Cell Picking Device

Abstract

The present invention provides a cell picking device that can efficiently aspirate cells in a sample. The aspiration arm is moved along the axial direction of the pipette tip in a manner that the pipette tip mounted on the aspiration arm is tilted relative to the vertical direction and the front end of the pipette tip contacts the bottom surface of the sample container. Next, the aspiration arm is moved in a manner that the front end of the pipette tip scans in the horizontal direction toward a specified position in the sample container. Next, the aspiration arm is further tilted at a specified angle in a manner that the front end of the pipette tip rises and the base end of the pipette tip descends at a specified position. Thereafter, the aspiration arm is actuated to aspirate the sample from the front end of the pipette tip.

Description

Technical Field

[0001] The invention relates to a cell picking device. Background Art

[0002] When aspirating specific cells from a container such as a cell culture container, an operator manually aspirates the cells using an aspiration device such as a pipette while confirming the position of the target cells through a microscope. However, since this operation requires skill, it is not easy for an unskilled operator to aspirate the cells. Therefore, a cell aspiration system that supports the aspiration of cells has been proposed (for example, see Patent Document 1).

[0003] In the cell suction system described in Patent Document 1, a tubular tip for sucking cells contained in a container is attached to the suction unit. The suction unit is three-dimensionally positionally adjusted by a conveying unit so that the tip of the tip approaches specific cells.

[0004] Patent Document 1: Japanese Patent Application Publication No. 2016-112012 Summary of the invention

[0005] [Problems to be solved by the invention]

[0006] In the cell suction system, the smaller the target cell is, the higher the moving resolution of the suction unit is required. Therefore, when the cell is greatly separated from the tip of the suction tip, it takes a long time to guide the tip of the suction tip into the cell, which reduces the efficiency of the suction operation. In addition, since the cell is adsorbed on the bottom surface of the container, it is not necessarily possible to efficiently suck the cell into the suction tip.

[0007] An object of the present invention is to provide a cell picking device capable of efficiently aspirating cells in a sample.

[0008] [Technical means to solve the problem]

[0009] According to one aspect of the present invention, there is provided a cell picking device for aspirating cells from a liquid sample in a container, the cell picking device comprising: a suction arm capable of mounting a pipette tip; a first driving unit for driving the suction arm and causing the suction arm to perform a suction action; and a control unit for controlling the action of the first driving unit, the control unit comprising: a moving unit for causing the suction arm to move along the axial direction of the pipette tip mounted on the suction arm in a manner such that the pipette tip is tilted relative to a vertical direction and the front end of the pipette tip contacts the bottom surface of the container; a scanning unit for moving the suction arm in a manner such that the front end of the pipette tip scans in a horizontal direction toward a specified position in the container; a tilting unit for further tilting the suction arm at a specified angle in a manner such that the front end of the pipette tip rises at the specified position and the base end of the pipette tip descends; and a suction unit for causing the suction arm to perform a suction action in a manner such that the sample is sucked from the front end of the pipette tip.

[0010] [Effects of the Invention]

[0011] According to the present invention, cells in a sample can be efficiently aspirated. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 This is a schematic diagram showing the structure of a cell picking device according to one embodiment of the present invention.

[0013] Figure 2 Yes means Figure 1 Schematic diagram of the structure of the suction device.

[0014] Figure 3 It is a diagram for explaining the operation of sucking cells using the suction device.

[0015] Figure 4 It is a diagram for explaining the operation of sucking cells using the suction device.

[0016] Figure 5 It is a diagram for explaining the operation of sucking cells using the suction device.

[0017] Figure 6 It is a diagram for explaining the operation of sucking cells using the suction device.

[0018] Figure 7 It is a diagram for explaining the operation of sucking cells using the suction device.

[0019] Figure 8 It is a diagram for explaining the operation of sucking cells using the suction device.

[0020] Fig. 9It is a diagram for explaining the operation of sucking cells using the suction device.

[0021] Fig.10 It is a diagram for explaining the operation of sucking cells using the suction device.

[0022] Fig.11 It is a diagram for explaining the discharge operation of cells using the suction device.

[0023] Fig.12 It is a diagram for explaining the discharge operation of cells using the suction device.

[0024] Fig.13 Yes means Figure 1 Figure 2 is a diagram of the structure of a control unit.

[0025] Fig.14 This is a flowchart showing an example of an algorithm of the cell storage process executed by the control unit.

[0026] Fig.15 It means that the suction processing unit performs Fig.14 Flowchart of an example of an algorithm for cell aspiration processing.

[0027] Fig.16 It means that the discharge processing unit performs Fig.14 Flowchart of an example of an algorithm for cell ejection processing. DETAILED DESCRIPTION

[0028] (1) Structure of the cell picking device

[0029] Hereinafter, a cell picking device according to an embodiment of the present invention will be described in detail with reference to the drawings. Figure 1 Schematic diagram showing the structure of a cell picking device according to one embodiment of the present invention. Figure 1 As shown, the cell picking device 100 includes a suction device 10, an observation device 20, a plate changer 30, a display unit 40, and a control unit 50. In addition, the cell picking device 100 is provided with a sample container 110, a culture plate 120, and a pipette tip rack 130 (hereinafter referred to as the rack 130).

[0030] The sample container 110 is, for example, a culture dish that contains a sample containing cells. The culture plate 120 is a multi-well plate in which a plurality of wells 121 are arranged, and is used for culturing cells. The rack 130 holds a plurality of replacement pipette tips 131 (hereinafter referred to as replacement tips 131). In this example, in the culture plate 120, 24 wells 121 are arranged in 4 rows × 6 columns. In addition, 96 replacement tips 131 are held in the rack 130 in a state of being arranged in 8 rows × 12 columns.

[0031] The suction device 10 includes a pipette-type suction arm 11. Any replacement suction tip 131 previously held by the bracket 130 is installed at the front end of the suction arm 11. Hereinafter, the replacement suction tip 131 installed in the suction arm 11 is simply referred to as the suction tip 12. The suction device 10 suctions the cells in the sample container 110 through the suction tip 12 and discharges (seeds) them into any well 121 of the culture plate 120. Thereafter, the same action is repeated using a new replacement suction tip 131 and well 121. The detailed structure and action of the suction device 10 will be described later.

[0032] The observation device 20 includes a stage 21, an illumination unit 22, a camera unit 23, and a microscope unit 24, and is arranged adjacent to the suction device 10. A sample container 110 is placed on the stage 21. The illumination unit 22 is arranged above the stage 21. The illumination unit 22 includes a light source such as a light emitting diode, and illuminates the sample container 110 placed on the stage 21. The stage 21 is light-transmissive. Alternatively, an opening may be formed in the stage 21 to allow light from the illumination unit 22 to pass downward.

[0033] The imaging unit 23 is disposed below the stage 21. The imaging unit 23 includes a plurality of lenses and cameras, and magnifies and photographs the sample in the sample container 110 illuminated by the illumination unit 22. The microscope unit 24 includes an eyepiece, a lens barrel, an objective lens, and the like, and is used by the user when magnifying and observing the sample in the sample container 110 placed on the stage 21.

[0034] The plate changer 30 is an optional device that is arranged in a manner facing the observation device 20 while sandwiching the suction device 10, and is configured to be loadable and detachable relative to the suction device 10. The plate changer 30 includes a base 31, a vertical shaft 32, a loading portion 33, and a driving portion 34. The vertical shaft 32 is provided in a manner extending in the up-down direction within the base 31. The upper portion of the vertical shaft 32 protrudes from the base 31. The loading portion 33 is mounted on the upper end of the vertical shaft 32 in a horizontal posture. The culture plate 120 and the bracket 130 are loaded on the loading portion 33.

[0035] The driving unit 34 includes a rotating unit 35 and a moving unit 36, and is connected to the mounting unit 33 via a vertical shaft 32 in the base 31. The rotating unit 35 includes, for example, an electric motor, and rotates the mounting unit 33 in a horizontal plane. Thus, the culture plate 120 and the rack 130 mounted on the mounting unit 33 are selectively moved to the vicinity of the suction device 10.

[0036] Specifically, when the suction device 10 is to discharge cells into any of the wells 121, the culture plate 120 is moved to the vicinity of the suction device 10. On the other hand, when any of the replacement tips 131 is to be mounted on the suction arm 11, the holder 130 is moved to the vicinity of the suction device 10. According to the above structure, the movement range of the placement portion 33 can be prevented from becoming larger.

[0037] The moving part 36 includes, for example, a stepping motor, and moves the placing part 33 in parallel in a horizontal plane. Specifically, the moving part 36 moves any well 121 of the culture plate 120 or any replacement suction head 131 of the rack 130 to a position where the suction arm 11 can suction (for example, below the suction arm 11). Thus, cells can be discharged from the suction device 10 to the well 121, or the replacement suction head 131 can be mounted on the suction arm 11.

[0038] The display unit 40 includes, for example, a liquid crystal display (LCD) screen or an organic electroluminescence (EL) screen, and displays the image generated by the imaging unit 23 of the observation device 20. The control unit 50 is, for example, a personal computer, including a central processing unit (CPU) and a memory, etc. The control unit 50 controls the operation of the suction device 10 and the plate changer 30.

[0039] (2) Structure of the suction device

[0040] Figure 2 Yes means Figure 1 Schematic diagram of the structure of the suction device 10. Figure 2 As shown in the figure, the suction device 10 includes a suction arm 11, a suction head 12, a holder 13, a base 14, a vertical shaft 15, and a driving unit 16. The driving unit 16 includes a rotating unit 17, a rotating unit 18, and a suction driving unit 19. The holder 13 holds the suction arm 11 on the suction driving unit 19. The vertical shaft 15 is provided on the upper surface of the base 14 so as to extend in the up-down direction.

[0041] The rotating part 17 includes, for example, an electric motor, and is rotatably mounted on the upper end of the vertical shaft 15 in the horizontal plane. The rotating part 18 includes, for example, an electric motor, and is rotatably mounted on the rotating part 17 in the vertical plane. The rotating parts 17 and 18 may also include a single electric motor that is rotatable in the horizontal plane and in the vertical plane.

[0042] The suction drive unit 19 includes, for example, a stepping motor, and is mounted on the rotating unit 18 so as to be able to move forward and backward along a predetermined direction (the up-down direction when the rotating unit 18 is not rotating in the vertical plane). In addition, the suction drive unit 19 includes a suction mechanism configured to be able to suction and discharge cells from the suction arm 11. Furthermore, the suction drive unit 19 includes a tip detachment mechanism configured to be able to detach the tip 12 from the front end of the suction arm 11.

[0043] (3) Cell suction action

[0044] Figures 3 to 10 1 is a diagram for explaining the cell suction operation performed by the suction device 10. Figure 3 As shown in FIG. 1 , a sample container 110 placed on a stage 21 contains a predetermined volume of a liquid sample 1. The sample 1 contains cells 2 to be sucked. The cells 2 are adsorbed on the bottom surface of the sample container 110 at approximately the center of the sample container 110. Figure 3 In the figure, in order to make the stage 21 and the sample container 110 easier to see, the microscope unit 24 is omitted.

[0045] During the cell suction operation, the rotating unit 17 is rotated in the horizontal plane so that the suction arm 11 and the suction head 12 face the observation device 20. In addition, the rotating unit 18 is rotated in the vertical plane so that the suction head 12 attached to the suction arm 11 is tilted at a predetermined angle. The position of the suction head 12 at this time is called a standby position.

[0046] Then, the suction drive unit 19 moves toward the front end along the axial direction of the suction head 12. Figure 4 As shown by the arrow A in the middle, the front end of the suction head 12 contacts the bottom surface of the sample container 110. Here, since the front end of the suction head 12 is pressed against the bottom surface of the sample container 110, the front end of the suction head 12 can be slightly elastically bent (refer to Figure 5 ).

[0047] Next, the suction drive unit 19 moves further toward the front end of the suction head 12. Figure 5 As shown by the middle arrow B, the suction head 12 scans along the bottom surface of the sample container 110 toward the center of the sample container 110. As a result, the tip of the suction head 12 contacts the cell 2, and the cell 2 adsorbed on the bottom surface of the sample container 110 is detached from the bottom surface.

[0048] Then, the rotating part 18 is slightly rotated in the vertical plane in such a way that the suction head 12 is further tilted. Figure 6 As shown by the arrow C, the tip of the pipette head 12 slightly rises, and the base of the pipette head 12 slightly descends, thereby separating the cells 2 from the bottom surface of the sample container 110. In the following description, the operation of tilting the pipette head 12 is referred to as a tilting operation.

[0049] The tilt angle of the suction head 12 during the tilting operation is preferably greater than 0 degrees, for example. In this case, the cells 2 can be easily peeled off from the bottom surface of the sample container 110. In addition, the tilt angle of the suction head 12 during the tilting operation is preferably less than 2 degrees, for example. In this case, the tip of the suction head 12 can be prevented from moving to the bottom surface of the sample container 110. Figure 1 The front end of the suction tip 12 can be easily observed by the user by magnifying the front end of the suction tip 12.

[0050] Then, the suction mechanism of the suction drive unit 19 is operated, as shown in FIG. Figure 7 As shown, the cells 2 are sucked into the suction head 12. In this example, the suction is started at a time point after the tilting action starts and before the tilting action stops, and the suction is stopped after a predetermined time has passed since the tilting action stops. In this case, the cells 2 can be sucked efficiently.

[0051] However, the timing of the puff is not limited to the above example, and the puff may be started at a time point after the tilting action stops, or at the same time as the tilting action starts. Alternatively, the puff may be stopped at a time point before the tilting action ends, or at the same time as the tilting action stops.

[0052] After the suction of the cells 2 is completed, the rotating part 18 slightly rotates in the reverse direction in the vertical plane. Figure 8 As shown by the arrow D in the figure, the front end of the suction head 12 is slightly lowered, and the base end of the suction head 12 is slightly raised, and the posture of the suction head 12 is restored to the posture before the tilting action. That is, the tilting action is released. In this case, by repeating Figures 4 to 8 The action of can easily carry out the continuous suction of cell 2. In the continuous suction of cell 2, Figure 8 After the action of the rotation unit 17 can be slightly rotated in the horizontal plane. In this case, the cell 2 at a position slightly different from the last suction position can be sucked.

[0053] After the suction of the cells 2 is completed, the suction drive unit 19 moves a predetermined distance in the axial direction of the suction head 12 at a predetermined first speed toward the base end. Fig. 9As shown by the arrow E in the middle, the suction head 12 rises at the first speed. The suction head 12 continues to rise at the first speed until the front end of the suction head 12 reaches a predetermined height. In this example, the predetermined height is the liquid level of the sample 1. The liquid level of the sample 1 can be estimated based on the depth of the sample container 110. In addition, the position of the front end of the suction head 12 can also be determined based on the number of pulses of the stepping motor of the suction drive unit 19.

[0054] After that, the suction drive unit 19 further moves a predetermined distance in the axial direction of the suction head 12 toward the base end at a second speed greater than the first speed. Fig.10 As shown by the middle arrow F, the suction head 12 further rises at a second speed. The second speed is, for example, more than 10 times the first speed, and in this example, it is about 70 times the first speed. The suction head 12 continues to rise at the second speed until the suction head 12 returns to the standby position.

[0055] According to the above operation, before the suction head 12 is pulled out from the sample 1, the rising speed of the suction head 12 is low, so even if the sucked cell 2 is adsorbed to the sample 1 due to surface tension, etc., the cell 2 can be prevented from falling into the sample 1 again. On the other hand, after the suction head 12 is pulled out from the sample 1, the rising speed of the suction head 12 is high, so the suction head 12 can be returned to the standby position in a short time. As a result, the operability of the cell picking device 100 is improved. In addition, the cell 2 can be prevented from being exposed to the atmosphere for a long time.

[0056] (4) Cell excretion action

[0057] Fig.11 and Fig.12 1 is a diagram for explaining the discharge operation of cells by the suction device 10. Fig.11 As shown in the figure, during the cell discharge operation, the rotating part 17 rotates in the horizontal plane so that the suction arm 11 and the suction head 12 face the plate changer 30. In addition, the rotating part 35 rotates in the horizontal plane so that the culture plate 120 is located closer to the suction device 10 than the rack 130. Furthermore, the moving part 36 moves parallel in the horizontal plane so that any well 121 of the culture plate 120 is located below the suction head 12 installed on the suction arm 11.

[0058] In this state, the suction mechanism of the suction drive unit 19 is operated, and the cells 2 in the suction head 12 are discharged downward. As a result, the discharged cells 2 are accommodated in the well 121 of the culture plate 120. After the cells 2 are discharged from the suction head 12, the suction head detachment mechanism of the suction drive unit 19 is operated, thereby detaching the suction head 12 from the front end of the suction arm 11. The detached suction head 12 is discarded in a discarding portion not shown.

[0059] Afterwards, if Fig.12As shown in the figure, the rotating part 35 rotates in the horizontal plane so that the support 130 is located closer to the suction device 10 than the culture plate 120. In addition, the moving part 36 moves parallel to the horizontal plane so that any replacement suction head 131 held in the support 130 is located below the front end of the suction arm 11. In the above state, the suction drive part 19 moves downward. In the above case, the replacement suction head 131 held in the support 130 is installed as the suction head 12 at the front end of the suction arm 11. In this way, it is possible to repeat Figures 3 to 10 The suction action of cell 2.

[0060] In the culture plate 120, the order of the wells 121 for accommodating the cells 2 is pre-registered in the control unit 50. Similarly, in the rack 130, the order of the replacement tips 131 mounted on the suction arm 11 is pre-registered in the control unit 50. In the case of repeating the suction operation of the cells 2, new replacement tips 131 and wells 121 are used in accordance with the order of the wells 121 and replacement tips 131 registered in the control unit 50, and the discharge operation of the cells 2 is repeated. In this way, the cells 2 can be automatically and chronologically accommodated in the plurality of wells 121 of the culture plate 120.

[0061] Furthermore, in this example, when the number of wells 121 in the culture plate 120 that do not contain cells 2 (the number of vacant wells 121) decreases to a specified number, the control unit 50 notifies the user. Also, when the number of replacement tips 131 held in the rack 130 decreases to a specified number, the control unit 50 notifies the user. By recognizing the notification, the user can prepare a new culture plate 120 or rack 130 and place it on the placement unit 33 at an appropriate time.

[0062] As a method of notification, a character string corresponding to the content of the notification may be displayed on the display unit 40. Alternatively, when the cell picking device 100 includes a sound output device, a sound corresponding to the content of the notification (including a notification sound such as a buzzer) may be output from the sound output device. In addition, when the cell picking device 100 includes a display light such as a lamp, the display light may be turned on or off in a manner corresponding to the content of the notification.

[0063] In the above embodiment, when the suction operation of the cell 2 is not repeated, the Fig.12 The new replacement suction head 131 is installed on the suction arm 11. In addition, in the initial state, when the suction head 12 is not installed on the suction arm 11, Figures 3 to 10 Before the aspiration of cell 2 begins, execute Fig.12 The replacement suction head 131 is installed on the suction arm 11.

[0064] (5) Cell collection and processing

[0065] Fig.13 Yes means Figure 1 FIG. 5 is a diagram showing a structure of a control unit 50. Fig.14 FIG. 5 is a flowchart showing an example of an algorithm for the cell storage process executed by the control unit 50. Fig.13 As shown in FIG. 1 , the control unit 50 includes an information acquisition unit 51, a suction processing unit 60, and a discharge processing unit 70 as functional units. The CPU of the control unit 50 implements the functional units of the control unit 50 by executing the cell storage program stored in the memory. Part or all of the functional units of the control unit 50 may also be implemented by hardware such as electronic circuits. Fig.13 The control unit 50 and Fig.14 Flowchart illustrating the cell containment process.

[0066] First, the information acquisition unit 51 acquires various information registered by the user (hereinafter referred to as registration information) (step S1). The user can register a position in the sample container 110 where the cell 2 is likely to exist or a position near the position as the suction position. In addition, the user can register the number of repetitions of continuous suction and the number of times the cell 2 is accommodated.

[0067] Furthermore, the user can register information related to the sample container 110, the culture plate 120, and the rack 130. The information related to the sample container 110 includes the depth and other dimensions of the sample container 110. The information related to the culture plate 120 includes the number of wells 121 and the order of the wells 121 for accommodating the cells 2. The information related to the rack 130 includes the number of replacement tips 131 held and the order of the replacement tips 131 mounted on the suction arm 11.

[0068] Next, the suction processing unit 60 performs a cell suction process (step S2). The cell suction process is a process of suctioning cells 2 from the sample 1 contained in the sample container 110 into the suction head 12 based on the registration information acquired in step S1. In this example, the suction head 12 is mounted on the suction arm 11 in the initial state. However, if the suction head 12 is not mounted on the suction arm 11 in the initial state, the following steps are performed between step S1 and step S2. Fig.16 Steps S26 to S29.

[0069] Next, the discharge processing unit 70 performs a cell discharge process (step S3). The cell discharge process is a process of discharging the cells 2 sucked into the tip 12 in the cell aspiration process of step S2 into any well 121 of the culture plate 120 and then replacing the tip 12. Details of the cell aspiration process and the cell discharge process will be described later.

[0070] After that, the moving section 61 described later of the suction processing section 60 determines whether to continue to accommodate the cell 2 (step S4). When the number of times the cell 2 is accommodated is less than the registered number (the number obtained in step S1), the moving section 61 determines that the cell 2 is to be accommodated and returns to step S2. Steps S2 to S4 are repeated until the number of times the cell 2 is accommodated reaches the registered number. When the number of times the cell 2 is accommodated reaches the registered number, the moving section 61 determines that the cell 2 is not to be accommodated and ends the cell accommodation process.

[0071] (6) Cell aspiration treatment

[0072] Fig.15 It means that the suction processing unit 60 performs Fig.14 Flowchart of an example of an algorithm for cell aspiration processing. Fig.13 As shown in FIG. 1 , the suction processing unit 60 includes a moving unit 61, a scanning unit 62, a tilting unit 63, a suction unit 64, a tilt release unit 65, a first retreat unit 66, and a second retreat unit 67 as further functional units. Figures 3 to 10 Suction arm 11, Fig.13 The suction processing unit 60 and Fig.15 Flowchart illustrating the cell aspiration process.

[0073] First, the advancing unit 61 controls the rotating unit 17, the rotating unit 18 and the suction driving unit 19 to advance the suction head 12 mounted on the suction arm 11 to the sample 1 in the sample container 110 ( Figure 3 , Figure 4 In addition, the scanning unit 62 controls the suction drive unit 19 to scan the suction head 12 in such a way that the front end of the suction head 12 faces the suction position obtained in step S1 ( Figure 5 and step S12).

[0074] Next, the tilting unit 63 controls the rotating unit 18 to tilt the suction head 12 ( Figure 6 In addition, the suction unit 64 controls the suction drive unit 19 to suck the cells 2 into the suction head 12 ( Figure 7 Step S14 is executed before step S13 is completed. Next, the tilt release unit 65 releases the tilting action of the suction head 12 by controlling the rotating unit 18 ( Figure 8 and step S15).

[0075] After that, the scanning unit 62 determines whether to continue suction (step S16). When continuous suction is not performed, the scanning unit 62 determines that suction is not continued, and enters step S17. When continuous suction is performed, if the number of repetitions of continuous suction performed is less than the registered number (the number obtained in step S1), the scanning unit 62 determines that suction is continued, and returns to step S12. Steps S12 to S16 are repeated until the number of repetitions of continuous suction performed reaches the registered number. When the number of repetitions of continuous suction performed reaches the registered number, the scanning unit 62 determines that suction is not continued, and enters step S17.

[0076] In step S17, the first retracting unit 66 controls the suction driving unit 19 to retract the suction head 12 from the sample 1 at a first speed ( Fig. 9 Next, the first retracting portion 66 determines whether the front end of the suction head 12 has reached a predetermined height (step S18). If the front end of the suction head 12 has not reached the predetermined height, steps S17 and S18 are repeated until the front end of the suction head 12 reaches the predetermined height.

[0077] When the tip of the suction head 12 reaches a predetermined height, the second retracting unit 67 controls the suction driving unit 19 to retract the suction head 12 from the sample 1 at a second speed ( Fig.10 Then, the second retracting unit 67 determines whether the suction head 12 has returned to the standby position (step S20). If the suction head 12 has not returned to the standby position, steps S19 and S20 are repeated until the suction head 12 returns to the standby position. If the suction head 12 returns to the standby position, the second retracting unit 67 ends the cell aspiration process.

[0078] (7) Cell excretion treatment

[0079] Fig.16 This indicates that the discharge processing unit 70 performs Fig.14 Flowchart of an example of an algorithm for cell ejection processing. Fig.13 As shown in FIG. 1 , the discharge processing unit 70 includes a first position adjustment unit 71, a discharge unit 72, a disassembly unit 73, a first notification unit 74, a second position adjustment unit 75, a mounting unit 76, and a second notification unit 77 as further functional units. Fig.11 and Fig.12 Suction arm 11, Fig.13 The discharge processing unit 70 and Fig.16 Flowchart illustrating the cell ejection process.

[0080] First, the first position adjustment unit 71 controls the rotating unit 17, the rotating unit 18, the rotating unit 35 and the moving unit 36 ​​according to the order of the wells 121 obtained in step S1, thereby adjusting the positional relationship between the suction arm 11 and the culture plate 120 ( Fig.11 In the above case, the next well 121 in the culture plate 120 that is to contain the cells 2 is located below the front end of the suction arm 11.

[0081] Next, the discharge unit 72 discharges the cells 2 in the suction head 12 by controlling the suction drive unit 19 (step S22). Thus, the cells 2 are contained in the well 121. Next, the detachment unit 73 detaches the suction head 12 from the suction arm 11 by controlling the suction drive unit 19 (step S23).

[0082] Afterwards, the first notification unit 74 determines whether the number of vacant wells 121 in the culture plate 120 is greater than or equal to a prescribed number based on the number of wells 121 acquired in step S1 (step S24). If the number of vacant wells 121 is greater than or equal to the prescribed number, the first notification unit 74 proceeds to step S26. If the number of vacant wells 121 is less than the prescribed number, the first notification unit 74 notifies the user (step S25) and proceeds to step S26.

[0083] In step S26, the second position adjustment unit 75 controls the rotating unit 17, the rotating unit 18, the rotating unit 35 and the moving unit 36 ​​according to the order of the replacement suction heads 131 obtained in step S1, thereby adjusting the positional relationship between the suction arm 11 and the bracket 130 ( Fig.12 In the above case, the next replacement suction head 131 to be mounted on the suction arm 11 in the bracket 130 is located below the front end of the suction arm 11 .

[0084] Next, the mounting unit 76 mounts the replacement suction head 131 on the suction arm 11 by controlling the suction drive unit 19 (step S27 ). Specifically, the replacement suction head 131 is mounted on the suction arm 11 as the suction head 12 by moving the suction arm 11 downward.

[0085] Thereafter, the second notification unit 77 determines whether the number of replacement tips 131 in the rack 130 is greater than or equal to a predetermined number based on the number of replacement tips 131 acquired in step S1 (step S28). If the number of replacement tips 131 is greater than or equal to the predetermined number, the second notification unit 77 terminates the cell discharge process. If the number of replacement tips 131 is less than the predetermined number, the second notification unit 77 notifies the user (step S29), and terminates the cell discharge process.

[0086] (8) Effect

[0087] In the cell picking device 100 of the present embodiment, the suction arm 11 is moved along the axial direction of the suction head 12 so that the suction head 12 attached to the suction arm 11 is tilted relative to the vertical direction and the tip of the suction head 12 contacts the bottom surface of the sample container 110. Then, the suction arm 11 is moved so that the tip of the suction head 12 scans in the horizontal direction toward a predetermined position in the sample container 110. Next, at the predetermined position, the suction arm 11 is further tilted at a predetermined angle so that the tip of the suction head 12 rises and the base of the suction head 12 falls. Thereafter, by performing the suction operation of the suction arm 11, the cells 2 in the sample 1 are sucked from the tip of the suction head 12.

[0088] According to the above structure, the tip of the suction head 12 is scanned toward a predetermined position while the tip of the suction head 12 is in contact with the bottom surface of the sample container 110, so that the cells 2 in the sample 1 are scraped by the tip of the suction head 12. Here, it is not necessary to scan the tip of the suction head 12 with high resolution. Therefore, even when the cells 2 are greatly separated from the tip of the suction head 12, the cells 2 in the sample 1 can be efficiently scraped to the tip of the suction head 12 by scanning the suction arm 11. In addition, even when the cells 2 are adsorbed on the bottom surface of the sample container 110, the cells 2 scraped by the tip of the suction head 12 are also peeled off from the bottom surface of the sample container 110 by further tilting the suction arm 11. As a result, the cells 2 in the sample 1 can be efficiently sucked.

[0089] (9) Other Implementations

[0090] (a) In the above embodiment, the suction arm 11 is not configured to be movable in parallel in a horizontal plane, but the embodiment is not limited thereto. The suction arm 11 may also be configured to be movable in parallel in a horizontal plane. Specifically, a moving portion identical to the moving portion 36 may be provided in the suction device 10. In the above case, the first position adjustment portion 71 or the second position adjustment portion 75 may control the moving portion of the suction device 10 instead of controlling the moving portion 36. In addition, the moving portion 36 may not be provided in the plate changer 30.

[0091] (b) In the above embodiment, the tilting action of the suction head 12 is released after the cells 2 are sucked into the suction head 12, but the embodiment is not limited to this. In the case where the cells 2 are not continuously sucked, the tilting action of the suction head 12 may not be released after the cells 2 are sucked into the suction head 12.

[0092] (c) In the above embodiment, the suction head 12 retreats at a first speed until its front end reaches a predetermined height, and then retreats at a second speed until it returns to the standby position, but the embodiment is not limited thereto. In the case where the sucked cells 2 are not adsorbed on the sample 1, the suction head 12 may retreat at a certain speed until it returns to the standby position.

[0093] (d) In the above embodiment, the predetermined height when the suction head 12 is retracted is the liquid level of the sample 1, but the embodiment is not limited to this. The predetermined height may be slightly lower than the liquid level of the sample 1. Alternatively, the predetermined height may be slightly higher than the liquid level of the sample 1.

[0094] (e) In the above embodiment, the driving unit 34 includes the rotating unit 35, but the embodiment is not limited thereto. In the case where the culture plate 120 and the rack 130 can be selectively moved to the vicinity of the suction device 10 by fully and largely moving the placing unit 33 in the horizontal plane using the moving unit 36, the driving unit 34 may not include the rotating unit 35.

[0095] (f) In the above embodiment, the suction head 12 on the suction arm 11 is replaced automatically, but the embodiment is not limited to this. The suction head 12 on the suction arm 11 may also be replaced manually by the user. In the above case, the driving unit 34 may not include the rotating unit 35, and the control unit 50 may not include the detaching unit 73, the second position adjusting unit 75, the mounting unit 76, and the second notification unit 77.

[0096] (g) In the above embodiment, the cell picking device 100 includes the plate changer 30, but the embodiment is not limited thereto. The plate changer 30 is an optional device, and the cell picking device 100 may not include the plate changer 30. Therefore, the cells 2 sucked by the suction head 12 may not be discharged to the culture plate 120 but may be discarded, for example.

[0097] (10) Morphology

[0098] Those skilled in the art will appreciate that the multiple exemplary embodiments described above are specific examples of the following embodiments.

[0099] (Item 1) A cell picking device in one form may be a cell picking device for aspirating cells from a liquid sample in a sample container, the cell picking device comprising:

[0100] Aspiration arm, capable of mounting pipette tips;

[0101] a first driving unit, driving the suction arm to enable the suction arm to perform a suction action; and

[0102] a control unit, controlling the action of the first driving unit,

[0103] The control unit includes:

[0104] a moving part, which moves the suction arm along the axial direction of the pipette tip in such a manner that the pipette tip mounted on the suction arm is tilted relative to the vertical direction and the front end of the pipette tip contacts the bottom surface of the sample container;

[0105] a scanning unit that moves the suction arm in such a manner that the front end of the pipette tip scans in the sample container in a horizontal direction toward a predetermined position;

[0106] an inclined portion that further inclines the suction arm at a predetermined angle so that the front end of the pipette tip rises and the base end of the pipette tip falls at the predetermined position; and

[0107] The suction unit causes the suction arm to perform a suction operation so as to suck a sample from the front end of the pipette tip.

[0108] In the cell picking device, the suction arm is moved along the axial direction of the pipette tip installed on the suction arm in such a manner that the pipette tip is tilted relative to the vertical direction and the front end of the pipette tip contacts the bottom surface of the sample container. Next, the suction arm is moved in such a manner that the front end of the pipette tip scans in the horizontal direction toward a specified position in the sample container. Next, the suction arm is further tilted at a specified angle in such a manner that the front end of the pipette tip rises and the base end of the pipette tip descends at a specified position. Thereafter, by performing a suction action of the suction arm, cells in the sample are sucked from the front end of the pipette tip.

[0109] According to the structure, the cells in the sample are scraped by the front end of the pipette tip by scanning toward a predetermined position while the front end of the pipette tip is in contact with the bottom surface of the sample container. Here, it is not necessary to scan the front end of the pipette tip with high resolution. Therefore, even when the cells are greatly separated from the front end of the pipette tip, the cells in the sample can be efficiently scraped to the front end of the pipette tip by scanning the suction arm. In addition, even when the cells are adsorbed on the bottom surface of the sample container, the cells scraped by the front end of the pipette tip are also peeled off from the bottom surface of the sample container by further tilting the suction arm. As a result, the cells in the sample can be efficiently sucked.

[0110] (Item 2) The cell picking device according to Item 1 may be:

[0111] The suction unit starts a suction operation of the suction arm during a period after control of the inclination of the suction arm by the inclination unit starts and before control of the inclination of the suction arm stops.

[0112] In this case, the cells detached from the bottom surface of the sample container by the tip of the pipette tip can be sucked more efficiently.

[0113] (Item 3) The cell picking device according to Item 1 or Item 2 may be:

[0114] The control unit further includes a tilt releasing unit configured to release the tilt of the suction arm performed by the tilting unit after the control of the suction operation performed by the suction unit is stopped.

[0115] In this case, the position of the pipette tip after aspirating the cells is restored to the position before the aspiration arm is tilted. Therefore, the aspiration of the cells can be continuously performed by simple control.

[0116] (Item 4) The cell picking device according to Item 1 or Item 2 may be:

[0117] The specified angle is greater than 0 degrees.

[0118] In such a case, the cells can be easily peeled off from the bottom surface of the sample container.

[0119] (Item 5) The cell picking device according to Item 1 or Item 2 may be:

[0120] The predetermined angle is less than 2 degrees.

[0121] In such a case, the position of the front end of the pipette tip hardly changes, so the user can easily magnify and observe the front end of the pipette tip.

[0122] (Item 6) The cell picking device according to Item 1 or Item 2 may be:

[0123] The control unit includes:

[0124] a first retracting section that, after the control of the suction operation by the suction section stops, causes the suction arm to retract along the axial direction at a first speed until the front end of the pipette tip reaches a predetermined height; and

[0125] The second retracting unit retracts the suction arm along the axial direction at a second speed greater than the first speed after the front end of the pipette tip reaches the predetermined height.

[0126] In the case described above, before the front end of the pipette tip reaches a predetermined height, the retraction speed of the pipette tip is relatively low. Therefore, even when the sucked cells are adsorbed on the sample due to surface tension, etc., the cells can be prevented from falling into the sample again. On the other hand, after the front end of the pipette tip reaches a predetermined height, the retraction speed of the pipette tip is relatively high. Therefore, the retraction of the pipette tip is completed in a short time. Thus, the operability of the cell picking device can be improved.

[0127] (Item 7) The cell picking device according to Item 6 may be:

[0128] The second speed is more than 10 times the first speed.

[0129] In the above case, before the front end of the pipette tip reaches the specified height, the retraction speed of the pipette tip is sufficiently slow, so that the cells can be sufficiently prevented from falling into the sample again. On the other hand, after the front end of the pipette tip reaches the specified height, the retraction speed of the pipette tip is sufficiently fast, so that the retraction of the pipette tip can be completed in a shorter time.

[0130] (Item 8) The cell picking device according to Item 6 may be:

[0131] The predetermined height is the liquid level of the sample in the sample container.

[0132] In the above case, before the front end of the pipette tip is separated from the sample, the withdrawal speed of the pipette tip is low, so it is possible to more reliably prevent the cells from falling into the sample again. On the other hand, after the front end of the pipette tip is separated from the sample, the withdrawal of the pipette tip can be completed in a short time. In addition, it is possible to prevent the cells from being exposed to the atmosphere for a long time.

[0133] (Item 9) The cell picking device according to Item 1 or Item 2 may further include:

[0134] a loading portion capable of loading a culture plate having a plurality of wells arranged thereon; and

[0135] A second driving unit drives the loading unit,

[0136] The control unit also includes:

[0137] a first position adjustment unit that controls the first drive unit or the second drive unit in such a manner that the position of the well in the culture plate that can be sucked by the suction arm changes sequentially; and

[0138] The discharge unit causes the suction arm to perform a discharge action in such a manner that the sample is discharged from the front end of the pipette tip.

[0139] Control of the suction operation by the suction unit and control of the discharge operation by the discharge unit are performed alternately.

[0140] In such a case, the aspirated cells can be successively received in a plurality of wells of the culture plate.

[0141] (Item 10) The cell picking device according to Item 9 may be:

[0142] A pipette tip rack for holding a plurality of replacement pipette tips is further placed on the placement portion.

[0143] The first driving unit is configured to be able to detach the pipette tip from the suction arm,

[0144] The control unit also includes:

[0145] a disassembly unit, configured to control the first driving unit in such a manner as to disassemble the pipette tip from the suction arm;

[0146] a second position adjustment unit that controls the first drive unit or the second drive unit in such a manner that the position of the replacement pipette tip that can be sucked by the suction arm in the pipette tip holder changes sequentially; and

[0147] The mounting unit controls the first driving unit or the second driving unit in such a manner that any replacement pipette tip in the pipette tip holder is mounted on the suction arm as the pipette tip,

[0148] Control of the suction operation by the suction section, control of the discharge operation by the discharge section, control of detachment of the pipette tip by the detachment section, and control of attachment of the pipette tip by the attachment section are alternately performed.

[0149] In the above case, after the cells are discharged from the pipette tip to any well of the culture plate, the pipette tip is removed from the suction arm. In addition, any replacement pipette tip of the pipette tip holder is mounted on the suction arm, and the cells are suctioned to the pipette tip. Thus, the suctioned cells can be automatically and continuously contained in a plurality of wells of the culture plate.

[0150] (Item 11) The cell picking device according to Item 10 may be:

[0151] The second driving unit includes a rotating unit that rotates the mounting unit in a horizontal plane.

[0152] The first position adjusting unit rotates the rotating unit in such a manner that the culture plate is located closer to the suction arm than the pipette tip holder when controlling the discharge operation performed by the discharge unit.

[0153] The second position adjustment unit rotates the rotating unit so that the pipette tip holder is located closer to the suction arm than the culture plate when controlling the installation of the pipette tip by the installation unit.

[0154] In this case, the culture plate and the pipette tip holder can be selectively moved to a position where the suction arm can perform suction without increasing the moving range of the placement unit.

Claims

1. A cell picking device for aspirating cells from a liquid sample in a sample container, the cell picking device comprising: Aspiration arm, capable of mounting pipette tips; a first driving unit, driving the suction arm to enable the suction arm to perform a suction action; as well as a control unit, controlling the action of the first driving unit, The control unit includes: The moving part moves the suction arm along the axial direction of the pipette tip in such a manner that the pipette tip mounted on the suction arm is inclined relative to the vertical direction and the front end of the pipette tip contacts the bottom surface of the sample container, wherein the front end of the pipette tip is pressed against the bottom surface of the sample container so that the front end of the pipette tip is elastically bent; a scanning unit, which moves the suction arm in such a manner that the tip of the pipette tip is horizontally scanned toward a predetermined position in the sample container and the cells adsorbed on the bottom surface of the sample container are detached when the tip of the pipette tip contacts the bottom surface of the sample container through the traveling unit and is in the elastically bent state; an inclined portion that further inclines the suction arm at a predetermined angle so that the front end of the pipette tip rises and the base end of the pipette tip falls at the predetermined position, thereby peeling the cells from the bottom surface of the sample container; and The suction section causes the suction arm to perform a suction operation so that the cells detached from the sample container are sucked from the tip of the pipette tip after the suction arm is tilted by the tilting section.

2. The cell picking device according to claim 1, characterized in that: The suction unit starts a suction operation of the suction arm during a period after control of the inclination of the suction arm by the inclination unit starts and before control of the inclination of the suction arm stops.

3. The cell picking device according to claim 1 or 2, characterized in that: The control unit further includes a tilt releasing unit configured to release the tilt of the suction arm performed by the tilting unit after the control of the suction operation performed by the suction unit is stopped.

4. The cell picking device according to claim 1 or 2, characterized in that: The specified angle is greater than 0 degrees.

5. The cell picking device according to claim 1 or 2, characterized in that: The predetermined angle is less than 2 degrees.

6. The cell picking device according to claim 1 or 2, characterized in that: The control unit includes: a first retracting section that, after the control of the suction operation by the suction section stops, causes the suction arm to retract along the axial direction at a first speed until the front end of the pipette tip reaches a predetermined height; and The second retracting unit retracts the suction arm along the axial direction at a second speed greater than the first speed after the front end of the pipette tip reaches the predetermined height.

7. The cell picking device according to claim 6, characterized in that: The second speed is more than 10 times the first speed.

8. The cell picking device according to claim 6, characterized in that: The predetermined height is the liquid level of the sample in the sample container.

9. The cell picking device according to claim 1 or 2, characterized in that: Also includes: A loading portion capable of loading a culture plate having a plurality of wells arranged therein; as well as A second driving unit drives the loading unit, The control unit also includes: a first position adjustment unit, controlling the first drive unit or the second drive unit in such a manner that the position of the well in the culture plate that can be sucked by the suction arm changes sequentially; as well as The discharge unit causes the suction arm to perform a discharge action in such a manner that the sample is discharged from the front end of the pipette tip. Control of the suction operation by the suction unit and control of the discharge operation by the discharge unit are performed alternately.

10. The cell picking device according to claim 9, characterized in that: A pipette tip rack for holding a plurality of replacement pipette tips is further placed on the placement portion. The first driving unit is configured to be able to detach the pipette tip from the suction arm, The control unit also includes: a disassembly unit, controlling the first driving unit in a manner of disassembling the pipette tip from the suction arm; a second position adjustment unit that controls the first drive unit or the second drive unit in such a manner that the position of the replacement pipette tip that can be sucked by the suction arm in the pipette tip holder changes sequentially; and The mounting unit controls the first driving unit or the second driving unit in such a manner that any replacement pipette tip in the pipette tip holder is mounted on the suction arm as the pipette tip, Control of the suction operation by the suction section, control of the discharge operation by the discharge section, control of detachment of the pipette tip by the detachment section, and control of attachment of the pipette tip by the attachment section are alternately performed.

11. The cell picking device according to claim 10, characterized in that: The second driving unit includes a rotating unit that rotates the mounting unit in a horizontal plane. When the discharge operation is controlled by the discharge unit, the first position adjustment unit rotates the rotating unit in such a manner that the culture plate is located closer to the suction arm than the pipette tip holder. When controlling the attachment of the pipette tip by the attachment portion, the second position adjustment portion rotates the rotation portion so that the pipette tip holder is located closer to the suction arm than to the culture plate.

Images