WO2021107008A1 - 薄肉成形品の製造方法及びウェルプレート - Google Patents

薄肉成形品の製造方法及びウェルプレート Download PDF

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Publication number
WO2021107008A1
WO2021107008A1 PCT/JP2020/044018 JP2020044018W WO2021107008A1 WO 2021107008 A1 WO2021107008 A1 WO 2021107008A1 JP 2020044018 W JP2020044018 W JP 2020044018W WO 2021107008 A1 WO2021107008 A1 WO 2021107008A1
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Prior art keywords
well
thin
mold
resin
thickness
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Ceased
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English (en)
French (fr)
Japanese (ja)
Inventor
真也 山平
勇司 平家
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St Luke's International University
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St Luke's International University
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Priority to US17/780,650 priority Critical patent/US20230008034A1/en
Priority to JP2021561487A priority patent/JP7708424B2/ja
Publication of WO2021107008A1 publication Critical patent/WO2021107008A1/ja
Anticipated expiration legal-status Critical
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C59/00—Surface shaping of articles, e.g. embossing; Apparatus therefor
    • B29C59/02—Surface shaping of articles, e.g. embossing; Apparatus therefor by mechanical means, e.g. pressing
    • B29C59/022—Surface shaping of articles, e.g. embossing; Apparatus therefor by mechanical means, e.g. pressing characterised by the disposition or the configuration, e.g. dimensions, of the embossments or the shaping tools therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Rigid containers without fluid transport within
    • B01L3/5085—Rigid containers without fluid transport within for multiple samples, e.g. microtitration plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B21—MECHANICAL METAL-WORKING WITHOUT ESSENTIALLY REMOVING MATERIAL; PUNCHING METAL
    • B21D—WORKING OR PROCESSING OF SHEET METAL OR METAL TUBES, RODS OR PROFILES WITHOUT ESSENTIALLY REMOVING MATERIAL; PUNCHING METAL
    • B21D22/00—Shaping without cutting, by stamping, spinning, or deep-drawing
    • B21D22/02—Stamping using rigid devices or tools
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B21—MECHANICAL METAL-WORKING WITHOUT ESSENTIALLY REMOVING MATERIAL; PUNCHING METAL
    • B21D—WORKING OR PROCESSING OF SHEET METAL OR METAL TUBES, RODS OR PROFILES WITHOUT ESSENTIALLY REMOVING MATERIAL; PUNCHING METAL
    • B21D22/00—Shaping without cutting, by stamping, spinning, or deep-drawing
    • B21D22/02—Stamping using rigid devices or tools
    • B21D22/022—Stamping using rigid devices or tools by heating the blank or stamping associated with heat treatment
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C33/00—Moulds or cores; Details thereof or accessories therefor
    • B29C33/38—Moulds or cores; Details thereof or accessories therefor characterised by the material or the manufacturing process
    • B29C33/3842—Manufacturing moulds, e.g. shaping the mould surface by machining
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C33/00—Moulds or cores; Details thereof or accessories therefor
    • B29C33/38—Moulds or cores; Details thereof or accessories therefor characterised by the material or the manufacturing process
    • B29C33/3842—Manufacturing moulds, e.g. shaping the mould surface by machining
    • B29C33/3857—Manufacturing moulds, e.g. shaping the mould surface by machining by making impressions of one or more parts of models, e.g. shaped articles and including possible subsequent assembly of the parts
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C33/00—Moulds or cores; Details thereof or accessories therefor
    • B29C33/42—Moulds or cores; Details thereof or accessories therefor characterised by the shape of the moulding surface, e.g. ribs or grooves
    • B29C33/424—Moulding surfaces provided with means for marking or patterning
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M3/00—Tissue, human, animal or plant cell, or virus culture apparatus
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12—Specific details about manufacturing devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0848—Specific forms of parts of containers
    • B01L2300/0851—Bottom walls
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0893—Geometry, shape and general structure having a very large number of wells, microfabricated wells
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2101/00—Use of unspecified macromolecular compounds as moulding material
    • B29K2101/12—Thermoplastic materials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2883/00—Use of polymers having silicon, with or without sulfur, nitrogen, oxygen, or carbon only, in the main chain, as mould material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2995/00—Properties of moulding materials, reinforcements, fillers, preformed parts or moulds
    • B29K2995/0037—Other properties
    • B29K2995/0039—Amorphous
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2995/00—Properties of moulding materials, reinforcements, fillers, preformed parts or moulds
    • B29K2995/0037—Other properties
    • B29K2995/0046—Elastic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
    • B29L2031/00—Other particular articles
    • B29L2031/712—Containers; Packaging elements or accessories, Packages

Definitions

  • the present invention relates to a method for producing a thin-walled molded product having a thin-walled portion in a part of the shape and a well plate.
  • the method of molding resin etc. into thin structures and films is a very important technology in the development and manufacture of parts for mobile phones and personal computers, and other precision equipment.
  • a method of molding a resin or the like into a thin structure is becoming more important.
  • a PCR container used for amplifying nucleic acids in basic research and medical tests is designed to be thin in order to efficiently conduct heat into the container.
  • a PCR container having a thin and flat bottom surface which enables PCR to be performed after analyzing cells with a microscope, is also on the market.
  • the focal length of the objective lens becomes shorter as the magnification increases, so the bottom surface of the container for high-magnification observation needs to be thinner.
  • products with a thin cover glass or film attached to the bottom of the container with an adhesive or the like have been sold as such a container for high-magnification observation, but the problem of adhesive elution and improvement of the container strength have been sold. Therefore, products in which the container and the bottom surface are integrally molded have been sold.
  • the method of producing a thin molded product is a very demanding technology.
  • a method using a complicated molding device incorporating many sensors and metal moving parts see, for example, Patent Document 1 and Patent Document 2
  • a method using a compound that makes it easy to produce a thin molded product for example, a patent.
  • Refer to Document 3 a method of setting strict conditions (see, for example, Patent Document 4), and the like have been reported.
  • a molding method such as injection molding or press molding using a metal mold (mold) is used for molding a product made of a thermoplastic material such as resin.
  • a metal mold is used for molding a product made of a thermoplastic material such as resin.
  • injection molding it is very difficult to allow the molten resin to flow into the ultra-thin portion of the mold.
  • other molding methods such as injection molding and press molding, for example , in order to perform resin processing with a thickness of 50 ⁇ m or less over a wide range of several tens of cm 2 or more with a small error, deformation due to thermal expansion is included. It requires extremely highly designed and highly accurate molds and advanced molding processes.
  • mold making usually costs a very high cost of one million to tens of millions of yen, so it is highly advanced for the development and manufacture of such high value-added products. It requires technology and great cost.
  • a mold used for molding a resin or the like is made of a rigid material in order to make a molded product with good reproducibility.
  • no error is allowed. This is because the thickness at each point of the molded product changes greatly due to some errors in the mold and the molding process, and the mold breaks through the resin that is the source of the molded product to make a hole. Therefore, a method for forming a structure having a precise thin portion easily and inexpensively is strongly desired in the development and manufacture of various precision instruments and research / medical instruments.
  • the present invention has been made in view of the above problems, and is a thin-wall molding capable of easily and inexpensively molding a thin shape and molding a thin structure over a wide area with a small error. It is an object of the present invention to provide a manufacturing method of an article and a well plate.
  • the method for producing a thin-walled molded product according to the first aspect of the present invention is a method of manufacturing a resin or metal from a mold provided with protrusions made of an elastic body having a heat resistance temperature higher than the softening temperature of the resin or metal, and the mold.
  • the resin or metal softened by heat is sufficiently softer than the protrusions of the mold at the initial stage of the process, the resin or metal is deformed by being pressed from the mold to form a dent.
  • the force required to reduce the wall thickness of the bottom of the depression is mainly the force required to deform the resin or metal.
  • the force required to further reduce the wall thickness at the bottom of the depression is greater than the force required to deform the resin or metal.
  • the main force is required to discharge the resin or metal from the thin portion against the frictional force acting between the support and the resin or metal. This force increases dramatically as the thickness of the thin part becomes thinner.
  • the stress applied to the mold increases as the thin-walled portion becomes harder to deform, and the protrusions of the mold made of the elastic body are crushed to deform so as to widen the area of the thin-walled portion. At this time, the shape of the thin-walled portion is almost flat.
  • the frictional force acting between the resin or metal and the mold or support further increases, so as the thin part at the bottom of the depression becomes thinner, the wall thickness at the bottom of the depression increases. The force required to make it thinner increases at an accelerating rate.
  • a shape having a thin dent can be easily and inexpensively formed, and a structure having a thin dent can be formed over a wide area with a small error.
  • a thicker shape and a thinner shape can be integrally molded.
  • a thicker shape and a thinner shape can be continuously formed on a curved surface.
  • the method for producing a thin-walled molded product according to the second aspect of the present invention is the method for producing a thin-walled molded product according to the first aspect, and the resin has a glass transition point rather than the heat-resistant temperature of the elastic body of the mold.
  • the heat-softened resin is sufficiently softer than the protrusions of the mold, so that the resin is deformed by being pressed from the mold to form a dent.
  • the force required to reduce the wall thickness of the bottom of the recess is mainly the force required to deform the resin.
  • the force required to further reduce the wall thickness at the bottom of the depression is greater than the force required to deform the resin, such as the mold or support. Then, the force required to discharge the resin from the thin-walled portion against the frictional force acting between the resins is the main force.
  • the method for producing a thin-walled molded product according to the third aspect of the present invention is the method for producing a thin-walled molded product according to the first aspect, and the melting point of the metal is lower than the heat-resistant temperature of the elastic body of the mold.
  • the metal softened by heat is sufficiently softer than the protrusions of the mold, so that the metal is deformed by being pressed from the mold to form a dent.
  • the force required to reduce the wall thickness of the bottom of the depression is mainly the force required to deform the metal.
  • the force required to further reduce the wall thickness at the bottom of the depression is greater than the force required to deform the metal, such as the mold or support.
  • the force required to discharge the metal from the thin-walled part against the frictional force acting between the metals is the main force. This force increases dramatically as the thickness of the thin part becomes thinner.
  • the stress applied to the mold increases as the thin-walled portion becomes harder to deform, and the protrusions of the mold made of the elastic body are crushed to deform so as to widen the area of the thin-walled portion. At this time, the shape of the thin-walled portion is almost flat. As the area of the thin part increases, the frictional force acting between the metal and the mold or support further increases, so as the thin part at the bottom of the dent becomes thinner, the thickness of the bottom of the dent becomes thinner. The force required for this increases at an accelerating rate.
  • the method for producing a thin-walled molded product according to the fourth aspect of the present invention is the method for producing a thin-walled molded product according to the first or second aspect, and the resin is a thermoplastic resin.
  • a thin shape can be molded easily and inexpensively.
  • a thin structure can be formed over a wide area with a small error.
  • the method for producing a thin-walled molded product according to a fifth aspect of the present invention is the method for producing a thin-walled molded product according to any one of the first to fourth aspects, and is a through hole provided with a thin film of an elastic body on the surface.
  • the method for producing a thin-walled molded product according to a sixth aspect of the present invention is a method for producing a thin-walled molded product according to any one of the first to fifth aspects, wherein the elastic body is polydiMethylSiloxane (PDMS). ).
  • PDMS polydiMethylSiloxane
  • a shape having a thin dent can be easily and inexpensively formed, and a structure having a thin dent can be formed over a wide area with a small error.
  • the method for producing a thin-walled molded product according to the seventh aspect of the present invention is the method for producing 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.
  • a shape having a thin dent can be easily and inexpensively formed, and a structure having a thin dent can be formed over a wide area with a small error.
  • the well plate according to the eighth aspect of the present invention is a well plate made of resin and provided with at least one well, the well has a round bottom, and the thickness of the bottom central portion of the well is thick. It is 200 ⁇ m or less.
  • the wells have a round bottom, the cells seeded in the wells gather in the center of the bottom of the wells, so that it is possible to facilitate the observation of the cells. Further, since the thickness of the central portion of the bottom of the well is 200 ⁇ m or less, it can be observed with a high-magnification microscope.
  • 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. ..
  • the wells have a round bottom, the cells seeded in the wells gather in the center of the bottom of the wells, so that it is possible to facilitate the observation of the cells.
  • 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. is there.
  • the range of the shape of the bottom surface of the well is defined.
  • the well plate according to the tenth aspect of the present invention is the well plate according to the eighth or ninth aspect, and 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 center of the bottom surface of the well.
  • the range of the shape of the bottom surface of the well is defined.
  • the well plate according to the eleventh aspect of the present invention is a 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 ⁇ m or more.
  • the well plate according to the twelfth aspect of the present invention is a well plate according to any one of the eighth to eleventh aspects, and the thickness of the central portion of the bottom surface of the well is 150 ⁇ m or less.
  • the wells have a round bottom, the cells seeded in the wells gather in the center of the bottom of the wells, so that it is possible to facilitate the observation of the cells. Furthermore, since the thickness of the central part of the bottom surface of the well is 150 ⁇ m or less, the focus can be focused on the cells existing on the bottom surface of the well even with an oil-immersed 100x objective lens, and details of a small number of cells from one cell. Can reliably perform microscopic analysis.
  • a thin shape can be easily and inexpensively formed.
  • a thin structure can be formed over a wide area with a small error.
  • a thicker shape and a thinner shape can be integrally molded.
  • a thicker shape and a thinner shape can be continuously formed on a curved surface.
  • a press molding technique capable of forming an extremely thin structure having a wall thickness on the order of 10 ⁇ m has not been reported, and this technique is also excellent in terms of accuracy.
  • FIG. 6A is an overall image of the PDMS template taken from above with a stereomicroscope.
  • FIG. 6B is a magnified image of the PDMS template taken from above with a stereomicroscope.
  • FIG. 6 (c) is a magnified image of the PDMS template taken obliquely from above with a stereomicroscope.
  • FIG. 6D is a magnified image of the PDMS template taken obliquely upward from another angle with a stereomicroscope.
  • FIG. 7A is an overall image of the molded product taken from above with a stereomicroscope.
  • FIG. 7B is a magnified image of the PDMS template taken from above with a stereomicroscope.
  • FIG. 7 (c) is a magnified image of the PDMS template taken obliquely from above with a stereomicroscope.
  • FIG. 7D is a magnified image of the PDMS template taken obliquely upward from another angle with a stereomicroscope.
  • FIG. 7A is an overall image of the molded product taken from above with a stereomicroscope.
  • FIG. 7B is a magnified image of the PDMS template taken from above with a stereomicroscope.
  • FIG. 7 (c) is
  • FIG. 8A is an overall image of bright-field observation of the bottom surface of the well according to Example 1 using a microscope.
  • FIG. 8B is a 1-well magnified image of a bright-field observation of the bottom of the well according to Example 1 using a microscope.
  • FIG. 9A is a graph showing the distribution of the heights of the protrusions of the PDMS template according to Example 1.
  • FIG. 9B is a graph showing the distribution of the thickness of the well bottom of the molded product according to Example 1.
  • FIG. 9C is a graph showing the distribution of well depths of the molded product according to Example 1.
  • FIG. 10A is a cross-sectional observation image of the protrusion of the PDMS mold according to the first embodiment.
  • FIG. 10A is a cross-sectional observation image of the protrusion of the PDMS mold according to the first embodiment.
  • FIG. 10B 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.
  • FIG. 11A is an overall image of the bright field observation of the bottom surface of the well according to Example 2 using a microscope.
  • FIG. 11B is a 1-well magnified image of a bright-field observation of the bottom of the well according to Example 2 using a microscope.
  • FIG. 12A is a graph showing the distribution of the heights of the protrusions of the PDMS template according to Example 2.
  • FIG. 12B is a graph showing the distribution of the thickness of the well bottom of the molded product according to Example 2.
  • Example 12 (c) is a graph showing the distribution of well depths of the molded product according to Example 2. It is a cross-sectional observation image of the bottom surface of the well of the molded product according to Example 2. This is an example of Ba / F3 cells imaged using an oil-immersed 100x objective lens in the case of various bottom thicknesses. It is a figure which shows an example of the characteristic breakage which increases depending on the thickness of the bottom surface of a well. It is a table showing the experimental result of the relationship between the average thickness of the thinnest part of the well bottom and the broken well rate in 384 wells. This is an example of a vertical cross-sectional image of a well obtained by a confocal microscope.
  • the present embodiment it is devised to add a shape correction function to the mold itself, instead of constructing the mold and the molding process precisely. That is, in the present embodiment, at least the protruding portion of the mold is made of a material (that is, an elastic body) that flexibly deforms, so that the thickness of each thin portion of the material that is the source of the molded product is the same. The mold is deformed, and a thin structure can be formed with a small error even in a large area.
  • a material that is, an elastic body
  • a well plate is given as an example of a thin-walled molded product having a thin-walled portion as a part of the shape, and a method for manufacturing the well plate will be described.
  • a thin-walled molded product here, a well plate as an example
  • a molded product to be molded
  • FIG. 1 is a schematic view showing a schematic process of a method for manufacturing a well plate according to the present embodiment.
  • FIG. 2 is a flowchart showing an example of a flow of a method for manufacturing a well plate according to the present embodiment.
  • Step S10 a thin film of an elastic body is formed.
  • the elastic body is, for example, polydiMethylSiloxane (PDMS), and a PDMS thin film is formed.
  • PDMS polydiMethylSiloxane
  • Step S20 Next, using the thin film formed in step S10 (for example, PDMS thin film), a jig with a through hole having an elastic thin film provided on the surface is created.
  • the jig with a through hole is provided with a through hole in an array of 24 columns x 16 rows so as to correspond to the hole of the well plate.
  • the PDMS thin film 111 is formed on the surface of the through-hole jig 10 as shown in the partial cross-sectional view shown in FIG. 1 (a).
  • Step S30 Next, as shown in a partial cross-sectional view shown in FIG. 1 (b), the PDMS thin film is sucked and / or depressurized from the back surface side of the jig 10 with a through hole at a set pressure through the through hole. 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 reducing the pressure.
  • Step S40 Next, as shown in a partial cross-sectional view shown in FIG. 1 (c), an elastic solution 112 (for example, PDMS solution) is injected over the PDMS thin film that has been bent after suction.
  • an elastic solution 112 for example, PDMS solution
  • a mold for example, PDMS mold
  • the elastic solution 112 for example, PDMS solution
  • a template material for example, PDMS
  • a mold 110 having protrusions in a shape is formed.
  • the mold 110 has a PDMS cured layer 112b formed on the PDMS thin film 111.
  • Step S60 Next, as shown in a partial cross-sectional view shown in FIG. 1 (e), a surface (also referred to as a convex surface) provided with protrusions of a mold 110 (for example, a PDMS mold) is brought into contact with the resin plate 114.
  • a force to the mold 110 in the direction of the resin plate 114 (directions A2 and A3 of arrows A2 and A3 in FIG. 1E) (here, as an example, the surface of the mold on which the protrusions are provided).
  • Heat while pressing from the opposite side) (for example, heat press at a predetermined temperature exceeding the glass transition point of the mold 110 and the glass transition point of the resin plate 114).
  • the resin plate 114 is made of a thermoplastic resin.
  • the thermoplastic resin include polyolefin resins such as polyethylene (PE), polypropylene (PP), polycycloolefin, and ethylene- ⁇ -olefin copolymer (for example, ethylene-propylene copolymer), polystyrene, and styrene-butadiene-.
  • Styrene block copolymer SBS
  • SEBS styrene / ethylene / butylene / styrene block copolymer
  • SEBS styrene / isoprene / styrene block copolymer
  • SEPS styrene block copolymer
  • Polystyrene resin such as hydrogenated styrene / butadiene random copolymer (HSBR), polyester resin such as polybutylene terephthalate, polyethylene terephthalate and polyethylene naphthalate, polyamide resin such as nylon 6, nylon 66 and nylon 46.
  • HSBR hydrogenated styrene / butadiene random copolymer
  • polyester resin such as polybutylene terephthalate, polyethylene terephthalate and polyethylene naphthalate
  • polyamide resin such as nylon 6, nylon 66 and nylon 46.
  • Acrylic resin such as polymethylmethacrylate (PMMA), polycarbonate resin, polyvinyl chloride resin, polyvinylidene chloride resin and the like can be exemplified, and these can be used alone or in combination of two or more. ..
  • the resin plate 114 is provided on a glass plate 113 which is an example of a support.
  • the protrusions of the PDMS mold are deformed and the tips of the protrusions are flattened, and the dents (also referred to as wells) formed in the resin plate accordingly.
  • the bottom surface of the recess (well) can be flattened, and the thickness between the bottom surface of the recess (well) and the bottom surface of the resin plate (hereinafter referred to as the thickness of the bottom surface of the recess (well)) can be reduced.
  • the resin plate is a resin whose temperature deformed by heat is lower than the heat resistant temperature of the mold.
  • the glass transition point when the resin plate is amorphous plastic, or the melting point when the resin plate is crystalline plastic. is lower than the heat resistant temperature of the elastic body (for example, PDMS) of the mold.
  • the resin softened by heat is sufficiently softer than the protrusions of the mold at the initial stage of the process, the resin is deformed by being pressed from the mold to form a dent.
  • the force required to reduce the wall thickness of the bottom of the recess is mainly the force required to deform the resin.
  • the force required to further reduce the wall thickness at the bottom of the depression is greater than the force required to deform the resin, such as the mold or support. Then, the force required to discharge the resin from the thin-walled portion against the frictional force acting between the resins is the main force. This force increases dramatically as the thickness of the thin part becomes thinner.
  • the stress applied to the mold increases as the thin-walled portion becomes harder to deform, and the protrusions of the mold made of the elastic body are crushed to deform so as to widen the area of the thin-walled portion. At this time, the shape of the thin-walled portion is almost flat.
  • Step S70 Next, the mold 110 is removed.
  • the well plate 120 (for example, a multi-well plate) in which the bottom surface of the recess (well) is flat and the bottom surface of the recess (well) is thin. ) Can be manufactured (see the lower perspective view of FIG. 1 (g)).
  • a well plate having 384 wells having a thickness of the bottom surface of the recess (well) of about 10 ⁇ m can be manufactured.
  • resin is used as the material of the well plate as an example, but the present invention is not limited to this, and a metal whose deformation temperature due to heat may be lower than the heat resistant temperature of the mold may be used.
  • the melting point of the metal may be lower than the heat resistant temperature of the elastic body of the mold.
  • the force required to further reduce the wall thickness at the bottom of the depression is greater than the force required to deform the metal, such as the mold or support.
  • the force required to discharge the metal from the thin-walled part against the frictional force acting between the metals is the main force. This force increases dramatically as the thickness of the thin part becomes thinner.
  • the stress applied to the mold increases as the thin-walled portion becomes harder to deform, and the protrusions of the mold made of the elastic body are crushed to deform so as to widen the area of the thin-walled portion. At this time, the shape of the thin-walled portion is almost flat.
  • the resin or metal is made of a mold provided with protrusions made of an elastic body having a heat resistance temperature higher than the softening temperature of the resin or metal, and the mold is harder than the mold.
  • the resin or metal softened by heat at the initial stage of the process is sufficiently softer than the protrusions of the mold, so that the resin or metal is deformed by being pressed from the mold to form a dent.
  • the force required to reduce the wall thickness of the bottom of the depression is mainly the force required to deform the resin or metal.
  • the force required to further reduce the wall thickness at the bottom of the depression is greater than the force required to deform the resin or metal.
  • the main force is required to discharge the resin or metal from the thin portion against the frictional force acting between the support and the resin or metal. This force increases dramatically as the thickness of the thin part becomes thinner.
  • the stress applied to the mold increases as the thin-walled portion becomes harder to deform, and the protrusions of the mold made of the elastic body are crushed to deform so as to widen the area of the thin-walled portion. At this time, the shape of the thin-walled portion is almost flat.
  • the frictional force acting between the resin or metal and the mold or support further increases, so as the thin part at the bottom of the depression becomes thinner, the wall thickness at the bottom of the depression increases. The force required to make it thinner increases at an accelerating rate.
  • a thin-walled molded product for example, a well plate
  • the bottom surface of the recess is flat and the thickness (thickness) of the bottom surface of the recess is thin.
  • a shape having a thin dent can be easily and inexpensively formed, and a structure having a thin dent can be formed over a wide area with a small error.
  • a thicker shape and a thinner shape can be integrally molded.
  • a thicker shape and a thinner shape can be continuously formed on a curved surface.
  • the method for manufacturing a thin-walled molded product includes a step of manufacturing a jig with a through hole provided with a thin film of an elastic body on the front surface and a step of sucking the thin film from the back surface side through the through hole. Further, it includes a step of injecting a solution of an elastic body from above a thin film bent after suction, and a step of forming the mold by heating and curing the solution.
  • Example 1> Hereinafter, the method of each step according to the first embodiment 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 air bubbles, and then spun at a predetermined rotation speed with a spin coater for a first set time. I coated it. This is placed on a second size tempered glass (for example, Tempax) larger than the first size and heated at a specified temperature higher than room temperature for a second set time.
  • PEN polyethylene naphthalate
  • a frame with a PDMS thin film (see FIG. 3) in which a PDMS thin film is provided in a hollow portion of the acrylic frame is produced.
  • FIG. 3 is an exploded perspective view for explaining attachment of the PDMS thin film to a jig with a through hole.
  • the frame 11 with a PDMS thin film provided with the PDMS thin film 111 is produced by the above-mentioned method for producing a PDMS thin film.
  • the well plate processing member 12 removes the adhesive from the bottom surface of the well plate without a bottom surface (here, as an example, a 384-well plate without a bottom surface), and at the time of attachment, the bottom surface side is on the upper side (frame 11 side with PDMS thin film).
  • the well plate processing member 12 is formed by cutting the outer peripheral frame portion on the bottom surface side by a predetermined length (for example, after processing with an ultrasonic cutter and then hooking it with a canna), and forming a portion into which an acrylic frame with a PDMS thin film is fitted.
  • a packing 17 is provided on the contact surface with the plate 14 having a plurality of through holes, which will be described later, by using a silicone adhesive and a polypropylene plate.
  • the shim plate is placed on the outer peripheral frame portion of the well plate processing member and sandwiched between the shim plate 13 and the frame 11 with the PDMS thin film, and the height of the well portion of the well plate processing member 12 and the frame with the PDMS thin film are formed.
  • the height of 11 is adjusted to be about the same.
  • the plate 14 with a plurality of through holes is, for example, an acrylic plate in which a plurality of (for example, 384) through holes are provided at intervals from each other.
  • Stage 15 is, for example, an aluminum stage. The stage 15 is placed in a die-cast box 16 described later, and is supported from below so that the plate 14 with a plurality of through holes is not distorted during suction.
  • the die-cast box 16 is an aluminum die-cast box.
  • 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 in one side plate of the die-cast box 16 by thread cutting, and a hollow member 18 (for example, a tube joint) is attached to the through hole.
  • the hollow member 18 serves as an intake port for suction.
  • the upper surface of the die-cast box 16 is open, and packing 19 is provided on the upper surface side edge of each of the four side plates. As a result, the packing 17 and the packing 19 are brought into close contact with each other, so that the bottom surface of the well plate processing member 12 and the die-cast box 16 can be sealed to prevent air from escaping.
  • 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 is the change distance at the center of the PDMS thin film
  • the horizontal axis is the suction pressure.
  • FIG. 4 shows the results of measuring the change distance of the center of the PDMS thin film using a confocal microscope by 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.
  • a mold having protrusions of a desired height can be produced, so that a well plate having a desired depth can be produced.
  • the measurement was performed by the following method.
  • the PDMS template preparation system of FIG. 3 was set upside down on the stage of a confocal microscope. At that time, the upper optical system (halogen lamp, etc.) of the confocal microscope was tilted backward, and the safety switch at the base of the upper optical system was always pressed by the silicone plate.
  • the diaphragm pump and regulator were connected to a set of jigs for making a PDMS mold and sucked at -0 to -0.06 mPa, and the 3D shape of the PDMS thin film at that time was observed in ZStack mode.
  • this 0.027 mPa was used as the set pressure at the time of suction in the mold making this time.
  • FIG. 5 is a schematic diagram for explaining a method for producing a PDMS template. As shown in FIG. 5, using the PDMS mold making system of FIG. 3, a mold having protrusions having a height of about 1.65 mm is made by PDMS.
  • the silicone rubber bank 21 was placed so as to surround the well plate processing member 12 on the PDMS thin film from four sides. A predetermined amount of the PDMS solution was dropped from above, and nitrogen gas was sprayed to develop the PDMS solution so as to cover the wells. This was placed in a desiccator and defoamed under reduced pressure. A diaphragm pump and a regulator were connected to the hollow member 18 in the PDMS mold making system, and the pressure was reduced by -0.027 mPa.
  • a specified amount of PDMS solution 22 is dropped onto the tempered glass 23 (for example, Tempax), and the tempered glass 23 and the PDMS solution 22 on the PDMS thin film are brought into contact with each other from this as a starting point to prevent bubbles from entering the tempered glass 23.
  • Tempax a specified amount of PDMS solution 22 is dropped onto the tempered glass 23
  • the tempered glass 23 and the PDMS solution 22 on the PDMS thin film are brought into contact with each other from this as a starting point to prevent bubbles from entering the tempered glass 23.
  • the space between the upper and lower stages of the heat press was covered with aluminum foil to keep it warm.
  • the PDMS mold making system was disassembled, the PDMS mold (PDMS + Tempax) was taken out, and the PDMS was completely cured by heating at a second temperature higher than the first temperature for a predetermined time. ..
  • FIG. 6A is an overall image of the PDMS template taken from above with a stereomicroscope.
  • FIG. 6B is a magnified image of the PDMS template taken from above with a stereomicroscope.
  • FIG. 6 (c) is a magnified image of the PDMS template taken obliquely from above with a stereomicroscope.
  • FIG. 6D is a magnified image of the PDMS template taken obliquely upward from another angle with a stereomicroscope.
  • the height of the protrusion represents the average ⁇ standard deviation of the height of the protrusion for 4 wells located in the center of each plate.
  • ⁇ Measurement method of protrusion height The appearance of the prepared PDMS mold was photographed and observed with a stereomicroscope.
  • a PDMS template is placed on the stage of a confocal microscope with the protrusions facing down, and the Z coordinates of the outside of the well and the tip of the protrusion (also called a convex part) are measured by detecting the reflection of a 488 nm laser, and the difference is used to measure the PDMS template.
  • N 4 wells, excitation wavelength: 488 nm, fluorescence wavelength: 483-493 nm).
  • the 3D shape was confirmed by autofluorescence of the PDMS template (excitation wavelength: 405 nm, fluorescence wavelength: 435 to 445 nm).
  • ⁇ Well plate molding method> Using a mold with a protrusion height of about 1.65 mm as an example, heat press molding of polycarbonate is performed, the appearance of the molded product is observed, and the 3D shape of each well is analyzed using a confocal microscope. went.
  • a resin plate for example, a polycarbonate plate
  • a tempered glass for example, Tempax
  • PDMS mold is placed on the resin plate (for example, a polycarbonate plate), and then the temperature is raised to the first predetermined temperature.
  • pressing was performed with a predetermined force for a second set time longer than the first set time.
  • the mold was water-cooled, and when the temperature reached the second predetermined temperature lower than the first predetermined temperature, the pressure was released and the molded product was taken out. The appearance of the molded product was photographed and observed with a stereomicroscope.
  • FIG. 8A is an overall image of bright-field observation of the bottom surface of the well according to Example 1 using a microscope.
  • FIG. 8B is a 1-well magnified image of a bright-field observation of the bottom of the well according to Example 1 using a microscope. Further, as shown in FIGS. 8 (a) and 8 (b), only interference fringes generated due to the thinness of the well are observed on the bottom surface of the well, and any serious damage such as breakage or penetration is observed. It was not confirmed in the well.
  • FIG. 9A is a graph showing the distribution of the heights of the protrusions of the PDMS template according to Example 1.
  • FIG. 9B is a graph showing the distribution of the thickness of the well bottom of the molded product.
  • FIG. 9C is a graph showing the distribution of well depths of the molded product according to Example 1.
  • the standard deviation of the PDMS template was relatively large at 26.5 ⁇ m (difference of up to about 300 ⁇ m), but the thickness of the well bottom of the molded product was less than 1/10 of the standard deviation of 2.43 ⁇ m (difference of about 14.2 ⁇ m at maximum).
  • the depth of the well itself of the molded product was 1565.2 ⁇ 21.1 ⁇ m.
  • FIG. 10A is a cross-sectional observation image of the protrusion of the PDMS mold according to the first embodiment.
  • FIG. 10B 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 is flatter than that of the mold, and as shown in FIG. 10 (c), the height is in the range of approximately 1000 ⁇ m in diameter. The plane had an error of 10 ⁇ m or less.
  • Example 2 similarly to Example 1, a mold having protrusions (convex parts) in an array of 24 columns x 16 rows was prepared by PDMS, and this was pressed against a polystyrene resin plate under heating to make the bottom surface thick. A container having 384 wells having a size of about 25 ⁇ m was prepared.
  • a PDMS mold having a protrusion (convex portion) height of about 1.85 mm was prepared, and the 3D shape of the prepared PDMS mold was analyzed using a confocal microscope.
  • FIG. 11A is an overall image of bright-field observation of the bottom of the well according to Example 2 using a microscope.
  • FIG. 11B is a 1-well magnified image of a bright-field observation of the bottom of the well according to Example 2 using a microscope. As confirmed in FIGS. 11 (a) and 11 (b), no serious damage such as breakage or penetration was confirmed in any of the wells.
  • FIG. 12A is a graph showing the distribution of the heights of the protrusions of the PDMS template according to Example 2.
  • FIG. 12B is a graph showing the distribution of the thickness of the well bottom of the molded product according to Example 2.
  • FIG. 12 (c) is a graph showing the distribution of well depths of the molded product according to Example 2.
  • the heights of the protrusions (convex portions) of the PDMS mold are substantially uniform.
  • the standard deviation of the PDMS mold was 22.9 ⁇ m (maximum difference of about 150 ⁇ m), but the thickness of the well bottom surface of the molded product was 1/8 of the standard deviation of 2.9 ⁇ m (maximum difference of 18.3 ⁇ m). It was reduced to a degree.
  • the depth of the well itself of the molded product was 1612.3 ⁇ 15.2 ⁇ m.
  • FIG. 13 is a cross-sectional observation image of the bottom surface of the well of the molded product according to Example 2.
  • the bottom surface of the well of the molded product was a flat surface within a range of approximately 900 ⁇ m in diameter and within an error of 10 ⁇ m in the height direction. As described above, it was shown that this method can be applied to a wide range of resins as a material for molded products.
  • a thin shape can be easily and inexpensively formed.
  • a thin structure can be formed over a wide area with a small error.
  • a thicker shape and a thinner shape can be integrally molded.
  • a thicker shape and a thinner shape can be continuously formed on a curved surface.
  • the method for producing a mold in this embodiment is an example, and is not limited to this.
  • the second embodiment will be described.
  • the structure of the well plate manufactured by the manufacturing method according to the first embodiment will be described.
  • 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 portion of the well bottom is about 200 ⁇ m 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. The round bottom of the well allows cells to gather in the center of the bottom of the well.
  • the multi-well plate collects a small number of cells seeded in the well near the center due to its round bottom shape, and makes it easy to detect by microscopic observation or the like, so that a small number of cells from one cell, which has become important in recent years, is available. It is very useful in the study of precise analysis of individual cells.
  • microscopic observation using a high-magnification objective lens is often performed. For example, in a clinical sample test, the shape of an intracellular nucleus is observed using a 40x, 63x, or 100x objective lens.
  • a 63x or 100x objective lens is used in the FISH test for detecting a specific sequence in the nucleus and the method for observing an intracellular organelle or a specific molecule by staining it with a fluorescent dye or the like.
  • a 100x objective lens is used for finer structures, three-dimensional detailed observations, and ultra-resolution microscope observations that won the 2014 Nobel Prize in Chemistry. After the phenotype of such cells is analyzed, the genotype is often analyzed by PCR or the like. Therefore, in detailed microscopic analysis of a small number of cells from one cell targeted by the multi-well plate, it is desirable that up to a 100x objective lens can be applied. Since the focal length is short with a high-magnification objective lens, there is a limit to the thickness of the bottom surface of the well where the sample can be observed.
  • well plates of wells having a diameter of 2 mm with various well bottom surface thicknesses were produced.
  • polycarbonate was used as an example of the resin to be composed.
  • Ba / F3 cells in a well (polycarbonate) having a diameter of 2 mm were observed by changing the thickness t of the bottom of the well using an oil-immersed 100x objective lens.
  • FIG. 14 is an example of Ba / F3 cells imaged using an oil-immersed 100x objective lens in the case of various bottom thicknesses. It was possible to focus on the cells located on the bottom of the well up to a thickness t of the bottom of the figure of 133.3 ⁇ m, but on the bottom of 156.2 ⁇ m, the focus was achieved even if the oil-immersed 100x objective lens was brought into contact with the bottom of the well. Can not be matched. Therefore, the thickness of the bottom surface of the well is preferably 150 ⁇ m or less.
  • the well plate according to the second embodiment is a well plate made of resin and provided with at least one well, the well has a round bottom, and the thickness of the center portion of the bottom of the well.
  • the size is preferably 150 ⁇ m or less.
  • the wells since the wells have a round bottom, the cells seeded in the wells are concentrated in the center of the bottoms of the wells, so that the observation of the cells can be facilitated.
  • the thickness of the central part of the bottom surface of the well is 150 ⁇ m or less, the focus can be focused on the cells existing on the bottom surface of the well even with an oil-immersed 100x objective lens, and details of a small number of cells from one cell. Can reliably perform microscopic analysis.
  • FIG. 15 is a diagram showing an example of characteristic damage that increases depending on the thinness of the bottom surface of the well.
  • Image G1 is a phase image of a normal well 5x objective lens without damage.
  • image G2 is a phase image of a 5x objective lens of a damaged well. As shown by the arrow A1 in the image G2, a crescent-shaped scratch is formed on the bottom surface of the well. In this way, as the bottom surface of the well is made thinner, the number of cases where crescent-shaped scratches are confirmed on the bottom surface of the well increases.
  • 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 broken well rate in the 384 wells.
  • FIG. 16 shows the experimental results of a set of press time, average thickness of the center of the bottom surface of the well (also referred to as the average thickness of the center of the bottom surface), the number of broken wells, and the broken well rate.
  • the average thickness of the thinnest part of the well bottom is represented by the average value of 384 wells of the thinnest part of the well bottom and a standard error. No damaged wells were confirmed until the average thickness of the thinnest part of the well bottom was 8.24 ⁇ 1.57 ⁇ m.
  • the average thickness of the thinnest part of the bottom of the well became thinner than 7.98 ⁇ 1.45 ⁇ m, a well with breakage was confirmed. That is, it is critical that the average thickness of the central portion of the bottom surface of the well (or the thickness of the thinnest portion of the bottom surface of the well) is 8 ⁇ m or more.
  • the average thickness of the thinnest part of the well bottom is 7.52 ⁇ 1.69 ⁇ m, and the breakage rate is 5.21%.
  • the average thickness of the thinnest part of the well bottom is 7.05 ⁇ 1.23 ⁇ m, and the breakage rate is 7.81%.
  • the average thickness of the thinnest part of the well bottom is 6.97 ⁇ 1.77 ⁇ m and the damage rate is 16.81%, and the average thickness of the thinnest part of the well bottom is 6.93 ⁇ 1.58 ⁇ m and the damage rate is 20. It was .83%, and the damage rate exceeded 20%.
  • the breakage rate sharply increases. That is, it is critical that the average thickness of the central portion of the bottom surface of the well (or the thickness of the thinnest portion of the bottom surface of the well) is 7 ⁇ m or more.
  • the average thickness of the thinnest part of the well bottom (or the thickness of the thinnest part of the well bottom). ) Is preferably 7 ⁇ m or more. Further, from the viewpoint of a plate having sufficient strength so that all wells cannot be damaged in manufacturing or the like, it is more preferable that the average thickness of the thinnest part of the well bottom (or the thickness of the thinnest part of the well bottom) is 8 ⁇ m or more. ..
  • FIG. 17 is an example of an image of a vertical cross section of a well obtained by a confocal microscope. 30% (0.3 mm as an example) of the well radius r (1 mm here as an example) away from the center P0 of the bottom of the well, and 60% (0.6 mm as an example) of points P1 on the bottom of the well.
  • a point P2 on the bottom of the well and a point P3 on the bottom of the well 90% (0.9 mm as an example) away are shown.
  • the radius of the well is the radius of the circle indicated by the horizontal cross section of the well at a height above the bottom of the well by 80% of the height between the bottom of the well and the opening, except that the radius of the well is above the bottom of the well.
  • the bottom surface of the well In the range of 80% to 100% of the height between the bottom surface and the opening, if there is no well wall surface where the tangent line of the well wall surface in the vertical cross section of the well is 80 ° to 90 ° with respect to the horizontal plane, the bottom surface of the well The radius of the circle indicated by the horizontal cross section of the well at a height above the bottom of the well by 50% of the height from to the opening. A circle C1 passing through this point P1, P2, P3 is shown. In the present embodiment, the radius of the circle C1 is defined as the radius of curvature of the bottom surface of the well.
  • FIG. 18 is an example of a vertical cross-sectional image of a well obtained by a confocal microscope in the case of various bottom thicknesses.
  • FIG. 18A shows the thickness t of the thinnest part of the well bottom 14 ⁇ m
  • FIG. 18B shows the thickness t of the thinnest part of the well bottom 38 ⁇ m
  • FIG. 18C shows the thickness of the thinnest part of the well bottom.
  • FIG. 18 (d) shows an example of a vertical cross-sectional image of a well when t is 76 ⁇ m
  • FIG. 18 (d) shows a thickness t of the thinnest part of the well bottom of 144 ⁇ m
  • 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 portion of the well bottom.
  • the shape of the wells obtained in the experimental results of FIG. 18 will be qualitatively described with reference to FIG.
  • the radius of the well is 1 mm.
  • the radius of curvature is 0.91 mm, which is smaller than 1 mm when the mold is not deformed, as represented by the circle C11 of the radius of curvature.
  • the thickness t of the thinnest portion of the well bottom is around 19 ⁇ m, as shown by the circle C12 having the radius of curvature, for example, the smallest radius of curvature is 0.82 mm. It is considered that this is because, as a principle of this resin processing method, the bottom surface of the mold near the glass plate to be the underlay receives a particularly large stress, so that the bottom surface of the mold is greatly deformed as compared with other parts of the mold. ..
  • the radius of curvature is 0.92 mm, which is smaller than 1 mm when the mold is not deformed, as represented by the circle C13 of the radius of curvature.
  • the thickness t of the thinnest part of the well bottom becomes thicker than about 76 ⁇ m, the action of receiving a particularly large stress on the bottom surface of the mold becomes small, and the entire mold is uniformly stressed and deformed into a flat shape. ..
  • the radius of curvature is 1.2 mm
  • the radius of curvature is 1.3 mm. The radius of curvature increases, exceeding the radius of curvature of 1 mm when the mold is not deformed.
  • 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 divided by the radius of the well.
  • the well plate manufactured by the manufacturing method according to the present embodiment has a characteristic well bottom shape, and is the ratio of the thickness of the thinnest part of the well bottom and the radius of curvature of the well bottom divided by the radius of the well.
  • the relationship with is as shown in the graph of FIG.
  • the radius of curvature of the bottom surface of the well used to calculate the ratio of each plot of the graph of FIG. 20 is the average value of four values measured from the arcs of the bottom surfaces of the four sides of the well.
  • the four sides of the well are parallel to the vertical row of wells and in two opposite directions passing through the center of the well bottom, and parallel to the horizontal row of wells and passing through the center of the well bottom in two opposite directions. is there.
  • the four directions for measuring the radius of curvature of the bottom surface of the well may be directions perpendicular to each other.
  • Each plot in the graph of FIG. 20 represents a representative example point.
  • 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 defined as y.
  • the coefficient of determination R 2 of this regression equation is 0.9999.
  • the thickness x of the thinnest part of the well bottom is in the range of 0 to 200 ⁇ m
  • the ratio of the radius of curvature of the well bottom divided by the radius of the well is 0.7 to 1.5. Is. According to this configuration, the thickness of the bottom surface of the well can be reduced with a round bottom.
  • the present invention is not limited to the above-described embodiment as it is, and at the implementation stage, the components can be modified and embodied within a range that does not deviate from the gist thereof.
  • various inventions can be formed by an appropriate combination of the plurality of components disclosed in the above-described embodiment. For example, some components may be removed from all the components shown in the embodiments. Further, components over different embodiments may be combined as appropriate.

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PCT/JP2020/044018 2019-11-29 2020-11-26 薄肉成形品の製造方法及びウェルプレート Ceased WO2021107008A1 (ja)

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Publication number Priority date Publication date Assignee Title
JP2012249547A (ja) * 2011-05-31 2012-12-20 Oji Holdings Corp 細胞培養用基材及びその製造方法
JP2013248749A (ja) * 2012-05-30 2013-12-12 Toshiba Mach Co Ltd 型および型の製造方法

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US8633052B2 (en) 2008-04-18 2014-01-21 1366 Technologies Inc. Wedge imprint patterning of irregular surface
EP2758999A4 (en) 2011-09-23 2016-01-27 1366 Tech Inc METHOD FOR IMPROVED PRINTING OF A SOFT MATERIAL ON A SUBSTRATE BY MEANS OF A STAMP WITH A SUBSTITUTE FOR PRODUCING A COLUMN AND A PULSATING STAMP

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012249547A (ja) * 2011-05-31 2012-12-20 Oji Holdings Corp 細胞培養用基材及びその製造方法
JP2013248749A (ja) * 2012-05-30 2013-12-12 Toshiba Mach Co Ltd 型および型の製造方法

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