Cell culture device

Abstract

To provide a cell culture device that allows operation units for different functions to be driven in a more optimized environment.SOLUTION: A device includes a first space (such as the internal space of a culture medium exchange unit 22) that satisfies a first standard (such as ISO class 5) for the standard of air cleanliness, a second space (such as the internal space of a portion other than the culture medium exchange unit 22) that satisfies a second standard (such as ISO class 6 to 7) that is lower than the first standard for the standard of air cleanliness, a culture medium exchange robot 42 that is installed in the first space and capable of performing operations related to culture medium exchange, a transport robot 40 that is installed in the second space and capable of performing operations to move a well plate 52 in which culture medium is stored, and a control unit that sets the movable range of the culture medium exchange robot 42 when performing operations related to culture medium exchange within the first space and the movable range of the transport robot 40 when moving the well plate 52 within the second space and the first space.SELECTED DRAWING: Figure 2

Description

Technical Field

[0001] The present invention relates to a cell culture device including, for example, a plurality of operating robots.

Background Art

[0002] Patent Document 1 (Claim 1, etc.) described later discloses an invention related to an automatic culture operation device in which a first robot and a second robot are arranged in a work chamber such that a part of their movable ranges overlaps. In Patent Document 1, a liquid supply means and a temporary placement part are provided in the overlapping movable range of the first robot and the second robot. Then, the liquid supply means supplies liquids such as a culture medium and a chemical solution to containers held by the robot, and the first robot and the second robot transfer the containers at the temporary placement part.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] By the way, Patent Document 1 describes that purified air is circulated to maintain a positive pressure in the work chamber. However, Patent Document 1 does not describe optimizing the installation environment and working environment of operating parts having different functions such as the first robot and the second robot.

[0005] An object of the present invention is to provide a cell culture device capable of operating operating parts with different functions in a more optimized environment.

Means for Solving the Problems

[0006] A cell culture device according to an embodiment of the present invention is A first space that meets the first standard as the air cleanliness standard, a second space that meets a second standard lower than the first standard as the air cleanliness standard, a first operation unit installed in the first space and capable of performing operations related to medium replacement, a second operation unit installed in the second space and capable of performing a movement operation of a cell culture container storing a medium, operation unit control means that sets the movable range when the first operation unit performs an operation related to medium replacement within the first space, and sets the movable range when the second operation unit moves the cell culture container to the second space and the first space and includes.

Effect of the Invention

[0007] According to the present invention, it is possible to provide a cell culture device capable of operating operation units with different functions in a more optimized environment.

Brief Description of the Drawings

[0008]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

Mode for Carrying Out the Invention

[0009] <Basic Configuration of Cell Culture Apparatus 10> Hereinafter, the cell culture apparatus 10 according to the embodiment will be described with reference to the drawings. FIG. 1 shows the cell culture apparatus 10 according to the embodiment. The cell culture apparatus 10 includes an incubator unit 12, an image inspection unit 14, a stocker supply unit 16, a product take-out unit 18, a transfer robot unit 20, and a medium exchange unit 22. Hereinafter, these may be collectively referred to as "each part".

[0010] Also, in the present embodiment, the stocker supply unit 16 and the product take-out unit 18 are integrated. For this reason, for example, it is possible to refer to both of them as a "stocker supply take-out unit" or a "stocker supply discharge unit".

[0011] About 2 / 3 of the upper part of each part is surrounded by the wall part 10A. In the present embodiment, the wall part 10A is formed in a T-shaped shape when the cell culture apparatus 10 is viewed in plan from the ceiling side, and airtightly surrounds the inner space. A plurality of transparent window parts 10B that enable visual observation of each part by an operator A (shown by a two-dot chain line) and the like are formed in the wall part 10A. Note that the arrangement of the wall part 10A is not limited to the T shape, and can be variously changed, for example, to a rectangular shape, an L shape, etc. according to circumstances such as the shape of the installation space.

[0012] Figure 2 shows the state where the wall portion 10A is removed from the cell culture device 10 of FIG. 1. As shown in FIG. 2, the cell culture device 10 is provided with an incubator 32, an image inspection device 34, a transfer robot 40, and a medium replacement robot 42. The medium replacement robot 42 is provided in the medium replacement device 43. Details of these devices and each part will be described later.

[0013] Figure 3 shows the layout of each part. More specifically, FIG. 3 shows the state of the cell culture device 10 viewed from above in a plan view with the wall portion 10A removed. In the central part, the transfer robot part 20 among each part is arranged, and the other incubator part 12, image inspection part 14, stocker supply part 16, product take-out part 18, and medium replacement part 22 are arranged in order so as to surround the transfer robot part 20 clockwise in FIG. 3. Regarding the layout of each part, although it can be described in a plurality of other modes, other description modes will be described later.

[0014] <The First Space and the Second Space> The inside of the cell culture device 10 is partitioned into the internal space of the medium replacement part 22 and the internal space of the part other than the medium replacement part 22 (the incubator part 12, the image inspection part 14, the stocker supply part 16, the product take-out part 18, and the transfer robot part 20). The internal spaces of the parts other than the medium replacement part 22 are spatially connected. The internal space of the medium replacement part 22 is the first space, and the internal space of the part other than the medium replacement part 22 is the second space. Although details will be described later, inside the wall portion 10A (FIG. 1), as shown in FIG. 11, a part of the wall portion 22B of the medium replacement part 22 partitions the first space (the internal space of the medium replacement part 22) and the second space (the internal space other than the medium replacement part 22).

[0015] When the cell culture device 10 is in use, it is possible to make the air cleanliness levels of the first space and the second space different from each other. The first space satisfies the first standard as the air cleanliness standard, and the second section satisfies the second standard lower than the first standard.

[0016] In this embodiment, the first standard for the first space is, for example, Class 5 or lower according to ISO (International Organization for Standardization) (Class 100 according to the US Federal Standard). On the other hand, the second standard for the second space is, for example, Class 6 - 7 according to ISO (Class 1000 - 10000 according to the US Federal Standard). Note that as long as the air cleanliness of the medium exchange section can be maintained at a level necessary for medium exchange, the relationship between the air cleanliness of the first space and the second space is not limited to the above examples. For example, it is also possible to lower the air cleanliness of the second space by three ranks or more compared to the first space.

[0017] As shown in FIG. 1, outside the ceiling portion 24 in the medium exchange section 22, a filter unit 26 for the first space is provided. By this filter unit 26 for the first space, purified air (cleaned air) is supplied into the first space, and the air cleanliness of the first space is maintained. Outside the ceiling portion 23 in the transfer robot section 20, a filter unit 28 for the second space is provided. By this filter unit 28 for the second space, purified air is supplied into the second space, and the air cleanliness of the second space is maintained.

[0018] Note that the arrangement of the filter unit 28 for the second space is not limited to the ceiling portion 23 in the transfer robot section 20, and it may be the ceiling portion of other parts. Also, the filter unit 28 for the second space may be arranged at a plurality of locations. For example, FIG. 9(b) schematically shows the image inspection section 14 with the filter unit 28 for the second space arranged on the ceiling portion 25 of the image inspection section 14.

[0019] In the first space where parts other than the medium exchange unit 22 are arranged, a stocker 54 (described later) is supplied from the stocker supply unit 16. Further, a well plate 52 (described later) containing cells after culturing is taken out from the product take-out unit 18 while being placed on the stocker 54. Note that the supply and take-out of the stocker 54 can be performed by a transfer robot (not shown) installed outside the cell culture device 10. At this time, the work can be performed with the window portion 10B (which may be a manual door or an automatic door) facing the stocker supply unit 16 and the product take-out unit 18 open.

[0020] In the first space related to the medium exchange unit 22, various operations related to medium exchange as described later are performed under an air cleanliness environment higher than that of the second space related to other parts. Note that, according to the process, the automatic opening and closing shutter 152 (shown in FIG. 11 and described later) located at the boundary between the medium exchange unit 22 and the second space may be opened, and the tip of the transfer robot 40 installed in the first section may enter the second section to perform a predetermined operation.

[0021] Further, an opening and closing shutter unit 36 (FIG. 5) that partitions the second space and the space outside the cell culture device 10 (external space) is provided in the transfer robot unit 20 where the transfer robot 40 is installed. Then, depending on the situation, the opening and closing shutter unit 36 of the transfer robot unit 20 may be opened, and the operator A may enter and exit. The entry and exit of the operator A are limited to the maintenance of the incubator 32 and the transfer robot 40.

[0022] <The First Operation Unit and the Second Operation Unit> The cell culture device 10 includes a first operation unit and a second operation unit. The first operation unit is installed in the first space and can execute operations related to medium exchange. The medium exchange robot 42 corresponds to the first operation unit. The second operation unit is installed in the second space and can execute a movement operation of a cell culture container storing a medium. The transfer robot 40 corresponds to the second operation unit.

[0023] The medium exchange robot 42 and the transfer robot 40 are vertical articulated robots having six-axis (three orthogonal axes and rotations around each axis) degrees of freedom. Note that the medium exchange robot 42 and / or the transfer robot 40 may be an articulated robot having less than six axes or more than six axes. Also, the drive methods of the medium exchange robot 42 and the transfer robot 40 are both AC (DC) servo methods. The medium exchange robot 42 and the transfer robot 40 are respectively installed at fixed positions in the medium exchange unit 22 and the transfer robot unit 20, and their tip ends are moved (including rotational movement) within their respective movable ranges.

[0024] The medium exchange robot 42 (first operation unit) and the transfer robot 40 (second operation unit) are controlled by a control unit 46 (FIG. 5). The control unit 46 comprehensively shows the control units of the parts (incubator unit 12, image inspection unit 14, stocker supply unit 16, product extraction unit 18, transfer robot unit 20, and medium exchange unit 22) that involve computer control. This control unit 46 may include a control unit that comprehensively controls a plurality of parts among the respective parts.

[0025] Regarding the medium exchange robot 42 (first operation unit) and the transfer robot 40 (second operation unit), the control unit 46 sets the movable range when the medium exchange robot 42 performs an operation related to medium exchange within the first space, and controls the movable range when the transfer robot 40 moves a cell culture vessel (well plate 52, described later) to be within the second space and the first space. The control unit of the medium exchange robot 42 and the control unit of the transfer robot 40 can be collectively referred to as, for example, an operation unit control unit (operation unit control means).

[0026] Specifically, in the cell culture device 10, the movable range of the medium exchange robot 42 during medium exchange is limited to the inside of the medium exchange unit 22. In contrast, the movable range of the transfer robot 40 is not limited to the inside of the transfer robot unit 20, and includes the medium exchange unit 22 (here, a part of the medium exchange unit 22), the incubator unit 12, the image inspection unit 14, the stocker supply unit 16, and the product removal unit 18. And the transfer robot 40 can insert its tip into any of these parts.

[0027] Also, although details will be described later, in the medium exchange robot 42 and the transfer robot 40, various operating devices (operating devices) such as the aspirator tool 134 shown in FIG. 10, the micropipette tool 136, the pipetter tool 138, and the air gripper 68 shown in FIG. 7(a) are attached to the respective tips. And the medium exchange robot 42 and the transfer robot 40 perform predetermined operations using various operating devices within their respective movable ranges.

[0028] <Other Explanation 1 Regarding the Layout of Each Part (Arrangement in Multiple Quadrants)> Regarding the layout of each part (the incubator unit 12, the image inspection unit 14, the stocker supply unit 16, the product removal unit 18, the transfer robot unit 20, and the medium exchange unit 22), in addition to the description of arranging the transfer robot unit 20 as described above, the following description can also be made.

[0029] For example, as shown in FIG. 4(a), with the position of the rotation center of the transfer robot 40 as the origin, XY coordinates are set planar, and the space defined by these XY coordinates is divided into the first quadrant Q1 to the fourth quadrant Q4. And the central parts 12C, 14C, (16 + 18)C, 22C of each part are arranged in at least three of the first quadrant Q1 to the fourth quadrant Q4 (here, the first quadrant Q1, the boundary between the second quadrant Q2 and the third quadrant, and the fourth quadrant Q4).

[0030] Here, (16 + 18)C in FIG. 4(a) indicates that it is the central part between both the stocker supply unit 16 and the product take-out unit 18. Also, in FIG. 4(a), the illustration of the central part (20C) of the transfer robot unit 20 is omitted.

[0031] In the example of FIG. 4(a), the central part 12C of the incubator unit 12 is arranged in the first quadrant Q1, and the central part 14C of the image inspection unit 14 is arranged in the second quadrant Q2. Further, the central part (16 + 18)C combining the stocker supply unit 16 and the product take-out unit 18 is arranged between the second quadrant Q2 and the third quadrant Q3 (on the Y-axis). Furthermore, the central part 22C of the medium exchange unit 22 is arranged in the fourth quadrant Q4.

[0032] Although not shown in the figure, it is also possible to define that the central part (16 + 18)C combining the stocker supply unit 16 and the product take-out unit 18 is arranged straddling the second quadrant Q2 and the third quadrant Q3. Also, it is possible to define that the central part (16C) of the stocker supply unit 16 is arranged in the second quadrant Q2, and the central part (18C) of the product take-out unit 18 is arranged in the third quadrant. Furthermore, the central part 20C of the transfer robot unit 20 is arranged at the origin of the XY coordinates. Therefore, it is also possible to define that the central part 20C of the transfer robot unit 20 is arranged straddling the first quadrant Q1 to the fourth quadrant Q4.

[0033] Regarding the description of the layout based on such quadrants, for example, it can be expressed as follows. That is, in the cell culture device 10, in the orthogonal coordinate system centered on the second operation unit (such as the transfer robot 40) in a plan view, the respective central parts (central parts 22C, (16 + 18)C, 12C, 14C, etc.) in the first space (the internal space related to the medium exchange unit 22), the supply / discharge unit (such as the stocker supply unit 16), the cell culture unit (such as the incubator unit 12), and the inspection unit (such as the image inspection unit 14) are arranged divided into at least three quadrants (the first quadrant Q1, the second quadrant Q2 (or the third quadrant), and the fourth quadrant Q4, etc.).

[0034] <Another Explanation 2 Regarding the Layout of Each Part (Arrangement on Multiple Surfaces)> FIG. 4(b) shows another explanatory example regarding the layout of each part. In the example of FIG. 4(b), with the position of the rotation center of the transfer robot 40 as the origin, XY coordinates are set planar ly, and the space defined by these XY coordinates is divided into the first surface R1 to the fourth surface R4 according to its position and orientation. And each part is arranged on three of the first surface R1 to the fourth surface R4 (here, the first surface R1, the second surface R2, and the fourth surface R4).

[0035] In the example of FIG. 4(b), the incubator unit 12 and the image inspection unit 14 are arranged on the first surface R1, and the stocker supply unit 16 and the product take - out unit 18 are arranged on the second surface R2. Further, the culture medium exchange unit 22 is arranged on the third surface R3. The fourth surface, which is located between the first surface R1 and the third surface R3 and faces the second surface R2, is an open surface where no parts are arranged. The open surface (the fourth surface R4) is the surface on which the opening - closing shutter unit 36 (FIG. 5) of the transfer robot unit 20 is arranged. Note that in the example of FIG. 4(b), each part is arranged on three surfaces (three surfaces), but it may also be intensively arranged on two surfaces (two surfaces).

[0036] <Basic Configuration of Each Part> FIG. 5 shows the basic configurations of each part (the incubator unit 12, the image inspection unit 14, the stocker supply unit 16, the product take - out unit 18, the transfer robot unit 20, and the culture medium exchange unit 22). Hereinafter, the basic configurations of each part will be described. Prior to the description of each part, the well plate 52 that moves between each part and the stocker 54 on which the well plate 52 is placed will be described.

[0037] <Well Plate 52 and Stocker 54> FIG. 6 shows the well plate 52 and the stocker 54. The well plates 52 used in this embodiment all have the same shape and structure. A large number of recess - shaped wells 56 for accommodating a culture solution or the like are formed in each well plate 52. In this embodiment, 96 (= 8×12) wells 56 are formed in the well plate 52 in a matrix.

[0038] The well plate 52 is configured by covering a well plate body 52a with a lid 52b. Both the well plate body 52a and the lid 52b are formed in a rectangular container shape with one side open. By covering the well plate body 52a with the lid 52b, the surface of the well plate body 52a where the wells 56 are open is covered. Both the well plate body 52a and the lid 52b are formed of a transparent synthetic resin material. And it is possible to visually recognize the inside of the wells 56 from both the side of the lid 52b and the back side of the well plate body 52a (the side opposite to the side where the lid 52b is covered).

[0039] The lid 52b is only covered on the well plate body 52a, and the lid 52b is not fixed to the well plate body 52a. For this reason, by lifting (pulling up) the lid 52b, for example, in the positive direction (upward direction) in the Z direction in FIG. 6, the lid 52b is separated from the well plate body 52a.

[0040] The well plate 52 is placed on a rectangular plate-shaped stocker 54. A maximum of 15 (= 3×5) well plates 52 can be placed on one stocker 54. The well plates 52 can also be counted as "sheets" or "tiers". In the example of FIG. 6, the well plates 52 are stacked in the vertical direction (Z direction) in groups of 5. Further, three groups of well plates 52 are arranged with their longitudinal directions (Y direction in FIG. 6) aligned with the longitudinal direction of the stocker 54 (also the Y direction in FIG. 6).

[0041] The stocker 54 is formed using a material such as stainless steel, for example. At the edge of the stocker 54, a hole 58, a rectangular notch 60, a protrusion 62, a V-shaped notch 63, etc. are formed. The rectangular notch 60 is located at the center of each edge (each edge facing the short side (width direction)) extending in the longitudinal direction of the stocker 54.

[0042] The protruding portion 62 is located at the central portion in the longitudinal direction of the rectangular notch 60. The V-shaped notch 63 is arranged so as to sandwich the rectangular notch 60 in the longitudinal direction. The V-shaped notch 63 has a shape that narrows as it goes deeper (towards the back in the short side direction (width direction) of the stocker 54).

[0043] Furthermore, a large number (here, 16) of surrounding pins 64 are attached to the peripheral edge of the stocker 54. These surrounding pins 64 protrude substantially perpendicularly from the plate surface on which the well plate 52 is placed. Among these, 12 (= 6×2) surrounding pins 64 are arranged to face, at a predetermined interval (an interval of about several millimeters), the vicinity of the four corners with respect to the well plates 52 arranged in the longitudinal direction of the stocker 54.

[0044] And most of the side surfaces (the side surfaces constituting the longitudinal direction) of the three sets of well plates 52 are all exposed without being hidden by the surrounding pins 64. In this way, by arranging the surrounding pins 64 at intervals in the longitudinal direction of the stocker 54 (and the well plate 52), as will be described later, a space is secured for the gripping portion 76 (FIG. 7) of the transfer robot 40 to enter. Also, 4 (= 2×2) of the 12 surrounding pins 64 are arranged to face, at a predetermined interval (an interval of about several millimeters), the two corners of each of the two sets of well plates 52 at both ends.

[0045] The tip (the upper end in FIG. 6) of the surrounding pin 64 is formed to be sharp. When placing the well plate 52 on the stocker 54, the well plate 52 is placed from above on the portion surrounded by the surrounding pins 64 in a state of being handled by an air gripper 68 (described later) having a gripping portion 76 (FIG. 7). Since the tip (the upper end in FIG. 6) of the surrounding pin 64 is sharp, when the well plate 52 is placed on the stocker 54, the tip of the surrounding pin 64 is less likely to interfere with the well plate 52. Note that it is not essential to provide the surrounding pins 64, and it is also possible to omit the surrounding pins 64.

[0046] <Transfer Robot 40> The transfer of the stocker 54 is performed by the transfer robot 40. The transfer robot 40 is a vertically articulated robot as described above, and has a feeding accuracy of about ±0.02 mm, for example. The main functions of the transfer robot 40 are to grip (clamp) and transfer the stocker 54 and the well plate 52. The transfer robot 40 can grip and transfer the stocker 54 with the well plate 52 placed thereon, or can grip and transfer only the stocker 54 without placing the well plate 52.

[0047] Also, the transfer robot 40 can grip and transfer only the well plate 52. Further, the transfer robot 40 can also grip and transfer only the lid 52b in order to separate the lid 52b on the well plate 52 from the well plate body 52a or cover the well plate body 52a. The gripping and transfer of the stocker 54, the well plate 52, and the lid 52b by the transfer robot 40 are performed through the following mechanisms.

[0048] An arm plate 66 (Fig. 10) lightened by punching is attached to the tip of the transfer robot 40, and an air gripper 68 as shown in Fig. 7(a) is attached to one end of the arm plate 66. Here, the arm plate 66 and the air gripper 68 are used at various positions and orientations according to the process, but in Fig. 10, the arm plate 66 and the like in a plurality of processes are shown simultaneously. In Fig. 10, in order to show that the arm plate 66 is drawn virtually, an extension line by a two-dot chain line (virtual line) is attached to the arm plate 66.

[0049] The air gripper 68 includes one air cylinder 70 and two movable bodies 72. A plurality of pipe joints 74 are attached to the air cylinder 70. Although not shown in the figure, for example, flexible resin tubes are connected to each pipe joint 74. In the air cylinder 70, high-pressure air supplied from an air source (such as an air compressor) through a resin tube (not shown) is introduced and discharged. Then, the two movable bodies 72 perform an operation of expanding the interval or an operation of narrowing the interval as the high-pressure air is introduced and discharged.

[0050] A T-shaped gripping portion 76 is fixed to the movable body 72. At the tip of the gripping portion 76, a metal strip-shaped claw portion 78 is attached, and the claw portion 78 is provided with two resin blocks 80 and two locking pins 82 each. The resin block 80 is a member made of synthetic resin and partially covers the opposing edges of the two gripping portions 76.

[0051] The locking pin 82 is disposed at the longitudinal end of the claw portion 78. The locking pin 82 is formed in a stepped cylindrical shape and protrudes substantially perpendicular to the plate surface of the gripping portion 76. The locking pin 82 has a relatively small-diameter portion on the proximal side (the side closer to the claw portion 78) and a relatively large-diameter portion on the distal side (the side farther from the claw portion 78).

[0052] Figure 7(b) shows the situation where the gripping portion 76 is locked to the stocker 54. When gripping the stocker 54, the air cylinder 70 approaches the central portion of the stocker 54 from above, and with the well plate 52 and the stocker 54 straddled in the width direction, the gripping portion 76 is opposed to the edge of the well plate 52. Only one gripping portion 76 is shown in Figure 7(b).

[0053] As shown by arrow B in Fig. 7(b), when the two gripping portions 76 (only one is shown) approach each other, the claw portion 78 enters below the protruding portion 62 formed at the edge of the stocker 54. At this time, the two resin blocks 80 of the claw portion 78 reach a position with the protruding portion 62 therebetween and face the side surface of the lowermost well plate 52.

[0054] Also, the locking pin 82 approaches the V-shaped notch 63 formed at the edge of the stocker 54. Then, the thin-diameter base-end portion of the locking pin 82 enters the V-shaped notch 63, and the thick-diameter tip-end portion of the locking pin 82 partially overlaps the edge of the V-shaped notch 63.

[0055] With such a closing operation of the gripping portion 76, the four locking pins 82 are guided by the obliquely formed edges of the corresponding V-shaped notches 63. The four locking pins 82 respectively enter the depths of the V-shaped notches 63 and lock to the stocker 54. As a result, the stocker 54 is positioned with respect to the claw portion 78 and gripped by the gripping portion 76.

[0056] When the tip of the transfer robot 40 moves upward with the gripping portion 76 gripping the stocker 54, the air cylinder 70 also moves integrally. The claw portion 78 of the gripping portion 76 contacts the protruding portion 62 and other portions of the stocker 54 from below and rises, and the stocker 54 is lifted.

[0057] At this time, the force with which the gripping portion 76 grips the stocker 54 is not so large, and the force required for the claw portion 78 to support the stocker 54 is greater and dominant than the force with which the gripping portion 76 grips the stocker 54. Then, the transfer robot 40 transports the stocker 54 and the well plate 52 placed on the stocker 54 to the target position according to the process while keeping the stocker 54 horizontal.

[0058] The presence, number of stages, and arrangement of the well plate 52 placed on the stocker 54 vary according to the process. The air gripper 68 having an air cylinder 70, a gripping part 76, etc. supports and transports the stocker 54 in situations where the total weight and weight balance of the object to be gripped are different. The stocker 54 and the well plate 52 adopt unified sizes, structures, etc. respectively and are made common. For this reason, it is possible to transport a large number of stockers 54 and well plates 52 using a single (one type of) air gripper 68.

[0059] When the transfer robot 40 transports the well plate 52 with the lid 52b alone, with the lid 52b covering, the well plate body 52a is gripped, and the well plate body 52a is gripped together with the lid 52b. Also, when the transfer robot 40 transports the lid 52b alone, only the lid 52b is gripped and lifted, and it is removed from the well plate body 52a.

[0060] When the air gripper 68 grips the well plate 52 or the lid 52b, the lifting position (position in the vertical direction (Z direction)) of the air gripper 68 and the interval of the gripping part 76 (and the claw part 78) are different from the case of gripping the stocker 54. Also, the lifting position of the air gripper 68 and the interval of the gripping part 76 are different between the case of gripping the well plate 52 and the case of gripping the lid 52b.

[0061] When the air gripper 68 grips the well plate 52 or the lid 52b, the lifting position of the air gripper 68 becomes higher than the case of gripping the stocker 54, and the interval of the gripping part 76 becomes narrower than the case of gripping the stocker 54. Also, when the air gripper 68 grips the lid 52b, compared with the case of gripping the well plate 52 (the well plate body 52a), the lifting position of the air gripper 68 becomes higher, and the interval of the gripping part 76 becomes wider.

[0062] When the air gripper 68 grips the well plate 52 or the lid 52b, the two claw portions 78 of the gripping portion 76 gradually approach each other, and the four (2×2) resin blocks 80 come into contact with the side surface of the well plate main body 52a or the lid 52b. Then, without directly contacting the claw portion 78 with the well plate main body 52a or the lid 52b, the well plate main body 52a and the lid 52b are gripped by utilizing the frictional force accompanying the pressing from the side surface. Therefore, it is possible to prevent the well plate main body 52a and the lid 52b made of transparent resin from being damaged by the metal claw portion 78.

[0063] The transfer robot 40 can also rotate around each orthogonal axis (X, Y, and Z axes). For this reason, depending on the process, when transferring the well plate 52 and the stocker 54, the transfer robot 40 may rotate the well plate 52 and the stocker 54 at an angle such as 90 degrees while keeping them horizontal.

[0064] In addition, in the present embodiment, a fork portion 84 (two long claw portions in FIGS. 10) is formed at the other end of the arm plate 66 (FIG. 10) to which the air gripper 68 is attached at one end. As will be described later, the fork portion 84 can support both edge portions of the reservoir 120 used in the medium exchange portion 22 and hold the reservoirs 120 one by one. That is, the transfer robot 40 can transfer four types of objects: the stocker 54, the well plate 52, the lid 52b, and the reservoir 120.

[0065] <Path of transfer by transfer robot 40> The transfer robot 40 transfers the stocker 54 with the well plate 52 thereon, the well plate 52, and the lid 52b according to the process, for example, between the stocker supply unit 16 and the incubator unit 12, between the incubator unit 12 and the image inspection unit 14, between the incubator unit 12 and the medium exchange unit 22, and between the incubator unit 12 and the product extraction unit 18. In FIG. 5, as an example, the paths from the stocker supply unit 16 to the incubator unit 12 and from the incubator unit 12 to the product extraction unit 18 are schematically shown by arrows C1 and C2.

[0066] As shown by the thick arrows D and E in FIG. 8, in the four sections of the incubator unit 12, the image inspection unit 14, the stocker supply unit 16 (stocker supply and extraction unit), and the medium exchange unit 22, the orientation of the stocker 54 to be installed is set such that the longitudinal direction of the stocker 54 is parallel to the X-axis or the Y-axis. By arranging the stocker 54 in such an orientation, the transfer robot 40 can arrange the stocker 54 by pushing it in the longitudinal direction. Therefore, it is possible to prevent the stocker 54 from interfering with the surrounding parts, and it is easy to arrange a plurality of stockers 54.

[0067] Also, when the transfer robot 40 is not gripping the stocker 54, it is not necessary to greatly raise the tip of the transfer robot 40 so as to avoid the air gripper 68 interfering with the well plate 52 or the like. Therefore, it is possible to simplify the movement path of the transfer robot 40.

[0068] <Incubator unit 12> The stocker 54 with the well plate 52 placed thereon is taken in and out of the incubator section 12 by the transfer robot 40. As shown in FIGS. 2 and 5, the incubator section 12 is provided with an incubator 32 capable of temperature control inside the storage, and the incubator 32 is provided with an automatic door 86. The automatic door 86 is a single-sided hinge type door and pivots (rotates and displaces) in the horizontal direction. When the stocker 54 is taken in and out, for example, under the control of the control unit 46 (FIG. 5), the automatic door 86 is opened and closed. Here, FIG. 2 shows the state where the automatic door 86 is opened. Also, in FIG. 5, the state where the automatic door 86 is opened is shown by a dashed line. Further, the door 37 shown in the upper left part of FIG. 5 is also used for the operator A to enter and exit, etc.

[0069] <Image inspection unit 14> FIGS. 9(a) and (b) show an overview of the image inspection unit 14. The image inspection unit 14 is provided with an image inspection device 34, and the image inspection device 34 is installed with a camera 90. The camera 90 is arranged at a certain height and can take pictures downward. Although not shown in the figure, the image inspection device 34 is also provided with a camera that takes pictures upward from below.

[0070] The camera 90 moves within the XY plane by a two-axis linear guide device 92. The linear guide device 92 is configured by combining electric actuators 94 and 96 corresponding to each axis. In the example of FIGS. 9(a) and (b), one electric actuator 94 is for the X axis, and the other electric actuator 96 is for the Y axis. The electric actuator 94 for the X axis is installed on the electric actuator 96 for the Y axis via a support body 98 as shown in FIG. 9(b).

[0071] Note that the X-axis and Y-axis of the image inspection device 34 shown in FIGS. 9(a) and 9(b) are different from the X-axis and Y-axis directions of the cell culture device 10 shown in FIGS. 1 to 3, FIG. 8, etc. The X-axis direction of the image inspection device 34 coincides with the Y-axis direction of the cell culture device 10, and the Y-axis direction of the image inspection device 34 coincides with the X-axis direction of the cell culture device 10. Also, in the examples of FIGS. 9(a) and 9(b) and the examples of FIGS. 1 to 3 and FIG. 8, etc., the arrangement of the linear guide device 92 is also different. For example, it is possible to rotate the orientation of the image inspection device 34 in the examples of FIGS. 9(a) and 9(b) to match the orientation of FIGS. 1 to 3 and FIG. 8, etc.

[0072] The camera 90 constitutes an image inspection system. The image inspection system is constructed by combining the camera 90 with an industrial computer device (industrial PC), although not shown in the figure. The image inspection system has a function for determining the pass or fail of cells. Using the captured image of the camera 90, an inspection related to the cell culture state is performed, and the inspection data obtained by the inspection is stored in an external storage such as an HDD (Hard Disk Drive) or an SSD (Solid State Drive). Also, the inspection data is stored in association with information related to the history of cell culture.

[0073] In the image inspection unit 14, the stocker 54 taken out from the incubator unit 12 is conveyed by the transfer robot 40. In the image inspection unit 14, the stocker 54 is installed in a predetermined pre-inspection installation area 100 with its longitudinal direction facing the Y-axis direction (the X-axis direction of the cell culture device 10). From the stocker 54, the well plate 52 is conveyed and installed in the inspection area 102 below the camera 90 as indicated by the arrow F in FIG. 9(b).

[0074] As described above, the well plate main body 52a and the lid body 52b constituting the well plate 52 are transparent, and the inspection in the inspection area 102 is performed through the lid body 52b with the lid body 52b covering the well plate main body 52a. The well plate 52 (for example, the well plate main body 52a) is provided with an identification information display part (not shown in the figure), and an image of the identification information display part is acquired in the inspection area 102.

[0075] On this identification information display section, information (identification information) capable of individually identifying the well plate 52 is displayed. The identification information can be displayed by attaching a sticker with a barcode or a matrix-type two-dimensional code drawn thereon, or by engraving a symbol for identification. Further, the reading of the identification information is performed while illuminating the identification information display section with an illumination device (not shown).

[0076] When photographing and inspection of the well plate 52 placed in the inspection area 102 are completed by the camera 90, the well plate 52 is returned to the side of the pre-inspection installation area 100 as indicated by the arrow G. A temporary placement area 104 is provided adjacent to the pre-inspection installation area 100, and the well plate 52 that has completed the inspection is installed in the temporary placement area 104 by the transfer robot 40. A stocker 54 is installed in advance in the temporary placement area 104, and the well plate 52 that has completed the inspection is placed on the stocker 54 in the temporary placement area 104. The position of the temporary placement area 104 is between the pre-inspection installation area 100 and the inspection area 102 and is closer to the pre-inspection installation area 100.

[0077] Subsequent well plates 52 are similarly inspected, and the well plates 52 that have completed the inspection are sequentially stacked on the stocker 54 in the temporary placement area 104. When the number of stacked well plates 52 reaches a predetermined number (here, 5), subsequent (the 6th and subsequent) well plates 52 that have completed the inspection are stacked up to 5 in the adjacent position in the longitudinal direction on the stocker 54.

[0078] Five well plates 52 are stacked at three locations, and when the number of well plates 52 in the temporary placement area 104 reaches 15, the stocker 54 on which these well plates 52 are placed is gripped and transferred by the transfer robot 40 and accommodated in the incubator unit 12.

[0079] For example, the inspection of cells in the image inspection unit 14 is carried out by simultaneously photographing all (here, 96) wells 56 of the well plate body 52a from above, performing image recognition on the cells in each well 56, and performing predetermined image processing. For cells with sizes and shapes that do not meet the predetermined inspection criteria, a record indicating NG is made, and the inspection results are notified, for example, via a display device 106 (Fig. 1) provided outside the image inspection unit 14. Note that the content of the inspection, the inspection criteria, the method of notifying the inspection results, etc. are not limited to those described here, and can be variously changed or added.

[0080] In addition, it is possible to use AI (artificial intelligence) for the inspection. For example, it is possible to previously let the control unit 46 learn the relationship between the conditions regarding the size and shape of the imaged cells and the quality (OK / NG) of the cells, and for the control unit 46 to determine and notify as NG the cells whose correlation with the OK learning result does not fall within a predetermined amount. Also, it is possible to previously let the control unit 46 learn the growth record of the cells, and for the control unit 46 to predict the degree of subsequent growth from the growth record up to that point for the same sample. The content of the inspection using AI can also be variously changed.

[0081] Also, although not shown in the figure, it is possible to install a sterilization lamp (or germicidal lamp) using, for example, an ultraviolet (UV) light source (such as a UV LED) at an appropriate location inside the image inspection unit 14 to perform sterilization (or disinfection) inside the image inspection unit 14. The installation of such sterilization means (or disinfection means) is effective for preventing the propagation of bacteria, for example, when the culture solution drips (when there is liquid leakage) or when a person touches it, and for keeping the internal environment clean.

[0082] Sterilization (or disinfection) by light irradiation can be performed locally on areas where liquid dripping is likely to occur. By doing so, it becomes possible to select the installation location and appropriately arrange the ultraviolet light source. And, for example, it becomes possible to appropriately adjust the relationship between the position of a synthetic resin part that is likely to deteriorate due to ultraviolet light and the position of the ultraviolet light source so that the ultraviolet light does not hit the synthetic resin part, and to arrange the two. Furthermore, it is also possible to arrange the ultraviolet light source on a movable part of a part of the transfer robot 40 (for example, the arm plate 66, air gripper 68, etc. shown in FIG. 10).

[0083] Regarding the timing of sterilization (or disinfection) by light irradiation, for example, it is possible to perform light irradiation during a time period when various operations by the transfer robot 40 are not being performed (so-called idle time, standby state, etc.) under the control of the control unit 46.

[0084] <Culture medium exchange unit 22> FIG. 5 shows an overview of the culture medium exchange unit 22. In the culture medium exchange unit 22, in addition to the culture medium exchange robot 42 described above being installed on the workbench 110, an aspirator tool holder 112, waste BOXes 114, 115, a micropipette tool holder 116, a pipetter tool holder 118, a reservoir 120, a pipette bit 122, a suction bit 124, and a culture medium tank installation part 126, etc. are provided so as to surround the culture medium exchange robot 42.

[0085] Among these, at the tip of the culture medium exchange robot 42, as shown in FIG. 10, a tool changer 130 is attached. A tool adapter 132 is provided at the tip of the tool changer 130, and any of operating devices such as an aspirator tool 134, a micropipette tool 136, or a pipetter tool 138 can be attached to the tool adapter 132.

[0086] Note that FIGS. 5 and 10 each show an example regarding the arrangement of each device, and in FIGS. 5 and 10, the arrangements of the respective devices do not necessarily match.

[0087] In operating devices such as the aspirator tool 134, the micropipette tool 136, and the pipettor tool 138 shown in FIG. 10, the connection structure with the tool adapter 132 is standardized. Therefore, various operating devices (134, 136, 138, etc.) can be interchangeably connected to one tool adapter 132. In addition, the tool adapter 132 is provided with a fall prevention function for preventing the fall of the operating devices (134, 136, 138, etc.).

[0088] Among the operating devices (134, 136, 138, etc.), the aspirator tool 134 includes 12 tip bits (needles) 142 arranged parallel to each other, and through the tip bits 142, it is possible to simultaneously aspirate the culture medium (culture solution) in 12 wells 56 arranged in the longitudinal direction.

[0089] The micropipette tool 136 also includes 12 needles 144 arranged parallel to each other, and through the needles 144, it is possible to simultaneously discharge the culture medium (culture solution) to the 12 wells 56.

[0090] The pipettor tool 138 sucks up the culture solution from a culture solution bottle (not shown), and prior to the discharge of the culture medium by the micropipette tool 136, injects the culture solution into the reservoir 120. The culture solution in the reservoir 120 is aspirated by the micropipette tool 136 and discharged into the wells 56 of the well plate main body 52a. This pipettor tool 138 is of a rechargeable type.

[0091] The aspirator tool holder 112, the micropipette tool holder 116, and the pipettor tool holder 118 are respectively placed with the aspirator tool 134, the micropipette tool 136, and the pipettor tool 138 in a state where they are not mounted on the culture medium exchange robot 42 (non-use state).

[0092] The waste box 114 is used for discarding the tip bit 142 of the aspirator tool 134. The tip bit 142 is detachably attached to the aspirator tool 134 so that the used tip bit 142 can be removed from the aspirator tool 134 and discarded into the waste box 114.

[0093] The reservoir 120 is a portable container and is used not only for aspirating the culture medium but also for cleaning the tip bit 142. When cleaning the tip bit 142, cleaning alcohol is injected into the reservoir 120, and the reservoir 120 is placed in the reservoir installation area 128 on the workbench 110. The injection of the cleaning alcohol can be performed, for example, using a suction pump (not shown) provided in the medium exchange section 22.

[0094] The medium exchange robot 42 inserts the tip of the tip bit 142 attached to the aspirator tool 134 into the cleaning alcohol in the reservoir 120 and aspirates, for example, all of the cleaning alcohol in the reservoir 120. As a result of the aspiration, the cleaning alcohol is discharged into a waste liquid tank (not shown). Then, the tip bit 142 is automatically removed from the aspirator tool 134 and discarded into the waste box 114.

[0095] In the medium exchange section 22, as a countermeasure against liquid dripping from various operating devices (134, 136, 138, etc.), a plurality of receiving plates 148 made of stainless steel plates are installed, for example, as shown in FIG. 10, at positions below the moving lines (moving trajectories) of the various operating devices (134, 136, 138, etc.).

[0096] FIG. 11 schematically shows the configuration of the wall portion 22B and the like of the medium exchange section 22. The medium exchange section 22 includes an outer wall portion 22A, an inner wall portion 22B, and the like. The outer wall portion 22A constitutes a part of the wall portion 10A in the cell culture device 10. The inner wall portion 22B is located inside the wall portion 10A in the cell culture device 10 and divides the internal space of the wall portion 10A into a first space (the internal space of the medium exchange section 22) and a second space (the internal space other than the medium exchange section 22).

[0097] A manual opening and closing shutter 150 is provided on the outer wall portion 22A. This manual opening and closing shutter 150 is manually opened and closed, for example, when replenishing consumables such as a culture solution. The replenishment of the consumables can also be performed by a transfer robot (not shown) installed outside the cell culture device 10. The opening and closing direction of the manual opening and closing shutter 150 is the vertical direction as indicated by the arrow H in FIG. 11. The manual opening and closing shutter 150 is locked (locked out) so that it cannot be opened or closed during the operation of the medium exchange robot 42, for example. The locking of the manual opening and closing shutter 150 is performed via an electromagnetic locking device under the control of the control unit 46, for example.

[0098] An automatic opening and closing shutter 152 is provided on the inner wall portion 22B. The automatic opening and closing shutter 152 is controlled to open and close under the control of the control unit 46, for example. Specifically, the automatic opening and closing shutter 152 is opened when the transfer robot 40 causes the arm plate 66 (FIG. 10) to enter the internal space (the first space) of the medium exchange unit 22 from the second space. The opening and closing direction of the automatic opening and closing shutter 152 is the vertical direction as indicated by the arrow J in FIG. 11.

[0099] In addition, a sterilization lamp (or germicidal lamp) 154 using, for example, an ultraviolet (UV) light source (such as a UV LED) is installed in the medium exchange unit 22, and sterilization (or disinfection) is performed in the medium exchange unit 22. Such an arrangement of the sterilization means (or disinfection means) is performed at an appropriate location in the internal space (the first space) so as to prevent the propagation of bacteria, for example, when the culture solution drips or when a person touches it, and keep the internal environment clean. Examples of the location where the sterilization lamp 154 is arranged include one to four sides of the four sides of the ceiling portion 24 facing the internal space (the first space) and an appropriate position on the workbench 110.

[0100] Sterilization (or disinfection) by light irradiation can be performed locally on areas where liquid dripping is likely to occur. By doing so, it becomes possible to select an installation location and appropriately arrange the ultraviolet light source. And, for example, it becomes possible to appropriately adjust the relationship between the position of a synthetic resin part that is easily deteriorated by ultraviolet rays and the position of the ultraviolet light source so that the ultraviolet rays do not hit the synthetic resin part, and to arrange the two. Furthermore, it is also possible to arrange the ultraviolet light source on a movable part of a part of the medium exchange robot 42 (for example, the tool changer 130, the aspirator tool 134, the micropipette tool 136, or the pipetter tool 138, etc.).

[0101] Regarding the timing of sterilization (or disinfection) by light irradiation, for example, it is possible to perform light irradiation during a time period when various operations by the medium exchange robot 42 are not being performed (so-called free time, standby state, etc.) under the control of the control unit 46.

[0102] In the medium exchange unit 22 as described above, the stocker 54 taken out from the incubator unit 12 is conveyed by the transfer robot 40 and installed in the installation area 156 of the workbench 110. One well plate 52 is gripped from the stocker 54 by the transfer robot 40 and conveyed to the medium exchange area 157. The lid 52b is removed by the transfer robot 40, and for example, one stocker 120 at the uppermost stage is supported from among the plurality of stockers 120 stacked in the reservoir preparation area 158 and installed in the reservoir installation area 128. As described above, the support and conveyance of the stocker 120 are performed by the transfer robot 40 using the arm plate 66 (FIG. 10).

[0103] Subsequently, the old medium is sucked from the wells of the well plate main body 52a by the aspirator tool 134 attached to the medium exchange robot 42. Thereafter, at the position of the aspirator tool holder 112, the aspirator tool 134 is automatically removed from the tool adapter 132 of the medium exchange robot 42.

[0104] The medium exchange robot 42 moves the tool adapter 132 at the tip to the position of the pipetter tool holder 118, and the pipetter tool 138 is attached to the tool adapter 132. Further, the medium exchange robot 42 moves the pipetter tool 138 to the reservoir installation area 128. Then, the medium is electrically injected by the pipetter tool 138 into the reservoir 120 installed in the reservoir installation area 128.

[0105] Further, at the position of the pipetter tool holder 118, the pipetter tool 138 is automatically removed, and the medium exchange robot 42 moves the tool adapter 132 to the position of the micropipette tool holder 116. At the position of the micropipette tool holder 116, the micropipette tool 136 is automatically attached to the tool adapter 132. Then, the medium exchange robot 42 moves the micropipette tool 136 to the position of the reservoir 120, and the culture solution is sucked from the reservoir 120 into the needle 144 of the micropipette tool 136.

[0106] The medium exchange robot 42 transfers the micropipette tool 136 to the position of the well plate body 52a to be subjected to medium exchange, and the micropipette tool 136 injects the medium into the well 56 directly below. For example, when the medium exchange is completed for 15 well plates 52 in one stocker 54, the stocker 54 loaded with the well plates 52 (15 pieces) for which the medium exchange has been completed is returned to the incubator section 12 by the transfer robot 40.

[0107] When using the aspirator tool 134, the aspirator tool 134 (tip bit 142) is tilted obliquely at a predetermined angle with respect to the well 56 to aspirate the culture medium. According to the findings of the inventors, by doing so, when aspirating the culture medium, it is significantly less likely to suck up cells together with the culture medium from a part (for example, about 1 to 3) of the 96 wells 56. Although the verification of the factors has not been completely finished, according to the findings of the inventors, it is considered that aspirating the culture medium from an eccentric position with respect to the center of the well 56 is one of the factors for improvement.

[0108] When using the micropipette tool 136, by tilting the micropipette tool 136 (needle 144) obliquely at a predetermined angle with respect to the well 56 or making it eccentric, the culture solution can be applied to the inner wall of the well 56 and then injected, and the influence of the injection on the cells can be prevented as much as possible.

[0109] <Measures for improving safety> In the cell culture device 10, for example, various processes necessary for cell culture are automated, and the transfer robot 40 performs various operations. And for example, it is difficult for a person to predict the operation of the transfer robot 40. For this reason, it is desirable for the cell culture device 10 to adopt safety improvement measures to allow a person to safely enter the second space (parts other than the medium exchange unit 22).

[0110] As safety improvement measures, various methods can be adopted. For example, a human presence sensor 159 (Fig. 5) capable of detecting the presence of a person in the cell culture device 10 is provided, and under the control of the control unit 46, while the human presence sensor 159 detects a person, the transfer robot 40 is not allowed to perform operations such as gripping and transferring. As the human presence sensor 159, for example, various sensors such as a load sensor (weight sensor), a pressure sensor, an optical sensor (including a laser sensor), an infrared sensor, a microwave sensor, an ultrasonic sensor, a camera sensor (image recognition sensor), and an acoustic sensor can be used.

[0111] Also, when a person enters the cell culture apparatus 10, the opening / closing shutter unit 36 (Fig. 5) is opened. When a door opening sensor (not shown) detects the opening of the opening / closing shutter unit 36, the control unit 46 may stop the operation of the transfer robot 40. Further, when an operation (such as a button operation or a unlocking operation) for opening the opening / closing shutter unit 36 is performed, it is also possible to stop the operation of the transfer robot 40. Examples of the unlocking operation include inputting a security key (such as numbers or symbols) using a key input device for numbers or the like, inserting a key into a keyhole, or operating (such as rotating) the key inserted into the keyhole.

[0112] Also, when a person wears a device capable of transmitting radio waves (such as a radio transmitter or an identification information tag (RFID tag)) on their work clothes and the transmitted radio waves are detected by a receiving unit provided in the cell culture apparatus 10, it is also possible to stop the operation of the transfer robot 40. Further, it is also possible to enable the opening of the opening / closing shutter unit 36 only during a predetermined time period. In this case, control using the human sensor 159 or the door opening sensor (not shown) can be omitted.

[0113] Note that when stopping the operation of the transfer robot 40, the operation of the movable parts throughout the cell culture apparatus 10, including the medium exchange robot 42, may be stopped. Further, it is also possible to stop only the transfer robot 40 and the medium exchange robot 42.

[0114] Also, regarding the medium exchange robot 42, since it is partitioned in the wall portion 22B of the medium exchange unit 22 and the like, it is considered that safety is ensured. Further, in the cell culture apparatus 10 of the present embodiment, in terms of the process, a person does not enter the medium exchange unit 22. Therefore, even if the operation of the transfer robot 40 stops, the medium exchange robot 42 can be kept running and operations related to medium exchange can be performed.

[0115] <Main advantages of the cell culture apparatus 10> According to the cell culture device 10 of the present embodiment, a control unit 46 is provided that sets the movable range when the first operation unit (medium exchange robot 42) performs an operation related to medium exchange within the first space (the internal space of the medium exchange unit 22), and sets the movable range when the second operation unit (transfer robot 40) moves the well plate 52 to the second space and the first space.

[0116] Therefore, the movable range of the first operation unit (medium exchange robot 42) and the movable range of the second operation unit (transfer robot 40) can be overlapped, and the space efficiency within the cell culture device 10 can be optimized. As a result, space can be saved, and a compact cell culture device 10 can be provided.

[0117] In addition, the first operation unit capable of performing an operation related to medium exchange is selectively arranged in the first space with relatively high air cleanliness (high cleanliness), and the second operation unit capable of performing a moving operation of the cell culture container is arranged in the second space with relatively low air cleanliness. Since the movable range when the first operation unit performs an operation related to medium exchange is within the first space, and the movable range when the second operation unit moves the cell culture container is the second space and the first space, operation units with different functions can be operated in a more optimized environment.

[0118] In addition, each part (incubator unit 12, image inspection unit 14, stocker supply unit 16, product extraction unit 18, and medium exchange unit 22) is arranged around the transfer robot unit 20 with the transfer robot unit 20 as the center. Therefore, the space efficiency can also be optimized by this. As a result, space can be saved, and a compact cell culture device 10 can be provided.

[0119] In addition, with regard to the medium exchange unit 22, since various regions (regions for the aspirator tool holder 112, waste BOXes 114 and 115, micro pipette tool holder 116, pipettor tool holder 118, reservoir 120, pipette bit 122, suction bit 124, and the medium tank installation part 126, etc.) necessary for the medium exchange operation are arranged so as to surround the medium exchange robot 42, space efficiency can be optimized. And regarding the arrangement of the regions necessary for the medium exchange operation, space saving is possible, and a small-sized medium exchange unit 22 can be provided.

[0120] In addition, the well plate 52 is transported not only to a space (first space) with relatively high air cleanliness (high cleanliness), but also to a second space with relatively low air cleanliness. However, since the lid 52b is provided, it is possible to perform dust prevention for the wells 56 and keep the wells 56 clean.

[0121] In addition, most of the processes of storing the well plate 52 and the stocker 54 in the incubator 32, taking them out from the incubator 32, cell inspection in the image inspection unit 14, and medium exchange in the medium exchange unit 22 can be automated, and labor saving in cell culture is possible. Note that when inspecting cells, various inspection methods can be adopted, not limited to the image inspection as described in this embodiment.

[0122] In addition, with regard to the transfer robot 40, since a single (one type of) air gripper 68 grips (and transfers) different types of gripping targets (and transfer targets) such as the stocker 54, the well plate 52, and the lid 52b, it is not necessary to replace the air gripper 68 for each gripping target (and transfer target). Therefore, the transfer robot 40 can be made multifunctional. Furthermore, it becomes possible to easily automate the gripping (and transfer) of the gripping target (and transfer target).

[0123] Furthermore, multiple (here, five) well plates 52 are grouped together and multiple groups are arranged in the stocker 54. Therefore, it is possible to transport a large number of well plates 52 simultaneously.

[0124] Also, regarding the medium exchange robot 42, the tool changer 130 is equipped with the tool adapter 132, and various operating devices (such as the aspirator tool 134, the micropipette tool 136, or the pipetter tool 138, etc.) are interchangeably connected to one tool adapter 132. Therefore, the medium exchange robot 42 can be made multifunctional. Furthermore, the replacement of the operating devices is easy, and it is possible to easily automate the replacement of the operating devices.

[0125] Also, when the entry of a person is detected, the transport robot 40 stops, so that it is possible to operate the small cell culture device even more safely.

[0126] <Modification example related to the layout> Regarding the arrangement of each part (the incubator part 12, the image inspection part 14, the stocker supply part 16, the product extraction part 18, the transport robot part 20, and the medium exchange part 22), it is not limited to that shown in FIG. 1 etc., and various changes are possible. FIG. 12 shows a modification example of the layout. In the cell culture device 160 of the example of FIG. 12, four incubator parts 12-1 to 12-4 are provided, and three incubator parts 12-2 to 12-4 are added compared to the example of FIG. 1 etc. Here, in FIG. 12, the characters "Incubator (1)" to "Incubator (4)" are shown for the incubator parts 12-1 to 12-4, and the numerical values (1) to (4) for identifying the incubators are shown in round numbers.

[0127] In the cell culture device 160 shown in FIG. 12, a linear actuator 162 is added, and the four incubator units 12-1 to 12-4 are arranged along the linear actuator 162 extending linearly. As the incubator units 12-1 to 12-4, it is possible to adopt incubator units having the same configuration. In the example of FIG. 12, the incubator unit 12-1 is arranged at a position facing the medium exchange unit 22 in the same manner as in the example of FIG. 1 and the like, and the incubator units 12-2 and 12-3 are arranged so as to face each other with the linear actuator 162 interposed therebetween.

[0128] The transfer robot 40 is installed on the linear actuator 162 and is movable along the Y-axis direction in which the linear actuator 162 extends. In FIG. 12, the transfer robot 40 is shown at two locations, but the number of transfer robots 40 is one. In FIG. 12, the transfer robots 40 before and after the movement are both shown by solid lines. Then, the transfer robot 40 takes in and out the stocker 54 with respect to each of the incubator units 12-1 to 12-4 arranged along the linear actuator 162.

[0129] In such a cell culture device 160, the configuration can be expanded. As a result, more cells can be cultured. In addition, the cell culture device 160 becomes more multifunctional. Furthermore, it becomes possible to change the position of the transfer robot 40. And the transfer robot 40 can move linearly by the linear actuator 162 in addition to its six-axis operation. Therefore, also by this, the cell culture device 160 becomes more multifunctional.

[0130] Note that the added configuration is not limited to the incubator unit 12, and other configurations may be added. In the example of FIG. 12, the image inspection unit 14 is arranged so as to face the incubator units 12-1 to 12-4 with the linear actuator 162 interposed therebetween.

[0131] <Modification example regarding the arrangement of the medium exchange robot 42> Also, in the example of FIG. 11, the medium exchange robot 42 is installed on the workbench 110, but it is not limited to this. For example, as shown in FIG. 13, the medium exchange robot 42 can be of a ceiling-suspended type. In the example of FIG. 13, the medium exchange robot 42 is installed inside the ceiling portion 24 (on the internal space side) of the medium exchange unit 22 and extends downward from the ceiling portion 24. By doing so, an empty area can be secured on the workbench 110, and the workbench 110 can be used more widely. Also, since there is no need for a space to install the medium exchange robot 42 on the workbench 110, it is also possible to form the workbench 110 smaller than in the example of FIG. 11 and miniaturize the medium exchange unit 22.

[0132] <Inventions extractable from the embodiments> From the embodiments described so far, the following inventions can be extracted. (1) A first space (such as the internal space of the medium exchange unit 22) that satisfies a first standard (such as Class 5 according to ISO) as the air cleanliness standard, A second space (such as the internal space of parts other than the medium exchange unit 22) that satisfies a second standard (such as Class 6 - 7 according to ISO) lower than the first standard as the air cleanliness standard, A first operation unit (such as the medium exchange robot 42) installed in the first space and capable of performing operations related to medium exchange (such as suction and discharge of the culture solution), A second operation unit (such as the transfer robot 40) installed in the second space and capable of performing a moving operation of a cell culture container (such as the well plate 52) in which the medium is stored, An operation unit control means (such as the control unit 46) that sets the movable range when the first operation unit performs the operations related to medium exchange within the first space, and sets the movable range when the second operation unit moves the cell culture container within the second space and the first space A cell culture device comprising: Thereby, the movable ranges of the first operation unit and the second operation unit can be overlapped, and the effect of enabling miniaturization of the cell culture device is achieved. Furthermore, the effect of enabling the operation units with different functions to operate in a more optimized environment is achieved. (2) The operation unit control means controls the movement of the cell culture vessel from the second space to the first space by the second operation unit, and controls the operation related to the medium exchange to be performed on the cell culture vessel by the first operation unit. The cell culture apparatus according to (1) above. This has the effect of enabling miniaturization of the cell culture apparatus. (3) The cell culture vessel has a dust-proof part (such as a lid 52b) that can be attached and detached by the second operation unit. The cell culture apparatus according to (2) above. This has the effect of being able to keep the cell culture vessel clean. (4) The second operation unit is provided with a gripping mechanism (such as an air gripper 68) capable of gripping the cell culture vessel. The first operation unit is provided with a mounting mechanism (such as a tool adapter 132) that is shared among a plurality of types of operation devices (such as an aspirator tool 134, a micropipette tool 136, and a pipetter tool 138) corresponding to the content of the operation related to the medium exchange. The cell culture apparatus according to any one of (1) to (3) above. This has the effect of being able to easily automate the gripping of the cell culture vessel and the mounting of the operation device. (5) In the second space, a supply / discharge part (such as a stocker supply part 16 and a product take-out part 18, or a stocker supply / take-out part integrating both) where the cell culture vessel is carried in and out, a cell culture part (such as an incubator part 12) where the cells contained in the cell culture vessel are cultured, and an inspection part (such as an image inspection part 14) where the cell culture vessel is inspected are installed. The operation unit control means controls the movement operation of the cell culture vessel with respect to the supply / discharge part, the movement operation of the cell culture vessel with respect to the cell culture part, and the movement operation of the cell culture vessel with respect to the inspection part by the second operation unit. The cell culture apparatus according to (1) above. This has the effect of enabling miniaturization of the cell culture apparatus. (6) In an orthogonal coordinate system (such as an XYZ coordinate system) centered on the second operation unit in a plan view, the central parts (such as central parts (16 + 18)C, 12C, and 14C) in the first space, the supply and discharge unit, the cell culture unit, and the inspection unit are arranged separately in at least three quadrants (such as at least three of the first quadrant Q1 to the fourth quadrant Q4). The cell culture device according to (5) above. This has the effect of enabling miniaturization of the cell culture device. (7) The cell culture device according to any one of (1) to (3) above, comprising a sterilization light source unit (such as a sterilization lamp (or germicidal lamp) 154) for sterilizing the inside of the first space. This has the effect of being able to keep the internal environment of the first space clean. (8) The cell culture device according to any one of (1) to (3) above, comprising a moving unit (such as a linear actuator 162) capable of moving the second operation unit. This has the effect of making the cell culture device more multifunctional. (9) Comprising a container placement unit (such as a stocker 54) on which the cell culture container is placed, The gripping mechanism has a claw part (such as claw part 78) whose interval can be changed, and it is possible to change the interval of the claw part to transfer the cell culture container and the container placement unit. The cell culture device according to (4) above. This has the effect of making it possible to easily automate the gripping and conveyance of the cell culture container and the container placement unit. (10) The cell culture container is stacked on the container placement unit to form a stack (such as a set of up to five well plates 52), and in a state where a plurality (such as three sets) of the stacks are arranged on the container placement unit, the container placement unit is gripped by the gripping mechanism. The cell culture device according to (9) above. This has the effect of making it possible to convey a large number of cell culture containers simultaneously. (11) Comprising a stop condition detection means (such as a human sensor 159) capable of detecting a stop condition (such as a person entering) which is a condition for stopping the second operation unit, The cell culture device according to any one of (1) to (3) above, wherein when the stop condition is detected, the operation unit control means operates the first operation unit and stops the second operation unit. As a result, it is possible to operate a small cell culture device more safely.

[0133] <Others> Note that the present invention is not limited to the above-described various embodiments, and can be variously modified or combined with various embodiments without departing from the gist.

[0134] For example, in organoid culture, medium exchange may be performed by a mechanism and method similar to the medium exchange unit 22 of the above-described embodiment.

Industrial Applicability

[0135] The cell culture device according to the present invention can be applied to various cell cultures that perform medium exchange.

Explanation of Signs

[0136] 10: Cell culture device 10A: Wall part 10B: Window part 12: Incubator part 14: Image inspection part 16: Stocker supply part 18: Product extraction part 20: Conveyor robot part 22: Medium exchange part 26: Filter unit for the first space 28: Filter unit for the second space 32: Incubator 34: Image inspection device 36: Opening / closing shutter part 40: Conveyor robot 42: Medium exchange robot 46: Control part 52: Well plate 52a: Well plate body 52b: Lid 54: Stocker 56: Well 68: Air gripper 70: Air cylinder 72: Movable body 76: Gripping part 78: Claw part 80: Resin block 82: Locking pin 90: Camera 120: Reservoir 130: Tool changer 132: Tool adapter 134: Aspirator tool 136: Micropipette tool 138: Pipettor tool 142: Tip bit 144: Needle 148: Receiving plate 154: Sterilization lamp 159: Human sensor

Claims

1. a first space that satisfies a first standard as a standard for air cleanliness; A second space that satisfies a second standard, which is lower than the first standard, as a standard for the air cleanliness; A first operating unit installed in the first space and capable of performing an operation related to culture medium replacement; A second operation unit that is installed in the second space and is capable of performing a moving operation of a cell culture vessel in which a culture medium is stored; an operation unit control means for controlling a movable range of the first operation unit when performing an operation related to the culture medium exchange within the first space, and a movable range of the second operation unit when moving the cell culture vessel within the second space and the first space; A cell culture device comprising:

2. The operation unit control means The cell culture device according to claim 1, wherein the second operating unit controls the cell culture container to be moved from the second space to the first space, and the first operating unit controls the cell culture container to be subjected to an operation related to the medium replacement.

3. The cell culture device according to claim 2 , wherein the cell culture vessel has a dustproof part that is attached and detached by the second operation part.

4. The second operation unit is provided with a gripping mechanism capable of gripping the cell culture vessel, The cell culture device according to any one of claims 1 to 3, wherein the first operating unit is provided with an attachment mechanism that is common to a plurality of types of operating devices corresponding to the content of the operation related to the culture medium replacement.

5. In the second space, A supply and discharge section where the cell culture vessel is loaded and unloaded, a cell culture section where the cells accommodated in the cell culture vessel are cultured, and an inspection section where the cell culture vessel is inspected are provided, The operation unit control means The cell culture device according to claim 1 , wherein the second operation unit controls the movement of the cell culture container relative to the supply and discharge unit, the movement of the cell culture container relative to the cell culture unit, and the movement of the cell culture container relative to the inspection unit.

6. The cell culture device according to claim 5, wherein in a Cartesian coordinate system centered on the second operation unit in a planar view, the respective centers of the first space, the supply and discharge unit, the cell culture unit, and the inspection unit are arranged in at least three quadrants.

7. The cell culture device according to any one of claims 1 to 3, further comprising a sterilization light source unit for sterilizing the first space.

8. The cell culture device according to any one of claims 1 to 3, further comprising a moving part capable of moving the second operation part.

9. a container mounting part on which the cell culture container is mounted, The cell culture device according to claim 4 , wherein the gripping mechanism has claws whose interval is changeable, and the interval between the claws is changeable to enable switching between gripping the cell culture vessel and the vessel mounting part.

10. The cell culture device according to claim 9, wherein the cell culture containers are stacked on the container mounting portion to form a stack, and the container mounting portion is gripped by the gripping mechanism while a plurality of the stacks are arranged on the container mounting portion.

11. a stop condition detection means capable of detecting a stop condition which is a condition for stopping the second operation unit, The cell culture device according to any one of claims 1 to 3, wherein when the stop condition is detected, the operation unit control means operates the first operation unit and stops the second operation unit.

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