Method for selecting, collecting, and arranging samples, and apparatus for collecting and arranging samples

Abstract

To provide a method for selecting, collecting, and arranging samples and an apparatus for collecting and arranging samples, which make it possible to perform selection and collection in a shorter time with higher stability and higher positional accuracy.SOLUTION: A part of a gel sheet 4 on a film 2 is cut out so that a gel sheet portion 4E is collected inside a collection pin 141. The gel sheet portion 4E is pushed out from inside the collection pin 141 by pressing a placement pin 142 and is placed at a predetermined position outside the collection pin 141. The method further includes a first selection step of selecting, by an observation optical system, a collection position at which the collection pin 141 is to pierce the gel sheet portion 4E, and a second selection step of selecting, by the observation optical system, a predetermined position at which the gel sheet portion 4E is to be placed.SELECTED DRAWING: Figure 25

Description

[Technical Field]

[0001] The present invention relates to a method and an apparatus for selecting, collecting and placing samples. [Background technology]

[0002] In recent years, technologies for isolating cells and cell populations with desired characteristics from others have been rapidly developing. Cell selection methods such as limiting dilution, cell sorters, microfluidic devices, and colony picking have attracted attention as techniques for isolating target cells.

[0003] Furthermore, printing technology that handles minute droplets is attracting attention as a technique for manipulating a small number of isolated cells. Printing technologies include the inkjet method and the dispenser method.

[0004] However, in order to collect any cell in single cell units, that is, in extremely small amounts, a technology is required to collect even smaller amounts with high precision. In Japanese Patent No. 6640238 (Patent Document 1), a biological sample is cut and collected using a hollow collection needle. By injecting a liquid or the like into the collection needle, the collected sample in the collection needle is expelled from the collection needle. In addition, Japanese Patent Laid-Open No. 2022-90524 (Patent Document 2) discloses a cell collection method for aspirating cells from a liquid sample in a sample container. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 6640238 [Patent Document 2] Japanese Patent Publication No. 2022-90524 Summary of the Invention [Problem to be solved by the invention]

[0006] In Patent Document 1, the liquid injected into the inside of the collection needle causes the sample inside the cut collection needle to crumble and disperse. Furthermore, the cutting of the collection needle may cause damage to the cut sample.

[0007] In Patent Document 2, the suction member repeatedly moves horizontally to collect cells. This lengthens the takt time required for cell collection, reducing the throughput of moving large amounts of sample. Furthermore, in Patent Document 2, the cells are present in droplets. Therefore, even if the position coordinates of the cells to be selected are determined before collection, the positions of the cells may shift due to vibrations during operation of the device, making it impossible to collect them accurately.

[0008] The present invention has been made in view of the above-mentioned problems, and an object of the present invention is to provide a method and an apparatus for sorting, collecting and placing samples, which are capable of sorting and collecting samples with high stability and high positional accuracy in a shorter time. [Means for solving the problem]

[0009] A method for selecting, collecting, and placing a sample according to the present disclosure involves forming a gel sheet on a film, in the form of a sheet, that supports an object to be collected. The gel sheet on the film is punctured with a hollow collection pin, and a portion of the gel sheet is cut off, thereby collecting a portion of the gel sheet inside the collection pin. The portion of the gel sheet inside the collection pin is pushed out from the inside of the collection pin by pressing the placement pin, and placed in a predetermined position outside the collection pin. The method further includes a first selection step of selecting a collection position where the gel sheet will be punctured with the collection pin using an observation optical system, and a second selection step of selecting a predetermined position where the gel sheet portion will be placed using the observation optical system.

[0010] A sampling and placement device according to the present disclosure includes a sampling pin, a placement pin, and a fixing holder. The sampling pin is hollow and capable of cutting and sampling the material to be treated. The placement pin is insertable into the sampling pin and contacts the cut material to be treated inside the sampling pin by pressing the sampling pin, thereby pressing the material to be treated and placing the material outside the sampling pin. The sampling pin is fixed to the fixing holder. The material to be treated is a gel sheet formed from a sheet of gel that supports the object to be sampled. The sampling and placement device further includes a holding table and an observation optical system. The holding table holds the material to be cut by the sampling pin. The observation optical system selects a sampling position where the sampling pin will puncture the material to be treated, and a predetermined position where the portion of the material to be treated cut by puncturing will be placed. [Effects of the Invention]

[0011] According to the present disclosure, a method and device for sorting, collecting, and placing samples are provided, which include a first selection step of selecting a collection position where the gel sheet is punctured and a second selection step of selecting a predetermined position where the collected sample is to be placed, thereby enabling selection and collection in a shorter time with high stability and high positional accuracy. [Brief explanation of the drawings]

[0012] [Figure 1] 1 is a schematic front view of the inside of a collection and placement device according to an embodiment of the present invention. [Figure 2] 2 is a front view of the collection and placement mechanism constituting the collection and placement member of FIG. 1, viewed from the negative side in the Y direction. [Figure 3] 3 is a side view of the collection and placement mechanism of FIG. 2 as viewed from the negative side in the X direction. [Figure 4] 2 is a front view of the entire collection and placement member of FIG. 1, viewed from the negative side in the Y direction. [Figure 5] 5 is a side view of the collection and placement member of FIG. 4 as viewed from the negative side in the X direction. [Figure 6] 5 is a front view of the collection and placement member of FIG. 4, seen from the negative side in the Y direction, showing the operation of the process of cutting and collecting the material to be treated. [Figure 7]7 is a side view of the operation of FIG. 6 as viewed from the negative side in the X direction. [Figure 8] 3 is a front view of the collection and placement mechanism of FIG. 2, showing the operation of a first step of releasing and placing the material to be treated, as viewed from the negative side in the Y direction. [Figure 9] 9 is a front view showing the operation in the second step following FIG. 8, as viewed from the negative side in the Y direction. [Figure 10] 10 is a front view showing the operation in the third step following FIG. 9, as viewed from the negative side in the Y direction. [Figure 11] 11 is a side view of the operation of FIG. 10 as viewed from the negative side in the X direction. [Figure 12] 11 is a front view of the operation in the fourth step following FIG. 10, as viewed from the negative side in the Y direction. [Figure 13] 13 is a front view showing the operation in the fifth step following FIG. 12, as viewed from the negative side in the Y direction. [Figure 14] 1 is a schematic cross-sectional view showing a first step of a method for selecting, collecting, and arranging samples according to the first embodiment. FIG. [Figure 15] 5 is a schematic cross-sectional view showing a second step of the method for selecting, collecting and arranging samples according to the first embodiment. FIG. [Figure 16] 10 is a schematic cross-sectional view showing a third step of the method for selecting, collecting and arranging samples according to the first embodiment. FIG. [Figure 17] FIG. 10 is a schematic cross-sectional view showing a fourth step of the method for selecting, collecting and arranging samples according to the first embodiment. [Figure 18] FIG. 10 is a schematic cross-sectional view showing a fifth step of the method for selecting, collecting and arranging samples according to the first embodiment. [Figure 19] FIG. 19 is a schematic enlarged perspective view showing the plate included in FIG. 18 and the gel plate thereon. [Figure 20] FIG. 10 is a schematic cross-sectional view showing a sixth step of the method for selecting, collecting and arranging samples according to the first embodiment. [Figure 21] FIG. 10 is a schematic cross-sectional view showing a seventh step of the method for selecting, collecting and arranging samples according to the first embodiment. [Figure 22] FIG. 10 is a schematic cross-sectional view showing an eighth step of the method for selecting, collecting and arranging samples according to the first embodiment. [Figure 23]23 is a schematic enlarged cross-sectional view of the portion where the collection pin cuts off the gel plate immediately after FIG. 22. FIG. [Figure 24] FIG. 10 is a schematic enlarged cross-sectional view showing a ninth step of the method for selecting, collecting and arranging samples according to the first embodiment. [Figure 25] FIG. 10 is a schematic enlarged cross-sectional view showing a tenth step of the method for selecting, collecting and arranging samples according to the first embodiment. [Figure 26] FIG. 11 is a schematic enlarged cross-sectional view showing an eleventh step of the method for selecting, collecting and arranging samples according to the first embodiment. [Figure 27] FIG. 10 is a schematic cross-sectional view showing a fifth step of the method for selecting, collecting and arranging samples according to the second embodiment. [Figure 28] FIG. 10 is a schematic cross-sectional view showing a seventh step of the method for selecting, collecting and arranging samples according to the second embodiment. [Figure 29] FIG. 10 is a schematic enlarged cross-sectional view showing an eighth step of the method for selecting, collecting and arranging samples according to the second embodiment. [Figure 30] FIG. 10 is a schematic enlarged cross-sectional view showing a ninth step of the method for selecting, collecting and arranging samples according to the second embodiment. [Figure 31] FIG. 10 is a schematic enlarged cross-sectional view showing a tenth step of the method for selecting, collecting and arranging samples according to the second embodiment. [Figure 32] FIG. 11 is a schematic enlarged cross-sectional view showing an eleventh step of the method for selecting, collecting and arranging samples according to the second embodiment. [Figure 33] FIG. 13 is a schematic enlarged cross-sectional view showing a twelfth step of the method for selecting, collecting and arranging samples according to the second embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0013] Hereinafter, the present embodiment will be described with reference to the drawings.

[0014] (Introduction) First, a brief description will be given of a sample selection, collection, and placement method according to this embodiment. In this embodiment, as shown in FIG. 17, a gel 4D supporting a sample 4B to be collected is formed in a sheet shape on a film 2, thereby forming a gel sheet 4. As shown in FIGS. 22 and 23, the gel sheet 4 on the film 2 is punctured with a hollow collection pin 141, and a portion of the gel sheet 4 is cut off, thereby collecting a gel sheet portion 4E inside the collection pin 141. As shown in FIG. 24, the gel sheet portion 4E inside the collection pin 141 is pushed out from the inside of the collection pin 141 by pressing with a placement pin 142 and placed at a predetermined position outside the collection pin 141. As shown in FIGS. 18 and 20, the method further includes a first selection step of selecting, using the observation optical system 106, a collection position where the gel sheet 4 is punctured with the collection pin 141, and a second selection step of selecting, using the observation optical system, a predetermined position where the gel sheet portion 4E is placed.

[0015] (Embodiment 1) (Collection placement device) FIG. 1 is a schematic front view of the interior of a sampling and placement device according to this embodiment. For ease of explanation, the X, Y, and Z directions are introduced. As shown in FIG. 1, the sampling and placement device 100 is a device for sampling a sample from a gel plate 6, which serves as a specimen sample (described later). The sampling and placement device 100 mainly comprises a processing chamber, a sample XY stage 101 arranged inside the processing chamber, a container XY stage 102, and a sampling and placement member 104. Although the sampling and placement device 100 in FIG. 1 has only one sampling and placement member 104, it may include multiple members.

[0016] The sample XY stage 101 is movable horizontally, i.e., along the X and Y directions (X and Y directions). Specifically, for example, a guide unit is provided on the underside of the sample XY stage 101. The guide unit is slidably connected to a guide rail provided on the bottom surface of the processing chamber. The upper surface of the sample XY stage 101 (holding table) serves as a mounting surface on which a gel plate 6 can be fixed. A stage penetration portion 101A that penetrates at least a portion of the sample XY stage 101 is formed. The gel plate 6 is preferably fixed at a position that overlaps the stage penetration portion 101A.

[0017] An XY stage 102 for containers is disposed below the XY stage 101 for samples. The XY stage 102 for containers is movable horizontally, i.e., along the X and Y directions (X and Y directions). Specifically, for example, a guide unit is disposed on the underside of the XY stage 102 for containers. The guide unit is slidably connected to a guide rail disposed on the bottom surface of the processing chamber. The XY stage 102 for containers fixes a plate 8 on which a container 9A capable of accommodating a portion of a gel plate 6 is formed. As a result, in FIG. 1, the collection and placement member 104, the gel plate 6, and the plate 8 on which the container 9A is formed are disposed in this order from top to bottom in the Z direction.

[0018] The sampling and positioning member 104 and the observation optical system 106 are connected to a member movable in the Z direction, such as a Z-axis table. In other words, the sampling and positioning member 104 and the observation optical system 106 are held within the sample sampling device 100 so that they can move in the Z direction. The observation optical system 106 observes and measures the position of the sample to be sampled contained in the gel plate 6. The observation optical system 106 may be equipped with a CCD camera that converts the observed image into an electrical signal. Observation of the gel plate 6 and the like using the observation optical system 106 may be performed using visible light. However, observation of the gel plate 6 and the like is not limited to visible light, and may also be performed using infrared light, X-rays, ultrasound, and the like. Depending on the material of the gel plate 6, magnetic observation of the gel plate 6 is also possible. A gel plate 6 observed by means other than visible light does not need to be transparent or translucent and may be opaque.

[0019] Although not shown, a control unit is installed outside the processing chamber. The control unit has a monitor, a control computer, and an operation panel. In the control unit, a command value for the needle movement speed for sampling from the operation panel is input and stored in the control computer's storage device. For example, during a sample sampling operation, the speed command value is read from the storage device and sent to the control program for the sampling placement member 104. The control program for the sampling placement member 104 determines the rotation speed of the motor included in the sampling placement member 104 based on the command value and moves the sampling pin 141 and the placement pin 142 up and down at a predetermined speed. This causes the sampling operation of the sampling placement member 104 to be performed. If the control computer communicates with a control system located further upstream, the command value may be received from that control system. In addition, parameters corresponding to the material of the gel sheet from which the sample is to be sampled may be stored in the storage device, and a command value for the sampling operation speed may be calculated depending on the specified gel sheet material, thickness, and sampling method.

[0020] (Configuration of collection and placement mechanism) FIG. 2 is a front view of the sampling and positioning mechanism constituting the sampling and positioning member of FIG. 1, as viewed from the negative side in the Y direction. FIG. 3 is a side view of the sampling and positioning mechanism of FIG. 2, as viewed from the negative side in the X direction. As shown in FIGS. 2 and 3, the sampling and positioning member 104 of FIG. 1 includes a part of it, the sampling and positioning mechanism 104A. The sampling and positioning mechanism 104A mainly includes a sampling pin 141, a positioning pin 142, and a fixing holder 143. The sampling pin 141 is a pin (needle-shaped member) for cutting and sampling a processing target material including a sample, etc. The positioning pin 142 is a pin for releasing a sample, etc., sampled and held by the sampling pin 141 and placing it at a desired position. The sampling pin 141 and the positioning pin 142 are formed of, for example, a metal such as stainless steel or plastic.

[0021] The sampling pin 141 has a sampling pin body 141A and a sampling pin holder 141B. The sampling pin body 141A is pin-shaped (pipe-shaped) and cylindrical with a hollow center in a cross section intersecting the extension direction (the vertical direction in Figures 2 and 3: Z direction). The sampling pin holder 141B is inserted onto the outer peripheral surface of the upper part of the sampling pin body 141A. Therefore, the sampling pin holder 141B also has a hollow center in a cross section intersecting the Z direction in Figures 2 and 3. The sampling pin holder 141B is fixed onto the outer peripheral surface of the sampling pin body 141A by press-fitting. Alternatively, the sampling pin holder 141B is adhered to the outer peripheral surface of the sampling pin body 141A with adhesive 141C. 2 and 3, the sampling pin holder 141B is arranged so that the top surface is along the XY plane, but the bottom surface may be inclined with respect to the XY plane, with the outer periphery having a smaller dimension in the Z direction than the inner periphery. As described above, the sampling pin 141 has a hollow shape as a whole.

[0022] The positioning pin 142 has a positioning pin main body 142A and a positioning pin holder 142B. The positioning pin main body 142A is pin-shaped and extends in the Z direction. The positioning pin main body 142A may, for example, be solid inside. However, it is sufficient that at least the bottom surface of the positioning pin main body 142A in the Z direction is closed so as not to have a hole in the center or the like, and the inside may be hollow. The positioning pin holder 142B has a larger dimension along the X direction (and Y direction) than the positioning pin main body 142A. The positioning pin holder 142B holds the positioning pin main body 142A. For example, the bottom surface of the positioning pin holder 142B may be connected to the top surface of the positioning pin main body 142A, and the two may be integrated.

[0023] The location pin body 142A has a smaller cross-sectional dimension than the hollow portion of the sampling pin body 141A. Therefore, the location pin body 142A can be inserted into the interior of the sampling pin body 141A. On the other hand, the location pin holder 142B has a larger cross-sectional dimension than the hollow portion of the sampling pin body 141A. Therefore, the location pin holder 142B cannot be inserted into the interior of the sampling pin body 141A.

[0024] The sampling pin body 141A presses the material to be processed by descending, cutting out a portion of the material, and can store the cut-out portion inside the hollow cylindrical portion. The material to be processed is a gel sheet 4, which is a sheet of gel 4D that supports the sample 4B, the object to be sampled (see FIG. 16, described below). The positioning pin body 142A then moves inside the sampling pin body 141A. The positioning pin body 142A contacts the material to be processed inside the sampling pin 141 and presses against it. This causes the positioning pin body 142A to push the material to the outside of the sampling pin 141. The positioning pin body 142A can move up and down inside the hollow portion of the sampling pin body 141A. In other words, the positioning pin body 142A passes through the interior of the sampling pin body 141A. The positioning pin body 142A moves up and down by a first drive unit 144, described below. This allows the cut material to be placed in a desired position.

[0025] A spring 142C is installed in the area of ​​the interior of the positioning pin holder 142B adjacent to the positioning pin main body 142A, i.e., the lowest area within the positioning pin holder 142B. The spring 142C connects the positioning pin holder 142B to the top of the positioning pin main body 142A. The spring 142C absorbs the Z-direction force applied to the positioning pin holder 142B when the positioning pin main body 142A collides with the material to be processed, such as a substrate. The positioning pin 142 does not need to have the spring 142C. If the positioning pin 142 does not have the spring 142C, it will not be able to absorb the force during a collision. However, if the positioning pin 142 does not have the spring 142C, the effects of a collision can be eliminated by precisely controlling the descending position of the positioning pin 142.

[0026] The fixing holder 143 can hold the sampling pin 141. The fixing holder 143 is disposed above the sampling pin 141 in FIG. 2 and behind the positioning pin 142. The fixing holder 143 has, for example, a plate shape (rectangular parallelepiped shape), but is not limited to this. The sampling pin 141 is fixed to the fixing holder 143. Specifically, the top surface of the sampling pin holder 141B and the bottom surface of the fixing holder 143 are in contact with and fixed to each other at the fixing portion FXD. The fixing portion FXD may be detachably fixed by, for example, a stainless steel screw screwed near the fixing portion FXD of the sampling pin holder 141B and the magnetic force of a magnet embedded near the fixing portion FXD of the fixing holder 143. Alternatively, the fixing portion FXD may be detachably fixed by screwing the stainless steel screw screwed into the sampling pin holder 141B to the fixing holder 143.

[0027] A first driving unit 144 is provided on a front surface 143f (the surface on the negative side in the Y direction) of the fixing holder 143, above the positioning pin holder 142B in the Z direction. The first driving unit 144 includes a first motor 144A, a disk member 144B, and a link member 144C. The first driving unit 144 is attached to a positioning pin holder fixing portion 145.

[0028] The positioning pin holder fixing portion 145 has a first portion 145a and a second portion 145b. The first portion 145a has a plate shape and is installed so that its main surface on the back side contacts the front surface 143f of the fixing holder 143 and is slidable on the front surface 143f. The second portion 145b is a plate-shaped portion installed on the main surface on the front side opposite the main surface of the first portion 145a that contacts the front surface 143f, so as to be approximately perpendicular to the first portion 145a. The front surface 143f of the fixing holder 143 may be formed with, for example, a groove extending along the Z direction, along which the positioning pin holder fixing portion 145 slides.

[0029] The link member 144C is installed on the front side of the disc member 144B in Figure 2. The link member 144C has an elongated shape extending in the vertical direction, i.e., the Z direction. The main surface on the back side of the disc shape of the disc member 144B is in contact with the front surface 143f of the fixing holder 143. A first motor 144A is attached at a position overlapping with the circular center of the disc member 144B. At least a portion of the first motor 144A may be disposed within the fixing holder 143. The disc member 144B can be rotated around its center by the first motor 144A. A first end, which is one end of the link member 144C in the extension direction, is fixed to a part of the outer periphery of the disc member 144B.

[0030] A second end (the lower end in FIG. 2) of the link member 144C opposite the first end in the extension direction (Z direction) is fixed to the positioning pin holder fixing portion 145 so as to come into contact with the first portion 145a of the positioning pin holder fixing portion 145. The second end may be capable of coming into contact with the second portion 145b of the positioning pin holder fixing portion 145. As the first motor 144A rotates the disc member 144B, the link member 144C moves up and down, and the second end moves the positioning pin 142 up and down. This will be described in detail later.

[0031] To achieve this operation, the positioning pin holder fixing portion 145 is provided between the second end and the positioning pin 142 (positioning pin holder 142B), and the positioning pin 142 is fixed thereto. The positioning pin 142 is fixed so as to come into contact with both the first portion 145a and the second portion 145b of the positioning pin holder fixing portion 145. The positioning pin 142 (positioning pin holder 142B) and the positioning pin holder fixing portion 145 (first portion 145a and second portion 145b) may be detachably fixed to each other by, for example, magnetic force between a magnet embedded in the positioning pin holder 142B and a magnet embedded in the first portion 145a. Alternatively, the two may be detachably fixed to each other by screw fastening.

[0032] (Overall configuration of collection placement components) 4 is a front view of the entire collection and placement member of FIG. 1, viewed from the negative side in the Y direction. FIG. 5 is a side view of the collection and placement member of FIG. 4, viewed from the negative side in the X direction. As shown in FIGS. 4 and 5, the collection and placement member 104 further includes a second drive unit 146 in addition to the collection and placement mechanism 104A of FIGS. 2 and 3. The second drive unit 146 is disposed on the rear side of the fixed holder 143 of FIGS. 2 and 3, and includes a movable holder 146A. The movable holder 146A has, for example, a plate shape (rectangular parallelepiped shape) and is configured to store components therein, but is not limited to this. The movable holder 146A has a larger dimension in the Z direction than the fixed holder 143. The collection and placement mechanism 104A is attached to the movable holder 146A.

[0033] The second driving unit 146 is a slide mechanism that slides the collection and placement mechanism 104A, including the fixing holder 143, in the Z direction. In addition to the movable holder 146A, the second driving unit 146 also includes a second motor 146B, a vertically extending screw 146C, and a screw connecting unit 146D. The vertically extending screw 146C extends in the up-down direction and has a male thread formed on its outer periphery. The vertically extending screw 146C is disposed within the rectangular parallelepiped movable holder 146A, for example, and has a larger dimension in the Z direction than the fixing holder 143. The vertically extending screw 146C may be housed in a groove that is formed in the front surface 146f of the movable holder 146A and extends in the Z direction. The second motor 146B is attached to one end (upper end) of the vertically extending screw 146C within the movable holder 146A. The screw connecting portion 146D is attached to the back surface 143b (the surface opposite to the front surface 143f) of the fixing holder 143 so as to be able to connect the vertically extending screw 146C and the fixing holder 143. The screw connecting portion 146D has a female thread formed thereon, and this female thread is fastened to the male thread of the vertically extending screw 146C.

[0034] The vertically extending screw 146C is rotated by the second motor 146B. Although the vertically extending screw 146C does not move vertically when rotated, the screw connector 146D fastened to the vertically extending screw 146C moves vertically. As a result, the entire collection and placement mechanism 104A, including the fixing holder 143 and collection pin 141 attached to the screw connector 146D, moves vertically. This will be described in detail later.

[0035] (Collection process) FIG. 6 is a front view of the collection and placement member of FIG. 4, showing the operation of the process of cutting and collecting the material to be processed, as viewed from the negative side in the Y direction. FIG. 7 is a side view of the operation of FIG. 6, as viewed from the negative side in the X direction. As shown in FIGS. 6 and 7, the rotational motion of the second motor 146B is converted into vertical motion of the screw connection part 146D. The screw connection part 146D and the rear surface 143b of the fixing holder 143 are fixed by screws. Therefore, vertical movement of the screw connection part 146D moves the entire collection and placement mechanism 104A, including the fixing holder 143 and the collection pin 141, in the vertical direction. Note that a slide groove 146E (see FIG. 6) extending along the Z direction is preferably formed on the front surface 146f of the movable holder 146A, which faces the rear surface 143b of the fixing holder 143, to allow the screw connection part 146D to slide. The slide groove 146E is formed so that its depth extends from the front surface 146f toward the positive side in the Y direction (digging from the front side to the back side of the paper in FIG. 6). In this case, the screw connecting portion 146D is arranged so that at least a portion thereof is fitted into the slide groove 146E.

[0036] For example, the sampling and positioning mechanism 104A moves downward as indicated by arrow M1 in Figures 6 and 7. As a result, the tip of the sampling pin 141 (sampling pin body 141A) cuts out the material to be processed that is positioned below the tip. The cut-out portion of the material to be processed is stored in the hollow portion of the sampling pin body 141A.

[0037] (Placement process) FIG. 8 is a front view of the sampling and placement mechanism of FIG. 2, showing the operation of the first step of releasing and placing the material to be processed, as viewed from the negative side in the Y direction. As shown in FIG. 8, a first end of a link member 144C is fixed to a portion of the outer periphery of a disc member 144B by a joint 144D1. A second end of the link member 144C is fixed to the positioning pin holder fixing portion 145 by a joint 144D2. In the initial state of FIG. 8, the first end of the link member 144C is positioned at the top of the disc member 144B. Therefore, the positioning pin holder fixing portion 145 and the positioning pin 142 connected to the link member 144C are positioned at the top in the Z direction. The tip (bottom) of the positioning pin main body 142A is positioned above the bottom of the sampling pin main body 141A. In this state, the bottom of the sampling pin main body 141A becomes the bottom of the entire structure, and this portion can be used to cut out the material to be processed.

[0038] 9 is a front view of the operation in the second step following FIG. 8, as viewed from the negative side in the Y direction. As shown in FIG. 9, the first motor 144A (see FIG. 3) rotates the disk member 144B in the direction indicated by the arrow R in the figure. This causes the first end of the link member 144C to be positioned at the center position of the disk member 144B in the Z direction. Therefore, while the link member 144C is slightly inclined with respect to the Z direction, it lowers the positioning pin holder fixing portion 145 and the positioning pin 142 connected thereto, as indicated by the arrow M2 in the figure.

[0039] FIG. 10 is a front view of the operation in the third step following FIG. 9 , viewed from the negative Y-axis direction. FIG. 11 is a side view of the operation in FIG. 10 , viewed from the negative X-axis direction. As shown in FIGS. 10 and 11 , the disk member 144B further rotates from the state shown in FIG. 9 until the first end reaches the bottom of the disk member 144B. At this time, as indicated by arrow M2 in the figure, the positioning pin 142 moves to the lowest position relative to the sampling pin 141. As the positioning pin 142 moves downward, the tip of the positioning pin body 142A slides downward to penetrate the hollow portion of the sampling pin body 141A. As a result, the tip of the positioning pin body 142A contacts and presses downward against the material to be treated housed within the sampling pin body 141A, expelling it from the sampling pin body 141A and positioning it in the desired position.

[0040] Fig. 12 is a front view, seen from the negative side in the Y direction, of the operation in a fourth step following Fig. 10. Fig. 13 is a front view, seen from the negative side in the Y direction, of the operation in a fifth step following Fig. 12. As shown in Figs. 12 and 13, when the disk member 144B rotates further, the movement direction of the positioning pin 142 and the positioning pin holder fixing portion 145 is reversed as shown by arrow M3 in the figures, and they return to the initial state in Fig. 8 as shown in Fig. 13.

[0041] As a modified example instead of joints 144D1 and 144D2, the following configuration may be used: For example, a spring may be provided to connect positioning pin holder fixing portion 145 and link member 144C, and when link member 144C presses downward, positioning pin holder fixing portion 145 descends, but when link member 144C is not pressed, positioning pin holder fixing portion 145 rises due to the biasing force of the spring.

[0042] (Details of the method for selecting, collecting and arranging the target samples) FIG. 14 is a schematic cross-sectional view showing a first step of the method for selecting, collecting, and arranging samples according to the first embodiment. As shown in FIG. 14, a film 2 is placed on, for example, a glass slide 1. For example, the glass slide 1 is a thin glass plate approximately 1.2 mm thick. The film 2 is made of a soft material and is thin enough to be easily broken by a needle. For example, the film 2 is made of polyvinylidene chloride approximately 10 μm thick. Preferably, the film 2 is made of a thin film used for food packaging or a thin film of silicone rubber. A spacer 3 is placed on the film 2. The spacer 3 may be made of the same glass material as the glass slide 1. The spacer 3 may have a thickness of 100 μm or more and 200 μm or less. For example, the thickness of the spacer 3 may be 100 μm or 200 μm. A through-hole 3A is formed in the center of the spacer 3 when viewed from above (in a plan view) in FIG. 14 . The through-hole 3A penetrates the spacer 3. Therefore, the inside of through-hole 3A is hollow and is not filled with glass or other materials that constitute spacer 3. Through-hole 3A may have any planar shape, such as a rectangular shape.

[0043] Next, a fluid sample 4C, which includes one or more samples 4B as the target object and a fluid gel raw material 4A capable of forming a gel, is supplied into the through-hole 3A. The sample 4B is, for example, a cell to be collected. In FIG. 14, multiple samples 4B are arranged one by one at intervals. The gel raw material 4A is, for example, a 1.5% agarose gel in which a fluorescent dye is added to 1.5 mL of a gel precursor. However, the gel raw material 4A is not limited to this, and may also be, for example, collagen or a mixture of alginate and collagen.

[0044] 15 is a schematic cross-sectional view showing a second step of the method for selecting, collecting, and arranging samples according to embodiment 1. As shown in FIG. 15, a film 2 is attached to the underside of a glass slide 5. The glass slide 5 may be made of the same material and have the same size as the glass slide 1 in FIG. 14. The film 2 on the upper side of the flowing sample 4C in FIG. 15 may be made of the same material and have the same size as the film 2 in FIG. 14.

[0045] FIG. 16 is a schematic cross-sectional view showing the third step of the method for selecting, collecting, and arranging samples according to the first embodiment. As shown in FIG. 16, a glass slide 5 with a film 2 attached thereto is placed on a spacer 3. The film 2 attached to the glass slide 5 comes into contact with the flowing sample 4C and the spacer 3. The glass slide 5 and film 2 press the flowing sample 4C and the spacer 3 downward. As a result, the flowing sample 4C and the spacer 3 are sandwiched between the glass slide 1 with a film 2 attached thereto below and the glass slide 5 with a film 2 attached thereto above. As a result, the glass slide 1, film 2, spacer 3, flowing sample 4C, film 2, and glass slide 5 are stacked in this order from bottom to top.

[0046] Next, for example, if the gel raw material 4A is a material that solidifies depending on temperature, the entire layered structure is cooled to 4°C. By cooling, the gel raw material 4A that constitutes the fluid sample 4C solidifies into a gel 4D, and a gel sheet 4 is formed in the through-hole 3A with the sample 4B supported inside the gel 4D. Although the gel 4D is solidified, it is soft enough to be easily broken by puncturing with a needle. Note that "the sample 4B is supported by the gel 4D" means, for example, that the sample 4B is embedded so that it is surrounded by and buried in the hard gel 4D, and the sample 4B is in a non-fluid state.

[0047] FIG. 17 is a schematic cross-sectional view showing a fourth step of the sample selection, collection, and placement method according to the first embodiment. As shown in FIG. 17, after the gel sheet 4 is placed, the film 2 and slide glass 5 placed on top of the gel sheet 4 are removed, and the slide glass 1 and spacer 3 are also removed. This results in a gel plate 6 including the film 2 and the gel sheet 4 placed on the film 2. The gel sheet 4 is formed by supporting the sample 4B to be collected in a solidified gel 4D, for example, by embedding it therein. The gel 4D is formed in a sheet-like form on the film 2. That is, the gel sheet 4 is formed in a sheet-like form on the film 2 and includes the gel 4D that supports the sample 4B to be collected. In this embodiment, "providing the gel sheet 4" refers to the process of obtaining the gel sheet 4 by supporting the sample 4B in the gel 4D, for example, by embedding it therein, performed on the film 2. Alternatively, a gel sheet 4 previously formed externally may be attached to the film 2. The gel sheet 4 can be formed in advance on any flat surface.

[0048] FIG. 18 is a schematic cross-sectional view showing the fifth step of the method for selecting, collecting, and arranging a sample according to the first embodiment. FIG. 19 is a schematic enlarged perspective view showing the plate and the gel plate thereon shown in FIG. 18. As shown in FIGS. 18 and 19, a first selection step is performed to select a portion of the gel sheet 4 formed as a component of the gel plate 6, which will later be cut off by the sampling pin body 141A. The portion of the gel sheet 4 cut off by the sampling pin body 141A is called the gel sheet portion. In the first selection step, the sampling position, which is the portion of the gel sheet 4 to be punctured by the sampling pin 141, is selected by the observation optical system 106. More specifically, the sampling position is a portion of the gel sheet 4, which is the material to be processed, that will be cut off by the sampling pin 141 to become the gel sheet portion 4E. In other words, the portion of the gel sheet 4 to be cut off is positioned directly below the observation optical system 106 in the Z direction. There is a gap between the observation optical system 106 and the sampling position. In this position, the gel sheet 4 is observed by the observation optical system 106. The image acquired using the observation optical system 106 indicates the position (collection position) to which the collection pin 141 should be lowered when cutting out the gel sheet 4. In other words, the collection position is the position where the target sample 4B to be collected is located. This allows the sample 4B to be collected to be selected.

[0049] In the first selection step, the plate 8 may be fixed on the container XY stage 102 of the collection and placement device 100. In this case, the gel plate 6 may be placed on the fixed plate 8. In FIG. 18, the gel plate 6 is placed on the plate 8, but the gel plate 6 may be placed at a distance from the plate 8 in the Z direction. The plate 8 is a culture plate for cell culture. A plurality of containers 9A are formed on the plate 8 as collection sections. The plurality of containers 9A are recessed portions of the upper surface of the plate 8.

[0050] The multiple containers 9A may be spaced apart from one another, for example, in eight rows in the depth direction and twelve rows in the width direction in FIG. 19 , for a total of 96 containers 9A. The containers 9A may have any planar shape, such as a circle. In FIGS. 18 and 19 , the film 2 constituting the gel plate 6 contacts the upper surface of the plate 8 so as to cover at least a portion of the multiple containers 9A. In FIG. 18 , a portion of the gel sheet 4 to be cut with the collection pin 141 (collection position) is arranged so as to overlap with a portion of the plate 8 (predetermined position) where the gel sheet portion cut with the collection pin 141 should be placed. To achieve this, a portion (upper region) of the plate 8 may be placed within the stage penetration portion 101A in FIG. 1. The sample 4B to be collected is preferably placed directly above one of the multiple containers 9A.

[0051] For example, a sheet fixing member 21 may be placed above the gel plate 6. The sheet fixing member 21 prevents the gel plate 6 from shifting out of position due to force being applied from above to the gel 4D during the process of cutting out the gel sheet 4. Instead of the sheet fixing member 21, an adhesive film tape may be used as a means for preventing the gel plate 6 from shifting out of position.

[0052] Plate 8, on which vessel 9A as a culture vessel is formed, is made of any material selected from the group consisting of polystyrene, polypropylene, polycarbonate, and polyethylene terephthalate.

[0053] 20 is a schematic cross-sectional view showing the sixth step of the method for selecting, collecting, and arranging a sample according to embodiment 1. As shown in FIG. 20, a predetermined position is selected where a gel sheet portion to be cut out later is to be placed. The step of selecting the predetermined position is the second selection step. The first and second selection steps are performed after the step of forming the gel sheet 4 and before the step of collecting the gel sheet portion.

[0054] Here, the second selection step will be specifically described. The gel plate 6 placed on the plate 8 in the first selection step of FIG.

[0055] In FIG. 20, the gel plate 6 in FIG. 18 is removed from the plate 8. However, if the gel plate 6 is fixed to the sample XY stage 101 and the plate 8 is fixed to the container XY stage 102, the gel plate 6 is removed from the plate 8 by driving the sample XY stage 101. Either of the above is acceptable in this embodiment. In either case, the retraction of the gel plate 6 exposes the predetermined position where the gel sheet portion, which is the portion of the material to be treated that was cut out by puncturing, is to be placed directly below the observation optical system 106. This makes the predetermined position observable by the observation optical system 106. The surface of the plate 8 is observed using the observation optical system 106. This selects a portion (predetermined position) of the plate 8 where the gel sheet portion containing the sample 4B should be placed. The observation optical system 106 in the second selection step may be the same as the observation optical system 106 in the first selection step. However, the observation optical system 106 in the second selection step may be different from the observation optical system 106 in the first selection step. That is, the collection and placement device 100 of FIG.

[0056] The predetermined position selected in the second selection step is a partial position within one container 9A (well) of the plate 8 (well plate). The position within one container 9A refers to the position of the surface within the container 9A. In other words, the plate 8 has a plurality of containers 9A (in a matrix) arranged thereon, each capable of containing an object (a gel sheet portion containing a sample 4B). The predetermined position is at least a partial area constituting one of the containers 9A contained in the plate 8. The portion of the material to be treated (gel sheet 4) cut out by puncturing is placed at the predetermined position. This allows the cut-out gel sheet portion to be stably placed within the container 9A of the plate 8.

[0057] Fig. 21 is a schematic cross-sectional view showing a seventh step of the method for selecting, collecting, and arranging samples according to embodiment 1. As shown in Fig. 21, in the seventh step, after the first and second selection steps and before the actual collection step, the gel plate 6 is again placed above the plate 8, similar to the fifth step (first selection step) in Fig. 18.

[0058] As in FIG. 18, the sample 4B to be collected is placed directly above one of the multiple containers 9A. In the seventh step, the gel sheet 4 and plate 8 are moved so that both the collection position and the predetermined position are located directly below the collection pin 141. In other words, the seventh step is the first immediately preceding collection step, in which the gel sheet 4 is placed so that the collection position and the predetermined position overlap immediately before collecting the gel sheet portion. Here, "the collection position and the predetermined position overlap" means that the collection position and the predetermined position overlap so that they are at the same position in a plan view viewed from the Z direction. The gel sheet 4 (gel plate 6) may be moved in the X and Y directions by the sample XY stage 101, or may be placed on the plate 8. The plate 8 is moved in the X and Y directions by the container XY stage 102.

[0059] In the first selection step of FIG. 18 , the positions of multiple, mutually spaced portions of the gel sheet 4 are observed by the observation optical system 106, and the coordinates are stored, for example, in a storage device. The positions observed and stored may be those to become gel sheet portions. In the second selection step of FIG. 20 , the positions of multiple, mutually spaced portions of a container 9A included in a plate 8 are observed by the observation optical system 106, and the coordinates are stored, for example, in a storage device. The positions observed and stored may be those of multiple individual containers 9A within a single container 9A. The positions observed and stored may be those of multiple individual containers 9A included in a plate 8. In the first immediately preceding collection step, processing is performed based on the positions of the multiple portions of the gel sheet 4 and the containers 9A stored in the first and second selection steps. Therefore, in the first immediately preceding collection step of FIG. 21 , when the collection position and the predetermined position are overlapped, it is not necessary to observe and confirm the positions of the collection position and the predetermined position again using the observation optical system 106. This reduces the processing cycle time compared to when the collection position and the predetermined position are observed and confirmed again using the observation optical system 106. In the process of FIG. 21, the plate 8 and the gel sheet 4 are simultaneously moved in the X and Y directions, so that the collection position and the predetermined position overlap.

[0060] Figure 22 is a schematic cross-sectional view showing an eighth step of the method for selecting, collecting, and arranging samples according to embodiment 1. Figure 23 is a schematic enlarged cross-sectional view of the portion where the collection pin cuts out the gel plate immediately after the step shown in Figure 22. As shown in Figures 22 and 23, the formed gel plate 6 is punctured by the collection pin 141 descending from above. The mechanism by which the collection pin 141 descends during puncturing is as described above (Figures 6 and 7).

[0061] The entire collection positioning member 104, including the collection pin 141, is lowered from the state shown in Figure 21. For example, as shown in Figure 8, the location pin body 142A is positioned in the uppermost position, and while maintaining a state in which the bottom of the collection pin body 141A is positioned lower than the bottom of the location pin body 142A, the gel plate 6, and particularly the gel sheet 4, is punctured by the lowering of the collection pin body 141A. At this time, it is preferable that the volume of at least the hollow portion of the collection pin body 141A (the hollow portion from the bottom of the collection pin body 141A to the bottom of the location pin body 142A) be maintained large enough to accommodate a portion of the cut gel sheet 4.

[0062] The punctured portion of the gel sheet 4 is damaged by the passage of the sharp tip of the sampling pin body 141A. The sampling pin body 141A penetrates the gel sheet 4, tearing it apart. The portion of the gel sheet 4 cut away by the sampling pin body 141A so as to be separated from the original gel sheet 4 is the gel sheet portion 4E. The gel sheet portion 4E is preferably composed of a gel 4D and a sample 4B embedded therein. In this way, the sample 4B does not flow relative to the gel 4D. The cut gel sheet portion 4E is collected (stored) within the sampling pin body 141A.

[0063] After the gel sheet portion 4E has been cut off by the sampling pin body 141A, the sampling pin body 141A continues to descend while holding the gel sheet portion 4E inside (the hollow portion). This causes the sampling pin body 141A to pierce the portion of the film 2 located directly below the gel sheet 4 on the gel plate 6. This damages the film 2 as well as the gel sheet 4. The sampling pin body 141A descends until its tip reaches a position adjacent to the bottom surface of the container 9A.

[0064] Container 9A has a concave shape. Therefore, a portion of the cut gel sheet 4, i.e., gel sheet portion 4E, can be stored within container 9A. After being cut and before being placed, the cut gel sheet portion 4E may be pulled out from container 9A and film 2 while still held within the needle (sampling pin body 141A) and stored in another container or the like.

[0065] FIG. 24 is a schematic enlarged cross-sectional view showing the ninth step of the method for selecting, collecting, and arranging samples according to the first embodiment. As shown in FIG. 24, after the process shown in FIG. 23, the sampling pin 141 is stationary at a position approximately as shown in FIG. 23, and the positioning pin 142 is lowered in the direction indicated by the arrow in the figure. The positioning pin 142, particularly the positioning pin body 142A, is inserted through the hollow portion inside the sampling pin body 141A. FIG. 24 corresponds to the state shown in FIGS. 10 and 11 above, for example. The lowered positioning pin body 142A contacts and presses downward the gel sheet portion 4E collected and held by the sampling pin body 141A. This pushes the gel sheet portion 4E out of the inside of the sampling pin body 141A and places it in a predetermined position outside the sampling pin 141A. Specifically, the gel sheet portion 4E is placed on the inside (bottom surface) of the container 9A. The bottom surface of the container 9A may be a dry surface that is not coated with a highly viscous solution or the like.

[0066] Because the sampling pin body 141A penetrates the gel plate 6, the sampling pin body 141A breaks through both the gel sheet 4 and the film 2. However, as shown in Figure 23, it is preferable that only the gel sheet 4 is stored in the hollow shape portion 7C, and not the film 2. As a result, as shown in Figure 24, it is preferable that only the gel sheet portion 4E is collected in the container 9A, and not the film 2.

[0067] 25 is a schematic enlarged cross-sectional view showing the tenth step of the sample selection, collection, and placement method according to the first embodiment. As shown in FIG. 25, after the gel sheet portion 4E is placed on the bottom surface of the container 9A, the positioning pin main body 142A rises again. This corresponds to the state shown in FIGS. 12 and 13 above. This causes the entire positioning pin 142 to rise. Thereafter, the collection pin 141 also rises to above the gel plate 6. Note that the positioning pin 142 and the collection pin 141 may be raised simultaneously.

[0068] FIG. 26 is a schematic enlarged cross-sectional view showing the eleventh step of the sample selection, collection, and placement method according to the first embodiment. As shown in FIG. 26, the gel sheet portion 4E is placed in a predetermined position, the collection pin 141 and the placement pin 142 are raised, and then the gel plate 6 is moved in the X and Y directions. This removes the gel plate 6 from the plate 8. Next, the observation optical system 106 is placed directly above the predetermined position where the gel sheet portion 4E is placed in the container 9A. Conversely, the predetermined position of the gel sheet portion 4E is placed directly below the observation optical system 106 in the Z direction. In this positioning state, the observation optical system 106 observes that the gel sheet portion 4E is placed in the predetermined position. At this time, it may also be observed that the placed gel sheet portion 4E contains the desired sample 4B.

[0069] (Action and effect) In the sample selection, collection, and placement method according to the present disclosure, a gel 4D that supports an object to be collected (sample 4B) is formed in a sheet shape on a film 2, forming a gel sheet 4. The gel sheet 4 on the film 2 is punctured with a hollow collection pin 141, and a portion of the gel sheet 4 is cut off, thereby collecting a gel sheet portion 4E inside the collection pin 141. The gel sheet portion 4E inside the collection pin 141 is pushed out from the inside of the collection pin 141 by pressing with a placement pin 142, and placed at a predetermined position outside the collection pin 141. The method further includes a first selection step of selecting, using an observation optical system 106, a collection position where the gel sheet 4 is punctured with the collection pin 141, and a second selection step of selecting, using the observation optical system 106, a predetermined position where the gel sheet portion 4E is placed.

[0070] In this embodiment, the object (sample 4B) is supported by a solid gel 4D. Therefore, even if vibrations occur when the device is driven, the sample 4B does not shift position relative to the gel sheet 4. This allows the sample 4B to be stably selected and collected.

[0071] The positioning pin 142 presses against the gel sheet portion 4E. The positioning pin 142 preferably has a solid shape. This causes the gel sheet portion 4E to be pushed out from within the sampling pin 141 and released to the outside. This prevents problems such as the collapse and scattering of the target object, such as the sample 4B, which can occur when the gel sheet portion 4E is expelled from the sampling pin 141 using liquid pressure or the like. This improves the stability of the target object collection process and improves the positioning accuracy and reproducibility of the target object placement process.

[0072] The gel sheet 4 is punctured with the collection pin, and the gel sheet portion 4E is cut and collected within the collection pin 141. Then, the placement pin 142 presses the gel sheet portion 4E within the collection pin 141, thereby placing the gel sheet portion 4E in the desired, predetermined position. In particular, in this embodiment, both the process of collecting the gel sheet portion 4E and the process of placing it in the predetermined position are performed almost continuously without any movement of the gel sheet 4 or the like in the X and Y directions between the former and latter processes. Therefore, in this embodiment, the time required for processing can be reduced compared to a case where a component such as the gel sheet 4 containing the sample 4B is moved in a first direction when collecting the sample, and then moved in a second direction different from the first direction when placing the gel sheet portion 4E in the container 9A, thereby repeatedly moving the component in the horizontal direction. This reduces the processing time compared to a case where the component is moved in a first direction when collecting the sample, and then moved in a second direction different from the first direction when placing the gel sheet portion 4E in the container 9A. This allows the desired processing to be performed in a shorter time.

[0073] In this embodiment, it is more preferable to have the following: A first moving means (XY stage for sample 101) for controlling (moving) the position of (the gel plate 6 including) the collection position where the gel sheet portion 4E will be located is provided; and a second moving means (XY stage for container 102) for controlling (moving) the position of the plate 8 is provided. It is preferable that the first moving means and the second moving means be controlled to move simultaneously. Furthermore, it is preferable that the first moving means, the second moving means, and the third moving means (second drive unit 146) for controlling the positions of the collection pins 141 and the placement pins 142 (collection placement mechanism 104A) be controlled to move simultaneously. This further reduces the cycle time required for moving the gel plate 6 and the plate 8 in the X and Y directions (for example, when the gel plate 6 is placed on the XY stage for sample 101). It also further reduces the total time (cycle time) required for these movements and the movement of the collection placement mechanism 104A in the Z direction.

[0074] This embodiment includes a first selection step. That is, the sample 4B to be cut out and collected as a selection target is selected by observation from the gel 4D supporting the sample 4B. This reduces the possibility of damaging the sample 4B when cutting it. This allows the target to be selected and collected with high stability and positional accuracy. This embodiment also includes a second selection step. That is, the placement position of the cut-out gel sheet portion 4E is confirmed by observation. This allows the gel sheet portion 4E containing the cut-out sample 4B to be stably placed so as not to deviate from the desired position.

[0075] The sample selection, collection, and placement method according to the present disclosure further includes a first immediately preceding collection step, which is performed after the first and second selection steps and before the step of collecting the gel sheet portion 4E, in which the gel sheet 4 is placed so that the collection position to be cut and the predetermined position to be placed overlap. This allows both the step of collecting the gel sheet portion 4E and the step of placing it in the predetermined position to be performed almost continuously without any movement of the gel sheet 4 or the like in the X and Y directions between the former and latter steps. Therefore, in this embodiment, the time required for processing can be reduced compared to when a component, such as the collection pin 141 for collecting the sample 4B, moves in a first direction to collect the sample and then moves in a second direction different from the first direction to place the collected sample 4B, thereby repeatedly moving horizontally. This allows the desired processing to be performed in a shorter time.

[0076] The method for selecting, collecting, and arranging a sample according to the present disclosure further includes, after the step of arranging the gel sheet portion 4E in a predetermined position, a step of observing the gel sheet portion 4E being arranged in the predetermined position using the observation optical system, thereby making it possible to confirm that the gel sheet portion 4E containing the cut sample 4B is stably arranged without shifting from the desired position.

[0077] The sampling and placement device 100 according to the present disclosure includes a sampling pin 141, a placement pin 142, and a fixing holder 143. The sampling pin 141 is hollow and can cut and collect the material to be processed. The placement pin 142 can be inserted into the sampling pin 141, and when pressed by the sampling pin 141, it comes into contact with the cut material inside the sampling pin 141 and presses the material to place it outside the sampling pin 141. The sampling pin 141 is fixed to the fixing holder 143. The material to be processed is a gel sheet 4 formed of a sheet-shaped gel 4D that supports a sample 4B, which is the object to be sampled. The sampling and placement device 100 further includes a holding stage (sample XY stage 101) and an observation optical system 106. The holding stage (sample XY stage 101) holds the material to be cut by the sampling pin 141. The observation optical system 106 selects a sampling position where the material to be treated is punctured by the sampling pin 141, and a predetermined position where the portion of the material to be treated cut out by the puncturing is to be placed.

[0078] The material to be treated cut by the collection pin 141 is pushed out by the placement pin 142 and placed in the desired position (e.g., inside the container 9A). This prevents problems such as the collapse and scattering of objects such as the specimen 4B in the material to be treated, which are a concern when the material to be treated is discharged from the collection pin 141 using the pressure of a liquid, etc. This improves the stability of the collection process of the specimen 4B, etc., and improves the positional accuracy and reproducibility in the placement process of the specimen 4B, etc.

[0079] Furthermore, the sampling pin 141 is fixed to a fixing holder 143. This reduces the possibility of the sampling pin 141 moving unintentionally when an external vertical force is applied to the pin. This allows the target object to be cut out with high stability and reproducibility.

[0080] The observation optical system 106, which selects the collection position and the predetermined position, allows the gel sheet portion 4E containing the cut-out sample 4B to be stably collected and placed so as not to deviate from the desired position.

[0081] Additionally, in this embodiment, a gel 4D, i.e., a gel made by fixing the gel raw material 4A before solidification, is used as a material for supporting the specimen 4B. This has the effect of preventing shear stress from being applied directly to the specimen 4B. This reduces the possibility of damage to the cells, tissues, etc., that make up the specimen 4B.

[0082] (Embodiment 2) In the sample selection, collection, and placement method according to the second embodiment, the steps (first to fourth steps) shown in FIGS. 14 to 17 are the same as those in the first embodiment. FIG. 27 is a schematic cross-sectional view showing a fifth step of the sample selection, collection, and placement method according to the second embodiment. As shown in FIG. 27, in the present embodiment, a first selection step is performed using the observation optical system 106, similar to FIG. 18 (fifth step) in the first embodiment. As in the first embodiment, the first selection step is performed after the step of forming the gel sheet 4 and before the step of collecting the gel sheet portion 4E, for the purpose of selecting the sample 4B to be collected. In the first selection step shown in FIG. 27, the gel plate 6 is not placed on the upper surface of the plate 8. In FIG. 27, the gel plate 6 is placed at a different position from the plate 8 in the X and Y directions. In this respect, the present embodiment differs from the first embodiment, in which the gel plate 6 overlaps with the plate 8 during the first selection step, and the collection position and the predetermined position overlap.

[0083] Referring again to FIG. 20, in this embodiment, after the fifth step in FIG. 27, a sixth step in the second embodiment is performed, which is similar to the sixth step in the first embodiment in FIG. 20. That is, a predetermined position for the container 9A on the plate 8 fixed on the container XY stage 102 of the collection and placement device 100 is selected by the observation optical system 106. The predetermined position is the position where the gel sheet portion to be cut out later will be placed. This step is the second selection step similar to that in the first embodiment. As in the first embodiment, the second selection step is performed after the step of forming the gel sheet 4 and before the step of collecting the gel sheet portion 4E. Note that in this embodiment, there is no need to retract the gel plate 6 from the plate 8 during the sixth step. This is because the gel plate 6 is not placed on the plate 8 in the fifth step (see FIG. 27).

[0084] FIG. 28 is a schematic cross-sectional view showing the seventh step of the method for selecting, collecting, and arranging a sample according to the second embodiment. As shown in FIG. 28, after the first and second selection steps and before the step of collecting a gel sheet portion, a second immediately preceding collection step is performed in which the collection pin 141 is positioned directly above the collection position. The gel sheet 4 moves in the X and Y directions to achieve this configuration. At this time, the collection position and the predetermined position do not overlap each other in a plan view seen from the Z direction, but are positioned at different positions. In this respect, this embodiment (the second immediately preceding collection step) differs from the first immediately preceding collection step of the first embodiment in which the two are positioned so as to overlap each other.

[0085] FIG. 29 is a schematic enlarged cross-sectional view showing an eighth step of the method for selecting, collecting, and arranging a sample according to the second embodiment. As shown in FIG. 29, the gel sheet 4 of FIG. 28 is punctured by the sampling pin body 141A, and a portion of the gel sheet 4 is cut off. The cut-off portion of the gel sheet 4 is the gel sheet portion 4E. The gel sheet portion 4E is collected (stored) within the sampling pin body 141A. The manner in which the gel sheet 4 is cut off is the same as in FIGS. 22 and 23 of the first embodiment. The gel sheet 4 is cut off by the downward movement of the sampling pin body 141A. The cut-off gel sheet portion 4E contains the sample 4B to be sorted.

[0086] Figure 30 is a schematic enlarged cross-sectional view showing the ninth step of the method for selecting, collecting, and arranging a sample according to embodiment 2. As shown in Figure 30, the sampling pin body 141A and the arranging pin body 142A are raised while the gel sheet portion 4E collected in the step of Figure 29 is held within the sampling pin body 141A. The sampling pin 141 is raised to above the gel plate 6.

[0087] The steps in FIGS. 29 and 30 are performed while maintaining the positional relationship on the XY plane between the sampling pin 141, the gel sheet 4, and the plate 8, similar to the step in FIG.

[0088] FIG. 31 is a schematic enlarged cross-sectional view showing the tenth step of the method for selecting, collecting, and arranging a sample according to the second embodiment. As shown in FIG. 31, the collection pin 141 moves from directly above the collection position to directly above the predetermined position. To achieve this, the gel sheet 4 may be moved in the X and Y directions by, for example, the sample XY stage 101. The plate 8 moves in the X and Y directions by the container XY stage 102. This process is performed after the collection step (FIG. 29) and before the step of arranging the gel sheet portion 4E at the predetermined position (next FIG. 32). Note that in FIG. 31, the collection position and the predetermined position do not overlap each other in a plan view from the Z direction, and are located at different positions.

[0089] FIG. 32 is a schematic enlarged cross-sectional view showing the eleventh step of the method for selecting, collecting, and placing samples according to the second embodiment. As shown in FIG. 32, first, the entire collection and placement member 104, including the collection pin 141, descends. The collection pin 141 stops when it reaches a position in the Z direction approximately the same as the position shown in FIG. 23 relative to the container 9A. Thereafter, similar to the step shown in FIG. 24, the placement pin 142 is lowered in the direction indicated by the arrow in the figure while the collection pin 141 remains stationary. The lowered placement pin body 142A is pressed against the gel sheet portion 4E, which has been collected and held by the collection pin body 141A, and pushes it out of the interior of the collection pin 141, as shown in FIG. 24. As a result, the gel sheet portion 4E is placed at a predetermined position outside the collection pin 141. Specifically, the gel sheet portion 4E is placed on the interior (bottom) of the container 9A.

[0090] Figure 33 is a schematic enlarged cross-sectional view showing the 12th step of the method for selecting, collecting, and arranging samples according to embodiment 2. As shown in Figure 33, the arrangement pin 142 and the collecting pin 141 are raised, similar to the step in Figure 25. The collecting pin 141 is raised to above the plate 8.

[0091] 26 in the first embodiment is performed. That is, the observation optical system 106 observes that the gel sheet portion 4E is placed at a predetermined position.

[0092] (Action and effect) The sample selection, collection, and placement method of this embodiment includes a second immediately preceding collection step in which the collection pin 141 is placed directly above the collection position (the portion that will become the gel sheet portion 4E after cutting) after the first selection step and second selection step and before the step of collecting the gel sheet portion 4E. In the above selection, collection, and placement method, after the step of collecting the gel sheet portion 4E and before the step of placing the gel sheet portion 4E in a predetermined position, the collection pin 141 moves from directly above the collection position to directly above the predetermined position. At the time of the second immediately preceding collection step and the step of moving to directly above the predetermined position, the collection position and the predetermined position are located at positions other than where they overlap.

[0093] In this example, the movements of the gel sheet 4 and the plate 8 are slightly different from those in the example of embodiment 1, but the same effects as those in embodiment 1 can be obtained. For example, in addition to the repeated horizontal movements described in the effect column of embodiment 1, an example in which many parts move can be considered, such as rotating the part on which the container 9A is placed prior to the step of moving in the second direction. In this embodiment, at least compared to an example in which many parts move, the effect of reducing the takt time can be obtained.

[0094] The features described in the above-described embodiments may be applied in appropriate combinations within the scope of technical compatibility.

[0095] The embodiments disclosed herein should be considered to be illustrative in all respects and not restrictive. The scope of the present invention is defined by the claims, not by the above description, and is intended to include all modifications within the meaning and scope of the claims.

[0096] (Addendum) Various aspects of the present disclosure are summarized below as appendices.

[0097] (Appendix 1) A step of forming a gel sheet by forming a gel that supports the object to be collected on a film in a sheet shape; puncturing the gel sheet on the film with a hollow collection pin and cutting out a portion of the gel sheet to collect a portion of the gel sheet inside the collection pin; and a step of pushing the gel sheet portion inside the collection pin out from the inside of the collection pin by pressing with a placement pin and placing the gel sheet portion in a predetermined position outside the collection pin, The method for selecting, collecting, and placing a sample further comprises a first selection step of selecting, using an observation optical system, a collection position where the gel sheet is to be punctured with the collection pin, and a second selection step of selecting, using the observation optical system, the predetermined position where the gel sheet portion is to be placed.

[0098] (Appendix 2) A method for selecting, collecting, and placing samples as described in Appendix 1, wherein the predetermined position selected in the second selection step is a position within one of the wells included in a well plate (plate 8) in which multiple wells (container 9A) capable of storing the target object are arranged.

[0099] (Appendix 3) The method for selecting, collecting, and placing a sample described in Appendix 2, further comprising a first immediately before collection step of placing the gel sheet so that the collection position overlaps the predetermined position after the first selection step and the second selection step and before the collection step.

[0100] (Appendix 4) In the first selection step, positions of a plurality of portions of the gel sheet are observed and stored; In the second selection step, the positions of the plurality of wells included in the well plate are observed and stored; The method for selecting, collecting, and arranging samples described in Appendix 3, wherein the first immediately preceding collection step is performed based on the positions of the multiple portions of the gel sheet and the wells stored in the first selection step and the second selection step.

[0101] (Appendix 5) a second immediately preceding collection step of arranging the collection pin directly above the collection position after the first selection step and the second selection step and before the collection step; and after the collecting step and before the placing step, the collection pin is moved from directly above the collection position to directly above the predetermined position, A method for selecting, collecting, and placing samples as described in Appendix 2, wherein, at the time of the second immediately preceding collection step and the moving step, the collection position and the specified position are positioned at positions other than where they overlap with each other.

[0102] (Appendix 6) The method for selecting, collecting, and placing a sample according to any one of claims 1 to 5, further comprising, after the step of placing the gel sheet at the predetermined position, a step of observing using the observation optical system that the gel sheet portion has been placed at the predetermined position.

[0103] (Appendix 7) 7. The method for selecting, collecting and arranging samples according to any one of claims 1 to 6, wherein the arranging pin has a solid shape.

[0104] (Appendix 8) A hollow sampling pin capable of cutting and sampling the material to be treated; a positioning pin that can be inserted into the sampling pin, that contacts the material to be treated cut by pressing the sampling pin inside the sampling pin, and that presses the material to be treated to position the material to the outside of the sampling pin; a fixing holder to which the sampling pin is fixed, the treatment target material is a gel sheet in which a gel for supporting a target to be collected is formed into a sheet shape, a holder that holds the material to be treated that is cut out by the sampling pin; The sampling and placement device further comprises an observation optical system that selects a sampling position where the sampling pin punctures the material to be treated, and a predetermined position where the portion of the material to be treated cut out by the puncturing is to be placed. [Explanation of symbols]

[0105] 1, 5 slide glass, 2 film, 3 spacer, 3A through hole, 4 gel sheet, 4A gel raw material, 4B sample, 4C flow sample, 4D gel, 4E gel sheet portion, 6 gel plate, 8 plate, 9A container, 21 sheet fixing member, 100 collection and placement device, 101 sample XY stage, 101A stage penetration portion, 102 container XY stage, 104 collection and placement member, 104A collection and placement mechanism, 106 observation optical system, 141 collection pin, 141A collection pin main body, 141B collection pin holder, 142 placement pin, 142A placement pin main body, 142B placement pin holder, 142C spring, 143 fixing holder, 143f, 146f front, 143b back, 144 first drive unit, 144A first motor, 144B Disc member, 144C link member, 144D1, 144D2 joint, 145 positioning pin holder fixing portion, 145a first portion, 145b second portion, 146 second driving portion, 146A movable holder, 146B second motor, 146C vertically extending screw, 146D screw connection portion, 146E slide groove, FXD fixing portion.

Claims

1. A step of forming a gel sheet by forming a gel that supports the object to be collected on a film in a sheet shape; puncturing the gel sheet on the film with a hollow collection pin and cutting out a portion of the gel sheet to collect a portion of the gel sheet inside the collection pin; and a step of pushing the gel sheet portion inside the collection pin out from the inside of the collection pin by pressing with a placement pin and placing the gel sheet portion in a predetermined position outside the collection pin, The method for selecting, collecting, and placing a sample further comprises a first selection step of selecting, using an observation optical system, a collection position where the gel sheet is to be punctured with the collection pin, and a second selection step of selecting, using the observation optical system, the predetermined position where the gel sheet portion is to be placed.

2. 2. The method for selecting, collecting, and arranging samples according to claim 1, wherein the predetermined position selected in the second selection step is a position within one of the wells included in a well plate having an array of wells capable of accommodating the object.

3. 3. The method for selecting, collecting, and placing a sample according to claim 2, further comprising a first immediately prior to collection step of placing the gel sheet so that the collection position overlaps the predetermined position after the first selection step and the second selection step and before the collection step.

4. In the first selection step, positions of a plurality of portions of the gel sheet are observed and stored; In the second selection step, the positions of the plurality of wells included in the well plate are observed and stored; 4. The method for selecting, collecting, and arranging samples according to claim 3, wherein the first immediately preceding collection step is performed based on the positions of the multiple portions of the gel sheet and the wells stored in the first selection step and the second selection step.

5. a second immediately prior to sampling step of arranging the sampling pin directly above the sampling position after the first selection step and the second selection step and before the sampling step; and after the collecting step and before the placing step, the collection pin is moved from directly above the collection position to directly above the predetermined position, 3. The method for selecting, collecting, and arranging samples according to claim 2, wherein the collecting position and the predetermined position are arranged at positions other than where they overlap with each other at the time of the immediately preceding second collecting step and the moving step.

6. 2. The method for selecting, collecting, and arranging samples according to claim 1, further comprising, after the step of arranging at the predetermined position, a step of observing with the observation optical system that the gel sheet portion has been arranged at the predetermined position.

7. The method of claim 1 , wherein the location pin has a solid shape.

8. A hollow sampling pin capable of cutting and sampling the material to be treated; a placement pin that can be inserted into the sampling pin, that contacts the material to be treated cut by pressing the sampling pin inside the sampling pin, and that presses the material to be treated to place the material to be treated outside the sampling pin; a fixing holder to which the sampling pin is fixed, the treatment target material is a gel sheet in which a gel for supporting a target to be collected is formed into a sheet shape, a holder that holds the material to be treated that is cut out by the sampling pin; The sampling and placement device further comprises an observation optical system that selects a sampling position where the sampling pin punctures the material to be treated, and a predetermined position where the portion of the material to be treated cut out by the puncturing is to be placed.

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