Cell transfer apparatus

Abstract

This cell transfer apparatus is for transferring, to a second container, cells scattered in a first container. The cell transfer apparatus is provided with: a head for having, mounted to an opening at the leading end thereof, a suction tip at which suction force and discharge force can be generated; a transfer mechanism for the head; a cell identification unit that includes a camera for capturing an image of the first container and that performs positional identification of the cells on the basis of the image; and a control unit that controls, on the basis of a result of the positional identification, the head and the transfer mechanism for executing a transfer action of the cells. The control unit causes a set quantity, which has been set in advance to 2 or more, of target cells from among the cells scattered in the first container to be suctioned step-by-step into the suction tip, causes the head to be moved to the second container, and causes the set quantity of the target cells that have been suctioned in the suction tip to be discharged to the same location in the second container.

Description

cell transfer device

[0001] The present invention relates to a cell transfer device for transferring cells scattered in one container to another container.

[0002] For example, in the fields of medical and biological research, there is a need to move cultured single cells, cell colonies, etc. (sometimes simply referred to as "cells" in this specification) from a sorting container, in which the cells are selected, to a working container where they are inspected, observed, etc. For this purpose, a cell moving device is known that uses a head equipped with a suction tip to aspirate a single target cell from the sorting container and discharge the aspirated target cell into a well of the working container.

[0003] Depending on the type of research, it may be necessary to hold multiple cells in one well of the work container. In this case, the operation of aspirating one cell into the suction tip in the source sorting container and discharging the aspirated cell in the destination work container must be repeated multiple times. In other words, the head must move back and forth between the source container and the destination container multiple times, which increases the takt time.

[0004] Patent Document 1 discloses an object observation device equipped with a suction tip capable of suctioning and holding multiple cells. However, Patent Document 1 presupposes the use of a specially shaped suction tip equipped with a horizontal cell trapping portion.

[0005] Patent No. 5897733

[0006] An object of the present invention is to provide a cell transfer device that can efficiently transfer a plurality of cells scattered in one container to another container.

[0007] A cell movement device according to one aspect of the present invention is a cell movement device for moving cells scattered in a first container to a second container, and includes: a head to which an suction tip capable of suctioning and discharging the cells is attached, and which has a generating mechanism for generating suction and discharge forces at the tip opening of the suction tip; a movement mechanism for moving the head horizontally and vertically; a cell recognition unit including a camera for capturing images of the first container in which the cells are scattered, and which recognizes the positions of the cells based on the images; and a control unit for controlling the head and the movement mechanism to perform the cell movement operation based on the results of the position recognition, wherein the control unit gradually suctions a preset number of target cells, which is set to two or more, into the suction tip from among the cells scattered in the first container, moves the head to the second container, and then discharges the set number of target cells sucked into the suction tip into the same location in the second container.

[0008] FIG. 1 is a schematic diagram illustrating the configuration of a cell migration device according to an embodiment of the present invention. FIG. 2 is a cross-sectional view of an aspiration tip attached to the head of the cell migration device. FIG. 3(A) is a cross-sectional view of a syringe, which is a component of the aspiration tip, FIG. 3(B) is a cross-sectional view of a plunger, and FIG. 3(C) is an exploded perspective view of the aspiration tip. FIG. 4 is a block diagram illustrating the control configuration of the cell migration device. FIGS. 5(A) to 5(D) are diagrams illustrating the process of aspirating cells into the aspiration tip. FIGS. 6(A) to 6(D) are diagrams illustrating the process of aspirating cells into the aspiration tip. FIGS. 7(A) to 7(C) are diagrams illustrating the movement and discharge processes of aspirated cells. FIGS. 8(A) and 8(B) are example images of a first container having a storage compartment before and after cell aspiration, and FIG. 8(C) is an example image of a well in a second container into which cells have been discharged. FIGS. 9(A) and 9(B) are example images of a first container without a storage compartment before and after cell aspiration, and FIG. 9(C) is an example image of a well in a second container into which cells have been discharged. Fig. 10 is a flowchart showing an example of the operation of the cell movement device. Fig. 11 is a flowchart showing the operation of the cell movement process by the cell movement device. Fig. 12 is a flowchart showing details of the cell suction operation by the head. Fig. 13 is a diagram showing a pattern for confirming the success or failure of cell suction. Fig. 14 is a perspective view showing an example of a cell movement line that can be assembled to the cell movement device.

[0009] Embodiments of the present invention will be described in detail below with reference to the drawings. The cell migration device according to the present invention can suck and move various types of cells derived from living organisms. Examples of cells derived from living organisms include single cells such as blood cells and single cells, small tissue fragments such as histoculture, cell aggregates such as spheroids and organoids, individuals such as zebrafish, nematodes, and fertilized eggs, and 2D or 3D cell colonies.

[0010] [Overall Configuration of Cell Movement Device] Figure 1 is a diagram showing a schematic diagram of the overall configuration of a cell movement device S. Here, a cell movement device S that moves cells C between two containers is shown. The cell movement device S includes a light-transmitting base BP having a horizontal mounting surface, a camera unit 5 disposed below the base BP, and a head unit 6 disposed above the base BP. A first container 41, which is the source of the cells C, is placed at a first mounting position P1 on the base BP, and a second container 42, which is the destination of the cells C, is placed at a second mounting position P2.

[0011] The first container 41 includes a dish 43 that holds (arranges) cells C in a scattered manner. The second container 42 includes a large number of wells 45 that can accommodate cells C. The camera unit 5 and the head unit 6 are movable at least in the X direction. The head unit 6 includes a plurality of heads 61 to which suction tips 1 that suction and discharge cells C are attached. The heads 61 are movable in the Z direction.

[0012] In general, the cell movement device S moves cells C from a first container 41 at a first placement position P1 to a second container 42 at a second placement position P2. First, the cell movement device S selects target cells C to be moved from a large number of cells scattered on a dish 43 in the first container 41, and then aspirates and holds the target cells C using the suction tip 1. The suction tip 1 holding the cells C together with the head unit 6 is moved to the second container 42, where the cells C are discharged into a well 45 in the second container 42. As will be described in detail below, during the suction in the first container 41, a preset number of target cells C (two or more) are aspirated into the suction tip 1, and these cells C are discharged into one well 45 (the same location) in the second container 42. Each part of the cell movement device S is described below.

[0013] The base BP is a rectangular flat plate having a predetermined rigidity and partially or entirely made of a light-transmitting material. A preferred base BP is a glass plate. By making the base BP from a light-transmitting material such as a glass plate, it becomes possible for the camera unit 5 disposed below the base BP to capture images of the first container 41 and the second container 42 disposed on the upper surface of the base BP through the base BP.

[0014] The first container 41 stores the culture medium L and holds a cell sorting dish 43 immersed in the culture medium L. The dish 43 has a plurality of storage compartments 44 on its upper surface that can store the cells C. The storage compartments 44 are made up of recesses that can store the cells C and are arranged in a matrix. FIGS. 8(A) and 8(B) show top views of the dish 43. The culture medium L is not particularly limited as long as it does not deteriorate the properties of the cells C, and can be selected appropriately depending on the type of cells C.

[0015] The first container 41 has a rectangular upper opening 11H on its upper surface. The upper opening 11H is an opening for introducing cells C and for picking up selected cells C. Introducing cells C is a process of discharging a cell suspension containing a large amount of cells C from a dispensing tip (not shown). Picking up cells C is performed using the above-mentioned suction tip 1. The dish 43 is disposed below the upper opening 11H. The first container 41 and the dish 43 are made of a translucent resin material or glass. This is to enable observation of the cells C held in the dish 43 using a camera unit 5 disposed below the first container 41.

[0016] The second container 42 is, for example, a microplate equipped with a plurality of wells 45 (reservoirs). The wells 45 are bottomed holes that open to the top surface of the second container 42. Each well 45 accommodates a required number of cells C 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 discharging the cells C, the tip t of the suction tip 12 enters the well 45. Each well 45 has an opening diameter that allows the tip t to enter with ease.

[0017] The camera unit 5 (part of the cell recognition section) captures images of the cells C held in the first container 41 or the second container 42 from the underside thereof. The camera unit 5 includes a lens section 51 and a camera body 52. ​​The lens section 51 is an objective lens used in optical microscopes and includes a group of lenses that form an optical image at a predetermined magnification and a lens barrel that houses this group of lenses. The camera body 52 includes an imaging element such as a CCD image sensor. The lens section 51 forms an optical image of the object to be imaged on the light receiving surface of the imaging element. The camera unit 5 is capable of horizontal movement along a guide rail 5G extending in the X direction. The camera unit 5 may also be capable of movement in the Y direction, which is perpendicular to the plane of FIG. 1 , by a movement mechanism (not shown).

[0018] The head unit 6 is a unit responsible for picking cells C from the first container 41 and transferring them to the second container 42. It includes a head group 6H, which includes multiple heads 61, and a head main body 62 to which the head group 6H is attached. A suction tip 1 capable of suctioning and discharging cells C is attached to the tip of each head 61. Each head 61 is equipped with a generating mechanism that generates suction and discharge forces at the tip t of the suction tip 1. The head main body 62 holds the head 61 so that it can move up and down in the +Z and -Z directions. The head unit 6 moves along a guide rail 6G (moving mechanism) in the X direction, in which the first container 41 and the second container 42 are aligned. In practice, the head unit 6 is also movable in the Y direction, perpendicular to the plane of FIG. 1, by a moving mechanism (not shown). In this way, the head unit 6 functions as a moving mechanism that moves the suction tip 1 horizontally in the X and Y directions and moves it up and down in the Z direction.

[0019] [Structure of the suction tip] Next, the structure of the suction tip 1 attached to the head 61 will be described. Fig. 2 is a cross-sectional view of the suction tip 1. Fig. 3(A) is a cross-sectional view of the syringe 2, Fig. 3(B) is a cross-sectional view of the plunger 3, and Fig. 3(C) is an exploded perspective view of the suction tip 1. The suction tip 1 comprises the syringe 2 having therein a tubular passage 2P which serves as a suction path for the cells C, and the plunger 3 which is slidably housed within the tubular passage 2P.

[0020] The syringe 2 includes a syringe base end 21 having a large-diameter cylindrical shape, a syringe main body 22 having a small-diameter, long cylindrical shape, and a tapered tube portion 23 connecting the base end 21 and the main body 22. A tubular passage 2P is formed in the syringe main body 22. A tip portion t located at one end of the syringe main body 22 is provided with a tip opening 24 that serves as an intake or discharge port for cells C. One end of the tubular passage 2P is connected to this tip opening 24. The syringe base end 21 is connected to the other end of the syringe main body 22 via the tapered tube portion 23.

[0021] The plunger 3 is a member that is inserted into the tubular passage 2P of the syringe 2 and moves back and forth within the tubular passage 2P to generate a negative pressure for cell suction or a positive pressure for cell discharge at the tip opening 24. The plunger 3 includes a cylindrical plunger base end 31, a needle-shaped plunger main body 32, a hemispherical portion 33 connecting the base end 31 and the main body 32, and a plunger tip 34 that is the protruding tip of the plunger main body 32.

[0022] The syringe base end 21 has a cylindrical hollow portion 2H. The outer diameter of the plunger base end 31 is set to be smaller than the inner diameter of the hollow portion 2H by a predetermined length. The outer diameter of the plunger main body 32 is set to be slightly smaller than the inner diameter of the tubular passage 2P. The shape of the inner circumferential surface of the tapered tube portion 23 matches the curved shape of the outer circumferential surface of the hemispherical portion 33. The plunger 3 is assembled to the syringe 2 in such a manner that the plunger base end 31 is housed in the hollow portion 2H and the plunger main body 32 is inserted into the tubular passage 2P of the syringe main body 22.

[0023] While Fig. 3C shows the state in which the plunger 3 has been removed from the syringe 2, Fig. 2 shows the state in which the plunger body 32 is inserted deepest into the syringe body 22, i.e., the plunger 3 is at its lowest position. At this time, the hemispherical portion 33 is completely received in the cavity of the tapered cylindrical portion 23. The length of the plunger body 32 is slightly longer than that of the syringe body 22, and in the state shown in Fig. 2, the plunger tip 34 protrudes from the tip opening 24. Furthermore, there is a gap between the inner circumferential surface of the syringe base end 21 and the outer circumferential surface of the plunger base end 31.

[0024] The plunger 3 can move upward relative to the syringe 2 from the state shown in Figure 2. When the plunger 3 moves upward a predetermined distance, the plunger tip 34 sinks into the tubular passage 2P. At this time, a suction force is generated at the tip opening 24, and the fluid around the tip opening 24, in this embodiment, the culture medium L containing the cells C, can be sucked into the tubular passage 2P. After this suction, when the plunger 3 is moved downward, the fluid sucked into the tubular passage 2P can be discharged from the tip opening 24.

[0025] The suction tip 1 is attached to the tip portion of the head 61 shown in Fig. 2. The head 61 includes a first cylindrical rod 611, a second cylindrical rod 612 disposed on the outside of the first cylindrical rod 611, and a plunger rod 613 (generating mechanism / moving member) disposed in the hollow portion of the first cylindrical rod 611.

[0026] While the second cylindrical rod 612 is a fixed rod, the plunger rod 613 and the first cylindrical rod 611 move forward and backward independently. The plunger base end 31 is provided with an attachment hole 3H, which is a cylindrical hollow space. The lower end of the plunger rod 613 is press-fitted into this attachment 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 stationary second cylindrical rod 612 is press-fitted into the hollow portion 2H of the syringe base end 21. As the plunger rod 613 moves up and down, the plunger 3 moves up and down, and as described above, a suction force or a discharge force is generated at the tip opening 24. The first cylindrical rod 611 is lowered when the suction tip 1 is removed from the head 61.

[0027] 4 is a block diagram showing the electrical configuration of the cell migration device S. The cell migration device S is equipped with a control unit 7 that controls the movement of the head unit 6, the suction and discharge of cells C by the suction tip 1, the movement and image capture of the camera unit 5, etc. The cell migration device S also includes a camera axis drive unit 53 as a mechanism for horizontally moving the camera unit 5, an X-axis motor 63 and a Y-axis motor 64 as mechanisms 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 suctioning and discharging cells C, and further includes a display unit 54 and an input unit 55.

[0028] The camera axis drive unit 53 includes a drive motor that moves the camera unit 5 horizontally along the guide rails 5G. The X-axis motor 63 and the Y-axis motor 64 are drive sources for a movement mechanism that moves the head unit 6 horizontally along the guide rails 6G. A preferred embodiment of the movement mechanism includes ball screws and nut members for the X and Y axes, and the X-axis motor 63 and the Y-axis motor 64 each rotate the ball screws forward or backward.

[0029] The Z-axis motor 65 and 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 elevated position where most of the head 61 is housed in the head body 62. The plunger motor 66 raises and lowers a plunger rod 613 ( FIG. 2 ) disposed inside the head 61, thereby generating suction force and discharge force at the distal end opening 24 of the suction tip 1.

[0030] The display unit 54 is made up of a liquid crystal display or the like, and displays images captured by the camera unit 5, images that have been subjected to image processing or the like by the control unit 7, and the like.

[0031] The input unit 55 comprises a keyboard, a touch panel, or a communication unit that communicates data with other communication devices, and receives input of operation information and various data from the user. In this embodiment, the input unit 55 receives input from the user of a set number of cells C to be discharged into one well 45 of the destination second container 42. In other words, it receives input from the user of a set number of target cells C to be aspirated into one suction tip 1 in the first container 41.

[0032] The control unit 7 consists of a processor and the like that performs various types of calculation processing, and is equipped with an axis control unit 71 (part of the movement mechanism), a suction control unit 72, an imaging control unit 73, an image memory 74, an image processing unit 75 (part of the cell recognition unit), a selection unit 76, a judgment unit 77, and a memory unit 78.

[0033] The axis control unit 71 controls the operation of the X-axis motor 63 and the Y-axis motor 64 to move the head unit 6 to a predetermined target position in the horizontal direction. The movement of the head 61 equipped with the suction tip 1 between the first container 41 and the second container 42, the positioning thereof vertically above the storage compartment 44 of the dish 43, and the positioning thereof vertically above the well 45 of the second container 42 that is the discharge target are achieved by the control of the X-axis motor 63 and the Y-axis motor 64 by the axis control unit 71.

[0034] The suction control unit 72 controls the operation of the Z-axis motor 65 and the plunger motor 66 to cause the suction tip 1 to perform suction and discharge operations of the cells C. The suction control unit 72 controls the operation of the Z-axis motor 65 to lower and raise the head 61 to be controlled toward a predetermined target position. The suction control unit 72 also controls the operation of the plunger motor 66 equipped on the head 61 to be controlled, to generate a suction force or a discharge force at the distal end opening 24 of the suction tip 1 at a predetermined timing.

[0035] In this embodiment, the suction control unit 72 executes an operation of gradually aspirating a preset number of target cells C, which is two or more, from among the cells C scattered on the dish 43 of the first container 41 into one suction tip 1. The preset number is the number received from the user via the input unit 55. Furthermore, after the axis control unit 71 moves the head 61 to the second container 42, the suction control unit 72 executes an operation of discharging the preset number of target cells C aspirated into the suction tip 1 into the same location in the second container 42, i.e., into one well 45. These controls will be explained below with reference to FIGS. 5 to 7.

[0036] The imaging control unit 73 controls the camera axis driving unit 53 to move the camera unit 5 along the guide rail 5G. The imaging control unit 73 also controls the imaging operation of the camera unit 5 to capture an image of the first container 41 or the second container 42.

[0037] The image memory 74 is a storage area provided in the microcomputer, an external storage, etc. The image memory 74 temporarily stores image data acquired by the camera unit 5.

[0038] The image processing unit 75 processes the image data captured by the camera unit 5 and stored in the image memory 74. The image processing unit 75 performs processing to recognize the positions of the cells C on the dish 43 on the image based on an image of the dish 43 in the first container 41 after the cells C have been dispensed. In addition, the image processing unit 75 uses image processing techniques to perform processing to recognize the distribution of the cells C and processing to recognize the size, shape, color, etc. of the recognized cells C. 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 cells C, thereby performing the movement operation of the cells C.

[0039] The sorting unit 76 performs a process of selecting target cells C to be transferred to the second container 42 from a group of cells C dispersed in the first container 41 based on predetermined sorting criteria. The sorting unit 76 derives an evaluation value of the quality of the cells C scattered on the dish 43 of the first container 41 based on images captured by the camera unit 5. Specifically, feature quantities of the cells C, such as the area and estimated volume of the cells C, the color and pattern of the cells C, and the light intensity when the cells C fluoresce, are extracted based on the image processing results of the image processing unit 75. The number of cells C contained in one storage compartment 44 is also detected as one of the feature quantities. This is because, when multiple cells C are contained in the storage compartment 44, it is difficult to control the number of cells C sucked into the suction tip 1, and the cells C overlap, making accurate evaluation difficult.

[0040] Thereafter, the sorting unit 76 identifies cells whose evaluation value exceeds a predetermined threshold as the target cells C. That is, the extracted feature amount of each cell C is compared with selection criterion parameters predetermined as a range of cells C to be selected, and the target cells C are identified by evaluating whether or not they belong to the range of the selection criterion parameters. Through the processing of the sorting unit 76, only the cells C that are evaluated as having excellent quality from among the cells C contained in the first container 41 can be moved to the second container 42 as target cells C.

[0041] The determination unit 77 determines whether or not the set number of target cells C has been aspirated or discharged based on an image of the first container 41 after the suction tip 1 has performed the cell aspirating operation, or an image of the second container 42 after the suction tip 1 has performed the cell aspirating operation. This determination pattern will be described in detail below with reference to FIG. 13.

[0042] The memory unit 78 stores various setting values ​​and data for the cell movement device S. In addition, the memory unit 78 also stores selection criteria parameters for the cells C to be moved. The criteria for determining whether a cell C is good or bad may differ depending on its size and type, and it is desirable to have selection criteria for each size and type obtained, for example, from the results of machine learning. The selection unit 76 reads out the selection criteria stored in the memory unit 78 during the above selection process.

[0043] [Cell Transfer Operation] Next, the cell transfer operation by the cell transfer device S will be described with reference to Figures 5 to 7. The cell transfer operation includes the following steps (1) to (4) which are performed in sequence: (1) a preliminary treatment step of retaining a preliminary treatment solution in the suction tip 1, (2) a suction step of aspirating a set number of target cells C into the suction tip 1 in the first container 41, (3) a transfer step of moving the suction tip 1 which has aspirated the cells C to the second container 42, and (4) a discharge step of discharging all of the cells C in the suction tip 1 into the well 45 of the second container 42.

[0044] 5(A) to 5(D) and 6(A) to 6(D) are diagrams illustrating the preliminary treatment step (1) and the suction step (2). FIG. 5(A) shows the suction tip 1 with the preliminary treatment liquid LA held in the space between the syringe body 22 and the plunger body 32. In the preliminary treatment step (1), for example, the tip t of the syringe 2 is immersed in a container filled with the preliminary treatment liquid LA, and the plunger 3 is moved back and forth approximately three times. This action causes the preliminary treatment liquid LA to be entrapped in the space between the syringe body 22 and the plunger body 32. While physiological saline or the like may be used as the preliminary treatment liquid LA, it is preferable to use a culture medium L.

[0045] 5A and 5B are also diagrams showing the process of forming an air layer H in the tubular passage 2P before the execution of the suction step (2). As shown in FIG. 5A, the suction control unit 72 places the tip t of the suction tip 1 in air, and then drives the plunger motor 66 to raise the plunger 3 by a predetermined length from a state in which the plunger tip 34 protrudes from the tip opening 24 of the syringe 2. As a result, an air layer H is formed in the tubular passage 2P near the tip opening 24.

[0046] 5(C) to 6(D) sequentially show the execution status of the suction step (2). In these figures, the first container 41 is shown in simplified form. A first cell C1, a second cell C2, and a third cell C3, selected as target cells to be moved, are scattered throughout the culture medium L1 stored in the first container 41. Here, an example is shown in which the set number of target cells is three. Furthermore, the position coordinates of each of the cells C1, C2, and C3 are determined based on the image of the first container 41 before cell suction captured by the camera unit 5.

[0047] The suction control unit 72 gradually sucks the cells C1, C2, and C3 into one suction tip 1. At this time, it determines the order in which the cells C1, C2, and C3 will be sucked, i.e., how to set the movement route of the head 61. It is desirable to select the movement route that results in the shortest movement distance by referring to the position coordinates of the cells C1, C2, and C3 in order to shorten the takt time. Here, three target cells arranged horizontally are gradually sucked in the order of the first cell C1, the second cell C2, and the third cell C3.

[0048] Figure 5(C) shows the state in which the tip 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 positioned above the first container 41. At this time, the head 61 is moved so that the tip opening 24 of the suction tip 1 is positioned vertically above the first cell C1, with reference to the position coordinates of the first cell C1. The suction control unit 72 drives the Z-axis motor 65 to lower the head 61 until the tip t is immersed in the culture medium L1 in the first container 41, specifically until the tip opening 24 is positioned approximately directly above the first cell C1 in the culture medium L1. Figure 5(C) shows the state after this descent.

[0049] Next, the suction control unit 72 drives the plunger motor 66 to raise the plunger 3 a predetermined distance. This creates a negative pressure at the tip opening 24, generating a suction force, and a portion of the culture medium L1 in the first container 41 and the first cell C1 are sucked into the tubular passage 2P through the tip opening 24. Within the tubular passage 2P, the first cell C1 floats in the sucked culture medium L1a. Figure 5(D) shows the state after the first cell C1 has been sucked.

[0050] During the suction step (2), the preliminary treatment liquid LA is already held in the space between the syringe body 22 and the plunger body 32, preventing the medium L1 from rapidly rising up the tubular passage 2P due to capillary action, internal pressure, or the like. Furthermore, the air layer H functions as a sealing layer that separates the preliminary treatment liquid LA from the medium L1a containing the first cells C1 that are subsequently aspirated within the tubular passage 2P. Therefore, the aspirated first cells C1 do not migrate into the preliminary treatment liquid LA. This prevents the first cells C1 from becoming trapped between the syringe body 22 and the plunger body 32. Furthermore, the presence of the air layer H prevents the preliminary treatment liquid LA from mixing with the medium L1 or from being discharged into the second container 42 during the subsequent discharge step (4).

[0051] Similar operations are repeated for the set number of target cells. Figure 6(A) shows the state in which the head 61 is moved horizontally a small distance, aligning the tip opening 24 of the suction tip 1 with the second cell C2. The suction control unit 72 then drives the Z-axis motor 65 to lower the head 61 until the tip opening 24 of the suction tip 1 is positioned directly above the second cell C2. The suction control unit 72 then drives the plunger motor 66 to raise the plunger 3 a predetermined distance, generating a suction force at the tip opening 24 and sucking the second cell C2 through the tip opening 24. Figure 6(B) shows the state after the second cell C2 has been sucked. At this stage, the first cell C1 and the second cell C2 are held in the suction tip 1 so that they are aligned vertically.

[0052] Figure 6(C) shows the state in which the head 61 has been further moved horizontally a small distance, aligning the tip opening 24 of the suction tip 1 with the third cell C3. The suction control unit 72 drives the Z-axis motor 65 to lower the head 61 until the tip opening 24 of the suction tip 1 is positioned nearly directly above the third cell C3. The suction control unit 72 then drives the plunger motor 66 to further raise the plunger 3 a predetermined distance, generating a suction force at the tip opening 24 and sucking the third cell C3 through the tip opening 24. Figure 6(D) shows the state after the third cell C2 has been sucked. In this example, this completes the stepwise suction of the target cells. Upon completion of the suction step (2), the first cell C1, the second cell C2, and the third cell C3 are held in the suction tip 1 so that they are aligned vertically.

[0053] 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 positioned above the second container 42. In FIG. 7(B), the second container 42 is schematically depicted. The second container 42 also stores culture medium L2. In practice, the head unit 6 is moved so that the tip t of the suction tip 1 is aligned with one of the multiple wells 45 included in the second container 42 that is the target for discharging.

[0054] 7(C) shows the situation after the above-mentioned discharge step (3) has been performed. The suction control unit 72 drives the Z-axis motor 65 to lower the head 61 until the distal end opening 24 of the suction tip 1 is immersed in the culture medium L2 in the second container 42. Next, the suction control unit 72 drives the plunger motor 66 to lower the plunger 3 a predetermined distance. Specifically, the plunger 3 is lowered until the plunger distal end 34 protrudes from the distal end opening 24. As a result, as shown in FIG. 7(C), the culture medium L1a and the cells C1, C2, and C3 held in the suction tip 1 are discharged all at once into the culture medium L2 in the second container 42.

[0055] 8(A) and (B) are example images of a first container 41 having storage compartments 44 before and after cell suction. The first container 41 includes a dish 43 having storage compartments 44 arranged in a matrix, and a large number of cells C are dispersed in the dish 43. As shown in FIG. 8(A), among these cells C, cells Ca, Cb, and Cc, each stored in storage compartments 44a, 44b, and 44c, are identified as target cells to be suctioned into one suction tip 1.

[0056] In this case, the suction control unit 72 sets a movement route MR that passes through the storage compartments 44a, 44b, and 44c in the shortest distance as the movement route of the head 61 to which the suction tip 1 is attached. Then, while the axis control unit 71 intermittently moves the head 61 along the movement route MR, the suction control unit 72 causes the suction tip 1 to gradually suction the cells Ca, Cb, and Cc. In other words, the suction control unit 72 moves the head 61 across the storage compartments 44a, 44b, and 44c until the suction tip 1 has finished suctioning the set number of target cells, causing the suction tip 1 to perform the suction operation.

[0057] After suction, the storage compartments 44a, 44b, and 44c are empty, as shown in Figure 8(B). If cells Ca, Cb, and Cc remain in the storage compartments 44a, 44b, and 44c, the suction has failed. In other words, by capturing an image of the first container 41 after cell suction and confirming the presence of cells Ca, Cb, and Cc, it is possible to confirm whether the suction tip 1 has successfully suctioned the target cells.

[0058] The suction tip 1 that has aspirated the cells Ca, Cb, and Cc is moved to the second container 42, and the cells Ca, Cb, and Cc are ejected into one well 45. Figure 8(C) is an example of an image of one well 45 after the cells have been ejected. Required operations, such as adding a reagent, are performed on the well 45 containing the cells Ca, Cb, and Cc.

[0059] 9(A) and 9(B) are example images of a flat-bottomed first container 410 without a storage compartment 44, taken before and after cell suction. A large number of cells C are dispersed in the first container 410. As shown in FIG. 9(A), among these cells C, cells Cd, Ce, and Cf, each present in areas PA1, PA2, and PA3, are identified as target cells to be suctioned into one suction tip 1. In this case, too, a movement route passing through areas PA1, PA2, and PA3 in the shortest distance is determined, and cells Cd, Ce, and Cf are gradually suctioned into one suction tip 1. Whether or not the suction was successful can be determined, for example, by image matching between the pre-suction image in FIG. 9(A) and the post-suction image in FIG. 9(B). FIG. 9(C) is an example image of a well 45 after cells Cd, Ce, and Cf have been dispensed.

[0060] The above is an operation focusing on one suction tip 1. In reality, a set number of target cells C is gradually aspirated from the first container 41 into each of the suction tips 1 attached to the multiple heads 61 of the head unit 6. Then, the set number of target cells C is suddenly ejected from each suction tip 1 into each of the multiple wells 45 of the second container 42. In other words, two or more target cells C held by each suction tip 1 are ejected into the wells 45 assigned to each suction tip 1. According to this embodiment, a set number of target cells C can be transferred from each suction tip 1 to each well 45 of the second container 42 in a single movement operation from the first container 41 to the second container 42 of the head unit 6.

[0061] [Operational Flow of the Cell Migration Apparatus] Figure 10 is a flowchart showing an example of the operation of the cell migration apparatus S. First, the input unit 55 receives from the user the set number of target cells C to be sucked into one suction tip 1 (step S1). In the examples of Figures 5 to 7 described above, an example in which the set number = 3 is shown. If the set number is too large, it becomes difficult to suck the cells C into one suction tip 1, so it is desirable to select a set number from the range of approximately 2 to 5.

[0062] Next, the imaging control unit 73 controls the camera unit 5 to capture an image of the first container 41 before cell suction. The image processing unit 75 performs image processing on the acquired pre-suction image data to identify the positions of the cells C scattered throughout the first container 41 (step S2). Next, the selection unit 76 derives an evaluation value relating to the quality of the cells C based on the pre-suction image, and identifies cells whose evaluation value exceeds a predetermined threshold as target cells C to be moved (step S3).

[0063] Next, under the control of the axis control unit 71 and the suction control unit 72, a cell movement process including the above-mentioned preliminary processing step (1), suction step (2), movement step (3), and discharge step (4) is executed (step S4). After the aspirated target cells C are discharged into the second container 42, the imaging control unit 73 controls the camera unit 5 to capture an image of the first container 41 after cell aspirate. The determination unit 77 then compares the pre-suction image acquired in step S2 with the post-suction image acquired in this step to determine whether the aspirated target cells C, i.e., whether the movement of the target cells, was successful (step S5).

[0064] If the suction of all of the target cells C in the set number is successful (YES in step S6), the process ends. On the other hand, if the suction of some or all of the target cells C fails (NO in step S6), the process returns to step S3, and the cell movement process for recovery is executed again.

[0065] 11 is a flowchart showing the operation of the cell transfer process in step S4. Here, an example is shown in which the head unit 6 has three heads 61, there are nine cells to be transferred (C1 to C9), and three cells are to be transferred to the suction tips 1 attached to each head 61 (set number of target cells = 3). The three heads 61 are referred to as the first head, second head, and third head in the flowchart of FIG. 11.

[0066] 10, when target cells C1 to C9 are selected, the suction control unit 72 sets movement routes for the first, second, and third heads above the first container 41 for suction of these cells (step S11). Thereafter, the suction control unit 72 moves the first to third heads along the set movement routes, sequentially aspirating the target cells C1 to C9 into each suction tip 1, three at a time.

[0067] First, the suction control unit 72 sequentially suctions cells C1, C2, and C3 into the suction tip 1 attached to the first head (steps S12, S13, and S14). This series of suction operations involves the elevation and horizontal movement of the first head. Using the example of the dish 43 shown in FIG. 8A, in the first storage compartment 44a, a suction operation is performed, including lowering the first head, suctioning cell Ca (C1) into the suction tip 1, and lifting the first head (step S12). Next, the first head is horizontally moved above the second storage compartment 44b, and the suction operation is similarly performed on cell Cb (C2) (step S13). For the third storage compartment 44c, the first head is horizontally moved and the suction operation is similarly performed on cell Cc (C3) (step S14).

[0068] Next, the suction control unit 72 causes the suction tip 1 attached to the second head to gradually suction cells C4, C5, and C6 (steps S15, S16, and S17). Furthermore, the suction control unit 72 causes the suction tip 1 attached to the third head to gradually suction cells C7, C8, and C9 (steps S18, S19, and S20). The operations in these steps are the same as the suction operations for the first head (steps S12 to S14).

[0069] After the first to third heads have finished suctioning the target cells C1 to C9 into their respective suction tips 1, the axis control unit 71 moves the head unit 6 above the second container 42 (step S21). The suction control unit 72 then ejects the target cells C1 to C9 from the respective suction tips 1 of the first to third heads into the corresponding designated wells 45 (step S22). Specifically, the suction tip 1 of the first head is aligned with the pre-designated first well 45, and cells C1, C2, and C3 are ejected into the first well 45. Similarly, cells C4, C5, and C6 are ejected from the suction tip 1 of the second head into the pre-designated second well 45, and cells C7, C8, and C9 are ejected from the suction tip 1 of the third head into the pre-designated third well 45.

[0070] Fig. 12 is a flowchart showing the details of the cell suction operation of a set number of target cells C using the suction tip 1 of one head 61. The "head" in the flowchart of Fig. 12 corresponds to any one of the first head, second head, and third head in the flowchart of Fig. 11. Here, too, the set number of target cells C to be sucked by one suction tip 1 is set to three.

[0071] The suction control unit 72 causes the head 61 equipped with the suction tip 1 to perform three suction operations #1, #2, and #3 in the first container 41 in accordance with the set quantity of 3 (steps S31, S32, and S33). The suction operations #1, #2, and #3 are the same as those described above in steps S12, S13, and S14. The head 61 is then moved to the second container 42, and the suction control unit 72 ejects the target cells C aspirated by the suction operations #1, #2, and #3 into a predetermined well 45 (step S34).

[0072] Next, the determination unit 77 performs a process of determining whether the suction of the target cells C was successful by comparing an image of the first container 41 before the cell suction with an image of the first container 41 after the cell suction, or based on an image of the second container 42 after the cell discharge (step S36). If all of the suction operations #1, #2, and #3 were successful (YES in step S37), the process for the current head 61 (e.g., the first head) is completed, and processing moves on to the next head 61 (e.g., the second head). If all of the suction operations #1, #2, and #3 were not successful (NO in step S37), it is determined whether all of the suction operations #1, #2, and #3 were unsuccessful (step S38).

[0073] If all of the aspiration operations #1, #2, and #3 fail (YES in step S38), the aspiration control unit 72 retries the aspiration operation. Specifically, 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 three aspiration operations #1, #2, and #3 on the target cells C (steps S39, S40, and S41). The head 61 is then moved to the second container 42, and the aspiration control unit 72 ejects the target cells C aspirated in the retry aspiration operations #1, #2, and #3 into the predetermined well 45 (step S42). The determination unit 77 then determines whether the aspiration was successful (step S43). If all of the retry aspiration operations #1, #2, and #3 are successful, the process ends. Thereafter, if all of the aspiration operations #1, #2, and #3 are not successful, a retry may be performed, or the well 45 may be treated as NG without a retry.

[0074] If none of the aspiration operations #1, #2, and #3 failed (NO in step S38), the number of failed aspiration operations is confirmed (step S44). If the aspiration of two target cells C 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 two retry aspiration operations #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 aspiration control unit 72 discharges the target cells C aspirated in the retry aspiration operations #1 and #2 into the predetermined well 45 (step S47). The judgment unit 77 then judges whether the aspiration was successful (step S48).

[0075] If it is determined in step S44 that the suction of one target cell C has failed, the suction control unit 72 returns the head 61 to the first container and causes the suction tip 1 attached to the head 61 to perform one retry suction operation #1 on the target cell C (step S49). Next, the head 61 is moved to the second container 42, and the suction control unit 72 discharges the target cell C aspirated in the retry suction operation #1 into a predetermined well 45 (step S50). Thereafter, the determination unit 77 determines whether the suction was successful (step S51).

[0076] [Patterns for Confirming Cell Aspiration] Variations in the confirmation of the success or failure of cell aspiration by the determination unit 77, which are performed in step S5 of Fig. 10 and step S36 of Fig. 12, etc., are described with reference to Fig. 13. Fig. 13 illustrates three patterns, patterns 1 to 3. To summarize the flowchart in Fig. 12, the control unit 7 causes the head 61, to which the aspiration tip 1 is attached, to perform an aspiration operation 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 aspiration fails, the control unit 7 returns to the first container 41 and performs a retry aspiration operation of the target cell C (step #3), and discharges the target cell C again into the second container 42 (step #4).

[0077] The timing for the determination unit 77 to check whether the cell suction has been successful can be either between steps #1 and #2 or after step #2. In the former case, imaging the first container 41 is "Pattern 1," and in the latter case, imaging the first container 41 is "Pattern 2," and imaging the second container 42 is "Pattern 3."

[0078] In both patterns 1 and 2, after a set number of target cells C are aspirated from the first container 41 into the suction tip 1, the camera unit 5 is caused to capture a post-suction image of the first container 41. The determination unit 77 compares this post-suction image with a pre-suction image of the first container 41 acquired before the suction operation to determine whether the cell suction was successful. In pattern 1, success or failure is confirmed before step #2. According to pattern 1, success or failure is determined when the head 61 is near the first container 41, so it is possible to immediately perform retry suction when a suction failure is detected.

[0079] On the other hand, in Pattern 2, after step #2, i.e., after the set number of target cells C have been discharged into the second container 42, the camera unit 5 takes a post-suction image of the first container 41 to confirm whether the process was successful. If the state in which multiple cells C are aspirated into the suction tip 1 continues for a long time, these cells C may settle and form clumps within the suction tip 1 or block the tip opening 24. According to Pattern 2, the aspirated target cells C are discharged into the second container 42 first, thereby preventing the occurrence of such problems.

[0080] In pattern 3, after step #2, the camera unit 5 captures a post-discharge image of the second container 42, and the success or failure is confirmed. That is, the determination unit 77 determines the success or failure of cell aspiration by comparing this post-discharge image with the pre-suction image. In pattern 3, it is possible to confirm whether the set quantity of target cells C was successfully discharged from the second container 42 based on the post-discharge image. That is, the success or failure of aspiration can be determined based on the discharge result into the second container 42, allowing for a more reliable determination.

[0081] [Specific Example of Cell Migration Device] Next, referring to Figure 14, a more specific example of a cell migration device 8 incorporating the schematic cell migration device S shown in Figure 1 is shown. Figure 14 is a perspective view showing an example of the configuration of the cell migration device 8. The cell migration device 8 includes a cell migration line 80, a camera unit 5, a head unit 6, and an illumination unit 56. Figure 14 does not show the base that supports the cell migration line 80 or the migration mechanisms of each unit.

[0082] The camera unit 5 and head unit 6 are as described in Fig. 1. Fig. 14 illustrates a head unit 6 including eight heads 61 to which suction tips 1 are attached. The head unit 6 is movable in the X and Y directions, and can move along a predetermined movement path on the cell movement line 80. The heads 61 can also move up and down in the Z direction.

[0083] Cell migration line 80 is configured by arranging in the X direction elements necessary for carrying out a series of cell migration steps, which involves picking up cells contained in a first container 41 as a migration source and moving them to a second container 42 as a migration destination. Cell migration line 80 is configured by arranging, in order from the -X end, a dispensing tip stock unit 82, a cell stock unit 81, a tip stock unit 84, a tip imaging unit 85, a cell sorting unit 83, a black cover mounting unit 87, a cell transfer unit 86, and a tip disposal unit 88 in a line.

[0084] The cell stock section 81 is a section for storing the cell culture medium containing a large amount of dispersed cells, which is the source of dispensing. The cell stock section 81 includes a tube 811, which is a cylindrical container for storing the cell culture medium containing cells. The dispensing tip stock section 82 is a section for storing a plurality of dispensing tips 821. The dispensing tip stock section 82 is provided with a holder 822 that holds the dispensing tips 821 arranged in a matrix in an upright position.

[0085] The cell sorting unit 83 is a section for sorting cells of a desired size from a cell culture solution containing cells of various sizes. The cell sorting unit 83 includes a first container 41 that contains a cell culture solution, a holding table 831 that positions and holds the first container 41, and a table lid member 832 that covers the top surface of the first container 41. The first container 41 preferably includes a dish 43, similar to the first container 41 shown in FIG. 1. An image of the cells held in the first container 41 is captured by the camera unit 5 under illumination by the illumination unit 56. This identifies the position of the cells to be aspirated.

[0086] The tip stock section 84 includes a holding box 841 that holds a large number of the above-mentioned suction tips 1 arranged 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 perform the function of aspirating cells held in the first container 41, transporting the cells as the head unit 6 moves, and discharging the cells into the second container 42 of the cell transfer section 86. The suction tips 1 are held in 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 stock section 84 also has a reservoir 842 that stores an impregnation liquid that wets the tip opening 24 of the suction tip 1.

[0087] The tip imaging unit 85 is a pit that provides a position where an image of the suction tip 1 attached to the head 61 is captured. The image is captured by the camera unit 5. The XYZ coordinate position of the distal opening 24 of the suction tip 1 is determined based on the image of the suction tip 1 and the focal position information at the time of capturing the image. A correction value is derived from the difference between the coordinate position and a predetermined reference position, and is used as the correction value when controlling the movement of the head 61.

[0088] The cell transfer unit 86 is a destination for cells aspirated by the suction tip 1 from the first container 41 of the cell sorter 83. The cell transfer unit 86 includes a second container 42 and a holding table 861 that positions and holds the second container 42. As described above, the second container 42 is a plate in which a large number of wells 45, each open at the top, are arranged in a matrix. The cells held in the suction tip 1 are discharged into these wells 45.

[0089] The black cover mounting section 87 is a section where a first black cover 871 that covers the cell transfer section 86 and a second black cover 872 that covers the cell sorting section 83 are mounted. The first and second black covers 871, 872 are used when imaging cells held in the first container 41 or the second container 42 in a light-shielded state for fluorescent observation of the cells. The tip disposal section 88 is a section where used suction tips 1 and dispensing tips 821 are disposed of after the cell suction and discharge operations have been completed.

[0090] The cell movement device 8 includes a controller (not shown) that comprehensively controls the operation of the cell movement device 8. The controller causes the cell movement device 8 to perform, roughly speaking, a dispensing operation using the dispensing tip 821 and a cell movement operation using the suction tip 1. The controller sequentially executes the following controls 1 to 4 during the dispensing operation. [Control 1] The head unit 6 is moved above the dispensing tip stock section 82, and the dispensing tip 821 is attached to a dispensing nozzle (not shown) mounted on the head unit 6. [Control 2] The head unit 6 is moved above the cell stock section 81, and a predetermined amount of cell culture fluid containing cells stored in the tube 811 is aspirated into the dispensing tip 821. [Control 3] The head unit 6 is moved above the cell sorting section 83, and the cell culture fluid in the dispensing tip 821 is discharged into the first container 41. [Control 4] The head unit 6 is moved above the tip disposal unit 88, and the used dispensing tip 821 is removed from the dispensing nozzle and disposed of in the disposal unit 88.

[0091] The controller sequentially executes the following controls 5 to 8 during the cell transfer operation. [Control 5] The head unit 6 is moved above the tip stock section 84, and the suction tip 1 is fitted onto the tip of the head 61. [Control 6] The head unit 6 is moved above the cell sorting section 83, and the cells contained in the first container 41 are aspirated into the suction tip 1. At this time, a preset number of target cells, which may be two or more, are gradually aspirated into the suction tip 1. [Control 7] The head unit 6 is moved above the cell transfer section 86, and the set number of target cells in the suction tip 1 are ejected into the same location of the second container 42, i.e., one well 45. [Control 8] The head unit 6 is moved above 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.

[0092] According to the cell movement device described above, a set number of target cells C are aspirated into one suction tip 1 in the first container 41 and then discharged into one well 45 in the second container 41, thereby improving the efficiency of the cell C movement operation. In conventional methods, when multiple target cells C are to be moved to one well 45 in the second container 41, the head 61 must move back and forth between the first container 41 and the second container 42 multiple times, which requires a lot of time for the cell movement operation. In contrast, according to the cell movement device of this embodiment, a set number of target cells C are sequentially aspirated into the suction tip 1 in the first container 41, and then the head 61 is moved to the second container 42 and discharged into one well 45 at a time. This reduces the number of times the head 61 moves back and forth between the first container 41 and the second container 42, thereby shortening the time required for the cell movement operation.

[0093] [Inventions Included in the Above-Described Embodiments] The above-described specific embodiments mainly include inventions having the following configurations.

[0094] A cell movement device according to one aspect of the present invention is a cell movement device for moving cells scattered in a first container to a second container, and includes: a head to which an suction tip capable of suctioning and discharging the cells is attached, and which has a generating mechanism for generating suction and discharge forces at the tip opening of the suction tip; a movement mechanism for moving the head horizontally and vertically; a cell recognition unit including a camera for capturing images of the first container in which the cells are scattered, and which recognizes the positions of the cells based on the images; and a control unit for controlling the head and the movement mechanism to perform the cell movement operation based on the results of the position recognition, wherein the control unit gradually suctions a preset number of target cells, which is set to two or more, into the suction tip from among the cells scattered in the first container, moves the head to the second container, and then discharges the set number of target cells sucked into the suction tip into the same location in the second container.

[0095] This cell transfer device allows a set number of target cells to be aspirated into the suction tip in the first container and then dispensed into the same location in the second container, thereby improving the efficiency of cell transfer operations. In conventional methods, a single target cell is aspirated into the suction tip in the first container, transferred to the second container, and then dispensed into a specific location in the second container. In this method, when multiple target cells are to be transferred to the specific location in the second container, the head must move back and forth between the first and second containers multiple times, resulting in a long cell transfer operation. In contrast, the cell transfer device described above allows a set number of target cells to be sequentially aspirated into the suction tip in the first container, and then the head is moved to the second container and dispensed into the same location all at once. This reduces the number of times the head moves back and forth between the first and second containers, thereby shortening the time required for cell transfer operations.

[0096] In the above-mentioned cell movement device, the suction tip includes a syringe having a tubular passage connected to the tip opening, and a plunger that is slidably accommodated within the tubular passage and generates negative pressure at the tip opening, the head includes a moving member that moves the plunger back and forth as the generating mechanism, and the control unit may perform control to repeat the operations of moving the head to align the tip opening of the suction tip with the target cell, and moving the plunger to generate suction force at the tip opening to suck the target cell into the suction tip, the operations being repeated the set number of times.

[0097] According to this aspect, it is possible to sequentially aspirate a set number of target cells into the aspirating tip and then discharge them, simply by controlling the forward and backward movement of the plunger.

[0098] The above-mentioned cell movement device may further include a head unit having a plurality of the heads, the second plate having a plurality of storage sections from which the target cells are ejected, and the control section may cause each suction tip of the plurality of heads to suck in the set number of target cells, and eject the set number of target cells from each suction tip into each of the plurality of storage sections.

[0099] According to this aspect, a set number of target cells can be transferred from each suction tip to multiple storage sections of the second container in a single transfer operation from the first container to the second container of the head unit, thereby further reducing the time required for the cell transfer operation.

[0100] In the above-mentioned cell movement device, the control unit may be configured to derive an evaluation value of the quality of cells scattered within the first container based on the image captured by the camera, and to identify cells whose evaluation value exceeds a predetermined threshold as the target cells.

[0101] According to this aspect, only cells that are evaluated as having excellent quality among the cells contained in the first container can be transferred to the second container as target cells.

[0102] In the above-mentioned cell movement device, it is desirable that the control unit determines the movement route of the head when gradually aspirating the set number of target cells into the suction tip based on the image captured by the camera.

[0103] According to this aspect, it is possible to set an efficient movement route for the head by referring to the image of the first container, which makes it possible to improve the efficiency of the stepwise aspirating operation of target cells compared to when a set number of target cells are randomly aspirated into the aspirating tip.

[0104] In the above-mentioned cell movement device, the control unit may perform an operation of aspirating the set number of target cells from the first container into the suction tip, and then cause the camera to capture a post-suction image of the first container, and determine whether the suction tip has aspirated the set number of target cells based on the post-suction image.

[0105] According to this aspect, it is possible to confirm whether or not the set number of target cells has been successfully aspirated into the first container based on the post-aspiration image. Furthermore, if it is determined that aspirating has failed, it is possible to move the missing target cells to a predetermined location in the second container.

[0106] In the above cell migration device, it is preferable that the control unit, after discharging the set number of target cells into the second container, causes the camera to capture an image of the first container after suction.

[0107] If a plurality of cells are aspirated into the suction tip for a long period of time, the cells may settle and form clumps within the tip, or may block the tip opening. According to the above aspect, the aspirated target cells are discharged into the second container first, thereby preventing the occurrence of such problems.

[0108] In the above-mentioned cell movement device, the control unit may execute an operation of ejecting the set quantity of target cells from the suction tip into the second container, and then cause the camera to capture an image of the second container after ejection, and determine whether the suction tip has ejected the set quantity of target cells based on the image after ejection.

[0109] According to this aspect, it is possible to confirm whether the set number of target cells has been successfully discharged from the second container based on the post-discharge image. Furthermore, if it is determined that the discharge has failed, it is possible to move the missing target cells to a predetermined location in the second container.

[0110] In the above-mentioned cell movement device, the first container may have a plurality of storage compartments each capable of accommodating cells, and the control unit may move the head across the plurality of storage compartments to cause the suction tip to perform a suction operation until the suction tip has finished suctioning the set number of target cells.

[0111] According to this aspect, it is possible to perform an operation in which target cells present in a plurality of storage compartments are sucked into one suction tip and discharged into the same location in the second container.

Claims

1. A cell migration device for migrating cells scattered in a first container to a second container, comprising: a head to which an aspiration tip capable of aspirating and discharging the cells is attached and which is provided with a generating mechanism for generating a suction force and a discharge force at a tip opening of the aspiration tip; a moving mechanism for moving the head 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 that recognizes the positions of the cells based on the image; a control unit that controls the head and the moving mechanism to move the cell based on a result of the position recognition, The control unit gradually aspirates a preset number of target cells, which is set to two or more, from among the cells scattered in the first container into the aspirating tip, a cell moving device for moving the head to the second container, and then discharging the set number of target cells sucked into the suction tip to the same location in the second container; the first container has a plurality of storage compartments each formed of a recess capable of accommodating a cell, and the cells are held in a scattered manner in the first container by accommodating the cells in at least some of the storage compartments; The control unit of the cell movement device performs a suction operation in which a first target cell contained in a first storage compartment among multiple storage compartments in the first container is aspirated into the suction tip, then moves the suction tip to a second storage compartment different from the first storage compartment, and aspirates a second target cell contained in the second storage compartment into the suction tip.

2. 2. The cell migration device according to claim 1, The suction tip includes a syringe having a tubular passage connected to the tip opening, and a plunger slidably accommodated in the tubular passage and generating a negative pressure at the tip opening, the head includes a moving member that moves the plunger back and forth as the generating mechanism, The control unit of the cell movement device repeats the operation of moving the head to align the tip opening of the suction tip with the target cell, and moving the plunger to generate a suction force at the tip opening to suck the target cell into the suction tip the set number of times.

3. The cell migration device according to claim 1 or 2, The printer further includes a head unit including a plurality of the heads, the second container has a plurality of storage sections into which the target cells are discharged; The control unit is causing each of the aspiration tips of the plurality of heads to aspirate the set number of target cells; A cell movement device that ejects the set number of target cells from each suction tip into each of the plurality of storage units.

4. The cell migration device according to any one of claims 1 to 3, The control unit of the cell movement device derives an evaluation value of the quality of cells scattered within the first container based on the image captured by the camera, and identifies 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, The control unit determines a movement route of the head when gradually aspirating the set quantity of target cells into the suction tip based on an image captured by the camera.

6. The cell migration device according to any one of claims 1 to 5, The control unit is After performing an operation of aspirating the set number of target cells from the first container into the aspirating tip, the camera is caused to capture an image of the first container after aspirating; The cell migration device determines whether or not the suction tip has aspirated the set number of target cells based on the post-suction image.

7. The cell migration device according to claim 6, The control unit causes the camera to capture a post-suction image of the first container after discharging the set number of target cells into the second container.

8. The cell migration device according to any one of claims 1 to 5, The control unit is After executing an operation of discharging the set number of target cells from the suction tip into the second container, the camera is caused to capture an image of the second container after discharging; The cell movement device determines whether or not the suction tip has discharged the set number of target cells based on the post-discharge image.