JP6517510B2 - Cell processing method - Google Patents

Description

  The present invention relates to a cell processing method.

  In recent years, attempts have been made to implant various cells for the repair of damaged tissues and the like. For example, use of fetal cardiac muscle cells, skeletal myoblasts, mesenchymal stem cells, cardiac stem cells, ES cells, etc. is attempted to repair myocardial tissue damaged by ischemic heart disease such as angina pectoris or myocardial infarction. (Non-Patent Document 1).

As part of such attempts, cell structures formed using scaffolds and sheet-like cell cultures in which cells are formed into sheets have been developed (patent documents 1 to 5, non-patent document 2) .
For therapeutic application of sheet-like cell cultures, use of cultured epidermal sheet for skin damage caused by burns, use of corneal epithelial sheet-like cell culture for corneal damage, oral mucosal sheet for endoscopic resection of esophageal cancer Studies such as the use of cell cultures are underway.

  However, such sheet-like cell cultures and cell structures need to be produced in a clean environment and have a high level of knowledge and skills in production. Therefore, these cell cultures are conventionally manufactured manually by workers with specialized knowledge in a clean room called a cell culture center (CPC: Cell Processing Center), and the cost of manufacturing such cell cultures And the labor involved in manufacturing has been enormous.

  Therefore, there has been proposed an automatic cell culture apparatus which performs work on culture of these cells by a multijoint robot (Patent Document 6).

Japanese Patent Application Publication No. 2007-528755 WO 2006/080434 JP 2005-229869 A JP, 2010-81829, A Unexamined-Japanese-Patent No. 2010-226991 JP, 2006-149268, A

Haraguchi et al., Stem Cells Trans. Med. 2012 Feb; 1 (2): 136-41 Ohashi et al., Transplant Proc. 2011 Nov; 43 (9): 3188-91

  In the case where the present inventors carry out researches in this technical field and all the work relating to cell culture is automatically performed by a robot, the configuration of the device becomes complicated, and as a result, maintenance performance and system expandability are realized. We focused on the problem of being inferior and not being able to operate efficiently. And, in order to solve this problem, a system that can perform the whole operation in combination with the manual operation in an integrated manner rather than relying on a robot can be made more rationally so that the characteristic features of the cell culture technology can be flexibly dealt with. We came to the knowledge that it could contribute to culture technology.

  Therefore, an object of the present invention is to enable efficient production of cell cultures by a rational combination of robot operation and manual work, and a cell processing system having a relatively simple configuration, and efficiently cell cultures Cell processing method, liquid transfer method, and grasping tool for producing the same.

The above object can be achieved by a rational combination of robot operation and manual operation, and the object is achieved, for example, by the following means (1) to (30).
(1) A system used for processing cells using a container,
A base provided with a plurality of processing areas for processing using the container and a loading / unloading area capable of carrying in / out an object used for processing;
A robot provided on the base and having a gripping tool capable of gripping at least a part of the container;
A housing which covers the processing area, the robot, and at least a part of the loading / unloading area, and which can maintain the cleanliness of the inside;
One or more working units disposed on the housing or the base and configured to allow manual operation in the housing from outside the housing;
Have
The gripper of the robot is configured to be able to reach the processing area;
The housing is configured to be able to open and close a portion adjacent to the loading / unloading area,
In the working unit, the workable area overlaps with the processing area and / or the loading / unloading area, and between the processing area and the loading / unloading area via the working unit. A cell processing system that is configured to allow movement of objects used in processing.

(2) The cell processing system according to (1), wherein a plurality of the work units are provided, and workable areas of the adjacent work units overlap with each other.
(3) The cell processing system according to (1) or (2), wherein preparation for processing in the processing region manually can be performed by the working unit.
(4) The cell processing system according to any one of (1) to (3), wherein the processing is performed by a robot.

(5) The cell processing system according to any one of (1) to (4), wherein the working unit is a glove.
(6) The cell processing system according to any one of (1) to (5), wherein at least one of the processing regions is a region for dispensing liquid to the container.
(7) The cell processing system according to any one of (1) to (6), wherein at least one of the processing areas is an area for discarding liquid in the container.

(8) The cell processing system according to (6) or (7), wherein the liquid is a culture medium.
(9) The container has a container body and a lid,
The cell processing system according to any one of (1) to (8), wherein at least one of the processing areas is an area for desorption of the lid relative to the container body.
(10) Used to exchange the medium in the container, to dispense the medium into the container, to inoculate the cells to the container and / or to detach the cell tissue formed on the inner wall of the container, (1) The cell processing system in any one of-(9).

(11) A system used for processing cells using a container,
A base provided with one or more processing areas for processing using the container and a loading / unloading area of the container;
A robot provided on the base and having a gripping tool capable of gripping at least a part of the container;
A housing that covers at least the processing area and the robot and can maintain the inside of the housing;
Have
The gripper of the robot is configured to be able to reach the processing area,
The grasping tool includes a first grasping portion, and a second grasping portion which is disposed on the distal end side of the first grasping portion and has a larger distance of the grasping surface than the first grasping portion. Have
A part of the second grip portion is omitted near the central axis of the first grip portion.
Cell processing system.

(12) A holding tool for a robot used to operate a container for processing cells,
A first grip portion,
And a second grip disposed at a distal end side of the first grip and having a larger separation distance of the gripping surface than the first grip.
The grip according to claim 1, wherein a part of the second grip portion is omitted in the vicinity of a central axis of the first grip portion.
(13) The holding tool according to (12), wherein the second holding unit is disposed at a position corresponding to a side end of the holding surface of the first holding unit.

(14) The gripper according to (12) or (13), wherein the second gripping portion is disposed at a position corresponding to both lateral end portions of the gripping surface of the first gripping portion.
(15) The holding tool according to any one of (12) to (14), wherein the first holding portion has a recess in the vicinity of the center of the holding surface in the axial direction.
(16) The grip according to any one of (12) to (15), wherein the first grip portion and / or the second grip portion has a non-slip portion disposed on the grip surface.

(17) A cell processing method for processing cells using a plurality of containers having a lid and a container body,
1) arranging n (where n is an integer of 2 or more) the containers whose order of processing is determined;
2) Remove the lid of the container to be processed to the i-th (where i is an integer, 2 ≦ i ≦ n) by the robot from the container body, and the container body of the i-th to-be-processed container Step of attaching to
3) performing the processing using the container to be processed i-th,
A cell processing method having:

(18) The cell processing method according to (17), wherein step 2) and step 3) are repeated until i becomes 2 to n.
(19) The cell processing method according to (17) or (18), wherein the robot operates not to pass over the opening of the container body from which the lid is removed.

(20) Furthermore, before step 2), the robot is configured to remove the lid of the container to be treated first from the container body by a robot and arrange the lid in the lid storage space, any of (17) to (19) Cell treatment method described in.
(21) After the process of step 3) is performed on the n-th treated container, the robot attaches the lid disposed in the lid storage to the container body of the container, in (17) to (20) The cell processing method as described in any one.

(22) The cell processing method according to any one of (17) to (21), wherein the treatment in step 3) is the disposal of the liquid from the container and / or the injection of the liquid into the container.
(23) The cell processing method according to (22), wherein the liquid is a culture medium.
(24) The treatment is replacement of the culture medium in the container, dispensing of the culture medium into the container, seeding of cells into the container, or exfoliation of cell tissue formed on the inner wall surface of the container (17) The cell processing method in any one of-(23).

(25) a) holding the container holding the liquid by the holding tool of the robot;
b) transferring the liquid in the container to a collection container by rotating the held container;
A method of liquid transfer in cell processing, wherein in step a) and b) the robot operates not to pass on the vertical line of the opening of the collection container.
(26) The holding tool is configured to be rotatable,
The liquid transfer method according to (25), wherein in step b), the container is rotated in the same direction about an axis parallel to the rotation axis of the holding tool.

(27) The liquid transfer method according to (25) or (26), wherein in step b), when the opening of the container is directed downward, the container is reciprocated up and down.
(28) The liquid transfer method according to any one of (25) to (27), wherein in step b) rotation of the container is performed with translational movement.

(29) The liquid transfer method according to any one of (25) to (28), wherein in step a), the container is gripped such that the gripper is not present on the vertical line of the opening of the container.
(30) The liquid transfer method according to any one of (25) to (29), wherein the liquid is a culture medium.

  As described above, according to the present invention, a cell processing system capable of efficiently producing a cell culture and having a relatively simple configuration, a cell processing method for efficiently producing a cell culture, and a liquid transfer method , And a gripping tool can be provided.

FIG. 1 is a schematic view of a cell processing system according to a first embodiment of the present invention. FIG. 2 is a cross-sectional view of the cell processing system shown in FIG. It is a perspective view of the robot with which the cell processing system shown in FIG. 1 is provided. It is the elements on larger scale of the holding | gripping tool of the robot with which the cell processing system shown in FIG. 1 is provided. It is a schematic diagram explaining operation | movement of the holding tool shown in FIG. It is a schematic diagram explaining operation | movement of the holding tool shown in FIG. It is a schematic diagram which shows an example of the container used in the cell processing system concerning 1st embodiment. It is a schematic diagram which shows an example of the cassette of the container used in the cell processing system concerning 1st embodiment. It is a flowchart explaining the cell processing method concerning 1st embodiment of this invention. It is a flowchart explaining the cell processing method concerning 1st embodiment of this invention.

It is a schematic diagram explaining the cell processing method concerning 1st embodiment of this invention. It is a schematic diagram explaining the liquid transfer method concerning 1st embodiment of this invention. It is a schematic diagram explaining the conventional liquid transfer method. It is a schematic diagram explaining the cell processing method concerning 1st embodiment of this invention. It is sectional drawing of the cell processing system concerning 2nd embodiment of this invention. It is sectional drawing of the cell processing system concerning 3rd embodiment of this invention. It is a schematic diagram which shows an example of the cassette of the container used in the cell processing system shown in FIG. It is a schematic diagram which shows the other modification of this invention. It is a schematic diagram which shows the other modification of this invention.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the drawings.
First Embodiment
First, the first embodiment of the present invention will be described.
1 is a schematic view of a cell processing system according to a first embodiment of the present invention, FIG. 2 is a cross-sectional view of the cell processing system shown in FIG. 1 taken along plane xx, and FIG. 3 is a robot provided in the cell processing system shown in FIG. 4 is a partial enlarged view of the holding tool of the robot provided in the cell processing system shown in FIG. 1, FIG. 5 and FIG. 6 are schematic diagrams for explaining the operation of the holding tool shown in FIG. Fig. 8 is a schematic view showing an example of a container used in the cell processing system according to the embodiment, and Fig. 8 is a schematic view showing an example of a cassette of the container used in the cell processing system according to the first embodiment. In the drawings of the present application, the sizes of the respective members are appropriately emphasized in order to facilitate the description, and the illustrated members do not indicate actual sizes.

  The cell processing system 1 shown in FIG. 1 is used for processing cells using the container 100, and in particular, when the cells are cultured using the container 100 to obtain a cell culture, the liquid from the container 100 is used. It is used for discharging L and injecting liquid L into the container 100 (dispensing). In the present embodiment, the liquid L is a culture medium, and the cell processing system 1 is a medium exchange system used to exchange the culture medium (liquid L) in the container 100.

  In addition, cells used for processing in the cell processing system 1 are not particularly limited, and examples thereof include cells collected from a subject and cryopreserved cells.

  More specifically, cells usable in the cell processing system 1 include, but are not limited to, for example, adherent cells (adherent cells). Examples of adherent cells include adherent somatic cells (for example, cardiac muscle cells, fibroblasts, epithelial cells, endothelial cells, hepatocytes, hepatocytes, pancreatic cells, renal cells, adrenal cells, periodontal ligament cells, gingival cells, periosteal cells, Skin cells, synoviocytes, chondrocytes, etc. and stem cells (eg, myoblasts, tissue stem cells such as cardiac stem cells), embryonic stem cells, pluripotent stem cells such as iPS (induced pluripotent stem) cells, mesenchymal stem cells, etc. And the like. Somatic cells may be differentiated from stem cells, in particular iPS cells. Examples of such cells include, for example, myoblasts (eg, skeletal myoblasts, etc.), mesenchymal stem cells (eg, bone marrow, adipose tissue, peripheral blood, skin, hair root, muscle tissue, endometrium, etc. Placenta, cord blood, etc.), cardiomyocytes, fibroblasts, cardiac stem cells, embryonic stem cells, iPS cells, synoviocytes, chondrocytes, epithelial cells (eg, oral mucosal epithelial cells, retinal pigment epithelial cells, nose) Mucosal epithelial cells), endothelial cells (eg, vascular endothelial cells), liver cells (eg, hepatic parenchymal cells), pancreatic cells (eg, pancreatic islet cells), renal cells, adrenal cells, periodontal membrane cells, gingival cells , Periosteum cells, skin cells and the like.

  Moreover, it is also possible to form a cell culture in which cells such as a sheet-like cell culture are connected to each other by cell culture including treatment using the cell processing system 1.

  As used herein, "sheet-like cell culture" refers to cells in which cells are linked to each other into a sheet. In sheet-like cell cultures, the cells may be linked to each other directly (including via cell components such as adhesion molecules) and / or via an mediator. The mediator is not particularly limited as long as it is a substance capable of at least physically (mechanically) connecting cells to each other, and examples include extracellular matrix and the like. The mediator is preferably of cell origin, in particular from cells constituting the sheet cell culture. The cells are at least physically (mechanically) linked, but may be further functionally linked, for example, chemically or electrically. The sheet-like cell culture is composed of one cell layer (monolayer), but is composed of two or more cell layers (laminate (multilayer), for example, two layers, three layers, 4 Layers, five layers, six layers, etc.).

  The sheet-like cell culture preferably does not contain a scaffold (support). Scaffolds may be used in the art to attach cells on and / or within their surface and maintain the physical integrity of sheet cell cultures, such as polyvinylidene difluoride (eg, Membranes and the like made of PVDF are known. In addition, the sheet-like cell culture preferably comprises only substances derived from cells constituting the sheet-like cell culture, and does not contain any other substances.

  The cells described above can be derived from any organism that can be treated by sheet cell culture. Such organisms include, but are not limited to, humans, non-human primates, dogs, cats, pigs, horses, goats, sheep, rodents (eg, mice, rats, hamsters, guinea pigs, etc.), rabbits, etc. Is included.

  Although only one type of cell may be used to form a sheet-like cell culture, two types may be used. When there are two or more types of cells forming a sheet-like cell culture, the ratio (purity) of the largest number of cells is preferably about 60% or more, preferably at the start of sheeting culture or at the end of sheet-like cell culture production. Is about 70% or more, more preferably about 75% or more.

  In the present embodiment, as shown in FIGS. 7 and 8, the container 100 is a cell culture flask, and is configured to be able to be screwed into the container body 110 having the opening 111 and the opening 111 of the container body 110 And a lid 120 capable of sealing the opening 111. The container body 110 has two main surfaces 112 and 113 as its side surfaces, and can culture cells with one of the main surfaces 112 and 113 as the lower surface.

  In the present embodiment, the cell processing system 1 operates a plurality of containers 100, but a cassette 200 as shown in FIG. 8 can be used in management and operation of the plurality of containers 100. The cassette 200 is a plate-like base provided with a plurality of recesses 201 on its main surface. Each concave portion 201 has a shape corresponding to the shape of the container body 110 so that the container 100 can be disposed with the lid 120 facing upward. Moreover, the recessed part 201 has lined so that the container 100 may be aligned so that the main surfaces 112 of the several container 100 may become parallel. Further, in the cassette 200, a fixing hole capable of engaging a fixing pin 127 described later is formed on the main surface opposite to the main surface on which the concave portion 201 is formed (not shown).

  The cell processing system 1 shown in FIGS. 1 and 2 includes a base 10, a robot 20, a housing 30, and a working unit 40.

  The base 10 is a workbench for processing cells in the cell processing system 1. As shown in FIG. 2, the base 10 has a rectangular shape in a plan view, and the loading / unloading area 11 is in the vicinity of one end of the base 10 except the loading / unloading area 11. A plurality of processing areas 12A to 12C are arranged on the table. Moreover, the base 10 has the operation part 13 in the side surface of the carrying in / out area | region 11 vicinity.

  The loading / unloading area 11 is an area used for loading / unloading an object used for processing of the container 100, the cassette 200, materials necessary for processing of cells, medicines, culture media, instruments, devices and the like. In the present embodiment, the loading / unloading area 11 is disposed below a space (clean space) 15 formed by a housing 30 which will be described later. And the worker who exists in the said external environment can arrange | position the thing used for a process on the carrying in / out area | region 11 via the shutter 32 of the housing | casing 30 mentioned later. In addition, the operator can appropriately perform work on the carry-in / out area 11 as needed.

  The processing areas 12A to 12C are disposed adjacent to the robot 20 and the working unit 40 described later. The processing areas 12A to 12C are areas for performing processing. In the processing areas 12A to 12C, objects to be used for processing are arranged in accordance with the contents of processing to be performed.

  Specifically, the processing area 12A is a dispensing area for dispensing liquid to the container 100. Therefore, in the processing area 12A, the dispensing pump 121, the culture medium storage container 122 for storing the culture medium, the tube 123 for supplying the culture medium from the culture medium storage container 122 by the dispensing pump 121 to the container 100, and the liquid for the container 100 And a fluid volume sensor 124 for measuring the dispensing volume of the fluid.

  The processing area 12B is a medium recovery area for discarding and recovering the culture medium in the container 100, and a recovery container 125 for recovering the culture medium transferred from the container 100 and a sensor for measuring the recovery amount. And 126 are arranged. The collection container 125 is a bottle having a relatively large volume, and the sensor 126 is a weight sensor disposed below the collection container 125. The sensor is not limited to this, and may be, for example, an optical sensor that optically detects the amount of liquid.

  The processing area 12C is a lid detachment area for detachment of the lid 120 of the container 100, and the fixing pin 127 as a fixture for fixing the cassette 200 of the container 100 and the lid 120 detached from the container 100 A lid storage 128 for carrying is provided. The fixing pin 127 has a shape corresponding to the fixing hole of the cassette 200, and fixes the cassette 200 by engagement. The lid storage space 128 has a shape corresponding to the lid 120, and is configured to be able to be screwed with the lid 120.

  The operation unit 13 shown in FIG. 1 is configured to perform at least a part of operations for controlling the robot 20 and each device of the processing areas 12A to 12C in the cell processing system 1 and the atmosphere (environment) of the space 15 described later. It has various input units 131 and a display unit 132.

  The input unit 131 is configured to allow an operator to input an instruction to the cell processing system 1. In the input unit 131, the input instruction is transmitted to a control unit (not shown) in the base 10, and the control unit controls the cell processing system 1, more specifically, controls the robot 20 and the atmosphere. It is configured to be done. In the present embodiment, the input unit 131 is configured of a plurality of buttons and knobs, but is not limited to this. The input unit 131 is not limited to this. A pointing device such as a mouse, a trackball, or a pen tablet, a keyboard, a touch panel, or an input A connection terminal such as an output or input / output terminal, a joystick, a three-dimensional haptic / force sense interface device or the like can be appropriately configured singly or in combination.

  The display unit 132 is a display that displays information on the cell processing system 1 such as the state of the cell processing system 1 and the content of the input instruction. The display unit 132 is configured to be communicable with the control unit, and can display information according to an instruction from the control unit. In the present embodiment, the display unit 132 is a display, but the present invention is not limited to this, and the display unit 132 may be a lamp, a touch panel, or the like, or they may be combined. Good.

  Further, an intake port 14 is provided in the base 10 in the vicinity of a shutter 32 described later of the loading / unloading area 11. The air in the clean space 15 to be described later is sucked by the air inlet 14 to bring the clean space 15 into a reduced pressure state, thereby preventing the occurrence of unintended leakage outside the cell processing system 1. In addition, an air curtain is formed in the vicinity of the shutter 32 by the air flow generated between the air inlet 14 and the air inlet described later, and foreign matter is prevented from being mixed into the clean space 15 from outside the cell processing system 1 . The air aspirated at the air inlet 14 is appropriately sterilized by a sterilizing means (not shown) such as a HEPA filter installed in the cell processing system 1 and discharged out of the cell processing system 1.

  As shown in FIG. 3, the robot 20 is a vertical articulated robot disposed near the center of the base 10. The robot 20 has six axes. The robot 20 is connected to the base 21 rotatable with respect to the base 10 and the base 21, and the first arm 22 and the first arm 22 tiltable with respect to the vertical axis of the pivoting direction of the base 21. A second arm proximal end 23 connected to the distal end side and tiltable with respect to the first arm and a distal end side of the second arm proximal end 23 are connected to the axial direction of the second arm proximal end 23 Connected to the hand portion 25 which is connected to the tip end side of the rotatable second arm tip 24 and the tip end side of the second arm tip 24 and can be tilted with respect to the axial direction of the second arm tip 24; And a gripper (gripper) 26 that has been The hand unit 25 is configured to be rotatable along its axial direction.

  Further, the robot 20 is configured such that the grasping tool 26 can reach the area represented by the alternate long and short dash line in FIG. 2 and therefore can reach the desired position of each of the processing areas 12A to 12C in a desired posture. Thus, work in the processing areas 12A to 12C by the robot 20 is possible.

  In addition, the robot 20 is connected to the controller 300 and the control terminal 400 disposed outside the cell processing system 1 shown in FIG. 1 and can automatically operate according to an instruction input from the control terminal 400. .

  With such a configuration, the robot 20 can determine the position and orientation of the holding tool 26, rotate the holding tool 26, and open and close the holding tool 26, thereby holding the container 100 by the holding tool 26 and operating it. it can. More specifically, the container 100 can be transferred, tilted, and rotated by holding the container 100 with the holding tool 26, and the cover 120 can be held by holding the lid 120 and rotating the holding tool 26. It can be removed from or attached to the container body 110.

Here, the gripping tool 26 will be described in more detail.
The grasping tool 26 shown in FIG. 4 is a parallel gripper, and the grasping tool main body 261 whose base end side is connected to the hand 25 and the pair of guide members 262 which are disposed on the tip end side of the grasping tool main body 261 And a pair of claws (fingers) 263 fixed to the guide member 262.

  The gripper main body 261 includes an actuator and a linear guide (neither is shown) in its inside, and operates the guide member 262 by external instructions and power supply such as electric power. The sliding direction of the guide member 262 is fixed by the linear guide, and accurate approach or separation of the guide members 262 is possible.

  Each of the pair of claws 263 is fixed one by one to each of the pair of guide members 262, and can approach or separate from each other according to the operation of the guide members 262. Thereby, the claw portion 263 can grip at least a part of the container 100.

  The claw portion 263 includes a first grip portion 264 provided on the proximal end side and a second grip portion 265 provided on the distal end side (distal end side) of the first grip portion 264. Have. Further, the second gripping portion 265 is configured such that the separation distance between the gripping surfaces 267 is larger than that of the gripping surfaces 266 of the first gripping portion 264. The claw portion 263 can reduce the stroke of the grasping tool 26 and reduce the size of the grasping tool 26 by having two grasping portions having different separation distances, that is, different grasping widths. It can hold an object (workpiece). As a result, as shown in FIGS. 6 (a) to 6 (c), the lid 120 of the container 100 is gripped by the first grip portion 264, while on the other hand, as shown in FIGS. 5 (a) to 5 (c). As shown, the second grip portion 265 can grip the container body 110 of the container 100. Further, by rotating the first grip portion 264 together with the claw portion 263 in a state in which the lid 120 is gripped, removal of the lid 120 from the container main body 110 and attachment of the lid 120 to the container main body 110 become possible.

  In addition, a non-slip portion is disposed on the gripping surface 266 of the first gripping portion 264. As a result, the lid 120 can be held more reliably by the first gripping portion 264, and even when the lid 120 is rotated by the first gripping portion 264, the lid 120 can be held against the lid 120 by the first gripping portion 264. The rotational force can be transmitted more reliably. Further, as a result, for example, the gripping force by the first gripping portion 264 can be made relatively weak, and damage to the workpiece to be gripped by the lid 120 and the like can be prevented. The method of forming the non-slip portion is not particularly limited. For example, the non-slip portion is configured by disposing a high friction coefficient member such as rubber or elastomer on the gripping surface, and knurling is performed on the gripping surface 266 to achieve high friction and It is possible to adopt a method of forming by carrying out.

Further, as shown in FIG. 4, a part of the second grip portion 265 is omitted in the vicinity of the central axis l of the first grip portion 264. Thereby, when the lid 120 is gripped by the first grip portion 264 and the lid 120 is rotated with the first grip portion 264 about the central axis l, the second grip portion 265 is the container of the container 100. Interference with the main body 110 is prevented.
In the present specification, the central axis l is parallel to the main surfaces of the gripping surfaces 266 of the pair of first gripping portions 264 and extends from the proximal end side to the distal end side of the first gripping portions 264. , The central axis viewed from the pair of gripping surfaces 264.

  More specifically, in the present embodiment, the second grip portion 265 is disposed at a position corresponding to both lateral end portions of the grip surface 266 of the first grip portion 264. That is, it is comprised from four claws which project on the front end side from the side both ends of the 1st holding part 264, and it is comprised so that two points may be hold | gripped with two claws, respectively. With such a configuration, as shown in FIG. 6C, the second grip portion 265 is more reliably prevented from interfering with the container body 110. Further, as shown in FIG. 5C, since the second grip portion 265 can grip and fix the container body 110 at a plurality of positions, the container body 110 is gripped by the second grip portion 265. In this case, the container body 110 is prevented from rotating and tilting unintentionally. In addition, when the position of the second grip portion 265 is at both ends, the other of the second grip portion 265 is sufficiently against the rotational moment generated from one of the second grip portions 265 (for example, the lower side). It can be supported.

  The grip surface 267 of the second grip portion 265 is provided with a non-slip portion. Thereby, the container 100 can be held more reliably by the second holding portion 265. Further, even with a relatively weak gripping force, the workpiece such as the container 100 can be sufficiently gripped, and breakage of the workpiece such as the container 100 can be prevented.

  The housing 30 shown in FIGS. 1 and 2 covers the loading / unloading area 11 on the base 10 on the base 10, the processing areas 12A to 12C and the robot 20, and the space 15 on the base 10 is treated with cells. A ceiling that is configured to shield from the atmosphere outside the system 1 and that seals from above the space 15 formed by the side wall 31 and the shutter 32 and the side wall 31 and the shutter 32 erected near the periphery of the base 10 And a section 33.

The ceiling 33 incorporates a fan filter unit (not shown) in which a filter such as a HEPA filter and a fan are combined, and suctions air from the outside of the cell processing system 1 for sterilization and removal of foreign matter. Then, clean air is supplied onto the space 15 from the air supply port (not shown). Thus, the space 15 on the base 10 maintains the clean atmosphere by supplying clean air while blocking the atmosphere on the base 10 from the atmosphere outside the cell processing system 1 and the clean space 15 Become.
In the cell processing system 1, the cleanliness in the clean space 15 is in ISO class 1-9, preferably ISO class 1-8, more preferably ISO class 1-7, in accordance with ISO 14644-1. Can be configured to be

  The shutter 32 is a portion provided adjacent to the loading / unloading area 11 and is a slide shutter configured to be openable and closable. When the shutter 32 is closed, the clean space 15 is closed and the clean atmosphere is more reliably maintained. On the other hand, when the shutter 32 is opened, it becomes possible to move objects used for processing via the loading / unloading area 11 between the cell processing system 1 and the external environment, and a worker present in the external environment carries in -It becomes possible to work in the unloading area 11. The size of the opening formed by the shutter 32 is configured to be adjustable as appropriate.

Note that both of the side wall 31 and the shutter 32 constituting the housing 30 are formed using a transparent material, for example, a resin, and the inside of the housing 30 can be observed through these.
The working units 40A to 40D are tools and tools arranged along the side wall 31 of the housing 30 and configured to be able to work in the housing 30 manually from outside the housing 30, that is, in the clean space 15 is there. In the present embodiment, the working parts 40A to 40D are a pair of gloves arranged to penetrate the side wall 31. Thereby, the worker who exists outside the cell processing system 1 uses the working units 40A to 40D in the clean space 15 to transfer objects required for processing the cells using the container 100 and prepare for processing. It is possible to

  Further, workable areas of the working units 40A to 40D shown by dotted lines in FIG. 2, that is, work areas 41A to 41D overlap with any of the processing areas 12A to 12C and / or the loading / unloading area 11. ing. Specifically, in the working unit 40A, the work area 41A overlaps the loading / unloading area 11 and the processing areas 12A and 12B. In the working unit 40B, the work area 41B overlaps with the processing area 12B. In the working unit 40C, the work area 41C overlaps the loading / unloading area 11 and the processing area 12C. In the working unit 40D, the work area 41D overlaps with the processing area 12C.

  Further, the work areas 41B and 41D of the working units 40B and 40D do not overlap with the loading / unloading area 11, but overlap with the work areas 41A and 41C of the adjacent working units 40A and 40C. Thereby, although the work areas 41B and 41D do not overlap the loading / unloading area 11, the work areas 41B and 40D are used for processing via the work areas 41A and 41C of the overlapping working units 40A and 40C. It is configured to be able to move objects.

  With the working units 40A to 40D as described above, preparation for processing manually in any of the processing regions 12A to 12C, that is, loading and unloading of an object used for processing, installation of the object, and the like are possible. Although preparation for each process is generally complicated, by manually performing such an operation, the device configuration of the cell processing system 1 can be made relatively simple. Also, for example, for confirmation of the amount of culture medium necessary for replacement, confirmation of the installation status of each device used for processing, etc., manually performed by an operator rather than introducing an apparatus equipped with a sensor etc. Is simple. On the other hand, the robot 20 can perform the work quickly and accurately for relatively simple processes that require repeated operations such as removal and attachment of the lid 120, disposal of liquid (medium), and dispensing.

  In the cell processing system 1, the cell processing system 1 including the robot 20 automatically performs a relatively simple operation that needs to be repeated, and the worker is configured to perform other operations. By sharing the work performed in this way between the worker and the robot 20 according to the type thereof, the work including the processing performed in the cell processing system 1 can be streamlined, and the device configuration of the cell processing system 1 can be It can be relatively simple.

  In particular, the grasping tool 26 has the first grasping portion 264 and the second grasping portion 265 having different separation distances as described above, and a part of the second grasping portion 265 is a part of the first grasping portion 264. When omitted in the vicinity of the central axis l, workpieces having different sizes such as the container body 110 and the lid 120 can be gripped by the same gripping tool 26 and the lid 120 is rotated by the first gripping portion 264 Also in the second embodiment, interference between the second grip portion 265 and the container body 110 is prevented. As a result, a plurality of robots are installed for workpieces of different sizes, and the mechanism of the gripping tool is enlarged to increase the stroke of the gripping tool, and as a result, the size of the entire robot is prevented from increasing. Be done. Therefore, the configuration of the cell processing system 1 can be simplified by adopting a configuration such as the gripping tool 26.

  Next, the cell processing method and the liquid transfer method of the present embodiment using the cell processing system 1 described above will be described. 9 and 10 are flowcharts for explaining the cell processing method according to the first embodiment of the present invention, FIG. 11 is a schematic view for explaining the cell processing method according to the first embodiment of the present invention, and FIG. Fig. 13 is a schematic view illustrating a liquid transfer method according to one embodiment, Fig. 13 is a schematic view illustrating a conventional liquid transfer method, and Fig. 14 is a schematic view illustrating a cell processing method according to a first embodiment of the present invention. .

  In addition, since the cell processing system 1 is a thing used for replacement | exchange of a culture medium, in this embodiment, the liquid to replace | exchange is a culture medium. In the container 100 to be used, a sheet-like cell culture (cell tissue) 114 cultured in the medium L is described as being carried (adhered) on the inner wall surface of the main surface 113. .

In addition, the cell processing method of this embodiment relates to cell processing,
1) arranging n containers (where n is an integer of 2 or more) for which the order of processing has been determined;
2) Remove the lid of the container to be processed to the i-th (where i is an integer, 2 ≦ i ≦ n) by the robot from the container body, and the container body of the i-th to-be-processed container Step of attaching to
3) performing processing using the i-th treated container;
Have.

Moreover, the liquid transfer method of this embodiment is
a) holding a container holding a liquid by a robot holding tool;
b) transferring the liquid in the container to the recovery container by rotating the gripped container;
In the steps a) and b), the robot operates so as not to pass on the vertical line of the opening of the collection container.

The details will be described below.
First, the cell processing system 1 and peripheral systems (for example, the controller 300 and the control terminal 400) used for the cell processing system 1 are powered on to activate the cell processing system 1 (S-1).
Next, in the processing area 12A which is a dispensing area, equipment for performing dispensing and installation of materials are prepared (S-2). More specifically, the base material and the material are disposed on the loading / unloading area 11, and then the worker directly or the working unit 40A in the loading / unloading area 11 dispenses the dispensing pump 121, the culture medium storage container 122, the tube 123, the liquid amount sensor 124 is installed. After installation, perform priming as needed.

  Next, installation and preparation of equipment for recovering the culture medium are performed in the processing area 12B which is the culture medium recovery area (S-3). Specifically, the recovery container 125 and the sensor 126 are disposed in the loading / unloading area 11, and thereafter, they are transferred to the processing area 12B by the working unit 40A. Thereafter, the recovery container 125 and the sensor 126 are installed by the working unit 40A or the working unit 40B.

Next, in the treatment area 12C which is a lid detachment area, preparation for lid detachment is performed (S-4). Specifically, a plurality of containers 100 containing a culture medium are arranged in the cassette 200, and the cassette 200 is once arranged in the loading / unloading area 11. Thereafter, the cassette 200 is transferred to the processing area 12C by the working unit 40C. Thereafter, the cassette 200 is fixed to the fixing pin 127 by the working unit 40C or the working unit 40D to be fixed to the processing region 12C.
In addition, each device / equipment in the processing area 12A which is the dispensing area and the processing area 12B which is the culture medium recovery area is also fixed by a fixing pin or the like in a range having a predetermined positioning accuracy as needed.

  Further, in the present embodiment, the robot 20 is configured to determine the priority of the container 100 to be processed according to the position of the recess 201 of the cassette 200. Thus, by placing the containers 100 in the cassette 200, the order in which the containers 100 are processed is determined. Then, by fixing the cassette 200 to the processing area 12C, step 1) according to the present embodiment can be performed.

Next, an instruction is input by the control terminal 400, the controller 300 is operated (S-5), and the automatic processing by the cell processing system 1 including the robot 20 is executed (S-6). Thereby, the cell processing system 1 including the robot 20 automatically performs a predetermined operation according to the instruction and exchanges the culture medium in each container 100.
The operation (S-6) of the robot 20 is performed along the flowchart shown in FIG.

  First, the lid 120 of the container 100 to be processed at the i-th (initially i = 1) is removed from the container body 110. Specifically, the gripper 26 is moved by the robot onto the container 100 to be processed on the cassette 200 (A-1). Next, the lid 120 is gripped by the first grip portion 264 of the grip tool 26 (A-2). Next, the lid 120 is rotated a predetermined number of times by rotating the gripping tool 26, and the screwing between the lid 120 and the container body 110 is released (A-3). In general, the rotational direction is counterclockwise when the lid 120 is viewed from the gripping tool 26. Also, the number of rotations is set to a number sufficient to release the screwing. Next, the lid 120 in a state in which the screwing is released is lifted upward by the gripping tool 26. Thereby, the lid 120 is removed from the container body 110.

Next, the lid 120 removed by the holding tool 26 is placed at a predetermined position.
When i = 1, as shown in FIG. 11A, the holding tool 26 holding the lid 120 is moved above the lid storage space 128 (A-4), and the lid storage space 128 is in contact with the lid 120 The lid storage space 128 and the lid 120 are screwed together (A-5). Thereafter, the gripping of the lid 120 by the gripping tool 26 is released.

  On the other hand, when i is 2 or more, as shown to FIG.11 (b), (c), the removed lid 120 is attached to the container main body 110 processed to i -1st (step 2). For example, when i is 2, as shown in FIG. 11 (b), the lid 120 of the container 100 to be processed second is attached to the first processed container body 110, as shown in FIG. 11 (c) Then, the lid 120 of the third processing container 100 is attached to the second processing container body 110.

  Thereby, an operation of removing the lid 120 for processing and an operation of attaching the lid 120 after processing can be performed simultaneously. For this reason, when the lid 120 is removed, it is possible to omit performing the operation of once placing it in the lid storage space 128 and then attaching it to the container main body 110 from the lid storage space 128 each time. Thus, the operating path and working time required for removal and attachment of the lid 120 can be reduced and contamination is prevented because the time for which the inner surface of the lid 120 is exposed to the external environment is shortened. As a result, the reliability of the whole cell processing method using the cell processing system 1 is improved.

  Specifically, the holding tool 26 holding the lid 120 is moved to the upper side of the opening of the container body 110 that has been processed i-1st (A-6), and the opening is brought into contact with the lid 120 The container body 110 and the lid 120 are screwed together by rotating the container body 110 a predetermined number of times (A-7). Thereafter, the gripping of the lid 120 by the gripping tool 26 is released.

  Next, processing is performed on the container 100 from which the lid 120 has been removed (step 3). In the present embodiment, the culture medium (liquid) L in the container body 110 is discarded, and the culture medium in the container 100 is exchanged by injecting fresh medium into the container 100.

In the processing, first, the container body 110 is gripped (step a)). Specifically, the holding tool 26 is moved to the side of the container body 110 (A-8), and the container body 110 is held by the second holding part 262 of the holding tool 26 from the side (A-9). In addition, when the gripping tool 26 grips the side of the container body 110 in this manner, the robot 20 including the gripping tool 26 is prevented from passing over the opening of the container body 110. Also, when moving the gripping tool 26 to the side of the container body 110, it is preferable to move the robot 20 including the gripping tool 26 so as not to pass through the opening of the container body 110. As a result, dust and the like attached to the robot 20 is prevented from falling unintentionally into the container body 110.
Thereafter, the container body 110 is transferred to the vicinity of the collection container 125 of the processing area 12B which is the culture medium collection area (A-10).

  Next, the culture medium L in the container body 110 is transferred to the collection container 125 by rotating the held container body 110 (step b), A-11). In this embodiment, as shown in FIGS. 12A to 12G, the rotation of the container body 110 causes the container body 110 to rotate in the same direction with an axis parallel to the rotation axis of the holding tool 26 as a central axis. By doing.

  Generally, when transferring the culture medium L from the container body 110 to the collection container 125 manually, as shown in FIGS. 13 (a) to 13 (e), when the container body 110 is once tilted to discharge the culture medium L. Normally, the opening 111 of the container body 110 is directed vertically upward by returning the container body 110 in the opposite direction to the direction in which the container body 110 is inclined (FIG. 13 (d)). In this case, the culture medium L tends to remain near the inclined lower side of the opening 111 of the container body 110, and so-called dripping may occur when the culture medium L drips from the opening 111 of the container body 110 to the outside of the opening 111 (FIG. e)). In such a case, contamination in the container 110 starting from the medium L that has flowed out due to dripping tends to occur.

On the other hand, in the present embodiment, the culture medium L once remaining in the vicinity of the lower side of the inclined opening 111 is positioned in the vicinity of the upper part of the opening 111 because the opening 111 is also reversed by rotating the container body 110 in the same direction. (FIG. 12 (e), (f)). As a result, the culture medium L is transferred to the outer peripheral wall surface of the opening 111 to prevent the occurrence of liquid dripping (FIG. 12 (g)).
The container main body 110 is configured to be rotated by the robot 20 about an axis parallel to the rotation axis of the holding tool 26 as a central axis, but by using such an axis as the central axis, 360 by the robot 20 Rotation of the container body 110 in the same direction of ° is possible.

  Also, the rotation of the container body 110 may be performed with a translational movement. As a result, the opening 111 of the container body 110 can be disposed in the vicinity of the opening of the collection container 125, and the transfer of the culture medium L to the collection container 125 becomes easier and more reliable.

  Furthermore, it is preferable that the container main body 110 be reciprocated up and down when the container main body 110 is rotated and the opening 111 is directed to the lower vicinity in the vertical direction. By performing such an operation, the culture medium L can be more reliably transferred from the container body 110 to the collection container 125.

  Further, the sensor 126 located below the collection container 125 can measure the amount of the collected culture medium L. For this reason, it is possible to estimate from the amount of the culture medium L, such as whether or not the medium L has been properly transferred, and whether there is any abnormality in the cell culture in the container main body 110.

  In the present embodiment, the robot 20 is configured to operate so as not to pass along the vertical line of the opening of the collection container 125 in the above-mentioned disposal processing of the culture medium, that is, in steps a) and b). There is. As a result, it is possible to prevent foreign matter such as dust and abrasion powder adhering to the robot 20 from being mixed into the collection container 125. When analyzing the medium in the recovery container 125 to analyze whether the cell culture in the container 100 is performed normally, the presence of such foreign matter may inhibit the analysis, but in this embodiment, By preventing the contamination of such foreign substances, the cell processing system 1 and the cell processing method become highly reliable.

  As described above, after the medium L is transferred from the container body 110 to the collection container 125, the fresh medium L is dispensed to the container body 110. Specifically, first, the container body 110 is transferred to the processing region 12A, which is a dispensing region, while being held by the holding tool 26 (A-12). Next, the dispensing pump 121 is operated to dispense a predetermined amount of fresh culture medium L into the container body 110 via the tube 123 (A-13). The dispensing amount is measured over time by the liquid amount sensor 124, whereby the final dispensing amount is controlled.

  In addition, it is preferable to perform dispensing so that the culture medium L supplied from the tube 123 does not contact the cell culture 114 in the container main body 110 directly. For example, as shown in FIG. 14, when the cell culture 114 is cultured and attached on one main surface 113 of the container main body 110, the main surface 113 is on the upper surface and the main surface 112 is on the lower surface. It is preferable to supply the culture medium L from the opening 111 while the container main body 110 is inclined. This prevents inadvertent damage or detachment of the cell culture 114.

  Next, the container body 110 is transferred to the upper side of the cassette 200 (A-14), and then placed below the recess 201 of the cassette 200 (A-15).

  By repeating the above A-1 to A-13 until i becomes 1 to n which is the number of containers 100, the medium L of each container 100 can be exchanged automatically.

As soon as the container body 110 into which fresh culture medium L has been dispensed is placed in the recess 201, the lid 120 of the container 100 to be processed next is attached (A-7).
Further, when there is no container 100 to be processed next, that is, for the n-th container 100 to be processed, the lid 120 disposed at the lid storage 128 is attached.

  Specifically, the gripping tool 26 is moved onto the lid storage space 128 (A-16), and the lid 120 disposed in the lid storage space 128 is gripped by the second grip portion 264 of the gripping tool 26 (A-17) ). Next, the lid 120 is rotated by rotating the gripper 26, and the screwing between the lid storage space 128 and the lid 120 is released (A-18). Next, the lid 120 is disposed on the container body 110, and the gripping tool 26 is rotated together with the lid 120 in a state where the lid 120 is in contact with the opening 111 of the container body 110, and the lid 120 and the container body 110 are screwed together. (A-19).

  In the case where automatic processing using the robot 20 described above is performed under certain conditions, for example, when processing is completed for all the containers 100 on the cassette 200, when a culture medium of a predetermined amount or more is transferred to the collection container 125, When the medium L in the medium storage container 122 becomes less than a predetermined amount, the operation is stopped if any other unexpected event occurs, and the automatic operation is continued if such a condition does not occur. (S-7).

In this case, for example, the worker first determines whether all the containers 100 on the cassette 200 have been processed, and whether there is another container 100 to be processed that is not on the cell processing system 1. (S-8).
If the container 100 to be treated is present, then it is confirmed whether or not the medium L is present in the medium storage container 122 (S-9). If not, the medium L is added to the culture container 122 , Or replace the medium storage container 122 with one filled with a new medium L (S-10).

Next, it is confirmed whether a predetermined amount of culture medium L exists in the collection container 125 (S-11), and if it exists, the culture medium L is transferred to another container and discarded, or the collection container 125 is removed. It is replaced with a new collection container 125 (S-12).
Next, the cassette 200 is collected, and the processed container 100 is collected, and the remaining containers 100 are added to the cassette 200, and the above S-4 is executed.

When there is no container 100 to be processed in S-7, the equipment for dispensing and the material are removed and removed in the processing area 12A (S-13), and the collection is performed in the processing area 12B. The discarded culture medium L is discarded, and the equipment is removed (S-14), and the cassette 200 is removed in the processing area 12C (S-15).
Thereafter, the power of the cell processing system 1 is turned off, and the operation is completed (S-16).

As mentioned above, according to the method concerning this embodiment, processing of a cell can be performed efficiently.
In particular, in the disposal processing of the culture medium, the robot 20 is configured to operate so as not to pass along the vertical line of the opening of the collection container 125, thereby facilitating the analysis of the collected culture medium L and reliance on cell processing It is possible to improve the quality.
Further, in particular, by simultaneously performing the operation of removing the lid 120 for processing and the operation of attaching the lid 120 after processing, it is possible to shorten the operation path and operation time required for removing and mounting the lid 120 and Contamination is prevented because the time during which the inner surface of the metal is exposed to the external environment is shortened. As a result, the reliability of the whole cell processing method using the cell processing system 1 is improved.

Second Embodiment
Next, a second embodiment of the present invention will be described.
FIG. 15 is a cross-sectional view of a cell processing system according to a second embodiment of the present invention. In the figure, the same components as those of the cell processing system 1 are denoted by the same reference numerals.

Hereinafter, differences from the first embodiment of the present embodiment will be described in detail, and the description of the same matters will be omitted.
The cell processing system 1A according to the present embodiment shown in FIG. 15 is mainly a system for detaching the cell culture cultured in the container 100, and thus the cell processing system 1 according to the first embodiment and the cell processing system 1 according to the first embodiment. It is different.

  The base 10A in this embodiment has a processing area 12D for dispensing a buffer solution at the same position instead of the processing area 12A which is a dispensing area of culture medium, and a loading / unloading area 11 of the base 10A. A treatment area 12E for dispensing the cell dissociating agent is disposed on the far side of the screen.

  Dispensing pumps 121A and 121B, storage containers 122A and 122B, tubes 123A and 123B, and liquid amount sensors 124A and 124B are disposed in the processing regions 12D and 12E, respectively. Dispensing pumps 121A, 121B, storage containers 122A, 122B, tubes 123A, 123B, and liquid amount sensors 124A, 124B respectively, except for the use of different liquids, the dispensing pump 121, culture medium container 122, tubes 123, liquid amount It has the same configuration as the sensor 124.

The buffer solution to be dispensed in the treatment area 12D is not particularly limited, but acetate buffer, phosphate buffer, citrate buffer, borate buffer, tartrate buffer, Tris buffer, phosphate buffered saline Water etc. are mentioned.
The cell dissociating agent to be dispensed in the treated area 12E is not particularly limited, and examples thereof include collagenase, trypsin, dispase, ethylenediaminetetraacetic acid (EDTA), actase and the like. Also, the cell dissociation agent may be a liquid composition in which these components are dissolved or dispersed.

In addition, a working unit 40E is installed at the center on the opposite side to the loading / unloading area 11 of the base 10A, that is, at the center sidewall on the back side as viewed from the loading / unloading area 11.
In the working unit 40E, the working area 41E overlaps with the working area 41B of the working unit 40B and the working area 41D of the working unit 40D. Thus, the working unit 40E is configured to be able to move objects used for processing between the working unit 40A and the working unit 40B. For this reason, it is possible to receive an object to be used for processing from the loading / unloading area 11 via the working units 40A and 40B or the working units 40C and 40D. It is also possible to deliver an object from the working unit 40B or 40D to the working unit 40D or 40B.

  Further, in the working units 40B and 40E, the work areas 41B and 41E overlap with the processing area 12E, and work in the processing area 12E is configured to be possible. Therefore, in such a cell processing system 1A, the work in the processing area 12D is performed from the loading / unloading area 11 or using the working unit 40A, and the work in the processing area 12E is performed using the working unit 40B or the working unit 40E. It is possible.

  Next, the cell processing method of the present embodiment using the cell processing system 1A described above will be described. In the method of this embodiment, the processing in the processing regions 12D and 12E is performed instead of the processing in the processing region 12A as compared with the method of the first embodiment. Therefore, this point will be mainly described, and the same matters will not be described.

  As described above, since the cell processing system 1A has the processing regions 12D and 12E instead of the processing region 12A, instead of the work in the processing region 12A of the S-2 in the first embodiment described above, In the processing regions 12D and 12E, equipment and materials for dispensing the buffer solution and the cell dissociation agent are provided and prepared. Similarly, in place of the work in the processing area 12A of S-9 and S-10 in the first embodiment described above, a buffer solution and a cell dissociation agent are added as necessary in the processing areas 12D and 12E. Also, in place of the work in the processing area 12A of S-13 in the first embodiment described above, in the processing areas 12D and 12E, equipment for dispensing buffer solution and cell dissociation agent, removal and removal of materials Do.

Further, the automatic operation by the cell processing system 1A is performed in the following order.
First, the lid of the container 100 is removed by the same operation as A-1 to A-7 of the first embodiment.

Next, the medium L present in the container body 110 is transferred to the collection container 125 by the same operation as A-8 to A-11 of the first embodiment.
Next, in the processing area 12D, the buffer solution is dispensed into the container body 110. This operation can be performed in the same manner as A-12 and A-13 of the first embodiment.

  The aliquoted buffer is then used to rinse (rinse) the cell culture 114 present in the container body 110. This operation is performed, for example, by rotating the container main body 110 so that the main surface 113 of the container main body 110 is the lower surface using the holding tool 26 and then vibrating (reciprocating) the container main body 110 horizontally. be able to.

Next, in the same operation as A-8 to A-11 of the first embodiment, the buffer solution (rinsing solution after rinse) present in the container body 110 is transferred to the recovery container 125.
Next, in the processing area 12E, the cell dissociation agent is dispensed into the container body 110. This operation can be performed in the same manner as A-12 and A-13 of the first embodiment.

Next, the container 100 is placed on the cassette 200 by the same operation as A-14 and A-15 in the first embodiment.
The above operation is repeated, and after all the containers 100 have been treated, a lid is attached to the container body 110 which has been treated in the same manner as the operations A-16 to A-19.

Other operations can be performed in the same manner as the method of the first embodiment described above.
In addition, each container 100 that has been subjected to the above-described processing can be subjected to a cell dissociation reaction by the worker.
As described above, also by the cell processing system and method according to the present embodiment, the same effect as that of the first embodiment can be obtained.

Third Embodiment
Next, a third embodiment of the present invention will be described.
FIG. 16 is a cross-sectional view of a cell processing system according to a third embodiment of the present invention, and FIG. 17 is a schematic view showing an example of a cassette of a container used in the cell processing system shown in FIG. In the figure, the same components as those of the cell processing system 1 are denoted by the same reference numerals.

Hereinafter, differences from the first embodiment of the present embodiment will be described in detail, and the description of the same matters will be omitted.
The cell processing system 1B according to this embodiment shown in FIG. 16 is different from the cell processing system 1 according to the first embodiment in that the system is mainly a system for seeding cells in the container 100.

  The base 10B in this embodiment has a treatment area 12F for seeding cells at the same position, instead of the treatment area 12A which is a dispensing area of culture medium, for lid desorption at a position similar to the treatment area 12C. In the processing area 12G of the present invention, the processing area 12H as a place for placing the container 100 is disposed in the loading / unloading area 11, respectively, while the processing area 12B as a culture medium recovery area is omitted.

In the processing area 12F, a dispensing pump 121C, a storage container 122C, a tube 123C, and a liquid amount sensor 124C are disposed. The dispensing pump 121C, the storage container 122C, the tube 123C, and the liquid amount sensor 124C each have the same configuration as the dispensing pump 121, the medium storage container 122, the tube 123, and the liquid amount sensor 124 except that the liquid used is different. doing.
The liquid to be dispensed in the treatment area 12F is not particularly limited as long as it contains cells, and is, for example, a suspension in which the above-described cells are suspended in a liquid such as a culture medium or a buffer solution.

  In addition to the lid storage space 128, the processing area 12G is provided with a fixing base 129. The fixing table 129 is a table for fixing the container body 110, and is provided with a fixing hole 1291 which is a recess corresponding to the bottom surface of the container body 110. When the container main body 110 is disposed in the fixing hole 1291, the opening 111 of the container main body 110 is configured to face upward in the vertical direction, and when the lid 120 is rotated by the holding tool 26, the fixing hole 1291 is configured to fix the container main body 110 to the fixing base 129 so as not to rotate.

  The fixing pin 127A is disposed in the processing area 12H. The fixing pin 127A is rotatably configured and engageable with the cassette 200A. Then, the cassette 200A can be rotated together with the operation of the robot 20 by the drive mechanism disposed in the base 10B.

  The cassette 200A has a disk shape as shown in FIG. 17, and a hole which can be engaged with the fixing pin 127A is provided on the center back surface. In the cassette 200A, a plurality of concave portions 201A are formed in a radial shape. The concave portion 201A has a shape corresponding to the bottom surface of the container 100, and the container main body 110 is configured so that its major axis is disposed radially relative to the cassette 200A in a plan view.

  With such a configuration of the processing area 12H and the cassette 200A, it is possible to appropriately move the container 100 used for the processing to a position close to the robot 20. Therefore, the operation of the robot 20 can be simplified, and the processing can be streamlined.

  Next, the cell processing method of the present embodiment using the above-described cell processing system 1B will be described. The differences between the method of the present embodiment and the method of the first embodiment and the differences are mainly described, and the description of the same matters is omitted.

  First, equipment and materials necessary for seeding cells in the treatment areas 12F and 12H are prepared and prepared by the same operation as the first embodiment described above.

Moreover, about the automatic work by the cell processing system 1B, it is performed in the following order.
First, the lid of the container 100 is removed. In this regard, first, the container 100 is gripped from the side of the container main body 110 disposed in the cassette 200 by the second grip portion 262 of the grip tool 26.
Next, the held container 100 is disposed in the fixing hole 1291 of the fixing stand 129 of the processing area 12G.
Next, similarly to the above-described A-1 to A-7, the lid 120 of the container 100 disposed in the fixing hole 129 is removed and disposed at a predetermined place.

Next, the container body 110 is gripped in the same manner as A-8 and A-9, and the container body 110 is transferred to the treatment area 12F for seeding cells.
Next, the dispensing pump 121C is operated to dispense a predetermined amount of liquid containing cells to the container body 110 through the tube 123C.

Thereafter, in the same manner as A-14 and A-15, the container body 110 is disposed in the recess 201A of the cassette 200A.
The above operation is repeated, and after all the containers 100 have been treated, a lid is attached to the container body 110 which has been treated in the same manner as the operations A-16 to A-19.

Other operations can be performed in the same manner as the method of the first embodiment described above.
As described above, also by the cell processing system and method according to the present embodiment, the same effect as that of the first embodiment can be obtained.

  In addition, as a modification of the 1st embodiment-the 3rd embodiment mentioned above, for example, as shown in FIG. 18, the container main body 110 same as the container main body 110 of the other container 100 is employ | adopted as lid storage 128A, The example which omits the lid storage space installed in a base is mentioned. In such a case, even when the shape of the container 100 is changed, the lid storage space can be easily prepared by using the container 100 of the same type. That is, regardless of the shape of the container 100, it is possible to use the cell processing system.

  Moreover, what carried the force sensor was mentioned about the holding tool as another modification. In such a case, since the weight of the container can be sensed, the force sensor can measure the dispensing amount without using a sensor such as a weight sensor as an apparatus for dispensing. That is, it is possible to omit the sensor in the processing area for dispensing. In addition, by adopting a force sensor, for example, it can be determined whether or not the holding tool has contacted the container. As a result, for example, it is possible to confirm that the holding tool has contacted the container and to arrange the holding tool at a position suitable for holding, thereby making the holding more reliable.

  Moreover, in each embodiment mentioned above, although the holding | gripping tool demonstrated as what is a parallel gripper, it is possible to use various grippers, such as a rotation gripper, a one-side movable gripper, a both-sides movable gripper.

In addition, the shape of the holding tool can be changed as appropriate.
For example, in the holding tool 26A shown in FIG. 19, the concave portion 2661 is disposed in the axial direction near the center of the holding surface 266A of the first holding portion 264A. The recess 2661 has a v-shaped cross section, which increases the contact area between the first grip 264A and the lid 120 when the lid 120 is gripped by the first grip 264A. Do. Therefore, the lid 120 can be held more reliably by the first gripping portion 264A, and the lid 120 is rotated from the first gripping portion 264A relative to the lid 120 even when the lid 120 is rotated by the first gripping portion 264A. The rotational force can be transmitted more reliably.
Also, for example, the second gripping portion of the gripping tool may be provided only at one end of the first gripping portion.

  Moreover, the preparation by the operator of each processing area | region and removal of an apparatus and material can change the order suitably. Therefore, for example, in each of S-2 to S-4, S-9 to S-12, and S-13 to S-15 of the cell processing method according to the first embodiment, the order of each step can be changed. .

Although the present invention has been described above with reference to the illustrated embodiments, the present invention is not limited thereto.
In the present invention, each configuration may be replaced with any one capable of performing the same function, or any configuration may be added.

1, 1A, 1B Cell processing system 10, 10A, 10B Base 11 Loading / unloading area 12A, 12B, 12C, 12D, 12E, 12F, 12G, 12H Treatment area 121, 121A, 121B, 121C Dispensing pump 122 Medium storage Container 122A, 122B, 122C Storage container 123, 123A, 123B, 123C Tube 124, 124A, 124B, 124C Liquid volume sensor 125 Collection container 126 Sensor 127, 127A Fixing pin 128, 128A Lid storage place 129 Fixing base 1391 Fixing hole 13 Operation part 131 input unit 132 display unit 14 intake port 15 space (clean space)
Reference Signs List 20 robot 21 base 22 first arm 23 second arm proximal end 24 second arm distal end 25 hand 26 grip (gripper)
261 grip tool main body 262 guide member 263 claw portion 264 first grip portion 265 second grip portion 266, 266A grip surface 2661 concave portion 267 grip surface 30 case 31 side wall 32 shutter 33 ceiling portions 40A, 40B, 40C, 40D, 40E Working part 41A, 41B, 41C, 41D, 41E Working area 100 Container 110 Container body 111 Opening 112 Main surface 113 Main surface 114 Cell culture 120 Lid 200, 200A Cassette 201, 201A Recess 300 Controller 400 Control terminal

Claims (7)

A cell processing method for processing cells using a plurality of containers having a lid and a container body,
1) arranging n (where n is an integer of 2 or more) the containers whose order of processing is determined;
2) Remove the lid of the container to be processed to the i-th (where i is an integer, 2 ≦ i ≦ n) by the robot from the container body, and the container body of the i-th to-be-processed container Step of attaching to
3) performing the processing using the container to be processed i-th,
Prior to step 2), removing the lid of the container to be processed i-1st from the container body by an operator or a robot and placing the lid in the lid storage space;
A cell processing method having:   The cell processing method according to claim 1, wherein steps 2) and 3) are repeated until i changes from 2 to n.   The cell processing method according to claim 1, wherein the robot operates so as not to pass over the opening of the container body from which the lid is removed. The method according to any one of claims 1 to 3 , wherein after the processing of step 3) is performed on the n-th container to be processed, the lid disposed in the lid storage by an operator or a robot is attached to the container body of the container. The cell processing method as described in 1 item. The cell processing method according to any one of claims 1 to 4 , wherein the treatment in step 3) is the disposal of the liquid from the container and / or the injection of the liquid into the container. The cell processing method according to claim 5 , wherein the liquid is a culture medium. The process, the exchange of media in the container, the dispensing of the medium into the container, a release of a cell tissue formed on sowing or the container wall surface of the cells into the container, according to claim 1 to 6 The cell processing method as described in any one.