Coating mechanism, liquid material coating device, and liquid material coating method

Abstract

A coating mechanism is provided with a coating needle, a liquid material container (21), and a temperature control unit (28). The liquid material container (21) has a container through-hole (25A) formed at a bottom portion thereof. The temperature control unit (28) includes a block member (26) and a controller (37). The liquid material container (21) can be attached to the block member (26). The controller (37) is fixed to the block member (26) and can control the temperature of the block member (26). The block member (26) can be used to attach the liquid material container (21) so as to surround both the sides and the bottom portion of the liquid material container (21). The height of the lowest part of the container through-hole (25A) of the liquid material container (21) attached to the block member (26) is equal to the height of the lowest part of the block member (26).

Description

Coating mechanism, liquid material coating device, and liquid material coating method

[0001] The present invention relates to a coating mechanism, a liquid material coating device, and a liquid material coating method.

[0002] When handling cells in vitro, a three-dimensional cell tissue chip is constructed, and evaluations and experiments are performed on the three-dimensional tissue chip. This is important for the progress of drug discovery research and regenerative medicine research because cells actually grow three-dimensionally in vivo to form tissues and organs.

[0003] In recent years, it has become clear that in the construction of three-dimensional cell tissues, it is important to culture cells in a microenvironment that mimics the environment of the organs where the cells originally existed. Therefore, the use of collagen and Matrigel, etc. in the construction of cell tissues has attracted attention. Collagen and Matrigel are components of the microenvironment. Collagen and Matrigel are protein materials derived from living organisms.

[0004] Collagen and Matrigel gelate upon heating. If collagen or the like gels, it is impossible to transfer the collagen containing cells onto a substrate or the like. Therefore, in the production of cell tissues, it is important to control the temperature of the liquid material container provided in the coating mechanism so that the material does not gel.

[0005] Japanese Unexamined Patent Application Publication No. 2021-023906 (Patent Document 1) discloses an example of adjusting the temperature of the liquid material in the liquid material container using a Peltier element. This suppresses the thread dragging caused by the liquid material.

[0006] Japanese Unexamined Patent Application Publication No. 2021-023906

[0007] In Patent Document 1, temperature control by a Peltier element or similar component is limited to either the side or bottom portion of the liquid material container. Therefore, it is difficult to control the temperature of the entire liquid material container to be uniform. If the temperature of the liquid material cannot be controlled, the types of materials that can be applied are limited. For example, liquid materials containing cells, used in the construction of cell tissues, may be difficult to apply to using Patent Document 1. This is because if the solvent contained in the liquid material changes its physical properties with temperature, the liquid material may solidify unintentionally, making application impossible.

[0008] Furthermore, if temperature control elements such as Peltier elements are positioned to protrude downwards in the vertical direction (Z direction) relative to the liquid material container, the vertical gap between the liquid material container and the workpiece (substrate, plate, etc.) increases. This can destabilize the output of the coating process. In other words, the coating needle protruding from the liquid material container may not reach the workpiece, potentially limiting the area to which the liquid material is applied.

[0009] The present invention has been made in view of the above-mentioned problems. The object of the present invention is to provide a coating mechanism that can apply a wider variety of liquid materials more stably, a liquid material coating apparatus equipped with the coating mechanism, and a method for applying liquid materials using the coating mechanism.

[0010] The coating mechanism according to this disclosure comprises a coating needle, a liquid material container, and a temperature control unit. The coating needle coats the liquid material onto the workpiece. The liquid material container houses and holds the liquid material. The liquid material container has a through-hole at its bottom through which the coating needle can pass. The temperature control unit includes a block member and a controller. The block member is capable of mounting the liquid material container. The controller is fixed to the block member and can control the temperature of the block member. The block member is capable of mounting the liquid material container so as to surround both the sides and the bottom of the liquid material container. The height of the lowest part of the through-hole of the liquid material container mounted on the block member is equal to the height of the lowest part of the block member.

[0011] A liquid material dispensing apparatus according to this disclosure comprises the above-described dispensing mechanism and a holding base for holding a workpiece.

[0012] The method for applying a liquid material according to this disclosure uses the application mechanism described above. The liquid material attached to the tip of the application needle is supplied to the workpiece. The liquid material supplied to the workpiece is cooled to below room temperature.

[0013] According to this disclosure, the block member surrounds both the sides and the bottom of the liquid material container. The lowest point of the through-hole of the liquid material is at the same height as the lowest point of the block member. This makes it possible to provide a coating mechanism that can apply a wider variety of liquid materials more stably, a liquid material coating apparatus equipped with the coating mechanism, and a method for applying liquid materials using the coating mechanism.

[0014] This is a schematic front view showing a coating apparatus according to an embodiment. This is a schematic diagram showing the needle coating section of the coating apparatus shown in Figure 1. This is a perspective view of the coating mechanism according to this embodiment. This is a photograph of the temperature control unit included in Figure 3. This is a schematic cross-sectional view showing a block member to which a liquid material container is attached. This is a schematic enlarged cross-sectional view of the area VI enclosed by the dotted line in Figure 5. This is a schematic cross-sectional view showing the block member fixed to the cooling unit. This is a photograph of the block member holding the liquid material container as shown in Figure 7. This is a schematic side view showing how the frame surrounding the temperature control unit is fixed to the needle coating section and the housing section by the mounting section. This is a schematic side view showing the cooling fan in Figure 9 viewed from the negative side in the Y direction. This is a photograph of the connection between the housing section and the temperature control unit, including the fastener in Figure 10. This is a schematic cross-sectional view showing the temperature measurement location in Example 1 of the block member to which the liquid material container in Figure 5 is attached. This is a graph showing the results of temperature measurement at measurement positions A and B using thermocouples. This is the observation result of the object to be coated immediately after the first coating liquid is applied to the coating surface of the well. Figure 14 shows the observation results of the coated object after the culture medium was added to the first coating solution. The first coating solution was filled into a liquid material container, cooled, and allowed to stand for 35 minutes, and then the coated object was applied to the coating surface of the well and the culture medium was added immediately afterward. Figure 16 shows the observation results of the coated object after it had been left to stand for one day.

[0015] (Introduction) First, the coating mechanism according to this embodiment will be described. As shown in Figures 2 and 3, the coating mechanism 110 comprises a coating needle 24, a liquid material container 21, and a temperature control unit 28. The coating needle 24 coats the workpiece (e.g., inside the well 9A of the plate 8: see Figure 1) with the liquid material. The liquid material container 21 houses and holds the liquid material. As shown in Figure 7, the liquid material container 21 has a container through hole 25A formed at the bottom. The temperature control unit 28 can be fitted with the liquid material container 21. The temperature control unit 28 includes a block member 26 and a controller (cooling unit 37). The block member 26 can be fitted with the liquid material container 21. The cooling unit 37 is fixed to the block member 26 and can control the temperature of the block member 26. As shown in Figure 6, the block member 26 can accommodate the liquid material container 21 so as to surround both the side (outer peripheral side portion 21B1) and the bottom (outer peripheral bottom portion 21B2) of the liquid material container 21. The height of the lowest part 21P of the container through hole 25A of the liquid material container 21 attached to the block member 26 is equal to the height of the lowest part 26P of the block member 26.

[0016] (Embodiment) <Configuration of the coating apparatus> Figure 1 is a schematic front view showing a coating apparatus according to an embodiment. For the sake of explanation, the X, Y, and Z directions are introduced. Referring to Figure 1, the coating apparatus 100 (liquid material coating apparatus) includes a needle coating section 104 and a dropping section 105 as a coating section 107 capable of supplying the coating material to be coated. Thus, in this specification, "coating" includes both the supply of coating material using a coating needle, which will be described later, and the supply of coating material by dropping. For this reason, the former supply using a coating needle may be referred to as "needle coating" in this specification. The coating apparatus 100 in Figure 1 includes one needle coating section 104 and one dropping section 105. The needle coating section 104 and the dropping section 105 are spaced apart in the X direction. The distance between them in the X direction is constant and does not change. Note that Figure 1 only shows the needle application section 104 for the first coating solution, which is a bio-ink and will be described later, and the dropping section 105 for the second coating solution, and the dropping section for the culture medium is not shown.

[0017] The X-axis stage 101 (stage) is movable along the horizontal X-direction. The Y-axis stage 102 is also movable along the horizontal Y-direction. Specifically, for example, a guide is installed on the lower surface of the X-axis stage 101 or the Y-axis stage 102. This guide is slidably connected to a guide rail (not shown). For example, the upper surface of the X-axis stage 101 is a mounting surface on which a plate 8, which is the material to be processed, can be placed. The plate 8 is, for example, a multi-well plate having multiple wells 9A. In Figure 1, the X-axis stage 101 is placed on the Y-axis stage 102, and the plate 8 is placed on the X-axis stage 101. However, conversely, the X-axis stage 101 may be placed on the Y-axis stage 102, and the plate 8 may be placed on the X-axis stage 101.

[0018] The needle coating unit 104, the dropping unit 105, and the observation optical system 106 are connected to a member that can move in the Z direction, such as a Z-axis table. In other words, the needle coating unit 104, the dropping unit 105, and the observation optical system 106 are held within the coating apparatus 100 so as to be movable in the Z direction. The observation optical system 106 observes and measures the position on the plate 8 where the coating material should be applied. The observation optical system 106 may be equipped with a CCD camera that converts the observed image into an electrical signal. Observation of the plate 8 by the observation optical system 106 may be done using visible light. However, observation of the plate 8 is not limited to visible light; it may also be done using infrared light, X-rays, ultrasound, etc., and depending on the material of the plate 8, it may be possible to observe the plate 8 using magnetism. The plate 8 observed by means other than visible light does not need to be transparent or translucent; it may be opaque.

[0019] Figure 2 is a schematic diagram showing the needle application section of the coating apparatus shown in Figure 1. Referring to Figure 2, the needle application section 104 of this embodiment mainly includes a servo motor 41, a cam 43, a bearing 44 held in contact with the cam surface of the cam 43, a cam connecting plate 45, a movable part 46, a movable base 35A that holds the coating needle holder 20, and a liquid material container 21. The coating needle holder 20 is detachably attached to the movable base 35A. In other words, the movable base 35A, as a base body, detachably holds the coating needle holder 20.

[0020] In the needle application section 104, the servo motor 41 is installed so that its central axis extends in the direction along the Z-axis direction shown in Figure 1. A cam 43 is connected to the rotation axis of the servo motor 41. The cam 43 is rotatable about the central axis of the servo motor 41. The cam 43 includes a central part connected to the rotation axis of the servo motor 41 and a flange part connected to one end of the central part. The upper surface of the flange part (the surface on the servo motor 41 side) is the cam surface. This cam surface is formed in an annular shape along the outer circumference of the central part and is also formed in a slope shape so that the distance from the bottom surface of the flange part varies. Specifically, the cam surface includes an upper flat region where the distance from the bottom surface is the greatest (thickest), a lower flat region spaced apart from this upper flat region, and a slope part that smoothly connects the upper flat region and the lower flat region. The lower flat region is the region where the distance from the bottom surface is the greatest (thinnest).

[0021] A bearing 44 is positioned so as to be in contact with the cam surface of the cam 43. A cam connecting plate 45 is connected to this bearing 44. One end of the cam connecting plate 45 is connected to the bearing 44, and the other end opposite to the bearing 44 is fixed to a movable part 46. A movable base 35A, which serves as a base body, is connected to this movable part 46. A coating needle holder 20 is installed on this movable base 35A. The coating needle holder 20 includes a coating needle 24. The coating needle 24 is capable of applying coating material to the coating surface (the horizontal bottom surface) of, for example, a well 9A of the plate 8. The coating needle 24 is positioned to protrude from the coating needle holder 20 on the lower surface of the coating needle holder 20 (the lower side opposite to the side where the servo motor 41 is located). A liquid material container 21 is positioned below the coating needle holder 20. The coating needle 24 is held in an inserted state within the liquid material container 21.

[0022] A fixing pin is fixed to the movable part 46. The other fixing pin is fixed to the frame that holds the servo motor 41. A spring is installed to connect these fixing pins. Due to this spring, the movable part 46 is subjected to a force directed toward the liquid material container 21. Furthermore, the force of this spring maintains the bearing 44 in a state of being pressed against the cam surface of the cam 43.

[0023] Furthermore, the movable part 46 and the movable base 35A are connected to a linear guide installed on a frame that holds the servo motor 41, and are movable along the Z-axis direction.

[0024] In the needle application unit 104 described above, the servo motor 41 is driven to rotate its rotation axis, thereby rotating the cam 43. As a result, the position of the bearing 44 in contact with the cam surface of the cam 43 in the Z-axis direction changes according to the rotation of the servo motor 41's rotation axis. Then, in response to this change in the position of the bearing 44 in the Z-axis direction, the movable part 46 and the movable base 35A move in the Z-axis direction, thereby changing the position of the application needle 24 in the Z-axis direction. In other words, the application needle 24 can be made to reciprocate in the Z-axis direction. With this operation, when the application needle 24 is in the upper Z-axis direction, the tip of the application needle 24 is immersed in the liquid material container 21 containing the liquid material. In this state, the application operation is performed by the application needle 24 protruding downward from the tip hole at the bottom of the liquid material container 21. With the liquid material attached to the tip of the application needle 24, the tip of the application needle 24 protrudes from the tip hole at the bottom of the liquid material container 21 and exits the liquid material container 21. At this time, the liquid material is pulled upward by surface tension, and a nearly constant amount of liquid material adheres to the tip of the coating needle 24. This adhered liquid material is then transferred into the wells 9A of the plate 8, enabling a highly reproducible coating process. The movement of the coating needle 24 by the cam mechanism 43 may also be vertical movement by a mechanism including a servo motor 41, a disc member, and a link member, combined therewith.

[0025] <Configuration of the Coating Mechanism> Figure 3 is a perspective view of the coating mechanism according to this embodiment. As shown in Figure 3, the coating mechanism 110 is equipment for coating liquid material. The coating mechanism 110 includes the needle coating section 104 shown in Figures 1 and 2. The coating apparatus 100 of this embodiment actually has the coating mechanism 110 shown in Figure 3 instead of the needle coating section 104 shown in Figure 1. The needle coating section 104 in the coating mechanism 110 is located in the area enclosed by the dotted line in Figure 3. In addition to the needle coating section 104, the coating mechanism 110 mainly comprises a temperature control unit 28 and a housing section 75. In the coating mechanism 110, the needle coating section 104 and the temperature control unit 28 are supported by the housing section 75. In other words, the housing section 75 is a support column that supports the coating needle 24 and the liquid material container 21. Therefore, by moving the needle coating section 104 in the Z direction, the entire coating mechanism 110 can move in the Z direction.

[0026] The temperature control unit 28 is positioned within the coating mechanism 110, generally below the needle coating section 104 in the Z direction. The temperature control unit 28 can accommodate a liquid material container 21. The temperature control unit 28 can control the temperature of the liquid material container 21. The temperature control unit 28 includes a block member 26 and a cooling unit 37 as a controller.

[0027] The block member 26 in this embodiment is made of aluminum. However, the material used for the block member 26 is not limited to aluminum. It is preferable that the block member 26 be made of a material with high thermal conductivity. From this viewpoint, the block member 26 may be made of any of the group consisting of aluminum, copper, and stainless steel. Here, it is not limited to cases where it is made of only one of the above metal materials, but also includes cases where it is made of a material in which one of the above metal materials is the main component.

[0028] A liquid material container 21 can be inserted into the block member 26. In other words, the block member 26 is capable of having a liquid material container 21 attached to it. The liquid material container 21 is attached in the coating mechanism 110 so as to be in contact with the block member 26. The outside of the block member 26 is covered with an insulating material 27. The insulating material 27 may also be considered a component of the temperature control unit 28.

[0029] The cooling unit 37 is positioned within the coating mechanism 110 so as to be roughly aligned horizontally (for example, in the Y direction) with the block member 26. The cooling unit 37 is a unit for cooling the block member 26. Therefore, the cooling unit 37 can cool the liquid material container 21 attached to the block member 26 and the liquid material inside it. In this embodiment, the controller is the cooling unit 37. However, depending on the purpose of use of the coating mechanism 110, the controller may be a unit capable of heating the block member 26, etc. In any case, the controller can control the temperature of the block member 26.

[0030] The cooling unit 37 is fixed to the block member 26. The cooling unit 37 is detachably fixed to the block member 26 by screws. Although not shown, thermal conductive grease is applied to the joint surface between the cooling unit 37 and the block member 26. This improves the thermal conductivity between the cooling unit 37 and the block member 26, allowing the block member 26 to be cooled or heated efficiently.

[0031] Figure 4 is a photograph of the temperature control unit included in Figure 3. Figure 4 shows the unit viewed from approximately the same direction as in Figure 3. In addition to the temperature control unit 28, Figure 4 also includes a mounting portion 76 and a frame 74. The black rectangular parallelepiped members located in the upper right and lower left of Figure 4 are the mounting portions 76 in Figure 3. The mounting portion 76 is sandwiched between the housing portion 75 and the cooling unit 37. The housing portion 75 attaches the temperature control unit 28 (especially the cooling unit 37) to the mounting portion 76 in the upper right of Figures 3 and 4. In this way, the housing portion 75 supports the cooling unit 37. The needle application portion 104 is also fixed to the temperature control unit 28 by the mounting portion 76 in the lower left of Figures 3 and 4. However, the cooling unit 37 is surrounded by the frame 74. The frame 74 is installed to fix the cooling unit 37 to the needle application portion 104 and to allow the housing portion 75 to support it. A portion of the frame 74 is connected to the needle application portion 104 via the mounting portion 76. Furthermore, other parts of the frame 74 are connected to the housing 75 via other mounting parts 76.

[0032] Figure 5 is a schematic cross-sectional view showing a block member to which a liquid material container is attached. Figure 5 shows the cross-sectional view of the portion along the line V-V in Figure 3. As shown in Figure 5, a container mounting portion 26A is formed in the block member 26. The container mounting portion 26A is formed so as to extend from the upper surface of the three-dimensional structure forming the block member 26 to the block through hole 25B on the lower surface. The container mounting portion 26A, together with the block through hole 25B, penetrates the block member 26. The container mounting portion 26A is a space where a component such as aluminum that forms the block member 26 is missing. The space created by the absence of this component is the container mounting portion 26A. The container mounting portion 26A is a region into which the liquid material container 21 is inserted from above and which houses the liquid material container 21.

[0033] The liquid material container 21 has an inner circumferential surface 21A capable of storing and holding liquid material, an outer circumferential surface 21B as the outermost edge of the container, and a container through-hole 25A. The area inside the inner circumferential surface 21A is capable of holding the supplied liquid material. The inner circumferential surface 21A is formed as a hole into which the liquid material container 21 can be inserted from its uppermost part in the Z direction. The lowermost part of the inner circumferential surface 21A in the Z direction is connected to the container through-hole 25A. The container through-hole 25A is formed at the bottom (lowest region) of the liquid material container 21. Together with the container through-hole 25A, the inner circumferential surface 21A penetrates the liquid material container 21.

[0034] The container through-hole 25A extends in the Z direction to allow the application needle 24 inserted into the liquid material container 21 to pass through. The application needle 24 extends in the Z direction and is inserted downward from the upper opening of the liquid material container 21. The tip (lowest part) of the inserted application needle 24 is immersed in the liquid material contained within the inner circumferential surface 21A. With the liquid material adhering to the tip of the application needle 24, the application needle 24 penetrates the container through-hole 25A and exits the liquid material container 21 sequentially from the tip. The tip of the application needle 24 comes into contact with the coating surface of the workpiece, such as the plate 8 (well 9A). Alternatively, the liquid material (droplet) adhering to the tip of the application needle 24 comes into contact with the workpiece (substrate, plate 8). This coats the liquid material onto the coating surface. The liquid material may also be applied to an uncoated area of ​​the coating surface of the well 9A. Alternatively, the liquid material may be applied in contact with and overlapping with the liquid material already applied on the coating surface of well 9A.

[0035] As shown in Figure 5, the liquid material container 21 installed in the container mounting section 26A is surrounded on both its sides and bottom by aluminum or other materials that constitute the block member 26. In Figure 5, almost the entire portion of the outer peripheral surface 21B of the liquid material container 21 that extends along the Z direction (side) is in contact with the block member 26. As a result, the block member 26 is positioned in the regions adjacent to the outside of the liquid material container 21 in the X and Y directions of the portion of the outer peripheral surface 21B of the liquid material container 21 that extends along the Z direction (side). This state is described as the side of the liquid material container 21 being surrounded by the block member 26. Furthermore, the region below the region considered to be the side of the liquid material container 21, where the liquid material container 21 tapers to a point, is the bottom of the liquid material container 21. The block member 26 is also positioned in the regions adjacent to the outside of the liquid material container 21 in the X and Y directions of the bottom of the liquid material container 21 so as to be in contact with the liquid material container 21. This state is one in which the bottom of the liquid material container 21 is surrounded by the block member 26.

[0036] Figure 6 is a schematic enlarged cross-sectional view of the region VI enclosed by the dotted line in Figure 5. Figure 6 shows the cross-sectional view (vertical plane) perpendicular to the XY plane (horizontal plane) along the Z axis. The bottom of the liquid material container 21 in Figure 5 and its surroundings will be described in more detail with reference to Figure 6.

[0037] The inner circumferential surface 21A has an inner circumferential side portion 21A1 and an inner circumferential bottom portion 21A2. The inner circumferential side portion 21A1 is the region in which the inner circumferential surface 21A extends along the Z direction. The inner circumferential bottom portion 21A2 is located below (towards the bottom) in the Z direction from the inner circumferential side portion 21A1 in the liquid material container 21 inserted into the block member 26. The inner circumferential bottom portion 21A2 is formed at the bottom of the liquid material container 21. In the cross-sectional view of Figure 6, the inner circumferential bottom portion 21A2 is the region in which the inner circumferential surface 21A is inclined toward the center in a plan view of the liquid material container 21.

[0038] The outer peripheral surface 21B has an outer peripheral side portion 21B1 and an outer peripheral bottom portion 21B2. The outer peripheral side portion 21B1 is the portion of the outer peripheral surface 21B that extends along the Z direction. The outer peripheral bottom portion 21B2 is located below (towards the bottom) in the Z direction from the outer peripheral side portion 21B1 in the liquid material container 21 inserted into the block member 26. The outer peripheral bottom portion 21B2 is formed at the bottom of the liquid material container 21. In the cross-sectional view of Figure 6, the outer peripheral bottom portion 21B2 is a region (outer peripheral inclined portion) in which the inner peripheral surface 21A is inclined toward the center in a plan view of the liquid material container 21. In other words, in the cross-sectional view of Figure 6, the outer peripheral bottom portion 21B2 is inclined with respect to the Z direction in which the coating needle 24 extends.

[0039] The container mounting portion 26A of the block member 26 has a side contact portion 26A1 and a bottom contact portion 26A2. The side contact portion 26A1 extends along the Z direction. The bottom contact portion 26A2 is formed below (towards the bottom) the side contact portion 26A1 in the Z direction. The bottom contact portion 26A2 is a region that extends in a direction inclined with respect to the Z direction. The bottom contact portion 26A2 is connected to the side contact portion 26A1.

[0040] Both the outer peripheral side portion 21B1, which serves as the side of the liquid material container 21, and the outer peripheral bottom portion 21B2, which serves as the bottom, are in contact with the block member 26, and the container is surrounded by the block member 26 in the XY plane. Almost the entire outer peripheral side portion 21B1 is in contact with the side contact portion 26A1 of the block member 26 in the regions adjacent to the outside in the X and Y directions. A portion of the block member 26 is positioned in the regions adjacent to the side (outer peripheral side portion 21B1) of the liquid material container 21 in the X and Y directions.

[0041] At least a portion of the outer periphery bottom 21B2 contacts the bottom contact portion 26A2 of the block member 26 in the regions adjacent to the outside in the X and Y directions. However, the entire outer periphery bottom 21B2 may contact the bottom contact portion 26A2. In addition, at least a portion of the outer periphery bottom 21B2 contacts the bottom contact portion 26A2 of the block member 26 in the region adjacent to the outside (bottom) in the Z direction. This makes it preferable that a portion of the block member 26 is positioned in both the regions adjacent to the X and Y directions and the regions adjacent to the Z direction of the bottom (outer periphery bottom 21B2) of the liquid material container 21.

[0042] In the above description, the liquid material container 21 and the block member 26 are in contact with each other. However, this is not the only case. For example, although the outer peripheral side surface portion 21B1 and the outer peripheral bottom portion 21B2 do not contact the block member 26, they may face (adjacent) each other in a state of being very close to each other to such an extent that heat can be conducted.

[0043] In the cross-sectional view of FIG. 6, the inclination angle of the side surface contact portion 26A1 with respect to the bottom contact portion 26A2 is equal to the inclination angle of the outer peripheral bottom portion 21B2 with respect to the outer peripheral side surface portion 21B1. Thereby, not only a single point but also a region of a certain length in the inclination direction of the outer peripheral bottom portion 21B2 can contact the bottom contact portion 26A2. Within the range where such an effect can be obtained, the inclination angles of the bottom contact portion 26A2 and the outer peripheral bottom portion 21B2 described above are not limited to being exactly equal, and may have some errors.

[0044] Also, in the cross-sectional view of FIG. 6, the bottom contact portion 26A2 and the outer peripheral bottom portion 21B2 are inclined linearly. That is, in FIG. 6, the bottom contact portion 26A2 and the outer peripheral bottom portion 21B2 have a planar shape. However, this is not the only case. The bottom contact portion 26A2 and the outer peripheral bottom portion 21B2 may have a curved surface shape that is curved (for example, arc-shaped) in FIG. 6. In this case, the inclination angle of the outer peripheral bottom portion 21B2 (the tangent on the cross-sectional view) with respect to the vertical direction may increase as it approaches the lowermost part. That is, the outer peripheral bottom portion 21B2 extends so as to approach the X direction and the Y direction as it approaches the lowermost part. The same applies to the bottom contact portion 26A2.

[0045] The container installation portion 26A is narrower in the plan view from the Z direction at the bottom contact portion 26A2 than at the side surface contact portion 26A1. The liquid material container 21 is installed such that the narrowed bottom contact portion 26A2 fits the bottom on which the outer peripheral bottom portion 21B2 of the liquid material container 21 is formed. Thereby, the liquid material container 21 is mounted on the lowermost region of the block member 26 such that the outer peripheral bottom portion 21B2 overlaps the bottom contact portion 26A2.

[0046] At the lowermost portion of the block member 26 in the Z direction, a block through-hole 25B is formed. The block through-hole 25B is continuous with the lowermost portion of the bottom contact portion 26A2 of the block member 26. The block through-hole 25B extends along the Z direction. The height of the lowermost portion of the block through-hole 25B, that is, the height of the lowermost portion 26P of the block member 26, is equal to the height of the lowermost portion 21P of the container through-hole 25A of the liquid material container 21 attached to the block member 26. In particular, the height of the lowermost portion 21P of the outer peripheral bottom portion 21B2 is equal to the height of the lowermost portion 26P of the block member 26.

[0047] Here, the height of the lowermost portion means the height (coordinate position) in the Z direction, that is, the vertical direction. Here, being equal means not limited to the case of being completely equal, and includes the case where there is a certain error in the coordinate position in the Z direction between the two as long as the working effect described later is achieved. For example, it includes the case where there is an error in the coordinate position of less than 1 mm between the two. However, it is preferable that the error is less than 0.3 mm, and more preferably less than 0.1 mm. That is, if the error is ignored, no member is arranged below the container through-hole 25A of the liquid material container 21.

[0048] Both the container through-hole 25A and the block through-hole 25B have a substantially circular shape in a plan view from the Z direction. As shown in FIG. 6, the diameter of the block through-hole 25B is larger than the diameter of the container through-hole 25A. Specifically, it is preferable that the diameter of the block through-hole 25B is 5 times or less, more preferably 3 times or less, and still more preferably 2 times or less the diameter of the container through-hole 25A.

[0049] The portion of the block member 26 adjacent to the block through-hole 25B in the X and Y directions is located in the lowest region of the block member 26. In the lowermost region of this block member 26, the central region in a plan view from the Z direction has a bottom contact portion 26A2 formed on its upper surface, which is inclined in a C-shape. The bottom contact portion 26A2 is formed above the block through-hole 25B in the Z direction. The bottom contact portion 26A2 is inclined such that the thickness of the lowest region of the block member 26 in the vertical direction (Z direction) gradually decreases as it approaches the block through-hole 25B. The block through-hole 25B is formed in the innermost part of the block member 26 in a plan view. In other words, the bottom contact portion 26A2 is inclined such that the thickness of the lowest region of the block member 26 in the vertical direction (Z direction) gradually decreases as it approaches the center of the liquid material container 21 in the X and Y directions.

[0050] Figure 7 is a schematic cross-sectional view showing a configuration in which a block member is fixed to the cooling unit. Figure 7 shows a cross-sectional view of the portion along the line VII-VII in Figure 3. As shown in Figure 7, the cooling unit 37 includes a Peltier element 31, a heat sink 34, and a cooling fan 35. The Peltier element 31 has a heat transfer surface as its main surface, arranged, for example, along the XZ plane in Figure 7. The Peltier element 31 is fixed so that one of its heat transfer surfaces 31a is in contact with the surface of the block member 26. The heat conductive grease described above is applied to the heat transfer surface 31a.

[0051] The heat sink 34 is installed so as to be in contact with the Peltier element 31. Preferably, the heat sink 34 is installed so as to be in contact with the main surface on which heat is transferred from the Peltier element 31. The heat sink 34 is fixed so as to be in contact with the heat transfer surface 31b of the Peltier element 31 opposite to the heat transfer surface 31a. The cooling fan 35 is fixed so as to be in contact with the heat sink 34 on the side opposite to the Peltier element 31. In other words, the Peltier element 31, heat sink 34, and cooling fan 35 are arranged in that order from the block member 26 side.

[0052] The thermal insulation material 27 covers at least a portion of the top and side surfaces of the block member 26 from the outside. Specifically, the thermal insulation material 27 is arranged as shown in Figures 5 and 7, for example. Figure 8 is a photograph of the block member holding the liquid material container as shown in Figure 7. The thermal insulation material 27 shown in Figures 7 and 8 also covers a portion of the Peltier element 31. The thermal insulation material 27 is made of a material with very low thermal conductivity compared to the block member 26, etc., and is spread out in a thin plate shape. Specifically, for example, the thermal conductivity of the thermal insulation material 27 is 0.023 W / m / K. This is attached to the surface of the block member 26, etc. The thickness of the thermal insulation material 27 is preferably 5 mm or more.

[0053] The thermal insulation material 27 is not installed on the upper surface of the block member 26 in the area that overlaps with the inner circumferential surface 21A of the liquid material container 21 attached to the block member 26. A thermal insulation through-hole 25C is formed directly above the inner circumferential surface 21A, where there is no thermal insulation material 27. Furthermore, the thermal insulation material 27 is not installed on the lower surface of the block member 26 in the area that overlaps with the inner circumferential surface 21A in a plan view. Therefore, the thermal insulation material 27 is not positioned directly above or below the inner circumferential surface 21A. On the lower side of the block member 26, it is preferable that the thermal insulation material 27 is not installed in the area that overlaps with the area located outside the block through-hole 25B in the X and Y directions. In this way, the downward projection of the block member 26 in the Z direction relative to the liquid material container 21 can be suppressed in that area. This suppresses interference of the block member 26 with the workpiece (a member to be coated, such as a substrate or plate 8). It also suppresses an increase in the gap in the Z direction between the workpiece and the liquid material container 21. Therefore, problems such as a decrease in the accuracy of the application position of the application needle 24, caused by interference and increased gaps, can be suppressed. In addition, the possibility that the area to which the liquid material is applied will be limited, such as when the application needle 24 does not reach the workpiece, can be reduced. As a result, the liquid material can be applied to the workpiece more stably.

[0054] Figure 9 is a schematic side view showing how the frame surrounding the temperature control unit is fixed to the needle application unit and the housing unit by mounting parts. In Figure 9, as in Figure 7, a side view is shown from the negative side in the X direction. Figure 9 shows the same configuration as in Figure 7, with the addition of a frame 74, mounting parts 76, housing unit 75, and needle application unit 104. Although not shown in Figure 9, the frame 74 is fixed to the cooling unit 37 by screws. The frame 74 surrounds the lowest outer frame of the temperature control unit 28, which consists of a block member 26 covered with thermal insulation material 27 and a cooling unit 37. The frame 74 extends horizontally along the depth direction (X direction) of the paper in Figure 9, for example, the portion adjacent to the positive side in the Y direction of the block member 26 (first portion) (see Figures 3 and 4). Furthermore, the frame 74 has a portion (second portion) that, for example, largely overlaps with the portion where the Peltier element 31 is placed in a plan view from the Z direction, and this portion extends horizontally along the plane depth direction (X direction) of Figure 9 (see Figures 3 and 4). The second portion is positioned above the first portion in the Z direction.

[0055] Mounting portions 76 are installed so as to rest on the first and second portions of the frame 74. The mounting portion 76 on the first portion attaches the frame 74 (and the temperature control unit 28 enclosed within it) to the needle application portion 104. The mounting portion 76 on the second portion attaches the temperature control unit 28 to the housing portion 75. The housing portion 75 is a member having a shape that connects the uppermost part of the needle application portion 104 in the Z direction to the mounting portion 76 on the second portion.

[0056] The housing portion 75 has a third portion and a fourth portion, as described below. The third portion is fixed to the uppermost part of the needle application portion 104 in the Z direction. The third portion extends, for example, along the horizontal direction (Y direction). The fourth portion is fixed to the mounting portion 76 above the second portion. The fourth portion extends, for example, along the vertical direction (Z direction). At the boundary between the third portion and the fourth portion, it is bent such that its direction of extension changes by approximately 90°. As a result, when viewed from the negative side in the X direction, the housing portion 75 has a shape like an inverted L.

[0057] Figure 10 is a schematic side view showing the cooling fan of Figure 9 viewed from the negative side in the Y direction. As shown in Figure 10, when the cooling fan 35, located on the far right of Figure 9, is viewed from the side, the mounting portion 76 on the second part and the housing portion 75 (fourth part) above it are arranged side by side directly above it. A magnet 78 is embedded inside the mounting portion 76. Part of the surface of the magnet 78 may be exposed to the members constituting the mounting portion 76. The magnet 78 attaches the temperature control unit 28 (the second part of the frame 74 surrounding it) to the fourth part of the housing portion 75. In other words, the housing portion 75 is fixed to the temperature control unit 28 (frame 74). Similarly, the same magnet 78 is also embedded in the mounting portion 76 in the lower left of Figure 9. This magnet 78 fixes the temperature control unit 28 (the first part of the frame 74 surrounding it) to the lower part of the needle coating portion 104. The mounting portion 76 can be fixed in place by the magnet 78 if the housing portion 75, needle application portion 104, and frame 74, which are the mating members to be fixed, are made of a metal material that is attracted by the magnet. Alternatively, the mating members to which the mounting portion 76 is fixed may have magnets embedded in them, similar to the mounting portion 76. The embedded magnets may be exposed to the surface of the mating member.

[0058] Figure 11 is a photograph of the connection between the housing and the temperature control unit, including the fastener shown in Figure 10. In other words, Figure 11 shows a photograph of the part shown in Figure 10. As shown in Figures 10 and 11, the fastener 77 is locked to the fourth part of the housing 75. The fastener 77 may be a commercially available product that is generally known. For example, the fastener 77 may be a commercially available fastener. The fastener 77 has a shape that is bent, for example, in an L shape, as shown in Figure 10. The fastener 77 may be installed on the mounting part 76 and locked to a part of the housing 75. Alternatively, the fastener 77 may have two parts, a first part and a second part. That is, the fastener 77 is divided into a first part and a second part. An example of this is shown in Figure 11, for example. The first part is coupled to a part of either the frame 74 or the temperature control unit 28. The second part is coupled to the housing 75. Such a configuration is also possible. The coating mechanism 110 may have only a fastener 77, or it may have both a fastener 77 and a magnet 78 (a mounting portion 76 into which the magnet 78 is embedded).

[0059] <Shape characteristics of each component of the coating mechanism 110> In addition to the above, each component shown in each figure may have the following shape characteristics.

[0060] As shown in Figures 3 and 7, the block member 26 has a main body portion 26-1 and a fixing portion 26-2. The main body portion 26-1 and the fixing portion 26-2 constitute a single block member 26. The main body portion 26-1 is the central part of the entire block member 26. The main body portion 26-1 has a container mounting portion 26A for inserting the liquid material container 21.

[0061] As shown in Figure 7, the main body portion 26-1 protrudes downward in the Z direction from the region adjacent to the container mounting portion 26A, compared to the region outside that adjacent region in the X and Y directions (the region away from the container mounting portion 26A). The outer circumference of this portion slopes downward in a stepped manner. The lowest part of the liquid material container 21 (such as the outer bottom portion 21B2) can be placed in this portion.

[0062] The uppermost part of the main body 26-1 may also have an edge (projection) adjacent to the outer edge in the Y direction (horizontal direction) of the uppermost part of the liquid material container 21 (the part extending along the left-right direction in the figure). This edge (projection) is formed, for example, in the region of the main body 26-1 adjacent to the fixing part 26-2. It protrudes upward in the Z direction compared to the rest of the main body 26-1.

[0063] The fixing portion 26-2 is the region where the block member 26 is fixed to the cooling unit 37. The cooling unit 37 is adjacent to the negative side of the main body portion 26-1 in the Y direction. Attaching the cooling unit 37 to this portion is easy. The fixing portion 26-2 is positioned above the main body portion 26-1 in the Z direction. In the Z direction, the coordinate positions of the main body portion 26-1 and the fixing portion 26-2 partially overlap, but the fixing portion 26-2 protrudes above them. Also, the fixing portion 26-2 is not positioned at a location where the Z coordinate is equal to the lowest part of the main body portion 26-1. Therefore, the uppermost and lowest parts in the Z direction are stepped (have steps) at the boundary between the main body portion 26-1 and the fixing portion 26-2. In Figure 7, when the center line C in the left-right direction (Y direction) of the block member 26 is the axis of symmetry, the block member 26 is asymmetrical.

[0064] As shown in Figure 3, the fixing portion 26-2 of the block member 26 may be larger in the X direction (diagonal depth direction of the paper) than the main body portion 26-1. However, the fixing portion 26-2 may be smaller in the X direction than the main body portion 26-1, or they may be approximately equal in size. By increasing the X direction dimension of the fixing portion 26-2, the fixing portion 26-2 and the cooling unit 37 can be fixed over a larger area.

[0065] As shown in Figure 5, at the bottom of the block member 26, the outermost parts in the X and Y directions (horizontal direction) are formed on the container installation section 26A side (inward) compared to the areas other than the bottom. At the bottom of the block member 26, the heat insulating material 27 is formed thicker in the horizontal direction compared to the areas other than the bottom. This enhances the cooling effect of the liquid material, especially at the bottom of the block member 26.

[0066] The block member 26 has a bottom section (the area where the block through-hole 25B is formed) that protrudes inward in a plan view. The area immediately above this inwardly protruding area, and the area between it and the upper area, is thinner than the upper area in both the X and Y directions. This area is partially removed from the outer periphery. As a result, the outer periphery of this area forms a stepped structure. The block member 26 having the above configuration has a layout that is advantageous for achieving its intended effects.

[0067] As shown in Figure 3, the dimensions of the mounting portion 76 in the X and Y directions may be larger than those of the housing portion 75 (the fourth portion extending vertically) which is fixed directly above it. This increases the force with which the mounting portion 76 is fixed to the housing portion 75.

[0068] Frame 74 has a fifth portion connecting the first and second portions described above. The fifth portion is shown on the front side in the X direction in Figure 3 and in Figure 9. The fifth portion extends from the lower left to the upper right in Figures 3 and 9. The fifth portion extends diagonally in the YZ plane. In addition to the negative side (front side) in the X direction that appears in Figures 3 and 9, the fifth portion is similarly positioned on the positive side (back side) in the X direction. The temperature control unit 28 is positioned between this pair of fifth portions in the X direction. This fixes the position of the temperature control unit 28 in the X direction.

[0069] <Effects and Effects> The coating mechanism 110 according to this disclosure comprises a coating needle 24, a liquid material container 21, and a temperature control unit 28. The coating needle 24 coats the material to be processed (plate 8) with liquid material. The liquid material container 21 houses and holds the liquid material, and a container through-hole 25A is formed at the bottom through which the coating needle 24 can pass. The temperature control unit 28 can be fitted with the liquid material container 21. The temperature control unit 28 includes a block member 26 and a controller (cooling unit 37). The block member 26 can be fitted with the liquid material container 21. The cooling unit 37 is fixed to the block member 26 and can control the temperature of the block member 26. The block member 26 can be fitted with the liquid material container 21 so as to surround both the sides and the bottom of the liquid material container 21. The height (Z coordinate) of the lowest part 21P of the container through hole 25A of the liquid material container 21 attached to the block member 26 is equal to the height (Z coordinate) of the lowest part 26P of the block member 26.

[0070] A block member 26, whose temperature is controlled by a controller (cooling unit 37), surrounds both the sides and bottom of the liquid material container 21. Therefore, compared to surrounding only one of the sides or bottom, the block member 26 can uniformly control the temperature of the liquid material inside the liquid material container 21. This is because a wider area of ​​the liquid material container 21 is surrounded by the block member 26, and its temperature approaches that of the block member 26. As a result, the state of temperature-responsive liquid materials (those whose physical properties change, such as gelling, depending on the temperature) can be kept constant. Consequently, a wider variety of liquid materials can be stably applied while controlling their temperature. In other words, temperature-responsive liquid materials can be stably applied.

[0071] For example, if a liquid material contains a solvent that gels upon heating, it can be stably transferred by maintaining a sol state through cooling. In other words, the problem of difficulty in transfer with a coating needle due to the gelation of the liquid material can be suppressed. Furthermore, by controlling the temperature of the liquid material, the metabolism of cells contained in the liquid material can be reduced, thereby suppressing damage to the cells. In this embodiment, the liquid material in the liquid material container 21 is a gel raw material mainly composed of cells and biomaterials. Biomaterials include biologically derived protein materials. The gel raw material is a precursor for becoming a gel. That is, a gel is formed when the gel raw material is solidified. This allows for cell culture using the liquid material.

[0072] The height of the lowest part 21P of the container through-hole 25A is equal to the height of the lowest part 26P of the block member 26. This suppresses the downward projection of the block member 26 in the Z direction relative to the liquid material container 21. This suppresses interference of the block member 26 with the workpiece (a workpiece to be coated, such as a substrate or plate 8). It also suppresses an increase in the gap in the Z direction between the workpiece and the liquid material container 21. This suppresses problems such as a decrease in the accuracy of the coating position of the coating needle 24 caused by interference and an increase in the gap. It also reduces the possibility that the area to which the liquid material is coated will be limited, such as when the coating needle 24 cannot reach the workpiece. As a result, the liquid material can be applied to the workpiece more stably.

[0073] Furthermore, the container through-hole 25A does not protrude downward from the temperature control unit 28. As a result, the liquid material is less affected by the external temperature until just before application by the application needle 24. This makes it easier to control the temperature of the liquid material inside the liquid material container 21.

[0074] In the coating mechanism 110 described above, the outer peripheral surface 21B of the liquid material container 21 has an outer peripheral bottom portion 21B2 at the lower part of the liquid material container 21 that is inclined with respect to the extending direction (Z direction) of the coating needle 24. The height of the lowest part 21P of the outer peripheral bottom portion 21B2 and the lowest part 26P of the block member 26 may be equal. This provides the same effects as described above.

[0075] In the coating mechanism 110 described above, a block through-hole 25B is formed at the bottom of the block member 26. The diameter of the block through-hole 25B may be larger than the diameter of the container through-hole 25A. In this way, even if the liquid material container 21 is slightly misaligned during alignment, it will not affect the penetration operation of the coating needle 24. This is because even if the container through-hole 25A is misaligned, there is a high probability that the entire hole, or at least a part of it, will be positioned to overlap planarly with the block through-hole 25B.

[0076] In the coating mechanism 110 described above, the portion of the block member 26 adjacent to the outside of the block through-hole 25B may be inclined such that the thickness in the vertical direction (Z direction: direction along the vertical direction) gradually decreases as it approaches the block through-hole 25B.

[0077] In this way, the thickness of the bottom of the block member 26 is gradually changed. The bottom of the block member 26 is the region of the block member 26 that covers the bottom of the liquid material container 21. In the cross-sectional view of Figure 6, the outer circumferential surface of the bottom of the liquid material container 21 is an outer circumferential bottom 21B2 that is inclined with respect to the Z direction. Due to the outer circumferential bottom 21B2, the width of the liquid material container 21 narrows towards the center in a plan view. The bottom of the block member 26 has a bottom contact portion 26A2 as an inclined portion on its upper surface. Therefore, the bottom of the block member 26 becomes thinner in the vertical direction toward the center. As a result, the bottom contact portion 26A2 and the outer circumferential bottom 21B2 fit together so that they have a contact area as shown in Figure 6. Therefore, the bottom of the liquid material container 21 can be cooled by contact with the cooled block member 26. In other words, the entire liquid material container 21, including its bottom, can be uniformly temperature-controlled (cooled).

[0078] In the coating mechanism 110 described above, the controller is a cooling unit 37. The cooling unit 37 has a Peltier element 31 and a heat sink 34. The heat sink 34 is in contact with the Peltier element 31. This configuration is also acceptable.

[0079] As shown in Figure 7, the heat transfer surface 31a of the Peltier element 31 is in contact with the outer circumferential surface of the block member 26. The heat transfer surface 31b of the Peltier element 31 is in contact with the heat sink 34. In this way, the Peltier element 31 transfers heat from the heat transfer surface 31a side to the heat transfer surface 31b side of the block member 26. The heat transferred to the heat transfer surface 31b side is released to the outside of the block member 26 by the heat sink 34. In this way, the Peltier element 31 cools the block member 26 by transferring heat to the outside. As the block member 26 is cooled, the liquid material container 21 attached to it can also be cooled.

[0080] In Figure 7, a cooling fan 35 is installed on the outside of the heatsink 34. The air blown by the cooling fan 35 cools the heat that has moved from the block member 26 to the Peltier element 31 and then to the heatsink 34.

[0081] In the coating mechanism 110 described above, the insulating material may cover at least a portion of the top and side surfaces of the block member 26. This prevents external heat from being transferred from the area covered by the insulating material 27 to the block member 26, thus suppressing the problem of the cooled block member 26 rising again. Furthermore, by covering the block member 26 with the insulating material 27, heat exchange between the block member 26 and its surroundings can be minimized. Therefore, even if the cooling unit 37 is made small, the liquid material container 21 can be sufficiently cooled.

[0082] In the coating mechanism 110 described above, the heat insulating material 27 may have through-holes 25C formed in the upper surface of the block member 26 in a region that overlaps with the inner circumferential surface 21A of the liquid material container 21 attached to the block member 26. This prevents the problem of the heat insulating material 27 obstructing the penetration of the coating needle 24 into the liquid material container 21.

[0083] In the coating mechanism 110 described above, the block member may be made of aluminum. This allows for inexpensive and highly efficient temperature control of the block member 26. This is because aluminum has high thermal conductivity and is inexpensive.

[0084] The coating mechanism 110 may further include a housing portion 75 and a mounting portion 76. The housing portion 75 supports the coating needle 24 and the liquid material container 21. The mounting portion 76 attaches the temperature control unit 28 to the housing portion 75. The temperature control unit 28 may be attached to the housing portion 75 by a magnet 78 on the mounting portion 76.

[0085] In this way, the magnetic force of the magnet 78 firmly fixes the housing 75 and the temperature control unit 28 (and the frame 74 surrounding it). Also in this way, the magnetic force of the magnet 78 firmly fixes the needle coating unit 104 and the temperature control unit 28 (and the frame 74 surrounding it).

[0086] The coating mechanism 110 may further include a housing portion 75. The temperature control unit 28 can be fixed to the housing portion 75 by engaging the fastener 77 with the housing portion 75. Such a configuration is also acceptable.

[0087] In this way, the fastener 77 can fix the housing 75 and the temperature control unit 28 (and the frame surrounding it) more securely than in the case where it is not present (for example, when only the mounting portion 76 with the magnet 78 embedded is present). Furthermore, the needle application portion 104 and the temperature control unit 28 (and the frame surrounding it) can be fixed more securely.

[0088] Furthermore, the mounting portion 76 with the magnet 78 and the fastener 77 both allow the temperature control unit 28 to be easily attached to and detached from the housing portion 75 and the needle application portion 104. This reduces the cost of replacing the liquid material container 21 or the liquid material 70 inside it. Also, if the application mechanism 110 does not require temperature control of the liquid material container 21, the application can be performed with the temperature control unit 28 detached from the application mechanism 110.

[0089] A liquid material coating apparatus 100 according to this disclosure may include the coating mechanism 110 (see Figure 3) and a holding stage (X-axis stage 101, Y-axis stage 102) for holding the workpiece (plate 8), as shown in Figure 1. A liquid material coating apparatus 100 formed in this manner can achieve the same effects as described above.

[0090] Furthermore, the method for applying liquid materials using the above-described application mechanism 110 may have the following characteristics. In the method for applying liquid materials according to this disclosure, the liquid material attached to the tip of the application needle 24 is supplied to the workpiece (plate 8). In the step of supplying the liquid material, the supplied liquid material is cooled to below room temperature. This suppresses the gelation of liquid materials that gel upon heating, such as collagen and Matrigel. Therefore, liquid materials having such properties can be stably applied in a liquid (sol) state. The liquid material is cooled by the cooling unit 37 of the temperature control unit 28.

[0091] The performance of the temperature control unit 28 constituting the coating mechanism 110 described in the above embodiment was evaluated. Figure 12 is a schematic cross-sectional view showing the temperature measurement locations in Example 1 of the block member to which the liquid material container of Figure 5 is attached. In Figure 12, measurement positions A and B, where the temperature was measured in this embodiment, are shown on a block member 26 similar to that in Figure 5.

[0092] As shown in Figure 12, a liquid material container 21 for the coating method was installed in the temperature control unit 28 of the coating mechanism 110. The block member 26 and the liquid material container 21 were cooled by driving the Peltier element 31 (see Figure 7).

[0093] Figure 13 is a graph showing the results of temperature measurements at measurement positions A and B using thermocouples. Measurement position A is near the inner bottom portion 21A2 of the liquid material container 21. Measurement position B is the position where the upper part of the outer side surface portion 21B1 of the liquid material container 21 and the container mounting portion 26A of the block member 26 are in contact (adjacent).

[0094] At the time elapsed t1 shown in Figure 13, the set temperature of the cooling unit 37 was -1°C. The temperature at measurement position A at elapsed time t1 was 4.3°C. At the time elapsed t2 shown in Figure 13, the set temperature of the cooling unit 37 was set to -2°C. The temperature at measurement position A at elapsed time t2 was 3.2°C. The temperature at measurement position B was 2.7°C at elapsed time t1 and 1.7°C at elapsed time t2. The ambient temperature in the room where the coating mechanism 110 was installed at this time was 24°C. Elapsed time t1 is the point in time between 600 seconds and 1200 seconds from the start of measurement. Elapsed time t2 is the point in time after 1200 seconds from the start of measurement.

[0095] Generally, bio-derived protein materials such as collagen and Matrigel are used to construct three-dimensional cell tissues. Collagen and Matrigel maintain a sol state when cooled to 4°C. Therefore, it has been found that collagen and Matrigel can be used stably by using the temperature control unit 28 described above.

[0096] When the ambient temperature is around 24°C, it takes about 10 minutes from the start of cooling by the temperature control unit 28 until the temperature inside the liquid material container 21 stabilizes at the cooled temperature. For this reason, when using the coating mechanism 110, it is preferable to supply the liquid material into the liquid material container 21 at least 10 minutes after the start of cooling by the temperature control unit 28. In this way, the liquid material can be maintained at a cooled temperature of about 4°C.

[0097] A liquid material containing cells and a temperature-responsive bio-derived protein material is applied to the material to be processed. In this example, the stability of the liquid material application was evaluated using a temperature control unit. The room temperature during this evaluation was 24°C.

[0098] The coating materials used were a first coating solution (first bio-ink), a second coating solution (second bio-ink) supplied on top of it, and a culture medium dropped to immerse them. The first coating solution consisted of 10 mg / mL Matrigel as a solvent and normal human cardiac fibroblasts contained therein. The cell volume fraction in the first coating solution was 25%. The second coating solution consisted of phosphate-buffered saline (+) (PBS (+)) with methylcellulose added as a solvent. DMEM (High glucose) containing 10% by volume of FBS was used as the culture medium.

[0099] The first coating solution was filled into a liquid material container 21 that had been pre-cooled to 4°C or below. Specifically, the liquid material container 21, filled with the cooled first coating solution, was inserted and installed into the container mounting section 26A of the block member 26 of the temperature control unit 28, which had been pre-cooled to 1°C or more and 4°C or below. The temperature control unit 28 with the first coating solution installed in this manner was installed in the coating mechanism 110 (see Figure 3) together with the coating needle 24. The first coating solution was applied to the coating surface of the well 9A (see Figure 1) of the plate 8 using the needle coating section 104, and then the second coating solution was dropped from the dropping section 105 (see Figure 1) so as to cover the first coating solution. After that, the culture medium was dropped from a dropping section not shown in Figure 1. Cell tissue was constructed as a result of the above.

[0100] The process was basically carried out according to the procedure described above, but the state of the applied liquid was observed at appropriate intervals. The results are shown in Figures 14 to 17 below.

[0101] Figure 14 shows the observation results of the coated object immediately after the first coating solution was applied to the coating surface of the well. Figure 15 shows the observation results of the coated object after the culture medium was added to the first coating solution in Figure 14. Figure 14 shows the state immediately after the first coating solution was applied. Figure 15 shows the state after the second coating solution was dropped onto the first coating solution, and then the culture medium was dropped onto it. As shown in Figures 14 and 15, the coating solution containing Matrigel is applied stably. From this, it was found that Matrigel does not gel in the liquid material, but maintains a stably sol state in the liquid material container 21.

[0102] Figure 16 shows the observation of the coated object immediately after the first coating solution was filled into the liquid material container, allowed to stand for 35 minutes after cooling, and then applied to the coating surface of the well and the culture medium was added. Figure 17 shows the observation of the coated object from Figure 16 after it had stood for one day. In both Figures 16 and 17, the second coating solution was added dropwise to the first coating solution, and then the culture medium was added dropwise.

[0103] Matrigel requires 30 minutes to fully gel at 37°C. However, gelation of Matrigel progresses even at room temperature of around 25°C. As shown in Figure 16, even at room temperature of 24°C, the Matrigel in the liquid material container 21, which has been cooled for 35 minutes by the temperature control unit 28 installed in the room, can be applied from the application needle 24 without gelling, just as immediately after filling the liquid material container 21. Therefore, it was confirmed that the temperature control unit 28 has a cooling effect that allows Matrigel to maintain a stable sol state in the liquid material container 21 for more than 30 minutes, even at room temperature of 24°C. Furthermore, Figure 17 shows that the cells are adhering and spreading compared to Figure 16. Therefore, the cooling by the temperature control unit 28 does not affect the survival of cells in the liquid material container 21.

[0104] Furthermore, when the cooling unit 37 mounted on the temperature control unit 28 was set to -2°C, the liquid material (cell suspension) in the liquid material container 21 froze. From this, it was found that with the above setting temperature, the liquid material container 21 was cooled to below 0°C. Also, when the above setting temperature was set to 0°C, the liquid material (cell suspension) containing Matrigel neither gelled nor froze even after being left undisturbed for more than 30 minutes. From this, it can be concluded that with the above setting temperature, the temperature inside the liquid material container 21 was maintained between 0°C and 4°C.

[0105] <Other> In Example 2 above, a bio-derived protein material is used as the solvent included in the first coating solution. This material is selected because it is compatible with cells (has biocompatibility) and also has temperature responsiveness. However, in Example 2, other materials that are biocompatible and temperature responsive may be used as the solvent included in the first coating solution. Specifically, any of the following may be used as the solvent: protein, polysaccharide, or synthetic polymer. As the protein, either collagen or gelatin may be used. As the polysaccharide, either agarose or gellan gum may be used. As the synthetic polymer, poly-N-isopropylacrylamide (PIPAAm) may be used.

[0106] In the above-described Example 2, the temperature control unit 28 was used to suppress the gelation of the liquid material at room temperature. As in Example 2, the temperature control unit 28 may also be used to cool the liquid material in a liquid material container 21 containing only a small amount of liquid material that does not gel upon cooling, in order to suppress evaporation of the liquid material due to heating. When used for this purpose, the temperature control unit 28 allows a small amount of liquid material to be stably applied to the desired workpiece.

[0107] (Note) The various aspects of this disclosure are summarized below as an appendix.

[0108] (Note 1) An application mechanism comprising: an application needle for applying a liquid material to a workpiece; a liquid material container for storing and holding the liquid material, with a container through-hole formed at the bottom through which the application needle can pass; and a temperature control unit to which the liquid material container can be attached, wherein the temperature control unit includes a block member to which the liquid material container can be attached, and a controller fixed to the block member and capable of controlling the temperature of the block member, wherein the block member is capable of attaching the liquid material container so as to surround both the sides and the bottom of the liquid material container, and the height of the lowest part of the container through-hole of the liquid material container attached to the block member is equal to the height of the lowest part of the block member.

[0109] (Note 2) The coating mechanism according to Note 1, wherein the outer surface of the liquid material container has an outer bottom portion at the lower part of the liquid material container that is inclined with respect to the direction in which the coating needle extends, and the height of the lowest part of the outer bottom portion is equal to the height of the lowest part of the block member.

[0110] (Note 3) The coating mechanism according to Note 1 or 2, wherein a block through-hole is formed at the lowest part of the block member, and the diameter of the block through-hole is larger than the diameter of the container through-hole.

[0111] (Note 4) The coating mechanism described in Note 3, wherein the portion of the block member adjacent to the outside of the block through-hole is inclined such that its thickness in the vertical direction gradually decreases as it approaches the block through-hole.

[0112] (Note 5) The coating mechanism according to any one of Notes 1 to 4, wherein the controller is a cooling unit, and the cooling unit comprises a Peltier element and a heat sink in contact with the Peltier element.

[0113] (Note 6) The coating mechanism according to any one of Notes 1 to 5, wherein the upper surface and side surface of the block member are covered with an insulating material.

[0114] (Note 7) The coating mechanism according to Note 6, wherein the insulating material has through-holes formed in the upper surface of the block member in a region that overlaps with the inner circumferential surface of the liquid material container attached to the block member.

[0115] (Note 8) The coating mechanism according to any one of Notes 1 to 7, wherein the block member is made of aluminum.

[0116] (Note 9) The coating mechanism according to any one of Notes 1 to 8, further comprising a housing portion for supporting the coating needle and the liquid material container, and a mounting portion for attaching the temperature control unit to the housing portion, wherein the temperature control unit is attached to the housing portion by a magnet provided by the mounting portion.

[0117] (Note 10) The coating mechanism according to any one of Notes 1 to 8, further comprising a housing that supports the coating needle and the liquid material container, wherein the temperature control unit can be fixed to the housing by fasteners engaging with the housing.

[0118] (Note 11) A liquid material coating apparatus comprising a coating mechanism described in any one of Notes 1 to 10 and a holding base for holding the workpiece to be processed.

[0119] (Note 12) A method for applying a liquid material using the application mechanism described in any one of Notes 1 to 11, comprising the steps of: supplying the liquid material attached to the tip of the application needle to the workpiece; and cooling the liquid material supplied in the supply step to room temperature or below.

[0120] (Note 13) The method for applying the liquid material described in Note 12, wherein the liquid material is a gel raw material mainly composed of cells and biomaterials.

[0121] 20 Coating needle holder, 21 Liquid material container, 21A Inner circumferential surface, 21A1 Inner circumferential side surface, 21A2 Inner circumferential bottom surface, 21B Outer circumferential surface, 21B1 Outer circumferential side surface, 21B2 Outer circumferential bottom surface, 21P, 26P Bottommost part, 25A Container through hole, 25B Block through hole, 25C Insulation material through hole, 26 Block member, 26-1 Main body part, 26-2 Fixing part, 26A Container mounting part, 26A1 Side contact part, 26A2 Bottom contact part, 27 Insulation material, 31 Peltier element, 31a, 31b Heat transfer surface, 34 Heat sink, 35 Cooling fan, 35A Movable base, 37 Cooling unit, 41 Servo motor, 43 Cam, 44 Bearing, 45 Cam connecting plate, 46 Movable part, 74 Frame, 75 Housing part, 76 Mounting part, 77 Fastener, 78 Magnet, 100 Coating device, 101 X-axis stage, 102 Y-axis stage, 104 Needle coating part, 105 Dropping part, 106 Observation optical system, 107 Coating part, 110 Coating mechanism.

Claims

1. An application mechanism comprising: an application needle for applying a liquid material to a workpiece; a liquid material container for storing and holding the liquid material, with a container through-hole formed at the bottom through which the application needle can pass; and a temperature control unit to which the liquid material container can be attached, wherein the temperature control unit includes a block member to which the liquid material container can be attached, and a controller fixed to the block member and capable of controlling the temperature of the block member, wherein the block member is capable of attaching the liquid material container so as to surround both the sides and the bottom of the liquid material container, and the height of the lowest part of the container through-hole of the liquid material container attached to the block member is equal to the height of the lowest part of the block member.

2. The coating mechanism according to claim 1, wherein the outer circumferential surface of the liquid material container has an outer circumferential bottom portion at the lower part of the liquid material container that is inclined with respect to the extending direction of the coating needle, and the height of the lowest part of the outer circumferential bottom portion is equal to the height of the lowest part of the block member.

3. The coating mechanism according to claim 1, wherein a block through-hole is formed at the lowest part of the block member, and the diameter of the block through-hole is larger than the diameter of the container through-hole.

4. The coating mechanism according to claim 3, wherein the portion of the block member adjacent to the outside of the block through-hole is inclined such that its thickness in the vertical direction gradually decreases as it approaches the block through-hole.

5. The coating mechanism according to claim 1 or 2, wherein the controller is a cooling unit, and the cooling unit comprises a Peltier element and a heat sink in contact with the Peltier element.

6. The coating mechanism according to claim 1 or 2, wherein at least a portion of the upper surface and side surface of the block member is covered with an insulating material.

7. The coating mechanism according to claim 6, wherein the insulating material has through-holes formed in the upper surface of the block member in a region that overlaps with the inner circumferential surface of the liquid material container attached to the block member.

8. The coating mechanism according to claim 1 or 2, wherein the block member is made of aluminum.

9. The coating mechanism according to claim 1 or 2, further comprising a housing portion for supporting the coating needle and the liquid material container, and a mounting portion for attaching the temperature control unit to the housing portion, wherein the temperature control unit is attached to the housing portion by a magnet provided on the mounting portion.

10. The coating mechanism according to claim 1 or 2, further comprising a housing that supports the coating needle and the liquid material container, wherein the temperature control unit can be fixed to the housing by a fastener engaging with the housing.

11. A liquid material coating apparatus comprising the coating mechanism described in claim 1 and a holding base for holding the workpiece to be processed.

12. A method for applying a liquid material using the application mechanism described in claim 1, comprising the steps of: supplying the liquid material attached to the tip of the application needle to the workpiece; and cooling the liquid material supplied in the supply step to room temperature or below.

13. The method for applying a liquid material according to claim 12, wherein the liquid material is a gel raw material mainly composed of cells and biomaterials.

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