Collection and placement method

Abstract

According to the present invention, a sheet obtained by thinly spreading, on a film, a support part for supporting a sample to be collected is provided on the film. The sheet is punctured with a needle having a hollow-shaped section, and thereby a sheet portion, which is a part of the sheet, is cut out and collected in the hollow-shaped section. The sheet portion in the hollow-shaped section is discharged from the inside of the hollow-shaped section, and the sheet portion is placed in a container (9A). The container (9A) and part of a gel plate (6) serving as a sheet are installed on the same stage (102).

Description

Sampling and placement method

[0007]

[0001] The present invention relates to a sampling and placement method.

[0002] In Japanese Patent Application Laid-Open No. 2023-104589 (Patent Document 1), a processing target material including a sample to be sampled is cut and sampled by a sampling pin having a hollow shape. A placement pin is disposed inside the sampling pin. By pressing the processing target material with the placement pin, the processing target material is discharged outside the sampling pin, and the discharged processing target material is disposed in a container or the like. According to Japanese Patent Application Laid-Open No. 2023-104589, the sample is sampled and placed so as to have high stability, reproducibility, and positional accuracy.

[0003] Japanese Patent Application Laid-Open No. 2023-104589

[0004] The sample sampling device shown in FIG. 1 of Japanese Patent Application Laid-Open No. 2023-104589 has two stages: a sample stage and a container stage. Therefore, the size of the sample sampling device becomes large. If the size of the device is large and the two stages are arranged at intervals in the horizontal direction, the moving distance and the number of movements between the gel sheet on the sample stage and the container on the container stage increase. As a result, the tact time of the operation becomes long.

[0005] The present invention has been made in view of the above problems. An object of the present invention is to provide a sampling and placement method capable of placing a plurality of cut processing objects in a short tact time.

[0006] In the sampling and placement method according to the present disclosure, a sheet obtained by thinly spreading a support portion that supports a sample to be sampled on a film is provided on the film. By piercing the sheet on the film with a needle having a hollow shape, a part of the sheet is cut off, and a sheet portion that is a part of the cut sheet is sampled into the hollow shape. By discharging the sheet portion in the hollow shape from the hollow shape, the sheet portion is placed in a container. The sheet and the container are installed on the same stage.

[0007] According to this disclosure, the gel sheet and the container are placed on the same stage. Therefore, a sampling and placement method is provided that allows multiple cut pieces of the material to be processed to be placed in a short cycle time.

[0008] This is a schematic front view of the sampling and placement device according to this embodiment. This is a schematic plan view showing a configuration in which both the gel plate and the plate are placed on the XY stage, viewed from above in the Z direction. This is a front view of the sampling and placement mechanism constituting the sampling and placement member of Figure 1, viewed from the negative side in the Y direction. This is a side view of the sampling and placement mechanism of Figure 3, viewed from the negative side in the X direction. This is a front view of the entire sampling and placement member of Figure 1, viewed from the negative side in the Y direction. This is a side view of the sampling and placement member of Figure 5, viewed from the negative side in the X direction. This is a schematic cross-sectional view showing the first step of the method for manufacturing the gel plate according to this embodiment. This is a schematic cross-sectional view showing the second step of the method for manufacturing the gel plate according to this embodiment. This is a schematic cross-sectional view showing the third step of the method for manufacturing the gel plate according to this embodiment. This is a schematic cross-sectional view showing the fourth step of the method for manufacturing the gel plate according to this embodiment. This is a schematic perspective view of the plate. This is a flowchart detailing the preparation steps performed prior to the main step in the sampling and placement method according to this embodiment. This is a schematic cross-sectional view showing the first step of the preparation steps for sampling and placement in this embodiment. This is a schematic cross-sectional view showing the second step of the preparation steps for sampling and placement in this embodiment. This is a flowchart detailing the main step in the sampling and placement method according to this embodiment. This is a schematic cross-sectional view showing the first step of the main step in the sampling and placement method according to this embodiment. This is a schematic cross-sectional view showing the second step of the main process of the sampling and placement method according to this embodiment. This is a schematic cross-sectional view showing the third step of the main process of the sampling and placement method according to this embodiment. This is a schematic cross-sectional view showing the fourth step of the main process of the sampling and placement method according to this embodiment. This is a schematic cross-sectional view showing the fifth step of the main process of the sampling and placement method according to this embodiment. This is a schematic cross-sectional view showing the sixth step of the main process of the sampling and placement method according to this embodiment. This is a schematic cross-sectional view showing the seventh step of the main process of the sampling and placement method according to this embodiment. This is a schematic cross-sectional view showing the eighth step of the main process of the sampling and placement method according to this embodiment. This is a schematic cross-sectional view showing the ninth step of the main process of the sampling and placement method according to this embodiment. This is a schematic cross-sectional view showing the tenth step of the main process of the sampling and placement method according to this embodiment. This is a schematic cross-sectional view showing the eleventh step of the main process of the sampling and placement method according to this embodiment. This is a schematic diagram showing an example of the position and order of sampling / placement. This is a schematic diagram showing the configuration of the gel sheet according to this embodiment.This is a schematic cross-sectional view showing a gel sheet having the configuration of Figure 28, cut multiple times by the sampling and placement mechanism. This is a schematic cross-sectional view showing a first example of the shape of a container formed on a plate. This is a schematic cross-sectional view showing a second example of the shape of a container formed on a plate. This is a schematic cross-sectional view showing a third example of the shape of a container formed on a plate. This is a schematic diagram of a dish. This is a schematic cross-sectional view of the bottom surface of a dish. This is a schematic cross-sectional view of a sampling and placement device as a comparative example of this embodiment.

[0009] The embodiment will be described below with reference to the drawings. (Sampling and Placing Device) Figure 1 is a schematic front view of the sampling and placing device according to this embodiment. For the sake of explanation, the X, Y, and Z directions will be introduced. As shown in Figure 1, the sampling and placing device 100 of this embodiment is a device for collecting a sample from a gel plate 6. The sampling and placing device 100 mainly comprises a processing chamber, an XY stage 102 arranged inside the processing chamber, and a sampling and placing member 104. Although the sampling and placing device 100 in Figure 1 has only one sampling and placing member 104, it may include multiple members.

[0010] The XY stage 102 is movable horizontally, i.e., along the XY direction (X direction and Y direction). Specifically, for example, a guide is installed on the underside of the XY stage 102 for the container. This guide is slidably connected to a guide rail installed on the bottom surface of the processing chamber. The XY stage 102 fixes the gel plate 6 and the plate 8.

[0011] Figure 2 is a schematic plan view showing an XY stage with both the gel plate and the plate placed on it, viewed from above in the Z direction. As shown in Figure 2, the XY stage 102 includes a plate-like member on which the plates can be placed. Both the gel plate 6 and the plate 8 are placed on this plate-like member. For example, as shown in Figure 2, the plate-like member of the XY stage 102 has a rectangular planar shape with its sides aligned along the X and Y directions. The planar shape of the plate-like member may also be square. Hereafter, the plate-like member on which the gel plate 6 and the like are placed may be referred to as the XY stage 102.

[0012] A groove G for placing a plate 8 may be formed on the upper surface of the plate-shaped member of the XY stage 102. A groove G for placing a gel plate 6 may also be formed on the upper surface of the plate-shaped member of the XY stage 102. The groove G fixes the plate 8 and gel plate 6 to the upper surface of the plate-shaped member. The groove G divides the area on the plate-shaped member where the plate 8 and gel plate 6 are placed. The groove G may be formed to encircle each side of the rectangular shape when the plate 8 and gel plate 6 are viewed from above, as shown by the dotted lines in Figure 2. Alternatively, the groove G may be formed only at the four corners of the rectangular shape when the plate 8 and gel plate 6 are viewed from above. The groove G formed at the four corners may have the function of being able to slide on the upper surface of the plate-shaped member. This allows the size of the groove G to be adjusted according to the size of the plate 8 and gel plate 6. In other words, it can be fitted onto the plate-shaped member regardless of the size of the plate 8, etc.

[0013] For example, as shown in Figure 2, a plate 8 is placed on the upper left of the XY stage 102, and a gel plate 6 is placed on the lower right of the XY stage 102. In this way, the plate 8 and the gel plate 6 may be arranged diagonally on the XY stage 102. However, the positions of the plate 8 and the gel plate 6 on the XY stage 102 are not limited to this and are arbitrary. The plate 8 and the gel plate 6 are both placed on the XY stage 102 with a gap between them in the horizontal direction (XY direction). Nothing is placed between the plate 8 and the plate-like member of the XY stage 102. Nothing is placed between the gel plate 6 and the XY stage 102.

[0014] As described later, the gel plate 6 contains a gel sheet. The plate 8 contains multiple containers 9A. Therefore, when both the gel plate 6 and the plate 8 are placed on the XY stage 102, the gel sheet and the containers 9A are placed on the same stage, the XY stage 102. More specifically, both the gel plate 6 containing the gel sheet and the plate 8 on which the containers 9A are formed are directly placed on the surface of the same stage, the XY stage 102. In other words, a portion of the surfaces of the gel plate 6 and the plate 8 are in contact with the surface of the XY stage 102. The gel plate 6 and the plate 8 are placed with a gap between them along the horizontal XY direction. The gel sheet contains the sample to be collected. The containers 9A store (place) the sample cut from the gel sheet, etc.

[0015] In this case, the film 2 is interposed between the surface of the XY stage 102 and the gel sheet. However, at least the surface of the gel plate 6, including the gel sheet, is positioned to be in direct contact with the XY stage 102. For this reason, even in this case, the gel sheet is defined as being placed on the XY stage 102.

[0016] In addition, for example, the plate 8 may be positioned so as to be in direct contact with the surface of the XY stage 102, and the gel sheet may be positioned so as to be in direct contact with the plate 8. In this case as well, the gel sheet is defined as being placed on the XY stage 102.

[0017] In summary, in this specification, when both of the following first and second conditions are met, it is stated that "the gel sheet and the container 9A are placed on the same stage (XY stage 102)." The first condition is that at least a portion of both the gel sheet and the container 9A is arranged to overlap with the same stage in a plan view from the Z direction (vertical direction). The container 9A is not limited to the container 9A itself, but includes the plate 8 on which it is formed. The second condition is that both the gel sheet and the container 9A (or the plate 8 on which it is formed) are arranged to be in contact with the surface of the same stage, either directly or via another member (in this case, the film 2).

[0018] The sampling and placement member 104 and the observation optical system 106 are connected to a member that is movable in the Z direction, such as a Z-axis table. In other words, the sampling and placement member 104 and the observation optical system 106 are held within the sample collection device 100 so as to be movable in the Z direction. The observation optical system 106 observes and measures the position of the sample to be collected 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 by the observation optical system 106 may be performed using visible light. However, observation of the gel plate 6 is not limited to visible light; it may also be performed using infrared light, X-rays, ultrasound, etc., and depending on the material of the gel plate 6, it may be possible to observe the gel plate 6 using magnetism. The gel plate 6 observed by means other than visible light does not need to be transparent or translucent, and may be opaque.

[0019] (Configuration of the sampling and placement mechanism) Figure 3 is a front view of the sampling and placement mechanism that constitutes the sampling and placement member of Figure 1, viewed from the negative side in the Y direction. Figure 4 is a side view of the sampling and placement mechanism of Figure 3, viewed from the negative side in the X direction. Referring to Figures 3 and 4, the sampling and placement member 104 of Figure 1 includes the sampling and placement mechanism 104A, which is a part thereof. The sampling and placement mechanism 104A mainly comprises a sampling pin 141, a placement pin 142, and a fixing holder 143. The sampling pin 141 is a pin (needle-shaped member) for cutting and sampling the material to be processed, including the sample. The placement pin 142 is a pin for releasing the sample and other material collected and grasped by the sampling pin 141 and placing it in a desired position. The sampling pin 141 and the placement pin 142 are made of metal such as stainless steel or plastic.

[0020] The sampling pin 141 comprises a sampling pin body 141A and a sampling pin holder 141B. The sampling pin body 141A is pin-shaped (pipe-shaped) and has a hollow shape in the center of a cross-section that intersects the extending direction (up and down direction in Figures 3 and 4: Z direction). The hollow shape formed in the sampling pin body 141A is called the hollow shape portion. The sampling pin holder 141B is inserted onto the outer circumferential surface of the upper part of the sampling pin body 141A. Therefore, the sampling pin holder 141B also has a hollow shape in the center of a cross-section that intersects the Z direction in Figures 3 and 4. The sampling pin holder 141B is fixed to the outer circumferential surface of the sampling pin body 141A by press-fitting. Alternatively, the sampling pin holder 141B is bonded to the outer circumferential surface of the sampling pin body 141A with adhesive 141C. As shown in Figures 3 and 4, the sampling pin holder 141B may be configured such that, for example, its uppermost surface is aligned with the XY plane, but its lowermost surface is inclined with respect to the XY plane, and the outer circumference is smaller in the Z direction than the inner circumference. As a result, the sampling pin 141 has a hollow shape overall.

[0021] The placement pin 142 comprises a placement pin body 142A and a placement pin holder 142B. The placement pin body 142A is pin-shaped and extends in the Z direction. The placement pin body 142A may, for example, be solid inside. However, the placement pin body 142A only needs to have its lowest surface in the Z direction closed so that it does not have a hole in the center or elsewhere, and its interior may be hollow. The placement pin holder 142B has a larger dimension along the X direction (and Y direction) than the placement pin body 142A. The placement pin holder 142B holds the placement pin body 142A. For example, the lower surface of the placement pin holder 142B may be connected to the upper surface of the placement pin body 142A, so that the two are integrated.

[0022] The placement pin body 142A has a smaller cross-sectional dimension than the hollow portion of the sampling pin body 141A. Therefore, the placement pin body 142A can be inserted into the inside of the sampling pin body 141A. On the other hand, the placement pin holder 142B has a larger cross-sectional dimension than the hollow portion of the sampling pin body 141A. Therefore, the placement pin holder 142B cannot be inserted into the inside of the sampling pin body 141A.

[0023] The sampling pin body 141A presses against the material to be processed by descending, cuts off a portion of the material, and can store the cut-off portion inside the cylindrical hollow section. The material to be processed is a gel sheet 4 in which a gel 4D supporting the sample 4B, which is the object to be collected, is formed into a sheet (see Figure 16 described later). Subsequently, the placement pin body 142A moves inside the sampling pin body 141A. The placement pin body 142A contacts the material to be processed inside the sampling pin 141 and presses against the material. As a result, the placement pin body 142A pushes the material to be processed stored inside the sampling pin body 141A out of the sampling pin 141. The placement pin body 142A can move vertically inside the hollow section of the sampling pin body 141A. In other words, the placement pin body 142A passes through the inside of the sampling pin body 141A. The vertical movement of the placement pin body 142A is performed by the first drive unit 144, which will be described later. This allows the cut-out material to be placed in the desired position.

[0024] A spring 142C is installed in the area of ​​the placement pin holder 142B adjacent to the placement pin body 142A, that is, in the lowest area within the placement pin holder 142B. The spring 142C connects the placement pin holder 142B to the uppermost part of the placement pin body 142A. The spring 142C absorbs the Z-direction force applied to the placement pin holder 142B when the placement pin body 142A collides with a material to be processed, such as a substrate. The placement pin 142 does not necessarily have to have a spring 142C. If the placement pin 142 does not have a spring 142C, it will not be able to absorb the force during a collision. However, if the placement pin 142 does not have a spring 142C, the effects of the collision can be eliminated by precisely controlling the descent position of the placement pin 142.

[0025] The fixing holder 143 is capable of holding the sampling pin 141. The fixing holder 143 is located above the sampling pin 141 in Figure 3 and behind the placement pin 142. The fixing holder 143 may be, for example, plate-shaped (rectangular parallelepiped-shaped), but is not limited to this. The sampling pin 141 is fixed to the fixing holder 143. Specifically, the uppermost surface of the sampling pin holder 141B and the lowermost surface of the fixing holder 143 are in contact with and fixed to each other at the fixing portion FXD. At the fixing portion FXD, the sampling pin 141 may be detachably fixed by the magnetic force of a stainless steel screw screwed near the fixing portion FXD of the sampling pin holder 141B and a magnet embedded near the fixing portion FXD of the fixing holder 143. Alternatively, at the fixing portion FXD, the sampling pin 141B may be detachably fixed by a stainless steel screw screwed between it and the fixing holder 143.

[0026] On the front surface 143f (the negative surface in the Y direction) of the fixing holder 143, a first drive unit 144 is provided on the upper side in the Z direction of the arrangement pin holder 142B. The first drive unit 144 includes a first motor 144A, a disc member 144B, and a link member 144C. The first drive unit 144 is attached to the arrangement pin holder fixing part 145.

[0027] The arrangement pin holder fixing portion 145 has a first portion 145a and a second portion 145b. The first portion 145a is plate-shaped, and its main surface on the back side contacts the front surface 143f of the fixing holder 143, and is installed so as to be slidable on the front surface 143f. The second portion 145b is a plate-shaped portion installed on the front side main surface of the first portion 145a, opposite to the main surface that contacts the front surface 143f, so as to be substantially perpendicular to the first portion 145a. A groove, for example, may be formed on the front surface 143f of the fixing holder 143 so as to extend along the Z direction for the arrangement pin holder fixing portion 145 to slide.

[0028] The link member 144C is installed on the front side of the disc member 144B in Figure 3. The link member 144C has an elongated shape that extends 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. The first motor 144A is mounted at a position that coincides with the circular center of the disc member 144B. At least a part of the first motor 144A may be placed inside the fixing holder 143. The disc member 144B is rotatable around its center by the first motor 144A. The first end of the link member 144C, which is one end in the extending direction, is fixed to a part of the outer circumference of the disc member 144B.

[0029] The second end of the link member 144C, opposite to the first end in the extending direction (Z direction) (the lower end in Figure 3), is fixed to the arrangement pin holder fixing part 145 so as to contact the first portion 145a of the arrangement pin holder fixing part 145. The second end may also be able to contact the second portion 145b of the arrangement pin holder fixing part 145. As the disc member 144B rotates due to the first motor 144A, the link member 144C moves vertically, causing the second end to move the arrangement pin 142 vertically. The process by which the collected gel sheet is actually placed at the desired location will be described in detail later.

[0030] In this embodiment, it is not essential that the sampling and placement mechanism 104A uses a link member 144C and a disc member 144B, etc. The placement pin 142 in this embodiment may be driven vertically by an electric cylinder. Alternatively, the placement pin 142 may be driven by an air cylinder.

[0031] Furthermore, in this embodiment, the collection and placement mechanism 104A does not necessarily have to have a placement pin 142. Although not shown, for example, the collected gel sheet may be discharged by utilizing the pressure of the liquid or gas supplied into the collection pin body 141A descending within the collection pin body 141A.

[0032] To enable this operation, the placement pin holder fixing portion 145 is provided between the second end and the placement pin 142 (placement pin holder 142B), and the placement pin 142 is fixed to it. The placement pin 142 is fixed so as to be in contact with both the first portion 145a and the second portion 145b of the placement pin holder fixing portion 145. The placement pin 142 (placement pin holder 142B) and the placement pin holder fixing portion 145 (first portion 145a and second portion 145b) may be detachably fixed together, for example, by magnetic force between a magnet embedded in the placement pin holder 142B and a magnet embedded in the first portion 145a. Alternatively, they may be detachably fixed together by screws.

[0033] (Overall configuration of the sampling and placement member) Figure 5 is a front view of the entire sampling and placement member of Figure 1, viewed from the negative side in the Y direction. Figure 6 is a side view of the sampling and placement member of Figure 5, viewed from the negative side in the X direction. Referring to Figures 5 and 6, the sampling and placement member 104 further includes a second drive unit 146 in addition to the sampling and placement mechanism 104A of Figures 3 and 4. The second drive unit 146 is located on the rear side of the fixing holder 143 of Figures 3 and 4 and includes a movable holder 146A. The movable holder 146A has, for example, a plate shape (rectangular parallelepiped shape) and is configured to house a member inside, but is not limited to this. The movable holder 146A has a larger dimension in the Z direction than the fixing holder 143. The sampling and placement mechanism 104A is attached to the movable holder 146A.

[0034] The second drive unit 146 is a sliding mechanism that slides the sampling and placement mechanism 104A, which includes the fixing holder 143, in the Z direction. In addition to the movable holder 146A, the second drive unit 146 includes a second motor 146B, a vertically extending screw 146C, and a screw connecting part 146D. The vertically extending screw 146C extends in the vertical direction and has male threads formed on its outer circumference. The vertically extending screw 146C is arranged, for example, in a rectangular parallelepiped-shaped movable holder 146A 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 extending in the Z direction formed on the front surface 146f of the movable holder 146A. The second motor 146B is attached to one end (the upper end) of the vertically extending screw 146C inside the movable holder 146A. The screw connector 146D is mounted on the back surface 143b (the surface opposite to the front surface 143f) of the fixing holder 143 so as to enable connection between the vertically extending screw 146C and the fixing holder 143. The screw connector 146D has a female thread, which is fastened to the male thread of the vertically extending screw 146C.

[0035] The vertically extending screw 146C is rotated by the second motor 146B. Although the vertically extending screw 146C does not move vertically when it rotates, the screw connection part 146D fastened to the vertically extending screw 146C moves vertically. As a result, the entire sampling and placement mechanism 104A, including the fixing holder 143 and sampling pin 141 attached to the screw connection part 146D, moves vertically. The process by which a portion of the actual gel sheet is cut and collected through this operation will be described in detail later.

[0036] (Method for Manufacturing Gel Plates) Figure 7 is a schematic cross-sectional view showing the first step of the method for manufacturing gel plates according to this embodiment. Referring to Figure 7, for example, a film 2 is placed on a glass slide 1. As an example, the glass slide 1 is a thin glass plate material with a thickness of about 1.2 mm. The film 2 is made thin from a soft material so that it can be easily torn by needle puncture. As an example, the film 2 is, for example, polyvinylidene chloride with a thickness of about 10 μm. That is, it is preferable that the film 2 be, for example, a thin film 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 from the same glass material as the glass material that forms 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. The spacer 3 has a through hole 3A in its center when viewed from above (plan view) in Figure 7. The through hole 3A penetrates the spacer 3. Therefore, the through-hole 3A is hollow, and no material such as glass that constitutes the spacer 3 is placed inside. The planar shape of the through-hole 3A can be arbitrary, such as a rectangle.

[0037] Next, a fluid sample 4C, which contains one or more samples 4B as the target material, is supplied into the through-hole 3A, and is a fluid gel raw material 4A capable of forming a gel. Sample 4B is cells to be collected. In Figure 7, multiple samples 4B are arranged one by one with space between them. Gel raw material 4A is, for example, a 1.5% agarose gel, which is made by adding a fluorescent dye to 1.5 mL of gel precursor. However, gel raw material 4A is not limited to this, and may be collagen, or a mixture of alginic acid and collagen. Gel raw material 4A will be described in more detail later.

[0038] Figure 8 is a schematic cross-sectional view showing the second step of the method for manufacturing a gel plate according to this embodiment. Referring to Figure 8, a film 2 is attached to the lower surface of the slide glass 5. The slide glass 5 may be of the same material and size as the slide glass 1 in Figure 7. The film 2 on the upper side of the fluid sample 4C in Figure 8 may be of the same material and size as the film 2 in Figure 7.

[0039] Figure 9 is a schematic cross-sectional view showing the third step of the gel plate manufacturing method according to this embodiment. Referring to Figure 9, a glass slide 5 with the film 2 attached is placed on a spacer 3. The film 2 attached to the glass slide 5 comes into contact with the fluid sample 4C and the spacer 3. The glass slide 5 and the film 2 press down on the fluid sample 4C and the spacer 3. As a result, the fluid sample 4C and the spacer 3 are sandwiched between the glass slide 1 with the film 2 attached below it and the glass slide 5 with the film 2 attached above it. In this way, the layers are stacked from bottom to top in the order of glass slide 1, film 2, spacer 3 and fluid sample 4C, film 2, and glass slide 5.

[0040] Next, if, for example, the gel material 4A is a material that solidifies depending on temperature, the entire stacked structure is cooled to 4°C. Cooling causes the gel material 4A constituting the fluid sample 4C to solidify into a gel 4D, and a gel sheet 4 (sheet) is formed inside the through-hole 3A with the sample 4B supported within the gel 4D. Although the gel 4D is solidified, it is soft enough to be easily broken by needle puncture. The statement that the sample 4B is supported by the gel 4D means, for example, that the sample 4B is embedded so that it is covered and filled with the hard gel 4D, and the sample 4B is not fluid.

[0041] Figure 10 is a schematic cross-sectional view showing the fourth step of the method for manufacturing a gel plate according to this embodiment. Referring to Figure 10, after the gel sheet 4 is provided, 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 forms a gel plate 6 comprising the film 2 and the gel sheet 4 placed on the film 2. The gel sheet 4 is a sample 4B to be collected, supported, for example, by embedding in a solidified gel 4D. The gel 4D is formed in a sheet shape on the film 2. In other words, the gel sheet 4 is formed in a sheet shape on the film 2 and contains the gel 4D that supports the sample 4B to be collected. In this embodiment, "providing the gel sheet 4" means that the process of obtaining the gel sheet 4 by supporting the sample 4B with the gel 4D by embedding or the like may be performed on the film 2, or a gel sheet 4 that has been formed in advance externally may be attached to the film 2 afterward. As for the method of forming the gel sheet 4, it is conceivable to create it in advance on an arbitrary flat surface.

[0042] As described above, the gel 4D, which serves as a support for the sample 4B to be collected, is spread thinly on the film 2. This yields a sheet of gel 4D. In other words, the gel 4D is formed into a sheet. The gel sheet 4 is placed on the film 2. The gel sheet 4 and the film 2 form a gel plate 6.

[0043] In the above manufacturing method, the gel plate 6 (including the film 2) is usually placed on the XY stage 102 in Figure 1 after the gel plate 6 is completed. However, the manufacturing method of the plate 6 is not limited to the above. Alternatively, the film 2 may be placed first on the XY stage 102 in Figure 1 on which the gel plate 6 is to be placed. Subsequently, a gel sheet 4 may be formed on the film 2 on the XY stage 102. The gel sheet 4 is obtained by spreading a support portion (gel 4D) that supports the sample 4B to be collected thinly on the film 2.

[0044] (Regarding the Plate) Figure 11 is a schematic perspective view of the plate. As shown in Figure 11, the plate 8 is a so-called multi-well plate in which a plurality of containers 9A are formed. The plurality of containers 9A are concave portions where the upper surface of the plate 8 (plate body 8A) is recessed. A gel sheet portion or the like is stored (arranged) in the container 9A. In the plate 8, a plurality of containers 9A may be formed in a matrix with a spacing from each other, for example, 8 columns in the Y-axis direction and 12 columns in the X-axis direction in Figure 3, for a total of 96. The planar shape of the container 9A when viewed from above in the Z direction can be arbitrary, such as circular, rectangular, square, etc. Also, the number of containers 9A formed on the plate 8 is not limited to the above 96. The number of containers 9A on the plate 8 may be any of 6, 12, 24, 48, 96, 384, 1536. Usually, the maximum dimension when the container 9A is viewed from above in plan view exceeds 1 mm. Here, the maximum dimension is the value of the largest part among the dimensions of the container 9A in plan view. For example, if the container 9A is elliptical, the maximum dimension is the dimension in its major axis direction.

[0045] (Sampling and Arrangement Method) Figure 12 is a flowchart showing the details of the preparation process that is performed prior to this process among the sampling and arrangement methods according to the present embodiment. As shown in Figure 12, in the preparation process, the storage of the sampling position (S1) and the storage of the arrangement position (S2) are performed. The storage of the sampling position (S1) stores the position of the portion where the gel sheet is removed in order for the gel sheet to be cut out and sampled as the gel sheet portion.

[0046] Specifically, in the storage of the sampling position (S1), first, the gel sheet moves under the observation optical system (S11). Figure 13 is a schematic cross-sectional view showing the first step of the preparation process for sampling and arrangement in the present embodiment. As shown in Figure 13, for the purpose of selecting the sample to be sampled included in the gel sheet 4, the observation optical system 106 is arranged on the gel sheet 4 constituting the gel plate 6.

[0047] In step (S11) of FIG. 12, the observation optical system 106 is disposed at a position directly above the sample to be collected in the gel sheet 4. To achieve such a state, the XY stage 102 moves in the X and Y directions, and the sample to be collected is placed directly below the observation optical system 106. As shown in FIG. 12, after the sample to be collected is placed directly below the observation optical system 106, the observation optical system 106 stores the collection position coordinates of the collected sample (S12). In step (S12), the sample to be collected in the gel sheet 4 is observed by the observation optical system 106. At this time, the XYZ coordinates of the position of the sample to be collected are stored as the collection position coordinates. The observation optical system 106 moves up and down in the Z direction to focus, thereby confirming the sample to be collected. As a result, the XYZ coordinates of the sample to be collected are stored.

[0048] Next, a determination is made as to whether to continue storing (Q11). That is, when there are a plurality of samples to be collected in the gel sheet 4, the process proceeds in the YES direction in (Q11) of FIG. 12. As a result, steps (S11) and (S12) are repeated at positions on the gel sheet 4 different from the above steps (S11) and (S12). When steps (S11) and (S12) are repeated a plurality of times and there are no collection position coordinates to be continuously stored in (Q11), the process proceeds in the NO direction in (Q11) of FIG. 12. As a result, the storage of the collection position (S1) ends. Also, when there is only a single sample to be collected, the process proceeds in the NO direction in (Q11) of FIG. 12. As a result, the storage of the collection position (S1) ends.

[0049] Thus, in steps (S11) and (S12), the positions of a plurality of separated 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 to be observed and stored may be the positions that should be the gel sheet portion 4E.

[0050] Next, the placement position memory (S2) involves collecting the cut-out gel sheet portion and memorizing the position of the container where it should be placed. Specifically, in placement position memory (S2), it is first determined whether or not to use standard plate coordinates (Q21). Standard plate coordinates refer to the center coordinates of the bottom surface of each of the multiple containers 9A contained in the plate 8 (multiwell plate). Standard plate coordinates are the XYZ coordinates of the center of each container 9A formed on each plate 8, which are stored on the computer. Standard plate coordinates are stored by reading them from the computer. If standard plate coordinates are to be used, the process proceeds in the direction of YES in (Q21) in Figure 12. This reads the XYZ coordinates of the center of each container 9A on plates of each manufacturer and model number stored on the computer (S20). For example, in the case of a 96-well plate, the XYZ coordinates of the center positions of all 96 containers 9A formed on the plate 8 can be read. The placement position memory (S2) is completed when step (S20) is performed.

[0051] On the other hand, if a fixed plate coordinate is not used, the process proceeds in the direction of NO in (Q21) of Figure 12. In this case, during the storage of the placement position (S2), the plate first moves directly below the observation optical system (S21). Figure 14 is a schematic cross-sectional view showing the second step of the preparation process for sampling and placement in this embodiment. As shown in Figure 14, the predetermined position of the container 9A of the plate 8 fixed on the XY stage 102 is selected by the observation optical system 106.

[0052] In step (S21) of Figure 12, the observation optical system 106 is positioned directly above the center of the container 9A in which the cut sample is to be placed. To achieve this, the XY stage 102 moves in the X and Y directions so that the container 9A to be placed is positioned directly below the observation optical system 106. As shown in Figure 12, after the container 9A to be placed directly below the observation optical system 106 is positioned, the observation optical system 106 stores the position coordinates of the placement well (the container 9A to be placed) (S22). In step (S22), the center of the container 9A in which the cut gel sheet portion is to be placed is observed by the observation optical system 106. At this time, the XYZ coordinates of the position in which the sample is to be placed are stored as the placement position coordinates. The observation optical system 106 moves up and down in the Z direction to focus and confirm the position in which the sample is to be placed. This stores the XYZ coordinates of the position in which the sample is to be placed. For example, the placement position coordinates may have different X and Y coordinates than the sampling position coordinates, and the Z coordinate may be below the sampling position coordinates. The placement coordinates may also be the center coordinates of the bottom surfaces of each of the multiple containers 9A.

[0053] Next, a decision is made as to whether to continue storing the data (Q22). In other words, if there are multiple containers 9A in which the gel sheet portion should be placed, the process proceeds in the direction of YES in (Q22) of Figure 12. As a result, steps (S21) and (S22) are repeated at a different central position of container 9A than those in the above steps (S21) and (S22). If steps (S21) and (S22) are repeated multiple times and there are no container position coordinates to continue storing in (Q22), the process proceeds in the direction of NO in (Q22) of Figure 12. As a result, the storage of the placement position (S2) is completed. Similarly, if there is only one container 9A, the process proceeds in the direction of NO in (Q22) of Figure 12. As a result, the storage of the placement position (S2) is completed.

[0054] The order in which the sampling location is memorized (S1) and the placement location is memorized (S2) is irrelevant. Once these steps (S1) and (S2) are completed, the preparation process is finished and the process proceeds to the main process. The main process is in which the samples are actually collected and placed.

[0055] Figure 15 is a flowchart detailing the main step of the sampling and placement method according to this embodiment. As shown in Figure 15, the main steps in this process are determination of the sampling / placement position and order (S3), sampling (S4), placement (S5), and placement confirmation (S6).

[0056] In determining the position and order of sampling / placement (S3), the container 9A in which the cut-out gel sheet portion 4E should be placed is determined by selection (S31). Also, the position within the container 9A in which the gel sheet portion 4E should be placed is determined (S31). In step (S3), this selection and determination is made in one of the following two ways: Firstly, it is made arbitrarily by the operator. Secondly, it is made by using a placement pattern that is pre-set on a personal computer.

[0057] Furthermore, if the location from which the gel sheet 4 should actually be sampled among the sampling locations stored in step (S1) has not been determined at this point, the part of the gel sheet 4 to be sampled is determined by selection at this point. This selection and determination is carried out in the same manner as the selection and determination of the container 9A described above.

[0058] In the determination of the sampling / placement location and order (S3), the sampling order for each sampling location of the gel sheet portion 4E is determined (S32). That is, the order in which the multiple locations to be selected from the gel sheet portion 4E to be sampled is determined. Also in step (S3), the order in which the gel sheet portion 4E will be placed in each container 9A is determined (S32). That is, the order in which the multiple containers 9A to which the gel sheet portion 4E will be collected and placed will be placed is determined. This determination is made in one of the following two ways: Firstly, it is determined arbitrarily by the operator. Secondly, it is determined by a computer that calculates the process so that the work time is minimized. Steps (S1), (S2), and (S31) generally determine the combination of the sample to be sampled and the placement location. When performing the sampling and placement, it is preferable that the process is calculated so that the work time is minimized. The order in which steps (S31) and (S32) are performed is irrelevant.

[0059] Next, in sampling (S4), the sampling and placement member first moves to the sampling position coordinates (S41). Figure 16 is a schematic cross-sectional view showing the first step of the main process of the sampling and placement method according to this embodiment. As shown in Figure 16, the sampling and placement mechanism 104A is positioned directly above the gel sheet 4 that constitutes the gel plate 6. At this time, the sampling and placement mechanism 104A is positioned directly above the portion of the gel sheet 4 that is to be sampled first. The X and Y coordinates of this position are the sampling position coordinates stored in process (S12). The portion of the gel sheet 4 to be sampled is the portion where the sample 4B to be sampled is located.

[0060] As shown in Figure 15, in sampling (S4), the gel sheet portion is then sampled (S42). Figure 17 is a schematic cross-sectional view showing the second step of the main process of the sampling and placement method according to this embodiment. As shown in Figure 17, the entire sampling and placement mechanism 104A descends. As a result, the sampling pin body 141A, which is positioned at the bottom of the sampling and placement mechanism 104A as a needle, punctures the gel plate 6. The sampling pin 141 penetrates both the film 2 and the gel sheet 4 on top of it, and its tip reaches the underside of the bottom of the film 2. At this time, the portion of the gel sheet 4 that has been penetrated is cut off. In other words, a part of the gel sheet 4 is cut off. The cut-off portion of the gel sheet 4 is housed as a gel sheet portion 4E within the hollow-shaped portion of the sampling pin body 141A. In Figure 17, the gel sheet portion 4E housed within the hollow-shaped portion of the sampling pin body 141A is referred to as the gel sheet portion 4E1.

[0061] Figure 18 is a schematic cross-sectional view showing the third step of the main process of the sampling and placement method according to this embodiment. As shown in Figure 18, with the gel sheet portion 4E1 housed within the sampling pin 141 of the sampling and placement mechanism 104A, the entire sampling and placement mechanism 104A rises. As a result, the sampling pin 141 moves away from the upper side of the gel plate 6.

[0062] As shown in Figure 15, a decision is then made as to whether to continue sampling (Q41). In other words, if there are multiple gel sheet portions to be sampled, the process proceeds in the direction of YES in (Q41) of Figure 15. As a result, steps (S41) and (S42) are repeated at a different sampling location than the steps (S41) and (S42) described above. If steps (S41) and (S42) are repeated multiple times and there are no more gel sheet portions to be sampled in (Q41), the process proceeds in the direction of NO in (Q41) of Figure 15. This completes the sampling (S4). Similarly, if there is only one gel sheet portion to be sampled, the process proceeds in the direction of NO in (Q41) of Figure 15. This completes the sampling (S4).

[0063] Figure 19 is a schematic cross-sectional view showing the fourth step of the main process of the sampling and placement method according to this embodiment. As shown in Figure 19, if (Q41) in Figure 15 is YES, the entire sampling and placement mechanism 104A, including the sampling pin 141, moves to a sampling position different from the sampling position in the immediately preceding steps (S41) and (S42). As a result, the state at the different sampling position is the same as that in Figure 16.

[0064] Figure 20 is a schematic cross-sectional view showing the fifth step of the main process of the sampling and placement method according to this embodiment. As shown in Figure 20, the same process as in Figure 17 is performed at different sampling positions in Figure 19. That is, the sampling and placement mechanism 104A descends and the sampling pin 141 punctures the gel plate 6. As a result, a portion of the gel sheet 4 is cut out as a gel sheet portion 4E and stored in the hollow portion of the sampling pin body 141A. In Figure 20, the gel sheet portion 4E stored in the hollow portion of the sampling pin body 141A is referred to as gel sheet portion 4E2. The gel sheet portion 4E2, which is sampled later, is stored closer to the tip (lower) of the sampling pin 141 than the gel sheet portion 4E1, which is sampled earlier.

[0065] Figure 21 is a schematic cross-sectional view showing the sixth step of the main process of the sampling and placement method according to this embodiment. As shown in Figure 21, the same process as in Figure 18 is performed at different sampling positions in Figure 19. That is, with the gel sheet portion 4E1 and gel sheet portion 4E2 housed inside the sampling pin 141 of the sampling and placement mechanism 104A, the entire sampling and placement mechanism 104A is raised. In this way, during sampling (S4), the sampling pin body 141A cuts the gel sheet 4 multiple times, and houses the gel sheet portion 4E multiple times inside the hollow-shaped portion of the sampling pin body 141A. During sampling (S4), multiple gel sheet portions 4E1 and 4E2 are stacked inside the hollow-shaped portion of the sampling pin body 141A. In Figure 21, as an example, the gel sheet portion 4E is cut twice, but the number of times the gel sheet portion 4E is cut is arbitrary.

[0066] Next, in placement (S5), the sampling and placement member first moves to the placement position coordinates (S51). Figure 22 is a schematic cross-sectional view showing the seventh step of the main process of the sampling and placement method according to this embodiment. As shown in Figure 22, the sampling and placement mechanism 104A is placed directly above the container 9A in which the gel sheet portion 4E is to be placed. Multiple containers 9A are formed on the plate 8, but here the gel sheet portion 4E is placed in the first container 9A2 to be placed, so the sampling and placement mechanism 104A is placed directly above container 9A2. The X and Y coordinates of this position are the placement position coordinates stored in process (S22).

[0067] As shown in Figure 15, in the placement (S5), the gel sheet portion is placed next (S52). Figure 23 is a schematic cross-sectional view showing the eighth step of the main process of the sampling and placement method according to this embodiment. As shown in Figure 23, the placement pin 142 descends. The placement pin body 142A of the placement pin 142 presses against the gel sheet portion 4E. As a result, the gel sheet portion 4E inside the hollow-shaped portion of the sampling pin body 141A is discharged from the hollow-shaped portion. As a result, the gel sheet portion 4E is placed inside the container. In Figure 23, the gel sheet portion 4E2 is placed inside the container 9A2. This is because the gel sheet portion 4E2 was collected after the gel sheet portion 4E1 and is therefore stored on the tip side of the sampling pin 141.

[0068] In Figure 23, only one gel sheet portion 4E2 is placed in the container 9A2. However, the number of gel sheet portions 4E discharged from the sampling pin 141 in a single gel sheet portion 4E discharge process is arbitrary. In other words, multiple gel sheet portions 4E may be placed in the container 9A2 simultaneously. In that case, in process (S52), two or more of the required number of gel sheet portions 4E are placed in the container 9A2 at once. This adjustment is made as follows.

[0069] In the arrangement (S5), the amount of movement of the multiple gel sheet portions 4E1 and 4E2 within the hollow-shaped portion of the sampling pin body 141A is controlled. Specifically, in the arrangement (S5), the amount of movement of the multiple gel sheet portions 4E1 and 4E2 in the Z direction is controlled by the amount of pressure the arrangement pin 142 exerts on the multiple gel sheet portions 4E1 and 4E2.

[0070] As described above, the sampling and placement member 104 (sampling and placement mechanism 104A) is provided with a first motor 144A, a disc member 144B, and a first drive unit 144 including a link member 144C. The disc member 144B is rotated by the first motor 144A. This rotation causes the link member 144C, which is fixed to a part of the outer circumference of the disc member 144B, to be displaced in the Z direction. The link member 144C, displaced in the Z direction, applies pressure in the Z direction to the placement pin 142. As a result, the placement pin 142 moves in the Z direction so as to push in the multiple gel sheet portions 4E. Consequently, the gel sheet portions 4E inside the sampling pin body 141A descend and are discharged outside the sampling pin body 141A.

[0071] The amount of rotation of the disc member 144B is controlled by the amount of rotation of the first motor 144A. The force applied downward by the placement pin 142 to the gel sheet portion 4E is controlled according to this amount of rotation so that the gel sheet portion 4E is discharged. This controls the amount of gel sheet portion 4E discharged from the sampling pin 141. For example, let's assume that 10 gel sheet portions 4E can be discharged from the hollow shape of the sampling pin body 141A when the disc member 144B rotates once. In this case, one gel sheet portion 4E can be discharged at a time when the disc member 144B rotates 36°. Two gel sheet portions 4E can be placed in one container 9A at the same time when the disc member 144B rotates 72°. Thus, the number of gel sheet portions 4E placed in each container 9A is arbitrary. However, in Figures 22 to 26, one gel sheet portion 4E is placed in each container 9A as an example.

[0072] Figure 24 is a schematic cross-sectional view showing the ninth step of the main process of the sampling and placement method according to this embodiment. As shown in Figure 24, after the gel sheet portion 4E2 is placed inside the container 9A2, the entire sampling and placement member 104, including the placement pin 142, rises.

[0073] As shown in Figure 15, the next step is to determine whether or not to place the gel sheet portion at a location different from the location (container 9A) where the previous step (S52) was performed (Q51). In other words, if there are more gel sheet portions to be placed, the process proceeds in the direction of YES in (Q51) of Figure 15. As a result, steps (S51) and (S52) are repeated at placement locations different from those of the above steps (S51) and (S52). If steps (S51) and (S52) are repeated multiple times and there are no more gel sheet portions to be placed in (Q51), the process proceeds in the direction of NO in (Q51) of Figure 15. As a result, the placement (S5) is completed. Similarly, if there is only one gel sheet portion to be placed, the process proceeds in the direction of NO in (Q51) of Figure 15. As a result, the placement (S5) is completed.

[0074] Figure 25 is a schematic cross-sectional view showing the tenth step of the main process of the sampling and placement method according to this embodiment. As shown in Figure 25, if (Q51) in Figure 15 is YES, the entire sampling and placement mechanism 104A, including the placement pin 142, moves to a different placement position than the one in the previous steps (S51) and (S52). As a result, the state at the different placement position is the same as that in Figure 22. Specifically, since the gel sheet portion 4E is placed in the container 9A1, the sampling and placement mechanism 104A is placed directly above the container 9A1. The X and Y coordinates of this position are the placement position coordinates stored in step (S22).

[0075] Figure 26 is a schematic cross-sectional view showing the 11th step of the main process of the sampling and placement method according to this embodiment. As shown in Figure 26, the same process as in Figure 23 is performed on the container 9A1, which is a different sampling position from Figure 25. That is, the placement pin 142 descends, and the placement pin body 142A punctures the gel sheet portion 4E. As a result, the gel sheet portion 4E1 is placed inside the container 9A1. The gel sheet portion 4E1 is sampled before the gel sheet portion 4E2 and is stored above the gel sheet portion 4E2 within the sampling pin 141. At this time as well, two or more gel sheet portions 4E may be placed inside the container 9A1 at the same time as needed.

[0076] As shown in Figures 22 to 26, in the arrangement (S5), multiple gel sheet portions 4E may be stacked within the hollow-shaped portion by puncturing multiple times with the sampling pin body 141A during sampling (S4). These multiple gel sheet portions 4E may be discharged one by one in multiple steps. In Figures 22 to 26, as an example, the gel sheet portions 4E are discharged in two steps. However, as described above, multiple gel sheet portions 4E stacked within the hollow-shaped portion by the sampling pin body 141A may be discharged at one location (in one container 9A) at once. In this case, the gel sheet portions 4E may be placed at any position on the bottom surface of one container 9A. The layout of the positions in which each of the multiple gel sheet portions 4E is placed is arbitrary. Furthermore, multiple types of gel sheet portions 4E, each cut from multiple different gel sheets 4, may be stacked within the hollow-shaped portion and placed in one container 9A.

[0077] Finally, a placement confirmation (S6) may be performed. That is, as shown in Figure 15, it is determined whether it is necessary to confirm the gel sheet portion 4E placed in the container 9A (Q61). If this is necessary, proceed in the direction of YES in (Q61) of Figure 15. As a result, the observation optical system 106 moves to the placement position coordinates. The gel sheet portion 4E placed in the container 9A is confirmed (S60). On the other hand, if confirmation of the gel sheet portion 4E is not required, or when the confirmation of the gel sheet portion 4E has been completed, proceed in the direction of NO in (Q61) of Figure 15. As a result, the XY stage 102 and the sampling and placement member 104 move to their initial positions without performing the placement confirmation (S6) (S71). This process is completed in step (S71).

[0078] (Regarding the determination of the location and order of sampling / placement (S3)) Here, we will provide some supplementary information about process (S3). Figure 27 is a schematic diagram showing examples of the location and order of sampling / placement. Figure 27 shows five examples of the location and order of sampling / placement, from (A) to (E). However, the form of process (S3) is not limited to these five examples. In Figure 27, a multiwell-type plate 8 is used in which a total of 96 containers 9A are formed in 8 rows in the Y direction and 12 rows in the X direction. However, the number of containers 9A included in the plate 8 is not limited to this and can be arbitrary.

[0079] The first example of process (S3) is shown in Figure 27, (A). The numbered areas in the gel plate 6 in (A) are where the gel sheet portion is collected. The gel sheet portion is placed in the numbered containers in the plate 8 in (A). The numbers above indicate the order of collection / placement. In the figure, the center in the left-right direction shows the gel sheet portion housed in the collection pin body 141A. The numbers 1 to 6 indicate the order of collection, so 6, which is collected last, is placed at the very tip (bottom) of the collection pin body 141A. The areas with different hatching for each collection position in the gel plate 6 have different characteristics such as the type and properties of the sample (cells, etc.) that constitutes the gel sheet.

[0080] In (A), samples are taken from the gel plate 6 at six locations in a straight line along the X direction. The intervals between the samples taken from the gel sheet are approximately constant. In (A), the gel sheet portions are placed in the order they were taken into six containers 9A arranged in a straight line along the X direction of the plate 8. Therefore, in (A), the positions on the plate 8 are arranged to reproduce the sampling positions from the gel plate 6.

[0081] A second example of process (S3) is shown in Figure 27, (B). In (B), six gel sheet portions are taken from the gel plate 6 in such a way that the overall sampling time is minimized. The arrangement of the gel sheet portions on the plate 8 is the same as in (A).

[0082] A third example of process (S3) is shown in Figure 27, (C). In (C), sampling is performed between regions with different properties so that there are two types of properties in the gel sheet. 1, 2, and 3 in (C) have the same properties as the samples within the gel sheet. 4, 5, and 6 in (C) have the same properties as the samples within the gel sheet. However, 1 and 4 in (C) have different properties than the samples within the gel sheet. In (C), as in (B), 1, 2, and 3, which have the same properties, are arranged in a row so that they are aligned in the X direction, and 4, 5, and 6, which have different properties, are also arranged in a row so that they are aligned in the X direction. In (C), 1, 2, and 3 and 4, 5, and 6 are arranged in parallel in the Y direction.

[0083] A fourth example of process (S4) is shown in Figure 27 as (D). In (D), samples are taken from the same viewpoint as in (C), but the order of sampling is different from that of (C). Samples 1, 3, and 6 in (D) have the same characteristics as the samples within the gel sheet. Samples 2, 4, and 5 in (D) have the same characteristics as the samples within the gel sheet. However, samples 1 and 2 in (D) have different characteristics than the samples within the gel sheet. In (D), samples 1, 3, and 6 are arranged in a row so as to be aligned in the X direction, and samples 2, 4, and 5, which have different characteristics from these, are also arranged in a row so as to be aligned in the X direction. In (D), samples 1, 3, and 6 and samples 2, 4, and 5 are arranged in parallel in the Y direction.

[0084] A fifth example of process (S3) is shown in Figure 27 as (E). In (E), after the gel sheet portion is collected as in (B), 1 and 2 are placed in the same container. Similarly, 3 and 4 are placed in the same container, and 5 and 6 are placed in the same container.

[0085] The location from which the gel sheet portion is taken from the gel sheet 4 is not limited to the examples (A) to (E) above. In other words, the location from which the gel sheet portion is taken from the gel sheet 4 may be linear or matrix-like. Alternatively, the location from which it is taken may be random. The location from which it is taken may be arbitrarily determined by the operator. The locations from which the taken gel sheet portions are placed may be arranged sequentially from the container 9A at the edge of the plate 8, so as to ensure that no container 9A is left empty. Alternatively, the gel sheet portions may be arranged in a positional relationship similar to the location from which they were taken. The gel sheet portions may be reclassified according to the characteristics of the samples within them before placement. For example, as in (E), multiple gel sheet portions may be placed in a single container 9A. The placement locations may be arbitrarily determined by the operator.

[0086] The order in which the gel sheet portions are collected is not particularly limited. The order of collection may be random. The order of collection may be determined so that samples are collected together according to the characteristics of each type within the gel sheet portion. The order of collection may also be determined so as to minimize the distance the stages required for collection travel. As shown in Figures 27 (D) and (E), the first three (1, 2, 3) and the latter three (4, 5, 6) of the six collection locations may be in a positional relationship that is approximately point-symmetric with respect to the center of the gel plate 6 in a plan view.

[0087] The order in which the collected gel sheets are placed is not particularly limited. The order of placement may be random. The order of placement may be determined so that the gel sheets are grouped together according to the characteristics of the samples. The placement positions may be determined so as to minimize the distance the stage needs to travel for placement. Although not shown in the diagram, the first three (1, 2, 3) and the latter three (4, 5, 6) of the six placement locations may be in a positional relationship that is approximately point-symmetric with respect to the center of the plate 8 in a plan view.

[0088] Furthermore, the method for recognizing the characteristics of the sample in the gel sheet is not particularly limited. The recognition method may be determined arbitrarily by the operator. In other words, the recognition method may be determined by the operator's experience and intuition. Alternatively, the recognition method may be determined using image processing, machine learning, and statistical processing.

[0089] The method of capturing images when using image processing is not particularly limited. The method of capturing the images may be by phase-contrast microscopy, or by unstained imaging such as stereomicroscope imaging. Alternatively, the method of capturing the images may be by fluorescent labeling using antibodies or gene transfer, or by immunostaining.

[0090] The method of image acquisition using machine learning and statistical processing is not particularly limited. The acquisition method may be determined by multiple parameters obtained from the acquired image, such as cell viability, cell size, tissue size, shape (roundness, aspect ratio), brightness, expression levels of various proteins, and expression sites of various proteins. The acquisition method may be performed by both the method determined by the above parameters and one of the methods selected from the group consisting of k-means, Light GBM (Light Gradient Boosting Machine), support vector machine, random forest, hierarchical clustering, t-SNE (t-distributed Stochastic Neighbor Embedding), decision tree analysis, principal component analysis, etc. (other methods are also acceptable). Here, "both" means a combination.

[0091] When multiple gel sheet portions are arranged in a single container 9A, the container 9A in which the gel sheet portions in the plate 8 are arranged is not particularly limited. However, the container 9A may be linear or matrix-shaped. The positions of the containers 9A in which the gel sheet portions are arranged may be selected randomly.

[0092] (Coating material constituting the gel sheet) Figure 28 is a schematic diagram showing the configuration of the gel sheet according to this embodiment. As shown in Figure 28, the gel sheet 4 of this embodiment preferably includes a gel sheet body portion 4j and a coating material 4k. The coating material 4k is placed on the surface of the gel sheet body portion 4j so as to cover the surface. It is preferable that the coating material 4k is placed on the main surface of the gel sheet body portion 4j on the upper side in the Z direction.

[0093] The gel that supports the sample to be collected, as described above, is spread thinly on a film and corresponds to the gel sheet body portion 4j, which is the main part that makes up the gel sheet 4 in Figure 28. The gel sheet 4 does not necessarily have to have a covering material 4k. In this case, the entire gel sheet 4 may be the gel sheet body portion 4j.

[0094] The coating material 4k is preferably formed from one of the following: mineral oil, agarose gel, PDMS sheet, and polyvinyl chloride sheet. However, the material of the coating material 4k is not limited to these.

[0095] The thickness of the coating material 4k is preferably 1 μm or more and 1 cm or less. However, among the above, the thickness of the coating material 4k is more preferably 1 μm or more and 100 μm or less. In addition, in the gel sheet 4 of Figure 28, the ratio of the thickness of the gel sheet body 4j to the thickness of the coating material 4k may be within the following range. That is, the ratio of "thickness of gel sheet body 4j : thickness of coating material 4k" may be any ratio between 10:1 and 1:100.

[0096] The coating material 4k is preferably manufactured at the same time as the gel sheet body 4j. The coating material 4k is preferably used to cover the upper surface of the gel sheet body 4j as shown in Figure 28. However, the coating material 4k may cover both the upper and lower surfaces of the gel sheet body 4j as shown in Figure 28. The method for manufacturing the gel sheet 4 when forming a coating material 4k that covers only the upper surface of the gel sheet body 4j as shown in Figure 28 is as follows.

[0097] In Figure 28, the gel sheet 4 is first prepared by creating the gel sheet body 4j, and then the materials constituting the coating 4k are added onto the gel sheet body 4j. Finally, if the materials constituting the coating 4k are materials that gel, they are gelled. Through these steps, the gel sheet 4 shown in Figure 28 is obtained.

[0098] The above addition may be performed by uniformly supplying the liquid material constituting the coating material 4k onto the gel sheet body 4j. Alternatively, if the coating material 4k is already in sheet form, the gel sheet body 4j and the coating material 4k may become one simply by placing the sheet over the gel sheet body 4j.

[0099] In the case of a gel sheet 4 having a coating material 4k on both the upper and lower surfaces of the gel sheet body 4j, the liquid coating material 4k may be uniformly supplied onto the surface of the gel sheet body 4j as described above. Alternatively, a sheet-like coating material 4k may be placed on the surface of the gel sheet body 4j. For example, the coating material 4k for the upper surface of the gel sheet body 4j may be first formed into a sheet and gelled, then the gel sheet body 4j may be manufactured, and finally the coating material 4k for the upper surface may be placed on top of the gel sheet body 4j. For example, if a PDMS sheet or a polyvinyl chloride sheet is used as the coating material 4k, a method may be used in which the sheet is first formed independently, then formed into a sheet and gelled, and finally placed on top of the gel sheet body 4j.

[0100] The gelation of the coating material 4k may be performed after the liquid coating material 4k has been applied. The coating material 4k for the bottom surface may be gelled after uniform supply of the liquid material using the same procedure as for the coating material 4k in Figure 28.

[0101] Figure 29 is a schematic cross-sectional view showing a gel sheet having the configuration of Figure 28 that has been cut multiple times by the collection and placement mechanism. In other words, in Figure 29, similar to Figure 21, the collection pin body 141A cuts the gel sheet 4 of Figure 28 multiple times. The gel sheet portion 4E is then housed multiple times (twice) within the hollow-shaped portion of the collection pin body 141A. In Figure 29, similar to Figure 21, each gel sheet portion 4E is indicated as gel sheet portion 4E1, 4E2, and so on.

[0102] (Regarding materials) The materials used in each of the above components, and the types of substances, cells, etc. used in each of the above samples, are described below.

[0103] Gel sheet 4 contains a polymer compound and a solvent that constitute gel 4D. The material of the additive in gel 4D is not particularly limited. However, the additive may be a single cell, cell tissue, low molecular weight compound, medium molecular weight compound, or high molecular weight compound. The additive may be a single cell, cell tissue, cell growth factor, cytokine, hormone, transcription factor, neurotransmitter, protein, nucleic acid, antibody, antigen, mRNA / DNA, bacteria, virus, microorganism, nanoparticles (metal, magnetic), new drug candidate compound, pharmaceutical, pesticide, food, food additive, cosmetic, or salt.

[0104] The material of Gel 4D (Gel Raw Material 4A) is not particularly limited. Gel 4D may be made from natural polymer compounds, synthetic polymer compounds, etc. For example, as Gel 4D, any of the following may be used: collagen, fibrin, Matrigel, gelatin, sodium alginate, gelatin methacryloyl (GelMA), cellulose, cellulose nanofiber, chitin, chitosan, chitin nanofiber, chitosan nanofiber, methylcellulose, carboxymethylcellulose, hydroxybutylcellulose, sodium alginate, sodium hyaluronate, polyethylene glycol, gellan gum, carrageenan, pectin, xanthan gum, gelatin, agarose, and polyvinyl alcohol. Modified versions of these, such as cell adhesion RGD sequences or fluorescent functional groups, may also be used.

[0105] Alternatively, gel 4D may not be used in the portion referred to as gel sheet 4 above. In this case, the samples to be collected are various sections prepared by newly formed thin sections, fixed thin sections, and frozen thin sections, as well as cell sheets constructed by tissue engineering. In this case, the above-mentioned samples are used instead of gel 4D in the portion referred to as gel sheet 4 above. In this case, gel sheet 4 above is referred to as "sheet 4," and gel sheet portion 4E is referred to as "sheet portion 4E." In this case, the portion that supports the sample to be collected is referred to as the "support portion," and the above-mentioned additives are added to the support portion.

[0106] The solvent contained in the support portion, such as Gel 4D, is not particularly limited. However, the solvent is preferably either a culture medium or a buffer. For example, any of the following may be used as the solvent: DMEM, DMEM / Ham F-12, αMEM, RPMI-1640, William medium, M199, commercially available specialized culture media for various cells, PBS solution (+ or -), Tris buffer, or Tyrode's buffer.

[0107] The cells contained in the support portion of gel sheet 4, such as gel 4D, are not particularly limited. These cells may be, for example, normal cells, cells derived from various diseases, or genome-edited cells. The cells may be from humans, rats, mice, or monkeys. The cells may be differentiated cells derived from stem cells. In other words, the cells may be differentiated cells derived from iPS cells or ES cells. The cells may be stem cells such as iPS cells or ES cells. The cells may be mesenchymal stem cells. The cells may be primary cells or line-type cells.

[0108] The cell types may be any of the following: nerve cells, cardiomyocytes, fibroblasts, vascular endothelial cells, hepatocytes, Kupffer cells, hepatic stellate cells, pit cells, epithelial cells, and skeletal muscle cells, i.e., cells derived from various organs. Nerve cells include central nervous system cells, sympathetic nerve cells, parasympathetic nerve cells, sensory nerve cells, interneurons, motor nerve cells, microglia, astrocytes, oligodendrocytes, ependymal cells, Schwann cells, satellite cells, etc. Cardiomyocytes include ventricular myocytes, atrial myocytes, etc.

[0109] The term "single cell" above refers to a state in which multiple cells exist individually, separated from each other. The term "cellular tissue" above refers to a mass formed by the aggregation of one or more types of cells. Cellular tissue can be, for example, a spherical spheroid, a sheet-like cell sheet, or a rod-shaped cell fiber constructed using tissue engineering techniques. Furthermore, tissue collected and subdivided from organs of living organisms is also considered cellular tissue. Various types of sections obtained by preparing these cellular tissues—newly formed thin sections, fixed thin sections, and frozen thin sections—are also included in cellular tissue. Furthermore, immunostained sections obtained by immunostaining the above types of sections are also included in cellular tissue. Cells and cellular tissues may also be genome-edited using genetic engineering techniques.

[0110] The additives in Gel 4D, including low-molecular-weight compounds, medium-molecular-weight compounds, high-molecular-weight compounds, cell growth factors, cytokines, hormones, transcription factors, neurotransmitters, proteins, nucleic acids, antibodies, antigens, mRNA / DNA, viruses, bacteria, microorganisms, nanoparticles (metals, magnetic materials), new drug candidate compounds, pharmaceuticals, pesticides, foods, food additives, cosmetics, and salt, should be added according to their respective purposes. More details about these additives are as follows: This additive is used in new drug candidate compounds, pharmaceuticals, pesticides, foods, food additives, cosmetics, T3, T4, IGF (insulin-like growth factor: IGF-I), epidermal growth factor (EGF), TGF, basic fibroblast growth factor (bFGF), fibroblast growth factor (FGF2), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor (PDGF), EPO, TPO, hepatocyte growth factor (HGF), bone morphogenetic factor (BMP), retinoic acid, Activin A, Noggin, insulin, dexamethasone, B27® supplement, N2 The supplement may contain any of the following: fetal bovine serum (FBS), collagen, fibrin, Matrigel, gelatin, fibronectin, vitronectin, laminin, proteoglycan, nidogen, ROCK inhibitor, sodium alginate, GelMA, cellulose, cellulose nanofiber, chitin, chitosan, chitin nanofiber, chitosan nanofiber, methylcellulose, carboxymethylcellulose, hydroxybutylcellulose, sodium alginate, sodium hyaluronate, polyethylene glycol, gellan gum, carrageenan, pectin, xanthan gum, gelatin, agarose, or polyvinyl alcohol.

[0111] Alternatively, the additive may be any of the following: nicotine, GABA (gamma-aminobutyric acid), glutamic acid, adrenaline, dopamine, human coronavirus (e.g., any of SARS-CoV, MERS-CoV, or SARS-CoV-2 (COVID-19)), influenza virus, mycoplasma virus, rotavirus, norovirus, herpesvirus, human papillomavirus, Ebola virus, adenovirus, measles virus, rubella virus, hepatitis virus, HIV, Escherichia coli, Bifidobacterium, Bacillus subtilis, Lactobacillus, Intestinal bacteria, yeast, Candida, Aspergillus, Staphylococcus aureus, Salmonella, Bacillus cereus, Campylobacter, Helicobacter pylori, Clostridium perfringens, enterohemorrhagic Escherichia coli O157, Clostridium botulinum, Streptococcus pneumoniae, Pseudomonas, Clostridium tetani, Mycobacterium tuberculosis, Plague bacillus, and Treponema pallidum.

[0112] The plate 8 on which the gel sheet portion 4E containing cells is arranged is not particularly limited. The plate 8 may be a multiwell plate as shown in Figure 11 above.

[0113] The following various shapes are possible for the container 9A formed on the plate 8 described above. Figure 30 is a schematic cross-sectional view showing a first example of the shape of a container formed on the plate. As shown in Figure 30, the multiple containers 9A formed on the surface of the plate 8 (plate body 8A) may be formed to have a wall surface 91 extending in a direction intersecting the surface (uppermost surface 90) and a bottom surface 92 that spreads along the surface (uppermost surface 90). The bottom surface 92 is the plane of the container 9A that is located at the position furthest from the uppermost surface 90. The container 9A is formed by the bottom surface 92 and the wall surface 91 that is connected to the outer edge of the bottom surface 92 and spreads to intersect with the bottom surface 92.

[0114] Figure 31 is a schematic cross-sectional view showing a second example of the shape of a container formed on a plate. As shown in Figure 31, the container 9A formed on the plate body 8A has a wall surface 91 and a bottom surface 92. The wall surface 91 is the same as that of the container 9A in Figure 30. The bottom surface 92 is positioned to be continuous with the lowest part of the wall surface 91. In the container 9A of Figure 31, the bottom surface 92 (the bottom part furthest from the top surface 90) is curved. The curved surface as the bottom surface 92 may be part of a sphere or part of the surface of an ellipsoid. In Figure 31, the boundary between the planar wall surface 91 and the bottom surface 92 is a rounded curved surface in the cross-section of Figure 31. This boundary part may also be part of a sphere or part of the surface of an ellipsoid. As a result, the shape of the bottom surface 92 in the cross-section of Figure 31 is U-shaped.

[0115] Figure 32 is a schematic cross-sectional view showing a third example of the shape of a container formed on a plate. As shown in Figure 32, the container 9A formed on the plate body 8A has a wall surface 91 and a bottom surface 92. The wall surface 91 is the same as that of the container 9A in Figure 30. In the cross-section of Figure 32, both the wall surface 91 and the bottom surface 92 are inclined with respect to the vertical direction perpendicular to the top surface 90. In the container 9A formed on the plate body 8A, the angle between the bottom surface 92 (the bottom part furthest from the top surface 90) and the wall surface 91 with respect to the straight line extending in the vertical direction is different from that between them. In Figure 32, the boundary between the wall surface 91 and the bottom surface 92 connected thereto forms a ridge. In the cross-section of Figure 32, the bottom surface 92 has a larger angle with respect to the straight line extending in the vertical direction than the wall surface 91. The bottom surface 92 in Figure 32 is shaped like the side of a cone or pyramid, for example. Therefore, the lowest part of the bottom surface 92 may be pointed, like the apex of a cone or pyramid, in the cross-section of Figure 32. Based on the above, the shape of the bottom surface 92 in the cross-section of Figure 32 is V-shaped.

[0116] Plate 8 is not limited to a multiwell plate. Plate 8 may be any of the following: dishes of various diameters, microfluidic channels, glass slides, cell disc LFs, and PDMS substrates.

[0117] Figure 33 is a schematic diagram of the dish. Figure 34 is a schematic cross-sectional view of the bottom surface of the dish. If the plate 8 is a dish as shown in Figure 33, the gel sheet portion 4E containing cells is supplied onto the bottom surface of the dish. As shown in Figure 34, multiple depressions 9B are formed as recesses on the surface (uppermost surface 90) of the bottom surface of the dish. The depressions 9B are formed on the surface (uppermost surface 90) of the bottom surface of the dish by special microfabrication. A dish with such depressions 9B formed on it may be used as the plate 8.

[0118] The substrate for plate 8 may be a cell-adhering substrate. The cell-adhering substrate for plate 8 may be a cell-adhering polymer compound, a cell-adhering substrate with a contact angle controlled by radiation, or a cell-adhering substrate with irregularities created on its surface. The cell-adhering polymer compound may be collagen, gelatin, fibronectin, or Matrigel.

[0119] Alternatively, the substrate for plate 8 may be a low-cell-adhesion substrate. Plate 8 may be a low-cell-adhesion substrate using a low-cell-adhesion polymer compound, a low-cell-adhesion substrate with a contact angle controlled by radiation, or a low-cell-adhesion substrate with irregularities created on its surface. The low-cell-adhesion polymer compound may be an MPC polymer or P-HEMA. The substrate for plate 8 may be a substrate that instantly adheres to the gel sheet portion 4E. For example, the gel 4D and the substrate may be chemically modified with combinations of cyclodextrin groups and adamantane groups, azide groups and alkynyl groups, amino groups and ester groups, etc.

[0120] The coating material 4k (see Figure 28) constituting the gel sheet 4 is preferably selected from the group consisting of mineral oil, agarose gel, PDMS sheet, and polyvinyl chloride sheet, but is not particularly limited. For example, as the coating material 4k, in addition to any of the above group, any of the culture media and buffers such as sterile water, DMEM / Ham F-12, αMEM, RPMI-1640, William medium, M199, commercially available specialized culture media for various cells, PBS solution (+ or -), Tris buffer, and Tyrode's buffer may be used. Alternatively, the coating material 4k may be a gel or aqueous solution composed of natural polymer compounds or synthetic polymer compounds such as collagen, fibrin, Matrigel, gelatin, sodium alginate, GelMA, cellulose, cellulose nanofiber, chitin, chitosan, chitin nanofiber, chitosan nanofiber, methylcellulose, carboxymethylcellulose, hydroxybutylcellulose, sodium alginate, sodium hyaluronate, polyethylene glycol, gellan gum, carrageenan, pectin, xanthan gum, gelatin, agarose, and polyvinyl alcohol. Alternatively, the coating material 4k may be a sheet made of either PDMS or polyvinyl chloride polymer compounds. Note that the coating material 4k does not necessarily have to be included in a sheet such as the gel sheet 4.

[0121] (Effects) In the sampling and placement method according to this embodiment, a gel sheet 4, for example, is provided on the film 2 by spreading a support portion, such as a gel 4D, which supports the sample 4B to be collected, thinly on the film 2. The gel sheet 4 on the film 2 is punctured with a needle (sampling pin body 141A) having a hollow shape, thereby cutting off a part of the gel sheet 4, and the gel sheet portion 4E, which is a sheet portion that is a part of the gel sheet 4 that has been cut off, is collected in the hollow shape. The gel sheet portion 4E is discharged from the hollow shape, and the gel sheet portion 4E is placed in the container 9A. The gel sheet 4 and the container 9A are placed on the same stage 102.

[0122] In this way, especially when the gel sheet 4 (gel plate 6) and the container 9A (plate 8) are arranged along the horizontal direction (XY direction), multiple gel sheet sections 4E can be arranged in a short cycle time.

[0123] Figure 35 is a schematic cross-sectional view of a sample collection and placement apparatus as a comparative example of this embodiment. As shown in Figure 35, the comparative sample collection and placement apparatus 900 includes an XY stage 101 in addition to the XY stage 102 inside the processing chamber. The gel plate 6 containing the gel sheet 4 is placed on the XY stage 101 for the sample. The plate 8 containing the container 9A is placed on the XY stage 102 for the container. In other words, in Figure 35, the gel sheet 4 and the container 9A are placed on separate stages.

[0124] When using the sampling and placement device 900 shown in Figure 35, if the distance between the two stages is particularly long, the distance traveled between the gel sheet 4 and the container 9A to place the gel sheet portion 4E cut from the gel sheet 4 into the container 9A becomes long. As a result, the cycle time of the operation becomes longer. However, when using the sampling and placement device 100 of this embodiment, as shown in Figure 1, the gel sheet 4 and the container 9A are placed on the same XY stage 102. This makes it possible to shorten the distance traveled between the gel sheet 4 and the container 9A compared to the case where there are two stages as shown in Figure 35. In this embodiment, the X-direction dimension of the XY stage 102 in Figure 1 is preferably 40 mm or more and 260 mm or less, and the Y-direction dimension is preferably 40 mm or more and 260 mm or less. Among the above numerical ranges, it is particularly preferable that the X-direction dimension of the XY stage 102 is 90 mm or more and 180 mm or less, and the Y-direction dimension is preferably 90 mm or more and 180 mm or less.

[0125] Furthermore, in this embodiment, the sample stage and the container stage are shared by a single stage. Therefore, compared to cases where these stages are separate, the cost of the sampling and placement device 100 using the sampling and placement method can be reduced because the number of stages is reduced. In addition, the overall size of the sampling and placement device 100 can be made smaller.

[0126] In the above sampling and placement method, in the step of sampling the gel sheet portion 4E as a sheet portion, it is preferable that the needle (sampling pin body 141A) cuts the gel sheet 4 multiple times and stores the gel sheet portion 4E multiple times within the hollow-shaped portion. That is, the gel sheet 4 is cut multiple times in a row and stored multiple times in a row within the hollow-shaped portion. This allows multiple gel sheet portions 4E to be cut and placed in the container 9A in a shorter time than, for example, repeating the step of cutting the gel sheet 4 and the step of storing it in the hollow-shaped portion once each multiple times. This shortens the cycle time of the operation.

[0127] In the above sampling and placement method, it is preferable that multiple gel sheet portions 4E are stacked within the hollow-shaped portion during the step of sampling the gel sheet portion 4E. This allows multiple gel sheet portions 4E to be cut and placed in the container 9A in a shorter time than, for example, repeating the step of cutting the gel sheet 4 and the step of placing it in the hollow-shaped portion multiple times. This shortens the cycle time of the operation.

[0128] In the above sampling and placement method, in the step of placing the gel sheet portion 4E in the container 9A, the gel sheet portion 4E, which is a plurality of sheet portions stacked within the hollow-shaped portion, may be discharged one by one in multiple steps by puncturing it multiple times with the needle (sampling pin body 141A) during the sampling step. In this way, each of the gel sheet portions 4E that have been collected in succession can be stored individually in separate containers 9A. This makes it possible to perform the process of placing each gel sheet portion 4E into separate containers 9A in a short amount of time.

[0129] In the above sampling and placement method, the amount of movement of the gel sheet portion 4E within the hollow shape of the multiple gel sheet portions 4E is controlled during the process of placing the gel sheet portion 4E into the container 9A. This allows any number of the continuously sampled gel sheet portions 4E to be placed in each container 9A. In other words, it is possible to place one gel sheet portion 4E in each container 9A, or two gel sheet portions 4E in each container 9A.

[0130] In the above sampling and placement method, in the step of placing the gel sheet portion 4E as a sheet portion into the container 9A, the amount of movement of the multiple gel sheet portions 4E is controlled by the amount of pressure applied by the placement pin 142 to push and move the multiple gel sheet portions 4E. When the disc member 144B constituting the sampling and placement member 104 is rotated by a motor (first motor 144A), a link member 144C fixed to a part of the outer circumference of the disc member 144B is displaced, and the link member 144C applies pressure to the placement pin 142, causing the placement pin 142 to move in a manner that pushes in the multiple gel sheet portions 4E. Such a configuration is also acceptable.

[0131] In this way, by controlling the rotation angle of the first motor 144A, the amount by which the placement pin 142 pushes the gel sheet portion 4E downward can be controlled. As a result, any number of gel sheet portions 4E can be released from the tip of the sampling pin 141. Therefore, it is possible to control the placement of one or any number of gel sheet portions 4E in each container 9A.

[0132] In the above sampling and placement method, the support part is gel 4D, the sheet is gel sheet 4, and the sheet part is gel sheet part 4E. This allows the sampling and placement processes to be carried out smoothly.

[0133] In the above sampling and placement method, the gel sheet 4 may include a gel sheet body portion 4j and a coating material 4k. The coating material 4k is placed on the surface of the gel sheet body portion 4j. Because the gel sheet 4 has a coating material 4k, when multiple gel sheet portions 4E are sampled consecutively with the sampling pin 141, adhesion between multiple gel sheet portions 4E stacked within the sampling pin body 141A can be suppressed. In addition, the coating material 4k prevents the gel sheet 4 from drying out and suppresses the death of cells and tissues. Furthermore, the coating material 4k can suppress the denaturation of DNA, mRNA, proteins, etc.

[0134] Furthermore, if the gel sheet body 4j is made of a soft material, it may be difficult to collect the gel sheet 4 with the collection pin 141. In this case, the gel sheet 4 is reinforced by covering the gel sheet body 4j with the covering material 4k. This makes it easier to collect the gel sheet 4 with the collection pin 141.

[0135] When the purpose is to reinforce the gel sheet 4, it is preferable that the covering material 4k is harder than the gel sheet 4. This allows the gel sheet 4 to be easily harvested. In this case, the combination of materials of the gel sheet body 4j and the covering material 4k constituting the gel sheet 4 is preferably as follows. For example, if the gel sheet body 4j is collagen gel, it is preferable that the covering material 4k is agarose gel. If the gel sheet body 4j is collagen gel, it is preferable that the covering material 4k is either a PDMS sheet or a polyvinyl chloride sheet.

[0136] In the above-described sampling and placement method, it is preferable that the covering material 4k is formed from one selected from the group consisting of mineral oil, agarose gel, PDMS sheet, and polyvinyl chloride sheet. Using one selected from the group consisting of agarose gel, PDMS sheet, polyvinyl chloride sheet, and mineral oil can reduce the effect of the covering material 4k on cells or components that make up cells. For example, the gel sheet 4 may have a collagen gel as the gel sheet body portion 4j and a mineral oil as the covering material 4k.

[0137] In the above-described collection and placement method, in the step of placing the gel sheet portion 4E, which serves as the sheet portion, into the container 9A, the gel sheet portion 4E may be placed in the container 9A which is formed in a matrix on the multiwell plate (plate 8). For the preparation (manufacturing) of cell tissue, it is preferable to use a multiwell plate in which multiple containers 9A are formed. This makes it possible to easily prepare multiple types of cell tissue with controlled cell arrangement.

[0138] (Note) The various aspects of this disclosure are summarized below as an appendix.

[0139] (Note 1) A sampling and placement method comprising the steps of: placing a sheet obtained by spreading a support portion for supporting the sample to be collected thinly on a film onto the film; cutting a part of the sheet by puncturing the sheet on the film with a needle having a hollow shape portion, and collecting the sheet portion which is the cut-off part of the sheet into the hollow shape portion; and discharging the sheet portion from the hollow shape portion to place the sheet portion into a container, wherein the sheet and the container are placed on the same stage.

[0140] (Note 2) The sampling method according to Note 1, wherein in the sampling step, the needle cuts the sheet multiple times and stores the sheet portion multiple times within the hollow-shaped portion.

[0141] (Note 3) The sampling arrangement method according to Note 1 or 2, wherein in the sampling step, a plurality of the sheet portions are stacked within the hollow-shaped portion.

[0142] (Note 4) The sampling and sampling method according to any one of Notes 1 to 3, wherein in the sampling step, the needle punctures multiple times, causing the multiple sheet portions stacked in the hollow-shaped portion to be discharged one by one in multiple steps.

[0143] (Note 5) The sampling and placement method according to any one of Notes 1 to 4, wherein the amount of movement of the multiple sheet portions within the hollow-shaped portion is controlled in the placement step.

[0144] (Note 6) The sampling and placement method according to Note 5, wherein in the placement step, the amount of movement of the plurality of sheet portions is controlled by the amount of pressure exerted by the placement pin to push and move the plurality of sheet portions, and as the disc member constituting the sampling and placement member is rotated by a motor, a link member fixed to a part of the outer circumference of the disc member is displaced, and the link member applies pressure to the placement pin, causing the placement pin to move in a manner that pushes in the plurality of sheet portions.

[0145] (Note 7) The sampling and placement method according to any one of Notes 1 to 6, wherein the support portion is a gel, the sheet is a gel sheet, and the sheet portion is a gel sheet portion.

[0146] (Note 8) The sampling and placement method according to Note 7, wherein the gel sheet comprises a gel sheet body and a covering material placed on the surface of the gel sheet body.

[0147] (Note 9) The sampling and placement method described in Note 8, wherein the covering material is formed from one selected from the group consisting of mineral oil, agarose gel, PDMS sheet, and polyvinyl chloride sheet.

[0148] (Note 10) The sampling and placement method according to any one of Notes 1 to 9, wherein in the placement step, the sheet portion is placed in the container formed in a matrix on a multiwell plate.

[0149] 1, 5 Slide glass, 2 Film, 3 Spacer, 3A Through hole, 4 Gel sheet, 4A Gel raw material, 4B Sample, 4C Fluid sample, 4D Gel, 4j Gel sheet main body, 4k Covering material, 4E, 4E1, 4E2 Gel sheet part, 6 Gel plate, 8 Plate, 8A Plate body, 9A, 9A1, 9A2 Container, 9B Recess, 90 Top surface, 91 Wall surface, 92 Bottom surface, 100, 900 Sampling and placement device, 101, 102 XY stage, 104 Sampling and placement member, 104A Sampling and placement mechanism, 106 Observation optical system, 141 Sampling pin, 141A Sampling pin body, 141B Sampling pin holder, 141C Adhesive, 142 Placement pin, 142A Placement pin body, 142B Placement pin holder, 142C Spring, 143 Fixing holder, 143f, 146f Front view, 144 First drive unit, 144A First motor, 144B Disc member, 144C Link member, 145 Arrangement pin holder fixing part, 145a First part, 145b Second part, 146 Second drive unit, 146A Movable holder, 146B Second motor, 146C Vertically extending screw, 146D Screw connection part, FXD Fixing part, G Groove.

Claims

1. A sampling and placement method comprising the steps of: placing a sheet obtained by thinly spreading a support portion for supporting a sample to be collected on a film onto the film; puncturing the sheet on the film with a needle having a hollow shape portion to cut off a part of the sheet, and collecting the sheet portion, which is the cut-off part of the sheet, into the hollow shape portion; and discharging the sheet portion from the hollow shape portion to place the sheet portion into a container, wherein the sheet and the container are placed on the same stage.

2. The sampling method according to claim 1, wherein in the sampling step, the needle cuts the sheet multiple times and stores the sheet portion multiple times within the hollow-shaped portion.

3. The sampling arrangement method according to claim 1 or 2, wherein in the sampling step, a plurality of the sheet portions are stacked within the hollow-shaped portion.

4. The sampling and sampling method according to claim 1 or 2, wherein in the sampling step, the needle punctures multiple times, causing the multiple sheet portions stacked within the hollow-shaped portion to be discharged one by one in multiple steps.

5. The sampling and placement method according to claim 1 or 2, wherein the amount of movement of the multiple sheet portions within the hollow-shaped portion is controlled during the placement step.

6. The sampling and placement method according to claim 5, wherein in the placement step, the amount of movement of the plurality of sheet portions is controlled by the amount of pressure applied by the placement pin to move the plurality of sheet portions, and as the disc member constituting the sampling and placement member is rotated by a motor, a link member fixed to a part of the outer circumference of the disc member is displaced, and the link member applies pressure to the placement pin, causing the placement pin to move in a manner that pushes in the plurality of sheet portions.

7. The sampling and placement method according to claim 1 or 2, wherein the support portion is a gel, the sheet is a gel sheet, and the sheet portion is a gel sheet portion.

8. The sampling and placement method according to claim 7, wherein the gel sheet comprises a gel sheet body and a covering material placed on the surface of the gel sheet body.

9. The sampling and arranging method according to claim 8, wherein the coating material is formed from one selected from the group consisting of mineral oil, agarose gel, PDMS sheet, and polyvinyl chloride sheet.

10. The sampling and placement method according to claim 1 or 2, wherein in the placement step, the sheet portion is placed in the container formed in a matrix on a multiwell plate.

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