Cell suction system

Abstract

To provide a cell suction system capable of accurately moving a needle tip of a needle part of a chip to a position of a cell to be sucked after connecting a chip connection shaft of a suction unit to a chip base part of the chip held in a chip container.SOLUTION: A suction unit having a chip connection shaft connected to a chip base of a chip held in a chip container, the suction unit causing a needle portion of the chip to suck and hold a cell component or an entire cell from a cell through the needle tip in a state in which the chip is connected to the chip connection shaft, and a chip container holder configured to allow relative movement of the chip and the chip container with respect to the chip connection shaft to eliminate misalignment when the chip connection shaft is connected to the chip base of the chip held in the chip container; A tip container holding section that holds the tip container.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present disclosure relates to a cell aspiration system. [Background technology]

[0002] There is known a cell suction system that sucks cell components or whole cells from a cell through the needle tip of a chip needle and holds them (see, for example, Patent Documents 1 to 6). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Patent No. 6066110 [Patent Document 2] Patent No. 6090387 [Patent Document 3] Patent No. 6787274 [Patent Document 4] Patent No. 6953888 [Patent Document 5] Japanese Patent Publication No. 2023-18912 [Patent Document 6] Japanese Patent Publication No. 2023-17601 Summary of the Invention [Problem to be solved by the invention]

[0004] The object of the present disclosure is to provide a cell suction system that can accurately move the tip of the needle of the chip to the position of the cell to be suctioned after connecting the chip connection shaft of the suction unit to the chip base of the chip held in a chip container. [Means for solving the problem]

[0005] One aspect of the present disclosure is as follows.

[0006] [1] 1. A cell aspiration system, comprising: a suction unit having a tip connection shaft connected to a tip base of a tip held in a tip container, the suction unit sucking cell components or whole cells from a cell into a needle part of the tip from a needle tip while the tip is connected to the tip connection shaft, and holding the cell components or whole cells; A cell suction system having a chip container holding section that holds the chip container so as to allow relative movement of the chip and the chip container with respect to the chip connection shaft, eliminating misalignment when the chip connection shaft is connected to the chip base of the chip held in the chip container.

[0007] [2] The tip container is provided. The cell suction system according to [1], wherein the tip container holding part has a mounting part on which the tip container is mounted, and a tip container regulating part that regulates horizontal movement of the tip container while allowing the tip container to slide relative to the mounting part, thereby eliminating misalignment when the tip connection shaft is connected to the tip base of the tip held in the tip container.

[0008] [3] The tip container has four corners when viewed from above, The cell suction system according to [2], wherein only the four corners of the tip container are placed on the placement portion of the tip container holder.

[0009] [4] The tip container holding unit has a mounting unit on which the tip container is mounted, The cell suction system according to any one of [1] to [3], wherein the placement section has a base material and a surface layer applied to the upper surface of the base material and having a lower coefficient of friction than the upper surface.

[0010] [5] A first holding part that holds the tip container; The cell suction system according to any one of [1] to [4], further comprising: a second holding part that holds the first holding part while allowing relative movement of the first holding part with respect to the second holding part, thereby eliminating misalignment when the chip connection shaft is connected to the chip base of the chip held in the chip container.

[0011] [6] The cell suction system described in [5], wherein the second holding unit has a second holding unit main body and a rolling body that is rotatably held in the second holding unit main body and on which the first holding unit is placed.

[0012] [7] The cell suction system described in [6], wherein the rolling elements are ball-shaped.

[0013] [8] The cell suction system according to [6] or [7], wherein three or more rolling bodies are provided.

[0014] [9] The cell suction system described in any one of [6] to [8], wherein the second holding unit main body has a reduced diameter support surface that gradually reduces in diameter downward and slidably abuts against the underside of the rolling body to rotatably support the rolling body, and an ascent control part that controls the relative movement of the first holding unit upward with respect to the second holding unit main body so that the rolling body does not slip out of the reduced diameter support surface.

[0015]

[10] The cell suction system described in any one of [5] to [9], wherein the tip container holding unit has a positioning unit that changes its state between a positioning state in which the first holding unit is positioned horizontally relative to the second holding unit, and a positioning release state in which the positioning is released.

[0016]

[11] The cell suction system according to any one of [5] to

[10] , wherein the first holding part has a first holding part main body on which the tip container is placed, and a tip container positioning part that positions the tip container in the first holding part main body.

[0017]

[12] a chip connection work area where the chip connection shaft is connected to the chip held in the chip container; a cell suction working area in which the cell components or the whole cell are aspirated from the cell into the tip; The cell suction system according to any one of [1] to

[11] , wherein the ambient temperature of the tip connection work area is lower than the ambient temperature of the cell suction work area.

[0018]

[13] an imaging device that images the cellular components or the entire cell of the cell contained in the cell container; A cell suction system according to any one of [1] to

[12] , further comprising: a control device that controls the suction unit based on the imaging results of the imaging device so that the cellular components or the entire cell are sucked from the cell and held by the chip while the chip is connected to the chip connection shaft.

[0019]

[14] The cell suction system according to any one of [1] to

[13] , further comprising a transport device that transports the suction unit from a position where the chip connection shaft is connected to the chip held in the chip container to a position where the cell components or the entire cell are sucked from the cells contained in a cell container into the chip.

[0020]

[15] an imaging device that images the cellular components or the entire cell of the cell contained in the cell container;

[14] A cell suction system as described in

[14] , which has a control device that controls the conveying device and the suction unit based on the imaging results of the imaging device, so that the cell components or the entire cell are sucked from the cell and held by the chip while the chip is connected to the chip connection shaft.

[0021]

[16] The chip is provided. the tip has a tubular tip base portion that forms a connection port on the tip base end side, and the needle portion that has a sharpened tubular shape and extends from the tip base portion to the tip tip end side, The cell suction system according to any one of [1] to

[15] , wherein the chip connection shaft is connected to the chip base by being inserted into the connection port and fitted thereto. [Effects of the Invention]

[0022] According to the present disclosure, a cell suction system can be provided that can connect the chip connection shaft of the suction unit to the chip base of a chip held in a chip container, and then accurately move the needle tip of the needle part of the chip to the position of the cell to be suctioned. [Brief explanation of the drawings]

[0023] [Figure 1] FIG. 1 is a schematic diagram illustrating an entire cell aspiration system according to a comparative example of the present disclosure. [Figure 2] 2 is a schematic diagram showing the state immediately before the tip connection shaft of the suction unit is connected to the tip base of the tip held in the tip container in the cell suction system shown in FIG. 1. FIG. [Figure 3] 3 is a schematic diagram showing a state in which the tip connection shaft of the suction unit is connected to the tip base portion from the state shown in FIG. 2. FIG. [Figure 4] FIG. 10 is a schematic diagram showing a state in which the tip connection shaft of the suction unit is connected to the tip base of the tip held in the tip container in the cell suction system according to the first embodiment of the present disclosure. [Figure 5A] 5 is a detailed view showing the tip, tip container, and tip container holder shown in FIG. 4 from obliquely above. FIG. [Figure 5B] 5B is a detailed view showing the tip, tip container, and tip container holder shown in FIG. 5A from above. FIG. [Figure 5C] 5B is a cross-sectional view taken along the line AA in FIG. 5B. [Figure 6]FIG. 10 is a schematic diagram showing a state in which the tip connection shaft of the suction unit is connected to the tip base of the tip held in the tip container in the cell suction system according to the second embodiment of the present disclosure. [Figure 7A] 7 is a detailed view showing the tip, tip container, and tip container holder shown in FIG. 6 from obliquely above. FIG. [Figure 7B] 7B is a detailed view showing the tip, tip container, and tip container holder shown in FIG. 7A from above. FIG. [Figure 7C] FIG. 7B is a cross-sectional view of FIG. 7B. [Figure 7D] FIG. 7D is a partially enlarged view of FIG. 7C. DETAILED DESCRIPTION OF THE INVENTION

[0024] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the drawings.

[0025] The present embodiment relates to a cell suction system 10 that aspirates cellular components or whole cells from cells, and particularly to a cell suction system 10 that is suitable for aspirating a large number of cells.

[0026] In research on biological systems, it is common to identify characteristic cells from among many cells in a cell culture well and aspirate those cells or their components. For example, in the drug discovery process to discover and design new drugs, a drug discovery screening process is performed to find those that exhibit pharmacological efficacy and activity from among many candidate compounds. In this process, cells that show significantly unique changes are selected from a group of cells in a cell culture well to which a candidate compound has been added, and those cells or cell components are aspirated and analyzed by mass spectrometry or other methods.

[0027] When aspirating cells, a suction pipette or dispensing device equipped with a tip is used, and the cells are aspirated into the tip while being checked under a microscope.When aspirating cellular components, a fine tip called a nanospray tip is used, and the cellular components are aspirated into the tip while being checked under a microscope.

[0028] In addition to the task of aspirating and analyzing specific cells or cell components in a cell culture well, a cell analysis system has been put into practical use that takes microscopic images of large numbers of cells in a cell culture well and processes the images to identify individual cells and calculate the size, brightness, and other characteristics of each cell in real time.

[0029] Cell analysis systems can detect characteristic cells and observe changes over time based on calculated feature values. They also display the feature values ​​of each cell in histograms, scatter plots, or lists. However, cell analysis systems are limited to analyzing the feature values ​​obtained from images, and are not designed to perform detailed analysis of specific cells identified through analysis.

[0030] The task of aspirating cells and cell components requires visual inspection of each cell, selecting the cells to be analyzed, and aspirating them, which is extremely time-consuming when processing a large number of cells and places a heavy burden on the operator. For this reason, there is a need for a system that can easily detect candidate cells to be analyzed from a large number of cells and perform the aspirating task immediately. For example, the technology disclosed in Patent Document 1 above makes it possible to assist in the aspirating task of targeting characteristic cells from a large number of cells.

[0031] The cell suction system 10 of this embodiment is a cell suction system 10 suitable for suction work targeting characteristic cells among a large number of cells, and after connecting the tip connection shaft 322 of the suction unit 320 to the tip base 331 of the tip 330 held in the tip container 341, the needle tip of the needle portion 332 of the tip 330 can be moved with high precision to the position of the cell to be suctioned.

[0032] Before explaining the cell suction system 10 according to this embodiment, we will explain, as a comparative example, a cell suction system 10 in which it is difficult to accurately move the needle tip of the needle portion 332 of the tip 330 to the position of the cells to be suctioned after connecting the tip connection shaft 322 of the suction unit 320 to the tip base 331 of the tip 330 held in the tip container 341.

[0033] The cell suction system 10 according to this comparative example has the same configuration as the cell suction system 10 according to this embodiment, except that the configuration of the tip container holder 342 is different.

[0034] As shown in FIGS. 1 and 2, the cell suction system 10 according to this comparative example includes a cell container 100, an imaging device 200, a cell suction device 300, and a control device 400.

[0035] The cell container 100 has multiple storage sections 110 arranged on an XY plane (preferably a horizontal plane), and stores cells in each storage section 110. The cell container 100 is a cell culture container having cell culture wells as the storage sections 110. The cell container 100 is placed in the cell suction work area R2.

[0036] The imaging device 200 includes an optical system device 210 and an XY stage 220. The optical system device 210 captures images of cellular components or the entire cell contained in the cell container 100 placed on the XY stage 220 to generate an image. The image may be obtained by confocal two-color fluorescence observation, confocal one-color fluorescence observation, epi-fluorescence one-color observation, bright-field observation, or the like, and is not particularly limited. The XY stage 220 moves the cell container 100 in the X and Y directions relative to the optical system device 210 to a position required for observing the desired cell using the optical system device 210.

[0037] The cell suction device 300 has a transport device 310 (XYZ stage), a suction unit 320, a chip 330, a chip storage section 340, and a post-suction chip storage section 350. The chip storage section 340 is disposed in the chip connection working area R1. The post-suction chip storage section 350 is disposed in the chip detachment working area R3.

[0038] The transport device 310 transports the suction unit 320 to a desired position in the X, Y, and Z directions. The transport device 310 transports the suction unit 320 to a position (chip connection working area R1) where the chip connection shaft 322 is connected to the chip 330 held in the chip container 341, and after the chip 330 is connected, transports it from that position to a position (cell suction working area R2) where cellular components or entire cells are sucked from the cells contained in the cell container 100 into the chip 330, and after the suction operation, transports it from that position to a position (chip detachment working area R3) where the chip 330 is detached and held in the chip container after suction.

[0039] The suction unit 320 has a suction unit base 321, a tip connection shaft 322, and a tip connection / disconnection shaft 323. The suction unit base 321 is transported by the transport device 310. The tip connection shaft 322 is axially (preferably cylindrically) centered on a first central axis O1 extending downward from the suction unit base 321, and is connected to a tip base 331 of the tip 330. With the tip 330 connected to the tip connection shaft 322, the suction unit 320 sucks cellular components or entire cells from the cell into the needle portion 332 of the tip 330 from the needle tip and holds them.

[0040] This suction operation may be performed by changing the pressure inside the needle 332 using the suction unit base 321 via a hole (not shown) provided in the tip connection shaft 322 and the tip base 331. The suction operation may also be performed by surface tension generated inside the needle 332, since the tip of the needle 332 is thin and tubular. In cases where the suction force due to surface tension is too strong and would otherwise suck in not only the cellular component or the entire cell to be sucked in, but also surrounding components, the suction of surrounding components may be suppressed by applying positive pressure to the needle tip using the suction unit base 321.

[0041] The suction operation may be performed by generating an interaction between the needle tip and the cell, such as by changing the height of the needle tip to pierce the cell, and then switching the pressure supplied to the needle tip from the suction unit base 321 between negative and positive pressure depending on the timing of the interaction, thereby suctioning a desired cellular component or an entire cell from a desired location. The pressure (negative pressure, positive pressure) supplied to the needle tip is supplied from a pressure source such as a pump (not shown). The pressure supply path from the pressure source to the tip of the chip connection shaft 322 may include a pressure control component such as a valve for controlling the pressure.

[0042] The chip disconnection shaft 323 is held so as to be movable up and down relative to the suction unit base 321, and when the chip 330 is connected to the chip connection shaft 322, it moves downward relative to the suction unit base 321, thereby pressing down the chip base 331 and disconnecting the chip 330, thereby detaching the chip 330 from the chip connection shaft 322.

[0043] The tip 330 has a tubular (preferably cylindrical) tip base 331 centered on a second central axis O2 that forms a connection port 331a on the tip base end side, and a sharpened tubular (preferably cylindrical) needle portion 332 extending from the tip base 331 to the tip distal end side. The tip connection shaft 322 is connected by being inserted into the tip base 331 through the connection port 331a and fitted together. In this embodiment, the tip base 331 has a larger outer diameter than the needle portion 332. The tip 330 may be configured such that the outer diameter of the tip base 331 is equal to or smaller than the outer diameter of the needle portion 332. In this case, the configuration of the tip container 341 that holds the tip 330 can be appropriately set according to the shape of the tip 330.

[0044] Tip base 331 of tip 330 is made of an elastic material such as elastomer, resin, etc. By making tip base 331 out of an elastic material, when tip connection shaft 322 is inserted downward into connection port 331a of tip base 331 and fitted, cylindrical tip base 331 deforms to expand in the radial direction, generating contact pressure on tip connection shaft 322, and the frictional force generated by the contact pressure allows tip base 331 to be connected to tip connection shaft 322.

[0045] The method for forming needle portion 332 of tip 330 is not particularly limited, and it can be formed, for example, by heating, melting, and pulling a glass tube to create a constricted portion in the glass tube, and then separating the constricted portion to form a sharp needle tip. Needle portion 332 of tip 330 may also be formed by etching a crystalline material such as silicon with a chemical solution, creating a sharp portion due to differences in etching speed depending on the crystal orientation, and then forming the sharp portion into a sharp needle tip.

[0046] The tip storage section 340 has a tip container 341 and a tip container holder 342. The tip container 341 holds a plurality of tips 330 before they are used for cell aspiration. The tip container 341 has a tip base holder 341a that holds the tip base 331. The tip base holder 341a has a through-hole shape into which the needle 332 is passed downward and the tip base 331 is placed, and into which the outer circumferential surface of the tip base 331 fits. The tip container 341 is not limited to a configuration having the tip base holder 341a, and may be configured to hold the needle 332 instead of or in addition to the tip base 331, for example.

[0047] The post-suction tip storage section 350 has a post-suction tip container (not shown) and a post-suction tip container holder (not shown). The post-suction tip container holds multiple tips 330 after being used in a cell suction operation. The post-suction tip container has a similar configuration to the tip container 341, but is not limited to this.

[0048] The control device 400 has a computer that controls the operation of the XY stage 220, the optical system device 210, the transport device 310, and the suction unit 320, and controls the transport device 310 and the suction unit 320 based on the imaging results (images obtained by observing the cells) by the imaging device 200 so that cellular components or entire cells are sucked from the cells and held by the chip 330 with the chip 330 connected to the chip connection shaft 322. The control device 400 displays the imaging results on a display or the like, accepts instructions from an operator who views the displayed imaging results, and operates the transport device 310 and the suction unit 320 based on the accepted instructions. The cell suction system 10 is not limited to a configuration including the transport device 310 that transports the suction unit 320, and may be configured to include, for example, transport devices that transport the chip storage section 340, the post-suction chip storage section 350, and the XY stage 220, respectively, instead of the transport device 310. In this case, the control device 400 may be configured to control the above-mentioned conveying device and suction unit 320 based on the imaging results (images obtained by observing the cells) by the imaging device 200 so that cellular components or the entire cell are sucked from the cell and held by the chip 330 while the chip 330 is connected to the chip connection axis 322.

[0049] In this comparative example, the tip container holding part 342 holds the tip container 341 so that the tip container 341 does not move on the XY plane relative to the base (not shown) of the cell suction system 10 that supports the transport device 310. Therefore, in this comparative example, as shown in FIGS. 2 and 3, when the suction unit 320 is lowered by the transport device 310 in the tip connection working area R1 and inserted into the connection port 331a of the tip base 331 of the tip 330 held in the tip container 341, misalignment may occur, in which the first central axis O1 of the tip connection shaft 322 is misaligned from the second central axis O2 of the tip base 331. In this case, it becomes difficult to accurately move the needle tip of the needle part 332 of the tip 330 to the position of the cell to be suctioned.

[0050] 2 and 3, when the chip connecting shaft 322 is lowered at a position misaligned with the chip base 331 in the X or Y direction and inserted into the chip base 331, the chip container 341 is installed at the base of the cell suction system 10 so as not to move on the XY plane, and therefore the chip base 331 cannot move on the XY plane either, and therefore the chip base 331 is inserted in a state where it is deformed in a direction misaligned with the chip connecting shaft 322. This causes residual stress in the chip base 331 that is biased in the circumferential direction.

[0051] Therefore, when the transport device 310 subsequently raises the suction unit 320, lifts the tip 330 from the tip container 341, and moves the tip 330 to the cell suction working area R2 where the suction operation is performed, the residual stress in the tip base 331 is gradually released, causing the tip of the needle 332 to move on the XY plane, resulting in variation in the position of the needle tip.

[0052] The cell suction work area R2 may be heated to 37°C or higher to prevent cells from dying. In such cases, the ambient temperature of the chip connection work area R1 is usually lower than that of the cell suction work area R2, so movement to the cell suction work area R2 is likely to be affected by residual stress.

[0053] In particular, when aspirating components from specific intracellular sites, the needle tip must be aligned on the XY plane with an accuracy of several μm (e.g., 2 μm or less). However, it is difficult to control the position of the tip connection shaft 322 of the suction unit 320 relative to the tip 330 held in the tip container 341 by teaching the operation of the transport device 310 so that the misalignment of the needle tip caused by residual stress falls within the above accuracy range, which poses problems such as the need for special jigs and tools for teaching and the time required for teaching.

[0054] Furthermore, the tip containers 341 are often manufactured by resin molding, and the shape of the tip containers 341 themselves varies, which also causes variations in the positions of the tips 330 held in the tip containers 341.

[0055] In order to address the problem of needle tip misalignment due to misalignment during connection in this comparative example, in the cell suction system 10 according to the first embodiment of the present disclosure, as shown in Figures 4 to 5C, the tip container holding section 342 holds the tip container 341 so as to allow relative movement of the tip 330 and the tip container 341 with respect to the tip connection shaft 322, which eliminates misalignment when the tip connection shaft 322 is connected to the tip base 331 of the tip 330 held in the tip container 341.

[0056] The tip container holder 342 has a mounting portion 342a on which the tip container 341 is placed. The tip container 341 has four corners 341b when viewed from above. In this embodiment, only the four corners 341b of the tip container 341 are mounted on the mounting portion 342a of the tip container holder 342 to reduce sliding resistance. The mounting portion 342a is flat and extends along the XY plane. It is preferable that the mounting portion 342a be as slippery as possible. For this reason, the mounting portion 342a preferably has a base material 342a1 and a surface layer 342a2 coated on the upper surface of the base material 342a1 and having a lower coefficient of friction than the upper surface. The surface layer 342a2 is formed, for example, by PTFE coating or PTFE composite electroless nickel plating. Alternatively, the entire tip container holder 342 may be made of a material with a low coefficient of friction, such as PTFE.

[0057] In this embodiment, the tip container holding part 342 has a tip container regulating part 342b that regulates horizontal movement of the tip container 341 while allowing the tip container 341 to slide relative to the mounting part 342a, eliminating misalignment when the tip connection shaft 322 is connected to the tip base 331 of the tip 330 held in the tip container 341. The tip container regulating part 342b has four X-direction facing surfaces 342b1 and four Y-direction facing surfaces 342b2 that face each of the four corners 341b of the tip container 341 with gaps in the X and Y directions. The tip container regulating part 342b is composed of four upward convex parts having four X-direction facing surfaces 342b1 and four upward convex parts having four Y-direction facing surfaces 342b2, but is not limited to this. The tip container regulating portion 342b allows the tip container 341 to move on the XY plane (movement in the X direction, movement in the Y direction, and rotation accompanying these movements).

[0058] According to this embodiment, the tip 330 and tip container 341 are held and restricted from movement on the XY plane by the tip container restricting portion 342b, while within the range of this restriction, smooth sliding on the mounting portion 342a allows movement that eliminates the above-mentioned misalignment, thereby addressing the problem of needle tip misalignment due to misalignment during connection as described above.

[0059] The tip container holding part 342 may connect the tip connection shaft 322 to the tip base part 331 of the tip 330 held in the tip container 341, and then perform disconnection and connection once or multiple times to eliminate misalignment. However, from the viewpoint of work efficiency, a configuration in which misalignment is eliminated by a single connection is preferable.

[0060] The tip container holding part 342 may be configured to have a first holding part 342c that holds the tip container 341, and a second holding part 342d that holds the first holding part 342c while allowing horizontal relative movement of the first holding part 342c with respect to the second holding part 342d, eliminating misalignment when the tip connection shaft 322 is connected to the tip base 331 of the tip 330 held in the tip container 341, as in the second embodiment shown in Figures 6 to 7D.

[0061] The second holder 342d has a second holder body 342d1 and three or more ball-shaped rolling elements 342d2 that are rotatably held by the second holder body 342d1 and on which the first holder 342c is placed. As shown in the figure, the rolling elements 342d2 are preferably provided near each of the four corners 341b of the tip container 341. The rolling elements 342d2 are also preferably provided near the center of the tip container 341 when viewed from the bottom.

[0062] The second retaining portion main body 342d1 has a reduced-diameter support surface 342d3 that gradually reduces in diameter downward and slidably abuts against the lower surface of the rolling element 342d2 to rotatably support the rolling element 342d2, and an ascent restriction portion 342d4 that restricts upward movement of the first retaining portion 342c relative to the second retaining portion main body 342d1 to prevent the rolling element 342d2 from slipping out of the reduced-diameter support surface 342d3. The ascent restriction portion 342d4 restricts the first retaining portion 342c from rising relative to the second retaining portion main body 342d1 by an amount greater than the amount required for the rolling element 342d2 to slip out of the reduced-diameter support surface 342d3 when the first retaining portion 342c is placed on the rolling element 342d2. Therefore, the rolling element 342d2 is well retained within the reduced-diameter support surface 342d3.

[0063] The rise restricting portion 342d4 is configured by one or more setscrews 342e (multiple in this embodiment). The setscrews 342e have a screw shaft 342e1 attached to a female screw portion 342f provided on the second holding portion main body 342d1, and a screw head 342e2 connected to the upper end of the screw shaft 342e1. The screw head 342e2 has a large diameter portion 342e3, and a small diameter portion 342e4 having an outer diameter smaller than that of the large diameter portion 342e3 is provided between the large diameter portion 342e3 and the screw shaft 342e1. The first holding portion 342c has an opening 342c1 large enough to allow the screw shaft 342e1 and small diameter portion 342e4 to pass through but not the large diameter portion 342e3 to pass through. Therefore, the rise restricting portion 342d4 restricts the rise of the first retaining portion 342c relative to the second retaining portion main body 342d1 by the first retaining portion 342c abutting against the lower surface of the large diameter portion 342e3 of the setscrew 342e at the periphery of the opening 342c1. In this embodiment, the amount of threading of the screw shaft 342e1, which determines the allowable rise range, is determined by abutting the lower surface of the small diameter portion 342e4 against the upper surface of the second retaining portion main body 342d1. However, without being limited thereto, for example, a separately provided annular collar member having an inner diameter larger than the outer diameter of the screw shaft 342e1 may be disposed between the large diameter portion 342e3 and the upper surface of the second retaining portion main body 342d1, and the amount of threading may be determined by the vertical width of the collar member.

[0064] Furthermore, a gap 342g is provided between the small diameter portion 342e4 of the setscrew 342e and the outer peripheral edge of the opening 342c1, which allows relative movement (movement in the X direction, movement in the Y direction, and rotation accompanying these movements) of the tip 330, tip container 341, and first holding portion 342c with respect to the tip connecting shaft 322, eliminating the misalignment. Therefore, according to this embodiment, the small diameter portion 342e4 of the setscrew 342e restricts and holds the tip 330, tip container 341, and first holding portion 342c against movement on the XY plane, while allowing movement within the restricted range to eliminate the misalignment, thereby addressing the problem of misalignment of the needle tip due to misalignment.

[0065] In this embodiment, the tip container holder 342 includes a positioning unit 342h that changes its state between a positioning state in which the first holder 342c is positioned on the XY plane relative to the second holder 342d and a positioning release state in which the positioning is released. The positioning unit 342h is preferably positioned at a position on the XY plane that allows movement to eliminate the misalignment in all directions, and more preferably at the center of a restricted range in which movement on the XY plane is restricted. The positioning unit 342h allows the tip container holder 342 to be positioned appropriately to effectively address the problem of needle tip misalignment due to misalignment when the tip connection shaft 322 of the suction unit 320 is positioned relative to the tip 330 held in the tip container 341 by operation teaching of the transport device 310.

[0066] The positioning portion 342h is composed of a first through hole portion 342h1 which is circular in top view and provided in the first holding portion 342c, a first hole portion (not shown) which is circular in top view and provided in the second holding portion 342d, a first pin 342h2 which can be inserted into and removed from the first through hole portion 342h1 and the first hole portion, a second through hole portion 342h3 which is oval in top view and provided in the first holding portion 342c, a second hole portion (not shown) which is circular in top view and provided in the second holding portion 342d, and a second pin 342h4 which can be inserted into and removed from the second through hole portion 342h3 and the second hole portion. According to the above configuration, the tip vessel holding portion 342 can be positioned by inserting the first pin 342h2 into the first through-hole portion 342h1 and the first hole portion, and the second pin 342h4 into the second through-hole portion 342h3 and the second hole portion, and can be released from positioning by removing the first pin 342h2 and the second pin 342h4. Furthermore, since the second through-hole portion 342h3 has an oval shape when viewed from above, manufacturing errors of the first holding portion 342c and the second holding portion 342d can be absorbed.

[0067] The first holder 342c has a first holder body 342c2 on which the tip container 341 is placed, and a tip container positioning part 342i that positions the tip container 341 on the first holder body 342c2. The tip container positioning part 342i is composed of an X-direction pressing device 342i2 that presses the tip container 341 against an X-direction receiving surface 342i1 that is provided on the first holder body 342c2 and receives the tip container 341 in the X direction, and a Y-direction pressing device 342i4 that presses the tip container 341 against a Y-direction receiving surface 342i3 that is provided on the first holder body 342c2 and receives the tip container 341 in the Y direction. The tip container positioning part 342i can more effectively deal with the problem of needle tip misalignment due to core misalignment.

[0068] The X-direction pressing device 342i2 and the Y-direction pressing device 342i4 are each configured with a plurality of (three in this embodiment) ball plungers 342i5 each having, for example, a ball 342i6 that contacts the tip container 341, a ball accommodating portion 342i7 that accommodates the ball 342i6 so that it can move back and forth, and an elastic body (not shown) such as a compression spring that presses the ball 342i6 in the forward direction toward the tip container 341. The ball plungers 342i5 enable smooth placement of the tip container 341 in the first holding portion 342c. However, the X-direction pressing device 342i2 and the Y-direction pressing device 342i4 may each be configured to perform pressing by deformation of an elastic body such as a leaf spring or rubber without using the ball plunger 342i5.

[0069] Although the embodiments of the present disclosure have been described above, the present disclosure is not limited to the above-described embodiments, and the above-described embodiments can be modified in various ways without departing from the gist of the present disclosure. [Explanation of symbols]

[0070] 10 Cell Aspiration System 100 cell containers 110 Storage unit 200 Imaging device 210 Optical equipment 220 XY stage 300 cell suction device 310 Transfer device (XYZ stage) 320 Suction Unit 321 Suction unit base 322 Tip connection shaft 323 Chip disconnect shaft 330 chips 331 Tip base 331a Connection port 332 Needle 340 Chip storage section 341 Chip container 341a Tip base holder 341b corner 342 Tip container holder 342a Placement section 342a1 base material 342a2 surface layer 342b Tip container control section 342b1 X-direction opposing surface 342b2 Y direction opposing surface 342c 1st holding part 342c1 opening 342c2 1st holding part main body 342d 2nd holding part 342d1 Second holding part main body 342d2 Rolling element 342d3 Reduced diameter support surface 342d4 Rise control section 342e Set screw 342e1 screw shaft 342e2 screw head 342e3 Large diameter part 342e4 Small diameter section 342f female thread 342g gap 342h Positioning section 342h1 1st through hole part 342h2 1st pin 342h3 2nd through hole part 342h4 2nd pin 342i Tip container positioning unit 342i1 X-direction receiving surface 342i2 X-direction pressing device 342i3 Y-direction support surface 342i4 Y-direction pressing device 342i5 Ball Plunger 342i6 ball 342i7 Ball holder 350 Post-suction tip storage section 400 control device O1 1st central axis O2 2nd central axis R1 Chip connection work area R2 Cell suction work area R3 Chip removal work area

Claims

1. 1. A cell aspiration system, comprising: a suction unit having a tip connection shaft connected to a tip base of a tip held in a tip container, the suction unit sucking cell components or whole cells from a cell into a needle part of the tip from a needle tip while the tip is connected to the tip connection shaft, and holding the cell components or whole cells; A cell suction system having a chip container holding section that holds the chip container so as to allow relative movement of the chip and the chip container with respect to the chip connection shaft, eliminating misalignment when the chip connection shaft is connected to the chip base of the chip held in the chip container.

2. The tip container is provided. The cell suction system according to claim 1, wherein the tip container holding section has a mounting section on which the tip container is mounted, and a tip container regulating section that regulates horizontal movement of the tip container while allowing the tip container to slide relative to the mounting section, thereby eliminating misalignment when the tip connection shaft is connected to the tip base of the tip held in the tip container.

3. The tip container has four corners in a top view, The cell aspiration system according to claim 2 , wherein only the four corners of the tip container are placed on the placement portion of the tip container holder.

4. The tip container holding unit has a mounting unit on which the tip container is mounted, The cell suction system according to claim 1 , wherein the mounting portion has a base material and a surface layer that is applied to an upper surface of the base material and has a lower coefficient of friction than the upper surface.

5. A first holding part that holds the tip container; 2. The cell suction system according to claim 1, further comprising: a second holding unit that holds the first holding unit while allowing relative movement of the first holding unit with respect to the second holding unit, thereby eliminating misalignment when the chip connection shaft is connected to the chip base of the chip held in the chip container.

6. The cell suction system according to claim 5 , wherein the second holder comprises a second holder body and a rolling body that is rotatably held by the second holder body and on which the first holder is placed.

7. The cell suction system according to claim 6 , wherein the rolling elements are ball-shaped.

8. The cell suction system according to claim 6 , wherein three or more of the rolling elements are provided.

9. The cell suction system of claim 6, wherein the second holder body has a reduced diameter support surface that gradually reduces in diameter downward and rotatably supports the rolling body by slidably abutting against the underside of the rolling body, and an ascent restriction portion that restricts relative movement of the first holder upward with respect to the second holder body so that the rolling body does not slip out of the reduced diameter support surface.

10. The cell suction system according to claim 5, wherein the tip container holding unit has a positioning unit that changes its state between a positioning state in which the first holding unit is positioned horizontally relative to the second holding unit and a positioning release state in which the positioning is released.

11. The cell suction system according to claim 5 , wherein the first holder comprises a first holder body on which the tip container is placed, and a tip container positioning part that positions the tip container on the first holder body.

12. a chip connection work area where the chip connection shaft is connected to the chip held in the chip container; a cell suction working area in which the cell components or the whole cell are aspirated from the cell into the tip; The cell suction system according to claim 1 , wherein the ambient temperature of the tip connection working area is lower than the ambient temperature of the cell suction working area.

13. an imaging device that images the cellular components or the entire cell of the cell contained in the cell container; The cell suction system of claim 1, further comprising a control device that controls the suction unit based on the imaging results obtained by the imaging device so that the cellular components or the entire cell are sucked from the cell and held by the chip while the chip is connected to the chip connection shaft.

14. The cell suction system according to claim 1, further comprising a transport device that transports the suction unit from a position where the tip connection shaft is connected to the tip held in the tip container to a position where the cell components or the entire cell are sucked from the cell contained in a cell container into the tip.

15. an imaging device that images the cellular components or the entire cell of the cell contained in the cell container; The cell suction system of claim 14, further comprising a control device that controls the transport device and the suction unit based on the imaging results of the imaging device so that the cell components or the entire cell are sucked from the cell and held by the chip while the chip is connected to the chip connection shaft.

16. The chip is provided. the tip has a tubular tip base portion that forms a connection port on the tip base end side, and the needle portion that has a sharpened tubular shape and extends from the tip base portion to the tip tip end side, The cell suction system according to claim 1 , wherein the chip connection shaft is connected to the chip base by being inserted into the connection port and fitted thereto.

Images