Method for manufacturing a thin-walled molded article and well plate

Abstract

The present invention has: a step for heating a resin or a metal in a state in which the resin or metal is sandwiched by a mold provided with a projection that is constituted from an elastic body having a heat resistance temperature higher than the temperature at which the resin or the metal softens, and a support body which is harder than the mold and which is softened by heat at a higher temperature than the resin or the metal, while a force is applied to the mold in the direction toward the resin or the metal.

Description

Technical Field

[0001] The present invention relates to a method for manufacturing a thin-walled molded product having a thin portion in a part of its shape and a well plate.

Background Art

[0002] A technique for molding a resin or the like into a thin structure or film is a very important technique in the development and manufacture of components of mobile phones, personal computers, and other precision devices. In particular, in recent years, in high-value-added products used in advanced research and medical fields, the technique of molding a resin or the like into a thin structure has become increasingly important. For example, a container for PCR used for amplifying nucleic acids in basic research and medical examinations is designed to have a thin thickness in order to efficiently conduct heat conduction into the container. In addition, a PCR container with a thin and flat bottom surface that enables PCR to be performed after analyzing cells with a microscope is also on the market.

[0003] Also, in microscopic observation, since the focal length of the objective lens becomes shorter as the magnification increases, the bottom surface of the container for high-magnification observation needs to be thin. Conventionally, products in which a thin cover glass or film is attached to the bottom surface of the container with an adhesive or the like have been sold as such high-magnification observation containers. However, in order to avoid problems such as elution of the adhesive and improve the strength of the container, products in which the container and the bottom surface are integrally molded have come to be sold.

[0004] A method for producing a thin molded product is a very much in-demand technique. Conventionally, methods using a complicated molding device incorporating many sensors and metal movable parts (for example, see Patent Document 1 and Patent Document 2), methods using a compound that easily produces a thin molded product (for example, see Patent Document 3), methods that perform strict condition setting (for example, see Patent Document 4), etc. have been reported.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

[0006] However, these methods often require very advanced processing technologies and expensive equipment, and the materials are also often limited. Generally, for the molding of products made of thermoplastic materials such as resins, molding methods such as injection molding and press molding using metal molds are used. However, it is very difficult to make the molten resin flow into the extremely thin parts of the mold in injection molding. Also, in other molding methods such as injection molding and press molding, for example, for resin processing with a thickness of 50 μm or less over a wide range of several tens of cm 2 or more with little error, molds that are extremely highly designed and manufactured with high precision, including deformation due to thermal expansion, and advanced molding processes are required. In addition to such technical difficulties, mold manufacturing usually costs a very high amount of one million to tens of millions of yen, so a high level of technology and a large amount of cost are required for the development and manufacture of such high-value-added products. There is also a method of attaching a thin film instead of molding a thin part, but not only does the manufacturing process become complicated, but problems such as elution of the adhesive for attachment and reduction of structural strength also occur, so integral molding is desirable.

[0007] Usually, molds used for molding resins and the like are made of rigid materials in order to reproduce the molded product well. However, for a structure with a thickness of several tens of μm over a length of several tens of cm 2To mold the entire molded article or at each point, it is necessary to produce a precise mold that is completely free of distortion over a wide range, and there is also a problem that no error is allowed even in the molding process. This is because due to some errors in the mold and the molding process, the thickness at each point of the molded article changes greatly, and furthermore, the mold breaks through the resin that is the source of the molded article, creating holes. Therefore, a method for simply and inexpensively molding a structure with a precise thin part is strongly desired in the development and manufacture of various precision instruments and research / medical instruments.

[0008] The present invention has been made in view of the above problems, and aims to provide a method for manufacturing a thin-walled molded article and a well plate that can simply and inexpensively mold a thin shape and can mold a thin structure with a small error over a wide area.

Means for Solving the Problems

[0009] The method for manufacturing a thin-walled molded article according to the first aspect of the present invention includes a step of heating a resin or metal while sandwiching it between a mold provided with protrusions made of an elastomer having a heat-resistant temperature higher than the temperature at which they soften, and a support that is harder than the mold and has a higher temperature at which it softens by heat than the resin or the metal, and applying a force in the direction of the resin or the metal to the mold, and a step of removing the mold.

[0010] According to this configuration, in the initial stage of the process, since the resin or metal softened by heat is sufficiently softer than the protrusions of the mold, the resin or metal is deformed by being pressed by the mold to form a depression. When the thickness of the resin or metal is sufficient, the force required to reduce the thickness of the bottom of the depression is mainly the force required to deform the resin or metal. On the other hand, as the process progresses and the thin-walled portion at the bottom of the depression becomes thinner, the force required to further reduce the thickness of the bottom of the depression is mainly the force required to discharge the resin or metal from the thin-walled portion against the frictional force acting between the mold or the support and the resin or metal, rather than the force required to deform the resin or metal. This force increases dramatically as the thickness of the thin-walled portion decreases. Also, as the thin-walled portion becomes more difficult to deform, the stress on the mold increases, and the protrusions of the mold made of an elastic body are crushed and deformed to expand the area of the thin-walled portion. At this time, the shape of the thin-walled portion becomes nearly flat. As the area of the thin-walled portion expands, the frictional force acting between the resin or metal and the mold or the support further increases. Therefore, as the thin-walled portion at the bottom of the depression becomes thinner, the force required to further reduce the thickness of the bottom of the depression increases exponentially. Therefore, even if an error occurs in the pressure applied to the thin-walled portion at each point of the workpiece due to the difference in the shape of each protrusion of the mold or the imprecision of the pressing process, this pressure error is a very small force compared to the pressure required to change the thickness of the sufficiently thin thin-walled portion. As a result, a shape with a thin thickness of the depression can be formed simply and inexpensively, and a structure with a thin thickness of the depression can be formed over a wide area with a small error. As a result, a thin-walled molded product with a flat bottom surface of the depression and a thin thickness (wall thickness) of the bottom surface of the depression can be manufactured. Thus, a shape with a thin thickness of the depression can be formed simply and inexpensively, and a structure with a thin thickness of the depression can be formed over a wide area with a small error. Furthermore, a thicker shape and a thinner shape can be integrally molded. Furthermore, a thicker shape and a thinner shape can be continuously formed on a curved surface. Also, no technology has been reported that can form an extremely thin structure with a wall thickness on the order of 10 μm, and this technology is also excellent in terms of precision.

[0011] The method for manufacturing a thin-walled molded article according to the second aspect of the present invention is the method for manufacturing a thin-walled molded article according to the first aspect, wherein the resin is an amorphous plastic having a glass transition temperature lower than the heat-resistant temperature of the elastic body of the mold, or a crystalline plastic having a low melting point.

[0012] According to this configuration, in the initial stage of the process, since the resin softened by heat is sufficiently softer than the protrusions of the mold, the resin is deformed by being pressed by the mold to form a depression. When the thickness of the resin is sufficient, the force required to reduce the wall thickness at the bottom of the depression is mainly the force required to deform the resin. On the other hand, as the process progresses and the thin-walled portion at the bottom of the depression becomes thinner, the force required to further reduce the wall thickness at the bottom of the depression becomes mainly the force required to discharge the resin from the thin-walled portion against the frictional force acting between the mold or the support and the resin, rather than the force required to deform the resin. This force increases dramatically as the thickness of the thin-walled portion decreases. Also, as the thin-walled portion becomes more difficult to deform, the stress received by the mold increases, and the protrusions of the mold made of an elastic body are crushed and deformed so as to expand the area of the thin-walled portion. At this time, the shape of the thin-walled portion becomes a shape close to flat. As the area of the thin-walled portion expands, the frictional force acting between the resin and the mold or the support further increases. Therefore, as the thin-walled portion at the bottom of the depression becomes thinner, the force required to further reduce the wall thickness at the bottom of the depression increases acceleratively. Therefore, even if an error occurs in the pressure applied to the thin-walled portion at each point of the workpiece due to the difference in the shape of each protrusion of the mold or the non-precision of the pressing process, this pressure error becomes a very small force compared to the pressure required to change the thickness of the sufficiently thin thin-walled portion. As a result, a shape with a thin wall thickness in the depression can be formed simply and inexpensively, and a structure with a thin wall thickness in the depression can be formed over a wide area with a small error.

[0013] The method for manufacturing a thin-walled molded article according to the third aspect of the present invention is the method for manufacturing a thin-walled molded article according to the first aspect, wherein the melting point of the metal is lower than the heat-resistant temperature of the elastic body of the mold.

[0014] According to this configuration, at the initial stage of the process, since the metal softened by heat is sufficiently softer than the protrusions of the mold, the metal is deformed by being pressed by the mold to form a depression. When the thickness of the metal is sufficient, the force required to reduce the thickness of the bottom of the depression is mainly the force required to deform the metal. On the other hand, as the process progresses and the thin-walled portion at the bottom of the depression becomes thinner, the force required to further reduce the thickness of the bottom of the depression is mainly the force required to discharge the metal from the thin-walled portion against the frictional force acting between the mold or the support and the metal, rather than the force required to deform the metal. This force increases exponentially as the thickness of the thin-walled portion decreases. Also, as the thin-walled portion becomes more difficult to deform, the stress on the mold increases, and the protrusions of the mold made of an elastic body are crushed and deformed to expand the area of the thin-walled portion. At this time, the shape of the thin-walled portion becomes nearly flat. As the area of the thin-walled portion expands, the frictional force acting between the metal and the mold or the support further increases. Therefore, as the thin-walled portion at the bottom of the depression becomes thinner, the force required to further reduce the thickness of the bottom of the depression increases at an accelerating rate. Thus, even if an error occurs in the pressure applied to the thin-walled portion at each point of the workpiece due to differences in the shape of each protrusion of the mold or the imprecision of the pressing process, this pressure error becomes a very small force compared to the pressure required to change the thickness of the sufficiently thin thin-walled portion. As a result, a shape with a thin wall thickness of the depression can be formed simply and inexpensively, and a structure with a thin wall thickness of the depression can be formed over a wide area with a small error.

[0015] The method for manufacturing a thin-walled molded article according to the fourth aspect of the present invention is the method for manufacturing a thin-walled molded article according to the first or second aspect, wherein the resin is a thermoplastic resin.

[0016] According to this configuration, a shape with a small thickness can be formed simply and inexpensively. Also, a structure with a small thickness can be formed over a wide area with a small error.

[0017] The method for manufacturing a thin-walled molded product according to the fifth aspect of the present invention is the method for manufacturing a thin-walled molded product according to any one of the first to fourth aspects, and includes a step of manufacturing a jig with a through-hole provided with a thin film of an elastic body on the surface, a step of sucking the thin film through the through-hole from the back side, a step of injecting a solution of the elastic body onto the thin film bent after sucking, and a step of heating and curing the solution to form the mold.

[0018] According to this configuration, a mold provided with protrusions made of an elastic body can be manufactured. By heating this mold with the surface provided with the protrusions in contact with a resin or metal whose temperature for deformation by heat is lower than the heat resistance temperature of the mold, a thin-walled molded product with a flat bottom surface of the depression and a thin thickness of the bottom surface of the depression can be manufactured.

[0019] The method for manufacturing a thin-walled molded product according to the sixth aspect of the present invention is the method for manufacturing a thin-walled molded product according to any one of the first to fifth aspects, and the elastic body is polydimethylsiloxane (PDMS).

[0020] According to this configuration, a shape with a thin wall thickness of the depression can be molded simply and inexpensively, and a structure with a thin wall thickness of the depression can be molded with a small error over a wide area.

[0021] The method for manufacturing a thin-walled molded product according to the seventh aspect of the present invention is the method for manufacturing a thin-walled molded product according to any one of the first to sixth aspects, and the thin-walled molded product is a well plate.

[0022] According to this configuration, a shape with a thin wall thickness of the depression can be molded simply and inexpensively, and a structure with a thin wall thickness of the depression can be molded with a small error over a wide area.

[0023] The well plate according to the eighth aspect of the present invention is made of resin and is a well plate provided with at least one well, the well has a round bottom, and the thickness of the central part of the bottom of the well is 200 μm or less.

[0024] According to this configuration, since the well has a round bottom, the cells seeded in the well gather at the center of the bottom of the well, so that the observation of the cells can be facilitated. Further, since the thickness of the central portion of the bottom of the well is 200 μm or less, it can be observed with a high magnification microscope.

[0025] The well plate according to the ninth aspect of the present invention is the well plate according to the eighth aspect, and the ratio of the radius of curvature of the bottom surface of the well divided by the radius of the well is 0.7 to 1.5.

[0026] According to this configuration, since the well has a round bottom, the cells seeded in the well gather at the center of the bottom of the well, so that the observation of the cells can be facilitated.

[0027] The well plate according to the ninth aspect of the present invention is the well plate according to the eighth aspect, and the ratio of the radius of curvature of the bottom surface of the well divided by the radius of the well is 0.7 to 1.5.

[0028] According to this configuration, the range of the shape of the bottom surface of the well is defined.

[0029] The well plate according to the tenth aspect of the present invention is the well plate according to the eighth or ninth aspect. When the ratio of the radius of curvature of the bottom surface of the well divided by the radius of the well is y and the central portion of the bottom surface of the well is x [μm], the ratio y is within ± 10% of the value of y = -0.0093x + 0.9924 in the range where the central portion of the bottom surface of the well is 7 to 19 μm, and within ± 10% of the value of y = 0.0028x + 0.7572 in the range where the central portion of the bottom surface of the well is 19 to 200 μm.

[0030] According to this configuration, the range of the shape of the bottom surface of the well is defined.

[0031] The well plate according to the eleventh aspect of the present invention is the well plate according to any one of the eighth to tenth aspects, and the average thickness of the central portion of the bottom surface of the well is 7 μm or more.

[0032] According to this configuration, a well plate having a strength that can prevent damage to most wells can be realized.

[0033] The well plate according to the twelfth aspect of the present invention is the well plate according to any one of the eighth to eleventh aspects, wherein the thickness of the central portion of the bottom surface of the well is 150 μm or less.

[0034] According to this configuration, since the well has a round bottom, the cells seeded in the well gather at the center of the bottom of the well, facilitating the observation of the cells. Further, since the thickness of the central portion of the bottom surface of the well is 150 μm or less, even with an oil-immersion 100× objective lens, the focus can be adjusted to the cells present on the bottom surface of the well, and detailed microscopic analysis of a small number of cells starting from a single cell can be reliably performed.

Advantages of the Invention

[0035] According to one aspect of the present invention, a thin-thickness shape can be formed simply and inexpensively. Also, a thin-thickness structure can be formed over a wide area with a small error. Further, a thick shape and a thin shape can be integrally formed. Furthermore, a thick shape and a thin shape can be continuously formed on a curved surface. Also, there has been no reported press molding technology capable of forming an extremely thin structure with a wall thickness on the order of 10 μm, and this technology is also excellent in terms of precision.

Brief Description of the Drawings

[0036]

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Mode for Carrying Out the Invention

[0037] Hereinafter, each embodiment will be described with reference to the drawings. However, a more detailed description than necessary may be omitted. For example, detailed descriptions of well-known matters and duplicate descriptions of substantially the same configurations may be omitted. This is to avoid making the following description unnecessarily redundant and to facilitate the understanding of those skilled in the art.

[0038] <The First Embodiment> In this embodiment, instead of precisely constructing a mold or a molding process, it was devised to add a shape correction function to the mold itself. That is, in this embodiment, at least the protruding part of the mold is made of a material (i.e., an elastic body) that can be flexibly deformed, so that the mold deforms so that the thicknesses of the thin parts of the material that becomes the molded product are the same, and a thin structure can be molded with a small error even over a large area.

[0039] In this embodiment, as an example of a thin-walled molded product having a thin portion in a part of its shape, a well plate is cited, and a method for manufacturing the well plate will be described. In this embodiment, the thin-walled molded product to be molded (here, a well plate as an example) may also be referred to as a molded object.

[0040] With reference to FIG. 1 and using FIG. 2, a method for manufacturing the well plate according to this embodiment will be described. FIG. 1 is a schematic diagram showing a schematic process of the method for manufacturing the well plate according to this embodiment. FIG. 2 is a flowchart showing an example of the flow of the method for manufacturing the well plate according to this embodiment.

[0041] (Step S10) First, a thin film of an elastic body is formed. Here, the elastic body is, for example, polydimethylsiloxane (PDMS), and a PDMS thin film is formed.

[0042] (Step S20) Next, using the thin film (for example, the PDMS thin film) formed in Step S10, a jig with through holes provided with a thin film of an elastic body on its surface is created. The jig with through holes has through holes provided, for example, in an array of 24 columns x 16 rows so as to correspond to the holes of the well plate. As a result, as shown in the partial cross-sectional view of FIG. 1(a), a PDMS thin film 111 is formed on the surface of the jig 10 with through holes.

[0043] (Step S30) Next, as shown in the partial cross-sectional view of FIG. 1(b), the PDMS thin film is sucked and / or depressurized at a set pressure through the through holes from the back side of the jig 10 with through holes. As a result, the PDMS thin film bends in the direction of arrow A1 in FIG. 1(b). Here, as an example, the thin film is sucked by depressurizing.

[0044] (Step S40) Next, as shown in the partial cross-sectional view of FIG. 1(c), a solution 112 of an elastic body (for example, a PDMS solution) is injected from above the PDMS thin film that has bent after being sucked.

[0045] (Step S50) Next, as shown in the partial cross-sectional view of FIG. 1(d), a mold (e.g., a PDMS mold) is formed by heating and curing an elastomer solution 112 (e.g., a PDMS solution). In this way, with the PDMS thin film deformed into a convex shape, a material to be a mold (e.g., PDMS) is injected and cured, whereby a PDMS cured layer 112b is formed, and a mold 110 having protrusions in an array of, for example, 24 columns x 16 rows with PDMS is formed. The mold 110 has a PDMS cured layer 112b formed on the PDMS thin film 111.

[0046] (Step S60) Next, as shown in the partial cross-sectional view of Fig. 1(e), with the surface of the mold 110 (e.g., PDMS mold) provided with protrusions (also referred to as the convex surface) in contact with the resin plate 114, while applying a force to the mold 110 in the direction of the resin plate 114 (the directions of arrows A2 and A3 in Fig. 1(e)) (here, as an example, while pushing the mold from the surface opposite to the surface provided with the protrusions), heat is applied (e.g., hot pressing is performed at a predetermined temperature exceeding the glass transition point of the mold 110 and the glass transition point of the resin plate 114). Here, the resin plate 114 is made of a thermoplastic resin. Examples of such thermoplastic resins include polyolefin resins such as polyethylene (PE), polypropylene (PP), polycycloolefin, and ethylene-α-olefin copolymers (e.g., ethylene-propylene copolymer), polystyrene-based resins such as polystyrene, styrene-butadiene-styrene block copolymer (SBS), styrene-ethylene-butylene-styrene block copolymer (SEBS), styrene-isoprene-styrene block copolymer (SIS), styrene-ethylene-propylene-styrene block copolymer (SEPS), and hydrogenated styrene-butadiene random copolymer (HSBR), polyester-based resins such as polybutylene terephthalate, polyethylene terephthalate, and polyethylene naphthalate, polyamide-based resins such as nylon 6, nylon 66, and nylon 46, acrylic resins such as polymethyl methacrylate (PMMA), polycarbonate-based resins, polyvinyl chloride-based resins, and polyvinylidene chloride-based resins. These can be exemplified, and they can be used alone or in a mixture of two or more. This resin plate 114 is provided on a glass plate 113 which is an example of a support.

[0047] As a result, as shown in the partial cross-sectional view of Fig. 1(f), the protrusions of the PDMS mold are deformed and the tips of the protrusions become flat. Accordingly, the bottom surface of the depression (also referred to as a well) formed in the resin plate becomes flat, and the thickness between the bottom surface of the depression (well) and the bottom surface of the resin plate (hereinafter referred to as the thickness of the bottom surface of the depression (well)) can be made thinner.

[0048] Here, the resin plate is a resin whose temperature at which it deforms due to heat is lower than the heat resistance temperature of the mold. Specifically, the glass transition point in the case where the resin plate is an amorphous plastic, or the melting point in the case of a crystalline plastic, is lower than the heat resistance temperature of the elastomer (e.g., PDMS) of the mold. In the process of processing the resin plate, at the initial stage of the process, since the resin softened by heat is sufficiently softer than the protrusions of the mold, the resin is deformed by being pressed by the mold to form a depression. When the thickness of the resin is sufficient, the force required to thin the wall thickness at the bottom of the depression is mainly the force required to deform the resin. On the other hand, as the process progresses and the thin-walled portion at the bottom of the depression becomes thinner, the force required to further thin the wall thickness at the bottom of the depression is mainly the force required to discharge the resin from the thin-walled portion against the frictional force acting between the mold or the support and the resin, rather than the force required to deform the resin. This force increases exponentially as the thickness of the thin-walled portion decreases. Also, as the thin-walled portion becomes more difficult to deform, the stress on the mold increases, and the protrusions of the mold made of an elastomer are crushed and deformed so as to expand the area of the thin-walled portion. At this time, the shape of the thin-walled portion becomes nearly flat. As the area of the thin-walled portion expands, the frictional force acting between the resin and the mold or the support further increases. Therefore, as the thin-walled portion at the bottom of the depression becomes thinner, the force required to further thin the wall thickness at the bottom of the depression increases acceleratively. Therefore, even if an error occurs in the pressure applied to the thin-walled portion at each point of the processed product due to the difference in the shape of each protrusion of the mold or the non-precision of the pressing process, this pressure error becomes a very small force compared to the pressure required to change the thickness of the sufficiently thin thin-walled portion. As a result, a shape with a thin wall thickness of the depression can be formed simply and inexpensively, and a structure with a thin wall thickness of the depression can be formed over a wide area with a small error.

[0049] (Step S70) Next, the mold 110 is removed. As a result, as shown in the upper partial cross-sectional view of FIG. 1(g), a well plate 120 (e.g., a multi-well plate) with a flat bottom surface of the depression (well) and a thin thickness of the bottom surface of the depression (well) can be manufactured (see the lower perspective view of FIG. 1(g)). Specifically, for example, a well plate having 384 wells with a bottom thickness of the depression (well) of about 10 μm can be manufactured.

[0050] In this embodiment, as an example, resin is used as the material of the well plate, but it is not limited thereto, and a metal whose deformation temperature by heat is lower than the heat resistance temperature of the mold may be used. Specifically, the melting point of the metal may be lower than the heat resistance temperature of the elastomer of the mold. With this configuration, in the initial stage of the process, since the metal softened by heat is sufficiently softer than the protrusions of the mold, the metal is deformed by being pressed by the mold to form a depression. When the thickness of the metal is sufficient, the force required to thin the wall thickness of the bottom of the depression is mainly the force required to deform the metal. On the other hand, as the process progresses and the thin-walled portion at the bottom of the depression becomes thinner, the force required to further thin the wall thickness of the bottom of the depression is mainly the force required to discharge the metal from the thin-walled portion against the frictional force acting between the mold or the support and the metal, rather than the force required to deform the metal. This force increases dramatically as the thickness of the thin-walled portion decreases. Also, as the thin-walled portion becomes more difficult to deform, the stress on the mold increases, and the protrusions of the mold made of an elastomer are crushed and deformed to expand the area of the thin-walled portion. At this time, the shape of the thin-walled portion becomes nearly flat. As the area of the thin-walled portion expands, the frictional force acting between the metal and the mold or the support further increases. Therefore, as the thin-walled portion at the bottom of the depression becomes thinner, the force required to further thin the wall thickness of the bottom of the depression increases exponentially. Therefore, even if an error occurs in the pressure on the thin-walled portion at each point of the workpiece due to the difference in the shape of each protrusion of the mold or the imprecision of the pressing process, this pressure error becomes a very small force compared to the pressure required to change the thickness of the sufficiently thin thin-walled portion. As a result, a thin-walled molded product with a flat bottom surface of the depression and a thin thickness (wall thickness) of the bottom surface of the depression can be manufactured.

[0051] As described above, the method for manufacturing a thin-walled molded article according to the present embodiment includes a step of heating a resin or a metal while applying a force in the direction of the resin or the metal to a mold provided with protrusions made of an elastomer having a heat resistance temperature higher than the temperature at which they soften, with the resin or the metal sandwiched between the mold and a support that is harder than the mold and has a higher temperature at which it softens by heat than the resin or the metal, and a step of removing the mold.

[0052] With this configuration, at the initial stage of the process, since the resin or metal softened by heat is sufficiently softer than the projections of the mold, the resin or metal is deformed by being pressed by the mold to form a depression. When the thickness of the resin or metal is sufficient, the force required to reduce the wall thickness at the bottom of the depression is mainly the force required to deform the resin or metal. On the other hand, as the process progresses and the thin-walled portion at the bottom of the depression becomes thinner, the force required to further reduce the wall thickness at the bottom of the depression is mainly the force required to discharge the resin or metal from the thin-walled portion against the frictional force acting between the mold or the support and the resin or metal, rather than the force required to deform the resin or metal. This force increases exponentially as the thickness of the thin-walled portion decreases. Also, as the thin-walled portion becomes more difficult to deform, the stress on the mold increases, and the projections of the mold made of an elastic body are crushed and deformed to expand the area of the thin-walled portion. At this time, the shape of the thin-walled portion becomes nearly flat. As the area of the thin-walled portion expands, the frictional force acting between the resin or metal and the mold or the support further increases. Therefore, as the thin-walled portion at the bottom of the depression becomes thinner, the force required to further reduce the wall thickness at the bottom of the depression increases acceleratively. Thus, even if an error occurs in the pressure applied to the thin-walled portion at each point of the workpiece due to the difference in the shape of each projection of the mold or the imprecision of the pressing process, this pressure error is a very small force compared to the pressure required to change the thickness of the sufficiently thin thin-walled portion. As a result, a shape with a thin wall thickness of the depression can be formed simply and inexpensively, and a structure with a thin wall thickness of the depression can be formed over a wide area with a small error. As a result, a thin-walled molded product can be manufactured in which the bottom surface of the depression is flat and the thickness (wall thickness) of the bottom surface of the depression is thin. As a result, a thin-walled molded product (for example, a well plate) can be manufactured in which the bottom surface of the depression is flat and the thickness (wall thickness) of the bottom surface of the depression is thin. Thus, a shape with a thin wall thickness of the depression can be formed simply and inexpensively, and a structure with a thin wall thickness of the depression can be formed over a wide area with a small error. Furthermore, a thicker shape and a thinner shape can be integrally molded. Furthermore, a thicker shape and a thinner shape can be continuously formed on a curved surface.

[0053] In addition, the method for manufacturing a thin-walled molded article according to this embodiment further includes a step of manufacturing a jig with a through-hole provided with a thin film of an elastic body, a step of sucking the thin film through the through-hole from the back side, a step of injecting a solution of the elastic body onto the deflected thin film after suction, and a step of heating and curing the solution to form the mold.

[0054] With this configuration, a mold provided with protrusions made of an elastic body can be manufactured. By heating this mold in a state where the surface provided with the protrusions is in contact with a resin or metal whose temperature for deformation by heat is lower than the heat resistance temperature of the mold while applying a force in the direction of the resin to the mold, a thin-walled molded article (for example, a well plate) with a flat bottom surface of the depression and a thin thickness of the bottom surface of the depression can be manufactured.

[0055] <Example 1> Hereinafter, the method of each step according to Example 1 will be described. <An example of the method for manufacturing a PDMS thin film> Here, an example of the method for manufacturing a PDMS thin film in step S10 of FIG. 2 will be described. A PDMS solution was dropped onto a polyethylene naphthalate (PEN) film cut out to a first size, left for a certain period of time to remove bubbles, and then spin-coated at a predetermined rotational speed for a first set time using a spin coater. This was placed on a strengthened glass (for example, Tempax) of a second size larger than the first size and heated at a specified temperature higher than room temperature for a second set time. The PDMS thin film together with the strengthened glass (for example, Tempax) was taken out and cooled in a clean booth. Two silicone rubber double-sided tapes were attached to the frame portion of a hollow acrylic frame, and this was pressed onto the above PDMS thin film to adhere the acrylic frame and the PDMS thin film with the double-sided tape. The PDMS thin film was peeled off from the PEN film with the acrylic frame as a supporting substrate. Thereby, a frame with a PDMS thin film provided in the hollow portion of the acrylic frame (see FIG. 3) was manufactured.

[0056] <Method for manufacturing a jig with a through-hole provided with a PDMS thin film on the surface> Using FIG. 3, a method for fabricating a jig with through holes provided on the surface with a PDMS thin film will be described. FIG. 3 is an exploded perspective view for explaining the attachment of the PDMS thin film to the jig with through holes. In FIG. 3, the frame 11 with a PDMS thin film provided with the PDMS thin film 111 is fabricated by the method for fabricating the PDMS thin film described above.

[0057] The well plate processing member 12 removes the adhesive from the bottom surface of a well plate without a bottom surface (here, a 384-well plate without a bottom surface as an example), and at the time of attachment, this bottom surface side is set to the upper side (the side of the frame 11 with a PDMS thin film). The well plate processing member 12 has the outer peripheral frame portion on the bottom surface side cut by a predetermined length (for example, after processing with an ultrasonic cutter and then chamfering), and is formed into a portion for fitting a PDMS thin film acrylic frame. A packing 17 is provided on the contact surface with the plate 14 with a plurality of through holes described later using a silicone-based adhesive and a polypropylene plate.

[0058] The shim plate 13 for height adjustment is placed on the outer peripheral frame portion of the well plate processing member, sandwiched between the frame 11 with a PDMS thin film, and adjusted so that the height of the well portion of the well plate processing member 12 and the height of the frame 11 with a PDMS thin film are approximately the same.

[0059] The plate 14 with a plurality of through holes is, for example, an acrylic plate in which a plurality (for example, 384) of through holes are provided at intervals. The stage 15 is, for example, a stage made of aluminum. The stage 15 is placed in the die-cast box 16 described later and supports the plate 14 with a plurality of through holes from below so that it does not warp during suction.

[0060] The die-cast box 16 is a die-cast box made of aluminum. The die-cast box 16 has a rectangular bottom plate and four side plates connected to each side of the bottom plate. A through-hole is provided by threading on one of the side plates of the die-cast box 16, and a hollow member 18 (for example, a tube joint) is attached to the through-hole. This hollow member 18 serves as an air intake for suction. The die-cast box 16 has an open top surface, and packings 19 are provided at the upper surface edges of each of the four side plates. Thus, by the close contact of the packing 17 and the packing 19, it is possible to seal the space between the bottom surface of the well plate processing member 12 and the die-cast box 16 so that air does not escape.

[0061] As shown in FIG. 3, by assembling each component shown in FIG. 3, a jig with a through-hole provided with a PDMS thin film on its surface is fabricated. Then, by sucking air from the hollow member 18, the PDMS thin film is sucked.

[0062] With reference to FIG. 4, the relationship between the suction pressure and the distance by which the center of the PDMS thin film changes due to suction will be described. FIG. 4 is a graph showing an example of the experimental results of the relationship between the suction pressure and the change distance of the center of the PDMS thin film. The vertical axis represents the change distance of the center of the PDMS thin film, and the horizontal axis represents the suction pressure. This FIG. 4 is the result of measuring the change distance of the center of the PDMS thin film using a confocal microscope while changing the suction pressure. As shown in FIG. 4, it is shown that the change distance of the center of the PDMS thin film increases as the suction pressure increases. As shown in FIG. 4, by changing the suction pressure, a mold having protrusions of a desired height can be fabricated, so that a well plate of a desired depth can be fabricated. The measurement was carried out by the following method.

[0063] <Experimental method for measuring the change distance of the center of the PDMS thin film> The PDMS mold fabrication system of Fig. 3 was set upside down on the stage of a confocal microscope. At this time, the upper optical system (such as a halogen lamp) of the confocal microscope was tilted backward, and the safety switch at the base of the upper optical system was constantly pressed by a silicone plate. A diaphragm pump and a regulator were connected to the set of PDMS mold fabrication fixtures and suction was performed at -0 to -0.06 mPa, and the 3D shape of the PDMS thin film at that time was observed in the ZStack mode. The deformation distance of the film center due to suction was measured by detecting the reflection of a 488 nm laser for the Z coordinates of the outside and the center of the well, and obtained from the difference (n = 4 wells, excitation wavelength: 488 nm, fluorescence wavelength: 483 - 493 nm). Also, the film thickness was obtained from the difference in the Z coordinates of the upper and lower surfaces of the film in the same way (n = 4 wells, excitation wavelength: 488 nm, fluorescence wavelength: 483 - 493 nm).

[0064] When suction was performed at 0.027 mPa, the change distance at the center of the PDMS thin film was 1664.7 ± 12.5 μm (n = 4 wells). As an example, this 0.027 mPa was set as the suction pressure during the mold fabrication this time. The thickness of the PDMS thin film was 46.3 ± 0.7 μm (n = 4 wells).

[0065] <Method for fabricating a PDMS mold> Subsequently, an example of the method for fabricating a PDMS mold will be described with reference to Fig. 5. Fig. 5 is a schematic diagram for explaining the method for fabricating a PDMS mold. As shown in Fig. 5, using the PDMS mold fabrication system of Fig. 3, a mold having a protrusion with a height of about 1.65 mm is fabricated from PDMS.

[0066] In the PDMS mold manufacturing system, a silicone rubber embankment 21 was placed around the periphery of the well plate processing member 12 on the PDMS thin film so as to surround it from four sides. A predetermined amount of PDMS solution was dropped from above, and nitrogen gas was blown to spread the PDMS solution so as to cover the wells. This was placed in a desiccator and degassed under reduced pressure. A diaphragm pump and a regulator were connected to the hollow member 18 in the PDMS mold manufacturing system, and a reduced pressure of -0.027 mPa was applied. A specified amount of PDMS solution 22 was dropped onto the strengthened glass 23 (for example, Tempax), and by bringing the strengthened glass 23 into contact with the PDMS solution 22 on the PDMS thin film starting from this, the strengthened glass 23 was covered so that no bubbles would enter. This was placed on the lower stage of a hot press machine set at a first temperature higher than room temperature, the jack was raised, and the cylindrical rubber 24 connected to the center of the strengthened glass 23 was pressed down as a cushion on the upper stage. The space between the upper and lower stages of the hot press machine was covered with aluminum foil for heat preservation. After heating and curing for a specified time, the PDMS mold manufacturing system was disassembled to take out the PDMS mold (PDMS + Tempax), and the PDMS was completely cured by heating at a second temperature higher than the first temperature for a predetermined time.

[0067] Figure 6(a) is an overall image of the PDMS mold taken from above with a stereomicroscope. Figure 6(b) is an enlarged image of the PDMS mold taken from above with a stereomicroscope. Figure 6(c) is an enlarged image of the PDMS mold taken from an oblique upper angle with a stereomicroscope. Figure 6(d) is an enlarged image of the PDMS mold taken from another oblique upper angle with a stereomicroscope. As a result of manufacturing the PDMS mold, as shown in Figure 6(d), a PDMS mold with 384 protrusions with smooth arc-shaped vertices arranged in an array was manufactured. As a result of measurement by the following measurement method using a confocal microscope, the protrusion height was 1650.3 ± 7.2 μm (n = 4 wells, mean ± standard deviation), and it was confirmed that a mold with a shape close to the target height (about 1650 μm) could be manufactured. Here, the protrusion height represents the mean ± standard deviation of the protrusion heights of 4 wells located at the center of each plate.

[0068] <Measurement method of protrusion height> The appearance of the fabricated PDMS mold was photographed and observed under a stereomicroscope. Also, the PDMS mold was placed on the stage of a confocal microscope with the protrusions facing downwards, and the Z coordinates of the outer side of the well and the tip of the protrusion (also referred to as the convex part) were measured by detecting the reflection of a 488 nm laser. The convex height of the PDMS mold was determined from the difference (n = 4 wells, excitation wavelength: 488 nm, fluorescence wavelength: 483 - 493 nm). In addition, the 3D shape was confirmed by the autofluorescence of the PDMS mold (excitation wavelength: 405 nm, fluorescence wavelength: 435 - 445 nm).

[0069] To confirm the forming accuracy of the entire mold, all 384 wells of a single well plate were observed in a direction perpendicular to the bottom surface of the well using a confocal microscope, and the height of all the protrusions was measured (n = 384 wells, excitation wavelength: 488 nm, fluorescence wavelength: 483 - 493 nm). As a result, the average protrusion height was 1623.5 ± 26.5 μm (n = 384 wells: mean ± standard deviation).

[0070] <Well plate forming method> Using a mold with a protrusion height of approximately 1.65 mm as an example, thermoplastic molding of polycarbonate was performed, and the appearance of the molded product was observed and the 3D shape of each well was analyzed using a confocal microscope.

[0071] A resin plate (e.g., a polycarbonate plate) was placed on a strengthened glass (e.g., Tempax) coated with PDMS for release, and a PDMS mold was placed on it. After that, it was set on a press stage heated to a first predetermined temperature, preheated for a first set time, and then pressed with a predetermined force for a second set time longer than the first set time. After the pressing was completed, the mold was water-cooled, the pressure was released when it reached a second predetermined temperature lower than the first predetermined temperature, and the molded product was taken out. The appearance of the molded product was photographed and observed with a stereomicroscope. The damaged state of the bottom surface of the 384-well was observed using a confocal microscope (n = 384 well, bright field), the thickness of the bottom surface was measured and the cross-section was observed (n = 384 well, excitation wavelength: 488 nm, fluorescence wavelength: 483 - 493 nm), and the cross-section of the entire molded product was confirmed (excitation wavelength: 488 nm, fluorescence wavelength: 483 - 493 nm).

[0072] As a result, wells were formed in which the thick part forming the side surface and the thin part forming the bottom surface were connected by a smooth arc. Fig. 8(a) is an overall image of the bright field observation of the bottom surface of the well according to Example 1 by a microscope. Fig. 8(b) is an enlarged image of one well of the bright field observation of the bottom surface of the well according to Example 1 by a microscope. Also, as shown in Fig. 8(a) and Fig. 8(b), only interference fringes generated due to the thinness were observed on the bottom surface of the well, and no serious damage such as breakage or penetration was confirmed in any of the wells.

[0073] Fig. 9(a) is a graph showing the height distribution of the protrusions of the PDMS mold according to Example 1. Fig. 9(b) is a graph showing the thickness distribution of the well bottom of the molded product. Fig. 9(c) is a graph showing the depth distribution of the wells of the molded product according to Example 1. As shown in Fig. 9(a), the height of the convex part of the PDMS mold was 1623.5 ± 26.5 μm (n = 384 wells, mean ± standard deviation). As shown in Fig. 9(b), the thickness of the bottom surface of the molded product was 11.9 ± 2.4 μm (n = 384 wells, mean ± standard deviation). In the PDMS mold, the standard deviation was relatively large at 26.5 μm (a difference of up to about 300 μm), but the standard deviation of the thickness of the well bottom surface of the molded product was reduced to 2.43 μm (a difference of up to about 14.2 μm), which was less than 1 / 10. As shown in Fig. 9(c), the depth of the well itself of the molded product was 1565.2 ± 21.1 μm.

[0074] Fig. 10(a) is a cross-sectional observation image of the protrusion of the PDMS mold according to Example 1. Fig. 10(b) is a cross-sectional observation image of the entire molded product according to Example 1. Fig. 10(c) is a cross-sectional observation image of the bottom surface of the well of the molded product according to Example 1. As can be seen by comparing Fig. 10(a) and Fig. 10(b), the bottom surface part is flatter compared to the mold, and as shown in Fig. 10(c), it is a plane with a height error within 10 μm in a range of approximately 1000 μm in diameter. Thus, by using this technology, the error in the thin part of the molded product was corrected by the flexible mold, and precise processing with a wall thickness of about 10 μm was possible over a wide range without drilling holes in the bottom surface. Also, it was confirmed that a very thin structure could be connected to the thick part without a seam with a curved surface.

[0075] <Example 2> In Example 2, similar to Example 1, a mold having protrusions (convex parts) in an array of 24 columns x 16 rows was fabricated from PDMS, and by pressing this against a polystyrene resin plate under heating, a container having 384 wells with a bottom thickness of about 25 μm was fabricated.

[0076] <Fabrication of PDMS Mold> First, a PDMS mold with a protrusion (convex part) height of about 1.85 mm was fabricated, and the 3D shape of the fabricated PDMS mold was analyzed using a confocal microscope. As a result, the height of the protrusion (convex part) of the PDMS mold was 1835.1 ± 22.9 μm (n = 384 wells).

[0077] <Molding of a polystyrene well plate> Using the PDMS mold with the height of the produced protrusions (convex parts) being approximately 1.85 mm, in the same manner as in Example 1, the PDMS mold was pressed against the polystyrene plate with the surface provided with the protrusions to perform thermocompression molding.

[0078] Figure 11(a) is an overall image of the bright-field observation of the well bottom according to Example 2 by a microscope. Figure 11(b) is an enlarged image of one well of the bright-field observation of the well bottom according to Example 2 by a microscope. As confirmed in Figures 11(a) and 11(b), no serious damage such as breakage or penetration was confirmed in any of the wells.

[0079] Figure 12(a) is a graph showing the height distribution of the protrusions of the PDMS mold according to Example 2. Figure 12(b) is a graph showing the thickness distribution of the well bottom of the molded product according to Example 2. Figure 12(c) is a graph showing the depth distribution of the wells of the molded product according to Example 2. As shown in Figure 12(a), the height of the protrusions (convex parts) of the PDMS mold is almost uniform. As shown in Figure 12(b), the thickness of the bottom surface of the molded product is uniform, and the thickness of the bottom surface of the molded product was 27.4 ± 2.9 μm (n = 384 wells). As can be confirmed, the standard deviation of the PDMS mold was 22.9 μm (a difference of about 150 μm at most), but the standard deviation of the thickness of the well bottom surface of the molded product was reduced to about one-eighth, which was 2.9 μm (a difference of 18.3 μm at most). In addition, the depth of the well itself of the molded product was 1612.3 ± 15.2 μm.

[0080] Figure 13 is a cross-sectional observation image of the bottom surface of the well of the molded product according to Example 2. As shown in Figure 13, the bottom surface of the well of the molded product was a plane with an error within 10 μm in the height direction in a range of approximately 900 μm in diameter. Thus, it was shown that this method can be applied to a wide range of resins as the material of the molded product.

[0081] As described above, according to this embodiment, a thin-shaped object can be formed simply and inexpensively. In addition, a thin structure can be formed over a wide area with a small error. Furthermore, a thick shape and a thin shape can be integrally formed. Moreover, a thick shape and a thin shape can be continuously formed on a curved surface. Also, there has been no reported technology capable of forming an extremely thin structure with a wall thickness on the order of 10 μm in press forming, and this technology is also excellent in terms of precision.

[0082] Note that the method for manufacturing the mold in this embodiment is merely an example and is not limited thereto.

[0083] <Second Embodiment> Subsequently, a second embodiment will be described. In the second embodiment, the structure of the well plate manufactured by the manufacturing method according to the first embodiment will be described. Conventionally, there has been no well plate in which the well has a round bottom and the thickness at the center of the bottom surface of the well is 200 μm or less. In contrast, the well plate according to the second embodiment provides a well plate in which the well has a round bottom and the thickness of the thinnest part of the well bottom is approximately 200 μm or less. The well plate according to the second embodiment is made of resin and is provided with at least one well. The well has a round bottom. By having a round bottom for the well, cells can be made to gather at the center of the bottom of the well.

[0084] <Background: Importance of High-Magnification Observation> In previous cell research, cells have been treated as a group, and cell populations in units of wells or dishes have been used as one sample for various studies. For example, in cell analysis for understanding cells and life phenomena, a method of understanding cell functions by measuring the average value of a cell population has been used. General multi-well plates are manufactured for the purpose of observing the overall image of a cell population composed of such a large number of cells or performing cell assays or the like using a plate reader or the like to examine the general properties of the cell group.

[0085] However, in recent years, it has been found that even in a cell population that was thought to be uniform, there are a very small number of important cells such as stem cells and circulating cancer cells in the blood. Also, studies that analyze individual cells in detail, such as epigenetic studies, have reported that there are molecular-level differences, such as chemical modifications of histones, for each cell, and that phenotypes and functions, such as the cell cycle and protein expression levels, also differ for each cell. Furthermore, research on intratumoral heterogeneity, cancer treatment methods using immune cells typified by CAR-T therapy and TCR-T therapy, and elucidation of the immune mechanism, etc., which require precise analysis of individual cells, have become very important themes in medicine and life sciences. The multi-well plate is very useful in such research that precisely analyzes a small number of individual cells from one cell, which has become important in recent years, by collecting the small number of cells seeded in the wells near the center due to its round-bottom shape and making them easier to detect by microscopic observation or the like. As a detailed method for analyzing cells, microscopic observation using a high-magnification objective lens is often performed. For example, in clinical specimen tests, the shape of the nucleus inside the cell is observed using an objective lens of 40x, 63x, or 100x. Also, in FISH tests for detecting specific sequences in the nucleus, and methods for staining and observing intracellular organelles or specific molecules with fluorescent dyes, etc., an objective lens of 63x or 100x is used. Furthermore, for observing minute structures and three-dimensional details, and even for super-resolution microscopy observations that won the Nobel Prize in Chemistry in 2014, etc., an objective lens of 100x is used. Incidentally, after such analysis of the cell phenotype, genotype analysis by PCR or the like is often performed. Therefore, it is desirable that the multi-well plate be applicable up to an objective lens of 100x in the detailed microscopic analysis of a small number of cells from one cell that it targets. Since the focal length is short for high-magnification objective lenses, there is a limit to the thickness of the bottom surface of the well where the sample can be observed.

[0086] <Thickness of the bottom surface applicable to a high-magnification objective lens (100x)> Therefore, in this embodiment, the thickness of the bottom surface applicable to a 100x objective lens will be described. Using the manufacturing method according to the first embodiment, well plates with wells having a diameter of 2 mm and various well bottom thicknesses were manufactured. As an example of the resin constituting this well plate, polycarbonate was used. As shown in Fig. 14, using an oil-immersion 100x objective lens, Ba / F3 cells in a well (polycarbonate) with a diameter of 2 mm were observed while changing the thickness t of the bottom of the well.

[0087] Fig. 14 is an example of Ba / F3 cells imaged using an oil-immersion 100x objective lens in the case of various bottom surface thicknesses. When the thickness t of the bottom surface was up to 133.3 μm, the cells located on the bottom surface of the well could be focused, but at the bottom surface of 156.2 μm, the focus could not be achieved even when the oil-immersion 100x objective lens was brought into contact with the bottom surface of the well. Therefore, the thickness of the bottom surface of the well is preferably 150 μm or less.

[0088] Thus, the well plate according to the second embodiment is a well plate made of resin and provided with at least one well, the well having a round bottom, and the thickness of the central portion of the bottom of the well being preferably 150 μm or less. According to this configuration, since the well has a round bottom, the cells seeded in the well gather at the center of the bottom of the well, facilitating the observation of the cells. Furthermore, since the thickness of the central portion of the bottom surface of the well is 150 μm or less, the focus can be adjusted to the cells present on the bottom surface of the well even with an oil-immersion 100x objective lens, and detailed microscopic analysis of a small number of cells starting from one cell can be reliably performed.

[0089] <Regarding the definition of the lower limit of the thickness of the bottom surface of the well> Subsequently, as a result of experiments using a 384-well plate manufactured by the manufacturing method according to the first embodiment, the relationship between the thickness of the bottom surface of the well and the damaged well rate in the 384 wells will be described. Using polycarbonate as an example of the resin, after manufacturing multi-well plates with a diameter of 2 mm and various well bottom thicknesses, the ratio of wells having characteristic breakage (see Fig. 15) that increases depending on the well bottom thinness was counted. Fig. 15 is a diagram showing an example of characteristic breakage that increases depending on the well bottom thinness. Image G1 is a phase image at 5x magnification of a normal well without breakage. On the other hand, image G2 is a phase image at 5x magnification of a well with breakage. As indicated by arrow A1 in image G2, a crescent-shaped scratch has occurred on the well bottom. Thus, as the well bottom is made thinner, the chance of confirming a crescent-shaped scratch on the well bottom increases.

[0090] Fig. 16 is a table showing the experimental results of the relationship between the average thickness of the thinnest part of the well bottom and the breakage well rate among 384 wells. Fig. 16 shows the experimental results of the set of press time, the average thickness of the central part of the well bottom (also referred to as the average central part thickness of the well bottom), the number of breakage wells, and the breakage well rate. The average thickness of the thinnest part of the well bottom is represented by the average value and standard error of the 384 wells at the thinnest part of the well bottom. Wells with breakage were not confirmed until the average thickness of the thinnest part of the well bottom reached 8.24 ± 1.57 μm. Wells with breakage were confirmed when the average thickness of the thinnest part of the well bottom became thinner than 7.98 ± 1.45 μm. That is, it is critically significant that the average thickness of the central part of the well bottom (or the thickness of the thinnest part of the well bottom) is 8 μm or more.

[0091] The average thickness of the thinnest part of the well bottom is 7.52 ± 1.69 μm and the breakage rate is 5.21%. The average thickness of the thinnest part of the well bottom is 7.05 ± 1.23 μm and the breakage rate is 7.81%. The average thickness of the thinnest part of the well bottom is 6.97 ± 1.77 μm and the breakage rate is 16.81%, and the average thickness of the thinnest part of the well bottom is 6.93 ± 1.58 μm and the breakage rate is 20.83%, exceeding 20%. Thus, when the average thickness of the thinnest part of the well bottom becomes less than 7 μm, the breakage rate increases rapidly. That is, it is critically significant that the average thickness of the central part of the well bottom (or the thickness of the thinnest part of the well bottom) is 7 μm or more.

[0092] Therefore, from the perspective of a well plate having a strength that can prevent damage to most (specifically, for example, 80 to 90% or more) of the wells, it is preferable that the average thickness (or the thickness of the thinnest part of the well bottom) of the thinnest part of the well bottom is 7 μm or more. Further, from the perspective of a plate having sufficient strength to prevent damage to all wells in manufacturing and the like, it is more preferable that the average thickness (or the thickness of the thinnest part of the well bottom) of the thinnest part of the well bottom is 8 μm or more.

[0093] <Regarding the relationship between the thickness of the thinnest part of the well bottom and the curvature of the well bottom surface> Subsequently, after coating the well surface with a 1% BSA-TAMRA / PBS solution overnight, the fluorescence of BSA-TAMRA on the well surface was observed with a confocal microscope. FIG. 17 is an example of an image of a longitudinal section of a well obtained by a confocal microscope. From the center P0 of the well bottom surface, points P1 on the well bottom surface 30% (0.3 mm as an example) away from the well radius r (1 mm as an example) in the horizontal direction, point P2 on the well bottom surface 60% (0.6 mm as an example) away, and point P3 on the well bottom surface 90% (0.9 mm as an example) away are shown. Here, the well radius is the radius of the circle shown by the horizontal cross-section of the well at a height 80% above the well bottom surface of the height from the well bottom surface to the opening, provided that in the range from 80% to 100% of the height from the well bottom surface to the opening above the well bottom surface, if there is no well wall surface where the tangent of the well wall surface in the vertical cross-section of the well is 80° to 90° with respect to the horizontal plane, it is the radius of the circle shown by the horizontal cross-section of the well at a height 50% above the well bottom surface of the height from the well bottom surface to the opening. A circle C1 passing through these points P1, P2, and P3 is shown. In this embodiment, the radius of this circle C1 is defined as the radius of curvature of the well bottom surface.

[0094] FIG. 18 is an example of an image of a longitudinal section of a well obtained by a confocal microscope in the case of various bottom thicknesses. FIG. 18(a) shows the thickness t of the thinnest part of the well bottom is 14 μm, FIG. 18(b) shows the thickness t of the thinnest part of the well bottom is 38 μm, FIG. 18(c) shows the thickness t of the thinnest part of the well bottom is 76 μm, FIG. 18(d) shows the thickness t of the thinnest part of the well bottom is 144 μm, and FIG. 18(e) shows an example of an image of a longitudinal section of the well when the thickness t of the thinnest part of the well bottom is 211 μm. Thus, when the thickness t of the thinnest part of the well bottom changes, the shape of the well bottom changes, and the curvature of the well bottom changes.

[0095] FIG. 19 is a schematic diagram for explaining the difference in the radius of curvature due to the difference in the thickness t of the thinnest part of the well bottom. Using FIG. 19, a qualitative explanation will be given for the shape of the well obtained from the experimental results of FIG. 18. The radius of the well is 1 mm. When the thickness t of the thinnest part of the well bottom is 9 μm, as represented by the circle C11 of the radius of curvature, the radius of curvature is 0.91 mm, which is smaller than 1 mm when the mold does not deform. Also, when the thickness t of the thinnest part of the well bottom is around 19 μm, as represented by the circle C12 of the radius of curvature, for example, the smallest radius of curvature becomes 0.82 mm. This is considered to be because, as a principle of this resin processing method, the bottom surface part of the mold close to the underlying glass plate is particularly subjected to a large stress, so that the bottom surface part of the mold is deformed more greatly than other parts of the mold. When the thickness t of the thinnest part of the well bottom is 55 μm, as represented by the circle C13 of the radius of curvature, the radius of curvature is 0.92 mm, which is smaller than 1 mm when the mold does not deform.

[0096] On the other hand, when the thickness t of the thinnest part of the well bottom becomes thicker than approximately 76 μm, the effect of the bottom surface part of the mold being particularly subjected to a large stress becomes smaller, and the entire mold is uniformly subjected to stress and deformed into a flat shape. When the thickness t of the thinnest part of the well bottom is 144 μm, as represented by the circle C14 of the radius of curvature, for example, the radius of curvature is 1.2 mm, and when the thickness t of the thinnest part of the well bottom is 211 μm, for example, the radius of curvature is 1.3 mm, and the radius of curvature gradually increases and exceeds 1 mm when the mold does not deform.

[0097] FIG. 20 is a graph showing the experimental results of the relationship between the thickness of the thinnest part of the well bottom and the ratio of the radius of curvature of the well bottom surface divided by the radius of the well.

[0098] The well plate manufactured by the manufacturing method according to this embodiment has a characteristic well bottom surface shape, and the relationship between the thickness of the thinnest part of the well bottom and the ratio of the radius of curvature of the well bottom surface divided by the radius of the well has the relationship shown in the graph of FIG. 20. The radius of curvature of the well bottom surface used to calculate the ratio of each plot in the graph of FIG. 20 is the average value of four values measured from the arcs of the bottom surfaces on the four sides of the well. The four sides of the well are, as an example, two directions parallel to the longitudinal row of the well and passing through the center of the well bottom in opposite directions, and two directions parallel to the transverse row of the well and passing through the center of the well bottom in opposite directions. Note that the four directions for measuring the radius of curvature of the well bottom surface may be directions perpendicular to each other.

[0099] Each plot in the graph of FIG. 20 represents a representative example point. When a regression equation is applied to each plot in the range where the central part of the bottom surface of the well in FIG. 20 is 7 to 19 μm, if the ratio of the radius of curvature of the well bottom surface divided by the radius of the well is y, and the central part of the bottom surface of the well is x [μm], then the ratio y is represented by y = -0.0093x + 0.9924 in the range where the central part of the bottom surface of the well is 7 to 19 μm. The coefficient of determination R 2 of this regression equation is 0.9999. Also, both the representative example points and the points other than the representative example points fall within ±10% of the value of y = -0.0093x + 0.9924.

[0100] Therefore, the ratio y is within ±10% of the value of y = -0.0093x + 0.9924 in the range where the central part of the bottom surface of the well is 7 to 19 μm.

[0101] Also, when a regression equation is applied to each plot in the range where the central part of the bottom surface of the well in FIG. 20 is 19 to 200 μm, the ratio y is y = 0.0028x + 0.7572 in the range where the central part of the bottom surface of the well is 19 to 200 μm. The coefficient of determination R 2is 0.9769. Further, both the points of the representative examples and the points other than the representative examples fall within ±10% of the value of y = 0.0028x + 0.7572.

[0102] Therefore, for the ratio y, when the center of the bottom surface of the well is in the range of 19 to 200 μm, it is within ±10% of the value of y = 0.0028x + 0.7572. According to this configuration, a round bottom can be formed and the thickness of the bottom surface of the well can be reduced.

[0103] When the thickness x of the thinnest part of the well bottom is in the range of 0 to 200 μm with respect to the above two equations, the ratio obtained by dividing the radius of curvature of the well bottom surface by the radius of the well is 0.7 to 1.5. According to this configuration, a round bottom can be formed and the thickness of the bottom surface of the well can be reduced.

[0104] As described above, the present invention is not limited to the above-described embodiments as they are, and at the implementation stage, the components can be modified and embodied without departing from the gist thereof. Further, various inventions can be formed by appropriately combining a plurality of components disclosed in the above embodiments. For example, some components may be deleted from all the components shown in the embodiments. Furthermore, components from different embodiments may be appropriately combined.

Explanation of Reference Numerals

[0105] 11 Acrylic frame with PDMS thin film 12 Well plate processing member 13 Shim plate for height adjustment 14 Plate with a plurality of through holes 15 Stage 16 Die-cast box 17, 19 Packing 18 Hollow member 21 Silicon rubber embankment 22 PDMS solution 23 Reinforced glass 24 Rubber

Claims

1. A step of sandwiching a resin or a metal between a mold provided with protrusions made of an elastomer having a heat resistance temperature higher than the temperature at which they soften, and a support that is harder than the mold and has a higher temperature at which it softens by heat than the resin or the metal, and applying a force in the direction of the resin or the metal to the mold under heating conditions; A step of forming the resin or the metal by applying the force to form a recess having a thin portion on the bottom surface, wherein in the process of forming the recess, the protrusions of the mold are deformed so as to expand the area of the thin portion, thereby forming the flat thin portion; A step of removing the mold; A method for manufacturing a thin-walled molded article having the above steps.

2. The standard deviation of the thickness of the bottom surface of the thin-walled molded article is smaller than the standard deviation of the height of the protrusions in the mold; The method for manufacturing a thin-walled molded article according to Claim 1.

3. The standard deviation of the thickness of the bottom surface of the thin-walled molded article is 1 / 8 or less of the standard deviation of the height of the protrusions in the mold; The method for manufacturing a thin-walled molded article according to Claim 1.

4. The resin is an amorphous plastic resin having a glass transition point lower than the heat resistance temperature of the elastomer of the mold, or a crystalline plastic having a low melting point; The method for manufacturing a thin-walled molded article according to Claim 1.

5. The melting point of the metal is lower than the heat resistance temperature of the elastomer of the mold; The method for manufacturing a thin-walled molded article according to Claim 1.

6. The resin is a thermoplastic resin; The method for manufacturing a thin-walled molded article according to Claim 1.

7. A step of producing a jig with through holes provided with a thin film of an elastomer on the surface; A step of sucking the thin film through the through holes from the back side; A step of injecting a solution of the elastomer onto the deflected thin film after sucking; A step of forming the mold by heating and curing the solution; The method for manufacturing a thin-walled molded article according to any one of Claims 1 to 6, further comprising the above steps.

8. The elastomer is a silicone resin; The method for manufacturing a thin-walled molded article according to any one of Claims 1 to 7.

9. The elastomer is polydimethylsiloxane; The method for manufacturing a thin-walled molded article according to any one of Claims 1 to 8.

10. The thin-walled molded article is a well plate; The method for manufacturing a thin-walled molded article according to any one of Claims 1 to 9.

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