a plurality of first pulleys 5a. By winding the first wire rope 5 around the first winch 6 and sending it out, the volume of the culture space S can be reduced. With the change, the first lid member 4 can be moved up and down in a stepless manner while maintaining the horizontal posture. That is, the first wire rope 5 and the first winch 6 constitute a first vertical movement mechanism Mm1 capable of moving the first sealing mechanism Ms1 up and down as the volume of the culture space S changes.

Next, the operation of increasing the amount of the culture solution L in the culture space S, which is a feature of the flexible culture device 1 of the present embodiment, will be described.

In the state of FIG. 1, as indicated by the solid line in FIG. 3, the first expansion seal 9 is in an expanded state and presses the boundary portion 2c of the culture bag 2 against the housing 3, whereby the boundary portion 2c. Is sealed.

First, as shown by a dotted line in FIG. 3, the first expansion seal 9 is contracted to release the pressure of the boundary portion 2c to release the seal of the boundary portion 2c, and the first expansion seal 9 and the boundary portion 2c are separated from each other. To form a gap between.

Then, the culture solution L is supplied into the culture space S to increase the amount of the culture solution L in the culture space S, and at the same time, the first wire rope 5 is wound by the first winch 6, whereby the first lid member is formed. Raise 4 Then, the volume of the culture space S increases and the boundary 2c rises. At this time, since the boundary portion 2c is released from the seal, it does not slide inside and no foreign matter or the like is generated inside. Further, the cushion material 4a of the first lid member 4 fixes the upper portion of the culture bag 2 (or adheres to the upper portion of the culture bag 2), whereby the upper surface of the culture bag 2 and the first lid member 4 are integrated, and the culture is performed. The shape of the upper portion of the bag 2 is stable.

After that, when the culture liquid L in the culture space S reaches a predetermined amount, the supply of the culture liquid L is stopped. When the first lid member 4 reaches the predetermined position, the winding of the first wire rope 5 by the first winch 6 is stopped, and the lifting of the first lid member 4 is stopped. In this state, as shown by the solid line in FIG. 3, the first inflatable seal 9 is again inflated to press the boundary portion 2c of the culture bag 2 against the housing 3 to seal the boundary portion 2c.

With the above, the operation for increasing the amount of the culture solution L once is completed. This operation is repeated a plurality of times until the volume of the culture space S reaches the maximum volume of the culture bag 2, as shown in FIG. 2, depending on the culture situation.

The flexible culture device 1 of the present embodiment configured as described above can enjoy the following effects.

The first sealing mechanism Ms1 can seal and fix the boundary portion 2c between the used portion 2a and the expansion room portion 2b in the culture bag 2. Therefore, the culture solution L can be prevented from entering and accumulating inside the expansion room 2b. It is also possible to prevent the culture solution L from evaporating inside the expansion room 2b. It is also possible to prevent the expansion room 2b itself from entering the culture solution L. Therefore, it is possible to suppress the adverse effect caused by the expansion room 2b of the culture bag 2. The first seal mechanism Ms1 can be moved up and down by the first vertical movement mechanism Mm1 as the volume of the culture space S increases. Therefore, when the volume of the culture space S increases, Even if the boundary portion 2c between the used portion 2a and the expansion room portion 2b rises, it is possible to seal the boundary portion 2c. That is, according to the flexible culture device 1 of the present embodiment, in the culture tank including the culture bag and the housing, when the volume of the space for the culture in the culture bag changes, the expansion room of the culture bag causes the expansion room. It is possible to suppress the adverse effect of

Further, since the culture space S is formed inside the culture bag 2, it is not necessary to provide a lid having a peripheral edge that is in close contact with the inner surface of the culture tank in order to form a space for culture. Therefore, according to the flexible culture apparatus 1 of the present embodiment, the problem that the lid and the culture tank cannot be cleaned is solved, and the culture liquid of the foreign matter generated by the sliding movement of the lid with respect to the culture tank is generated. It is possible to prevent contamination with

Next, a second embodiment of the present invention will be described.

The main difference between the second embodiment shown in FIG. 4 and the first embodiment is that the second lid member 10 (support member) is arranged above the first lid member 4. Hereinafter, this point will be mainly described, the same components as those in the first embodiment will be denoted by the same reference numerals, and detailed description of the components will be omitted. The flexible culture device 1 of the present embodiment is intended to more reliably seal the expansion room 2b by alternately expanding and alternately raising the first expansion seal 9 and the second expansion seal 11. ..

The shape and material of the second lid member 10 are the same as those of the first lid member 4. However, the second lid member 10 does not have the cushion material 4a on the lower side.

The second lid member 10 is also provided with a second inflatable seal 11 (pressing member) capable of inflating and contracting over the entire outer circumference thereof. The second expansion seal 11 also operates by air pressure, but the expansion and contraction operations of the second expansion seal 11 can be performed independently of the expansion and contraction operations of the first expansion seal 9.

In the expanded state, the second expansion seal 11 presses the boundary portion 2c between the used portion 2a of the culture bag 2 and the expansion room 2b against the housing 3 from the outside of the culture bag 2. As a result, the second expansion seal 11 seals the boundary portion 2c and fixes it at a predetermined position. When the second expansion seal 11 is contracted from the state where the boundary portion 2c is sealed by the second expansion seal 11, the seal of the boundary portion 2c with respect to the housing 3 is released (seal release), and the boundary portion 2c is at a predetermined position. Is released from. In this way, the second lid member 10 and the second expansion seal 11 form a second sealing mechanism Ms2 capable of sealing and releasing the boundary 2c. Therefore, in the present embodiment, the seal mechanism capable of sealing and releasing the boundary portion 2c is arranged in two stages (first seal mechanism Ms1 and second seal mechanism Ms2) vertically. Further, the first sealing mechanism Ms1 and the second sealing mechanism Ms2 can seal and release the boundary portion 2c independently of each other.

As shown in FIG. 4, a second wire rope 12 that suspends and supports the second lid member 10 and a second winch 13 that can wind and send the second wire rope 12 are provided. The second wire rope 12 is attached to the second winch via a plurality of second pulleys 12a, and by winding the second wire rope 12 with the second winch 13 or sending it out, the culture space S As the volume changes, the second lid member 10 can be moved up and down in a stepless manner while maintaining the horizontal posture. That is, the second wire rope 12 and the second winch 13 compose a second vertical movement mechanism Mm2 capable of moving the second sealing mechanism Ms2 up and down as the volume of the culture space S changes. Therefore, in the present embodiment, the first seal mechanism Ms1 and the second seal mechanism Ms2 can move up and down independently of each other.

Next, the operation of increasing the amount of the culture solution L in the culture space S, which is a feature of the flexible culture device 1 of the present embodiment, will be described.

In the state of FIG. 4, as shown by the solid line in FIG. 5, the first expansion seal 9 and the second expansion seal 11 are in an expanded state, and press the upper and lower ends of the boundary portion 2c of the culture bag 2 against the housing 3. The upper and lower ends of the boundary 2c are thereby sealed.

First, as shown by the dotted line in FIG. 5, the second expansion seal 11 is contracted to release the pressure on the upper end of the boundary portion 2c to release the seal at the upper end of the boundary portion 2c. A gap is formed between the upper end of the boundary 2c (state of FIG. 6A).

Then, the second wire rope 12 is wound by the second winch 13 to raise the second lid member 10. At this time, since the boundary portion 2c is released from the seal, it does not slide inside and no foreign matter or the like is generated inside.

Next, when the second lid member 10 is raised to a predetermined position, the winding of the second wire rope 12 by the second winch 13 is stopped, and the raising of the second lid member 10 is stopped. In this state, as shown by the solid line in FIG. 5, the second expansion seal 11 is expanded again to press the upper end of the boundary 2c of the culture bag 2 against the housing 3 and seal the upper end of the boundary 2c. (State of FIG. 6B).

After that, as shown by the dotted line in FIG. 5, the first expansion seal 9 is contracted to release the pressure on the lower end of the boundary 2c to release the seal at the lower end of the boundary 2c, so that the boundary with the first expansion seal 9 is released. A gap is formed between the lower end of the portion 2c. Then, the culture solution L is supplied into the culture space S to increase the amount of the culture solution L in the culture space S, and at the same time, the first wire rope 5 is wound by the first winch 6, whereby the first lid member is formed. Raise 4 Then, the volume of the culture space S increases and the lower end of the boundary 2c rises. At this time, since the boundary portion 2c is released from the seal, it does not slide inside and no foreign matter or the like is generated inside. Further, the cushion material 4a of the first lid member 4 fixes the upper portion of the culture bag 2 (or adheres to the upper portion of the culture bag 2), whereby the upper surface of the culture bag 2 and the first lid member 4 are integrated, and the culture is performed. The shape of the upper portion of the bag 2 is stable. Moreover, since the upper end of the boundary portion 2c is already sealed by the second expansion seal 11, air can be prevented from entering the expansion room 2b at this time. Preventing air from entering the expansion room 2b is important for quality control of culture.

After that, when the culture liquid L in the culture space S reaches a predetermined amount, the supply of the culture liquid L is stopped. When the first lid member 4 reaches the predetermined position, the winding of the first wire rope 5 by the first winch 6 is stopped, and the lifting of the first lid member 4 is stopped. In this state, as shown by the solid line in FIG. 5 again, the first expansion seal 9 is expanded to press the lower end of the boundary 2c of the culture bag 2 against the housing 3 and seal the lower end of the boundary 2c. (State of FIG. 6C).

In this state, the slack portion 2d of the culture bag 2 is formed between the first lid member 4 and the second lid member 10. Then, as shown by the dotted line in FIG. 5 again, the second expansion seal 11 is contracted to release the pressure on the upper end of the boundary portion 2c to release the seal at the upper end of the boundary portion 2c. And a gap is formed between the upper end of the boundary 2c and Then, the slack portion 2d is extended upward. As a result, the expansion room 2b increases. Next, as shown by the solid line in FIG. 5, the second expansion seal 11 is expanded again to press the upper end of the boundary 2c of the culture bag 2 against the housing 3 to seal the upper end of the boundary 2c. ..

With the above, the operation for increasing the amount of the culture solution L once is completed. This operation is performed a plurality of times until the volume of the culture space S reaches the maximum volume of the culture bag 2 depending on the culture situation.

Next, a third embodiment of the present invention will be described.

The main difference between the third embodiment and the first embodiment shown in FIG. 7 is that the expansion room 2b of the culture bag 2 is provided on the inner peripheral side of the upper part of the culture bag 2 and the used portion. The point is that a pair of third expansion seals 14 (holding members) that seal the boundary 2c by sandwiching the boundary 2c between the 2a and the expansion room 2b are provided. Hereinafter, this point will be mainly described, the same components as those in the first embodiment will be denoted by the same reference numerals, and detailed description of the components will be omitted.

The upper side of the expansion room 2b of the culture bag 2 is wound around a winding core 16 whose axial ends are rotatably supported by the vertical movement member 15. The up-and-down moving member 15 can be moved up and down by a drive mechanism (not shown).

The pair of third expansion seals 14 are arranged on the pair of first extending portions 17a of the first frame member 17 so as to face each other. As shown in FIG. 8, the third expansion seal 14 is disposed so as to extend straight in the lateral direction. The pair of first extending portions 17a of the first frame member 17 has a shape that extends straight in the extending direction of the third expansion seal. Both ends of the pair of first extending portions 17a in the longitudinal direction are fixed by the first fixing portions 17b.

The third expansion seal 14 is also expandable and contractible, and is pneumatically actuated in this embodiment. The pair of third expansion seals 14 sandwich the boundary portion 2c between the used portion 2a and the expansion room portion 2b of the culture bag 2 from the outside of the culture bag 2 in the expanded state. As a result, the third expansion seal 14 seals the boundary portion 2c and fixes it at a predetermined position. When the third expansion seal 14 is contracted from the state where the boundary portion 2c is sealed by the third expansion seal 14, the seal of the boundary portion 2c is released (seal release), and the boundary portion 2c is released from the predetermined position. It In this way, the first frame member 17 and the pair of third expansion seals 14 constitute a third sealing mechanism Ms3 capable of sealing and releasing the boundary portion 2c.

The first frame member 17 is suspended and supported by a third wire rope 20 via a first auxiliary wire rope 18 and a plate-shaped first auxiliary member 19. Further, a third winch 21 capable of winding and sending out the third wire rope 20 via a plurality of third pulleys 20a is provided. In addition, as shown in FIG. 8, the boundary portion 2c and the expansion room portion 2b of the culture bag 2 are in a folded state. The materials of the first frame member 17 and the first auxiliary member 19 are the same as those of the first lid member 4.

By winding the third wire rope 20 around the third winch 21 and sending it out, the first frame member 17 is continuously moved up and down in accordance with the change in the volume of the culture space S while maintaining the horizontal posture. be able to. That is, the third wire rope 20 and the third winch 21 constitute a third vertical movement mechanism Mm3 capable of moving the third sealing mechanism Ms3 up and down in accordance with the change in the volume of the culture space S.

Next, the operation of increasing the amount of the culture solution L in the culture space S, which is a feature of the flexible culture device 1 of the present embodiment, will be described.

In the state of FIG. 7, the pair of third expansion seals 14 sandwich the boundary portion 2c in an expanded state, thereby sealing the boundary portion 2c.

First, the vertical movement member 15 is raised. Then, since the winding core 16 is rotatable with respect to the vertically moving member 15 and the boundary portion 2c is sandwiched and fixed by the pair of third expansion seals 14, the expansion margin portion 2b wound around the winding core 16 is , Is extended downward. When the vertical movement member 15 reaches a predetermined position, the vertical movement member 15 stops rising.

Next, the pair of third expansion seals 14 is contracted, the sandwiching of the boundary portion 2c is released to release the seal of the boundary portion 2c, and a gap is formed between the pair of first expansion seals 9 and the boundary portion 2c. Form.

Then, by winding the third wire rope 20 around the third winch 21, the first frame member 17 is raised. At this time, since the boundary portion 2c is released from the seal, it does not slide inside and no foreign matter or the like is generated inside.

After that, when the first frame member 17 reaches a predetermined position, the winding of the third wire rope 20 by the third winch 21 is stopped, and the lifting of the first frame member 17 is stopped. In this state, the pair of third expansion seals 14 is again inflated to sandwich the upper end of the boundary 2c and seal the upper end of the boundary 2c.

Then, the culture solution L is supplied into the culture space S to increase the amount of the culture solution L in the culture space S. Then, the volume of the culture space S increases and the lower end of the boundary 2c rises. When the culture solution L in the culture space S reaches a predetermined amount, the supply of the culture solution L is stopped.

With the above, the operation for increasing the amount of the culture solution L once is completed. This operation is performed a plurality of times until the volume of the culture space S reaches the maximum volume of the culture bag 2, as shown in FIG. 9, depending on the culture situation.

In the present embodiment, the boundary portion 2c of the culture bag 2 is sandwiched by the pair of third expansion seals 14, but as shown in FIGS. 10 and 11, one third expansion seal 14 (sandwich member) is used. The boundary portion 2c of the culture bag 2 may be held by the first frame member 17 (holding member). In this case, the third sealing mechanism Ms3 has a pair of sandwiching members (third expansion seal 14, first frame member 17) that sandwich the boundary 2c of the culture bag 2 to seal the boundary 2c. Become.

More specifically, the third expansion seal 14 is not disposed on one of the pair of first extending portions 17a of the first frame member 17, and one third expansion seal 14 in an expanded state and The boundary portion 2c of the culture bag 2 is sandwiched from the outside of the culture bag 2 by the first extension portion 17a facing the three expansion seals 14. Other configurations are the same as those in the third embodiment described with reference to FIGS. 7 to 9, and therefore, the same configurations are denoted by the same reference numerals and description thereof is omitted.

Next, a fourth embodiment of the present invention will be described.

The fourth embodiment shown in FIG. 12 mainly differs from the third embodiment in that the second frame member 22 is arranged above the first frame member 17. Hereinafter, this point will be mainly described, the same configurations as those of the third embodiment will be denoted by the same reference numerals, and detailed description of the configurations will be omitted.

The shape and material of the second frame member 22 are the same as those of the first frame member 17. The second frame member 22 is also provided with a fourth expansion seal 23 (holding member) that can expand and contract. The pair of fourth expansion seals 23 also seal the boundary 2c by sandwiching the boundary 2c.

The pair of fourth expansion seals 23 are arranged on the second frame member 22 so as to face each other. The second frame member 22 has a shape similar to that of the first frame member 17, and the second frame member 22 has a fourth extending portion 22a corresponding to the first extending portion 17a of the first frame member 17 and a fourth extending portion 22a. The expansion seal 23 is provided. Further, at the second fixing portion 22b of the second frame member 22 corresponding to the first fixing portion 17b of the first frame member 17, both ends in the longitudinal direction of the pair of second extending portions 22a are fixed. The shape of the fourth expansion seal 23 is similar to that of the third expansion seal 14.

The fourth expansion seal 23 also operates similarly to the third expansion seal 14. Therefore, the second frame member 22 and the pair of fourth expansion seals 23 form a fourth sealing mechanism Ms4 capable of sealing and releasing the boundary portion 2c from the outside of the culture bag 2. Therefore, in the present embodiment, the seal mechanisms capable of sealing and releasing the boundary portion 2c are arranged in the upper and lower two stages (third seal mechanism Ms3 and fourth seal mechanism Ms4). Further, the expansion and contraction operations of the fourth expansion seal 11 can be performed independently of the expansion and contraction operations of the third expansion seal 14. Therefore, the third sealing mechanism Ms3 and the fourth sealing mechanism Ms4 can seal and release the boundary portion 2c independently of each other.

The second frame member 22 is suspended and supported by the fourth wire rope 26 via the second auxiliary wire rope 24 and the second auxiliary member 25. Further, a fourth winch 27 capable of winding and sending out the fourth wire rope 26 via a plurality of fourth pulleys 26a is provided. The boundary 2c and the expansion room 2b of the culture bag 2 are in a folded state, as in the third embodiment (see FIG. 8). The shape and material of the second auxiliary member 25 are similar to those of the first auxiliary member 19.

By winding up and feeding out the fourth wire rope 26 with the fourth winch 27, the second frame member 22 is moved up and down in a stepless manner while maintaining the horizontal posture as the volume of the culture space S changes. be able to. That is, the fourth wire rope 26 and the fourth winch 27 constitute a fourth vertical movement mechanism Mm4 capable of moving the fourth sealing mechanism Ms4 up and down in accordance with the change in the volume of the culture space S. Therefore, in the present embodiment, the third seal mechanism Ms3 and the fourth seal mechanism Ms4 can move up and down independently of each other.

Next, the operation of increasing the amount of the culture solution L in the culture space S, which is a feature of the flexible culture device 1 of the present embodiment, will be described.

In the state of FIG. 12, the pair of third expansion seals 14 and the pair of fourth expansion seals 23 are in an expanded state, and sandwich the upper and lower ends of the boundary portion 2c of the culture bag 2, whereby the upper and lower sides of the boundary portion 2c are sandwiched. The ends are sealed (state of FIG. 13(A)).

First, the vertical movement member 15 is raised. Then, since the winding core 16 is rotatable with respect to the vertically moving member 15 and the boundary portion 2c is sandwiched and fixed by the pair of third expansion seals 14, the expansion margin portion 2b wound around the winding core 16 is , Is extended downward.

Then, the pair of fourth expansion seals 23 is contracted to release the upper end of the boundary portion 2c from releasing the sandwiching of the upper end of the boundary portion 2c, and the pair of fourth expansion seals 23 and the upper end of the boundary portion 2c are released. Form a gap between them.

Then, the fourth wire rope 26 is wound by the fourth winch 27 to raise the second frame member 22. At this time, since the boundary portion 2c is released from the seal, it does not slide inside and no foreign matter or the like is generated inside.

Next, when the vertical movement member 15 reaches a predetermined position, the vertical movement member 15 is stopped from rising. Then, when the second frame member 22 is lifted to a predetermined position, the winding of the fourth wire rope 26 by the fourth winch 27 is stopped, and the lifting of the second frame member 22 is stopped. In this state, the pair of fourth expansion seals 23 is again inflated to sandwich the upper end of the boundary 2c of the culture bag 2 and seal the upper end of the boundary 2c (the state of FIG. 13B).

After that, the pair of third expansion seals 14 is contracted, the lower end of the boundary portion 2c is released to release the seal at the lower end of the boundary portion 2c, and the pair of third expansion seals 14 and the lower end of the boundary portion 2c are released. To form a gap between. Then, by winding the third wire rope 20 around the third winch 21, the first frame member 17 is raised. At this time, since the boundary portion 2c is released from the seal, it does not slide inside and no foreign matter or the like is generated inside. Further, since the upper end of the boundary 2c is already sealed by the fourth expansion seal 23, it is possible to prevent air from entering the expansion room 2b at this time.

After that, when the first frame member 17 rises to a predetermined position, the winding of the third wire rope 20 by the third winch 21 is stopped, and the rise of the first frame member 17 is stopped. In this state, the third expansion seal 14 is again inflated to sandwich the boundary 2c of the culture bag 2 and seal the boundary 2c (the state of FIG. 13C).

In this state, unlike the second embodiment, the slack portion 2d of the culture bag 2 does not occur between the first frame member 17 and the second frame member 22. Therefore, the operation for extending the slack portion 2d of the culture bag 2 is unnecessary.

Then, the culture solution L is supplied into the culture space S to increase the amount of the culture solution L in the culture space S. Then, the volume of the culture space S increases and the lower end of the boundary 2c rises. When the culture solution L in the culture space S reaches a predetermined amount, the supply of the culture solution L is stopped.

With the above, the operation for increasing the amount of the culture solution L once is completed. This operation is performed a plurality of times until the volume of the culture space S reaches the maximum volume of the culture bag 2 depending on the culture situation.

The present invention is not limited to the above embodiment, and various modifications can be made within the scope of the technical idea thereof. For example, in the first and second embodiments, the support member on which the expansion seal is arranged on the outer circumference is the disk-shaped lid member, but it is sufficient if the expansion seal can be arranged on the outer circumference. It may be an annular plate member.

Further, in the above embodiment, the one having an expansion seal was used as the sealing mechanism, but any mechanism capable of sealing and releasing the boundary of the culture bag may be used, for example, one having a cylinder mechanism or the like. May be used.

Further, in the above embodiment, as the vertical movement mechanism, one having a wire rope and a winch was used, but it is sufficient if the sealing mechanism can be moved up and down, and the sealing mechanism is, for example, an air cylinder, a hydraulic cylinder, or the like. It may be moved up and down by another mechanism.

1 Flexible Culture Device 2 Culture Bag 2a Used Part 2b Expansion Room 2c Boundary 3 Housing 4 First Lid Member (Support Member)
9 First expansion seal (pressing member)
10 Second lid member (support member)
11 Second expansion seal (pressing member)
14 Third expansion seal (clamping member)
17 First frame member (holding member)
17a 1st extension part 17b 1st fixed part 22 2nd frame member (holding member)
22a 2nd extension part 22b 2nd fixed part 23 4th expansion seal (clamping member)
Mm1 First vertical movement mechanism Mm2 Second vertical movement mechanism Mm3 Third vertical movement mechanism Mm4 Fourth vertical movement mechanism Ms1 First sealing mechanism Ms2 Second sealing mechanism Ms3 Third sealing mechanism Ms4 Fourth sealing mechanism S Culture space

Claims (7)

In a flexible culture device comprising a flexible culture bag capable of forming a culture space for culturing inside, and a housing containing the culture bag,
The volume of the culture space can be variably set below the maximum volume of the culture bag,
When the volume of the culture space is set to be less than the maximum volume of the culture bag, the culture bag has a lower use portion that forms the culture space and an upper expansion room portion thereof. ,
A sealing mechanism capable of sealing and releasing the boundary between the used portion and the expansion room and a vertically moving mechanism capable of vertically moving the sealing mechanism according to a change in the volume of the culture space are provided. A flexible culture device characterized by the above. The sealing mechanism is arranged in a plurality of upper and lower stages,
The flexible culture device according to claim 1, wherein the sealing mechanisms in a plurality of stages can seal and release the boundary portion independently of each other. The flexible culture device according to claim 2, wherein a plurality of stages of the sealing mechanisms can move up and down independently of each other. The flexible culture device according to any one of claims 1 to 3, wherein the sealing mechanism has a pressing member that seals the boundary by pressing the boundary against the housing. The sealing mechanism has a support member arranged above the culture bag,
The flexible culture device according to claim 4, wherein the pressing member is arranged on the outer periphery of the support member. The flexible culture device according to claim 4 or 5, wherein the pressing member is an expansion seal capable of expanding and contracting. The flexible culture device according to any one of claims 1 to 3, wherein the sealing mechanism has a pair of sandwiching members that seal the boundary by sandwiching the boundary.

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