Cell pickup device and cell pickup method

Abstract

A cell pickup device and a cell pickup method are provided. The cell pickup device is used to aspirate cells from a liquid sample in a sample container. The cell pickup device includes: an aspiration member on which a pipette tip can be mounted; a drive unit that moves the aspiration member and performs aspiration through the aspiration member and the pipette tip; an operation mode switching unit that switches the operation mode of the drive unit between a first mode and a second mode; and a control unit that controls the drive unit.

Description

Technical Field

[0001] This invention relates to a cell picking device and a cell picking method. Background Technology

[0002] When aspirating specific cells from containers such as cell culture vessels, the operator manually aspirates the cells using a pipette or other aspiration instruments while confirming the cell's position under a microscope. However, this operation requires skill, making cell aspiration difficult for inexperienced operators. Therefore, a cell aspiration system that assists in the cell aspiration process has been proposed (see, for example, Japanese Patent Application Publication No. 2016-112012).

[0003] In the cell aspiration system described in Japanese Patent Application Publication No. 2016-112012, a tubular suction tip for aspirating cells contained in a container is installed in the aspiration section. The transport section performs three-dimensional positional adjustment of the aspiration section so that the tip of the suction tip approaches a specific cell. Summary of the Invention

[0004] However, in the cell aspiration system described above, depending on the state of the cells in the sample, it is sometimes impossible to efficiently aspirate the cells into the aspirator.

[0005] The purpose of this invention is to provide a cell pickup device and method that can efficiently attract cells based on the state of cells in a sample.

[0006] A cell pickup device according to one aspect of the present invention is used to aspirate cells from a liquid sample in a sample container. The cell pickup device may also include: an aspiration member capable of being fitted with a pipette tip; a drive unit that moves the aspiration member and performs aspiration via the aspiration member and the pipette tip; an operation mode switching unit that switches the operation mode of the drive unit between a first mode and a second mode; and a control unit that controls the drive unit, wherein the control unit controls the drive unit in the first mode to perform a first traveling action, a scanning action, a pitching action, and an aspiration action. The first traveling action involves moving the aspiration member along the axial direction of the pipette tip while the pipette tip mounted on the aspiration member is tilted relative to the vertical direction, thereby bringing the tip of the pipette tip into contact with the bottom surface inside the sample container. The scanning action is an action of moving the suction member horizontally to scan the bottom surface of the sample container with the tip of the pipette tip toward the first position. The pitching action is an action of tilting the suction member further relative to the vertical direction to raise the tip of the pipette tip at the first position and lower the base of the pipette tip. The suction action is an action of attracting the sample in the sample container by the suction member and the pipette tip. In the second mode, the control unit controls the drive unit to perform the second traveling action and the suction action. The second traveling action is an action of moving the suction member along the axial direction of the pipette tip while the pipette tip mounted on the suction member is tilted relative to the vertical direction, so that the tip of the pipette tip moves to a second position in the sample container above the first position.

[0007] A cell pickup method according to other aspects of the present invention is used to aspirate cells from a liquid sample in a sample container. The cell pickup method may also include the following steps: switching an operating mode between a first mode and a second mode; in the first mode, performing a first traveling motion, a scanning motion, a pitching motion, and an aspiration motion, wherein the first traveling motion is an action in which the aspiration member is moved axially along the pipette tip while the pipette tip is tilted relative to the vertical direction, thereby bringing the tip of the pipette tip into contact with the bottom surface of the sample container; the scanning motion is an action in which the aspiration member is moved horizontally so that the tip of the pipette tip moves towards a first position. The action of scanning the bottom surface of the sample container in a certain manner, wherein the pitching action is an action of further tilting the suction member relative to the vertical direction, thereby raising the tip of the pipette tip at the first position and lowering the base of the pipette tip, and the suction action is an action of attracting the sample in the sample container by the suction member and the pipette tip; and in the second mode, a second traveling action and a suction action are performed, wherein the second traveling action is an action of moving the suction member along the axial direction of the pipette tip while the pipette tip mounted on the suction member is tilted relative to the vertical direction, thereby moving the tip of the pipette tip to a second position in the sample container that is above the first position. Attached Figure Description

[0008] Figure 1 This is a schematic front view illustrating the structure of a cell pickup device according to one embodiment of the present invention.

[0009] Figure 2 It is shown Figure 1 A schematic three-dimensional diagram of the structure of the attraction device.

[0010] Figure 3 This shows the process of creating the plan. Figure 1 This is a schematic diagram of an example of a selection screen displayed in the display section.

[0011] Figure 4 This is a block diagram showing the functional structure of the control unit.

[0012] Figure 5 It is shown Figure 4 A flowchart illustrating an example of the control of cell attraction actions performed by the control unit.

[0013] Figure 6 It is shown Figure 5 A flowchart illustrating an example of the control of adhesion cell patterns.

[0014] Figure 7 It is shown Figure 5 A flowchart illustrating an example of controlling the suspended cell pattern.

[0015] Figure 8 This is a diagram illustrating the cell attraction action of the adhesion pattern performed by the attraction device.

[0016] Figure 9 This is a diagram illustrating the cell attraction action of the adhesion pattern performed by the attraction device.

[0017] Figure 10 This is a diagram illustrating the cell attraction action of the adhesion pattern performed by the attraction device.

[0018] Figure 11 This is a diagram illustrating the cell attraction action of the adhesion pattern performed by the attraction device.

[0019] Figure 12 This is a diagram illustrating the cell attraction action of the adhesion pattern performed by the attraction device.

[0020] Figure 13 This is a diagram illustrating the cell attraction action of the adhesion pattern performed by the attraction device.

[0021] Figure 14 This is a diagram illustrating the cell attraction action of the adhesion pattern performed by the attraction device.

[0022] Figure 15 This is a diagram illustrating the cell aspiration action of the suspension cell pattern performed by the aspiration device.

[0023] Figure 16 This is an example of a screen displayed on the display unit for the purpose of confirming the attraction of cells. Detailed Implementation

[0024] The cell pickup device according to embodiments of the present invention will now be described in detail with reference to the accompanying drawings.

[0025] (1) Structure of the cell pickup device

[0026] Figure 1 This is a schematic front view illustrating the structure of a cell pickup device according to one embodiment of the present invention. Figure 1 As shown, the cell pickup device 100 includes an aspiration device 10, an observation device 20, a plate changer 30, a display unit 40, an operation unit 50, and a control unit 60. Additionally, a sample container 110, a culture plate 120, and a pipette tip holder 130 (hereinafter referred to as holder 130) can be installed in the cell pickup device 100.

[0027] The sample container 110, for example, is a culture dish, used to hold a liquid sample containing cells. The sample contains the target cells. The culture plate 120 is a multi-well plate with multiple wells 121 arranged for cell culture. The rack 130 is used to hold multiple replaceable pipette tips 131 (hereinafter referred to as replaceable tips 131). In this example, the culture plate 120 has 24 wells 121 arranged in 4 rows × 6 columns. In addition, 96 replaceable tips 131 are held on the rack 130 in an 8 rows × 12 columns arrangement.

[0028] The aspiration device 10 includes a pipette-type aspiration arm 11. The tip of the aspiration arm 11 can be fitted with any replacement pipette tip 131 held on the holder 130. (Hereinafter, the replacement pipette tip 131 fitted to the aspiration arm 11 will be referred to as tip 12.) The aspiration device 10 can aspirate cells from the sample container 110 via the pipette tip 12.

[0029] In this example, the configuration allows the action of drawing cells from the sample container 110 into the pipette tip 12 to switch between a first mode and a second mode. Hereinafter, the action of drawing cells from the sample container 110 into the pipette tip 12 is referred to as the cell aspiration action. Furthermore, the first mode is referred to as the cell adhesion mode, and the second mode as the cell suspension mode. Details regarding the cell aspiration action, the cell adhesion mode, and the cell suspension mode will be described later.

[0030] Additionally, the suction device 10 is capable of discharging cells aspirated from the pipette tip 12. Hereinafter, the action of discharging cells aspirated from the pipette tip 12 is referred to as the cell discharging action. The cell discharging action includes seeding cells into any well 121 of the culture plate 120 and discharging cells into a waste liquid section (not shown). Details regarding the cell discharging action will be described later.

[0031] The observation device 20 includes a stage 21, an illumination unit 22, an imaging unit 23, and a microscope unit 24, and is configured adjacent to the suction device 10. A sample container 110 can be placed on the stage 21. The illumination unit 22 is positioned above the stage 21. The illumination unit 22 includes, for example, a light source such as a light-emitting diode, for illuminating the sample container 110 placed on the stage 21. Furthermore, the stage 21 is translucent. Alternatively, an opening may be formed in the stage 21 to allow light from the illumination unit 22 to pass through to the bottom.

[0032] The imaging unit 23 includes multiple lenses and a camera, etc., to magnify and photograph the sample inside the sample container 110 illuminated by the illumination unit 22. The camera of the imaging unit 23 is positioned above the microscope unit 24, and the lens is positioned below the stage 21. The microscope unit 24 includes an eyepiece, a microscope tube, and an objective lens, etc., and is used by the user when magnifying and observing the sample placed in the sample container 110 on the stage 21.

[0033] The plate changer 30 is an optional device configured to face the observation device 20 across the suction device 10, and is designed to be detachable from the suction device 10. The plate changer 30 includes a base 31, a vertical shaft 32, a mounting section 33, and a drive section 34. The vertical shaft 32 is configured to extend vertically within the base 31. The upper part of the vertical shaft 32 protrudes from the base 31. The mounting section 33 is mounted horizontally at the upper end of the vertical shaft 32. The culture plate 120 and the rack 130 can be mounted on the mounting section 33.

[0034] The drive unit 34 includes a rotating part 35 and a moving part 36, and is connected to the placement part 33 within the base 31 via a vertical shaft 32. The rotating part 35 includes, for example, an electric motor, for rotating the placement part 33 in a horizontal plane. As a result, the culture plate 120 and the rack 130 placed in the placement part 33 are selectively moved to the vicinity of the suction device 10.

[0035] Specifically, when the suction device 10 inoculates cells into any well 121, the culture plate 120 is moved to the vicinity of the suction device 10. On the other hand, when any replacement pipette tip 131 is installed into the suction arm 11, the holder 130 is moved to the vicinity of the suction device 10. With this structure, it is possible to prevent the movement range of the mounting portion 33 from becoming too large.

[0036] The moving part 36 includes, for example, a stepper motor for moving the mounting part 33 horizontally in the horizontal plane. Specifically, the moving part 36 moves any hole 121 of the culture plate 120 or any replacement pipette tip 131 of the holder 130 to a position accessible to the suction arm 11 (e.g., below the suction arm 11). This allows for the seeding of cells from the suction device 10 into the hole 121, or the installation of the replacement pipette tip 131 onto the suction arm 11.

[0037] The display unit 40 includes, for example, an LCD (liquid crystal display) panel or an organic EL (electroluminescent) panel. Furthermore, the display unit 40 displays multiple GUIs (Graphical User Interfaces) as selection screens for selecting the operation content of the suction device 10 and the observation device 20. The display unit 40 also displays images generated by the camera unit 23 of the observation device 20. Additionally, the display unit 40 displays operation screens for receiving instructions during the operation of the cell pickup device 100.

[0038] The operation unit 50 includes a keyboard and a pointing device. A mouse or pen can be used as the pointing device. The display unit 40 and the operation unit 50 can also be integrated into a single unit via a touch panel display. The user can use the operation unit 50 to operate buttons or drop-down menus on the selection screen or action screen displayed on the display unit 40.

[0039] The control unit 60 is, for example, a personal computer, including a CPU (central processing unit) and memory. The control unit 60 registers operation processes (hereinafter referred to as schemes) that include the operation content received through the selection screen displayed on the display unit 40. In this example, the scheme includes an operation process from cell aspiration to cell expulsion. Furthermore, the selection screen includes a selection of cell adhesion mode and cell suspension mode for the cell aspiration operation. The control unit 60 controls the operation of the aspiration device 10, the observation device 20, and the plate changer 30 according to the registered scheme.

[0040] (2) Structure of the suction device

[0041] Figure 2 It is shown Figure 1 A schematic perspective view of the structure of the attraction device 10. (See diagram below.) Figure 2 As shown, 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 drive unit 16. The drive unit 16 includes rotating parts 17 and 18 and a suction drive unit 19. The holder 13 holds the suction arm 11 in the suction drive unit 19. The vertical shaft 15 is provided on the upper surface of the base 14 in a vertical direction.

[0042] Rotating part 17, for example, includes an electric motor and is mounted on the upper end of vertical shaft 15 in a manner that enables rotation in a horizontal plane. Rotating part 18, for example, includes an electric motor and is mounted on rotating part 17 in a manner that enables rotation in a vertical plane. Rotating parts 17 and 18 may also be composed of a single electric motor or the like, capable of rotation in both the horizontal and vertical planes.

[0043] The suction drive unit 19 includes, for example, a stepper motor, which is mounted on the rotating part 18 in a manner that allows it to move forward and backward in a predetermined direction (the up-down direction when the rotating part 18 is not rotating in the vertical plane). In addition, the suction drive unit 19 includes a suction mechanism configured to suction and expel cells from the suction arm 11.

[0044] During cell aspiration, the rotating part 17 rotates in the horizontal plane so that the suction arm 11 and the suction head 12 of the suction device 10 are oriented toward the observation device 20. The rotating part 18 rotates in the vertical plane so that the suction head 12 mounted on the suction arm 11 is tilted at a predetermined angle. The position of the suction head 12 at this time is called the standby position.

[0045] During the cell discharge process, when cells are seeded into well 121, the rotating part 17 rotates in the horizontal plane so that the suction arm 11 and the pipette tip 12 of the suction device 10 are oriented toward the plate changer 30. Additionally, the rotating part 35 rotates in the horizontal plane so that the culture plate 120 is positioned near the suction device 10 relative to the holder 130. Furthermore, the moving part 36 moves parallel in the horizontal plane so that any well 121 of the culture plate 120 is positioned below the pipette tip 12 mounted on the suction arm 11.

[0046] (3) Proposal Development

[0047] Figure 3 This shows the process of creating the plan. Figure 1 This is a schematic diagram of an example of a selection screen displayed in the display unit 40. Figure 3 The action mode selection screen 42 is shown in the image.

[0048] like Figure 3 As shown, the action mode selection screen 42 displays a drop-down menu 42a, an adhered cell mode button 42b, a floating cell mode button 42c, a pick-up mode button 42d, a remove mode button 42e, and a button 42f for proceeding to the next step.

[0049] The user selects from the sample container displayed in drop-down menu 42a Figure 1 The type of sample container 110. In this example, such as... Figure 3 The sample container 110 is selected as shown. In this example, registration information corresponding to the sample container 110 is pre-stored in the memory of the control unit 60 for the sample container displayed in the drop-down menu 42a. The registration information corresponding to the sample container 110 includes the position of the tip of the suction head 12 when the first travel action and the second travel action stop, as described later. The control unit 60 controls the operation of the suction device 10 based on the registration information corresponding to the selected sample container.

[0050] Regarding the cell aspiration operation, the user selects either the cell adhesion mode button 42b or the cell suspension mode button 42c, depending on the state of the cells within the sample container 110. When the cells within the sample container 110 are adhered to the bottom surface of the sample container 110, the user selects the cell adhesion mode button 42b. Conversely, when the cells within the sample container 110 are suspended within the sample container 110, the user selects the cell suspension mode button 42c. Thus, the operation mode of the cell aspiration device 10 is switched.

[0051] Regarding the cell expulsion action, select either the pickup mode button 42d or the removal mode button 42e. This switches the operation mode of the cell expulsion action of the suction device 10. When the user selects the pickup mode button 42d, the cell expulsion action is performed in pickup mode. When the user selects the removal mode button 42e, the cell expulsion action is performed in removal mode.

[0052] In pick-up mode, cells aspirated from pipette tip 12 are seeded into wells 121 of culture plate 120. In removal mode, cells aspirated from pipette tip 12 are discarded into a waste liquid section (not shown). Cells are thus removed from sample container 110. When the button 42f for proceeding to the next step is pressed, the selection in the action mode selection screen 42 is determined. Next, a plan representing the cell aspiration and cell dissipation actions is created by sequentially setting the action procedures. The created plan is stored in a storage medium such as memory.

[0053] (4) Functional structure of the control unit 60

[0054] Figure 4 This is a block diagram showing the functional structure of the control unit 60. (Example) Figure 4 As shown, the control unit 60 includes an information acquisition unit 61, an operation mode switching unit 62, an expulsion command receiving unit 63, a display control unit 64, an attraction operation control unit 70, and an expulsion operation control unit 80 as its functional units. The functions of the control unit 60 are implemented by the CPU of the control unit 60 executing a cell containment program stored in memory. Some or all of the functions of the control unit 60 can also be implemented using hardware such as electronic circuits.

[0055] The information acquisition unit 61 acquires registration information from the memory. The operation mode switching unit 62 switches the operation mode of the cell attraction operation to the selected cell adhesion mode or cell suspension mode according to the plan. In addition, the operation mode switching unit 62 switches the operation mode of the cell attraction operation to the cell adhesion mode or cell suspension mode selected by the user.

[0056] The discharge command receiving unit 63 receives a command from the program to discharge cells from the pipette tip 12 into the sample container 110. Furthermore, the discharge command receiving unit 63 receives the command to discharge cells from the pipette tip 12 into the sample container 110 based on the user's operation of the operating unit 50. The display control unit 64 causes the display unit 40 to display multiple GUIs (Graphical User Interfaces) as selection screens for selecting the operation content of the suction device 10 and the observation device 20. Additionally, the display control unit 64 causes the display unit 40 to display images generated by the camera unit 23 of the observation device 20. Furthermore, the display control unit 64 causes the display unit 40 to display an operation screen for receiving commands during the operation of the cell pickup device 100. Additionally, the display control unit 64 controls the operation of the operation mode switching unit 62 based on commands issued by the user from the operating unit 50.

[0057] The suction action control unit 70 causes the suction device 10 to perform cell suction action. The suction action control unit 70 includes a travel control unit 71, a scanning control unit 72, a pitch control unit 73, a suction control unit 74, a pitch release control unit 75, a first retraction control unit 76, a second retraction control unit 77, and a discharge control unit 78.

[0058] The travel control unit 71 controls the rotation units 17 and 18 and the suction drive unit 19 to cause the suction arm 11 to travel along the axial direction of the suction head 12, which is mounted on the suction arm 11 and tilted relative to the vertical direction. This causes the tip of the suction head 12 to contact the bottom surface inside the sample container 110; this action is called the first travel action. Similarly, the action of moving the tip of the suction head 12 to a position inside the sample container 110 above the bottom surface is called the second travel action.

[0059] The scanning control unit 72 controls the rotation unit 17 to move the suction arm 11 in the horizontal direction. As a result, the tip of the suction head 12 scans the bottom surface inside the sample container 110 towards approximately the center of the sample container 110. In this example, the suction arm 11 moves in an arc within the horizontal plane. This action will be referred to as the scanning action below.

[0060] The pitch control unit 73 controls the rotation unit 18 to further tilt the suction arm 11, which is tilted by the travel control unit 71, relative to the vertical direction. As a result, the tip of the suction head 12 at approximately the center of the sample container 110 rises and the base of the suction head 12 falls. This action will be referred to as the pitch action below.

[0061] The suction control unit 74 controls the suction drive unit 19 so that the suction arm 11 and the suction head 12 draw the sample in the sample container 110 into the suction head 12. This action is referred to as the suction action below.

[0062] The pitch release control unit 75 controls the rotation unit 18 to restore the tilt angle of the suction arm 11, which has tilted due to the pitch movement of the pitch control unit 73, to the angle before the pitch movement. This action will be referred to as the pitch release action below.

[0063] The first retraction control unit 76 controls the suction drive unit 19 to retract the suction arm 11 axially at a first speed until the tip of the suction head 12 reaches a predetermined height. This action is referred to below as the first retraction action. In this example, the predetermined height is the height of the liquid surface of the sample. Alternatively, the position of the tip of the suction head 12 can also be determined by the number of pulses from the stepper motor of the suction drive unit 19.

[0064] The second retraction control unit 77 controls the suction drive unit 19 to retract the suction arm 11 axially at a second speed greater than the first speed after the tip of the suction head 12 reaches the height of the liquid surface of the sample. This action is referred to as the second retraction action. A position for switching between the first retraction action and the second retraction action is pre-stored.

[0065] The discharge control unit 78 controls the suction drive unit 19 to cause the suction head 12 to discharge cells into the sample container 110. This action is referred to below as the cell return action. Details about the cell return action will be described later.

[0066] The discharge action control unit 80 causes the suction device 10 and the plate changer 30 to perform the cell discharge action.

[0067] (5) Cell attraction action

[0068] (5-1) Control of cell attraction

[0069] Figure 5 It is shown Figure 4 A flowchart illustrating an example of the control of cell aspiration actions performed by the control unit 60. The cell aspiration action is performed according to the planned operation procedure.

[0070] First, the information acquisition unit 61 acquires the registration information corresponding to the sample container 110 (step S1). The operation mode switching unit 62 determines whether the cell adhesion mode has been selected in the protocol (step S2). The operation mode switching unit 62 can also determine whether the cell adhesion mode has been selected by the user through an operation performed by the operation unit 50. If the cell adhesion mode has been selected, the operation mode switching unit 62 switches the operation mode to the cell adhesion mode (step S3). At this time, the suction action control unit 70 controls the drive unit 16 to cause the suction device 10 to perform a cell suction action based on the cell adhesion mode (step S4). The cell suction action of the suction device 10 based on the cell adhesion mode will be described later.

[0071] exist Figure 5 If the cell adhesion mode is not selected in step S2, the operation mode switching unit 62 switches the operation mode to the suspension cell mode (step S5). At this time, the suction action control unit 70 controls the drive unit 16 to cause the suction device 10 to perform a cell suction action based on the suspension cell mode (step S6). The cell suction action of the suction device 10 based on the suspension cell mode will be described later.

[0072] exist Figure 5 After the cell aspiration action based on the adherent cell mode in step S4 or the cell aspiration action based on the suspended cell mode in step S6 is completed, a cell discharge action controlled by the discharge action control unit 80 is performed.

[0073] (5-2) Adhesive cell pattern

[0074] Figure 6 It is shown Figure 5 A flowchart illustrating an example of the control of adhesion cell patterns. Figures 8 to 14 This is a schematic diagram illustrating the cell attraction action of the cell adhesion pattern performed by the attraction device 10. For example... Figure 8 As shown, the cells adhere to the bottom surface of the sample container 110, which is located approximately in the center of the sample container 110.

[0075] First, the travel control unit 71 controls the suction drive unit 19 to perform the first travel action. Figure 6 Step S11). Thus, as Figure 8 As indicated by arrow A, the suction tip 12 travels axially (towards the tip). In this case, the tip of the suction tip 12 contacts the bottom surface of the sample container 110. Alternatively, the tip of the suction tip 12 can be slightly bent elastically by pressing it against the bottom surface of the sample container 110 (see reference). Figure 9 The travel of the suction head 12 is stopped based on the registration information obtained by the information acquisition unit 61. Therefore, in cell adhesion mode, damage to the tip of the suction head 12 can be prevented.

[0076] Next, the scanning control unit 72 controls the rotating unit 17 to perform a scanning operation (step S12). Thus, as... Figure 9 As indicated by arrow B, the tip of the pipette tip 12 scans the bottom surface of the sample container 110 towards the center. As a result, the tip of the pipette tip 12 contacts the cells, and cells adhering to the bottom surface of the sample container 110 detach from the bottom surface. Then, the pitch control unit 73 controls the rotation unit 18 to perform a pitching motion (step S13). Thus, as... Figure 10 As indicated by arrow C, the suction tip 12 performs a pitching motion. As a result, cells are detached from the bottom surface of the sample container 110.

[0077] Next, the suction control unit 74 controls the suction drive unit 19 to perform a suction action (step S14). Thus, as... Figure 11 As shown, cells are drawn into the suction head 12. In this example, the suction begins at a time point later than the start of the pitching motion and earlier than the end of the pitching motion, and stops after a predetermined time has elapsed from the end of the pitching motion. In this case, cells can be drawn efficiently. The timing of suction is not limited to the example above; suction can also begin at a time point later than the end of the pitching motion, or simultaneously with the start of the pitching motion. Alternatively, suction can end at a time point earlier than the end of the pitching motion, or simultaneously with the end of the pitching motion.

[0078] After the attraction action is completed, the pitch release control unit 75 controls the rotation unit 18 to perform the pitch release action (step S15). Thus, as... Figure 12 As indicated by arrow D, the suction head 12 returns to its position before the pitching motion.

[0079] By repeating Figures 8-12 The actions in steps S11-S15 facilitate continuous cell attraction. During continuous cell attraction, in... Figure 12 After the action, the rotating part 17 can also rotate slightly in the horizontal plane. In this case, it is able to attract cells at a slightly different position than the previous attraction position.

[0080] After the suction action is completed, the first retraction control unit 76 controls the suction drive unit 19 to perform the first retraction action (step S16). Thus, as... Figure 13 As indicated by arrow E, the pipette tip 12 retracts at a first speed (step S16). In this case, the retraction of the pipette tip 12 at the first speed continues until the tip of the pipette tip 12 reaches the height of the liquid surface of the sample (step S17).

[0081] According to the first retraction action, the upward speed of the suction head 12 is relatively small before it is pulled up from the sample. Therefore, even if the attracted cells adhere to the sample due to surface tension, etc., it can prevent the cells from falling back into the sample.

[0082] After the tip of the suction head 12 reaches the liquid level of the sample, the second retraction control unit 77 controls the suction drive unit 19 to perform a second retraction action (step S18). Thus, as... Figure 14As indicated by arrow F, the suction head 12 further retracts at a second speed. In this case, the retraction of the suction head 12 at the second speed continues until the suction head 12 returns to the standby position (step S19). When the suction head 12 returns to the standby position, the cell aspiration action ends.

[0083] According to the second retraction action, after the pipette tip 12 is pulled up from the sample, the retraction speed of the pipette tip 12 is greater than the retraction speed of the first retraction action, thus enabling the pipette tip 12 to return to the standby position in a short time. This improves the operability of the cell pickup device 100. Furthermore, it prevents cells from being exposed to the atmosphere for extended periods.

[0084] (5-3) Suspension cell mode

[0085] Figure 7 It is shown Figure 5 A flowchart illustrating an example of controlling the suspended cell pattern. Figure 15 This is a schematic diagram illustrating the cell aspiration action of the aspiration device 10 in the suspended cell mode. The differences between the suspended cell mode and the adherent cell mode are as follows.

[0086] like Figure 15 As shown, cells are suspended within the sample in sample container 110. First, the travel control unit 71 controls the suction drive unit 19 to perform a second travel action ( Figure 7 Step S21). Thus, as Figure 15 As indicated by arrow A, the pipette tip 12 travels axially (towards the tip). In this case, the tip of the pipette tip 12 is located between the liquid surface of the sample in the sample container 110 and the bottom surface of the sample container 110. The travel of the pipette tip 12 is stopped based on the registration information acquired by the information acquisition unit 61, thus preventing the tip of the pipette tip 12 from contacting the bottom surface of the sample container 110 in suspended cell mode.

[0087] Then, the suction control unit 74 controls the suction drive unit 19 to perform the suction action (step S22). As a result, cells suspended in the sample within the sample container 110 are drawn into the suction head 12. The subsequent steps S23 to S26 are similar to... Figure 6 The actions in steps S16 to S19 shown are the same.

[0088] (5-4) Confirmation of attracting cells

[0089] In the cell adhesion mode of cell attraction action, it is also possible to... Figure 6 Between steps S14 and S15, the user confirms the cell aspiration. Similarly, in the suspension cell mode of the cell aspiration action, this can also be done... Figure 7Between steps S22 and S23, the user performs a cell aspiration confirmation. This cell aspiration confirmation is performed to confirm whether the cells have been aspirated into the suction head 12.

[0090] Figure 16 This is a schematic diagram illustrating an example of a screen displayed on the display unit 40 for confirming the attraction of cells. The following will... Figure 16 The screen displayed is called the cell aspiration confirmation screen 45. The cell aspiration confirmation screen 45 includes an image display area 45A and a GUI display area 45B. The image display area 45A displays an image in real time containing the tip of the pipette tip 12 inside the sample container 110 and the cell X. The image displayed in the image display area 45A is generated by the camera unit 23 of the observation device 20.

[0091] The GUI display area 45B includes a return button 45a, an aspiration button 45b, and a button 45c for proceeding to the next step. When the return button 45a is activated, a cell return operation is performed. As a result, the cells contained in the pipette tip 12 are expelled into the sample container 110. When the aspiration button 45b is activated, the sample in the sample container 110 is aspirated. When the button 45c for proceeding to the next step is activated, the cell expulsion operation of the aspiration device 10 begins.

[0092] (6) Effects of the implementation method

[0093] According to the cell pickup device 100 of this embodiment, the operating mode of the drive unit 16 can be selectively switched between an adherent cell mode and a suspended cell mode. In the adherent cell mode, with the tip of the suction head 12 in contact with the bottom surface of the sample container 110, the tip of the suction head 12 scans the bottom surface of the sample container 110 in a horizontal direction. As a result, cells adhered to the bottom surface of the sample container 110 are scraped off. In the suspended cell mode, the sample is attracted with the tip of the suction head 12 positioned between the bottom surface of the sample container 110 and the liquid surface of the sample. As a result, suspended cells in the liquid sample within the sample container 110 are attracted. Consequently, by switching the operating mode of the drive unit 16 according to the state of the cells within the sample, cells can be attracted efficiently.

[0094] Furthermore, in both the adherent cell mode and the suspended cell mode, if the number of cells attracted within the pipette tip 12 is not the desired number, it is not necessary to wait for the cells to fall naturally from the pipette tip 12 after aspiration stops. Therefore, the cells within the pipette tip 12 can be immediately returned to the sample container 110 by user instruction. Consequently, the time before the aspiration device 10 resumes aspiration is shortened.

[0095] (7) Other implementation methods

[0096] In the above embodiments, the specified heights for the first and second retraction actions of the cell aspiration action are the heights from the bottom surface of the sample container 110 to the liquid surface, but for example, they can also be set to any height within the sample container 110 based on the depth of the sample container 110.

[0097] In the above embodiments, a first retreating action is performed at a first speed during the cell attraction action, and a second retreating action is performed at a second speed greater than the first speed. However, the first retreating action and the second retreating action can also be performed at the same speed.

[0098] In the above embodiments, the pitch release action is performed in the cell adhesion mode, but for example, the pitch release action may not be performed if continuous cell attraction is not performed.

[0099] (8) The correspondence between the structural elements of the claims and the parts of the embodiments.

[0100] Hereinafter, examples of the correspondence between the structural elements of the claims and the elements of the embodiments will be described. In the above embodiments, the suction arm 11 is an example of a suction member, the information acquisition unit 61 is an example of a registration information receiving unit, and the suction action control unit 70 is an example of a control unit.

[0101] (9) Method

[0102] Those skilled in the art will understand that the above-described exemplary embodiments are specific examples of the following approaches.

[0103] (Item 1) A cell pickup device according to one method is used to aspirate cells from a liquid sample in a sample container, said cell pickup device may also include:

[0104] A suction component that can be fitted with a pipette tip;

[0105] A drive unit that moves the suction component and performs suction through the suction component and the pipette tip;

[0106] An operation mode switching unit switches the operation mode of the drive unit between a first mode and a second mode; and

[0107] The control unit controls the drive unit.

[0108] In the first mode, the control unit controls the drive unit to perform a first traveling action, a scanning action, a pitching action, and a suction action. The first traveling action involves moving the suction member along the axial direction of the pipette tip while the pipette tip is tilted relative to the vertical direction, causing the tip of the pipette tip to contact the bottom surface of the sample container. The scanning action involves moving the suction member horizontally to scan the bottom surface of the sample container with the tip of the pipette tip moving towards a first position. The pitching action involves further tilting the suction member relative to the vertical direction, causing the tip of the pipette tip at the first position to rise and the base of the pipette tip to fall. The suction action involves using the suction member and the pipette tip to attract the sample from the sample container.

[0109] In the second mode, the control unit controls the drive unit to perform a second traveling action and an aspiration action. The second traveling action is to move the aspiration member along the axial direction of the pipette tip while the pipette tip mounted on the aspiration member is tilted relative to the vertical direction, thereby moving the tip of the pipette tip to a second position in the sample container that is above the first position.

[0110] According to the cell pickup device described in item 1, the operating mode of the drive unit can be switched between a first mode and a second mode. In the first mode, the pipette tip is used to scan the bottom surface of the sample container horizontally and aspirate the sample while the tip of the pipette tip is in contact with the bottom surface of the sample container. This allows cells adhering to the bottom surface of the sample container to be scraped off by the tip of the pipette tip. In the second mode, the sample is aspirated while the tip of the pipette tip is positioned between the bottom surface of the sample container and the liquid surface of the sample. This allows cells suspended in the liquid sample within the sample container to be aspirated. As a result, by switching the operating mode of the drive unit according to the state of the cells within the sample, cells within the sample can be aspirated efficiently.

[0111] (Item 2) The cell pickup device described in Item 1 may also include a discharge command receiving unit, which receives a command for a first discharge action in a first mode or a second mode. The first discharge action is the action of discharging the sample aspirated into the pipette tip into the sample container.

[0112] When the discharge command receiving unit receives a command for the first discharge action, the control unit controls the drive unit to perform the first discharge action.

[0113] According to the cell pickup device described in item 2, in both the first and second modes, if the number of cells aspirated into the pipette tip is not the desired number, the cells do not need to wait for aspiration to stop before naturally falling from the pipette tip. Therefore, the cells can be immediately returned from the pipette tip to the sample container via user instruction. This shortens the time required for subsequent aspiration actions.

[0114] (Item 3) The cell pickup device described in Item 1 or Item 2 may also include a registration information receiving unit, which receives registration information corresponding to the sample container.

[0115] In the first mode, the control unit controls the drive unit to terminate the first movement based on the registration information received by the registration information receiving unit.

[0116] According to the cell pickup device described in item 3, the control unit can stop the movement of the suction member when the tip of the pipette tip contacts the bottom surface of the sample container. This prevents damage to the tip of the pipette tip.

[0117] (Item 4) In the cell pickup device described in Item 3, the control unit may control the drive unit in the second mode to end the second movement based on the registration information received by the registration information receiving unit.

[0118] According to the cell pickup device described in item 4, the control unit can stop the movement of the suction member to prevent the tip of the pipette tip from contacting the bottom surface of the sample container. This prevents the tip of the pipette tip from contacting the bottom surface of the sample container during the second movement.

[0119] (Item 5) In any of the cell picking devices described in items 1 to 4, the control unit may control the drive unit in a first mode or a second mode to perform a first retraction action and a second retraction action. The first retraction action is an action in which the suction member retracts axially at a first speed until the tip of the pipette tip reaches a predetermined height after the suction action is completed. The second retraction action is an action in which the suction member retracts axially at a second speed greater than the first speed after the tip of the pipette tip reaches the predetermined height.

[0120] According to the cell pickup device described in item 5, the retraction speed of the pipette tip is relatively low before the tip reaches the predetermined height. Therefore, even if the attracted cells adhere to the sample due to surface tension, etc., it is possible to prevent the cells from falling back into the sample. On the other hand, after the tip reaches the 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. This improves the operability of the cell pickup device.

[0121] (Item 6) In the cell pickup device described in Item 5, the specified height may be the height from the bottom surface of the sample container to the liquid level of the sample in the sample container.

[0122] According to the cell pickup device described in item 6, the retraction speed of the pipette tip is relatively slow before the tip detaches from the sample, thus more reliably preventing cells from falling back into the sample. Furthermore, after the tip detaches from the sample, the retraction of the pipette tip can be completed in a short time. Additionally, it prevents cells from being exposed to the atmosphere for extended periods.

[0123] (Item 7) In the cell pickup device described in items 1 to 6, the control unit may control the drive unit in the first mode to perform a suction action during the pitching motion.

[0124] According to the cell pickup device described in item 7, cells detached from the bottom of the sample container by the tip of the pipette tip can be picked up more efficiently.

[0125] (Item 8) In the cell pickup device described in items 1 to 7, the control unit may control the drive unit in the first mode to perform a pitch release action after the suction action is completed. The pitch release action is an action to release the tilt of the suction member that has been tilted by the pitch action.

[0126] According to the cell pickup device described in item 8, the position of the pipette tip after aspirating cells returns to the position before the pitching motion of the aspiration member. Therefore, the aforementioned cell aspiration can be performed continuously with simple control.

[0127] (Item 9) Other cell pickup methods are used to aspirate cells from a liquid sample within a sample container, and the cell pickup method may also include the following steps:

[0128] Switch the action mode between the first mode and the second mode;

[0129] In the first mode, a first traveling action, a scanning action, a pitching action, and a suction action are performed. The first traveling action involves moving the suction member along the axial direction of the pipette tip while the pipette tip is tilted relative to the vertical direction, causing the tip of the pipette tip to contact the bottom surface of the sample container. The scanning action involves moving the suction member horizontally to scan the bottom surface of the sample container with the tip of the pipette tip towards a first position. The pitching action involves further tilting the suction member relative to the vertical direction, causing the tip of the pipette tip at the first position to rise and the base of the pipette tip to fall. The suction action involves attracting the sample from the sample container using the suction member and the pipette tip.

[0130] In the second mode, a second traveling action and an aspiration action are performed. The second traveling action is to move the aspiration member along the axial direction of the pipette tip while the pipette tip mounted on the aspiration member is tilted relative to the vertical direction, thereby moving the tip of the pipette tip to a second position in the sample container that is above the first position.

[0131] According to the cell pickup method described in item 9, the operating mode of the drive unit can be switched between a first mode and a second mode. In the first mode, the pipette tip is used to scan the bottom surface of the sample container horizontally and aspirate the sample while the tip of the pipette tip is in contact with the bottom surface of the sample container. This allows cells adhering to the bottom surface of the sample container to be scraped off by the tip of the pipette tip. In the second mode, the sample is aspirated while the tip of the pipette tip is positioned between the bottom surface of the sample container and the liquid surface of the sample. This allows cells suspended in the liquid sample within the sample container to be aspirated. As a result, by switching the operating mode of the drive unit according to the state of the cells within the sample, cells within the sample can be aspirated efficiently.

Claims

1. A cell pickup device for drawing cells from a liquid sample in a sample container, the cell pickup device comprising: A suction component that can be fitted with a pipette tip; A drive unit that moves the suction member and performs suction through the suction member and the pipette tip; An operation mode switching unit switches the operation mode of the drive unit between a first mode and a second mode; as well as The control unit controls the drive unit. in, In the first mode, the control unit controls the drive unit to perform a first traveling action, a scanning action, a pitching action, and a suction action. The first traveling action involves moving the suction member along the axial direction of the pipette tip while the pipette tip is tilted relative to the vertical direction, causing the tip of the pipette tip to contact the bottom surface of the sample container. The scanning action involves moving the suction member horizontally to scan the bottom surface of the sample container with the tip of the pipette tip moving towards a first position. The pitching action involves further tilting the suction member relative to the vertical direction, causing the tip of the pipette tip at the first position to rise and the base of the pipette tip to fall. The suction action involves using the suction member and the pipette tip to attract the sample from the sample container. In the second mode, the control unit controls the drive unit to perform a second traveling action and the suction action. The second traveling action is to move the suction member along the axial direction of the pipette tip while the pipette tip mounted on the suction member is tilted relative to the vertical direction, thereby moving the tip of the pipette tip to a second position in the sample container that is above the first position. in, The control unit controls the drive unit in the first mode to perform a pitch release action after the attraction action ends. The pitch release action is an action to release the tilt of the attraction member that has been tilted by the pitch action. In the first mode, the user confirms the suction cells between the suction action and the pitch release action; as well as The control unit controls the drive unit in either the first mode or the second mode to perform a first retraction action and a second retraction action. The first retraction action is an action in which the suction member retracts along the axial direction at a first speed until the tip of the pipette tip reaches a predetermined height after the suction action is completed. The second retraction action is an action in which the suction member retracts along the axial direction at a second speed greater than the first speed after the tip of the pipette tip reaches the predetermined height.

2. The cell pickup device according to claim 1, wherein, It also includes a discharge command receiving unit, which accepts a command for a first discharge action in either the first mode or the second mode. The first discharge action is the action of discharging the sample aspirated into the pipette tip into the sample container. When the discharge command receiving unit receives a command for the first discharge action, the control unit controls the drive unit to perform the first discharge action.

3. The cell pickup device according to claim 1 or 2, wherein, It also includes a registration information receiving unit, which receives registration information corresponding to the sample container, and the control unit controls the drive unit in the first mode to end the first movement action based on the registration information received by the registration information receiving unit.

4. The cell pickup device according to claim 3, wherein, In the second mode, the control unit controls the drive unit to terminate the second movement based on the registration information received by the registration information receiving unit.

5. The cell pickup device according to claim 1, wherein, The specified height is the height from the bottom surface of the sample container to the liquid level of the sample within the sample container.

6. The cell pickup device according to claim 1 or 2, wherein, The control unit controls the drive unit in the first mode to perform the suction action during the pitching motion.

7. A cell pickup method for aspirating cells from a liquid sample within a sample container, the cell pickup method comprising the following steps: Switch the action mode between the first mode and the second mode; In the first mode, a first traveling action, a scanning action, a pitching action, and a suction action are performed. The first traveling action is to move the suction member along the axial direction of the pipette tip while the pipette tip is tilted relative to the vertical direction, so that the tip of the pipette tip contacts the bottom surface of the sample container. The scanning action is to move the suction member horizontally to scan the bottom surface of the sample container with the tip of the pipette tip heading towards a first position. The pitching action is to further tilt the suction member relative to the vertical direction, so that the tip of the pipette tip at the first position rises and the base of the pipette tip falls. The suction action is to attract the sample in the sample container through the suction member and the pipette tip. as well as In the second mode, a second traveling action and the suction action are performed. The second traveling action is to move the suction member along the axial direction of the pipette tip while the pipette tip mounted on the suction member is tilted relative to the vertical direction, thereby moving the tip of the pipette tip to a second position in the sample container that is above the first position. in, In the first mode, a pitch release action is performed after the attraction action ends. The pitch release action is an action to release the tilt of the attraction member that has been tilted by the pitch action. In the first mode, the user confirms the suction cells between the suction action and the pitch release action; as well as In either the first mode or the second mode, a first retraction action and a second retraction action are performed. The first retraction action is an action in which the suction member retracts along the axial direction at a first speed until the tip of the pipette tip reaches a predetermined height after the suction action is completed. The second retraction action is an action in which the suction member retracts along the axial direction at a second speed greater than the first speed after the tip of the pipette tip reaches the predetermined height.

Images