Filter device, filtration device, and cell culture system

Abstract

A filter device according to the present disclosure comprises: a first filter that filters a culture solution by passing it downward; a second filter that is disposed below the first filter, is finer than the first filter, and filters the culture solution having passed through the first filter; and a first seal portion that seals a gap between the outer peripheral edge of the first filter and the outer peripheral edge of the second filter.

Description

Filter device, filtration device, and cell culture system

[0001] This application claims priority to Japanese Patent Application No. 2023-223166, filed on December 28, 2023, the contents of which are incorporated herein by reference.

[0002] Patent Document 1 discloses a cell culture system that includes an isolator (clean bench) in which various operations such as dispensing of culture fluid are performed in a sterile environment, and an incubator in which cell culture is performed in an appropriate environment where the temperature, humidity, carbon dioxide concentration, etc. are controlled.

[0003] Utility Model Registration No. 3203002

[0004] Cell culture systems include a process for filtering the culture medium in which cells are cultured. If the filter becomes clogged with cells or other particles during this process, the required amount of filtrate cannot be recovered. For this reason, there is a need to filter the culture medium appropriately and stably without clogging the filter with cells. Furthermore, in order to automate the filtration process, there is a need to simplify the assembly work of the filtration device within the automated system.

[0005] The present disclosure has been made to solve the above-mentioned problems, and aims to provide a filter device, a filtration device, and a cell culture system that can perform filtration operations appropriately and stably while simplifying assembly work.

[0006] In order to solve the above problems, the filter device of the present disclosure includes a first filter that filters the culture solution by passing it downward, a second filter that is positioned below the first filter and has finer mesh than the first filter, and that filters the culture solution that has passed through the first filter, and a first sealing portion that seals the gap between the outer periphery of the first filter and the outer periphery of the second filter.

[0007] The filtration device according to the present disclosure comprises the above-described filter device, a filter laminate including a well plate disposed below the second filter and capable of containing culture solution that has passed through the second filter, a container that contains the filter laminate and has a lid portion formed with a through hole that passes through in the vertical direction above the filter laminate, a base that is contained in the container and supports the filter laminate from below, a second sealing portion that is provided between the lid portion and the filter laminate along the through hole and seals the gap between the lid portion and the first filter, a pressing portion that generates a pressing force in the vertical direction to bring the lid portion and the filter laminate closer together, and a vacuum device that exhausts air from inside the container below the filter laminate and draws a vacuum in the container.

[0008] The cell culture system according to the present disclosure includes a clean bench equipped with the above-described filtration device.

[0009] According to the filter device, filtration apparatus, and cell culture system of the present disclosure, it is possible to perform filtration operations appropriately and stably while achieving simplified assembly work.

[0010] Fig. 1 is a schematic plan view showing a general configuration of a cell culture system according to an embodiment of the present disclosure; Fig. 2 is a perspective view of a filtration device according to an embodiment of the present disclosure; Fig. 3 is a view of the internal configuration of a filtration device according to an embodiment of the present disclosure, viewed from a second horizontal direction; Fig. 4 is a view of a filtration device according to an embodiment of the present disclosure, viewed from above; Fig. 5 is a view of a first seal portion and a second filter according to an embodiment of the present disclosure, viewed from above; Fig. 6 is a view of the internal configuration of a main part of a filtration device according to a modified example of the present disclosure, viewed from a second horizontal direction.

[0011]

[0016] Hereinafter, an embodiment of the present disclosure will be described in detail with reference to the drawings. The cell culture system 100 of this embodiment shown in Fig. 1 is a system for culturing cells and analyzing the cells after culturing using workpieces such as well plates 30 (see Fig. 3) and flasks, and these processes are performed, for example, unmanned and automatically. The workpieces contain cells and a culture solution L containing a medium supplemented with nutrients necessary for cell growth.

[0012] <Cell Culture System> As shown in FIG. 1, the cell culture system 100 includes a first stocker 110, a second stocker 120, an incubator 130, a clean bench 140, and a pass box 150.

[0013] <First Stocker> The first stocker 110 is a facility for storing a plurality of workpieces. The area within the first stocker 110 is designated as a first storage area R1.

[0014] <Second Stocker> The second stocker 120 is provided adjacent to the first stocker 110. The second stocker 120 is provided with equipment such as a base on which a workpiece can be placed and a refrigerator 4 in which a culture medium can be stored. The area within the second stocker 120 is designated as a second storage area R2.

[0015] <Incubator> The incubator 130 is a facility for growing cells in a culture solution. The incubator 130 has a culture area R3 formed inside where the workpiece is cultured. The atmosphere in the culture area R3 is controlled to a temperature, humidity, and carbon dioxide concentration suitable for cell culture.

[0016] <Clean bench> The clean bench 140 is a facility for performing various liquid manipulations and processes on workpieces. The clean bench 140 forms a clean space S1 inside, and also forms a liquid manipulation area R4 inside the clean space S1, where operations such as dispensing are performed on the workpieces. The liquid manipulation area R4 is a highly clean, sterile space (a bio-clean room). Within the liquid manipulation area R4, air circulates as a downflow (descending air current).

[0017] The clean bench 140 is equipped with various equipment such as a dispensing device, a filtering device 5, a sealing device 3, a waste liquid draining device, a workpiece recovery system, etc. Outside the clean bench 140, a culture medium supplying device capable of supplying culture medium to the dispensing device, a cell analysis device capable of analyzing the culture solution dispensed by the dispensing device, etc. are provided.

[0018] Here, the clean bench 140 is disposed adjacent to the first stocker 110 and the second stocker 120. A first stocker door 110a is provided within the first stocker 110, separating the first storage area R1 from the liquid handling area R4. When the first stocker door 110a is in an open state, the first storage area R1 and the liquid handling area R4 are in a connected state, allowing workpieces to be moved between these areas. When the first stocker door 110a is in a closed state, the first storage area R1 and the liquid handling area R4 are not connected to each other, and these areas are isolated from each other.

[0019] A second stocker door 120a is provided in the second stocker 120 to separate the second storage area R2 from the liquid handling area R4. When the second stocker door 120a is in an open state, the second storage area R2 and the liquid handling area R4 are in a connected state, allowing workpieces to be moved between these areas. When the first stocker door 110a is in a closed state, the first storage area R1 and the liquid handling area R4 are not in a connected state, and these areas are isolated from each other.

[0020] <Pass Box> The pass box 150 is installed between the incubator 130 and the clean bench 140 so as to be in contact with them. The pass box 150 has a first pass door 150a and a second pass door 150b. When the first pass door 150a is open, the incubation area R3 and the area inside the pass box 150 are in communication with each other. When the second pass door 150b is open, the liquid handling area R4 and the area inside the pass box 150 are in communication with each other. Therefore, opening and closing the first pass door 150a and the second pass door 150b switches between an isolated state for the incubation area R3 and the liquid handling area R4 and a state where workpieces can move between these areas. Note that the first pass door 150a and the second pass door 150b are never open at the same time. Therefore, the incubation area R3 and the liquid handling area R4 are not in communication with each other, and the atmospheric conditions of each area are maintained.

[0021] <Transportation Device> Each of the first storage area R1, second storage area R2, culture area R3, and liquid handling area R4 is provided with a transport robot that can move, for example, horizontally as a transport device. This allows workpieces to be moved between each area. The opening and closing of each door is coordinated with the operation of the transport robot, allowing workpieces to move between each area.

[0022] <Detailed Structure of the Filtering Device> However, over time, cells in the culture solution L die, antibodies are produced in the culture solution L, and other unwanted foreign matter (particles) is generated in the culture solution L. If such foreign matter is present in the culture solution L, accurate analysis cannot be performed. For this reason, a filtering device 5 is provided to remove foreign matter from the culture solution L and filter the culture solution L. The detailed structure of this filtering device 5 will be described below.

[0023] 2 and 3 , the filtration device 5 includes a filter stack 10, a container 40, a base 60, a second sealing portion 6, a pressing portion 7, and a vacuum device 70. Hereinafter, one horizontal direction will be referred to as a horizontal first direction Dh1, and the horizontal direction perpendicular to the horizontal first direction Dh1 will be referred to as a horizontal second direction Dh2.

[0024] <Filter Laminate> The filter laminate 10 includes a filter device 8 and a well plate 30 .

[0025] <Filter Device> The filter device 8 includes a first filter 11 , a second filter 12 , and a first seal portion 20 .

[0026] <First Filter> The first filter 11 filters the culture solution L dropped from above by passing it downward. As shown in Fig. 4 , the first filter 11 is formed in the shape of a rectangular plate extending horizontally with its longitudinal direction aligned with a first horizontal direction Dh1. The first filter 11 also has a number of first passages 13 formed therein that penetrate in the up-down direction Dv. Unwanted foreign matter is removed from the culture solution L as it passes through the first passages 13.

[0027] <Second Filter> The second filter 12 is disposed below the first filter 11. The second filter 12 filters the culture solution L that has passed through the first filter 11. As shown in FIG. 5 , the second filter 12 has the same shape as the first filter 11 when viewed from above, and is formed as a rectangular plate extending horizontally with its longitudinal direction aligned with the first horizontal direction Dh1. The second filter 12 also has a plurality of second passages 14 that penetrate in the up-down direction Dv. The mesh of the second filter 12 is finer than that of the first filter 11. That is, the hole diameter of the second passages 14 of the second filter 12 is larger than the hole diameter of the first passages 13 of the first filter 11. As the culture solution L passes through the second passages 14, debris and other foreign matter that has passed through the first filter 11 is removed.

[0028] <First Seal Portion> The first seal portion 20 seals the gap between the outer circumferential edge of the first filter 11 and the outer circumferential edge of the second filter 12. The first seal portion 20 has a first gasket 21 and a fixing jig 22.

[0029] <First Gasket> The two first gaskets 21 are spaced apart in the vertical direction Dv. The two first gaskets 21 spaced apart in the vertical direction Dv are formed to have the same shape. The first gasket 21 extends horizontally along the outer peripheral edge of the first filter 11 or the outer peripheral edge of the second filter 12 and is formed in the shape of a rectangular frame with its longitudinal direction aligned with the horizontal first direction Dh1. The first gasket 21 is a sheet made of, for example, silicone or the like.

[0030] <Fixing Jig> The fixing jig 22 fixes the first gaskets 21 to the first filter 11 and the second filter 12. The fixing jig 22 has a frame 22b and an inner member 22a. The frame 22b surrounds the two first gaskets 21, which are spaced apart in the up-down direction Dv, from the outer periphery. When viewed from above, the frame 22b is formed along the outer peripheries of the first filter 11 and the second filter 12, extends horizontally, and has a rectangular frame shape with its longitudinal direction aligned with the first horizontal direction Dh1. The inner member 22a protrudes horizontally from the frame 22b toward the inner periphery and is disposed between the two first gaskets 21, which are spaced apart in the up-down direction Dv. The inner member 22a presses the upper first gasket 21 against the first filter 11 and presses the lower first gasket 21 against the second filter 12.

[0031] The above-described first seal portion 20 is assembled to the first filter 11 and the second filter 12, for example, by the sealing device 3. Note that the first seal portion 20 may also be assembled to the first filter 11 and the second filter 12 outside the clean bench 140, for example, manually.

[0032] <Well Plate> The well plate 30 is disposed below the second filter 12. The well plate 30 contains the culture solution L that has passed through the second filter 12. The well plate 30 has a plurality of wells 31 that are open upward. The culture solution L is contained in each well 31.

[0033] <Ventilation Section> A ventilation section 32 is provided between the second filter 12 and the well plate 30. The ventilation section 32 exhausts air A from between the second filter 12 and the well plate 30. In this embodiment, the ventilation section 32 is an opening formed on the outer periphery of the upper surface 46a of the well plate 30. The gap between the second filter 12 and the well plate 30 may also be used as the ventilation section 32.

[0034] <Container> The container 40 accommodates the filter laminate 10 and a base 60 (described later) inside. The container 40 has a base 41, a first sheet 42, a body 43, a second sheet 44, and a lid 45.

[0035] <Base> A pedestal 60 is placed on the base 41. The base 41 is made of metal. The base 41 is fixed to a support surface F of a work table installed on the clean bench 140. The base 41 has a base main body 46 and a base flange 47. The base main body 46 is formed in a rectangular parallelepiped shape extending in the horizontal direction. When viewed from above, the base main body 46 is formed in a rectangular shape with its longitudinal direction aligned with the first horizontal direction. An exhaust space S is formed inside the base main body 46. A base through-hole 46b is formed in the upper surface 46a of the base main body 46, penetrating in the up-down direction Dv and communicating with the exhaust space S. A plurality of base through-holes 46b are provided. The base flange 47 protrudes horizontally from the outer periphery of the upper surface 46a of the base main body 46. The base flange 47 is formed in the shape of a rectangular frame that extends horizontally and has a longitudinal direction that is the first horizontal direction Dh1.

[0036] <First Sheet> The first sheet 42 is a rectangular frame-shaped sheet placed on the base flange 47. The first sheet 42 brings the base 41 and the body 43 into close contact with each other. The first sheet 42 is a sheet made of, for example, silicone.

[0037] <Body> The body 43 is placed on the base 41 via the first sheet 42. The body 43 is in close contact with the base 41 and is provided so as to surround the filter laminate 10 and the pedestal 60. The body 43 is formed in a rectangular tubular shape extending upward from the base main body 46. The body 43 is made of metal.

[0038] A lower flange 48 is formed at the lower end of the body 43, and an upper flange 49 is formed at the upper end of the body 43. The lower flange 48 extends horizontally and is formed into a rectangular frame shape with its longitudinal direction aligned with the first horizontal direction Dh1. The lower flange 48 and the base flange 47 sandwich the first sheet 42, thereby compressing the first sheet 42 in the up-down direction Dv. This brings the lower flange 48 and the base flange 47 into tight contact with each other without any gaps, sealing the gap between the base 41 and the body 43. The upper flange 49 extends horizontally and is formed into a rectangular frame shape with its longitudinal direction aligned with the first horizontal direction Dh1.

[0039] <Second Sheet> The second sheet 44 is a rectangular frame-shaped sheet placed on the upper flange 49. The second sheet 44 tightly contacts the body portion 43 and the lid portion 45. The second sheet 44 is a sheet made of, for example, silicone.

[0040] <Lid> The lid 45 is placed on the body 43. The lid 45 is in close contact with the body 43 via the second sheet 44 and closes the upper opening of the body 43. The lid 45 is made of metal. The lid 45 has a first lid portion 50, a second lid portion 51, and a third lid portion 52.

[0041] The first lid portion 50 is placed on the second sheet 44. The first lid portion 50 is formed in a rectangular frame shape. The first lid portion 50 and the upper flange 49 sandwich the second sheet 44, thereby compressing the second sheet 44 in the up-down direction Dv. This brings the first lid portion 50 and the upper flange 49 into tight contact with each other without any gaps, and seals any gaps between the lid portion 45 and the body portion 43.

[0042] The second lid portion 51 is formed in a rectangular tubular shape extending upward from the inner peripheral edge of the first lid portion 50. The third lid portion 52 is provided to close the upper opening of the second lid portion 51. A through hole 52a penetrating in the up-down direction Dv is formed in the center of the third lid portion 52. The through hole 52a extends horizontally and is formed in a rectangular shape with its longitudinal direction aligned with the first horizontal direction Dh1. The through hole 52a is provided above the filter stack 10.

[0043] <Base> The base 60 is housed in the container 40 and supports the filter laminate 10 from below. The base 60 has a jack portion 61 and a mounting plate 62. The jack portion 61 is provided so as to be extendable and retractable in the up-down direction Dv. The mounting plate 62 is supported from below by the jack. A recess 63 that opens upward is formed in the upper surface 46a of the mounting plate 62. The well plate 30 of the filter laminate 10 is fitted into the recess 63.

[0044] <Second seal portion> The second seal portion 6 is provided along the through-hole 52a between the lid portion 45 and the filter stack 10. The second seal portion 6 seals the gap between the lid portion 45 and the first filter 11. The second seal portion 6 is formed in a rectangular frame shape so as to annularly surround the multiple first passages 13 of the first filter 11. The second seal portion 6 is formed from, for example, silicone.

[0045] <Pressing portion> The pressing portion 7 generates a pressing force in the vertical direction Dv that brings the lid portion 45 and the filter stack 10 closer together. The pressing portion 7 in this embodiment is a weight that is placed on the lid portion 45 and formed in a ring shape along the through hole 52a. Therefore, the pressing portion 7 in this embodiment generates a downward pressing force that presses the lid portion 45 against the filter stack 10. Furthermore, the pressing portion 7 is formed in the shape of a rectangular frame that extends in the horizontal direction and has a longitudinal direction that is the horizontal first direction Dh1.

[0046] <Vacuum Device> The vacuum device 70 is a device that exhausts air A from inside the container 40 from below the filter laminate 10 to evacuate the container 40. The vacuum device 70 has a tube 71 and a pump 72. The tube 71 is connected to the base 41 of the container 40. The tube 71 is in communication with the exhaust space S inside the base 41. The pump 72 is also connected to the tube 71 and exhausts air A from inside the container 40 to the outside via the tube 71.

[0047] <Assembly of the Filtration Device> Next, the procedure for assembling the filtration device will be described. First, the filtration device 5 is assembled. The assembly of the filtration device 5 is performed automatically by a robot (not shown) installed in the clean bench 140. The base 41 of the container 40 of the filtration device 5 is fixed to the installation position of the filtration device 5. The filter laminate 10 of the filtration device 5 is assembled outside the base 41. Next, the pedestal 60, the filter laminate 10, and the second seal portion 6 are placed on the base 41 in this order from below. After that, the first sheet 42, the body portion 43, the second sheet 44, and the lid portion 45 are placed on the base 41 in this order from below. Then, the pressing portion 7 is placed on the lid portion 45. The load of the pressing portion 7 crushes the second seal portion 6. This causes the lid portion 45 and the filter laminate 10 to tightly contact each other. This completes the assembly of the filtration device 5.

[0048] <Filtration Procedure> Next, the filtration procedure will be described. After completing the assembly of the filtration device 5, the culture solution L is dripped from above the first filter 11. Then, the vacuum device 70 is operated to draw a vacuum inside the container 40. This generates a downward flow of air A (downflow) through the through-holes 52a in the lid 45. The air A that enters the filtration device 5 through the through-holes 52a in the lid 45 flows through the filtration device 5 in the following order: the first filter 11, the second filter 12, the ventilation section 32, the interior of the container 40, the exhaust space S in the base 41, and the tube 71. This flow of air A allows the culture solution L to flow smoothly through the first filter 11, the second filter 12, and the well plate 30. Foreign matter (particles), such as dead cells, in the culture solution L is removed by the first filter 11 and the second filter 12, and the well plate 30 contains culture solution L with little foreign matter. This completes the filtration procedure.

[0049] Thereafter, the well plate 30 is removed from the filtration device 5 and transported to each facility within the cell culture system 100. The well plate 30 is transported, for example, by a transport device to the refrigerator 4 in the second stocker 120. Note that the well plate 30 may be transported as the filter stack 10 with the filter device 8 assembled thereto, or may be transported separately from the filter device 8.

[0050] <Operation and Effect> In the present embodiment, the filter laminate 10 includes a first filter 11, a second filter 12, and a first sealing portion 20. The first filter 11 filters the culture solution L by passing it downward. The second filter 12 is disposed below the first filter 11. The second filter 12 has finer mesh than the first filter 11 and filters the culture solution L that has passed through the first filter 11. The first sealing portion 20 seals the gap between the outer periphery of the first filter 11 and the outer periphery of the second filter 12.

[0051] The culture solution L is first filtered through the first filter 11. The first filter 11 removes relatively large impurities from the culture solution L. The culture solution L is then filtered through the second filter 12. The second filter 12 removes relatively small impurity fragments that have passed through the first filter 11. In this manner, the culture solution L can be filtered using a dual filter system. Therefore, in this embodiment, larger particles are removed through the large-mesh first filter 11, and the reduced particle amount is passed through the fine-mesh second filter 12. This prevents clogging of the second filter 12 and ensures stable filtration. Furthermore, the first filter 11 and the second filter 12 are provided separately. This allows selection of the first filter 11 and the second filter 12 that are appropriate for the culture solution L to be filtered. This prevents clogging of the culture solution L and improves the filtration rate. This enables appropriate and stable filtration. The gap between the first filter 11 and the second filter 12 is sealed by the first seal portion 20. This allows the first filter 11 and the second filter 12 to be tightly attached to each other. Therefore, when the container 40 is evacuated using the vacuum device 70 and air A flows from the first filter 11 to the second filter 12, as in this embodiment, this flow of air A is prevented from leaking through the gap between the first filter 11 and the second filter 12. This sufficiently reduces the pressure inside the container 40, allowing the flow of air A to smoothly move the culture solution L from the first filter 11 to the second filter 12, further improving the filtration rate. Furthermore, the filter stack 10 can be easily assembled by simply stacking the second filter 12, the first seal portion 20, and the first filter 11 in this order from below. Thus, this embodiment simplifies the assembly process.

[0052] The first seal portion 20 includes two first gaskets 21 spaced apart in the vertical direction Dv and a fixing jig 22 that fixes the first gaskets 21 to the first filter 11 and the second filter 12. The fixing jig 22 includes a frame 22b and an inner member 22a. The frame 22b surrounds the two first gaskets 21 spaced apart in the vertical direction Dv from the outer periphery. The inner member 22a protrudes horizontally from the frame 22b toward the inner periphery and is located between the two first gaskets 21 spaced apart in the vertical direction Dv. The inner member 22a presses the upper first gasket 21 against the first filter 11 and presses the lower first gasket 21 against the second filter 12.

[0053] The first filter 11, the second filter 12, and the first gasket 21 are fixed in place while being surrounded from the outer periphery by the frame 22b of the fixing jig 22. This prevents misalignment between the first filter 11, the second filter 12, and the first gasket 21, improving adhesion between the first filter 11 and the second filter 12. Furthermore, for example, when the filter device 8 is assembled to the well plate 30 and automatically transported as the filter stack 10 by a transport device, misalignment between the first filter 11 and the second filter 12 can be prevented even if vibrations during transport are transmitted to the filter device 8.

[0054] The filtration device 5 includes a filter laminate 10, a container 40, a base 60, a second seal unit 6, a pressing unit 7, and a vacuum device 70. The filter laminate 10 includes a filter device 8 and a well plate 30 disposed below the second filter 12 and capable of containing the culture solution L that has passed through the second filter 12. The container 40 accommodates the filter laminate 10. The container 40 has a lid unit 45 formed with a through-hole 52a that penetrates in the vertical direction Dv above the filter laminate 10. The base 60 is accommodated in the container 40 and supports the filter laminate 10 from below. The second seal unit 6 is provided between the lid unit 45 and the filter laminate 10 along the through-hole 52a and seals the gap between the lid unit 45 and the first filter 11. The pressing unit 7 generates a pressing force in the vertical direction Dv that brings the lid unit 45 and the filter laminate 10 closer together. The vacuum device 70 exhausts the air A from inside the container 40 from below the filter laminate 10 to draw a vacuum in the container 40 .

[0055] According to this embodiment, the first seal 20 tightly seals the first filter 11 and the second filter 12, and the second seal 6 tightly seals the first filter 11 against the edge of the through-hole 52a in the lid 45. Furthermore, the pressing portion 7 brings the first filter 11 and the lid 45 closer together, improving the seal provided by the second filter 12. In this state, the vacuum device 70 is driven to evacuate the container 40, sufficiently reducing the pressure inside the container 40 and generating a flow of air A from the first filter 11 toward the second filter 12. This allows the culture solution L to smoothly pass through the first filter 11 and the second filter 12, improving the filtration rate. Furthermore, these components can be easily assembled by simply stacking the filter stack 10, second seal 6, and lid 45 on the base 60 in this order from below. Thus, this embodiment simplifies the assembly process.

[0056] The filter stack 10 further includes a ventilation section 32 that is provided between the second filter 12 and the well plate 30 and that discharges air A from between the second filter 12 and the well plate 30 .

[0057] For example, when the filter device 8 is installed so that air A flows from the first filter 11 to the second filter 12, the first sealing portion 20 prevents air A from leaking out of the gap between the first filter 11 and the second filter 12, while the ventilation portion 32 allows air A that has passed through the first filter 11 and the second filter 12 to be smoothly discharged.

[0058] The container 40 further includes a base 41 on which the seat 60 is placed, and a body 43 placed on the base 41, in close contact with the base 41, and surrounding the filter laminate 10 and the seat 60. The lid 45 is placed on the body 43, in close contact with the body 43, and closes the body 43.

[0059] This allows the container 40 to be easily assembled by simply stacking the base 41, the body 43, and the lid 45 in this order from below. Also, the base 60 and the filter laminate 10 can be easily installed inside the container 40. In this way, according to this embodiment, the assembly process can be simplified.

[0060] The pressing portion 7 is a weight placed on the lid portion 45 and formed in a ring shape along the through hole 52a.

[0061] In this embodiment, the second seal portion 6 and a weight are provided along the through hole 52 a. The weight applies a downward pressing force to the lid portion 45 at a position that overlaps with the second seal portion 6, thereby improving the adhesion of the second seal portion 6.

[0062] <Modifications> Next, a modification of the filtration device 5 will be described. As shown in Fig. 6, the lid portion 45 may have a protrusion 52b that protrudes downward and is provided at a position overlapping the second seal portion 6 in the up-down direction Dv. The protrusion 52b is provided on the lower surface of the third lid portion 52 of the lid portion 45, along the through hole 52a. A plurality of protrusions 52b may be provided along the through hole 52a, or may be formed in the shape of a rectangular frame that follows the through hole 52a.

[0063] In this modification, the pressing force of the pressing portion 7 is concentrated on the second seal portion 6 by the protrusions 52b, thereby improving the adhesion of the second seal portion 6.

[0064] <Other Embodiments> Although the embodiments of the present disclosure have been described in detail above with reference to the drawings, the specific configuration is not limited to this embodiment, and design changes and the like are also included within the scope that does not deviate from the gist of the present disclosure.

[0065] In the above-described embodiment, the first seal portion 20 includes the first packing 21 and the fixing jig 22, but is not limited to this. The first seal portion 20 may be a silicone sheet, clay, or the like.

[0066] In the above-described embodiment, the pressing unit 7 is a weight placed on the lid unit 45, but this is not limiting. The pressing unit 7 may be, for example, a hydraulic cylinder or a robot arm. Furthermore, the pressing unit 7 may generate an upward pressing force that presses the filter stack 10 against the lid unit 45.

[0067] <Additional Notes> The filter device 8, the filtration device 5, and the cell culture system 100 described in each embodiment can be understood, for example, as follows.

[0068] (1) The filter device 8 according to the first aspect includes a first filter 11 that filters the culture solution L by passing it downward, a second filter 12 that is arranged below the first filter 11, has finer mesh than the first filter 11, and filters the culture solution L that has passed through the first filter 11, and a first sealing portion 20 that seals the gap between the outer periphery of the first filter 11 and the outer periphery of the second filter 12.

[0069] The culture solution L is first filtered through the first filter 11. The first filter 11 removes relatively large impurities from the culture solution L. The culture solution L is then filtered through the second filter 12. The second filter 12 removes relatively small impurity fragments that have passed through the first filter 11. In this manner, the culture solution L can be filtered using a dual filter system. Therefore, in this embodiment, larger particles are removed through the large-mesh first filter 11, and the reduced particle amount is passed through the fine-mesh second filter 12. This prevents clogging of the second filter 12 and ensures stable filtration. Furthermore, the first filter 11 and the second filter 12 are provided separately. This allows selection of the first filter 11 and the second filter 12 that are suitable for the culture solution L to be filtered. This prevents clogging of the culture solution L and improves the filtration rate. This enables appropriate and stable filtration. The gap between the first filter 11 and the second filter 12 is sealed by the first seal portion 20. This allows the first filter 11 and the second filter 12 to be tightly attached to each other. Therefore, for example, when the filter device 8 is installed so that air A flows from the first filter 11 to the second filter 12, this prevents the flow of air A from leaking through the gap between the first filter 11 and the second filter 12. This allows the culture solution L to move smoothly from the first filter 11 to the second filter 12, further improving the filtration rate. Furthermore, the filter stack 10 can be easily assembled by simply stacking the second filter 12, the first seal portion 20, and the first filter 11 in this order from below. In this way, this embodiment can simplify the assembly process.

[0070] (2) A second aspect of the filter device 8 is the filter device 8 of (1), wherein the first seal portion 20 has two first gaskets 21 spaced apart in the vertical direction Dv and a fixing jig 22 that fixes the first gaskets 21 to the first filter 11 and the second filter 12, and the fixing jig 22 may have a frame body 22b that surrounds the two first gaskets 21 spaced apart in the vertical direction Dv from the outer periphery, and an inner member 22a that protrudes horizontally from the frame body 22b toward the inner periphery and is located between the two first gaskets 21 spaced apart in the vertical direction Dv, and presses the upper first gasket 21 against the first filter 11 and presses the lower first gasket 21 against the second filter 12.

[0071] The first filter 11, the second filter 12, and the first packing 21 are fixed in a state in which they are surrounded from the outer periphery by the frame body 22b of the fixing jig 22. This prevents misalignment between the first filter 11, the second filter 12, and the first packing 21, and improves the adhesion between the first filter 11 and the second filter 12.

[0072] (3) A third aspect of the filtration device 5 includes: a filter laminate 10 including one of the filter devices 8 of (1) or (2); a well plate 30 arranged below the second filter 12 and capable of containing culture solution L that has passed through the second filter 12; a container 40 that contains the filter laminate 10 and has a lid portion 45 with a through hole 52 a formed above the filter laminate 10 and penetrating in the vertical direction Dv; a base 60 that is contained in the container 40 and supports the filter laminate 10 from below; a second sealing portion 6 that is provided along the through hole 52 a between the lid portion 45 and the filter laminate 10 and seals the gap between the lid portion 45 and the first filter 11; a pressing portion 7 that generates a pressing force in the vertical direction Dv to bring the lid portion 45 and the filter laminate 10 closer together; and a vacuum device 70 that exhausts air A from inside the container 40 below the filter laminate 10 and draws a vacuum in the container 40.

[0073] According to this embodiment, the first seal 20 tightly seals the first filter 11 and the second filter 12, and the second seal 6 tightly seals the first filter 11 against the edge of the through-hole 52a in the lid 45. Furthermore, the pressing portion 7 brings the first filter 11 and the lid 45 closer together, improving the seal provided by the second filter 12. In this state, the vacuum device 70 is driven to evacuate the container 40, sufficiently reducing the pressure inside the container 40 and generating a flow of air A from the first filter 11 to the second filter 12. This allows the culture solution L to smoothly pass through the first filter 11 and the second filter 12, improving the filtration rate. Furthermore, the filter stack 10, the second seal 6, and the lid 45 can be easily assembled by simply stacking these components on the base 60 in this order from below. Thus, this embodiment simplifies the assembly process.

[0074] (4) A fourth aspect of the filtration device 5 is the filtration device 5 of (3), wherein the filter stack 10 is provided between the second filter 12 and the well plate 30 and may further include a ventilation section 32 for discharging air A from between the second filter 12 and the well plate 30.

[0075] For example, when the filter device 8 is installed so that air A flows from the first filter 11 to the second filter 12, the first sealing portion 20 prevents air A from leaking out of the gap between the first filter 11 and the second filter 12, while the ventilation portion 32 allows air A that has passed through the first filter 11 and the second filter 12 to be smoothly discharged.

[0076] (5) A fifth aspect of the filtration device 5 is the filtration device 5 of (3) or (4), wherein the container 40 further comprises a base 41 on which the pedestal 60 is placed, and a body 43 placed on the base 41, in close contact with the base 41, and surrounding the filter laminate 10 and the pedestal 60, and the lid 45 may be placed on the body 43, in close contact with the body 43, and closing the body 43.

[0077] This allows the container 40 to be easily assembled by simply stacking the base 41, the body 43, and the lid 45 in this order from below. Also, the base 60 and the filter laminate 10 can be easily installed inside the container 40. In this way, this embodiment can simplify the assembly process.

[0078] (6) The sixth aspect of the filtration device 5 is any one of the filtration devices 5 of (3) to (5), and the pressing portion 7 may be a weight placed on the lid portion 45 and formed in a ring shape along the through hole 52a.

[0079] In this embodiment, the second seal portion 6 and a weight are provided along the through hole 52 a. The weight applies a downward pressing force to the lid portion 45 at a position that overlaps with the second seal portion 6, thereby improving the adhesion of the second seal portion 6.

[0080] (7) The seventh aspect of the filtration device 5 is any one of the filtration devices 5 of (3) to (6), and the lid portion 45 may have a protrusion portion 52b that protrudes downward and is positioned so as to overlap the second seal portion 6 in the vertical direction Dv.

[0081] In this embodiment, the pressing force of the pressing portion 7 is concentrated on the second seal portion 6 by the protrusions 52b, thereby improving the adhesion of the second seal portion 6.

[0082] (8) The cell culture system 100 of the eighth aspect includes a clean bench 140 equipped with a filtration device 5 according to any one of (3) to (7).

[0083] According to the filter device, filtration apparatus, and cell culture system of the present disclosure, it is possible to perform filtration operations appropriately and stably while achieving simplified assembly work.

[0084] REFRIGERATOR 5 FILTRATION DEVICE 6 SECOND SEALING PORTION 7 PRESSURE PORTION 8 FILTRATION DEVICE 10 FILTER LAYER 11 FIRST FILTER 12 SECOND FILTER 13 FIRST PASSAGE 14 SECOND PASSAGE 20 FIRST SEALING PORTION 21 FIRST GASKETS 22 FIXING JIG 22a INNER MEMBER 22b FRAME 30 WELL PLATE 31 WELL 32 VENTILATION PORTION 40 CONTAINER 41 BASE 42 FIRST SHEET 43 BODY 44 SECOND SHEET 45 LIQUID 46 BASE BODY 46a UPPER SURFACE 46b BASE THROUGH-HOLE 47 BASE FLANGE 48 LOWER FLANGE 49 UPPER FLANGE 50 LIQUID FIRST PORTION 51 LIQUID SECOND PORTION 52 LIQUID THIRD PORTION 52a THROUGH-HOLE 52b PROJECTION 60 BASE 61 JACK PORTION 62 Mounting plate 63 Recess 70 Vacuum device 71 Tube 72 Pump 100 Cell culture system 110 First stocker 110a First stocker door 120 Second stocker 120a Second stocker door 130 Incubator 140 Clean bench 150 Pass box 150a First pass door 150b Second pass door A Air Dv Up-down direction Dh1 Horizontal first direction Dh2 Horizontal second direction F Mounting surface L Culture fluid R1 First storage area R2 Second storage area R3 Culture area R4 Liquid handling area S Exhaust space

Claims

1. A filter device comprising: a first filter that filters by allowing a culture solution to pass downward; a second filter disposed below the first filter, having finer pores than the first filter, and filtering the culture solution that has passed through the first filter; and a first sealing portion that seals a gap between an outer peripheral edge of the first filter and an outer peripheral edge of the second filter.

2. The filter device according to claim 1, wherein the first sealing portion includes two first packings provided apart in the vertical direction, and a fixing jig that fixes the first packings to the first filter and the second filter, the fixing jig including a frame body that surrounds the two first packings provided apart in the vertical direction from the outer peripheral side, and an inner member that protrudes from the frame body in the horizontal direction toward the inner peripheral side, is provided between the two first packings provided apart in the vertical direction, presses the upper first packing against the first filter, and presses the lower first packing against the second filter.

3. A filtering device comprising: the filter device according to claim 1 or 2; a filter laminate including a well plate disposed below the second filter and capable of accommodating the culture solution that has passed through the second filter; a container that houses the filter laminate and has a lid portion formed with a through hole that penetrates vertically above the filter laminate; a pedestal that is housed in the container and supports the filter laminate from below; a second sealing portion that is provided along the through hole between the lid portion and the filter laminate and seals a gap between the lid portion and the first filter; a pressing portion that generates a vertical pressing force for bringing the lid portion and the filter laminate closer to each other; and a vacuum device that discharges air in the container from below the filter laminate and evacuates the container.

4. The filtering device according to claim 3, wherein the filter laminate further includes a vent portion provided between the second filter and the well plate and configured to discharge air from between the second filter and the well plate.

5. The container further includes a base portion on which the pedestal is placed, and a body portion that is placed on the base portion, is in close contact with the base portion, and surrounds the filter laminate and the pedestal. The lid portion is placed on the body portion, is in close contact with the body portion, and closes the body portion. The filtration device according to claim 3.

6. The pressing portion is a weight that is placed on the lid portion and is formed in an annular shape along the through hole. The filtration device according to claim 3.

7. The lid portion has a protrusion that protrudes downward and is provided at a position that vertically overlaps the second seal portion. The filtration device according to claim 3.

8. A cell culture system comprising a clean bench equipped with the filtration device according to claim 3.

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