Cell culture device

Abstract

To provide a cell culture device capable of operating operation units with different functions in a more optimized environment. A first space (such as the internal space of the medium exchange unit 22) that meets 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 meets a second standard lower than the first standard (such as Class 6 - 7 according to ISO) as the air cleanliness standard, a medium exchange robot (42) installed in the first space and capable of performing operations related to medium exchange, a transfer robot (40) installed in the second space and capable of performing a transfer operation of a well plate (52) in which a medium is stored, and a control unit that sets the movable range when the medium exchange robot (42) performs an operation related to medium exchange within the first space and sets the movable range when the transfer robot (40) moves the well plate (52) to the second space and the first space.

Description

Technical Field

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

Background Art

[0002] Patent Document 1 (Claim 1, etc.) described later discloses an invention related to an automatic culture operation apparatus 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 maintaining a positive pressure in the work chamber by circulating purified air. However, Patent Document 1 does not describe optimizing the installation environment and work environment of operation units 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 apparatus capable of operating operation units with different functions in a more optimized environment.

Means for Solving the Problems

[0006] A cell culture apparatus 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 moving operation of a cell culture container storing a medium, An 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 is provided A cell culture device, the supply of air to the first space is performed by a filter unit for the first space, the supply of air to the second space is performed by a filter unit for the second space, the filter unit for the first space takes in air outside the cell culture device independently of the filter unit for the second space, the air to the first space is supplied from the filter unit for the first space to the first space, the second operation unit is provided with a gripping mechanism capable of gripping the cell culture vessel, the first operation unit is provided with a mounting mechanism common to a plurality of types of operation devices corresponding to the content of the operation related to the medium exchange, the operation device is provided with a holder unit on which different experimental devices can be mounted .

Advantages 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]

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Embodiments for Carrying Out the Invention

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

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

[0011] Approximately two-thirds of each unit from the top is surrounded by the wall portion 10A. In the present embodiment, the wall portion 10A is formed in a T-shaped configuration when the cell culture device 10 is viewed in plan from the ceiling side, and encloses the inner space airtightly. A plurality of transparent window portions 10B are formed in the wall portion 10A to enable visual observation of each unit by an operator A (indicated by a two-dot chain line). Note that the arrangement of the wall portion 10A is not limited to the T-shaped configuration, and can be variously changed, for example, to a rectangular shape, an L-shaped configuration, etc., according to circumstances such as the shape of the installation space.

[0012] FIG. 2 shows a state in which 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 transport robot 40, and a medium exchange robot 42. The medium exchange robot 42 is provided in the medium exchange device 43. Details of these devices and each unit will be described later.

[0013] Figure 3 shows the layout of each part. More specifically, Figure 3 shows the state of the cell culture device 10 with the wall portion 10A removed and viewed from above in a plan view. 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 extraction part 18, and medium exchange part 22 are arranged in order so as to surround the transfer robot part 20 clockwise in Figure 3. Regarding the layout of each part, it can be described in a plurality of other modes, but 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 exchange part 22 and the internal spaces of the parts other than the medium exchange part 22 (the incubator part 12, the image inspection part 14, the stocker supply part 16, the product extraction part 18, and the transfer robot part 20). The internal spaces of the parts other than the medium exchange part 22 are spatially connected. The internal space of the medium exchange part 22 is the first space, and the internal spaces of the parts other than the medium exchange part 22 are the second space. Although details will be described later, inside the wall portion 10A (Figure 1), as shown in Figure 11, a part of the wall portion 22B of the medium exchange part 22 partitions the first space (the internal space of the medium exchange part 22) and the second space (the internal space other than the medium exchange 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 US Federal Standard). On the other hand, the second standard for the second space is, for example, Class 6 to 7 according to ISO (Class 1000 to 10000 according to 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 example. 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 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, which will be described later, is supplied from the stocker supply unit 16. Also, a well plate 52 (to be 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 apparatus 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, depending on the process, the automatic opening and closing shutter 152 (shown in FIG. 11 and to be described later) located at the boundary between the medium exchange unit 22 and the second space is 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] Also, in the transfer robot unit 20 where the transfer robot 40 is installed, an opening and closing shutter unit 36 (FIG. 5) is provided that partitions the second space and the space outside the cell culture apparatus 10 (external space). 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 apparatus 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 vertically 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 articulated robots having less than six axes or more than six axes. Also, the drive systems of the medium exchange robot 42 and the transfer robot 40 are both AC (DC) servo systems. 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 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 operations related to medium exchange within the first space, and controls the movable range when the transfer robot 40 moves the cell culture vessel (well plate 52, described later) to be 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 generally referred to as, for example, an operation unit control unit (operation unit control means).

[0026] Specifically, in the cell culture apparatus 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 enter its tip into any of these units.

[0027] Also, although details will be described later, in the medium exchange robot 42 and the transfer robot 40, various operating devices (operating apparatuses) such as, for example, 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] <Another Explanation 1 Regarding the Layout of Each Unit (Arrangement in Multiple Quadrants)> Regarding the layout of each unit (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 explanation that they are arranged to surround the transfer robot unit 20 as described above, the following explanations 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 unit 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 illustration, 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. For this reason, 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 apparatus 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)> Figure 4(b) shows another explanatory example regarding the layout of each part. In the example of Figure 4(b), 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 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 Figure 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 extraction unit 18 are arranged on the second surface R2. Further, the 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 where the opening and closing shutter unit 36 (Figure 5) of the transfer robot unit 20 is arranged. Note that in the example of Figure 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> Figure 5 shows the basic configurations of each part (the incubator unit 12, the image inspection unit 14, the stocker supply unit 16, the product extraction unit 18, the transfer robot unit 20, and the 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> Figure 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 recessed 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 shape.

[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 lid 52b on the well plate body 52a, the surface of the well plate body 52a where the well 56 is 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 well 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 of 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. Up to 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 direction (width direction)) extending in the longitudinal direction of the stocker 54.

[0042] The protrusion 62 is located at the center in the length direction of the rectangular notch 60. The V-shaped notch 63 is arranged so as to sandwich the rectangular notch 60 in the length direction. The V-shaped notch 63 has a shape that narrows toward the back (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. Twelve (= 6×2) of these surrounding pins 64 are arranged to face the vicinity of the four corners of the well plates 52 arranged in the longitudinal direction of the stocker 54 at a predetermined interval (an interval of about several millimeters).

[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 for inserting the gripping portion 76 (FIG. 7) of the transfer robot 40 is secured. Also, four (= 2×2) of the twelve surrounding pins 64 are arranged to face the two corners of the two sets of well plates 52 at both ends at a predetermined interval (an interval of about several millimeters).

[0045] The tip (the upper end in FIG. 6) of the surrounding pin 64 is formed 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 while 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 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. Furthermore, 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 and 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. 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 of locking the gripping portion 76 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) are brought closer to 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 side portion of the locking pin 82 enters the V-shaped notch 63, and the thick-diameter tip end side 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 in a state where the gripping portion 76 grips the stocker 54, the air cylinder 70 is also displaced 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 larger 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 plates 52 placed on the stocker 54 vary according to the process. The air gripper 68 having an air cylinder 70, a gripping portion 76, etc. supports and conveys 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 convey a number of stockers 54 and well plates 52 using a single (one type of) air gripper 68.

[0059] When the transfer robot 40 conveys the well plate 52 with the lid 52b alone, with the lid 52b covered, the well plate main body 52a is gripped, and the well plate main body 52a is gripped together with the lid 52b. Also, when the transfer robot 40 conveys the lid 52b alone, only the lid 52b is gripped and lifted, and it is removed from the well plate main 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 between the gripping portions 76 (and the claw portions 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 portions 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 portions 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 (well plate main body 52a), the lifting position of the air gripper 68 becomes higher, and the interval of the gripping portions 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). Therefore, 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] <Route of transfer by the transfer robot 40> The transfer robot 40 transfers the well plate 52, 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 stocker 54 is not being gripped, it is not necessary to greatly raise the tip of the transfer robot 40 so as to avoid the air gripper 68 from interfering with the well plate 52 or the like. Therefore, the movement path of the transfer robot 40 can be made simple.

[0068] <Incubator unit 12> The stocker 54 with the well plate 52 on it 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 rotates (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 broken 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, the image inspection device 34 is also provided with a camera that takes pictures upward from below.

[0070] The camera 90 moves in 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 examples 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 of determining whether cells are acceptable or not. 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 section (not shown in the figure), and an image of the identification information display section is acquired in the inspection area 102.

[0075] On this identification information display unit, 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 two-dimensional code drawn thereon, or by engraving symbols for identification. Further, the reading of the identification information is performed while illuminating the identification information display unit 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 after 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 after 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 closer to the pre-inspection installation area 100.

[0077] Subsequent well plates 52 are similarly inspected, and the well plates 52 after 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 after inspection are stacked up to 5 on 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 performed 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 result is notified via, for example, 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 result, 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, the relationship between the conditions regarding the size and shape of the imaged cells and the quality (OK / NG) of the cells is previously learned by the control unit 46, and the control unit 46 determines and notifies as NG the cells whose correlation with the OK learning result does not fall within a predetermined amount. Also, it is possible to previously learn the growth record of the cells by the control unit 46, and the control unit 46 predicts 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, a sterilization lamp (or germicidal lamp) using, for example, an ultraviolet (UV) light source (such as a UV LED) can be installed at an appropriate location within the image inspection unit 14 to perform sterilization (or disinfection) within 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, the ultraviolet light source can be appropriately placed by selecting the installation location. And, for example, it is possible to appropriately adjust the relationship between the position of a synthetic resin part that is easily deteriorated by ultraviolet light and the position of the ultraviolet light source so that the ultraviolet light does not hit the synthetic resin part, and arrange the two. Furthermore, it is also possible to place 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 free 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 related to the arrangement of each device, and in FIGS. 5 and 10, the arrangement of each device does 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 shared. 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 operating devices (134, 136, 138, etc.) from falling.

[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 12 wells 56.

[0090] The pipettor tool 138 sucks up the culture solution from a culture solution bottle (not shown) and pours the culture solution into the reservoir 120 prior to the discharge of the culture medium by the micropipette tool 136. The culture solution in the reservoir 120 is sucked by the micropipette tool 136 and discharged into the wells 56 of the well plate 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 the disposal of 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 in 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 unit 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, the entire amount of the cleaning alcohol in the reservoir 120. As a result of the aspiration, the cleaning alcohol is discharged to a waste liquid tank (not shown). Then, the tip bit 142 is automatically removed from the aspirator tool 134 and discarded in the waste box 114.

[0095] In the medium exchange unit 22, as a countermeasure against liquid dripping from various operating devices (134, 136, 138, etc.), a plurality of receiving plates 148 formed 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 unit 22. The medium exchange unit 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 unit 22) and a second space (the internal space other than the medium exchange unit 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 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 enters the arm plate 66 (FIG. 10) from the second space into the internal space (first space) of the medium exchange unit 22. 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 (first space) so as to prevent the growth 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 (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 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 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 idle 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 reservoir 120 at the uppermost stage is supported from among the plurality of reservoirs 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 reservoir 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] Furthermore, 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 aspirated 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 medium-exchanged well plates 52 (15 pieces) 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] <Safety improvement measures> 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 it is difficult for a person to predict the operation of the transfer robot 40, for example. Therefore, 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 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 sensor 159 detects a person, the transfer robot 40 is not allowed to perform operations such as gripping and transfer. As the human 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] When a person enters the cell culture device 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 can stop the operation of the transfer robot 40. Furthermore, 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, 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 device 10, it is also possible to stop the operation of the transfer robot 40. Furthermore, 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 presence sensor 159 and the door opening sensor (not shown) can be omitted.

[0113] When stopping the operation of the transfer robot 40, the operation of the movable parts in the entire cell culture device 10, including the medium exchange robot 42, may be stopped. Furthermore, it is also possible to stop only the transfer robot 40 and the medium exchange robot 42.

[0114] Regarding the medium exchange robot 42, since it is partitioned by the wall portion 22B of the medium exchange unit 22 and the like, it is considered that safety is ensured. Furthermore, in the cell culture device 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, it is also possible to cause the medium exchange robot 42 not to stop and perform operations related to medium exchange.

[0115] <Main advantages of the cell culture device 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 movement 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, regarding the medium exchange unit 22 as well, since various regions (such as the holder 112 for the aspirator tool, the waste boxes 114 and 115, the holder 116 for the micropipette tool, the holder 118 for the pipetter tool, the reservoir 120, the bit 122 for the pipette, the bit 124 for aspiration, and the region for the medium tank installation part 126, etc.) necessary for the operation of medium exchange are arranged so as to surround the medium exchange robot 42, the space efficiency can be optimized. And regarding the arrangement of the regions necessary for the operation of medium exchange, it is possible to save space, and it becomes possible to provide a compact medium exchange unit 22.

[0120] In addition, the well plate 52 is transported not only to a space (the 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 prevent dust from entering the wells 56, and it is possible to 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] Regarding the transfer robot 40 as well, 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, it is possible to make the transfer robot 40 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 stacked in a stocker 54 in groups of multiple (here, five). Therefore, it is possible to transport a large number of well plates 52 simultaneously.

[0124] Also, regarding the medium exchange robot 42, a tool adapter 132 is equipped on the tool changer 130, and various operating devices (such as an aspirator tool 134, a micropipette tool 136, or a 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> Note that the arrangement of each part (incubator unit 12, image inspection unit 14, stocker supply unit 16, product extraction unit 18, transport robot unit 20, and medium exchange unit 22) is not limited to that shown in FIG. 1 etc., and can be variously changed. FIG. 12 shows a modification example of the layout. In the cell culture device 160 of the example of FIG. 12, four incubator units 12-1 to 12-4 are provided, and three incubator units 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 units 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 with 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 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. Also, 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 own six-axis operation. Therefore, this also makes the cell culture device 160 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 thereto. 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 widely used. In addition, since there is no need for a space for installing 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] <Supplement regarding air intake> In the cell culture apparatus 10 as described so far, the supply of air to the internal space (first space) of the medium exchange unit 22 is performed by the first space filter unit 26, and the supply of air to the space other than the internal space of the medium exchange unit 22 (second space) is performed by the second space filter unit 28. Further, the first space filter unit 26 independently takes in air outside the cell culture apparatus 10 with respect to the second space filter unit 28, and the air to the internal space (first space) of the medium exchange unit 22 is supplied from the first space filter unit 26 to the internal space (first space) of the medium exchange unit 22.

[0133] Then, the air outside the cell culture apparatus 10 can be taken in independently as the air for the internal space (first space) of the medium exchange unit 22 and the air for the other internal space (second space), and can be supplied to the internal space (first space) of the medium exchange unit 22 and the other internal space (second space) without being branched on the way. Further, for example, even in a simplified structure that does not perform autoclave sterilization, relatively clean air can be supplied to the internal space (first space) of the medium exchange unit 22.

[0134] In addition, since a normal environment can be maintained without relying on steam sterilization, it is possible to keep the inside of the cell culture device at an air cleanliness level suitable for the operation content without the need for thermal countermeasures such as steam temperature control, blocking of heat conduction (and heat transfer) paths, opening and closing of the sealing door, etc. Also, when the transfer robot 40 moves into the internal space (first space) of the medium exchange unit 22, processes such as stopping midway for sterilization can be omitted. From this, the transfer robot 40 can move quickly from the space outside the medium exchange unit 22 (second space) to the internal space (first space) of the medium exchange unit 22.

[0135] <Supplement regarding the function of the air gripper 68> Regarding the above-described air gripper 68 (Figs. 7(a), (b), etc.), in addition to the previous explanations, it can also be explained as follows. For example, the air gripper 68 can perform some common operations to transport different objects. Therefore, the air gripper 68 diversifies the functions of the transfer robot 40 with a limited number of types (modes) of operations.

[0136] Specifically, the air gripper 68 is used for transporting the stocker 54, the well plate 52, and the lid 52b, etc. When transporting any object, the air gripper 68 performs the common operation of closing the gripping part 76. Furthermore, after performing such a common operation, the air gripper 68 grips different objects according to the difference in the interval between the claw parts 78 (also referred to as the difference in the amount of operation or the difference in the displacement amount, etc.). Therefore, it is possible to transport a large number of stockers 54 and well plates 52 using a single (one type of) air gripper 68.

[0137] Furthermore, specifically, when the air gripper 68 transports the stocker 54, as described above, with the closing operation of the gripping part 76, the four locking pins 82 enter the V-shaped notches 63 provided in the claw part 78 and lock to the stocker 54 respectively. As a result, the stocker 54 is positioned with respect to the claw part 78 and gripped by the gripping part 76.

[0138] When the tip of the transfer robot 40 moves upward with the gripping part 76 gripping the stocker 54, the air cylinder 70 is also displaced integrally. When the claw part 78 of the gripping part 76 contacts the protruding part 62 or other parts of the stocker 54 from below and rises, the stocker 54 is lifted. At this time, the force with which the gripping part 76 grips the stocker 54 is not so large, and the force required for the claw part 78 to support the stocker 54 is larger and dominant than the force with which the gripping part 76 grips the stocker 54.

[0139] On the other hand, when the air gripper 68 grips the well plate 52 or the lid body 52b, the two claw parts 78 of the gripping part 76 gradually approach each other, and the four (2×2) resin blocks 80 contact the side surface of the well plate main body 52a or the lid body 52b. Then, without directly contacting the metal claw part 78 with the well plate main body 52a or the lid body 52b, the well plate main body 52a and the lid body 52b are gripped by utilizing the frictional force accompanying the pressurization from the side surface.

[0140] Furthermore, when the air gripper 68 grips the well plate 52 with the lid body 52b, the well plate main body 52a is gripped with the lid body 52b covered, and the well plate main body 52a is gripped together with the lid body 52b.

[0141] When the air gripper 68 grips the well plate 52 or the lid body 52b, the lifting position (position in the vertical direction (Z direction)) of the air gripper 68 and the interval between the gripping parts 76 (and the claw parts 78) are different from those when gripping the stocker 54. Also, when gripping the well plate 52 and when gripping the lid body 52b, the lifting position of the air gripper 68 and the interval between the gripping parts 76 are different.

[0142] As described above, in the cell culture device 10, by using a single air gripper 68 that performs the operation of closing the gripping part 76, it is possible to transfer a plurality of objects having different widths and heights. For this reason, with a simple configuration, it is possible to automate many processes necessary for cell culture.

[0143] In addition, it is also possible to perform different gripping operations according to the weight and size of the object. For relatively light objects (such as well plates 52 and lids 52b), the claws 78 can be used to sandwich them, and for relatively heavy objects (such as stockers 54), the claws 78 can be used to support them, and such differentiated uses are possible. The operations for such differentiated uses are suppressed to the minimum. As a result, it is possible to grip relatively light and heavy objects while performing common operations (such as closing and opening the gripping part 76) in many parts.

[0144] <Utilization of Commercially Available Experimental Equipment> <<Introduction>> In the cell culture device 10, measures are taken to make the best use of commercially available experimental equipment (commercially available experimental equipment) as much as possible. Examples of the commercially available experimental equipment here include, for example, the multi-channel micropipette 182 (Fig. 14) attached to the micropipette tool 136 (Fig. 10), and the electric pipettor 192 (Fig. 15) attached to the pipettor tool 138 (Fig. 10).

[0145] In addition, examples of the commercially available experimental equipment also include the tip bit 142 of the aspirator tool 134 (Fig. 10), the pipette tip 146 attached to the electric pipettor 192 (Fig. 15), etc. Furthermore, the reservoir 120 (Fig. 5), the incubator 32 (Figs. 2 and 5), etc. are also included in the commercially available experimental equipment. In the cell culture device 10, many other commercially available experimental equipment are also used.

[0146] Commercially available experimental equipment is supplied to the market by multiple companies and brands. However, among the same type of experimental equipment, although their shapes and dimensions are similar, they are not common and often slightly different. And to make the cell culture device 10 low-cost and multifunctional, it is important to be able to utilize multiple types of commercially available experimental equipment regardless of differences in shape, dimensions (size), etc. In the cell culture device 10, measures have been taken to enable the utilization of various commercially available experimental equipment as much as possible. Hereinafter, mainly the measures regarding the commercially available experimental equipment described above will be explained.

[0147] <<Measures Regarding the Use of the Multi-Channel Micropipette 182>> As the multi-channel micropipette 182 (Fig. 14), commercially available products supplied by multiple companies and brands can be adopted. However, as described above, among the same type of experimental equipment, although their shapes and dimensions are similar, they are not common and often slightly different.

[0148] Therefore, in order to enable a commercially available experimental device with different shapes, dimensions (sizes), etc. to be used by a single medium exchange robot 42, for example, as shown in FIG. 14, a driven roller 184 and an air cylinder (not shown) are provided on a micropipette tool 136. The air cylinder (not shown) is disposed inside a box 183 provided on the micropipette tool 136. The piston of the air cylinder (not shown) is in contact with a piston button 186 of a multi-channel micropipette 182 via a power transmission unit (not shown). The driven roller 184, the air cylinder (not shown), the power transmission unit (not shown), etc. constitute a push button drive mechanism unit. And the air cylinder (not shown) automatically presses the piston button 186 of the multi-channel micropipette 182. By pressing (lowering) the piston button 186, a dispensing operation is automatically performed. The piston button 186 can be pressed (lowered) by the force generated in the air cylinder (not shown) as long as no pressing force is applied to a position deviated from the piston button 186 or an extremely biased position on the piston button 186.

[0149] An elastic body (not shown) such as a coil spring is attached to the piston button 186. And when the piston button 186 is released from the force generated in the air cylinder (not shown), it receives the elastic restoring force of the elastic body (not shown) and returns (rises) to its original position (non-pressed position). By the rising of the piston button 186, a suction operation is automatically performed. The driven roller 184 follows these movements of the piston button 186.

[0150] In this way, by operating the piston button 186, the multi-channel micropipette 182, which is a commercially available experimental device, can be operated even if there are some differences in shape, dimensions (sizes), etc. And the differences in models of the multi-channel micropipette 182 can be absorbed. Furthermore, different models of the multi-channel micropipette 182 can be handled by a single medium exchange robot 42.

[0151] In the example of FIG. 14, another driven roller 185 also contacts a shoulder (shoulder of the multi-channel micropipette 182) 187 that protrudes below the piston button 186. The shoulder 187 is also a movable part combined with an elastic body such as a coil spring (not shown). Similar to the piston button 186, it is pressed by a drive mechanism part (shoulder drive mechanism part) composed of a driven roller 185, an air cylinder (not shown) in the box 183, a power transmission part (not shown), etc., and moves up and down. When the shoulder 187 is pushed down, the needle 144 attached to the multi-channel micropipette 182 automatically detaches from the multi-channel micropipette 182 by air pressure.

[0152] Instead of the air cylinder (not shown) that drives the piston button 186 and the shoulder 187, for example, a motor may be used. The motor may be an air motor using air as a power source or an electric motor using electricity as a power source.

[0153] The multi-channel micropipette 182 is held by the holder part 188. In the holder part 188, for example, different types of multi-channel micropipettes 182 with similar shapes can be held due to differences in the screwing amount (also referred to as tightening amount, clamping amount, etc.) of the bolt 189.

[0154] The holder part 188 functions as a jig for holding a commercially available experimental device (here, the multi-channel micropipette 182) so that it can be used. When a curved design is applied to a commercially available experimental device (here, the multi-channel micropipette 182), generally, it becomes difficult to incorporate it into the micropipette tool 136. However, by adopting a jig structure such as the holder part 188, it becomes possible to flexibly respond to differences in the types of multi-channel micropipettes 182.

[0155] Note that, in Fig. 14, what is indicated by reference numeral 133 is the tool-side adapter. The tool-side adapter 133 is connected to a tool adapter 132 (Fig. 10, etc.) provided at the tip of the medium exchange robot 42. The illustration of the micropipette tool 136 (Fig. 10) in a state of being attached to the medium exchange robot 42 is omitted.

[0156] <<Ingenuity Regarding the Use of the Electric Pipettor 192>> As the electric pipettor 192 (Fig. 15) as well, commercially available products supplied from a plurality of manufacturers and brands can be adopted. However, as described above, in the case of the same type of experimental equipment, although their shapes, dimensions, etc. are similar, they are not common and often slightly different. In the pipettor tool 138 shown in Fig. 15, the electric pipettor 192 is held using a holder portion 193.

[0157] The holder portion 193 includes two plate-shaped frame portions 194 with cutouts, and the electric pipettor 192 is sandwiched between the frame portions 194. A plurality of roller portions 196 are provided between the frame portions 194, and the roller portions 196 are supported by the frame portions 194 with their ends inserted into long holes 198. The roller portions 196 are in contact with the outer peripheral portion of the electric pipettor 192. The longitudinal direction of each long hole 198 faces either one of two directions orthogonal to the plane of the frame portion 194.

[0158] The electric pipettor 192 is surrounded by the frame portions 194 and the roller portions 196 and is held by the pipettor tool 138. Since the roller portions 196 are inserted into the long holes 198, they can move within the range of the long holes 198. For this reason, the position of the roller portions 196 changes according to the difference in the dimensions (size) of the electric pipettor 192.

[0159] A plurality of bolts 200 are screwed into the frame portion 194. The bolt 200 moves forward and backward by being screwed in or loosened. When the bolt 200 is screwed in and advanced toward the electric pipettor 192, the tip of the bolt 200 presses the electric pipettor 192. And when the bolt 200 is screwed in, the electric pipettor 192 is held more firmly than before it was screwed in.

[0160] In addition, by attaching a protective member (buffer member), for example, made of synthetic resin (including synthetic rubber) to the tip of the bolt 200, the bolt 200 can be prevented from damaging the electric pipettor 192. Also, it is possible to adopt synthetic resin (synthetic resin having sufficient rigidity) as the material of the bolt 200.

[0161] In this way, the electric pipettor 192 is held by the pipettor tool 138 using the displaceable roller portion 196 and the displaceable bolt 200. And the electric pipettor 192 is held at a position according to the shape, dimensions (size), etc. by displaceable members (displaceable members) such as the bolt 200 and the roller portion 196.

[0162] Therefore, the electric pipettor 192, which is a commercially available experimental device, can be held even if there are some differences in shape, dimensions (size), etc. And the differences in models of the electric pipettor 192 can be absorbed. Furthermore, it is possible to handle different models of the electric pipettor 192 with one medium exchange robot 42.

[0163] Also, the electric pipettor 192 is provided with two push buttons (not shown), and these push buttons are pressed by two movable parts (not shown) provided in the button operation part 195. In FIG. 15, the push buttons and the movable parts are hidden in the shadow of the frame portion 194. The functions of the two push buttons are for dispensing and suction, and the two movable parts individually press the corresponding push buttons to perform the dispensing operation and the suction operation. The driving of the movable part is performed by pneumatic pressure.

[0164] The driving of the two movable parts (not shown) in the button operation unit 195 can be individually performed, for example, by using two air cylinders (driving sources) provided in the pipetter tool 138. In this case, the movable part (not shown) can be connected to the piston of the air cylinder.

[0165] The frame part 194 functions as a jig for holding a commercially available experimental device (here, an electric pipetter 192) so that it can be used. The frame part 194 includes a roller part 196 and bolts 200. When a commercially available experimental device (here, an electric pipetter 192) has a curved design, generally, it becomes difficult to incorporate it into the pipetter tool 138. However, by adopting a jig structure such as the frame part 194, it becomes possible to flexibly respond to differences in the types of electric pipettes 192.

[0166] Note that the electric pipetter 192 may be held while utilizing the leaf spring force (elastic restoring force of the leaf spring) of the plate-shaped frame part 194. Also, what is indicated by reference numeral 133 in FIG. 15 is a tool-side adapter. The tool-side adapter 133 is connected to a tool adapter 132 (FIG. 10, etc.) provided at the tip of the medium exchange robot 42. The illustration of the pipetter tool 138 (FIG. 10) in a state of being attached to the medium exchange robot 42 is omitted.

[0167] <<Ingenuity Regarding the Use of the Tip Bit 142 and the Needle 144>> The tip bit 142 (FIG. 10) is attached to the aspirator tool 134 (FIG. 10). A multi-aspirator 202 (FIGS. 16(a) and (b)) is attached to the aspirator tool 134 (FIG. 10), and an aspirator connector 204 is provided on the multi-aspirator 202. The tip bit 142 is attached to the aspirator connector 204 by a procedure as shown in FIGS. 16(a) and (b), for example.

[0168] As shown in FIG. 16(a), a number of tip bits 142 are arranged and accommodated in a matrix in the pit box 206. In FIG. 16(a), only one row of the tip bits 142 is shown. One row is composed of 12 tip bits 142. The aspirator tool 134 (FIG. 10) is attached to the medium exchange robot 42. Illustration of the aspirator tool 134 (FIG. 10) in a state of being attached to the medium exchange robot 42 is omitted.

[0169] The multi-aspirator 202 is attached to the aspirator tool 134. The multi-aspirator 202 is provided with a predetermined number (here, 12) of aspirator connectors 204 protruding parallel to each other.

[0170] The aspirator connector 204 has tapered portions 208 and 210 that taper towards the tip and the middle. The material of the aspirator connector 204 is made of a metal such as stainless steel, for example. Then, the medium exchange robot 42 lowers the multi-aspirator 202 together with the aspirator tool 134 towards the row of tip bits 142 as indicated by the arrow K.

[0171] As shown in FIG. 16(b), the aspirator connector 204 reaches the tip bit 142 and enters the opening at the base end portion (the root portion) of the tip bit 142. Further, as the multi-aspirator 202 continues to descend, the tapered portion 210 in the middle of the aspirator connector 204 reaches the opening at the base end portion of the tip bit 142.

[0172] The aspirator connector 204 generates a force from the inside to the outside at the base end portion of the tip bit 142 by the tapered portion 210. A situation occurs where the aspirator connector 204 is pressed against the tip bit 142 with a predetermined force. The material of the tip bit 142 is a synthetic resin. Then, the aspirator connector 204 is press-fitted into the tip bit 142, and the aspirator connector 204 and the tip bit 142 are coupled.

[0173] When the process of connecting the aspirator connector 204 and the tip bit 142 is completed, as shown in FIG. 17(b), the multi-aspirator 202 rises while holding the tip bit 142. However, prior to this rising process, as shown in FIG. 17(a), the fall prevention plate 207 moves forward. Here, the "forward movement" refers to the movement from the rear to the front accompanying the arc-shaped displacement as indicated by the arrow L, as shown in FIG. 18. FIG. 18 shows the state of FIG. 17(a) viewed from the side (the direction of the arrow M in FIG. 17(a)).

[0174] The fall prevention plate 207 constitutes a fall prevention mechanism. The fall prevention plate 207 is formed using a plate bent in an L shape. Further, a plurality of claw portions 211 extending parallel to each other are provided at the edge on the tip side of the fall prevention plate 207, and the claw portions 211 enter between adjacent tip bits 142. A flange portion 212 protruding cylindrically around is provided on the tip bit 142. And the claw portions 211 partially face the flange portion 212 protruding in a stepped manner from below.

[0175] Therefore, for example, even if some of the aspirator connectors 204 do not fully enter the corresponding tip bits 142, the connection becomes loose, and the tip bits 142 fall out of the aspirator connectors 204, the tip bits 142 can be hooked on the claw portions 211. Thus, it is possible to prevent the tip bits 142 from falling onto the workbench 110 (FIG. 5).

[0176] When a commercially available experimental device is used as the tip bit 142, depending on the shape, dimensions, etc. of the used tip bit 142, or the angle (posture) in the situation of being accommodated in the pit box 206, it is conceivable that the multi-aspirator 202 may rise with an insufficient connection to the aspirator connector 204. When the tip bit 142 falls, depending on the situation, it is necessary to stop the automatic operation of the cell culture device 10, and the operator A (FIG. 1, etc.) enters the cell culture device 10 (or inserts an arm) to remove the tip bit 142 from the cell culture device 10.

[0177] In addition, in the cell culture device 10, when it is used in such a way that, for example, the processes necessary for cell culture are executed continuously for 10 days or more once the operation (action) is started, the drop of the tip bit 142 may have an adverse effect on the cell culture over the previous several days. Also, the air cleanliness may decrease when the doors and shutters are opened.

[0178] However, as shown in FIGS. 17(a) and (b), by preventing the drop of the tip bit 142, it becomes possible to operate the cell culture device 10 while maintaining an optimized environment without stopping the processes necessary for cell culture.

[0179] Moreover, the fall prevention mechanism including the fall prevention plate 207 not only prevents the drop of the tip bit 142, but also, as shown in FIG. 19, a tip bit detection sensor 214 capable of detecting the presence or absence of a drop is provided. As the tip bit detection sensor 214, for example, an optical sensor composed of a light projecting part 216 and a light receiving part 218 can be adopted.

[0180] When detecting the presence or absence of the drop of the tip bit 142, for example, the multi aspirator 202 holding a row of tip bits 142 is moved by the medium exchange robot 42 toward the tip bit detection sensor 214 as shown by the arrow N. The tip bit detection sensor 214 is arranged in the medium exchange part 22, similarly to the medium exchange robot 42.

[0181] The medium exchange robot 42 linearly moves the multi aspirator 202 at a constant speed so that the tip bit 142 passes between the light projecting part 216 and the light receiving part 218 in order. The tip bit detection sensor 214 can be installed, for example, on the workbench 110. However, it is not limited to this, and for example, a shelf (not shown) or the like can be provided at a position higher than the workbench 110, and the tip bit detection sensor 214 can be installed on this shelf.

[0182] When there is no drop, a predetermined number (here, 12) of tip bits 142 intermittently and regularly block the light between the light projecting unit 216 and the light receiving unit 218. However, when there is a drop, the period during which the tip bit 142 is not detected becomes longer than when there is no drop. Therefore, by monitoring the waveform of the output signal of the light receiving unit 218, for example, by the control unit 46 (Fig. 5) or the like, it is possible to determine the presence or absence of the drop of the tip bit 142 and the position where the drop has occurred. Here, the tip bit detection sensor 214 may be of a type that detects the reflected light from the tip bit 142.

[0183] Here, the tip bit 142 attached to the aspirator tool 134 (Fig. 10) has been described. However, it is also possible to adopt a similar attachment mechanism, attachment method, fall prevention structure, and fall prevention method for the needle 144 of the micropipette tool 136. The micropipette tool 136 in the example of Fig. 14 is provided with a fall prevention plate 219 in the same manner as the aspirator tool 134 (Figs. 10, 17, 18). Also, it is possible to provide a needle detection sensor (not shown). Furthermore, the tip bit detection sensor 214 can be made into an optical sensor that also serves as a needle detection sensor.

[0184] <<Ingenuity Regarding the Use of the Pipette Chip 146>> The pipette chip 146 (Fig. 10) is a large and long commercially available experimental device compared to the tip bit 142 and the needle 144. The pipette chip 146 is attached to the electric pipettor 192 (Fig. 15). The electric pipettor 192 (Fig. 15) is held by the pipettor tool 138. The attachment of the pipette chip 146 to the electric pipettor 192 is performed, for example, according to the procedure shown in Figs. 20(a) and (b).

[0185] In Fig. 20(a), a single pipette tip 146 is held by a movable mechanism unit 220A. The movable mechanism unit 220A is connected to a drive source such as an air cylinder, and as shown by arrow P, it is possible to raise the pipette tip 146 at a predetermined speed (for example, about several cm to 10 cm / second). As the pipette tip 146 rises, it approaches the electric pipettor 192.

[0186] The pipette tip 146 comes into contact with the tip connector 221 of the electric pipettor 192 and continues to rise. Then, relatively, the tip connector 221 enters the pipette tip 146. Further, the tip connector 221 is press-fitted into the pipette tip 146, and the pipette tip 146 is connected to the electric pipettor 192.

[0187] Here, in the examples of Figs. 20(a) and (b), the movable mechanism unit 220A is shown as simply contacting the pipette tip 146 from below and pushing up the pipette tip 146. However, it is not limited to this, and it is also possible for the movable mechanism unit 220A to grip and lift the pipette tip 146 from the horizontal direction.

[0188] At this time, a pressurizing mechanism unit 220B is in contact with the electric pipettor 192 from above. The pressurizing mechanism unit 220B is formed of a member such as an aluminum profile, and moves so as to approach and move away from the electric pipettor 192. In the examples of Figs. 20(a) and (b), the pressurizing mechanism unit 220B is moved so as to contact the electric pipettor 192 from above.

[0189] The pressurizing mechanism unit 220B receives the force by which the electric pipettor 192 is pushed upward by the pipette tip 146, and generates a downward force on the electric pipettor 192 as indicated by an arrow Q in Fig. 20(b). The pressurizing mechanism unit 220B may apply an upward force to the electric pipettor 192, or may simply be in contact with the electric pipettor 192. Even if the pressurizing mechanism unit 220B is merely in contact with the electric pipettor 192, a reaction force is generated by the force from below the movable mechanism unit 220A being transmitted to the electric pipettor 192 via the pipette tip 146.

[0190] As a result, a force can be generated to cause the chip connector 221 to enter toward the opening at the upper part of the pipette tip 146. Then, while sufficiently ensuring the upward force of the pipette tip 146 (the upward pushing force of the movable mechanism unit 220A), the pipette tip 146 can be attached to the electric pipettor 192.

[0191] In other words, by supporting the electric pipettor 192 from above by the pressurizing mechanism unit 220B, the force for attaching the pipette tip 146 to the electric pipettor 192 can be supplemented (enhanced or increased). Furthermore, since the pressurizing mechanism unit 220B receives the upward force of the movable mechanism unit 220A, the load applied to the culture medium exchange robot 42 can be minimized.

[0192] Also, there is no need to increase the size or load of the movable mechanism unit 220A or the drive system of the movable mechanism unit 220A. That is, it is possible to make the drive system of the movable mechanism unit 220A small with a low load. Furthermore, there is no need to introduce a dedicated large device for attaching the pipette tip 146 to the electric pipettor 192. For this reason, the cell culture apparatus 10 can be miniaturized.

[0193] <<Devises Regarding Use of Incubator 32>> Regarding the incubator 32, the opening and closing of the door in a commercially available incubator are automated. Further, in this automation, modification of the incubator is not required, and an inexpensive and compact configuration is achieved.

[0194] As described above, the incubator 32 (Figs. 2 and 5) is provided with an automatic door 86. The automatic door 86 is a single-sided hinge type door and rotates (rotational displacement) horizontally while being supported by the incubator main body 230. Fig. 21(a) shows the state where the automatic door 86 is closed, and Fig. 21(b) shows the state where the automatic door 86 is opened. The automatic door 86 functions as the outer door of the incubator 32. Further, as shown in Figs. 21(b) and 22, an inner door 232 is provided inside the automatic door 86. The inner door 232 is also a single-sided hinge type door and rotates (rotational displacement) horizontally while being supported by the incubator main body 230.

[0195] The automatic door 86 is formed by bending a sheet metal into a rectangular box shape, and the entire automatic door 86 is subjected to painting or the like. For this reason, the inside of the incubator 32 cannot be visually recognized through the automatic door 86. On the other hand, a transparent resin, glass, or the like is used for the inner door 232. And if only the inner door 232 is closed, the inside of the incubator 32 can be visually recognized through the inner door 232. Thus, the incubator 32 has a double-door structure.

[0196] The automatic door 86 and the inner door 232 are individually opened and closed under the control of, for example, the control unit 46 (Fig. 5). As shown in Figs. 21(b) and 22, piston rods 235 and 237 of air cylinders 234 and 236 are connected to the automatic door 86 and the inner door 232. The connection between the automatic door 86 and the inner door 232 and the piston rods 235 and 237 is performed using strip-shaped holding members 238 and 240. There are two holding members 238 for the automatic door 86, and one holding member 238 for the inner door 232. The portions where the automatic door 86 and the inner door 232 are connected to the piston rods 235 and 237 are fixed portions 246 and 248.

[0197] The holding members 238 and 240 are arranged outside the automatic door 86 and the inner door 232 with their longitudinal directions oriented in the vertical direction. The end portions of the holding members 238 and 240 in the longitudinal direction (vertical direction) have a bent shape. And the holding members 238 and 240 are attached to the automatic door 86 and the inner door 232 via a sandwiching structure (a sandwiching structure) that sandwiches the top and bottom of the automatic door 86 and the inner door 232. Specifically, the holding members 238 and 240 are configured by combining an L-shaped sheet metal member or a resin plate member with a plate-shaped aluminum frame.

[0198] The two holding members 238 of the automatic door 86 are connected to each other by a connecting plate (bracket) 242. As shown in FIGS. 23(a) and (b), the holding member 238 is screwed to the automatic door 86 in a state of being overlapped with the connecting plate 242 from the outside. The connecting plate 242 is screwed to the automatic door 86 in a state of being overlapped with the automatic door 86.

[0199] The fixing of the holding member 238 and the connecting plate 242 to the automatic door 86 is performed by screwing screws into existing holes in the automatic door 86. Further, as shown in FIGS. 23(a) and (b), an L-shaped metal fitting 244 is also inserted and fixed into the gap between the existing door packing 243 of the automatic door 86 and the frame 245. A long hole 247 is formed at the end of the holding member 238, and the fixing position can be adjusted within the range of the long hole 247. By using the holding member 238, the connecting plate 242, and the L-shaped metal fitting 244, a force for sandwiching the automatic door 86 from the vertical direction by the holding member 238 and a force for sandwiching the automatic door 86 from the thickness direction (a sandwiching force) by the holding member 238 and the L-shaped metal fitting 244 can be generated. And with such a structure, even when the number of existing holes in the automatic door 86 is small (for example, one), and the fixing force by screwing is small, a sufficient fixing force for transmitting the force of the air cylinder 234 to the automatic door 86 can be ensured.

[0200] The piston rod 235 of the air cylinder 234 is connected to a connecting plate 242 provided along the lower side of the automatic door 86 (Fig. 23(b)). The connection of the piston rod 235 to the connecting plate 242 is made in a state where relative displacement in the horizontal direction is possible around the pivot of the fixing portion 246. Although not shown, the base end side of the air cylinder 234 connected to the incubator main body 230 can also have relative displacement in the horizontal direction around the pivot.

[0201] As shown in Fig. 22, the longitudinal ends of the holding member 238 of the inner door 232 protrude above and below the inner door 232. The piston rod 237 of the air cylinder 236 corresponding to the inner door 232 is connected to a fixing portion 248 formed at the lower end portion of the holding member 238. Although detailed illustration is omitted, the connection of the piston rod 237 to the holding member 238 is made in a state where relative displacement in the horizontal direction is possible around the pivot of the fixing portion 248. Although not shown, the base end side of the air cylinder 236 connected to the incubator main body 230 can also have relative displacement in the horizontal direction around the pivot.

[0202] The automatic door 86 and the inner door 232 are opened by being pushed by the air cylinders 234, 236 and closed by being pulled by the air cylinders 234, 236. In Fig. 22, the automatic door 86 and the inner door 232 are both open at different opening degrees.

[0203] As the air cylinders 234, 236, those with a closed center specification are used. In the air cylinders 234, 236 with a closed center specification, the positions of the piston rods 235, 237 are maintained in an intermediate position state. In the example of Fig. 21(a), the piston rods 235, 237 are in the intermediate position state. In the example of Fig. 22, the piston rod 235 connected to the automatic door 86 is in a state protruding more than the intermediate position state, and the piston rod 237 connected to the inner door 232 is in the intermediate position state.

[0204] The displacement speeds of the piston rods 235 and 237 are adjusted using a speed controller. The thrust of the piston rods 235 and 237 is adjusted using a regulator (pneumatic regulator).

[0205] The incubator 32 is one of the commercially available experimental devices. When a commercially available incubator 32 is used, conventionally, the automatic door 86 and the inner door 232 were opened and closed manually. However, in the cell culture apparatus 10, the opening and closing of the automatic door 86 and the inner door 232 are automated, and the opening and closing of the door of the commercially available experimental device, the incubator 32, is automated.

[0206] The air cylinders 234 and 236 are controlled so as to reproduce the way of opening and closing the automatic door 86 and the inner door 232 by a human in the processes necessary for cell culture. Also, the air (compressed air) for driving the air cylinders 234 and 236 is introduced through an independent air system, not the air used for, for example, the medium exchange robot 42.

[0207] In the incubator 32 shown in the examples of FIGS. 21 to 23, the inner door 232 was provided with a manual locking mechanism. However, in the examples of FIGS. 21 to 23, it has been removed because more devices are required to automate the operation of the locking mechanism. Note that it is also possible to leave the locking mechanism without removing it and not use it. Further, if the operation of the locking mechanism can be performed by a simple device, the locking mechanism may be automated.

[0208] The matters regarding the incubator 32 as described above can be organized as follows. (1) In the incubator 32, the air cylinders 234 and 236 are used as the drive sources for opening and closing the doors (opening and closing of the automatic door 86 and / or the inner door 232). (2) The air cylinders 234 and 236 are compactly arranged outside (here, the lower part) of the incubator 32. (3) No separate link mechanism is combined with the air cylinders 234 and 236, and the doors (automatic door 86 and inner door 232) are directly connected to the air cylinders 234 and 236 at the fixing parts 246 and 248. The doors (automatic door 86 and inner door 232) and the air cylinders 234 and 236 are directly connected at the fixing parts 246 and 248, and the air cylinders 234 and 236 themselves serve as the links. Therefore, it is possible to arrange the mechanical configuration for automatically opening and closing the doors (automatic door 86 and inner door 232) in a space-saving manner. (4) The air cylinders 234 and 236 are of the closed center type, and when the piston rod 235 (and / or piston rod 237) is in the intermediate position state, the closed state of the automatic door 86 (and / or inner door 232) is maintained. Therefore, there is no need to provide a separate locking mechanism. (5) The opening and closing speeds of the doors (automatic door 86 and inner door 232) can be individually adjusted using a spicon (speed controller), and the thrust for opening and closing the doors can be adjusted using a regulator (pneumatic regulator). And since air equipment (pneumatic equipment) is used, the opening and closing of the doors can be easily adjusted and controlled by the spicon and the regulator. Therefore, the configuration for opening and closing the doors (automatic door 86 and inner door 232) can be realized at low cost. (6) Holding members 238 and 240 are attached to the doors (automatic door 86 and inner door 232) by a sandwiching structure, and the holding members 238 and 240 are fixed to the air cylinders 234 and 236. Fixing the doors (automatic door 86 and inner door 232) and the drive part (here, the air cylinders 234 and 236) in this way is for the following reasons. That is, when using a commercially available incubator, major modifications such as replacing (exchanging) the rotation axis of the incubator or making holes in the door are not preferred because the performance guarantee by the manufacturer of the incubator etc. cannot be obtained or the cost increases. (7) The automatic door 86 and the inner door 232 are each driven by two independent air cylinders 234 and 236. In many commercially available incubators, the door is configured with two doors, an outer door and an inner door. The outer door is formed to be opaque and have high heat insulation performance. Also, the inner door is formed of glass or a transparent resin. By having such a two-door configuration, there are advantages such as less heat loss when opening and closing the door, and the ability to check the inside without opening the inner door. In the cell culture apparatus 10, the door is opened in the order of the outer door (automatic door 86) → the inner door 232, and the door is closed in the order of the inner door 232 → the outer door (automatic door 86).

[0209] <<Summary of Utilization of Commercially Available Experimental Equipment>> As described above, various commercially available experimental equipment is being utilized. And in the cell culture apparatus 10, commercially available experimental equipment that is manually operated by humans is incorporated into an automated system and used.

[0210] Note that not only the medium exchange robot 42, but also, for example, in the transfer robot 40, it is possible to hold commercially available experimental equipment. Regarding the transfer robot 40, for example, commercially available ones can be used as the well plate 52 and the lid 52b. And in this case, it can be said that a device has been made so that a plurality of types of commercially available experimental equipment can be used by the air gripper 68 with some common operations.

[0211] <Drive Mode of Shutter> Regarding the shutter mechanism such as the above-described automatic opening and closing shutter 152 (FIG. 11), by making it possible to adjust the opening area, it is possible to enhance the sealing effect as much as possible. Specifically, for example, as shown in FIG. 24(a), two automatic opening and closing shutters 152A and 152B are arranged side by side in the lateral direction (left-right direction, horizontal direction). The automatic opening and closing shutters 152A and 152B are individually installed in the openings 252A and 252B of the culture medium exchange unit 22, as shown in FIGS. 24(b) and 25(a). The automatic opening and closing shutters 152A and 152B constitute the inner wall portion 22B in the culture medium exchange unit 22 and face the transfer robot 40.

[0212] The automatic opening and closing shutters 152A and 152B are individually controlled to open and close, for example, under the control of the control unit 46 (FIG. 5). For example, as shown in FIG. 24(b), one of the automatic opening and closing shutters 152A is opened. Although not shown, in this state, the transfer robot 40 causes the arm plate 66 (FIG. 10) to enter the culture medium exchange device 43 through the opening 252A. After the transfer robot 40 finishes the operation using the air gripper 68 in the culture medium exchange area 157 (FIG. 5), the arm plate 66 (FIG. 10) is moved outside the culture medium exchange device 43.

[0213] The one automatic opening and closing shutter 152A that was open rises, the opening 252A is closed, and the other automatic opening and closing shutter 152B that was closed is opened as shown in FIG. 25(a). Although not shown, the transfer robot 40 directs the fork portion 84 (two long claw portions) of the arm plate 66 (FIG. 10) toward the culture medium exchange device 43 and causes it to enter the culture medium exchange device 43 through the opening 252B.

[0214] After that, the transfer robot 40 supports one reservoir 120 at the uppermost stage from among the plurality of reservoirs 120 stacked in the reservoir preparation area 158 and installs it in the reservoir installation area 128. Prior to the installation of the reservoir 120 in the reservoir installation area 128, the transfer robot 40 performs an operation (shaking operation) of moving the arm plate 66 up and down at a short cycle, as shown in FIG. 26, which will be described later.

[0215] The transfer robot 40 moves the arm plate 66 (Fig. 10) outside the culture medium replacement device 43. Then, the automatically opening and closing shutter 152B that was open rises and closes, and both automatically opening and closing shutters 152A and 152B are in a closed state.

[0216] The amount (degree of opening, opening degree) by which the automatically opening and closing shutters 152A and 152B open can be individually and arbitrarily changed between 0 (fully closed) and 100% (fully open). For this reason, the automatically opening and closing shutters 152A and 152B can be opened at the minimum necessary opening degree. And it is possible to finely adjust and minimize the opening areas of the openings 252A and 252B.

[0217] Fig. 25(b) shows a state where the opening degree of one of the automatically opening and closing shutters 152A (and the opening 252A) is about 50% and the opening degree of the other automatically opening and closing shutter 152B (and the opening 252B) is 0%.

[0218] For example, as shown in Fig. 25(a), with the opening degree of the automatically opening and closing shutter 152B being 100%, and with the longitudinal direction of the arm plate 66 (Fig. 10) oriented vertically, it is possible to move the arm plate 66 (Fig. 10) into the opening 252B. Further, as shown in Fig. 25(b), with the opening degree of the automatically opening and closing shutter 152A being 50%, and with the longitudinal direction of the arm plate 66 (Fig. 10) oriented front and back (the front and rear directions in the horizontal direction), it is possible to move the arm plate 66 (Fig. 10) into the opening 252A.

[0219] And by the combination of opening and closing and the opening degree of the two horizontally arranged automatically opening and closing shutters 152A and 152B, it is possible to finely adjust and minimize the area of the opening in the same plane. Further, it is possible to minimize the area of the opening through which the transfer robot 40 with the arm plate 66 attached enters and exits. Here, regarding the "area of the opening", it is possible to adjust both the areas of the openings 252A and 252B and the total area.

[0220] Note that the internal space (first space) of the medium exchange device 43 is maintained at a positive pressure by the air from the filter unit 26 for the first space. Therefore, when the automatic opening / closing shutters 152A and 152B are opened, the air in the second space does not immediately enter. However, since the transfer robot 40 and the arm plate 66 enter and exit, it is effective to minimize the opening areas of the openings 252A and 252B.

[0221] Also, since the automatic opening / closing shutters 152A and 152B are displaced vertically, it is possible to prevent the automatic opening / closing shutters 152A and 152B from interfering with the devices and instruments in the medium exchange device 43. In addition, the vertical space of the cell culture device 10 can be effectively utilized, and the medium exchange device 43 and the cell culture device 10 can be miniaturized in the left-right and front-back (Y direction and X direction in FIGS. 1 and 2). Note that the number of the automatic opening / closing shutters 152A and 152B may be one or three or more. Also, a fixed window portion (fixed window) or a pillar or the like may be provided between the automatic opening / closing shutters 152A and 152B. Including such cases, it can be said that the automatic opening / closing shutters 152A and 152B are arranged side by side in the horizontal direction.

[0222] <Gripping of one reservoir 120> As described above, the transfer robot 40 performs an operation (shaking operation) of moving the arm plate 66 up and down at a short cycle. By this operation, the transfer robot 40 surely supports one reservoir 120 located at the uppermost stage among the plurality of reservoirs 120 stacked in the reservoir preparation area 158.

[0223] The reservoir 120 is molded using a synthetic resin material to have a certain degree of flexibility. The degree of flexibility is such that it can be visually elastically deformed by hand. Such flexibility is obtained not only from the properties of the synthetic resin material but also from the wall thickness of the reservoir 120. Also, each reservoir 120 is molded, for example, into a container shape with an opening in a rectangular shape. And each reservoir 120 has the same shape and is stacked in a state where the unevenness of each other is fitted to some extent.

[0224] Due to these factors, the reservoirs 120 stacked in the reservoir preparation area 158 may be in close contact with the reservoir in the next stage (lower stage), and the upper and lower reservoirs 120 may be stuck to each other. Furthermore, three or more reservoirs 120 may be stuck together. However, the arm plate 66 grips and raises one reservoir 120 at the uppermost stage and moves up and down at a short cycle (for example, 1 to 2 times / second) as indicated by the arrow R in FIG. 26.

[0225] The gripping by the arm plate 66 (also referred to as gripping by the transfer robot 40) is performed by sandwiching the object to be gripped (here, the reservoir 120) between some gripping pins 259 provided on the fork portion 84 (only shown on one side in FIG. 26). The gripping pin 259 is formed in a cylindrical shape and protrudes vertically from the fork portion 84. When gripping the reservoir 120, the flange portion 120A formed on the periphery of the reservoir 120 is supported from below by the fork portion 84.

[0226] By performing such a shaking operation, the reservoirs 120 from the second stage and below that are not directly gripped are shaken off. As a result, only the reservoir 120 at the uppermost stage can be gripped and only one reservoir 120 can be surely installed in the reservoir installation area 128.

[0227] In addition, for example, in the reservoir installation area 128, it is also possible to detect whether there is only one reservoir 120. More specifically, although not shown in the figure, an optical sensor having a light emitter and a light receiver is installed in the reservoir installation area 128. The optical sensor is arranged such that the reservoir 120 is located in between. When a foreign object (here, the reservoir 120) exists at a position exceeding the height of one reservoir 120, the detection light of the optical sensor is blocked. Then, based on the interruption of the detection of light, the control unit 46 determines that a plurality of reservoirs 120 remain overlapping. Note that the optical sensor may be of a type that detects reflected light from the reservoir 120.

[0228] <Structure for maintaining air cleanliness> <<Structure for discarding into the waste BOX 114>> Inside the medium exchange device 43, the upper and lower spaces are partitioned by the workbench 110. As shown in FIGS. 27(a) and 27(b), a waste shutter 262 is provided on the workbench 110. FIGS. 27(a) and 27(b) show a partial longitudinal section of the lower part of the medium exchange unit 22.

[0229] The waste shutter 262 is normally closed as shown in FIG. 27(a). However, when the waste BOX 114 is used, the waste shutter 262 slides in the horizontal direction (Y direction in FIG. 1) as shown in FIG. 27(b) to expose the internal waste opening 264. The sliding of the waste shutter 262 can be automatically performed under the control of the control unit 46 (FIG. 5).

[0230] The size of the internal waste opening 264 is approximately the same as the opening 266 of one waste BOX 114. For example, the tip bit 142 of the aspirator tool 134 (FIG. 10) and the like are discarded into the waste BOX 114. The removal of the tip bit 142 can be performed using air pressure. Also, in the micropipette tool 136 (FIGS. 10 and 14), the needle 144 removed by pressing down the shoulder 187 of the multi-channel micropipette 182 can be dropped into the waste BOX 114 for discarding.

[0231] Also, normally, the waste shutter 262 is closed, preventing the liquid such as the culture solution from falling into the waste BOX 114. The waste shutter 262 is automatically controlled to open and close, for example, by the control unit 46 (Fig. 5).

[0232] In this way, by providing the waste shutter 262, it is possible to automate the waste operation into the waste BOX 114. And, for example, it is possible to maintain the air cleanliness of the surrounding environment related to the medium exchange robot 42 compared to the case where an operator opens the medium exchange section 22 and performs the waste manually.

[0233] <<Structure partitioning the inside of the medium exchange device 43>> The workbench 110 uses a sheet metal member made of metal such as a stainless steel material. As the plate material of the workbench 110, as shown in Fig. 28, a punching panel having a large number of through holes 276 is adopted at least in part. And the air from the first space filter unit 26 flows (downflows) toward the workbench 110 and flows into the lower space 278 through the through holes 276 of the workbench 110.

[0234] In the upper space 279 of the workbench 110, operations by the medium exchange robot 42 are performed, and in the lower space 278, installations such as the waste BOX 114 are made. The air in the environment around the medium exchange robot 42 is discharged from the upper space 279 to the lower space 278. Further, the air in the lower space 278 is discharged from the medium exchange device 43 to the outside of the cell culture device 10.

[0235] In this way, inside the medium exchange device 43, a relatively clean space (upper space 279) and a relatively less clean space (lower space 278) are partitioned. And the operation by the medium exchange robot 42 is performed in the relatively clean space (upper space 279). Also, since the air from the first space filter unit 26 flows toward the workbench 110, this also prevents the air in the lower space 278 from returning to the upper space 279. And from these facts, it is possible to maintain the air cleanliness of the surrounding environment related to the medium exchange robot 42.

[0236] <<Structure for opening and closing the lower space 278>> As shown in FIG. 29, two external waste outlets 282 are provided in the lower part of the outer wall portion 22A in the medium exchange portion 22 so as to be openable and closable. The external waste outlet 282 is interposed between the lower space 278 in the medium exchange portion 22 and the external space of the medium exchange portion 22 (here, the external space of the cell culture device 10).

[0237] Normally, as shown on the left side in the figure, the external waste outlet 282 is closed by the external waste outlet door 284. However, when replacing the waste BOX 114, as shown on the right side in the figure, the external waste outlet door 284 is opened. And the waste BOX 114 is taken in and out through the external waste outlet 282. When the external waste outlet door 284 is opened, at least part of the air in the lower space 278 is ventilated. The external waste outlet door 284 shown on the left side in the figure can also be opened and closed in the same way.

[0238] The external waste outlet door 284 is supported by a hinge 286 to be openable and closable with respect to the medium exchange portion 22. Further, the closed state of the external waste outlet door 284 is maintained by a latch mechanism 287. The external waste outlet door 284 is opened and closed manually.

[0239] <Discharge of contaminated fluid> As described above, the old medium is aspirated from the wells of the well plate body 52a (Fig. 6 etc.) by the aspirator tool 134 (Fig. 10) attached to the medium exchange robot 42. The old medium aspirated from the tip bit 142 of the aspirator tool 134 is aggregated into the waste liquid pipe 292 provided in the medium exchange robot 42 as shown in Fig. 30, and is collected from the tip side to the base end side of the medium exchange robot 42 through the waste liquid pipe 292. In addition, the aspirator tool 134 may aspirate cleaning alcohol from the tip bit 142 for cleaning.

[0240] The waste liquid pipe 292 is a flexible type spiral tube (spiral pipe) and is made of synthetic resin. Most of the waste liquid pipe 292 is arranged outside the medium exchange robot 42 rather than inside the medium exchange robot 42. By using a spiral tube as the waste liquid pipe 292, the waste liquid pipe 292 can operate within a large range while being outside the medium exchange robot 42. That is, the waste liquid pipe 292 does not inhibit the operation of the medium exchange robot 42. Also, the waste liquid pipe 292 is not pulled with excessive tension by the operation of the medium exchange robot 42. The upper end side (base end side of the medium exchange robot 42) of the waste liquid pipe 292 can be supported by the ceiling part 24 in the medium exchange part 22. Furthermore, the replacement of the waste liquid pipe 292 is performed by an operation (manual work) from the outside of the medium exchange robot 42, by removing the end part from the medium exchange robot 42. Therefore, when replacing the waste liquid pipe 292, operations such as opening the working opening (not shown) of the medium exchange robot 42 and taking out most of the waste liquid pipe 292 from the inside to the outside of the medium exchange robot 42 are not required. And the man-hours required for the replacement work can be suppressed.

[0241] Inside the medium exchange robot 42, there are provided pipes for liquids, pipes for air, etc. The waste liquid pipe 292 is more likely to be contaminated compared to other pipes, and the frequency of replacement is high. And if the working opening (not shown) of the medium exchange robot 42 is opened to the outside and taken out for replacement work each time, a lot of man-hours are required. Therefore, by arranging the waste liquid pipe 292 outside the medium exchange robot 42, the replacement of the waste liquid pipe 292 can be easily performed.

[0242] <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, and 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 to 7 according to ISO) lower than the first standard as the air cleanliness standard, and 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), and A second operation unit (such as the transfer robot 40) installed in the second space and capable of performing a movement operation of a cell culture container (such as the well plate 52) in which the medium is stored, and Operation unit control means (such as the control unit 46) in which the movable range when the first operation unit performs the 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 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 that the cell culture device can be miniaturized is achieved. Furthermore, the effect that the operation units with different functions can be operated in a more optimized environment is achieved. (2) The operation unit control means Controlling the cell culture container to be moved from the second space to the first space by the second operation unit, and controlling the first operation unit to perform an operation related to medium exchange on the cell culture container, the cell culture apparatus according to (1) above. This has the effect of enabling miniaturization of the cell culture apparatus. (3) The cell culture container 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 container clean. (4) The second operation unit is provided with a gripping mechanism (such as an air gripper 68) capable of gripping the cell culture container, 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 medium exchange, the cell culture apparatus according to any one of (1) to (3) above. This has the effect of enabling easy automation of gripping the cell culture container and mounting the operation device. (5) In the second space, A supply / discharge unit (such as a stocker supply unit 16 and a product take-out unit 18, or a stocker supply / take-out unit integrating both) where the cell culture container is carried in and out, a cell culture unit (such as an incubator unit 12) where cells contained in the cell culture container are cultured, and an inspection unit (such as an image inspection unit 14) where the cell culture container is inspected are installed, The operation unit control means, Controlling the second operation unit to perform a movement operation of the cell culture container with respect to the supply / discharge unit, a movement operation of the cell culture container with respect to the cell culture unit, and a movement operation of the cell culture container with respect to the inspection unit, the cell culture apparatus according to any one of (1) to (4) above. This has the effect of enabling miniaturization of the cell culture apparatus. (6) In a Cartesian coordinate system (such as an XYZ coordinate system) centered on the second operation unit in a plan view, the central parts (such as the central parts (16 + 18)C, 12C, and 14C) in the first space, the supply / 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 any one of (1) 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 (6) 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 (7) 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 a claw part 78) whose interval can be changed, and by changing the interval of the claw part, it is possible to transfer the cell culture container and the container placement unit. The cell culture device according to (4) to (8) above. This has the effect of enabling easy automation of gripping and transporting 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 enabling simultaneous transportation of a large number of cell culture containers. (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 (10) 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, there is an effect that a small cell culture device can be operated more safely. (12) Air is supplied to the first space by a first space filter unit (such as the first space filter unit 26), Air is supplied to the second space by a second space filter unit (such as the second space filter unit 28), The first space filter unit independently takes in air outside the cell culture device with respect to the second space filter unit, The cell culture device according to any one of (1) to (11) above, wherein air to the first space is supplied from the first space filter unit to the first space. As a result, there is an effect that air outside the cell culture device can be independently taken in as air for the first space and air for the second space, and supplied to the first space and the second space without being diverted midway. (13) A shutter member (such as the automatic opening and closing shutters 152A and 152B) that partitions the first space and the second space, A shutter member control unit (such as the control unit 46) capable of controlling the opening and closing and the opening degree of the shutter member, The cell culture device according to any one of (1) to (12) above, wherein the area of an opening (each of the openings 252A and 252B, or the total of the openings 252A and 252B, etc.) between the first space and the second space can be adjusted by the combination of opening and closing and the degree of opening of the shutter member. As a result, there is an effect that the shutter member can be opened with the minimum necessary opening degree. (14) The cell culture device according to (13) above, wherein a plurality of the shutter members are provided and the plurality of shutter members are arranged side by side in the lateral direction. This makes it possible to minimize the area of the opening in the same plane. (15) The cell culture device according to (13) or (14) above, wherein the second operation unit is capable of moving the cell culture container between the second space and the first space through the opening. This makes it possible to minimize the area of the opening through which the second operation unit enters and exits. (16) A workbench portion (such as workbench 110) on which the cell culture container can be placed is provided in the first space. The cell culture device according to any one of (1) to (15) above, wherein a plurality of air passage holes (such as through holes 276) through which air supplied from the first space filter unit to the first space can pass are provided in the workbench portion. This makes it possible to partition the inside of the first space into a relatively clean space (upper space 279) and a relatively less clean space (lower space 278). (17) A holder portion (such as holder portion 188 for the multi-channel micropipette 182 and holder portion 193 for the electric pipettor 192) on which different experimental instruments (such as multi-channel micropipette 182 and electric pipettor 192) can be mounted is provided on the operation device (such as micropipette tool 136 and pipettor tool 138). The cell culture device according to (4) to (16) above. This makes it possible to utilize commercially available experimental instruments of different types. (18) A push button operation mechanism portion (such as driven rollers 184, 185, air cylinder, power transmission portion, etc.) capable of operating push buttons (such as piston button 186 and shoulder 187) of different experimental instruments is provided on the operation device (such as micropipette tool 136). The cell culture device according to (4) to (17) above. This makes it possible to utilize commercially available experimental instruments of different types equipped with push buttons. (19) An experimental device (such as a multi-aspirator 202, a multi-channel micropipette 182, etc.) can be mounted on the operating device (such as an aspirator tool 134, a micropipette tool 136, etc.), The experimental device can automatically mount a plurality of tubular devices (such as a tip bit 142, a needle 144, etc.), The cell culture device according to (4) to (18) above, wherein the operating device is provided with a fall prevention mechanism (such as a fall prevention mechanism including a fall prevention plate 207) for preventing the fall of the tubular device. As a result, it has the effect of preventing the fall of the tubular device. (20) An experimental device (such as an electric pipette 192, etc.) can be mounted on the operating device (such as a pipetter tool 138, etc.), The experimental device can automatically mount a tubular device (such as a pipette tip 146, etc.), When mounting the tubular device on the experimental device (such as when the movable mechanism part 220A mounts the pipette tip 146 on the electric pipette 192), a mounting force enhancement part (such as a pressurizing mechanism part 220B) that supports the experimental device from the opposite direction to the direction in which the tubular device is pressed against the experimental device and compensates for the force with which the tubular device is pressed against the experimental device. The cell culture device according to (4) to (19) above. As a result, it has the effect of being able to mount the tubular device on the experimental device with a small force. (21) An incubator (such as an incubator 32, etc.) is provided in the second space, The incubator is provided with a door (such as an automatic door 86, an inner door 232, etc.) that opens and closes in the horizontal direction, The cell culture device according to (1) to (20) above, which is provided with an air cylinder (such as air cylinders 234, 236, etc.) that generates a force for opening and closing the door. As a result, it has the effect of being able to utilize a commercially available incubator. (22) The cell culture device according to (1) to (21) above, wherein at least one of the first operation unit and the second operation unit performs a rocking motion in the vertical direction while holding a reservoir (such as reservoir 120) in the first space. This has the effect of being able to accurately grip one reservoir. (23) The first operation unit is provided with a waste liquid pipe (such as waste liquid pipe 292) through which waste liquid (such as old culture medium) passes. The cell culture device according to (1) to (22) above, wherein the waste liquid pipe is disposed outside the first operation unit. This has the effect of being able to remove the waste liquid pipe without performing the operation of taking out the waste liquid pipe from the first operation unit.

[0243] <Others> Note that the present invention is not limited to the various embodiments described above, and can be variously modified or combined with various embodiments without departing from the gist.

[0244] 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

[0245] The cell culture device according to the present invention can be applied to various cell cultures for which medium exchange is performed. Cross-reference to related applications

[0246] This application claims priority based on Japanese Patent Application No. 2023-214803 filed with the Japan Patent Office on December 20, 2023, and all of its disclosures are hereby incorporated by reference in their entirety.

Explanation of Reference Numerals

[0247] 10: Cell culture device 10A: Wall portion 10B: Window portion 12: Incubator unit 14: Image inspection unit 16: Stocking supply unit 18: Product extraction section 20: Conveyor robot section 22: Culture medium replacement section 26: Filter unit for the first space 28: Filter unit for the second space 32: Incubator 34: Image inspection device 36: Opening / closing shutter section 40: Conveyor robot 42: Culture medium replacement robot 46: Control section 52: Well plate 52a: Well plate body 52b: Lid 54: Stocker 56: Well 68: Air gripper 70: Air cylinder 72: Movable body 76: Gripping section 78: Claw section 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 146: Pipette tip 148: Receiving plate 152A, 152B: Automatic opening / closing shutter 154: Sterilization lamp 159: Human presence sensor 182: Micropipette 184, 185: Driven roller 186: Piston button 187: Shoulder 188, 193: Holder part 189: Bolt 192: Electric pipettor 194: Frame part 195: Button operation part 196: Roller part 198: Elongated hole 200: Bolt 202: Multi aspirator 204: Connector for aspirator 206: Pit box 207: Fall prevention plate 208, 210: Taper part 211: Claw part 212: Flange part 214: Tip bit detection sensor 216: Light projecting part 218: Light receiving part 219: Fall prevention plate 220A: Movable mechanism part 220B: Pressurizing mechanism part 221: Connector for chip 232: Inner door 234, 236: Air cylinder 235, 237: Piston rod 238, 240: Holding member 242: Connecting plate 243: Door packing 244: L-shaped metal fitting 245: Frame 246, 248: Fixed part 247: Elongated hole 252A, 252B: Opening 259: Gripping pin 262: Shutter for waste disposal 264: Internal waste outlet 266: Opening 276: Through hole 278: Lower space 279: Upper space 282, 284: External waste outlet 286: Hinge 287: Latch mechanism 292: Waste liquid pipe

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: Air is supplied to the first space by a first space filter unit, Air is supplied to the second space by a second space filter unit, the first spatial filter unit takes in air outside the cell culture device independently of the second spatial filter unit; Air to the first space is supplied to the first space from the first space filter unit, The second operation unit is provided with a gripping mechanism capable of gripping the cell culture vessel, The first operating unit is provided with a mounting mechanism common to a plurality of types of operating devices corresponding to the contents of the operation related to the culture medium replacement, The cell culture device, wherein the operation device is provided with a holder portion to which different experimental equipment can be attached.

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 cell culture device according to claim 2 , wherein the operation device is provided with a push button drive mechanism capable of operating push buttons of different experimental equipment.

5. The operating device can be fitted with experimental equipment; the laboratory instrument is capable of automatically mounting a plurality of tubular instruments; The cell culture device according to claim 2 , wherein the operation device is provided with a fall prevention mechanism for preventing the tubular device from falling.

6. The operating device can be fitted with experimental equipment; the laboratory instrument is capable of automatically mounting a tubular instrument; The cell culture device according to claim 2, further comprising an attachment force enhancing section that supports the laboratory equipment from a direction opposite to a direction in which the tubular equipment is pressed against the laboratory equipment when the tubular equipment is attached to the laboratory equipment, thereby compensating for the force with which the tubular equipment is pressed against the laboratory equipment.

7. An incubator is provided in the second space; The incubator has a door that opens and closes horizontally, The cell culture device according to any one of claims 1 to 4, further comprising an air cylinder that generates a force for opening and closing the door.

8. The gripping mechanism can grip a reservoir instead of the cell culture vessel, The cell culture device according to any one of claims 1 to 6, wherein the second operation unit performs a vertical rocking motion while gripping the reservoir in the first space.

9. The first operation unit is provided with a waste liquid pipe through which waste liquid passes, The cell culture device according to any one of claims 1 to 6, wherein the waste liquid pipe is disposed outside the first operation unit.

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