Cell culture apparatus

Abstract

Provided is a cell culture apparatus that enables operation units having different functions to operate in a more optimized environment. The cell culture apparatus is provided with: a first space (such as the internal space of a culture medium exchange section 22) that satisfies first criteria according to air cleanliness standards (such as ISO class 5); a second space (such as the internal space of a section other than the culture medium exchange section 22) that satisfies second criteria lower than the first criteria according to the air cleanliness standards (such as ISO class 6-7); a culture medium exchange robot (42) that is arranged in the first space and can perform an operation relating to medium exchange; a transfer robot (40) that is arranged in the second space and can perform an operation of moving a well plate (52) containing a culture medium; and a control unit that sets the movable range of the culture medium exchange robot (42) to the first space when the culture medium exchange robot (42) performs the operation relating to medium exchange, and sets the movable range of the transfer robot (40) to the second space and the first space when the transfer robot (40) moves the well plate (52).

Description

Cell culture device

[0001] The present invention relates to, for example, a cell culture device equipped with a plurality of manipulation robots.

[0002] Patent Document 1 (claim 1, etc.) listed below discloses an invention relating to an automatic culture manipulation device in which a first robot and a second robot are arranged in a work chamber so that their movement ranges partially overlap. In Patent Document 1, a liquid supply means and a temporary storage unit are provided in the overlapping movement ranges of the first robot and the second robot. The liquid supply means supplies liquids such as culture media and chemical solutions to containers held by the robots, and the first robot and the second robot transfer the containers in the temporary storage unit.

[0003] Patent No. 6358429

[0004] Incidentally, Patent Document 1 describes circulating purified air to maintain a positive pressure in the work chamber, but does not describe how to further optimize 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 device that allows operation units with different functions to operate under a more optimized environment.

[0006] A cell culture device according to one embodiment of the present invention comprises: a first space that satisfies a first standard as a standard for air cleanliness; a second space that satisfies a second standard as a standard for the air cleanliness that is lower than the first standard; a first operation unit that is installed in the first space and is capable of performing operations related to culture medium replacement; a second operation unit that is installed in the second space and is capable of performing operations to move a cell culture vessel in which a culture medium is stored; and an operation unit control means that sets the movable range of the first operation unit when performing the operations related to culture medium replacement to within the first space, and sets the movable range of the second operation unit when moving the cell culture vessel to within the second space and the first space.

[0007] According to the present invention, it is possible to provide a cell culture device that allows operation units with different functions to operate under a more optimized environment.

[0008] 1 is a perspective view showing a cell culture device of an embodiment; FIG. 2 is a perspective view showing a cell culture device with a wall portion removed; FIG. 3 is an explanatory view showing the layout of each part; (a) is an explanatory view showing another explanatory aspect of the layout, and (b) is an explanatory view showing yet another explanatory aspect of the layout; FIG. 4 is an explanatory view showing the basic configuration of each part; FIG. 5 is a perspective view showing a well plate and a stocker; (a) is a perspective view showing an air gripper, and (b) is an explanatory view showing the operation of the gripping part gripping the stocker; FIG. 6 is an explanatory view showing the orientation of the stocker; (a) is an explanatory view showing an image inspection part in plan view, and (b) is an explanatory view showing an image inspection part in side view; FIG. 7 is an explanatory view showing a medium exchange part; (b) is an explanatory view showing the relationship between the medium exchange part and a transport robot; (c) is an explanatory view showing a modified layout of each part; (d) is an explanatory view showing a modified arrangement of the medium exchange robot; (e) is a perspective view showing a micropipette tool to which a multichannel micropipette is attached; (f) is a perspective view showing a pipetter tool to which an electric pipetter is attached; 1A is an explanatory diagram showing the state before the tip bit is attached to the multi-aspirator, and FIG. 1B is an explanatory diagram showing the state after the tip bit is attached to the multi-aspirator. (a) is an explanatory diagram showing the state in which the fall prevention plate is advanced, and (b) is an explanatory diagram showing the state in which the multi-aspirator with the tip bit attached is rising. (b) is an explanatory diagram showing the state in which the fall prevention plate is advanced. (a) is an explanatory diagram showing from the side the state in which the presence or absence of the tip bit 142 has fallen, and (b) is an explanatory diagram showing from the direction of advancement the state in which the presence or absence of the tip bit 142 has fallen is detected. (a) is an explanatory diagram showing from diagonally above the state in which the force for attaching a pipette tip to a pipetter tool is assisted, and (b) is an explanatory diagram showing from the side the state in which the force for attaching a pipette tip to a pipetter tool is assisted. (a) is an explanatory diagram showing from diagonally above the state in which the automatic door of the incubator is closed, and (b) is an explanatory diagram showing from diagonally above the state in which the automatic door of the incubator is open. 1A is an explanatory view showing a part of the upper side of the automatic door of the incubator from an obliquely upper side when the inner door of the incubator is open, and FIG. 1B is an explanatory view showing a part of the lower side of the automatic door of the incubator from an obliquely lower side when the inner door of the incubator is open.1A is an explanatory diagram showing, from an obliquely above perspective, a state in which two automatic opening / closing shutters of the culture medium exchanging unit facing the second space are both closed, and FIG. 1B is an explanatory diagram showing, from an obliquely above perspective, a state in which one automatic opening / closing shutter of the culture medium exchanging unit is fully open. 1A is an explanatory diagram showing, from an obliquely above perspective, a state in which the other automatic opening / closing shutter of the culture medium exchanging unit is fully open, and FIG. 1B is an explanatory diagram showing, from an obliquely above perspective, a state in which one automatic opening / closing shutter of the culture medium exchanging unit is half-open. 1B is an explanatory diagram showing a rocking motion for gripping one reservoir. 1A is an explanatory diagram showing, from a side perspective, a state in which the disposal shutter is closed, and FIG. 1B is an explanatory diagram showing, from a side perspective, a state in which the disposal shutter is open. 1C is an explanatory diagram showing a downflow of air in the first space. 1D is an explanatory diagram showing a state in which one external disposal port is open on the outer wall of the culture medium exchanging unit. 1E is an explanatory diagram showing a waste liquid pipe of the culture medium exchanging robot.

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

[0010] In this embodiment, the stocker supply unit 16 and the product removal unit 18 are integrated. Therefore, for example, both units can be collectively referred to as the "stocker supply removal unit" or the "stocker supply discharge unit."

[0011] Approximately two-thirds of each section is enclosed by a wall 10A. In this embodiment, the wall 10A is formed in a T-shape when the cell culture device 10 is viewed from the ceiling side in plan view, and airtightly encloses the internal space. The wall 10A has a plurality of transparent windows 10B formed therein, allowing an operator A (shown by a two-dot chain line) or the like to visually observe each section. The arrangement of the wall 10A is not limited to a T-shape, and can be variously modified, such as a rectangular or L-shape, depending on the shape of the installation space and other circumstances.

[0012] Fig. 2 shows the cell culture device 10 of Fig. 1 with the wall portion 10A removed. 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 culture medium exchange robot 42. The culture medium exchange robot 42 is provided in a culture medium exchange device 43. Details of these devices and each part will be described later.

[0013] Fig. 3 shows the layout of each section. More specifically, Fig. 3 shows the cell culture device 10 in a plan view from above with the wall section 10A removed. Of the sections, the transport robot section 20 is located in the center, and the other sections, the incubator section 12, the image inspection section 14, the stocker supply section 16, the product removal section 18, and the culture medium replacement section 22, are arranged in this order to surround the transport robot section 20 in a clockwise direction in Fig. 3. The layout of each section can be described in multiple other ways, and these other explanations will be described later.

[0014] <First Space and Second Space> The interior of the cell culture device 10 is partitioned into an internal space of the culture medium exchanging unit 22 and an internal space of the portion other than the culture medium exchanging unit 22 (the incubator unit 12, the image inspection unit 14, the stocker supply unit 16, the product unloading unit 18, and the transport robot unit 20). The internal spaces of the portions other than the culture medium exchanging unit 22 are spatially connected. The internal space of the culture medium exchanging unit 22 is a first space, and the internal space of the portion other than the culture medium exchanging unit 22 is a second space. Details will be described later, but the inside of the wall 10A (FIG. 1) is partitioned into a first space (the internal space of the culture medium exchanging unit 22) and a second space (the internal space other than the culture medium exchanging unit 22) by a wall portion 22B of the culture medium exchanging unit 22, as shown in FIG. 11 .

[0015] When the cell culture device 10 is in use, the first space and the second space can have different air cleanliness levels. The first space satisfies a first standard as a standard for air cleanliness, and the second space satisfies a second standard that is lower than the first standard.

[0016] In this embodiment, the first standard for the first space is, for example, ISO (International Organization for Standardization) Class 5 (US Federal Standard Class 100) or lower. In contrast, the second standard for the second space is, for example, ISO Class 6 to 7 (US Federal Standard Class 1000 to 10,000). Note that the relationship between the air cleanliness of the first space and the second space is not limited to the above example, as long as the air cleanliness of the culture medium exchange section can be maintained at a level necessary for culture medium exchange. For example, it is also possible to lower the air cleanliness of the second space by three or more ranks compared to the first space.

[0017] 1 , a first space filter unit 26 is provided on the outside of the ceiling portion 24 of the culture medium exchange section 22. This first space filter unit 26 supplies purified air (cleaned air) into the first space, maintaining the air cleanliness of the first space. A second space filter unit 28 is provided on the outside of the ceiling portion 23 of the transfer robot section 20. This second space filter unit 28 supplies purified air into the second space, maintaining the air cleanliness of the second space.

[0018] The second spatial filter unit 28 may be disposed not only on the ceiling 23 of the transport robot section 20 but also on the ceiling of another section. The second spatial filter unit 28 may be disposed in multiple locations. For example, FIG. 9B schematically shows the image inspection section 14 with the second spatial filter unit 28 disposed on the ceiling 25 of the image inspection section 14.

[0019] A stocker 54, which will be described later, is supplied from the stocker supply unit 16 to the first space in which the components other than the culture medium exchange unit 22 are arranged. A well plate 52 (which will be described later) containing cultured cells is removed from the product removal unit 18 while placed on the stocker 54. The stocker 54 can be supplied and removed by a transport robot (not shown) installed outside the cell culture device 10. In this case, work can be performed with the window 10B (which may be a manual door or an automatic door) facing the stocker supply unit 16 or the product removal unit 18 open.

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

[0021] The transport robot section 20 in which the transport robot 40 is installed is provided with an opening / closing shutter section 36 ( FIG. 5 ) that separates the second space from the space outside the cell culture device 10 (external space). Depending on the situation, the opening / closing shutter section 36 of the transport robot section 20 may be opened to allow the worker A to enter or exit the second space. The worker A may enter or exit the second space only when performing maintenance on the incubator 32 or the transport robot 40.

[0022] <First Operation Unit and Second Operation Unit> The cell culture device 10 includes a first operation unit and a second operation unit. The first operation unit is installed in the first space and is capable of performing operations related to culture medium replacement. The culture medium replacement robot 42 corresponds to the first operation unit. The second operation unit is installed in the second space and is capable of performing operations to move cell culture vessels in which culture medium is stored. The transport robot 40 corresponds to the second operation unit.

[0023] The culture medium exchange robot 42 and the transport robot 40 are vertically articulated robots with six degrees of freedom (three orthogonal axes and rotation around each axis). Note that the culture medium exchange robot 42 and / or the transport robot 40 may be articulated robots with fewer than six axes or more than six axes. The drive system of the culture medium exchange robot 42 and the transport robot 40 is an AC (direct current) servo system. The culture medium exchange robot 42 and the transport robot 40 are installed at fixed positions in the culture medium exchange unit 22 and the transport robot unit 20, respectively, and their tips are moved (including rotational movement) within their respective movable ranges.

[0024] The culture medium exchange robot 42 (first operation unit) and the transport robot 40 (second operation unit) are controlled by a control unit 46 ( FIG. 5 ). The control unit 46 collectively represents the control units of the computer-controlled parts of each unit (incubator unit 12, image inspection unit 14, stocker supply unit 16, product removal unit 18, transport robot unit 20, and culture medium exchange unit 22). The control unit 46 may include a control unit that comprehensively controls multiple parts of each unit.

[0025] The control unit 46 has a function of controlling the medium exchange robot 42 (first operation unit) and the transport robot 40 (second operation unit) so that the range of movement of the medium exchange robot 42 when performing operations related to medium exchange is within the first space, and the range of movement of the transport robot 40 when moving a cell culture vessel (well plate 52, described later) is within the second space and the first space. The control unit of the medium exchange robot 42 and the control unit of the transport robot 40 can be collectively referred to as an operation unit control unit (operation unit control means), for example.

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

[0027] Furthermore, as will be described in detail below, various operating devices (operating apparatuses) such as an aspirator tool 134, a micropipette tool 136, and a pipetter tool 138 shown in Fig. 10, and an air gripper 68 shown in Fig. 7(a) are attached to the tip of the culture medium exchange robot 42 and the transport robot 40. The culture medium exchange robot 42 and the transport robot 40 perform predetermined operations using the various operating devices within their respective ranges of movement.

[0028] <Other explanation 1 regarding the layout of each section (arrangement in multiple quadrants)> Regarding the layout of each section (incubator section 12, image inspection section 14, stocker supply section 16, product removal section 18, transport robot section 20, and culture medium replacement section 22), in addition to the explanation that they are arranged to surround the transport robot section 20 as mentioned above, the following explanation is also possible.

[0029] 4A, for example, X and Y coordinates are set on a plane with the position of the rotation center of the transfer robot 40 as the origin, and the space in which positions are defined by these X and Y coordinates is divided into a first quadrant Q1 to a fourth quadrant Q4. Then, the centers 12C, 14C, (16+18)C, and 22C of each part are placed in at least three quadrants (here, the first quadrant Q1, the boundary between the second quadrant Q2 and the third quadrant, and the fourth quadrant Q4) out of the first quadrant Q1 to the fourth quadrant Q4.

[0030] Here, (16+18)C in Fig. 4(a) indicates the center between both the stocker supply section 16 and the product removal section 18. Also, in Fig. 4(a), the center section (20C) of the transport robot section 20 is omitted from the illustration.

[0031] In the example of Figure 4(a), the central portion 12C of the incubator section 12 is located in the first quadrant Q1, and the central portion 14C of the image inspection section 14 is located in the second quadrant Q2. Furthermore, the central portion (16 + 18)C, which is the combination of the stocker supply section 16 and the product removal section 18, is located between the second quadrant Q2 and the third quadrant Q3 (on the Y axis). Furthermore, the central portion 22C of the culture medium exchange section 22 is located in the fourth quadrant Q4.

[0032] Although not shown in the figure, the center (16+18)C, which is the combination of the stocker supply section 16 and the product removal section 18, can also be defined as being located across the second quadrant Q2 and the third quadrant Q3. It is also possible to define the center (16C) of the stocker supply section 16 as being located in the second quadrant Q2, and the center (18C) of the product removal section 18 as being located in the third quadrant. Furthermore, the center 20C of the transport robot section 20 is located at the origin of the XY coordinate system. Therefore, the center 20C of the transport robot section 20 can also be defined as being located across the first quadrant Q1 to the fourth quadrant Q4.

[0033] Such a quadrant-based layout can be described, for example, as follows: In the cell culture device 10, in a Cartesian coordinate system centered on the second operation unit (transport robot 40, etc.) in a plan view, the respective central portions (e.g., central portion 22C, (16+18)C, 12C, 14C, etc.) of the first space (internal space related to the culture medium exchange unit 22), the supply / discharge unit (e.g., stocker supply unit 16), the cell culture unit (e.g., incubator unit 12), and the inspection unit (e.g., image inspection unit 14) are arranged in at least three quadrants (e.g., first quadrant Q1, second quadrant Q2 (or third quadrant), and 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 of the layout of each part. In the example of Figure 4(b), an XY coordinate system is set on a plane with the position of the center of rotation of the transfer robot 40 as the origin, and the space in which positions are defined by these XY coordinates is divided into a first surface R1 to a fourth surface R4 according to their positions and orientations. Each part is arranged on three surfaces (here, the first surface R1, the second surface R2, and the fourth surface R4) of the first surface R1 to the fourth surface R4.

[0035] In the example of FIG. 4(b), the incubator section 12 and the image inspection section 14 are arranged on the first surface R1, and the stocker supply section 16 and the product removal section 18 are arranged on the second surface R2. Furthermore, the culture medium exchange section 22 is arranged on the third surface R3. The fourth surface, located between the first surface R1 and the third surface R3 and facing the second surface R2, is an open surface on which the various components are not arranged. The open surface (fourth surface R4) is the surface on which the open / close shutter section 36 (FIG. 5) of the transport robot section 20 is arranged. Note that, although the various components are arranged on three surfaces (three faces) in the example of FIG. 4(b), they may also be arranged collectively on two surfaces (two faces).

[0036] 5 shows the basic configuration of each section (incubator section 12, image inspection section 14, stocker supply section 16, product removal section 18, transport robot section 20, and culture medium replacement section 22). The basic configuration of each section will be described below, but prior to describing each section, the well plate 52 that moves between each section 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 a well plate 52 and a stocker 54. All well plates 52 used in this embodiment have a common shape and structure. Each well plate 52 has a large number of recessed wells 56 formed therein for containing culture medium or the like. In this embodiment, the well plate 52 has 96 (= 8 x 12) wells 56 formed in a matrix.

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

[0039] The lid 52b is simply placed on the well plate body 52a and is not fixed to the well plate body 52a. Therefore, by lifting the lid 52b, for example, in the positive direction (upward) in the Z direction in FIG. 6, the lid 52b is separated from the well plate body 52a.

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

[0041] The stocker 54 is made of a material such as stainless steel. Holes 58, rectangular cutouts 60, protrusions 62, and V-shaped cutouts 63 are formed on the edges of the stocker 54. The rectangular cutouts 60 are located in the center of each edge extending in the longitudinal direction of the stocker 54 (each edge facing in the short direction (width direction)).

[0042] The protrusion 62 is located in the center in the longitudinal direction of the rectangular cutout 60. The V-shaped cutout 63 is arranged to sandwich the rectangular cutout 60 in the longitudinal direction. The V-shaped cutout 63 has a shape that narrows as it goes to the back (the back in the short side direction (width direction) of the stocker 54).

[0043] Furthermore, a large number (16 in this example) of shroud pins 64 are attached to the periphery of the stocker 54. These shroud pins 64 protrude almost perpendicularly from the surface on which the well plates 52 are placed. Of these, 12 (=6 × 2) shroud pins 64 are arranged facing the well plates 52 arranged in the longitudinal direction of the stocker 54, near the four corners, with a predetermined interval (approximately several millimeters) between them.

[0044] Most of the side surfaces (side surfaces forming the longitudinal direction) of the three sets of well plates 52 are exposed and not hidden by the shroud pins 64. By arranging the shroud pins 64 at intervals along the longitudinal direction of the stocker 54 (and the well plates 52) in this way, a space is secured for the gripper 76 ( FIG. 7 ) of the transport robot 40 to enter, as will be described later. Furthermore, four (= 2 × 2) of the twelve shroud pins 64 are arranged to face each other at two corners of the two sets of well plates 52 at both ends, with a predetermined interval (approximately several millimeters) between them.

[0045] The tips (upper ends in FIG. 6 ) of the shroud pins 64 are sharp. When the well plate 52 is placed on the stocker 54, the well plate 52 is handled by an air gripper 68 (described below) having a gripping portion 76 ( FIG. 7 ) and placed from above on the area surrounded by the shroud pins 64. Because the tips (upper ends in FIG. 6 ) of the shroud pins 64 are sharp, the tips of the shroud pins 64 are unlikely to interfere with the well plate 52 when the well plate 52 is placed on the stocker 54. Note that providing the shroud pins 64 is not essential, and the shroud pins 64 can be omitted.

[0046] <Transport Robot 40> The stocker 54 is transported by the transport robot 40. As described above, the transport robot 40 is a vertical articulated robot with a feed accuracy of, for example, approximately ±0.02 mm. The main function of the transport robot 40 is to grasp (hold) and transport the stocker 54 and well plate 52. The transport robot 40 can grasp and transport the stocker 54 with the well plate 52 placed on it, or can grasp and transport only the stocker 54 without the well plate 52 placed on it.

[0047] The transfer robot 40 can also grasp and transport only the well plate 52. Furthermore, the transfer robot 40 can also grasp and transport only the lid 52b of the well plate 52 in order to separate the lid 52b from the well plate body 52a or to place the lid on the well plate body 52a. The transfer robot 40 grasps and transports the stocker 54, well plate 52, and lid 52b via the following mechanism.

[0048] An arm plate 66 ( FIG. 10 ) that has been lightened by hollowing out 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 this arm plate 66. Here, the arm plate 66 and air gripper 68 are used in various positions and orientations depending on the process, and FIG. 10 shows the arm plate 66 and the like in multiple processes at the same time. In FIG. 10 , to indicate that the arm plate 66 is drawn imaginarily, a leader line is added to the arm plate 66 using a two-dot chain line (imaginary line).

[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, and although not shown, each pipe joint 74 is connected to, for example, a flexible plastic tube. High-pressure air supplied from an air source (such as an air compressor) via a plastic tube (not shown) is introduced into and discharged from the air cylinder 70. The two movable bodies 72 then widen or narrow the gap between them as the high-pressure air is introduced or discharged.

[0050] A T-shaped gripping portion 76 is fixed to the movable body 72. A metal, strip-shaped claw (jaw) portion 78 is attached to the tip of the gripping portion 76, and two resin blocks 80 and two locking pins 82 are provided on each of the claw portions 78. The resin blocks 80 are made of synthetic resin and partially cover the edges of the two gripping portions 76 that face each other.

[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 almost perpendicularly from the plate surface of the grip portion 76. The locking pin 82 has a relatively small diameter portion on the base end side (the side closer to the claw portion 78) and a relatively large diameter portion on the tip end side (the side farther from the claw portion 78).

[0052] 7(b) shows the state in which the gripper 76 is engaged with the stocker 54. When gripping the stocker 54, the air cylinder 70 approaches the center of the stocker 54 from above, and with the gripper 76 spanning the well plate 52 and the stocker 54 in the width direction, the gripper 76 is brought into opposition to the edge of the well plate 52. Only one of the grippers 76 is shown in FIG.

[0053] 7(b), when the two gripping portions 76 (only one is shown) are brought closer to each other, the claw portion 78 enters under the protrusion 62 formed on the edge of the stocker 54. At this time, the two resin blocks 80 of the claw portion 78 reach a position where the protrusion 62 is placed between them, and they face the side surface of the bottom well plate 52.

[0054] Furthermore, the locking pin 82 approaches the V-shaped notch 63 formed in the edge of the stocker 54. Then, the small-diameter base end portion of the locking pin 82 enters the V-shaped notch 63, and the large-diameter tip end portion of the locking pin 82 partially overlaps the edge of the V-shaped notch 63.

[0055] As the gripping portion 76 closes in this manner, the four locking pins 82 are guided by the obliquely formed edges of the corresponding V-shaped notches 63. The four locking pins 82 enter the depths of the V-shaped notches 63 and lock onto the stocker 54. As a result, the stocker 54 is positioned relative to the claws 78 and is gripped by the gripping portion 76.

[0056] When the tip of the transport robot 40 moves upward with the gripper 76 gripping the stocker 54, the air cylinder 70 is displaced integrally. The claws 78 of the gripper 76 come into contact with the protrusion 62 and other parts of the stocker 54 from below and rise, lifting the stocker 54.

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

[0058] The presence or absence, number of tiers, and arrangement of well plates 52 placed on the stocker 54 vary depending on the process. The air gripper 68, which has an air cylinder 70, a gripping portion 76, etc., supports and transports the stocker 54 even when the total weight and weight balance of the object to be gripped vary. The stockers 54 and well plates 52 are standardized, adopting a unified size, structure, etc. Therefore, it is possible to transport a large number of stockers 54 and well plates 52 using a single (one type) air gripper 68.

[0059] When the transfer robot 40 transfers the well plate 52 with the lid 52b attached by itself, the well plate body 52a is grasped with the lid 52b still in place, and the well plate body 52a is grasped together with the lid 52b. When the transfer robot 40 transfers the lid 52b by itself, only the lid 52b is grasped, lifted, and removed from the well plate body 52a.

[0060] When the air gripper 68 grips the well plate 52 or the lid 52b, the lifting position (position in the vertical direction (Z direction)) of the air gripper 68 and the spacing between the gripping portions 76 (and the claws 78) are different from those when gripping the stocker 54. Furthermore, the lifting position of the air gripper 68 and the spacing between the gripping portions 76 are different when gripping the well plate 52 and when 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 is higher than when gripping the stocker 54, and the spacing between the gripping parts 76 is narrower than when gripping the stocker 54. Furthermore, when the air gripper 68 grips the lid 52b, the lifting position of the air gripper 68 is higher and the spacing between the gripping parts 76 is wider than when gripping the well plate 52 (well plate main body 52a).

[0062] When the air gripper 68 grips the well plate 52 or the lid 52b, the two claws 78 of the gripping portion 76 gradually approach each other, and the four (2 x 2) resin blocks 80 come into contact with the side surfaces of the well plate body 52a or the lid body 52b. The well plate body 52a or the lid body 52b is gripped by the frictional force generated by pressure applied from the side surfaces, without the claws 78 directly contacting the well plate body 52a or the lid body 52b. This prevents the transparent resin well plate body 52a or the lid body 52b from being damaged by the metal claws 78.

[0063] The transfer robot 40 can also rotate around orthogonal axes (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 by an angle such as 90 degrees while maintaining the well plate 52 and the stocker 54 horizontally.

[0064] In this embodiment, a fork 84 (two long claws in FIG. 10 ) is formed at one end of the arm plate 66 ( FIG. 10 ), to which the air gripper 68 is attached. The fork 84 supports both edges of the reservoirs 120 used in the culture medium exchange unit 22, as will be described later, and can hold each reservoir 120 individually. In other words, the transport robot 40 can transport four types of objects: the stocker 54, the well plate 52, the lid 52 b, and the reservoir 120.

[0065] <Transportation Path by Transfer Robot 40> The transfer robot 40 transports the stocker 54 carrying the well plate 52, the well plate 52, and the lid 52b, depending on 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 culture medium exchange unit 22, and between the incubator unit 12 and the product removal unit 18. In Figure 5, as an example, the path from the stocker supply unit 16 to the incubator unit 12 and the path from the incubator unit 12 to the product removal unit 18 are schematically shown by arrows C1 and C2.

[0066] As indicated by the thick arrows D and E in Figure 8, the orientation of the stockers 54 installed in the four sections of the incubator section 12, the image inspection section 14, the stocker supply section 16 (stocker supply / unload section), and the culture medium exchange section 22 is set so that the longitudinal direction of the stocker 54 is parallel to the X-axis or Y-axis. By arranging the stocker 54 in this orientation, the transfer robot 40 can position the stocker 54 by pushing it in the longitudinal direction. This prevents the stocker 54 from interfering with surrounding areas, making it easy to position multiple stockers 54.

[0067] Furthermore, when the transport robot 40 is not gripping a stocker 54, there is no need to significantly raise the tip of the transport robot 40 to avoid interference between the air gripper 68 and the well plate 52, etc. Therefore, the movement path of the transport robot 40 can be simplified.

[0068] <Incubator Section 12> The stocker 54 carrying the well plate 52 is moved into 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 controlling the temperature inside the incubator 32, and the incubator 32 is provided with an automatic door 86. The automatic door 86 is a one-sided hinged door that pivots (rotates) horizontally. When the stocker 54 is moved into and out of the incubator section 12, the automatic door 86 is opened and closed under the control of, for example, the control unit 46 (FIG. 5). Here, FIG. 2 shows the automatic door 86 in an open state. In FIG. 5, the open state of the automatic door 86 is indicated by a dashed line. Furthermore, the door 37 shown in the upper left portion of FIG. 5 is also used for the entrance and exit of worker A.

[0069] 9(a) and 9(b) show an overview of the image inspection unit 14. The image inspection unit 14 is provided with an image inspection device 34, and a camera 90 is installed in the image inspection device 34. The camera 90 is placed at a certain height and is capable of taking pictures facing downward. Although not shown, the image inspection device 34 is also provided with a camera that takes pictures from below facing upward.

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

[0071] The X-axis and Y-axis of the image inspection device 34 shown in Figures 9(a) and (b) are different from the X-axis and Y-axis of the cell culture device 10 shown in Figures 1 to 3, Figure 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. The arrangement of the linear guide device 92 also differs between the examples shown in Figures 9(a) and (b) and the examples shown in Figures 1 to 3, Figure 8, etc. For example, the orientation of the image inspection device 34 in the examples shown in Figures 9(a) and (b) can be rotated to match the orientation shown in Figures 1 to 3, Figure 8, etc.

[0072] The camera 90 constitutes an image inspection system. Although not shown, the image inspection system is constructed by combining the camera 90 with industrial computer equipment (industrial PC). The image inspection system has a function for determining whether the cells pass or fail. Inspection of the cell culture state is performed using images captured by the camera 90, and the inspection data obtained by the inspection is stored in external storage such as an HDD (hard disk drive) or an SSD (solid state drive). The inspection data is also stored in association with information related to the cell culture history.

[0073] The transport robot 40 transports the stocker 54 removed from the incubator unit 12 to the image inspection unit 14. 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). The well plate 52 is transported from the stocker 54 to the inspection area 102 below the camera 90 as shown by arrow F in FIG. 9(b) and installed there.

[0074] As described above, the well plate body 52a and the lid 52b constituting the well plate 52 are transparent, and the inspection in the inspection area 102 is performed through the lid 52b while the lid 52b remains on the well plate body 52a. An identification information display unit (not shown) is provided on the well plate 52 (for example, the well plate body 52a), and an image of the identification information display unit is acquired in the inspection area 102.

[0075] The identification information display section displays information (identification information) that allows individual identification of the well plate 52. The identification information can be displayed by attaching a sticker with a barcode or a matrix-type two-dimensional code, or by imprinting an identification symbol. The identification information is read while illuminating the identification information display section with an illumination device (not shown).

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

[0077] Subsequent well plates 52 are similarly inspected, and the inspected well plates 52 are stacked in order on the stocker 54 in the temporary storage area 104. When the number of stacked well plates 52 reaches a predetermined number (here, five), the subsequent (sixth and subsequent) inspected well plates 52 are stacked in adjacent positions in the longitudinal direction on the stocker 54, up to a total of five.

[0078] Five well plates 52 are stacked in each of three locations, and when the number of well plates 52 in the temporary storage area 104 reaches 15, the stocker 54 carrying these well plates 52 is grasped and transported by the transport robot 40 and stored in the incubator section 12.

[0079] For example, cell inspection in the image inspection unit 14 is carried out by simultaneously photographing all (here, 96) wells 56 of the well plate body 52a from above, image-recognizing the cells in each well 56, and performing predetermined image processing. Cells whose size or shape does not meet the predetermined inspection criteria are recorded as NG, and the inspection results are notified, for example, via a display device 106 (FIG. 1) provided outside the image inspection unit 14. Note that the content of the inspection, the inspection criteria, the method of notifying the inspection results, etc. are not limited to those described here, and various changes and additions can be made.

[0080] It is possible to use AI (artificial intelligence) for the inspection. For example, the control unit 46 can be trained in advance on the relationship between the conditions related to the size and shape of the imaged cells and the quality (OK / NG) of the cells, and the control unit 46 can judge and report as NG cells if the correlation with the learned result of OK is not within a predetermined amount. It is also possible to train the control unit 46 in advance on the growth record of cells, and the control unit 46 can predict the degree of future growth based on the growth record of the same sample up to that point. The content of the inspection using AI can also be modified in various ways.

[0081] Although not shown, a sterilization lamp (or germicidal lamp) using, for example, an ultraviolet (UV) light source (such as an ultraviolet 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 a sterilization means (or disinfection means) is effective in preventing the proliferation of bacteria when, for example, the culture medium drips (or drips) or when a person comes into contact with the culture medium, and in keeping the internal environment clean.

[0082] Sterilization (or disinfection) by light irradiation can be performed locally in areas where dripping or the like is likely to occur. This allows the installation location of the ultraviolet light source to be selected and appropriately positioned. For example, the relationship between the position of the synthetic resin parts that are easily deteriorated by ultraviolet light and the position of the ultraviolet light source can be appropriately adjusted so that the ultraviolet light does not hit the synthetic resin parts. Furthermore, the ultraviolet light source can also be positioned 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] Furthermore, regarding the timing of sterilization (or disinfection) by light irradiation, it is possible, for example, to irradiate light during a time period when various operations are not being performed by the transport robot 40 (so-called idle time, when in standby state, etc.) under the control of the control unit 46.

[0084] 5 shows an overview of the culture medium exchanging unit 22. In the culture medium exchanging unit 22, the aforementioned culture medium exchanging robot 42 is installed on a workbench 110, and surrounding the periphery of the culture medium exchanging robot 42, an aspirator tool holder 112, waste boxes 114 and 115, a micropipette tool holder 116, a pipetter tool holder 118, a reservoir 120, a pipette bit 122, an aspiration bit 124, a culture medium tank installation unit 126, and the like are provided.

[0085] 10, a tool changer 130 is attached to the tip of the culture medium exchange robot 42. A tool adaptor 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 adaptor 132.

[0086] 5 and 10 each show an example of the arrangement of the devices, and the arrangement of the devices in FIG. 5 and FIG. 10 does not necessarily match.

[0087] 10, the aspirator tool 134, micropipette tool 136, and pipetter tool 138 share a common connection structure with the tool adaptor 132. This allows various types of operating devices (134, 136, 138, etc.) to be interchangeably connected to one tool adaptor 132. The tool adaptor 132 also has a drop prevention function for preventing the operating devices (134, 136, 138, etc.) from dropping.

[0088] Among the operating instruments (134, 136, 138, etc.), the aspirator tool 134 has twelve tip bits (needles) 142 arranged parallel to each other, and can simultaneously aspirate the culture medium (culture fluid) from twelve wells 56 aligned longitudinally via the tip bits 142.

[0089] The micropipette tool 136 also has 12 needles 144 arranged in parallel to each other, and is capable of simultaneously discharging the medium (culture solution) into the 12 wells 56 via the needles 144 .

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

[0091] The aspirator tool holder 112, the micropipette tool holder 116, and the pipetter tool holder 118 respectively hold an aspirator tool 134, a micropipette tool 136, and a pipetter tool 138 that are not attached to the culture medium replacement robot 42 (in an unused state).

[0092] The disposal box 114 is used to dispose of the tip bit 142 of the aspirator tool 134. The tip bit 142 is attached to the aspirator tool 134 so as to be automatically detachable, and the used tip bit 142 is removed from the aspirator tool 134 and disposed of in the disposal box 114.

[0093] The reservoir 120 is a portable container that 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 poured into the reservoir 120, and the reservoir 120 is placed in a reservoir placement area 128 on the workbench 110. The cleaning alcohol can be poured using, for example, a suction pump (not shown) provided in the culture medium exchange unit 22.

[0094] The culture medium replacement 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 cleaning alcohol in the reservoir 120. As a result of the aspirating, the cleaning alcohol is discharged into a waste liquid tank (not shown). Thereafter, the tip bit 142 is automatically removed from the aspirator tool 134 and discarded in the waste box 114.

[0095] In the culture medium exchange section 22, as a measure to prevent dripping from the various operating devices (134, 136, 138, etc.), a plurality of receiving plates 148 made of stainless steel plates are installed below the movement paths (movement trajectories) of the various operating devices (134, 136, 138, etc.), as shown in FIG. 10, for example.

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

[0097] A manual shutter 150 is provided on the outer wall 22A. This manual shutter 150 is manually opened and closed, for example, when replenishing consumables such as culture medium. Replenishing 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 shutter 150 is the up and down direction, as indicated by arrow H in FIG. 11 . The manual shutter 150 is locked (locked out) so that it cannot be opened or closed, for example, while the culture medium replacement robot 42 is in operation. The manual shutter 150 is locked, for example, via an electromagnetic locking device under the control of the control unit 46.

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

[0099] Furthermore, a sterilization lamp (or germicidal lamp) 154 using, for example, an ultraviolet (UV) light source (such as an ultraviolet LED) is installed within the culture medium exchange unit 22, and sterilization (or disinfection) is performed within the culture medium exchange unit 22. Such a sterilization means (or disinfection means) is disposed in an appropriate location within the internal space (first space) to prevent bacterial growth in the event of, for example, dripping of the culture medium or human contact, and to maintain a clean internal environment. The sterilization lamp 154 ​​may be disposed on one to four of the four sides of the ceiling portion 24 facing the internal space (first space), or in an appropriate position on the workbench 110.

[0100] Sterilization (or disinfection) by light irradiation can be performed locally in areas prone to dripping, etc. This allows the installation location of the ultraviolet light source to be selected and appropriately positioned. For example, 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 can be appropriately adjusted so that the ultraviolet light does not hit the synthetic resin part, and the two can be positioned accordingly. Furthermore, the ultraviolet light source can also be positioned on a movable part of a part of the culture medium exchange robot 42 (e.g., the tool changer 130, the aspirator tool 134, the micropipette tool 136, or the pipetter tool 138).

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

[0102] To the culture medium exchange unit 22 as described above, the transfer robot 40 transfers the stocker 54 removed from the incubator unit 12 and places it in the placement area 156 of the workbench 110. The transfer robot 40 grasps one well plate 52 from the stocker 54 and transfers it to the culture medium exchange area 157. The transfer robot 40 removes the lid 52b, supports one reservoir 120, for example the topmost one, from among the multiple reservoirs 120 stacked in the reservoir preparation area 158 and places it in the reservoir placement area 128. As described above, the support and transfer of the reservoir 120 are performed by the transfer robot 40 using the arm plate 66 ( FIG. 10 ).

[0103] Next, the old culture medium is aspirated from the wells of the well plate body 52a by the aspirator tool 134 attached to the culture medium replacement robot 42. Thereafter, the aspirator tool 134 is automatically detached from the tool adapter 132 of the culture medium replacement robot 42 at the position of the aspirator tool holder 112.

[0104] The culture medium replacement robot 42 moves the tool adaptor 132 at the tip end to the position of the pipetter tool holder 118, and a pipetter tool 138 is attached to the tool adaptor 132. The culture medium replacement robot 42 then moves the pipetter tool 138 to the reservoir installation area 128. The pipetter tool 138 then electrically injects the culture medium into the reservoir 120 installed in the reservoir installation area 128.

[0105] Furthermore, the pipetter tool 138 is automatically removed from the position of the pipetter tool holder 118, and the culture medium replacement robot 42 moves the tool adaptor 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 adaptor 132. Then, the culture medium replacement robot 42 moves the micropipette tool 136 to the position of the reservoir 120, and the culture medium is aspirated from the reservoir 120 into the needle 144 of the micropipette tool 136.

[0106] The culture medium replacement robot 42 transfers the micropipette tool 136 to the position of the well plate body 52a that is the target of culture medium replacement, and the micropipette tool 136 injects the culture medium into the well 56 directly below. For example, when the culture medium replacement is completed for 15 well plates 52 in one stocker 54, the stocker 54 containing the well plates 52 (15 plates) for which the culture medium has been replaced is returned to the incubator unit 12 by the transport robot 40.

[0107] When using the aspirator tool 134, the aspirator tool 134 (tip bit 142) is tilted at a predetermined angle with respect to the wells 56 to aspirate the culture medium. According to the inventors' findings, by doing so, it has become significantly less likely that cells will be sucked up along with the culture medium from only a portion (for example, about 1 to 3) of the 96 wells 56. Although the reasons for this have not been fully verified, the inventors' findings suggest that aspirating the culture medium from a position eccentric to the center of the wells 56 is one factor contributing to the improvement.

[0108] When using the micropipette tool 136, the micropipette tool 136 (needle 144) can be tilted or decentered at a predetermined angle relative to the well 56, allowing the culture medium to hit the inner wall of the well 56 before injection, thereby preventing the injection from affecting the cells as much as possible.

[0109] <Safety Improvement Measures> In the cell culture device 10, for example, various processes required for cell culture are automated, and the transport robot 40 performs a variety of operations. It is difficult for a person to predict the operations of the transport robot 40. For this reason, it is desirable to employ safety improvement measures in the cell culture device 10 to enable a person to safely enter the second space (a portion other than the culture medium exchange unit 22).

[0110] Various methods can be adopted as measures to improve safety. For example, a human presence sensor 159 ( FIG. 5 ) that can detect the presence of a person inside the cell culture device 10 can be provided, and under the control of the control unit 46, the transport robot 40 can be prevented from performing operations such as gripping and transporting while the human presence sensor 159 detects a person. As the human presence sensor 159, various types of sensors can be used, 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), an acoustic sensor, etc.

[0111] Furthermore, when a person enters the cell culture device 10, the opening / closing shutter unit 36 ​​( FIG. 5 ) is opened, and when a door opening sensor (not shown) detects that the opening / closing shutter unit 36 ​​is open, the control unit 46 can stop the operation of the transport robot 40. Furthermore, when an operation (such as a button operation or an unlocking operation) to open the opening / closing shutter unit 36 ​​is performed, the operation of the transport robot 40 can be stopped. Examples of the unlocking operation include inputting a security key (such as a number or symbol) using a key input device with numbers or the like, inserting a key into a keyhole, or operating (such as turning) the key inserted in the keyhole.

[0112] It is also possible for a worker to wear a device capable of transmitting radio waves (such as a radio transmitter or an identification information tag (RFID tag)) on his or her work clothes, and when the transmitted radio waves are detected by a receiver provided in the cell culture device 10, the operation of the transport robot 40 can be stopped. Furthermore, it is also possible to allow the opening of the opening / closing shutter unit 36 ​​only during a predetermined period of time. In this case, control using the human sensor 159 or the door opening sensor (not shown) can be omitted.

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

[0114] Furthermore, safety of the culture medium exchange robot 42 is considered to be ensured because it is partitioned by the wall 22B of the culture medium exchange unit 22. Furthermore, in the cell culture device 10 of this embodiment, no person enters the culture medium exchange unit 22 during the process. Therefore, even if the operation of the transport robot 40 stops, the culture medium exchange robot 42 does not stop, and it is possible to have the robot 42 perform operations related to culture medium exchange.

[0115] <Major Advantages of the Cell Culture Device 10> The cell culture device 10 of this embodiment is provided with a control unit 46 that defines the range of movement of the first operation unit (culture medium exchange robot 42) when performing operations related to culture medium exchange as within the first space (the internal space of the culture medium exchange unit 22), and the range of movement of the second operation unit (transport robot 40) when moving the well plate 52 as within the second space and the first space.

[0116] Therefore, the range of movement of the first operation unit (culture medium exchange robot 42) and the range of movement of the second operation unit (transport robot 40) can be overlapped, optimizing the space efficiency within the cell culture device 10. This also enables space saving and makes it possible to provide a compact cell culture device 10.

[0117] Furthermore, a first operating unit capable of performing operations related to culture medium replacement is selectively placed in the first space, which has a relatively high air cleanliness (high cleanliness), and a second operating unit capable of performing operations to move the cell culture vessel is placed in the second space, which has a relatively low air cleanliness.Since the range of movement of the first operating unit when performing operations related to culture medium replacement is within the first space, and the range of movement of the second operating unit when moving the cell culture vessel is within the second space and the first space, operating units with different functions can be operated in a more optimized environment.

[0118] Furthermore, each section (incubator section 12, image inspection section 14, stocker supply section 16, product removal section 18, and culture medium replacement section 22) is arranged around the transport robot section 20, with the transport robot section 20 at the center. This also makes it possible to optimize space efficiency. This also makes it possible to save space and provide a compact cell culture device 10.

[0119] Furthermore, in the culture medium exchange unit 22, the various areas necessary for the culture medium exchange operation (areas for the aspirator tool holder 112, waste boxes 114, 115, micropipette tool holder 116, pipetter tool holder 118, reservoir 120, pipette bit 122, suction bit 124, and culture medium tank installation unit 126, etc.) are arranged to surround the culture medium exchange robot 42, thereby optimizing space efficiency. This also makes it possible to save space in terms of the arrangement of the areas necessary for the culture medium exchange operation, making it possible to provide a compact culture medium exchange unit 22.

[0120] Furthermore, the well plate 52 is transported not only to a space (first space) with a relatively high air cleanliness (high cleanliness) but also to a second space with a relatively low air cleanliness, but since the lid 52b is provided, it is possible to protect the well 56 from dust and keep the well 56 clean.

[0121] Furthermore, most of the steps of storing the well plates 52 and stockers 54 in the incubator 32, removing them from the incubator 32, cell inspection in the image inspection unit 14, and medium replacement in the medium replacement unit 22 can be automated, thereby reducing the labor required for cell culture. Note that the cell inspection is not limited to the image inspection described in this embodiment, and various other inspection methods can be used.

[0122] Furthermore, with regard to the transfer robot 40, a single (one type of) air gripper 68 can grip (and transport) different types of gripping objects (and transport objects), such as the stocker 54, well plate 52, and lid 52b, so there is no need to replace the air gripper 68 for each gripping object (and transport object). This makes it possible to make the transfer robot 40 multifunctional. Furthermore, it is possible to easily automate the gripping (and transport) of gripping objects (and transport objects).

[0123] Furthermore, a plurality of well plates 52 (here, five plates) are arranged in a set in the stocker 54. Therefore, a large number of well plates 52 can be transported simultaneously.

[0124] Also, with regard to the culture medium replacement robot 42, a tool changer 130 is equipped with a tool adapter 132, and various operating devices (such as an aspirator tool 134, a micropipette tool 136, or a pipetter tool 138) are exchangeably connected to one tool adapter 132. This makes it possible to make the culture medium replacement robot 42 multifunctional. Furthermore, the operating devices are easily exchangeable, and the exchange of operating devices can be easily automated.

[0125] Furthermore, since the transport robot 40 stops when a person's entry is detected, the small cell culture device can be operated even more safely.

[0126] <Modifications Related to Layout> The arrangement of each section (incubator section 12, image inspection section 14, stocker supply section 16, product removal section 18, transport robot section 20, and culture medium replacement section 22) is not limited to that shown in FIG. 1 and the like, and can be modified in various ways. FIG. 12 shows an example of a modified layout. The cell culture device 160 in the example of FIG. 12 is provided with four incubator sections 12-1 to 12-4, and three incubator sections 12-2 to 12-4 are added compared to the example of FIG. 1 and the like. Here, in FIG. 12, the incubator sections 12-1 to 12-4 are labeled "incubator (1)" to "incubator (4)," and the numbers (1) to (4) used to identify the incubators are indicated using circled numbers.

[0127] In the cell culture device 160 shown in Figure 12, a linear actuator 162 is added, and the four incubator units 12-1 to 12-4 are arranged along the linear actuator 162. Incubator units with the same configuration can be used as the incubator units 12-1 to 12-4. In the example of Figure 12, the incubator unit 12-1 is arranged in a position facing the culture medium exchange unit 22, as in the example of Figure 1, and the incubator units 12-2 and 12-3 are arranged to face each other with the linear actuator 162 between them.

[0128] The transport robot 40 is installed on a linear actuator 162 and is movable along the Y-axis direction along which the linear actuator 162 extends. Although the transport robot 40 is shown in two locations in Fig. 12, there is only one transport robot 40, and in Fig. 12, the transport robot 40 before and after movement are both shown by solid lines. The transport robot 40 takes stockers 54 in and out of each of the incubator sections 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, it becomes possible to culture a larger number of cells. In addition, the cell culture device 160 becomes more multifunctional. Furthermore, it becomes possible to change the position of the transport robot 40. Then, the transport robot 40 can move linearly using the linear actuator 162 in addition to its own six-axis movement. Therefore, this also makes the cell culture device 160 more multifunctional.

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

[0131] <Modifications Related to the Arrangement of the Culture Medium Exchange Robot 42> In the example of FIG. 11 , the culture medium exchange robot 42 is installed on the workbench 110. However, this is not limiting. For example, as shown in FIG. 13 , the culture medium exchange robot 42 can be a ceiling-suspended type. In the example of FIG. 13 , the culture medium exchange robot 42 is installed inside (on the interior space side of) the ceiling 24 of the culture medium exchange unit 22 and extends downward from the ceiling 24. This arrangement ensures free space on the workbench 110, allowing for wider use of the workbench 110. Furthermore, because no space is required on the workbench 110 to install the culture medium exchange robot 42, the workbench 110 can be made smaller than the example of FIG. 11 , thereby enabling the culture medium exchange unit 22 to be miniaturized.

[0132] <Additional Information Regarding Air Intake> In the cell culture device 10 as described above, air is supplied to the internal space (first space) of the culture medium exchanging unit 22 by the first space filter unit 26, and air is supplied to a space (second space) other than the internal space of the culture medium exchanging unit 22 by the second space filter unit 28. Furthermore, the first space filter unit 26 takes in air from outside the cell culture device 10 independently of the second space filter unit 28, and air for the internal space (first space) of the culture medium exchanging unit 22 is supplied to the internal space (first space) of the culture medium exchanging unit 22 from the first space filter unit 26.

[0133] The air outside the cell culture device 10 can be taken in independently as air for the internal space (first space) of the culture medium exchanging unit 22 and air for the other internal space (second space), and can be supplied to the internal space (first space) of the culture medium exchanging unit 22 and the other internal space (second space) without being diverted along the way. Furthermore, even in a simplified structure that does not require autoclave sterilization, for example, relatively clean air can be supplied to the internal space (first space) of the culture medium exchanging unit 22.

[0134] Furthermore, because a normal environment can be maintained without relying on steam sterilization, it is possible to maintain the air cleanliness inside the cell culture device at a level appropriate for the operation, without the need for thermal countermeasures such as steam temperature control, blocking of heat conduction (and heat transfer) paths, opening and closing of airtight doors, etc. Furthermore, it is possible to omit the step of stopping the transfer robot 40 midway to sterilize it when it moves to the internal space (first space) of the culture medium exchanging unit 22, which enables the transfer robot 40 to move quickly from the space (second space) outside the culture medium exchanging unit 22 to the internal space (first space) of the culture medium exchanging unit 22.

[0135] <Supplementary Information Regarding the Function of the Air Gripper 68> In addition to the explanation given above, the air gripper 68 (see, for example, FIGS. 7(a) and 7(b)) can also be explained as follows. For example, the air grippers 68 can transport different objects by performing some common operations. Therefore, the air grippers 68 diversify the functions of the transport robot 40 by performing a limited number of operations (modes).

[0136] Specifically, the air gripper 68 is used to transport the stocker 54, well plate 52, lid 52b, and the like. When transporting any object, the air gripper 68 performs a common operation of closing the gripping portion 76. Furthermore, after performing this common operation, the air gripper 68 grips different objects by varying the spacing of the claws 78 (also referred to as different amounts of movement or different amounts of displacement). Therefore, a single (one type of) air gripper 68 can be used to transport a large number of stockers 54 and well plates 52.

[0137] More specifically, when the air gripper 68 transports the stocker 54, as described above, as the gripping portion 76 closes, the four locking pins 82 enter the V-shaped notches 63 provided in the claw portion 78 and lock onto the stocker 54. As a result, the stocker 54 is positioned relative to the claw portion 78 and is gripped by the gripping portion 76.

[0138] When the tip of the transport robot 40 moves upward with the gripper 76 gripping the stocker 54, the air cylinder 70 is displaced integrally. The claws 78 of the gripper 76 come into contact with the protrusion 62 and other parts of the stocker 54 from below and rise, lifting the stocker 54. At this time, the force with which the gripper 76 grips the stocker 54 is not particularly large, and the force required for the claws 78 to support the stocker 54 is greater and dominant than the force with which the gripper 76 grips the stocker 54.

[0139] On the other hand, when the air gripper 68 grips the well plate 52 or the lid 52 b, the two claws 78 of the gripping portion 76 gradually approach each other, and the four (2 × 2) resin blocks 80 come into contact with the side surfaces of the well plate body 52 a or the lid body 52 b. The well plate body 52 a or the lid body 52 b is then gripped by the frictional force caused by pressure from the side surfaces, without the metal claws 78 coming into direct contact with the well plate body 52 a or the lid body 52 b.

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

[0141] 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 spacing between the gripping portions 76 (and the claws 78) are different from those when gripping the stocker 54. Furthermore, the lifting position of the air gripper 68 and the spacing between the gripping portions 76 are different when gripping the well plate 52 and when gripping the lid 52b.

[0142] As described above, the cell culture device 10 is capable of transporting multiple objects of different widths and heights by using a single air gripper 68 that closes the gripping portion 76. This makes it possible to automate many of the processes required for cell culture with a simple configuration.

[0143] Furthermore, different gripping operations can be performed depending on the weight and size of the object. For relatively light objects (such as the well plate 52 and the lid 52b), the claws 78 can be used to clamp the object, and for relatively heavy objects (such as the stocker 54), the claws 78 can be used to support the object. The operations required for such different operations are kept to a minimum. As a result, it is possible to grip both relatively light and heavy objects while performing common operations (such as opening and closing the gripping portions 76) in many parts.

[0144] <Utilization of Commercially Available Laboratory Equipment> <<Introduction>> The cell culture device 10 is designed to utilize as much commercially available laboratory equipment (commercially available laboratory equipment) as possible. Examples of commercially available laboratory equipment include a multichannel micropipette 182 (FIG. 14) attached to a micropipette tool 136 (FIG. 10) and an electric pipettor 192 (FIG. 15) attached to a pipettor tool 138 (FIG. 10).

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

[0146] Commercially available laboratory equipment is available on the market from multiple businesses and brands. However, while the shapes and dimensions of the same type of laboratory equipment are similar, they are often not universal and are slightly different. To make the cell culture device 10 low-cost and multifunctional, it is important to be able to utilize multiple types of commercially available laboratory equipment regardless of differences in shape, dimension (size), etc. The cell culture device 10 is designed to enable the use of various types of commercially available laboratory equipment as much as possible. Below, we will mainly discuss the design features related to the aforementioned commercially available laboratory equipment.

[0147] <<Ideas for Using the Multichannel Micropipette 182>> The multichannel micropipette 182 (Figure 14) can be a commercially available product supplied by multiple companies and brands. However, as mentioned above, even though the shapes and dimensions of similar laboratory equipment are similar, they are not common and often have slight differences.

[0148] Therefore, in order to enable a single medium exchange robot 42 to use commercially available laboratory equipment of different shapes, dimensions (sizes), etc., a micropipette tool 136 is provided with a driven roller 184 and an air cylinder (not shown), as shown in FIG. 14 . The air cylinder (not shown) is disposed inside a box 183 provided in the micropipette tool 136. The piston of the air cylinder (not shown) contacts a piston button 186 of a multichannel micropipette 182 via a power transmission unit (not shown). The driven roller 184, air cylinder (not shown), power transmission unit (not shown), etc. constitute a push button drive mechanism. The air cylinder (not shown) then automatically presses the piston button 186 of the multichannel micropipette 182. The dispensing operation is performed automatically by pressing (lowering) the piston button 186. As long as the pressing force is not applied to a position that is off the piston button 186 or to a position that is significantly offset from the piston button 186, the piston button 186 can be pressed down (lowered) by the force generated in the air cylinder (not shown).

[0149] An elastic body (not shown), such as a coil spring, is attached to the piston button 186. When the piston button 186 is released from the force generated by the air cylinder (not shown), it receives the elastic restoring force of the elastic body (not shown) and returns (rises) to its original position (unpressed position). The rising of the piston button 186 automatically performs the suction operation. The driven roller 184 follows this movement of the piston button 186.

[0150] In this way, by operating the piston button 186, it is possible to operate commercially available multichannel micropipettes 182, which are laboratory equipment, even if there are slight differences in shape, dimensions (size), etc. This also accommodates differences in the models of multichannel micropipettes 182. Furthermore, it is possible to handle different models of multichannel micropipettes 182 with a single culture medium exchange robot 42.

[0151] 14, another driven roller 185 also contacts a shoulder 187 (shoulder of the multichannel micropipette 182) that protrudes below the piston button 186. The shoulder 187 is also a movable part combined with an elastic body (not shown) such as a coil spring, and like the piston button 186, it moves up and down when pressed by a drive mechanism (shoulder drive mechanism) that is composed of the driven roller 185, an air cylinder (not shown) in the box 183, a power transmission unit (not shown), etc. When the shoulder 187 is pressed down, the needle 144 attached to the multichannel micropipette 182 automatically falls off the multichannel micropipette 182 due to air pressure.

[0152] For example, a motor may be used instead of the air cylinder (not shown) that drives the piston button 186 and the shoulder portion 187. The motor may be an air motor powered by air or an electric motor powered by electricity.

[0153] The multichannel micropipette 182 is held by a holder 188. The holder 188 can hold different types of multichannel micropipettes 182 with similar shapes, for example, by varying the amount of screwing (also referred to as the amount of tightening or tightening) of the bolt 189.

[0154] The holder portion 188 functions as a jig that holds commercially available laboratory equipment (here, the multichannel micropipette 182) for use. If the commercially available laboratory equipment (here, the multichannel micropipette 182) has a curved design, it is generally difficult to incorporate it into the micropipette tool 136. However, by adopting a jig structure such as the holder portion 188, it becomes possible to flexibly accommodate different types of multichannel micropipettes 182.

[0155] 14, the reference numeral 133 denotes a tool-side adapter. The tool-side adapter 133 is connected to a tool adapter 132 (see, for example, FIG. 10) provided at the tip of the culture medium exchange robot 42. The micropipette tool 136 (see FIG. 10) is not shown in the state where it is attached to the culture medium exchange robot 42.

[0156] <<Ideas for Using the Electric Pipettor 192>> The electric pipettor 192 (Figure 15) can be a commercially available product supplied by multiple companies and brands, but as mentioned above, even though the shapes and dimensions of the same type of laboratory equipment are similar, they are not common and often have slight differences. In the pipettor tool 138 shown in Figure 15, the electric pipettor 192 is held using a holder part 193.

[0157] The holder section 193 has two plate-like frame sections 194 with cutouts, and the electric pipetter 192 is sandwiched between the frame sections 194. A plurality of roller sections 196 are provided between the frame sections 194, and the roller sections 196 are supported by the frame sections 194 with their ends inserted into elongated holes 198. The roller sections 196 are in contact with the outer periphery of the electric pipetter 192. The longitudinal direction of each elongated hole 198 faces one of two orthogonal directions on the plane of the frame sections 194.

[0158] The electric pipettor 192 is surrounded by a frame portion 194 and a roller portion 196 and is held by the pipettor tool 138. The roller portion 196 is inserted into a long hole 198, and is therefore movable within the range of the long hole 198. Therefore, the position of the roller portion 196 changes depending on the size of the electric pipettor 192.

[0159] A plurality of bolts 200 are screwed into the frame portion 194. The bolts 200 are displaced forward and backward by being screwed in and loosened. When the bolts 200 are screwed in and advanced toward the electric pipetter 192, the tips of the bolts 200 press against the electric pipetter 192. When the bolts 200 are screwed in, the electric pipetter 192 is held more firmly than before being screwed in.

[0160] Note that, for example, by attaching a protective member (buffer member) made of synthetic resin (including synthetic rubber) to the tip of the bolt 200, it is possible to prevent the bolt 200 from damaging the electric pipetter 192. Furthermore, it is also possible to use synthetic resin (synthetic resin with sufficient rigidity) as the material for the bolt 200.

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

[0162] Therefore, it is possible to hold commercially available electric pipetters 192, which are laboratory equipment, even if there are slight differences in shape, dimensions (size), etc., and it is possible to accommodate differences in the model of the electric pipetter 192. Furthermore, it is possible to handle different models of electric pipetters 192 with a single medium exchange robot 42.

[0163] The electric pipetter 192 is also provided with two push buttons (not shown), which are pressed by two movable parts (not shown) provided on the button operation unit 195. In FIG. 15, the push buttons and movable parts are hidden behind the frame part 194. The functions of the two push buttons are for dispensing and aspirating, and the two movable parts individually press the corresponding push buttons to perform dispensing and aspirating operations. The movable parts are driven by air pressure.

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

[0165] The frame portion 194 functions as a jig that holds commercially available laboratory equipment (here, the electric pipettor 192) so that it can be used. The frame portion 194 is equipped with rollers 196 and bolts 200. If the commercially available laboratory equipment (here, the electric pipettor 192) has a curved design, it is generally difficult to incorporate it into the pipettor tool 138. However, by employing a jig structure such as the frame portion 194, it becomes possible to flexibly accommodate different types of electric pipettors 192.

[0166] The electric pipetter 192 may be held by utilizing the leaf spring force (elastic restoring force of a leaf spring) of the plate-shaped frame portion 194. Also, reference numeral 133 in Fig. 15 denotes 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 culture medium exchange robot 42. The pipetter tool 138 (Fig. 10) is not shown attached to the culture medium exchange robot 42.

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

[0168] As shown in Figure 16(a), a large number of tip bits 142 are stored in a pit box 206 and arranged in a matrix. In Figure 16(a), only one row of tip bits 142 is shown. One row is made up of 12 tip bits 142. The aspirator tool 134 (Figure 10) is attached to the culture medium replacement robot 42. The aspirator tool 134 (Figure 10) is not shown in the state where it is attached to the culture medium replacement robot 42.

[0169] The multi-aspirator 202 is attached to the aspirator tool 134. The multi-aspirator 202 is provided with a predetermined number (12 in this example) of aspirator connectors 204 that protrude parallel to one another.

[0170] The aspirator connector 204 has tapered portions 208, 210 at its tip and middle. The aspirator connector 204 is made of a metal such as stainless steel. The culture medium replacement robot 42 then lowers the multi-aspirator 202 together with the aspirator tool 134 toward the row of tip bits 142, as indicated by arrow K.

[0171] 16( b), the aspirator connector 204 reaches the tip bit 142 and enters the opening at the base end (root portion) of the tip bit 142. 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 of the tip bit 142.

[0172] The tapered portion 210 of the aspirator connector 204 generates a force from the inside to the outside at the base end of the tip bit 142. A situation arises in which the aspirator connector 204 is pressed against the tip bit 142 with a predetermined force. The tip bit 142 is made of synthetic resin. The aspirator connector 204 is then press-fitted into the tip bit 142, and the aspirator connector 204 and the tip bit 142 are coupled together.

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

[0174] The fall prevention plate 207 constitutes the fall prevention mechanism. The fall prevention plate 207 is formed using a plate bent into an L shape. Furthermore, a plurality of claws 211 extending parallel to each other are provided on the edge portion on the tip side of the fall prevention plate 207, and the claws 211 fit between adjacent tip bits 142. The tip bit 142 is provided with a cylindrically protruding flange 212 on its periphery. The claws 211 partially face the stepped flange 212 from below.

[0175] Therefore, even if, for example, some of the aspirator connectors 204 are not fully inserted into the corresponding tip bits 142, causing the connection to loosen and the tip bits 142 to fall out of the aspirator connectors 204, the tip bits 142 can be hooked onto the claw portions 211. This prevents 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 tip bit 142 used, or the angle (posture) at which the tip bit 142 is stored in the pit box 206, it is possible that the multi-aspirator 202 may rise without being fully connected to the aspirator connector 204. If the tip bit 142 falls, depending on the situation, it may be necessary to stop the automatic operation of the cell culture device 10 and have operator A ( FIG. 1 , etc.) enter the cell culture device 10 (or insert his / her arm) to remove the tip bit 142 from the cell culture device 10.

[0177] Furthermore, in some cases, the cell culture device 10 is used in such a way that, once a single operation (operation) is started, the processes necessary for cell culture are performed for, for example, 10 days or more continuously. Therefore, the falling of the tip bit 142 may adversely affect the cell culture that has been going on for several days. Furthermore, the opening of doors and shutters may reduce the cleanliness of the air.

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

[0179] Furthermore, the fall prevention mechanism including the fall prevention plate 207 not only prevents the tip bit 142 from falling, but also provides a tip bit detection sensor 214 that can detect whether or not the tip bit 142 has fallen, as shown in Fig. 19. As the tip bit detection sensor 214, for example, an optical sensor composed of a light-emitting section 216 and a light-receiving section 218 can be used.

[0180] To detect whether or not the tip bits 142 have fallen, for example, the multi-aspirator 202 holding a row of tip bits 142 is moved by the culture medium changing robot 42 toward the tip bit detection sensor 214 as shown by arrow N. The tip bit detection sensor 214 is disposed in the culture medium changing unit 22, similar to the culture medium changing robot 42.

[0181] The culture medium replacement robot 42 moves the multi-aspirator 202 linearly at a constant speed so that the tip bit 142 passes between the light-emitting unit 216 and the light-receiving unit 218 in order. The tip bit detection sensor 214 can be installed on, for example, the workbench 110. However, this is not limitative, 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 no tip bits 142 have fallen, a predetermined number (here, 12) of tip bits 142 intermittently and regularly block the light between the light-emitting unit 216 and the light-receiving unit 218. However, when a tip bit 142 has fallen, the period during which the tip bit 142 is not detected becomes longer than when no tip bit has fallen. Therefore, by monitoring the waveform related to the output signal of the light-receiving unit 218, for example, with the control unit 46 (FIG. 5), it is possible to determine whether or not a tip bit 142 has fallen and the location where the tip bit has fallen. Here, the tip bit detection sensor 214 may be of a type that detects light reflected from the tip bit 142.

[0183] While the tip bit 142 attached to the aspirator tool 134 (FIG. 10) has been described above, a similar attachment mechanism, attachment method, fall prevention structure, and fall prevention method can also be adopted 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, similar to the aspirator tool 134 (FIGS. 10, 17, and 18). It can also be provided with a needle detection sensor (not shown). Furthermore, the tip bit detection sensor 214 can be an optical sensor that also serves as the needle detection sensor.

[0184] <<Ideas for Using the Pipette Tip 146>> The pipette tip 146 (FIG. 10) is a commercially available laboratory device that is larger and longer than the tip bit 142 and needle 144. The pipette tip 146 is attached to an electric pipetter 192 (FIG. 15). The electric pipetter 192 (FIG. 15) is held by a pipetter tool 138. The pipette tip 146 is attached to the electric pipetter 192, for example, in the procedure shown in FIGS. 20(a) and 20(b).

[0185] 20(a), one pipette tip 146 is held by a movable mechanism 220A. The movable mechanism 220A is connected to a drive source such as an air cylinder, and is capable of raising the pipette tip 146 at a predetermined speed (e.g., several cm to 10 cm / sec), as indicated by arrow P. As the pipette tip 146 rises, it approaches the electric pipetter 192.

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

[0187] 20(a) and 20(b), the movable mechanism 220A is shown as simply contacting the pipette tip 146 from below and pushing up the pipette tip 146. However, this is not limiting, and the movable mechanism 220A can also grasp and lift the pipette tip 146 from a horizontal direction.

[0188] At this time, the pressure mechanism 220B contacts the electric pipetter 192 from above. The pressure mechanism 220B is formed, for example, from a member such as an aluminum profile, and moves toward and away from the electric pipetter 192. In the example of Figures 20(a) and (b), the pressure mechanism 220B is moved so as to contact the electric pipetter 192 from above.

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

[0190] As a result, a force can be generated that moves the tip connector 221 toward the opening at the top of the pipette tip 146. Then, the pipette tip 146 can be attached to the electric pipetter 192 while ensuring a sufficient force to lift the pipette tip 146 (the force pushing up the movable mechanism part 220A).

[0191] In other words, by supporting the electric pipetter 192 from above by the pressure mechanism 220B, it is possible to supplement (strengthen or increase) the force with which the pipette tip 146 is attached to the electric pipetter 192. Furthermore, because the pressure mechanism 220B receives the force with which the movable mechanism 220A rises, it is possible to minimize the load on the culture medium exchange robot 42.

[0192] Furthermore, 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. In other words, the drive system of the movable mechanism unit 220A can be made small and low-load. Furthermore, there is no need to introduce a dedicated large device to attach the pipette tip 146 to the electric pipetter 192. This makes it possible to reduce the size of the cell culture device 10.

[0193] <<Ideas for Use of Incubator 32>> Regarding the incubator 32, the door opening and closing of a commercially available incubator is automated. Furthermore, automation does not require modification of the incubator, and an inexpensive, compact configuration is realized.

[0194] As described above, the incubator 32 (FIGS. 2 and 5) is provided with an automatic door 86. The automatic door 86 is a one-side hinge type door that swings (rotates) horizontally while supported by the incubator main body 230. FIG. 21(a) shows the automatic door 86 in a closed state, and FIG. 21(b) shows the automatic door 86 in an open state. The automatic door 86 functions as the outer door of the incubator 32. Furthermore, an inner door 232 is provided inside the automatic door 86, as shown in FIGS. 21(b) and 22. The inner door 232 is also a one-side hinge type door that swings (rotates) horizontally while supported by the incubator main body 230.

[0195] The automatic door 86 is formed by bending a metal sheet into a rectangular box shape, and the entire automatic door 86 is painted or the like. Therefore, the interior of the incubator 32 cannot be seen through the automatic door 86. In contrast, the inner door 232 is made of transparent resin, glass, or the like. When only the inner door 232 is closed, the interior of the incubator 32 can be seen through the inner door 232. In this way, the incubator 32 has a double-door structure.

[0196] The automatic door 86 and the inner door 232 are opened and closed individually under the control of, for example, the control unit 46 (FIG. 5). As shown in FIGS. 21(b) and 22, piston rods 235, 237 of air cylinders 234, 236 are connected to the automatic door 86 and the inner door 232. The automatic door 86 and the inner door 232 are connected to the piston rods 235, 237 using band-shaped holding members 238, 240. The automatic door 86 has two holding members 238, and the inner door 232 has one holding member 238. The parts connecting the automatic door 86 and the inner door 232 to the piston rods 235, 237 are fixed portions 246, 248.

[0197] The holding members 238, 240 are arranged on the outside of the automatic door 86 and the inner door 232 with their longitudinal directions facing in the vertical direction. The longitudinal (vertical) ends of the holding members 238, 240 have a bent shape. The holding members 238, 240 are attached to the automatic door 86 and the inner door 232 via a sandwiching structure that holds the automatic door 86 and the inner door 232 in place from the top and bottom. Specifically, the holding members 238, 240 are configured by combining an L-shaped sheet metal member or 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 Figures 23(a) and 23(b), the holding member 238 is secured to the automatic door 86 with screws while being placed on the connecting plate 242 from the outside. The connecting plate 242 is secured to the automatic door 86 with screws while being placed on top of the automatic door 86.

[0199] The retaining member 238 and the connecting plate 242 are fixed to the automatic door 86 by screwing screws into existing holes in the automatic door 86. Furthermore, as shown in Figures 23(a) and (b), an L-shaped bracket 244 can also be inserted and fixed into the gap between the existing door gasket 243 and frame 245 of the automatic door 86. An elongated hole 247 is formed at the end of the retaining member 238, allowing the fixing position to be adjusted within the range of the elongated hole 247. By using the retaining member 238, the connecting plate 242, and the L-shaped bracket 244, the retaining member 238 can generate a clamping force to hold the automatic door 86 from above and below, and the retaining member 238 and the L-shaped bracket 244 can generate a clamping force to hold the automatic door 86 from the thickness direction. This structure ensures sufficient fixing force to transmit the force of the air cylinder 234 to the automatic door 86, even if the automatic door 86 has a small number of existing holes (e.g., one) and the fixing force by screws is small.

[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 piston rod 235 is connected to the connecting plate 242 in a state in which it can be relatively displaced in the horizontal direction around the pivot of a fixing part 246. Although not shown, the base end of the air cylinder 234 connected to the incubator main body 230 can also be relatively displaced in the horizontal direction around the pivot.

[0201] 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 not shown in detail, the piston rod 237 is connected to the holding member 238 in a manner that allows relative displacement in the horizontal direction around the pivot of the fixing portion 248. Although not shown in the figure, the base end of the air cylinder 236 connected to the incubator main body 230 is also capable of 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 to different degrees.

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

[0204] The displacement speed of the piston rods 235 and 237 is adjusted using a speed controller, and the thrust of the piston rods 235 and 237 is adjusted using a regulator (air pressure regulator).

[0205] The incubator 32 is one of commercially available experimental devices, and when a commercially available incubator 32 is used, conventionally, the automatic door 86 and the inner door 232 have been opened and closed manually. However, in the cell culture device 10, the opening and closing of the automatic door 86 and the inner door 232 is automated, and the opening and closing of the doors of the incubator 32, which is commercially available experimental device, has been automated.

[0206] The air cylinders 234, 236 are controlled to replicate the manner in which a human opens and closes the automatic door 86 and the inner door 232 during the steps required for cell culture. In addition, the air used to drive the air cylinders 234, 236 is not the same as the air used by the culture medium exchange robot 42, for example, but is introduced through an independent air system.

[0207] In the incubator 32 shown in the example of Figures 21 to 23, a manual locking mechanism is provided on the inner door 232. However, automating the operation of the locking mechanism requires the installation of more equipment, and therefore, in the examples of Figures 21 to 23, the locking mechanism has been removed. It is also possible to leave the locking mechanism in place and not use it. Furthermore, if the locking mechanism can be operated using simple equipment, the locking mechanism may be automated.

[0208] The above-described matters regarding the incubator 32 can be summarized as follows: (1) In the incubator 32, air cylinders 234, 236 are used as drive sources for opening and closing the doors (opening and closing the automatic door 86 and / or the inner door 232). (2) The air cylinders 234, 236 are compactly arranged outside (here, at the bottom) of the incubator 32. (3) No separate link mechanism is combined with the air cylinders 234, 236; the doors (automatic door 86 and inner door 232) and the air cylinders 234, 236 are directly connected at the fixing portions 246, 248. The doors (automatic door 86 and inner door 232) and the air cylinders 234, 236 are directly connected at the fixing portions 246, 248, and the air cylinders 234, 236 themselves function as links. This allows the mechanical components for automatically opening and closing the doors (automatic door 86 and inner door 232) to be arranged in a space-saving manner. (4) The air cylinders 234, 236 are of closed-center type, so that the automatic door 86 (and / or inner door 232) remains closed when the piston rod 235 (and / or piston rod 237) is in the intermediate position. Therefore, a separate locking mechanism is not required. (5) The opening and closing speed of the doors (automatic door 86 and inner door 232) can be individually adjusted using a speed controller, and the thrust for opening and closing the doors can be adjusted using a regulator. Furthermore, because air equipment (pneumatic equipment) is used, the door opening and closing can be easily adjusted and controlled using the speed controller and regulator. Therefore, a configuration for opening and closing the doors (automatic door 86 and inner door 232) can be realized inexpensively. (6) Holding members 238, 240 are attached to the doors (automatic door 86 and inner door 232) using a clamping structure, and these holding members 238, 240 are fixed to the air cylinders 234, 236. The reason why the doors (automatic door 86 and inner door 232) and the drive units (here, air cylinders 234, 236) are fixed in this manner is as follows.That is, when using a commercially available incubator, major modifications such as swapping (replacing) the incubator's rotation axis or drilling holes in the door are undesirable because they void the incubator manufacturer's performance guarantee and increase costs. (7) The automatic door 86 and the inner door 232 are driven by two independent air cylinders 234, 236, respectively. Many commercially available incubators have a two-door structure consisting of an outer door and an inner door. The outer door is opaque and designed for high thermal insulation. The inner door is made of glass or transparent resin. This two-door structure offers advantages such as reduced heat loss when the doors are opened and closed, and the ability to check the interior without opening the inner door. In the cell culture device 10, the doors are opened in the order of the outer door (automatic door 86) → inner door 232, and closed in the order of the inner door 232 → outer door (automatic door 86).

[0209] <<Summary of Use of Commercially Available Laboratory Equipment>> As described above, various types of commercially available laboratory equipment are utilized. In the cell culture device 10, commercially available laboratory equipment that is operated manually by humans is incorporated into an automated system and utilized.

[0210] It should be noted that not only the culture medium exchange robot 42 but also, for example, the transport robot 40 can hold commercially available experimental equipment. For the transport robot 40, for example, commercially available well plates 52 and lids 52b can be used. In this case, it can be said that the air gripper 68 is devised so that it can use multiple types of commercially available experimental equipment with a partially common operation.

[0211] <Shutter Driving Mode> By making the opening area adjustable for a shutter mechanism such as the automatic shutter 152 ( FIG. 11 ), it is possible to maximize the sealing effect. Specifically, for example, as shown in FIG. 24( a), two automatic shutters 152A and 152B are installed side by side (left and right, horizontally). As shown in FIGS. 24( b) and 25( a), the automatic shutters 152A and 152B are installed individually in openings 252A and 252B of the culture medium exchanging unit 22. The automatic shutters 152A and 152B form the inner wall 22B of the culture medium exchanging unit 22 and face the transfer robot 40.

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

[0213] One of the automatic shutters 152A that was open rises, closing the opening 252A, and the other automatic shutter 152B that was closed opens as shown in Fig. 25(a). Although not shown, the transport robot 40 points 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] Thereafter, the transfer robot 40 picks up one reservoir 120 that is at the top of the multiple reservoirs 120 stacked in the reservoir preparation area 158, and places it in the reservoir placement area 128. Prior to placing the reservoir 120 in the reservoir placement area 128, the transfer robot 40 performs an operation (swinging operation) of moving the arm plate 66 up and down in short cycles, as shown in FIG. 26 , which will be described later.

[0215] The transport robot 40 moves the arm plate 66 (FIG. 10) to the outside of the culture medium exchange device 43. Then, the automatic opening / closing shutter 152B, which was open, rises and closes, and both the automatic opening / closing shutters 152A and 152B are closed.

[0216] The opening amount (degree of opening, opening angle) of the automatic shutters 152A, 152B can be changed individually and arbitrarily between 0 (fully closed) and 100% (fully open). This allows the automatic shutters 152A, 152B to be opened at the minimum necessary opening angle. Furthermore, the opening area of ​​the openings 252A, 252B can be finely adjusted to keep it to the minimum necessary.

[0217] FIG. 25(b) shows a state in which the opening degree of one automatic opening / closing shutter 152A (and opening 252A) is set to about 50%, and the opening degree of the other automatic opening / closing shutter 152B (and opening 252B) is set to 0%.

[0218] For example, as shown in Fig. 25(a), the automatic opening / closing shutter 152B can be opened 100% and the arm plate 66 (Fig. 10) can be inserted into the opening 252B with its longitudinal direction facing vertically.Furthermore, as shown in Fig. 25(b), the automatic opening / closing shutter 152A can be opened 50% and the arm plate 66 (Fig. 10) can be inserted into the opening 252A with its longitudinal direction facing forward and backward (horizontally forward and backward).

[0219] By combining the opening and closing states and the opening degrees of the two automatic opening / closing shutters 152A, 152B arranged laterally, it is possible to finely adjust and minimize the area of ​​the opening within the same plane. Furthermore, it is possible to minimize the area of ​​the opening through which the transfer robot 40 equipped with the arm plate 66 enters and exits. Here, the "area of ​​the opening" can be adjusted for both the area of ​​each of the openings 252A, 252B and the total area.

[0220] The internal space (first space) of the culture medium exchange device 43 is maintained at a positive pressure by the air from the first space filter unit 26. Therefore, air from the second space does not immediately enter when the automatic opening / closing shutters 152A, 152B are opened. However, because the transfer robot 40 and arm plate 66 move in and out, it is effective to keep the opening area of ​​the openings 252A, 252B to a necessary minimum.

[0221] Furthermore, because the automatic shutters 152A, 152B are displaced up and down, the automatic shutters 152A, 152B can be prevented from interfering with equipment and instruments within the culture medium exchange device 43. Furthermore, the vertical space of the cell culture device 10 can be effectively utilized, allowing the culture medium exchange device 43 and the cell culture device 10 to be miniaturized left and right and front and rear (Y and X directions in FIGS. 1 and 2). The number of automatic shutters 152A, 152B may be one, or three or more. A fixed window (fixed window), pillar, or the like may be provided between the automatic shutters 152A, 152B. Including such cases, the automatic shutters 152A, 152B can be said to be arranged side by side in the horizontal direction.

[0222] <Gripping One Reservoir 120> As described above, the transfer robot 40 performs an operation (swinging operation) of moving the arm plate 66 up and down in short cycles. By this operation, the transfer robot 40 securely supports one reservoir 120 that is at the top of the multiple reservoirs 120 stacked in the reservoir preparation area 158.

[0223] The reservoirs 120 are molded using a synthetic resin material to have a certain degree of flexibility. The degree of flexibility allows for apparent elastic deformation by hand. This flexibility is achieved not only by the properties of the synthetic resin material but also by the thickness of the reservoirs 120. Each reservoir 120 is molded, for example, into a container shape with a rectangular opening. Each reservoir 120 has the same shape and is stacked with its projections and recesses fitting together 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 (lower) tier, with the upper and lower reservoirs 120 sometimes sticking together. Furthermore, there may be cases where three or more reservoirs 120 are stuck together. However, the arm plate 66 grasps one reservoir 120 in the top tier and rises, moving up and down in a short cycle (for example, 1 to 2 times per second) as shown by arrow R in FIG. 26 .

[0225] Grasping by the arm plate 66 (also referred to as grasping by the transport robot 40) is performed by pinching the object to be grasped (here, the reservoir 120) between some of the gripping pins 259 (only one side is shown in FIG. 26 ) provided on the fork portion 84. The gripping pins 259 are formed in a cylindrical shape and protrude vertically from the fork portion 84. When grasping the reservoir 120, a 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 that are not directly grasped and are in the second row from the top down are shaken off. As a result, it is possible to grasp only the top reservoir 120 and reliably place only one reservoir 120 in the reservoir placement area 128.

[0227] It is also possible to detect, for example, whether there is only one reservoir 120 in the reservoir installation area 128. More specifically, although not shown, an optical sensor having a light emitter and a light receiver is installed in the reservoir installation area 128. The optical sensor is positioned so that the reservoir 120 is located between the optical sensor. If a foreign object (here, the reservoir 120) is present at a position higher than one reservoir 120, the detection light of the optical sensor is blocked. Then, based on the interruption of light detection, the control unit 46 determines that multiple reservoirs 120 remain overlapping. It is also possible for the optical sensor to be of a type that detects reflected light from the reservoir 120.

[0228] <Structure for maintaining air cleanliness> <<Structure for disposal into disposal box 114>> Inside the culture medium exchanging device 43, an upper and lower space is divided by a workbench 110. As shown in Figures 27(a) and (b), a disposal shutter 262 is provided on the workbench 110. Figures 27(a) and (b) show partial vertical cross sections of the lower part of the culture medium exchanging unit 22.

[0229] The disposal shutter 262 is normally closed as shown in Fig. 27(a). However, when the disposal box 114 is in use, the disposal shutter 262 slides horizontally (Y direction in Fig. 1) as shown in Fig. 27(b) to expose the internal disposal opening 264. The disposal shutter 262 can be slid automatically under the control of the control unit 46 (Fig. 5).

[0230] The size of the internal waste port 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) is disposed of in the waste box 114. The tip bit 142 can be removed using air pressure. In addition, in the micropipette tool 136 (FIGS. 10 and 14), the needle 144 can be removed by pressing down the shoulder 187 of the multichannel micropipette 182 and dropped into the waste box 114 for disposal.

[0231] Furthermore, the disposal shutter 262 is normally closed to prevent liquid such as culture medium from falling into the disposal box 114. The disposal shutter 262 is automatically controlled to open and close by, for example, the control unit 46 (FIG. 5).

[0232] In this way, by providing the disposal shutter 262, it is possible to automate the work of disposing of the medium into the disposal box 114. Furthermore, compared to when an operator opens the culture medium replacement unit 22 and performs disposal manually, for example, it is possible to maintain the air cleanliness of the environment surrounding the culture medium replacement robot 42.

[0233] <<Structure Comparting the Interior of the Culture Medium Exchange Device 43>> The workbench 110 uses a metal sheet metal member such as stainless steel. As shown in Fig. 28 , a punched panel having a large number of through holes 276 is used for at least a portion of the plate material of the workbench 110. Air from the first space filter unit 26 flows (downflows) toward the workbench 110, passes through the through holes 276 in the workbench 110, and flows into the lower space 278.

[0234] The culture medium exchange robot 42 performs operations in the upper space 279 of the workbench 110, and the waste box 114 and the like are installed in the lower space 278. Air in the environment around the culture medium exchange robot 42 is discharged from the upper space 279 to the lower space 278. Furthermore, the air in the lower space 278 is discharged from the culture medium exchange device 43 to the outside of the cell culture device 10.

[0235] In this way, the interior of the culture medium exchange device 43 is divided into a space with a relatively high level of cleanliness (upper space 279) and a space with a relatively low level of cleanliness (lower space 278). Operation by the culture medium exchange robot 42 is performed in the space with a relatively high level of cleanliness (upper space 279). Furthermore, air from the first spatial filter unit 26 flows toward the workbench 110, which also prevents air in the lower space 278 from returning to the upper space 279. These factors also make it possible to maintain the air cleanliness of the environment surrounding the culture medium exchange robot 42.

[0236] 29 , two external waste ports 282 are provided in an openable and closable manner in the lower part of the outer wall 22A of the culture medium exchanging unit 22. The external waste ports 282 are interposed between the lower space 278 in the culture medium exchanging unit 22 and the external space of the culture medium exchanging unit 22 (here, the external space of the cell culture device 10).

[0237] Normally, as shown on the left side of the figure, the external waste outlet 282 is closed by an external waste outlet door 284. However, when replacing the waste box 114, the external waste outlet door 284 is opened as shown on the right side of the figure. The waste box 114 is then inserted or removed via the external waste outlet 282. When the external waste outlet door 284 is open, at least a portion of the air in the lower space 278 is ventilated. The external waste outlet door 284 shown on the left side of the figure can also be opened and closed in a similar manner.

[0238] The external waste outlet door 284 is supported by the culture medium exchanging unit 22 by a hinge 286 so as to be openable and closable. Furthermore, a latch mechanism 287 maintains the external waste outlet door 284 in a closed state. The external waste outlet door 284 is opened and closed manually.

[0239] <Discharge of Contaminated Fluid> As described above, old culture medium is aspirated from the wells of the well plate body 52a (e.g., FIG. 6) by the aspirator tool 134 ( FIG. 10 ) attached to the culture medium replacement robot 42. The old culture medium aspirated from the tip bit 142 of the aspirator tool 134 is collected in a waste liquid pipe 292 provided on the culture medium replacement robot 42, as shown in FIG. 30 , and is collected from the tip end to the base end of the culture medium replacement robot 42 through the waste liquid pipe 292. The aspirator tool 134 may also aspirate cleaning alcohol from the tip bit 142 for cleaning purposes.

[0240] The waste liquid pipe 292 is a flexible spiral tube (spiral-shaped piping) made of synthetic resin. Most of the waste liquid pipe 292 is located outside the culture medium exchange robot 42, not inside it. By using a spiral tube as the waste liquid pipe 292, the culture medium exchange robot 42 can operate over a wide range, even though the waste liquid pipe 292 is located outside the culture medium exchange robot 42. In other words, the waste liquid pipe 292 does not interfere with the operation of the culture medium exchange robot 42. Furthermore, the waste liquid pipe 292 is not pulled with excessive tension by the operation of the culture medium exchange robot 42. The upper end side of the waste liquid pipe 292 (the base end side of the culture medium exchange robot 42) can be supported by the ceiling portion 24 of the culture medium exchange unit 22. Furthermore, the waste liquid pipe 292 is replaced by removing the end from the culture medium exchange robot 42 (manually) from outside the culture medium exchange robot 42. Therefore, when replacing the waste liquid pipe 292, it is not necessary to open an access opening (not shown) of the culture medium replacement robot 42 and remove most of the waste liquid pipe 292 from the inside to the outside of the culture medium replacement robot 42. This also makes it possible to reduce the number of steps required for the replacement work.

[0241] The culture medium replacement robot 42 is provided with pipes for liquids, pipes for air, and the like inside. The waste liquid pipe 292 is more susceptible to contamination than other pipes and therefore requires more frequent replacement. Furthermore, if the culture medium replacement robot 42 were to be removed to the outside through an access opening (not shown) each time it was replaced, this would require a large number of steps. Therefore, by locating the waste liquid pipe 292 outside the culture medium replacement robot 42, the waste liquid pipe 292 can be easily replaced.

[0242] <Inventions Extractable from the Embodiments> The following inventions can be extracted from the embodiments described so far: (1) A cell culture device comprising: a first space (such as the internal space of the culture medium exchanging unit 22) that satisfies a first standard (such as ISO Class 5) as an air cleanliness standard; a second space (such as the internal space of a portion other than the culture medium exchanging unit 22) that satisfies a second standard (such as ISO Class 6 to 7) that is lower than the first standard as an air cleanliness standard; a first operation unit (such as the culture medium exchanging robot 42) that is installed in the first space and is capable of performing operations related to culture medium exchange (such as aspirating and discharging culture medium); a second operation unit (such as the transport robot 40) that is installed in the second space and is capable of performing operations to move cell culture vessels (such as well plates 52) that store culture medium; and operation unit control means (such as the control unit 46) that sets the range of movement of the first operation unit when performing the culture medium exchange within the first space and sets the range of movement of the second operation unit when moving the cell culture vessel within the second space and the first space. This allows the ranges of movement of the first operation unit and the second operation unit to overlap, thereby enabling the miniaturization of the cell culture device. Furthermore, this also allows operation units with different functions to operate in a more optimized environment. (2) The cell culture device described in (1) above, wherein the operation unit control means controls the second operation unit to move the cell culture vessel from the second space to the first space, and controls the first operation unit to perform the medium replacement operation on the cell culture vessel. This also allows the miniaturization of the cell culture device. (3) The cell culture device described in (2) above, wherein the cell culture vessel has a dustproof part (e.g., lid 52b) that is attached and detached by the second operation unit. This also allows the cell culture vessel to be kept clean.(4) The cell culture device according to any one of (1) to (3), wherein the second operation unit is provided with a gripping mechanism (such as an air gripper 68) capable of gripping the cell culture vessel, and the first operation unit is provided with an attachment mechanism (such as a tool adapter 132) that is common to 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 contents of the operation related to the culture medium exchange. This provides the effect of easily automating the gripping of the cell culture vessel and the attachment of the operation devices. (5) The cell culture device according to any one of (1) to (4) above, wherein the second space is provided with a supply / discharge section (such as a stocker supply section 16 and a product unloading section 18, or a stocker supply / unloading section integrating both) where the cell culture vessels are loaded and unloaded, a cell culture section (such as an incubator section 12) where cells housed in the cell culture vessels are cultured, and an inspection section (such as an image inspection section 14) where the cell culture vessels are inspected, and the operation section control means controls the second operation section to move the cell culture vessels relative to the supply / discharge section, the cell culture vessels relative to the cell culture section, and the cell culture vessels relative to the inspection section. This has the effect of enabling the cell culture device to be miniaturized. (6) The cell culture device according to any one of (1) to (5) above, wherein in a Cartesian coordinate system (such as an XYZ coordinate system) centered on the second operation unit in a plan view, the respective centers (such as centers (16+18)C, 12C, and 14C) of the first space, the supply and discharge unit, the cell culture unit, and the inspection unit are arranged in at least three quadrants (such as at least three quadrants out of the first quadrant Q1 to the fourth quadrant Q4). This has the effect of enabling the cell culture device to be miniaturized. (7) The cell culture device according to any one of (1) to (6) above, further comprising a sterilization light source unit (such as a sterilization lamp (or sterilization lamp) 154) that sterilizes the first space. This has the effect of maintaining a clean internal environment of the first space.(8) The cell culture device according to any one of (1) to (7), further comprising a moving unit (e.g., linear actuator 162) capable of moving the second operation unit. This provides the effect of making the cell culture device more multifunctional. (9) The cell culture device according to (4) to (8), further comprising a container mounting unit (e.g., stocker 54) on which the cell culture vessel is mounted, and the gripping mechanism has adjustable claws (e.g., claws 78) that allow the cell culture vessel to be switched between the container mounting unit and the container mounting unit by changing the spacing of the claws. This provides the effect of easily automating the gripping and transport of the cell culture vessel and the container mounting unit. (10) The cell culture device according to (9), further comprising: a stack of cell culture vessels on the container mounting unit (a set of up to five well plates 52); and a plurality of stacks (e.g., three sets) of the stacks arranged on the container mounting unit, and the container mounting unit is gripped by the gripping mechanism. This provides the effect of enabling simultaneous transport of a large number of cell culture vessels. (11) The cell culture device according to any one of (1) to (10) above, further comprising a stop condition detection means (such as a human presence sensor 159) capable of detecting a stop condition (such as a human entry) that is a condition for stopping the second operation unit, and when the stop condition is detected, the operation unit control means operates the first operation unit and stops the second operation unit. This provides the effect of enabling even safer operation of a small cell culture device. (12) A cell culture device according to any one of (1) to (11) above, wherein air is supplied to the first space by a first space filter unit (such as first space filter unit 26), air is supplied to the second space by a second space filter unit (such as second space filter unit 28), the first space filter unit takes in air outside the cell culture device independently of the second space filter unit, and air to the first space is supplied to the first space from the first space filter unit.This provides the advantage that air outside the cell culture device can be taken in independently 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 along the way. (13) The cell culture device according to any one of (1) to (12) above, comprising: shutter members (e.g., automatic opening / closing shutters 152A, 152B) that separate the first space from the second space; and a shutter member control unit (e.g., control unit 46) that can control the opening and closing and the degree of opening of the shutter members, and that the area of ​​the opening (e.g., each of openings 252A, 252B, or the total of openings 252A, 252B) between the first space and the second space can be adjusted by combining the opening and closing of the shutter members and the degree of opening. This provides the advantage that the shutter members can be opened at the minimum necessary opening degree. (14) The cell culture device according to (13) above, wherein a plurality of shutter members are provided, and the plurality of shutter members are arranged side by side in the horizontal direction. This provides the effect of minimizing the area of ​​the opening in the same plane. (15) The cell culture device according to (13) or (14), wherein the second operation unit is capable of moving the cell culture vessel between the second space and the first space through the opening. This provides the effect of minimizing the area of ​​the opening through which the second operation unit enters and exits. (16) The cell culture device according to any one of (1) to (15), wherein the first space is provided with a work table (such as work 110) on which the cell culture vessel can be placed, and the work table is provided with 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. This provides the effect of partitioning the first space into a space with a relatively high level of cleanliness (upper space 279) and a space with a relatively low level of cleanliness (lower space 278).(17) The cell culture device according to any one of (4) to (16) above, wherein the operation device (e.g., micropipette tool 136, pipetter tool 138) is provided with a holder unit (e.g., holder unit 188 for multichannel micropipette 182, holder unit 193 for electric pipetter 192) to which different experimental equipment (e.g., multichannel micropipette 182, electric pipetter 192) can be attached. This provides the advantage of enabling the use of different types of commercially available experimental equipment. (18) The cell culture device according to any one of (4) to (17) above, wherein the operation device (e.g., micropipette tool 136) is provided with a push button operation mechanism unit (e.g., driven rollers 184, 185, air cylinder, power transmission unit) that can operate the push buttons (e.g., piston button 186, shoulder unit 187) of different experimental equipment. This provides the advantage of enabling the use of different types of commercially available experimental equipment equipped with push buttons. (19) The cell culture device according to any one of (4) to (18) above, wherein an experimental device (such as a multi-aspirator 202 or a multi-channel micropipette 182) can be attached to the operating device (such as an aspirator tool 134 or a micropipette tool 136), wherein a plurality of tubular devices (such as a tip bit 142 or a needle 144) can be automatically attached to the experimental device, and wherein the operating device is provided with a fall prevention mechanism (such as a fall prevention mechanism including a fall prevention plate 207) that prevents the tubular devices from falling. This provides the effect of preventing the tubular devices from falling. (20) A cell culture device according to any one of (4) to (19) above, wherein an experimental device (such as an electric pipetter 192) can be attached to the operating device (such as a pipetter tool 138), wherein a tubular device (such as a pipette tip 146) can be automatically attached to the experimental device, and wherein when the tubular device is attached to the experimental device (such as when the movable mechanism part 220A attaches the pipette tip 146 to the electric pipetter 192), the cell culture device is provided with an attachment force enhancing part (such as a pressure 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.This provides the effect of allowing the tubular device to be attached to the experimental device with a small force. (21) The cell culture device according to any one of (1) to (20) above, further comprising an incubator (e.g., incubator 32) in the second space, the incubator having a door (e.g., automatic door 86, inner door 232) that opens and closes horizontally, and an air cylinder (e.g., air cylinders 234, 236) that generates force to open and close the door. This provides the effect of allowing the use of commercially available incubators. (22) The cell culture device according to any one of (1) to (21) above, further comprising: at least one of the first operating unit and the second operating unit performing a rocking motion in the up and down direction while gripping a reservoir (e.g., reservoir 120) in the first space. This provides the effect of allowing a single reservoir to be gripped accurately. (23) The cell culture device according to any one of (1) to (22) above, wherein the first operation unit is provided with a waste liquid pipe (such as the waste liquid pipe 292) through which waste liquid (such as old culture medium) passes, and the waste liquid pipe is disposed outside the first operation unit, thereby achieving the effect of enabling the waste liquid pipe to be removed without the need to remove the waste liquid pipe from the first operation unit.

[0243] <Others> The present invention is not limited to the various embodiments described above, and various modifications and combinations of the various embodiments are possible without departing from the gist of the present invention.

[0244] For example, in organoid culture, culture medium exchange may be performed using a mechanism or method similar to that of the culture medium exchange unit 22 of the above-described embodiment.

[0245] The cell culture device according to the present invention can be applied to various cell cultures that require culture medium exchange. 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, the entire disclosure of which is incorporated herein by reference in its entirety.

[0247] DESCRIPTION OF SYMBOLS 10: Cell culture device 10A: Wall 10B: Window 12: Incubator 14: Image inspection unit 16: Stocker supply unit 18: Product removal unit 20: Transport robot 22: Culture medium replacement unit 26: First space filter unit 28: Second space filter unit 32: Incubator 34: Image inspection device 36: Open / close shutter unit 40: Transport robot 42: Culture medium replacement robot 46: Control unit 52: Well plate 52a: Well plate body 52b: Lid 54: Stocker 56: Well 68: Air gripper 70: Air cylinder 72: Movable body 76: Grip unit 78: Claw unit 80: Resin block 82: Locking pin 90: Camera 120 : Reservoir 130 : Tool changer 132 : Tool adapter 134 : Aspirator tool 136 : Micropipette tool 138 : Pipetter tool 142 : Tip bit 144 : Needle 146 : Pipette tip 148 : Receiving plate 152A, 152B : Automatic opening and closing shutter 154 : Sterilization lamp 159 : Human sensor 182 : Micropipette 184, 185 : Driven roller 186 : Piston button 187 : Shoulder part 188, 193 : Holder part 189 : Bolt 192 : Electric pipetter 194 : Frame part 195 : Button operation part 196 : Roller part 198 : Slot 200 : Bolt 202 : Multi-aspirator 204 : Aspirator connector 206: Pit box 207: Fall prevention plate 208, 210: Tapered portion 211: Claw portion 212: Flange portion 214: Tip bit detection sensor 216: Light emitting portion 218: Light receiving portion 219: Fall prevention plate220A: Movable mechanism 220B: Pressure mechanism 221: Tip connector 232: Inner door 234, 236: Air cylinder 235, 237: Piston rod 238, 240: Holding member 242: Connecting plate 243: Door packing 244: L-shaped bracket 245: Frame 246, 248: Fixing part 247: Slot 252A, 252B: Opening 259: Grip pin 262: Disposal shutter 264: Internal disposal port 266: Opening 276: Through hole 278: Lower space 279: Upper space 282, 284: External disposal port 286: Hinge 287: Latch mechanism 292: Waste pipe

Claims

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

2. The cell culture device described in claim 1, wherein the operation unit control means controls the second operation unit to move the cell culture vessel from the second space to the first space, and controls the first operation unit to perform an operation related to the culture medium replacement on the cell culture vessel.

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 operating part.

4. A cell culture device as described in any one of claims 1 to 3, wherein the second operating unit is provided with a gripping mechanism capable of gripping the cell culture vessel, and the first operating unit is provided with an attachment mechanism common to multiple types of operating devices corresponding to the content of the operation related to the culture medium replacement.

5. The cell culture device of claim 1, wherein the second space is provided with a supply and discharge section in which the cell culture vessel is loaded and unloaded, a cell culture section in which cells contained in the cell culture vessel are cultured, and an inspection section in which inspections of the cell culture vessel are performed, and the operation section control means controls the second operation section to move the cell culture vessel relative to the supply and discharge section, the cell culture vessel relative to the cell culture section, and the cell culture vessel relative to the inspection section.

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

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

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

9. A cell culture device as described in claim 4, comprising a container mounting section on which the cell culture container is placed, the gripping mechanism having claw portions whose spacing can be changed, and the spacing of the claw portions can be changed to enable switching between holding the cell culture container and the container mounting section.

10. A cell culture device as described in claim 9, wherein the cell culture vessels are stacked on the vessel mounting portion to form a stack, and the vessel mounting portion is grasped by the gripping mechanism with a plurality of the stacks arranged on the vessel mounting portion.

11. A cell culture device as described in any one of claims 1 to 3, further comprising a stop condition detection means capable of detecting a stop condition which is a condition for stopping the second operating unit, and when the stop condition is detected, the operating unit control means operates the first operating unit and stops the second operating unit.

12. A cell culture device according to any one of claims 1 to 3, wherein 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 space filter unit takes in air outside the cell culture device independently of the second space filter unit, and air to the first space is supplied to the first space from the first space filter unit.

13. A cell culture device as described in any one of claims 1 to 3, comprising: a shutter member that separates the first space and the second space; and a shutter member control unit that can control the opening and closing and the degree of opening of the shutter member, and it is possible to adjust the area of ​​the opening between the first space and the second space by the combination of opening and closing of the shutter member and the degree of opening.

14. The cell culture device according to claim 13, wherein a plurality of the shutter members are provided, and the plurality of the shutter members are arranged side by side in the horizontal direction.

15. The cell culture device according to claim 13, wherein the second operating unit is capable of moving the cell culture vessel between the second space and the first space via the opening.

16. A cell culture device as described in any one of claims 1 to 3, wherein a work table portion on which the cell culture container can be placed is provided in the first space, and the work table portion is provided with a plurality of air passage holes through which air supplied from the first space filter unit to the first space can pass.

17. The cell culture device according to claim 4, wherein the operating device is provided with a holder portion to which different experimental equipment can be attached.

18. The cell culture device according to claim 4, wherein the operation device is provided with a push button drive mechanism capable of operating push buttons of different experimental equipment.

19. A cell culture device as described in claim 4, wherein the operating device is capable of being fitted with experimental equipment, the experimental equipment is capable of automatically fitting a plurality of tubular equipment, and the operating device is provided with a fall prevention mechanism for preventing the tubular equipment from falling.

20. A cell culture device as described in claim 4, wherein the operating device is capable of mounting experimental equipment, the experimental equipment is capable of automatically mounting a tubular equipment, and the device is provided with a mounting force enhancing section that supports the experimental equipment from a direction opposite to the direction in which the tubular equipment is pressed against the experimental equipment when the tubular equipment is mounted on the experimental equipment, and compensates for the force with which the tubular equipment is pressed against the experimental equipment.

21. A cell culture device according to any one of claims 1 to 3, comprising an incubator in the second space, the incubator having a door that opens and closes horizontally, and an air cylinder that generates a force to open and close the door.

22. A cell culture device according to any one of claims 1 to 3, wherein at least one of the first operating unit and the second operating unit performs an up-and-down rocking motion while gripping the reservoir in the first space.

23. A cell culture device according to any one of claims 1 to 3, wherein the first operating section is provided with a waste liquid pipe through which waste liquid passes, and the waste liquid pipe is positioned outside the first operating section.

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