Cell moving device

Abstract

The cell transfer device transfers the cells dispersed in the first container to the second container. The cell movement device includes: a head for mounting a suction tip capable of generating a suction force and a discharge force at a distal opening; a moving mechanism of the head; a cell recognition unit that includes a camera that captures an image of the first container, and that recognizes the position of the cell on the basis of the image; and a control unit that, on the basis of the result of the position recognition, controls the head and the movement mechanism so as to perform a movement operation of the cells. The control unit periodically sucks a set number of target cells, which are set in advance to two or more, into the suction tip among the cells dispersed in the first container, and, after moving the head to the second container, sucks the target cells into the suction tip. The set number of target cells sucked by the suction tip are discharged to the same place in the second container.

Description

Technical Field

[0001] The present invention relates to a cell moving device for moving cells dispersed in one container to another container. Background Art

[0002] For example, in the field of medical and biological research, there is sometimes an operation of moving single cells or cell colonies (sometimes referred to simply as "cells" in this specification) that are sorted and cultured from a sorting container to a working container for inspection, observation, etc. In order to perform this operation, there is known a cell moving device that uses a head equipped with a suction tip to perform an operation of sucking a target cell from the sorting container and discharge the sucked target cell into a hole in the working container.

[0003] Depending on the research method, it is sometimes necessary to hold a plurality of cells in one hole of the working container. In this case, it is necessary to repeat the operation of aspirating a cell with the suction tip in the sorting container at the moving origin and discharging the aspirated cell in the working container at the moving destination multiple times. In other words, it is necessary to perform multiple reciprocating movements of the head between the moving origin container and the moving destination container, which increases the takt time.

[0004] Patent Document 1 discloses an object observation apparatus including a suction tip capable of suctioning and holding a plurality of cells. However, Patent Document 1 is based on the premise of using a suction tip of a special shape including a cell capturing portion having a horizontal portion.

[0005] Prior art literature

[0006] Patent Literature

[0007] Patent Document 1: Japanese Patent Gazette No. 5897733 Summary of the invention

[0008] An object of the present invention is to provide a cell transfer device capable of efficiently transferring a plurality of cells dispersed in one container to another container.

[0009] Solutions for solving problems

[0010] A cell moving device according to one aspect of the present invention moves cells scattered in a first container to a second container, and includes: a head for mounting a suction tip capable of sucking and discharging the cells, and having a generating mechanism for generating suction force and discharge force at a distal opening of the suction tip; a moving mechanism for causing the head to move horizontally and vertically; a cell recognition unit including a camera for capturing an image of the first container in which the cells are scattered, and for performing position recognition of the cells based on the image; and a control unit for controlling the head and the moving mechanism to execute the cell moving action based on a result of the position recognition, wherein the control unit causes a set number of target cells, which is preset to be two or more, to be sucked into the suction tip in stages among the cells scattered in the first container, and, after causing the head to move to the second container, causes the set number of target cells sucked into the suction tip to be discharged to the same location of the second container. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 It is a schematic diagram schematically showing the structure of a cell migration device according to an embodiment of the present invention.

[0012] Figure 2 This is a cross-sectional view of the suction tip mounted on the head of the cell moving device.

[0013] Figure 3 (A) is a cross-sectional view of the suction piece as a component of the suction tip. Figure 3 (B) is a cross-sectional view of the plunger. Figure 3 (C) is an exploded perspective view of the suction tip.

[0014] Figure 4 This is a block diagram showing the control structure of the cell moving device.

[0015] Figure 5 (A) to (D) are diagrams showing the steps of aspirating cells into the aspiration tip.

[0016] Figure 6 (A) to (D) are diagrams showing the steps of aspirating cells into the aspiration tip.

[0017] Figure 7 (A) to (C) are diagrams showing the moving step and the discharge step of the aspirated cells.

[0018] Figure 8 (A) and (B) are examples of images of the first container having a storage area before and after aspiration of cells. Figure 8 (C) is an example of an image of the well of the second container after the cells have been discharged.

[0019] Fig. 9(A) and (B) are examples of images before and after aspiration of cells from a first container without a storage area. Fig. 9 (C) is an example of an image of the well of the second container after the cells have been discharged.

[0020] Fig.10 This is a flowchart showing an example of the operation of the cell moving device.

[0021] Fig.11 This is a flowchart showing the operation of the cell movement step performed by the cell movement device.

[0022] Fig.12 This is a flowchart showing the details of the cell aspiration operation performed by the head.

[0023] Fig.13 The figure shows a method of confirming whether the aspiration of cells is successful or not.

[0024] Fig.14 This is a perspective view showing an example of a cell moving wire incorporated in the cell moving device. DETAILED DESCRIPTION

[0025] The following is a detailed description of the embodiments of the present invention based on the accompanying drawings. The cell moving device of the present invention can be used to suck and move cells from various organisms. Cells from organisms include single cells such as blood cells and single cells; small pieces of tissue such as in vitro tissue culture (histoculture); cell aggregates such as spheres and organoids; individuals such as zebrafish, nematodes, and fertilized eggs; 2D or 3D cell colonies, etc.

[0026] [Overall structure of the cell migration device]

[0027] Figure 1 : is a diagram schematically showing the overall structure of a cell moving device S. Here, a cell moving device S that moves cells C between two containers is exemplified. The cell moving device S includes: a light-transmitting base BP having a horizontal mounting surface; a camera unit 5 disposed on the lower side of the base BP; and a head unit 6 disposed on the upper side of the base BP. A first container 41, which is a starting point for the movement of cells C, is placed at a first mounting position P1 of the base BP, and a second container 42, which is a destination for the movement of cells C, is placed at a second mounting position P2.

[0028] The first container 41 includes a dish 43 for holding (arranging) the cells C in a dispersed state. The second container 42 includes a plurality of holes 45 capable of accommodating the cells C. The camera unit 5 and the head unit 6 are movable in at least the X direction. The head unit 6 includes a plurality of heads 61 for mounting the suction tips 1 for suctioning and discharging the cells C. The heads 61 are movable in the Z direction.

[0029] In general, the cell moving device S moves cells C from the first container 41 at the first loading position P1 to the second container 42 at the second loading position P2. First, the cell moving device S selects target cells C as the moving object from a plurality of cells scattered on the dish 43 of the first container 41, and uses the suction tip 1 to suck and hold the target cells C. The suction tip 1 holding the cells C is moved to the second container 42 together with the head unit 6, and the cells C are discharged into the hole 45 of the second container 42. As described in detail later, when the suction is performed in the first container 41, a set number of target cells C set to two or more in advance are sucked into the suction tip 1, and these cells C are discharged into one hole 45 (the same place) of the second container 42. The following describes each part of the cell moving device S.

[0030] The base BP is a rectangular flat plate having a specified rigidity and partially or entirely formed of a light-transmitting material. A preferred base BP is a glass plate. By forming the base BP from a light-transmitting material such as a glass plate, the first container 41 and the second container 42 arranged on the upper surface of the base BP can be photographed through the base BP using the camera unit 5 arranged below the base BP.

[0031] The first container 41 stores the culture medium L and holds the dish 43 for cell separation in a state of being immersed in the culture medium L. The dish 43 has a plurality of receiving areas 44 capable of receiving cells C on the upper surface side. The receiving areas 44 are formed by recesses capable of receiving cells C and are arranged in a matrix. Figure 8 (A) and Figure 8 (B) shows a top view of the dish 43. The culture medium L is not particularly limited as long as it does not deteriorate the characteristics of the cells C, and can be appropriately selected according to the type of the cells C.

[0032] The first container 41 has a rectangular upper opening 11H on its upper surface side. The upper opening 11H is an opening for injecting cells C and picking up sorted cells C. Injecting cells C is a step of discharging a cell suspension containing a large number of cells C from a dispensing tip (not shown). Picking up cells C is performed by the above-mentioned suction tip 1. The dish 43 is arranged below the upper opening 11H. The first container 41 and the dish 43 are made of a light-transmitting resin material or glass. This is to be able to observe the cells C carried on the dish 43 using the camera unit 5 arranged below the first container 41.

[0033] The second container 42 is, for example, a microtiter plate having a plurality of wells 45 (receiving portions). The wells 45 are bottomed wells that are open on the upper surface of the second container 42. A necessary number of cells C are received in one well 45 together with the culture medium L. The second container 42 is also made of a light-transmitting resin material or glass for imaging by the camera unit 5. When the cells C are discharged, the distal end t of the suction tip 12 enters the well 45. Each well 45 has an opening diameter that allows the distal end t to enter with a margin.

[0034] The camera unit 5 (a part of the cell identification section) captures the image of the cell C held in the first container 41 or the second container 42 from their lower surface side. The camera unit 5 includes a lens section 51 and a camera body 52. ​​The lens section 51 is an objective lens used in an optical microscope, and includes a lens group that forms an optical image of a specified magnification and a lens barrel that accommodates the lens group. The camera body 52 includes a photographing element such as a CCD image sensor. The lens section 51 forms an optical image of the object being photographed on the light receiving surface of the photographing element. The camera unit 5 can move horizontally along a guide rail 5G extending in the X direction. In addition, the camera unit 5 can also move vertically in the X direction using a moving mechanism (not shown). Figure 1 Move in the Y direction of the paper.

[0035] The head unit 6 is a unit responsible for picking up cells C from the first container 41 and moving them to the second container 42, and includes a head group 6H having a plurality of heads 61 as described above and a head body 62 for assembling the head group 6H. A suction tip 1 capable of aspirating and discharging cells C is installed at the distal end of each head 61. Each head 61 includes a generation mechanism for generating suction force and discharge force at the distal end t of the suction tip 1. The head body 62 holds the head 61 in a manner capable of being raised and lowered in the +Z and -Z directions. The head unit 6 moves along the guide rail 6G (moving mechanism) in the X direction in which the first container 41 and the second container 42 are arranged. In fact, the head unit 6 can also move perpendicular to the X direction using a moving mechanism (not shown). Figure 1 Thus, the head unit 6 functions as a moving mechanism that moves the suction tip 1 horizontally in the XY directions and moves it up and down in the Z direction.

[0036] [Structure of the suction tip]

[0037] Next, the structure of the suction tip 1 attached to the head 61 will be described. Figure 2 is a cross-sectional view of the suction tip 1 . Figure 3 (A) is a cross-sectional view of the injection and suction member 2, Figure 3 (B) is a cross-sectional view of the plunger 3, Figure 3(C) is an exploded perspective view of the suction tip 1. The suction tip 1 includes: a suction tool 2 having a tubular channel 2P serving as a suction path for the cells C; and a plunger 3 slidably accommodated in the tubular channel 2P.

[0038] The suction piece 2 includes: a large-diameter suction piece base end portion 21 in the shape of a cylinder; a thin-diameter suction piece body portion 22 in the shape of an elongated cylinder; and a tapered cylinder portion 23 connecting the base end portion 21 and the body portion 22. The tubular channel 2P is formed in the suction piece body portion 22. A distal opening 24 serving as a suction port or a discharge port for the cell C is provided at a distal end portion t located at one end of the suction piece body portion 22. One end of the tubular channel 2P is connected to the distal opening 24. The suction piece base end portion 21 is continuously provided on the other end side of the suction piece body portion 22 through the tapered cylinder portion 23.

[0039] The plunger 3 is a member that is inserted into the tubular channel 2P of the injection / aspiration member 2 and moves forward and backward in the tubular channel 2P, thereby generating negative pressure for aspirating cells or positive pressure for discharging cells at the distal opening 24. The plunger 3 includes a plunger base end portion 31 in a cylindrical shape, a needle-shaped plunger main body portion 32, a hemispherical portion 33 connecting the base end portion 31 and the main body portion 32, and a plunger distal end portion 34 that is a protruding distal end of the plunger main body portion 32.

[0040] The base end portion 21 of the injection and suction member has a cylindrical hollow portion 2H. The outer diameter of the plunger base end portion 31 is set to be smaller than the inner diameter of the hollow portion 2H by a specified length. The outer diameter of the plunger body portion 32 is set to be slightly smaller than the inner diameter of the tubular passage 2P. In addition, the shape of the inner circumferential surface of the tapered cylindrical portion 23 is consistent with the curved surface shape of the outer circumferential surface of the hemispherical portion 33. In a state where the plunger base end portion 31 is accommodated in the hollow portion 2H and the plunger body portion 32 is inserted into the tubular passage 2P of the injection and suction member body portion 22, the plunger 3 is assembled to the injection and suction member 2.

[0041] exist Figure 3 (C) shows the state where the plunger 3 is pulled out from the injection and suction member 2, while Figure 2 In the figure, the plunger body 32 is inserted deepest into the injection and suction member body 22, that is, the plunger 3 is in the most descended state. At this time, the hemispherical portion 33 is completely accommodated in the cavity of the conical cylinder 23. The length of the plunger body 32 is slightly longer than that of the injection and suction member body 22. Figure 2 In the state, the plunger distal end portion 34 protrudes from the distal end opening 24. In addition, there is a gap between the inner peripheral surface of the suction member base end portion 21 and the outer peripheral surface of the plunger base end portion 31.

[0042] The plunger 3 can be Figure 2The state of the plunger 3 is moved upward relative to the injection and suction member 2. If the plunger 3 moves upward by a specified length, the plunger distal end 34 is immersed in the interior of the tubular channel 2P. At this time, a suction force is generated at the distal opening 24, and the fluid around the distal opening 24, in this embodiment, the culture medium L containing cells C, can be sucked into the tubular channel 2P. After the suction, if the plunger 3 is moved downward, the fluid sucked into the tubular channel 2P can be discharged from the distal opening 24.

[0043] The suction tip 1 is mounted on Figure 2 The distal end portion of the head 61 is shown. The head 61 includes: a first cylindrical rod 611; a second cylindrical rod 612 arranged outside the first cylindrical rod 611; and a plunger rod 613 (generating mechanism / moving member) arranged in the hollow portion of the first cylindrical rod 611.

[0044] The second cylindrical rod 612 is a fixed rod, while the plunger rod 613 and the first cylindrical rod 611 move forward and backward independently. The plunger base end 31 is provided with a mounting hole 3H as a cylindrical hollow space. The lower end of the plunger rod 613 is pressed into the mounting hole 3H. The upper end surface of the plunger base end 31 faces the lower end surface of the first cylindrical rod 611. The lower end of the immovable second cylindrical rod 612 is pressed into the hollow portion 2H of the injection and suction member base end 21. The plunger rod 613 moves up and down, thereby moving the plunger 3 up and down, and as described above, a suction force or a discharge force is generated at the distal opening 24. The first cylindrical rod 611 descends when the suction tip 1 is removed from the head 61.

[0045] [Electrical structure of the cell migration device]

[0046] Figure 4 : is a block diagram showing the electrical structure of the cell moving device S. The cell moving device S includes a control unit 7 that controls the movement of the head unit 6, the suction and discharge of the cells C by the suction tip 1, and the movement and shooting of the camera unit 5. In addition, the cell moving device S includes: a camera axis driving unit 53 as a mechanism for horizontally moving the camera unit 5; an X-axis motor 63 and a Y-axis motor 64 as a mechanism for horizontally moving the head unit 6; a Z-axis motor 65 as a mechanism for raising and lowering the head 61; a plunger motor 66 as a mechanism for performing the suction and discharge of the cells C, and also includes a display unit 54 and an input unit 55.

[0047] The camera axis driving unit 53 includes a driving motor for horizontally moving the camera unit 5 along the guide rail 5G. The X-axis motor 63 and the Y-axis motor 64 are driving sources of a moving mechanism for horizontally moving the head unit 6 along the guide rail 6G. A preferred embodiment of the moving mechanism is a mode in which a ball screw and a nut member for the X-axis and the Y-axis are provided, and the X-axis motor 63 and the Y-axis motor 64 each rotate the ball screw forward or reversely.

[0048] The Z-axis motor 65 and the plunger motor 66 are built into the head body 62. The Z-axis motor 65 moves the head 61 up and down between a lowered position where the head 61 extends downward from the head body 62 and an ascending position where most of the head 61 is accommodated in the head body 62. The plunger motor 66 moves the plunger rod 613 ( Figure 2 ) rises, thereby generating suction force and expulsion force at the distal opening 24 of the suction tip 1.

[0049] The display unit 54 includes a liquid crystal display or the like, and displays images captured by the camera unit 5 , images subjected to image processing by the control unit 7 , and the like.

[0050] The input unit 55 includes a keyboard or a touch panel, or a communication unit for performing data communication with other communication devices, and receives input of operation information and various data from the user. In the present embodiment, the input unit 55 receives input of the set number of cells C discharged to one hole 45 of the second container 42 to be moved from the user. In other words, the input of the set number of target cells C to be aspirated by one aspiration tip 1 in the first container 41 is received from the user.

[0051] The control unit 7 includes a processor for performing various calculations, and includes an axis control unit 71 (part of the moving mechanism), a suction control unit 72, a camera control unit 73, an image memory 74, an image processing unit 75 (part of the cell identification unit), a sorting unit 76, a determination unit 77 and a storage unit 78.

[0052] The axis control unit 71 moves the head unit 6 to a designated target position in the horizontal direction by controlling the operation of the X-axis motor 63 and the Y-axis motor 64. The movement of the head 61 equipped with the suction tip 1 between the first container 41 and the second container 42, the positioning of the head 61 vertically above the storage area 44 of the dish 43, and the positioning of the head 61 vertically above the hole 45 of the second container 42 as the discharge target are realized by the control of the X-axis motor 63 and the Y-axis motor 64 by the axis control unit 71.

[0053] The suction control unit 72 controls the operation of the Z-axis motor 65 and the plunger motor 66 to allow the suction tip 1 to perform the suction and discharge operation of the cell C. The suction control unit 72 controls the operation of the Z-axis motor 65 to lower and raise the head 61 as the control object toward the specified target position. In addition, the suction control unit 72 controls the operation of the plunger motor 66 provided in the head 61 as the control object to generate a suction force or a discharge force at the distal end opening 24 of the suction tip 1 at a specified timing.

[0054] In the present embodiment, the suction control unit 72 causes the operation of gradually sucking a set number of target cells C, which is set to two or more, from the cells C scattered on the dish 43 of the first container 41 into one suction tip 1. The set number is a number received from the user to the input unit 55. In addition, after the head 61 is moved to the second container 42 by the axis control unit 71, the suction control unit 72 causes the operation of discharging the set number of target cells C sucked into the suction tip 1 into the same place in the second container 42, that is, into one hole 45. Regarding these controls, the following will be based on Figures 5 to 7 Provide graphic explanation.

[0055] The imaging control unit 73 controls the camera axis driving unit 53 to move the camera unit 5 along the guide rail 5G. In addition, the imaging control unit 73 controls the imaging operation of the camera unit 5 with respect to the first container 41 or the second container 42.

[0056] The image memory 74 is a storage area provided in the microcomputer, an external storage, etc. The image memory 74 temporarily stores the image data acquired by the camera unit 5 .

[0057] The image processing unit 75 performs image processing on the image data captured by the camera unit 5 and stored in the image memory 74. The image processing unit 75 performs processing for recognizing the position of the cell C on the dish 43 on the image based on the image of the dish 43 of the first container 41 after the cell C is dispensed. In addition, the image processing unit 75 performs processing for recognizing the distribution of the cell C, and processing for recognizing the size, shape, color tone, etc. of the recognized cell C using image processing technology. The axis control unit 71 and the suction control unit 72 control the movement of the head 61 and the suction and discharge of the suction tip 1 based on the position recognition of the cell C, and perform the movement of the cell C.

[0058] The sorting unit 76 performs a process of sorting target cells C to be moved to the second container 42 from the cell C group dispersed in the first container 41 based on a predetermined sorting criterion. The sorting unit 76 derives an evaluation value of the mass of the cells C dispersed on the dish 43 of the first container 41 based on the image captured by the camera unit 5. Specifically, based on the image processing result of the image processing unit 75, feature quantities of the cells C such as the area or estimated volume of the cells C, the color or pattern of the cells C, and the light intensity when the cells C emit fluorescence are extracted. In addition, the number of cells C accommodated in one accommodation area 44 is also detected as one of the feature quantities. The reason is that if a plurality of cells C are accommodated in the accommodation area 44, it is difficult to control the number of cells C to be sucked into the suction tip 1, and it is difficult to accurately evaluate the cells C because they overlap.

[0059] Thereafter, the sorting unit 76 determines the cell whose evaluation value exceeds the specified threshold value as the target cell C. That is, the feature amount of each extracted cell C is compared with the selection reference parameter predetermined as the range of cells C to be selected, and the target cell C is determined by evaluating whether it falls within the range of the selection reference parameter. Through the processing of the sorting unit 76, only the cells C evaluated as having good quality among the cells C accommodated in the first container 41 can be moved as target cells C to the second container 42.

[0060] The determination unit 77 determines whether the set number of target cells C has been aspirated or discharged based on the image of the first container 41 after the aspiration tip 1 has performed the cell aspiration operation or the image of the second container 42 after the aspiration tip 1 has performed the cell aspiration operation. Fig.13 This will be described in detail later.

[0061] The storage unit 78 stores various setting values ​​and data of the cell moving device S. In addition, the storage unit 78 also stores the selection criterion parameters of the cells C to be moved. The criterion for judging whether the cells C are good or bad sometimes varies depending on their size and type, and it is preferable to have a sorting criterion obtained, for example, based on the result of machine learning for each size and type. When performing the above-mentioned sorting process, the sorting unit 76 reads the sorting criterion stored in the storage unit 78.

[0062] [Cell movement action]

[0063] Next, refer to Figure 5 to Figure 7 The cell moving operation performed by the cell moving device S will be described. The cell moving operation includes the following steps (1) to (4) performed in sequence.

[0064] (1) a preliminary treatment step of holding the suction tip 1 with the preliminary treatment liquid,

[0065] (2) a suction step of suctioning a set number of target cells C into the suction tip 1 in the first container 41,

[0066] (3) a step of moving the suction tip 1 that has sucked the cells C to the second container 42, and

[0067] (4) A discharge step of discharging all the cells C in the suction tip 1 into the hole 45 of the second container 42 .

[0068] Figure 5 (A) to (D) and Figure 6 (A) to (D) are diagrams showing the above-mentioned preliminary treatment step (1) and suction step (2). Figure 5(A) shows the suction tip 1 in a state where the preliminary treatment liquid LA is retained in the space between the suction piece body 22 and the plunger body 32. In the preliminary treatment step (1), for example, the distal end portion t of the suction piece 2 is immersed in a container containing the preliminary treatment liquid LA, and the plunger 3 is moved forward and backward about three times. Through this action, the preliminary treatment liquid LA is sucked into the space between the suction piece body 22 and the plunger body 32. The preliminary treatment liquid LA may be physiological saline or the like, but it is preferable to use a culture medium L.

[0069] Figure 5 (A) and (B) are also diagrams of the step of forming an air layer H in the tubular passage 2P before executing the suction step (2). Figure 5 As shown in (A), the distal end t of the suction tip 1 is placed in the air, and the plunger motor 66 is driven from the state where the plunger distal end 34 protrudes from the distal end opening 24 of the suction and injection member 2 to raise the plunger 3 by a specified length. Accordingly, an air layer H is formed in the tubular passage 2P near the distal end opening 24.

[0070] Figure 5 (C)~ Figure 6 (D) shows the execution status of the suction step (2) in sequence. In these figures, the first container 41 is shown in a simplified manner. In the culture medium L1 stored in the first container 41, the first cell C1, the second cell C2, and the third cell C3 selected as the target cells to be moved are scattered. Here, an example in which the set number of target cells = 3 is shown. In addition, based on the image of the first container 41 before the cells are sucked, which is taken by the camera unit 5, the position coordinates of each cell C1, C2, and C3 are obtained.

[0071] The suction control unit 72 causes cells C1, C2, and C3 to be sucked into one suction tip 1 in stages. At this time, the order in which cells C1, C2, and C3 are sucked is determined, that is, the moving route of the head 61 is set. In order to shorten the cycle time, the moving route is preferably selected with reference to the position coordinates of cells C1, C2, and C3 to select a route with the shortest moving distance. Here, three target cells arranged in a row are sucked in stages in the order of the first cell C1, the second cell C2, and the third cell C3.

[0072] Figure 5(C) shows a state where the distal opening 24 of the suction tip 1 is aligned with the first cell C1. The axis control unit 71 moves the head unit 6 so that the suction tip 1 is located above the first container 41. At this time, the head 61 is moved with reference to the position coordinates of the first cell C1 so that the distal opening 24 of the suction tip 1 is located vertically above the first cell C1. The suction control unit 72 drives the Z-axis motor 65 to lower the head 61 until the distal end t is immersed in the culture medium L1 in the first container 41, specifically, until the distal opening 24 is located near directly above the first cell C1 in the culture medium L1. Figure 5 (C) shows the state after the decline.

[0073] Next, the suction control unit 72 drives the plunger motor 66 to raise the plunger 3 by a specified distance. As a result, the distal opening 24 is negatively pressurized to generate suction force, and a portion of the culture medium L1 in the first container 41 and the first cells C1 are sucked into the tubular channel 2P from the distal opening 24. In the tubular channel 2P, the first cells C1 float in the sucked culture medium L1a. Figure 5 (D) shows the state after aspiration of the first cell C1.

[0074] In the suction step (2), since the preliminary treatment liquid LA is previously retained in the space between the aspirator body 22 and the plunger body 32, the culture medium L1 does not rise sharply in the tubular channel 2P due to capillary phenomena or internal pressure. In addition, the air layer H functions as a sealing layer that isolates the preliminary treatment liquid LA and the culture medium L1a containing the first cell C1 to be aspirated later in the tubular channel 2P. Therefore, the aspirated first cell C1 does not transfer to the preliminary treatment liquid LA. Therefore, it is possible to prevent the first cell C1 from being sandwiched between the aspirator body 22 and the plunger body 32. In addition, due to the presence of the air layer H, it is possible to prevent the preliminary treatment liquid LA from mixing with the culture medium L1, or to prevent the preliminary treatment liquid LA from being discharged into the second container 42 in the subsequent discharge step (4).

[0075] Thereafter, the same operation is repeated a number of times corresponding to the set number of target cells. Figure 6 (A) shows a state where the head 61 moves horizontally a small distance and the distal opening 24 of the suction tip 1 is aligned with the second cell C2. Thereafter, the suction control unit 72 drives the Z-axis motor 65 to lower the head 61 until the distal opening 24 of the suction tip 1 is located near directly above the second cell C2. Next, the suction control unit 72 drives the plunger motor 66 to raise the plunger 3 by a specified distance, so that a suction force is generated at the distal opening 24, and the second cell C2 is sucked from the distal opening 24. Figure 6 (B) shows the state after the second cell C2 is aspirated. At this stage, the first cell C1 and the second cell C2 are held in the aspiration tip 1 in a vertical arrangement.

[0076] Figure 6 (C) shows a state where the head 61 further moves horizontally a small distance, and the distal opening 24 of the suction tip 1 is aligned with the third cell C3. The suction control unit 72 drives the Z-axis motor 65 to lower the head 61 until the distal opening 24 of the suction tip 1 is located near directly above the third cell C3. Next, the suction control unit 72 drives the plunger motor 66 to further raise the plunger 3 by a specified distance, so that a suction force is generated at the distal opening 24, and the third cell C3 is sucked from the distal opening 24. Figure 6 (D) shows the state after the third cell C2 is aspirated. In this example, the stepwise aspiration of the target cell ends here. When the aspiration step (2) is completed, the first cell C1, the second cell C2, and the third cell C3 are held in the aspiration tip 1 in a row from top to bottom.

[0077] Figure 7 (A) and (B) are diagrams showing the execution status of the above-mentioned moving step (3). After the suction step (2) is completed, the axis control unit 71 moves the head unit 6 so that the suction tip 1 holding the cells C1, C2, and C3 is located above the second container 42. Figure 7 (B) schematically shows the second container 42. The culture medium L2 is also stored in the second container 42. In practice, the head unit 6 moves so that the distal end portion t of the suction tip 1 is aligned with one of the plurality of holes 45 provided in the second container 42, which is the discharge target.

[0078] Figure 7 (C) is a diagram showing the state after the above-mentioned discharge step (3) is performed. The suction control unit 72 drives the Z-axis motor 65 to lower the head 61 until the distal opening 24 of the suction tip 1 is immersed in the culture medium L2 in the second container 42. Then, the suction control unit 72 drives the plunger motor 66 to lower the plunger 3 by a specified distance. In detail, the plunger 3 is lowered until the plunger distal end 34 protrudes from the distal opening 24. Accordingly, as Figure 7 As shown in (C), the culture medium L1 a and the cells C1 , C2 , and C3 held in the suction tip 1 are discharged at once into the culture medium L2 in the second container 42 .

[0079] Figure 8 (A) and (B) are examples of images of the first container 41 having the receiving area 44 before and after the cells are aspirated. The first container 41 includes a dish 43 having the receiving areas 44 arranged in a matrix, and a plurality of cells C are scattered on the dish 43. Figure 8 As shown in (A), it is assumed that among these cells C, cells Ca, Cb, and Cc accommodated one each in the accommodation areas 44 a, 44 b, and 44 c are determined as target cells to be sucked into one suction tip 1.

[0080] In this case, the suction control unit 72 sets a movement route MR that passes through the storage areas 44a, 44b, and 44c in the shortest distance as a movement route of the head 61 equipped with the one suction tip 1. Then, the axis control unit 71 intermittently moves the head 61 along the movement route MR, and the suction control unit 72 causes the cells Ca, Cb, and Cc to be suctioned into the one suction tip 1 in stages. That is, the suction control unit 72 causes the head 61 to move across the plurality of storage areas 44a, 44b, and 44c to cause the suction tip 1 to perform the suction action until the suction tip 1 completes the suction of the set number of target cells.

[0081] After suction, Figure 8 As shown in (B), the storage areas 44a, 44b, and 44c are empty. If cells Ca, Cb, and Cc remain in the storage areas 44a, 44b, and 44c, the aspiration has failed. That is, by taking an image of the first container 41 after aspirating the cells to confirm the presence of the cells Ca, Cb, and Cc, it is possible to confirm whether the aspiration of the target cells by the aspiration tip 1 is successful.

[0082] The suction tip 1 that has sucked the cells Ca, Cb, Cc is moved to the second container 42 , and the cells Ca, Cb, Cc are discharged into one hole 45 . Figure 8 (C) is an example of an image of one well 45 after the cells are discharged. The necessary operations such as adding reagents are performed on the wells 45 accommodating the cells Ca, Cb, and Cc.

[0083] Fig. 9 (A) and (B) are examples of images before and after aspiration of cells from a first container 410 having a flat bottom without a receiving area 44. A plurality of cells C are scattered in the first container 410. Fig. 9 As shown in (A), among these cells C, cells Cd, Ce, and Cf that exist one each in regions PA1, PA2, and PA3 are determined as target cells to be sucked toward one suction tip 1. In this case, a movement route that passes through regions PA1, PA2, and PA3 in the shortest distance is also specified, and cells Cd, Ce, and Cf are sucked into one suction tip 1 in stages. Whether the suction is successful can be determined by, for example Fig. 9 (A) Pre-suction image and Fig. 9 (B) The image after puffing is judged by image matching processing. Fig. 9 (C) is an example of an image after the cells Cd, Ce, and Cf are discharged into one hole 45 .

[0084] The above is an operation focusing on one suction tip 1. In fact, in the first container 41, a set number of target cells C are respectively sucked into each suction tip 1 mounted on a plurality of heads 61 provided in the head unit 6 in stages. Then, the set number of target cells C are discharged from each suction tip 1 into each of the plurality of holes 45 of the second container 42 at one go. In other words, two or more target cells C held by each suction tip 1 are discharged into the holes 45 assigned to each suction tip 1. According to the present embodiment, a set number of target cells C can be moved from each suction tip 1 to each hole 45 of the second container 42 by a single movement of the head unit 6 from the first container 41 to the second container 42.

[0085] [Operation flow of the cell migration device]

[0086] Fig.10 1 is a flowchart showing an example of the operation of the cell moving device S. First, the input unit 55 receives from the user the set number of target cells C to be aspirated by one aspiration tip 1 (step S1). Figure 5 to Figure 7 In the example of FIG. 1 , the setting number = 3 is shown. If the setting number is too large, it is difficult to aspirate cells C to one suction tip 1 , so it is preferable to select the setting number from a range of about 2 to 5.

[0087] Next, the imaging control unit 73 controls the camera unit 5 to capture an image of the first container 41 before the cells are aspirated. The image processing unit 75 performs image processing on the acquired pre-aspiration image data to identify the positions of the cells C scattered in the first container 41 (step S2). Next, the sorting unit 76 derives an evaluation value related to the quality of the cells C based on the pre-aspiration image, and identifies the cells whose evaluation value exceeds a specified threshold as target cells C to be moved (step S3).

[0088] Next, under the control of the axis control unit 71 and the suction control unit 72, a cell movement step (S4) including the above-mentioned preliminary processing step (1), suction step (2), movement step (3) and discharge step (4) is executed. After the aspirated target cells C are discharged into the second container 42, the camera control unit 73 controls the camera unit 5 to capture an image of the first container 41 after the cells are aspirated. Then, the determination unit 77 compares the pre-aspiration image acquired in step S2 with the post-aspiration image acquired in this step to confirm whether the aspiration of the target cells C is successful, that is, whether the movement of the target cells is successful (step S5).

[0089] If the suction of the set number of target cells C is successful (Yes in step S6), the process ends. On the other hand, if the suction of a part or all of the target cells C fails (No in step S6), the process returns to step S3 and executes the cell moving step for recovery again.

[0090] Fig.11 Flowchart showing the operation of the cell moving step of step S4. Here, an example is shown in which the head unit 6 has three heads 61, there are nine cells C1 to C9 to be moved, and three cells are sucked by the suction tip 1 installed in each head 61 (the set number of target cells = 3). Fig.11 In the flowchart of , the three heads 61 are referred to as a first head, a second head, and a third head.

[0091] If in Fig.10 In step S3 of the embodiment, the suction control unit 72 sets the movement routes of the first head, the second head, and the third head on the first container 41 to perform suction of the target cells C1 to C9, and then the suction control unit 72 moves the first to third heads along the set movement routes, and causes each suction tip 1 to sequentially suction three target cells C1 to C9.

[0092] First, the suction control unit 72 causes the cells C1, C2, and C3 to be sucked into the suction tip 1 mounted on the first head in stages (steps S12, S13, and S14). This series of suction actions is accompanied by the lifting and horizontal movement of the first head. Figure 8 In the example of the dish 43 shown in (A), the suction action including the descent of the first head, the suction of the cell Ca (C1) to the suction tip 1, and the rise of the first head is performed in the first approached storage area 44a (step S12). Then, the first head moves horizontally to the top of the second approached storage area 44b, and similarly performs the suction action on the cell Cb (C2) (step S13). For the third approached storage area 44c, the horizontal movement of the first head and the suction action on the cell Cc (C3) are also performed (step S14).

[0093] Next, the suction control unit 72 causes cells C4, C5, and C6 to be suctioned into the suction tip 1 mounted on the second head in stages (steps S15, S16, and S17). Furthermore, the suction control unit 72 causes cells C7, C8, and C9 to be suctioned into the suction tip 1 mounted on the third head in stages (steps S18, S19, and S20). The actions in these steps are the same as the suction actions of the first head (steps S12 to S14).

[0094] When the suction of the target cells C1 to C9 to the suction tips 1 of the first to third heads is completed, the axis control unit 71 moves the head unit 6 to the top of the second container 42 (step S21). Then, the suction control unit 72 causes the target cells C1 to C9 to be discharged from the suction tips 1 of the first to third heads to the designated holes 45 (step S22). Specifically, the suction tip 1 of the first head is aligned with the first hole 45 designated in advance, and cells C1, C2, and C3 are discharged to the first hole 45. Similarly, cells C4, C5, and C6 are discharged from the suction tip 1 of the second head to the second hole 45 designated in advance, and cells C7, C8, and C9 are discharged from the suction tip 1 of the third head to the third hole 45 designated in advance.

[0095] Fig.12 1 is a flowchart showing the details of the cell suction operation of a set number of target cells C performed by the suction tip 1 of one head 61. Fig.12 The "head" in the flowchart is equivalent to Fig.11 Here, it is also assumed that the set number of target cells C to be aspirated by one suction tip 1 = 3.

[0096] The suction control unit 72 causes the head 61 equipped with the suction tip 1 to perform three suction actions #1, #2, and #3 in the first container 41 according to the set number = 3 (steps S31, S32, and S33). The suction actions #1, #2, and #3 here are the same as the suction actions described in the previous steps S12, S13, and S14. Then, the head 61 is moved to the second container 42, and the suction control unit 72 causes the target cells C sucked in the suction actions #1, #2, and #3 to be discharged into the predetermined holes 45 (step S34).

[0097] Next, the determination unit 77 compares the image of the first container 41 before aspirating the cells with the image of the first container 41 after aspirating the cells, or compares the image of the second container 42 after the cells are discharged, and performs processing to determine whether the aspiration of the target cells C is successful (step S36). If the aspiration actions #1, #2, and #3 are all successful (yes in step S37), the processing of the head 61 (for example, the first head) is terminated, and the processing is transferred to the next head 61 (for example, the second head). If the aspiration actions #1, #2, and #3 are not all successful (no in step S37), it is determined whether the aspiration actions #1, #2, and #3 are all failed (step S38).

[0098] When all the suction actions #1, #2, and #3 fail (Yes in step S38), the suction control unit 72 performs a retry of the suction action. That is, the suction control unit 72 returns the head 61 to the first container, and causes the suction tip 1 mounted on the head 61 to perform three suction actions #1, #2, and #3 on the target cell C (steps S39, S40, and S41). Next, the head 61 is moved to the second container 42, and the suction control unit 72 causes the target cell C sucked in the retried suction actions #1, #2, and #3 to be discharged into the predetermined hole 45 (step S42). Then, the determination unit 77 determines whether the suction is successful or not (step S43). When all the retried suction actions #1, #2, and #3 succeed, the process ends. Afterwards, when all the suction actions #1, #2, and #3 fail, a retry may be performed again, or the hole 45 may be set as an abandoned object (failure) without retrying again.

[0099] If the suction actions #1, #2, and #3 have not all failed (No in step S38), the number of failed suction actions is confirmed (step S44). If the suction of two target cells C fails, the suction control unit 72 returns the head 61 to the first container, and allows the suction tip 1 installed in the head 61 to perform two retry suction actions #1 and #2 on the target cells C (steps S45 and S46). Next, the head 61 is moved to the second container 42, and the suction control unit 72 allows the target cells C sucked in the retry suction actions #1 and #2 to be discharged into the predetermined holes 45 (step S47). Then, the determination unit 77 determines whether the suction is successful or not (step S48).

[0100] When it is determined in step S44 that the aspiration of one target cell C has failed, the aspiration control unit 72 returns the head 61 to the first container, and causes the aspiration tip 1 attached to the head 61 to perform a retry aspiration operation #1 on the target cell C (step S49). Next, the head 61 is moved to the second container 42, and the aspiration control unit 72 causes the target cell C aspirated in the retry aspiration operation #1 to be discharged into the predetermined hole 45 (step S50). Then, the determination unit 77 determines whether the aspiration is successful or not (step S51).

[0101] [Method for confirming cell aspiration]

[0102] Reference Fig.13 Description Fig.10 Step S5, Fig.12 The change of the confirmation of the success or failure of cell aspiration by the determination unit 77 executed in step S36 etc. Fig.13 In the example, three methods 1 to 3 are shown. Fig.12According to the flowchart of FIG. 1 , the control unit 7 causes the head 61 equipped with the suction tip 1 to perform suction of the target cell C in the first container 41 (step #1), and discharge the target cell C into the second container 42 (step #2). If the suction fails, the head 61 returns to the first container 41 to perform a retry suction of the target cell C (step #3), and discharges the target cell C into the second container 42 again (step #4).

[0103] As the timing for executing the confirmation of the success or failure of cell aspiration by the determination unit 77, there are two examples: between the above steps #1 and #2, or after step #2. The former, that is, photographing the first container 41, is "method 1", and the latter, that is, photographing the first container 41, is "method 2", and photographing the second container 42, is "method 3".

[0104] In both methods 1 and 2, a set number of target cells C are sucked from the first container 41 to the suction tip 1, and then the camera unit 5 captures a post-suction image of the first container 41. The determination unit 77 determines whether the cell suction is successful or not by comparing the post-suction image with the pre-suction image of the first container 41 acquired before the suction operation. In method 1, the success or failure is confirmed before step #2. According to method 1, since the success or failure is known at the stage when the head 61 is present near the first container 41, retry suction can be performed directly when aspiration failure is detected.

[0105] On the other hand, in mode 2, after step #2, that is, after the set number of target cells C are discharged into the second container 42, the camera unit 5 captures the image of the first container 41 after the aspiration, and confirms the success or failure. If the state in which a plurality of cells C are aspirated in the aspiration tip 1 continues for a long time, these cells C may settle in the aspiration tip 1 and form a mass, or may block the distal opening 24. According to mode 2, since the aspirated target cells C are discharged into the second container 42 first, the occurrence of the above-mentioned inconvenience can be suppressed.

[0106] In the method 3, after step #2, the camera unit 5 captures a post-suction image of the second container 42, and confirms the success or failure. That is, the determination unit 77 determines the success or failure of the cell suction by comparing the post-discharge image with the pre-suction image. In the method 3, it is possible to confirm whether the set number of target cells C are successfully discharged from the second container 42 based on the post-discharge image. That is, since the success or failure of the suction can be determined based on the discharge result into the second container 42, a more reliable determination can be made.

[0107] [Specific example of cell migration device]

[0108] Next, refer to Fig.14 To illustrate the assembly Figure 1A more specific cell moving device 8 of the schematic cell moving device S shown. Fig.14 2 is a perspective view showing a configuration example of a cell moving device 8. The cell moving device 8 includes a cell moving line 80, a camera unit 5, a head unit 6, and an illumination unit 56. Fig.14 In the figure, description of the base supporting the cell moving wire 80 and the moving mechanism of each unit is omitted.

[0109] The camera unit 5 and the head unit 6 are as shown in Figure 1 As described in the description. Fig.14 , a head unit 6 including eight heads 61 for mounting the suction tip 1 is illustrated. The head unit 6 is movable in the X direction and the Y direction, and can move along a designated movement path on the cell movement line 80. In addition, the head 61 can be raised and lowered in the Z direction.

[0110] The cell moving line 80 is formed by arranging in the X direction the units required for a series of cell moving steps of picking up cells contained in the first container 41 at the moving starting point and moving them to the second container 42 at the moving destination. The cell moving line 80 is formed by arranging in a row, from the -X end, a dispensing tip reserve section 82, a cell reserve section 81, a tip reserve section 84, a tip imaging section 85, a cell sorting section 83, a black cover placement section 87, a cell transfer section 86, and a tip discarding section 88.

[0111] The cell storage section 81 is a part that stores a cell culture solution containing a large number of cells and serves as a dispensing source. The cell storage section 81 includes a tube 811 that is a cylindrical container that stores a cell culture solution containing cells. The dispensing tip storage section 82 is a part that stores a plurality of dispensing tips 821. The dispensing tip storage section 82 is provided with a support frame 822 that holds the dispensing tips 821 arranged in a matrix in an upright state.

[0112] The cell sorting section 83 is a part for sorting cells of a desired size from a cell culture medium containing cells of various sizes. The cell sorting section 83 includes a first container 41 for containing a cell culture medium, a holding table 831 for positioning and holding the first container 41, and a table cover member 832 covering the upper surface of the first container 41. Figure 1 The first container 41 shown in the figure preferably includes a dish 43. The camera unit 5 captures an image of the cells held in the first container 41 under illumination by the illumination unit 56. Based on this, the position of the cells to be aspirated is determined.

[0113] The tip reserve section 84 includes a holding box 841 that holds a plurality of the above-mentioned suction tips 1 in a matrix. The suction tips 1 can be attached to and detached from the head 61 of the head unit 6. The suction tips 1 have the function of sucking cells carried in the first container 41, transporting the cells along with the movement of the head unit 6, and discharging them into the second container 42 of the cell transfer section 86. The suction tips 1 are held by the holding box 841 in a state that allows them to be easily attached to the head 61 that moves in the Z direction. The tip reserve section 84 is also provided with a liquid storage tank 842 that stores an infiltration liquid for moistening the distal end opening 24 of the suction tips 1.

[0114] The tip imaging unit 85 is a pit that provides a position where an image of the suction tip 1 mounted on the head 61 is captured. The capturing is performed by the camera unit 5. Based on the image of the suction tip 1 and the focus position information at the time of capturing, the XYZ coordinate position of the distal end opening 24 of the suction tip 1 is obtained. A correction value is derived from the difference between the coordinate position and a predetermined reference position, and is used as a correction value when controlling the movement of the head 61.

[0115] The cell transfer section 86 is a portion to which the cells aspirated from the first container 41 of the cell sorting section 83 by the aspiration tip 1 are transferred. The cell transfer section 86 includes a second container 42 and a holding table 861 for positioning and holding the second container 42. The second container 42 is a plate having many holes 45 opened on the upper surface arranged in a matrix as described above. The cells held by the aspiration tip 1 are discharged into these holes 45.

[0116] The black cap placement portion 87 is a portion where the first black cap 871 placed on the cell transfer portion 86 and the second black cap 872 placed on the cell sorting portion 83 are placed. The first and second black caps 871 and 872 are used to photograph cells placed in the first container 41 or the second container 42 in a light-shielded state for fluorescent observation of cells. The tip discarding portion 88 is a portion where the used suction tip 1 and the dispensing tip 821 are discarded after the suction and discharge operations of the cells are completed.

[0117] The cell moving device 8 includes a controller (not shown) that generally controls the operation of the cell moving device 8. The controller causes the cell moving device 8 to roughly execute a dispensing operation using the dispensing tip 821 and a cell moving operation using the suction tip 1. The controller sequentially executes the following controls 1 to 4 during the dispensing operation.

[0118] [Control 1] The head unit 6 is moved to the dispensing tip reserve section 82 , and the dispensing tip 821 is mounted on a dispensing nozzle (not shown) mounted on the head unit 6 .

[0119] [Control 2] The head unit 6 is moved to the cell storage section 81 , and a cell culture solution containing cells stored in the tube 811 is sucked into the dispensing tip 821 by a predetermined amount.

[0120] [Control 3] The head unit 6 is moved to the cell sorting section 83 , and the cell culture solution in the dispensing tip 821 is discharged into the first container 41 .

[0121] [Control 4] The head unit 6 is moved to the tip disposal section 88 , and the used dispensing tip 821 is removed from the dispensing nozzle and disposed of in the disposal section 88 .

[0122] The controller sequentially performs the following controls 5 to 8 during the cell movement operation.

[0123] [Control 5] The head unit 6 is moved to the tip reserve portion 84 , and the suction tip 1 is externally mounted on the distal end portion of the head 61 .

[0124] [Control 6] The head unit 6 is moved to the cell sorting section 83 to aspirate the cells contained in the first container 41 into the aspiration tip 1. At this time, a set number of target cells set in advance to two or more are aspirated into the aspiration tip 1 in stages.

[0125] [Control 7] The head unit 6 is moved to the cell transfer section 86 to discharge a set number of target cells in the suction tip 1 into the same location in the second container 42 , that is, into one hole 45 .

[0126] [Control 8 ] The head unit 6 is moved to the tip disposal section 88 , and the used suction tip 1 is removed from the head 61 and disposed of in the tip disposal section 88 .

[0127] According to the cell moving device described above, a set number of target cells C are collectively sucked into one suction tip 1 in the first container 41, and are discharged into one hole 45 of the second container 41, so that the efficiency of the cell C moving operation can be achieved. In the conventional method, when it is required to move a plurality of target cells C to one hole 45 of the second container 41, it is necessary to make the head 61 go back and forth between the first container 41 and the second container 42 many times, and the cell moving operation requires a lot of time. In contrast, according to the cell moving device of this embodiment, a set number of target cells C are sequentially sucked into the suction tip 1 in the first container 41, and then the head 61 is moved to the second container 42, and the cells are discharged into one hole 45 at once. Therefore, the number of times the head 61 goes back and forth between the first container 41 and the second container 42 can be reduced, and the time required for the cell moving operation can be reduced.

[0128] [Inventions included in the above-mentioned embodiments]

[0129] In addition, the above-mentioned specific embodiments mainly include inventions having the following structures.

[0130] A cell moving device according to one aspect of the present invention moves cells scattered in a first container to a second container, and includes: a head for mounting a suction tip capable of sucking and discharging the cells, and having a generating mechanism for generating suction force and discharge force at a distal opening of the suction tip; a moving mechanism for causing the head to move horizontally and vertically; a cell recognition unit including a camera for capturing an image of the first container in which the cells are scattered, and for performing position recognition of the cells based on the image; and a control unit for controlling the head and the moving mechanism to execute the cell moving action based on a result of the position recognition, wherein the control unit causes a set number of target cells, which is preset to be two or more, to be sucked into the suction tip in stages among the cells scattered in the first container, and, after causing the head to move to the second container, causes the set number of target cells sucked into the suction tip to be discharged to the same location of the second container.

[0131] According to the cell moving device, a set number of target cells are collectively sucked into the suction tip in the first container, and they are discharged to the same place in the second container, so that the efficiency of the cell moving operation can be achieved. In the previous method, one target cell is sucked into the suction tip in the first container, and it is moved to the second container, so that the one target cell is discharged to a specific place in the second container. In this method, when it is required to move multiple target cells to the specific place of the second container, it is necessary to make the head go back and forth between the first container and the second container many times, and the cell moving operation requires a lot of time. In contrast, according to the above-mentioned cell moving device, a set number of target cells are sucked into the suction tip in the first container in sequence, and then the head is moved to the second container and discharged to the same place in one go. Therefore, the number of times the head goes back and forth between the first container and the second container can be reduced, and the time required for the cell moving operation can be reduced.

[0132] In the above-mentioned cell movement device, it can also be that: the suction tip includes: an injection and suction piece, having a tubular channel connected to the distal opening; and a plunger, which is accommodated in the tubular channel in a manner that can slide in contact and generates negative pressure at the distal opening, and the head includes a moving component that moves the plunger forward and backward as the generating mechanism, and the control unit controls the following action to be repeated a number of times corresponding to the set number, namely: the head is moved in a manner that the distal opening of the suction tip is aligned with the target cell, and the plunger is moved in a manner that generates a suction force at the distal opening, thereby sucking the target cell into the suction tip.

[0133] According to this technical solution, by simply controlling the forward and backward movement of the plunger, it is possible to perform sequential suction of a set number of target cells into the suction tip and discharge them.

[0134] In the above-mentioned cell movement device, it may also include: a head unit, comprising a plurality of heads, wherein the second plate has a plurality of receiving sections from which the target cells are discharged, and the control section causes each suction tip of the plurality of heads to suck the set number of target cells, and discharges the set number of target cells from each suction tip to each receiving section of the plurality of receiving sections.

[0135] According to this technical solution, a set number of target cells can be moved from each suction tip to a plurality of receiving portions of the second container by a single movement of the head unit from the first container to the second container. Therefore, the time required for the cell movement operation can be further reduced.

[0136] In the cell moving device described above, the control unit may derive an evaluation value of the mass of cells dispersed in the first container based on the image captured by the camera, and identify cells having the evaluation value exceeding a predetermined threshold as the target cells.

[0137] According to this aspect, only cells evaluated as having good quality among the cells accommodated in the first container can be moved to the second container as target cells.

[0138] In the above-mentioned cell moving device, preferably, the control unit determines a moving route of the head when the set number of target cells are sucked stepwise into the suction tip based on the image captured by the camera.

[0139] According to this technical solution, an efficient movement route of the head can be set with reference to the image of the first container. Therefore, compared with the case where a set number of target cells are randomly sucked into the suction tip, the efficiency of the stepwise suction action of the target cells can be achieved.

[0140] In the above-mentioned cell moving device, it may also be that: after the control unit executes the action of sucking the set number of target cells from the first container to the suction tip, the camera captures the post-suction image of the first container, and, based on the post-suction image, determines whether the suction tip has sucked the set number of target cells.

[0141] According to this technical solution, it is possible to confirm whether a set number of target cells have been successfully aspirated in the first container based on the post-aspiration image. In addition, if aspiration failure is known, the insufficient target cells can be additionally moved to a designated location in the second container.

[0142] In the above-mentioned cell transfer device, preferably, after the control unit discharges the set number of target cells into the second container, the control unit causes the camera to capture a post-aspiration image of the first container.

[0143] If the state of aspirating multiple cells in the aspiration tip continues for a long time, these cells may settle in the tip and form a mass, or block the distal opening. According to the above technical solution, since the aspirated target cells are first discharged into the second container, the occurrence of the above undesirable situation can be suppressed.

[0144] In the above-mentioned cell moving device, it may also be that: after the control unit executes the action of discharging the set number of target cells from the suction tip into the second container, the camera captures the post-discharge image of the second container, and, based on the post-discharge image, determines whether the suction tip has discharged the set number of target cells.

[0145] According to this technical solution, it is possible to confirm whether a set number of target cells have been successfully discharged from the second container based on the post-discharge image. In addition, if it is known that the discharge has failed, the insufficient target cells can be additionally moved to a designated location of the second container.

[0146] In the above-mentioned cell moving device, it may also be that: the first container has a plurality of receiving areas that can each receive cells, and the control unit moves the head across the plurality of receiving areas to allow the suction tip to perform a suction action until the suction tip completes the suction of the set number of target cells.

[0147] According to this aspect, it is possible to perform an operation of aspirating target cells existing in a plurality of storage areas into one aspiration tip and discharging the target cells into the same location of the second container.

Claims

1. A cell migration device, characterized in that: The method moves cells dispersed in a first container to a second container, and comprises: A head, used for mounting a suction tip capable of aspirating and discharging the cells, and having a generating mechanism for generating a suction force and a discharging force at a distal opening of the suction tip; A moving mechanism enables the head to move horizontally and vertically; a cell recognition unit including a camera that captures an image of the first container in which the cells are scattered, and recognizes the position of the cells based on the image; and The control unit controls the head and the moving mechanism to execute the movement of the cell based on the result of the position recognition, wherein: The control unit causes a set number of target cells, which is set in advance to be two or more, to be sucked into the suction tip in stages among the cells dispersed in the first container, and After the head is moved to the second container, the set number of target cells sucked into the suction tip are discharged to the same location in the second container.

2. The cell migration device according to claim 1, characterized in that The suction tip comprises: an injection and suction member having a tubular channel connected to the distal opening; and a plunger received in the tubular channel in a slidable contact manner and generating negative pressure at the distal opening. The head includes a moving member for moving the plunger forward and backward as the generating mechanism, The control unit repeatedly performs the following actions a number of times corresponding to the set number, namely, moving the head in such a manner that the distal opening of the suction tip is aligned with the target cell, and moving the plunger in such a manner that a suction force is generated at the distal opening, thereby sucking the target cell into the suction tip.

3. The cell migration device according to claim 1 or 2, characterized in that Also includes: A head unit comprises a plurality of the above-mentioned heads, wherein: The second container has a plurality of receiving parts into which the target cells are discharged. The control unit causes each suction tip of the plurality of heads to suction the set number of target cells, and causes each suction tip to discharge the set number of target cells into each of the plurality of storage portions.

4. The cell migration device according to any one of claims 1 to 3, characterized in that The control unit derives an evaluation value of the mass of cells dispersed in the first container based on the image captured by the camera, and specifies cells whose evaluation value exceeds a predetermined threshold as the target cells.

5. The cell migration device according to any one of claims 1 to 4, characterized in that: The control unit determines a movement route of the head when the set number of target cells are sucked into the suction tip in stages based on the image captured by the camera.

6. The cell migration device according to any one of claims 1 to 5, characterized in that: After the control unit executes the action of aspirating the set number of target cells from the first container to the suction tip, the control unit allows the camera to capture a post-aspiration image of the first container, and determines whether the suction tip has aspirated the set number of target cells based on the post-aspiration image.

7. The cell migration device according to claim 6, characterized in that The control unit causes the camera to capture a post-aspiration image of the first container after the set number of target cells are discharged into the second container.

8. The cell migration device according to any one of claims 1 to 5, characterized in that: After the control unit executes the action of discharging the set number of target cells from the suction tip into the second container, the control unit causes the camera to capture a post-discharge image of the second container, and determines whether the suction tip has discharged the set number of target cells based on the post-discharge image.

9. The cell migration device according to any one of claims 1 to 8, characterized in that The first container has a plurality of storage areas each capable of storing cells. The control unit moves the head across the plurality of receiving areas to allow the suction tip to perform a suction operation until the suction tip completes suction of the set number of target cells.

Images