JP5344414B2 - Manufacturing method of flow channel chip - Google Patents

Description

  The present invention relates to a method for manufacturing a channel chip.

  In recent years, a great deal of attention has been focused on separation / analysis chips for the purpose of environmental measurement and biological / bioanalysis applications. In order to improve the performance of the chip, a chip having a more complicated flow path is required. From such a viewpoint, a chip having a three-dimensional channel has been recently made. A three-dimensional chip is generally made by stacking planar structures. However, this method has a drawback that it takes time.

  Therefore, for example, a method has been reported in which a three-dimensional structure of a flow path is made with a metal wire or polymer thread, the periphery is solidified with a silicone resin, and then the metal wire or thread is pulled out from the silicone resin (Non-Patent Document 1, Non-patent document 2). There is also a method in which a 3D flow path template is made with solder and the periphery is solidified with silicone resin, and then the flow path is created by removing the solder inside the silicone resin by reducing the pressure while heating to about 200 ° C ( Non-patent document 3). In addition, a method of directly creating a three-dimensional structure inside a resin using stereolithography using materials other than silicone resin has been reported (Non-Patent Document 4).

Agrawal S, Morarka A, Paknikar KM, Bodas D: In sutu synthesis of Au nanoparticles in 3D circular microchannels in PDMS using a simple and reliable molding method.Microelectron Eng, Vol. 90, PP104-107, 2011 Verma MKS, Majumder A, Ghatak A: Embedded template-assisted fabrication of complex microchannels in PDMS and design of a microfluidic adhesive.Langmuir, Vol. 22, PP.10291-10295, 2006 S-H Song, C-K Lee, T-J Kim, I Shin, S-C Jun, H-I Jung: A rapid and simple fabrication method for circular microfluidic channel using metal wire removal process.Microfluid Nanofluid, Vol. 9, PP.533-540, 2010 Therriault D, White S, Lewis J: Chaotic mixing in three-dimensional microvascular networks fabricated by direct-write assembly.Nature mater, Vol. 2, PP.265-271, 2002

  With the methods described in Non-Patent Document 1 and Non-Patent Document 2, it is difficult to produce a long and complicated flow path. In addition, there is a problem that the operation for pulling out takes time. The method described in Non-Patent Document 3 is dangerous because it requires a special operation of depressurizing at a high temperature and the solder may be vaporized. In the method described in Non-Patent Document 4, there is a problem that materials and apparatuses are expensive.

  Accordingly, an object of the present invention is to provide a new method for producing a chip having a flow path inside, which can be formed even with a complicated flow path by a relatively simple operation.

A method of manufacturing a chip having a flow path therein,
(1) A coating material having a melting point at a temperature in the range of 0 to 150 ° C. is applied to the surface of a linear material that is solid at the melting point of the coating material and has a solubility, thereby producing a channel template. Process,
(2) a step of embedding the template in a curable chip forming material and then curing the chip forming material;
(3) A step of heating the cured material in which the template is embedded to a temperature equal to or higher than the melting point of the coating material applied to the template surface, melting the coating material on the template surface, and causing the cured material to flow out of the cured material;
(4) A method comprising a step of dissolving a linear material by injecting a solution for dissolving the linear material into a gap formed between the template and the cured product (first aspect of the present invention) ).

A method of manufacturing a chip having a flow path therein,
(11) A step of producing a channel template using a hollow linear material,
(12) a step of embedding the template in a curable chip forming material and then curing the chip forming material;
(13) A method comprising a step of injecting a solution for dissolving the linear material into the hollow portion of the template to dissolve the linear material to form a chip having a flow path therein (second embodiment of the present invention). Embodiment).

  According to the present invention, a chip having a flow path that can be formed even with a complicated flow path such as a three-dimensional flow path can be manufactured by a relatively simple operation.

FIG. 1 is a perspective explanatory view of an experimental operation in the first embodiment. FIG. 2 is a schematic cross-sectional explanatory diagram of the experimental operation in Example 1. FIG. 3 is a schematic cross-sectional explanatory diagram of the experimental operation in Example 2. FIG. 4 is a perspective explanatory view of an experimental operation in the second embodiment. FIG. 5 is a perspective explanatory view of an experimental operation in the third embodiment. FIG. 6 is an explanatory diagram of the photoreaction experimental apparatus used in Example 3. FIG. 7 shows the results of a photoreaction experiment using titanium oxide in Example 3. FIG. 8 is a photograph showing a state of coating the inner wall of the channel with an ultraviolet curable fluorine-based epoxy resin in the solvent resistance experiment of the chip channel in Example 4. FIG. 9 is a flowchart of two types of methods for forming a coating layer on the inner wall of the chip channel. FIG. 10 is a photograph showing a state of manufacturing a chip in Example 5 (method (1) on the left side of FIG. 9). FIG. 11 is a photograph showing a state of manufacturing a chip in Example 6 (method (2) on the left side of FIG. 9).

<First embodiment of the present invention>
The method for producing a chip having a flow channel inside the first aspect of the present invention is a method including the following steps (1) to (4).
(1) A coating material having a melting point at a temperature in the range of 0 to 150 ° C. is applied to the surface of a linear material that is solid at the melting point of the coating material and has a solubility, thereby producing a channel template. Process,
(2) a step of embedding the template in a curable chip forming material and then curing the chip forming material;
(3) A step of heating the cured material in which the template is embedded to a temperature equal to or higher than the melting point of the coating material applied to the template surface, melting the coating material on the template surface, and causing the cured material to flow out of the cured material;
(4) A method comprising a step of dissolving the linear material by injecting a solution for dissolving the linear material into a gap formed between the template and the cured product.

Process (1)
In step (1), a flow path template is prepared. The template is prepared by applying a coating material having a melting point at a temperature in the range of 0 to 150 ° C. to the surface of a linear material that is solid at the melting point of the coating material and has solubility. The coating material is preferably coated on the front surface excluding the end surface of the surface of the linear material, and the coating amount is appropriately determined according to the amount of gap to be formed between the template and the cured product in step (3). It is determined. The coating amount is, for example, in the range of 0.01 to 1.0 mm, preferably in the range of 0.05 to 0.5 mm, and more preferably in the range of 0.1 to 0.4 mm in terms of the thickness of the coating material.

  Coating materials having a melting point at a temperature in the range of 0 to 150 ° C. include, for example, polyethylene glycol, paraffin, low temperature solder (low melting point alloy), ionic liquid, petroleum jelly, wax (lipid), caprolactone, stearic acid, and palmitic acid. It can be at least one material selected from the group consisting of: Even if it is a material other than these, if it is a material which has melting | fusing point in the temperature of the range of 0-150 degreeC, it can use suitably as said coating | coated material. When the melting point of the coating material is less than 0 ° C., it is necessary to perform the coating operation at a temperature less than 0 ° C., which is complicated. When the melting point of the coating material exceeds 150 ° C., the melting operation in the step (3) must be performed at a temperature exceeding 150 ° C., and a material having high heat resistance is used as the curing material constituting the chip. Convenience is reduced, such as the need to come out and the need to carry out the melting operation at a high temperature. The melting point of the coating material is, for example, preferably in the range of 30 to 100 ° C., more preferably in the range of 50 to 100 ° C., considering the ease of operation.

  As the coating material, it is preferable to use polyethylene glycol having an arbitrary melting point depending on the molecular weight. Polyethylene glycol can have a molecular weight in the range of, for example, 600 (melting point 18-23 ° C.) to 300,000 (melting point approximately 65 ° C.), more preferably 1000 (melting point 35-39 ° C.) to 20,000 (melting point 58 -63 ° C).

  The linear material may be at least one material selected from the group consisting of a metal material, an inorganic material, and an organic material. Furthermore, the metal material can be a pure metal or an alloy material, and the inorganic material can be a glass or a ceramic material (eg, alumina). Examples of pure metals include iron, aluminum, copper, magnesium, zinc, tin, silicon, silver, lead, manganese, nickel, chromium and titanium. Examples of alloys include iron alloys (stainless steel, chromium molybdenum steel, manganese molybdenum steel, 42 alloy, invar, kovar, sendust, permendur, silicon steel, KS steel, Spiegel Eisen), copper alloys (brass, red copper) , Tomback, white, bronze, white bronze, bronze, constantan, kunife), aluminum alloy (duralumin, silmine), nickel alloy (nichrome, inconel, hastelloy, monel, permalloy), others (magnesium alloy, amalgam, solder) Can be mentioned. Examples of organic materials include DNA, polysaccharides (starch, cellulose, chitin, chitosan, pullulan, curdlan, alginic acid, hyaluronic acid, dextran, xanthan), peptides (gluten, zein), collagen, gelatin, fibroin, sericin, Examples thereof include keratin, casein, albumin, and polyamino acid (cyanophycin, polyglutamic acid, polylysine, polyaspartic acid).

  The linear material may be a solid material or a hollow material. However, in the case of a material having a small diameter, the formation of a hollow material is not easy, and thus a solid material is preferable. On the other hand, for a linear material having a relatively large diameter, formation of a hollow material is easy, and in step (4), a solution for dissolving the linear material is also injected into the hollow to dissolve the linear material. There is also an advantage that can be promoted. The linear material may have a circular cross section or a square shape (for example, a triangle, a square, a rectangle, or a pentagon or more polygon).

  The shape of the template can be determined as appropriate according to the structure of the flow channel desired to be formed in the chip. The shape of the template can be a three-dimensional structure, a two-dimensional structure or a one-dimensional structure. Depending on the structure of the flow path, a plurality of templates can be used. The linear material may have a uniform diameter in the length direction, or may have a partially changed diameter or a changed sectional shape.

Process (2)
In step (2), the template formed in step (1) is embedded in a curable chip forming material. The curable chip-forming material can be at least one material selected from the group consisting of organic materials. However, since the template has a coating layer made of a coating material having a melting point at a temperature in the range of 0 to 150 ° C., a chip forming material that can select conditions under which the coating layer does not melt when cured is appropriately selected. Is appropriate. Although it depends on the type of material constituting the coating layer, the curable chip forming material includes, for example, an epoxide, an epoxy (EP), a phenol formaldehyde (PF), a polyurethane (PUR), a urea- Examples include formaldehyde (UF), unsaturated polyester (UP), polymethyl methacrylate (PMMA), and silicone resin. In addition, polycaprolactone (PCL), which is a bioplastic material, can be exemplified as a kind of organic material.

  In the step (2), the curable chip forming material in which the template is embedded is cured. The curing method and conditions can be appropriately determined according to the type of chip forming material. For example, when the chip forming material is a photocurable material, a curable light beam such as ultraviolet light or visible light is irradiated. When the chip forming material is a thermosetting material, it is cured by heating. The photocuring and thermosetting methods and conditions can be determined as appropriate with reference to conventional methods.

Process (3)
In the step (3), the cured product in which the template is embedded is heated to a temperature equal to or higher than the melting point of the template surface coating material to melt the template surface coating material and flow out of the cured product. The coating material is a material having a melting point at a temperature in the range of 0 to 150 ° C. Therefore, the coating material on the template surface can be melted by heating to a temperature higher than the melting point. For example, when the coating material is polyethylene glycol 2000 (molecular weight 2000, melting point 45-55 ° C.), the coating material (polyethylene glycol 2000) is heated by heating to a temperature above the melting point, for example, 70 to 80 ° C. Can be melted.

  In the heating method, for example, the chip can be directly heated using an oven or a hot plate to melt the coating. Alternatively, for example, a microwave oven can be used. In this case, the coating can be melted by placing the chip in water and raising the temperature in the chip by heat conduction by heating the water in a microwave oven. By placing the chip in water or a medium other than water (for example, silicone oil) and heating the medium using an oven or a hot plate, the coating in the chip can be melted by heat conduction. Moreover, when the linear material which forms a template is a metal, it can be made to melt | dissolve by supplying current and heating.

  The melt of the coating material can be promoted to flow out of the cured product, for example, by sucking with aspirator or the like.

Process (4)
In the step (4), the linear material is dissolved by injecting a solution for dissolving the linear material into a gap formed between the template and the cured product. The solution for dissolving the linear material can be, for example, an acid aqueous solution, an acid and hydrogen peroxide mixed aqueous solution, a base aqueous solution or water, and can be appropriately selected according to the material of the linear material. Examples of the acid include hydrochloric acid, sulfuric acid, nitric acid, perchloric acid, hydrofluoric acid, oxalic acid and the like. Examples of the acid and hydrogen peroxide mixed aqueous solution include an aqueous solution obtained by mixing the acid and hydrogen peroxide solution. Examples of the base include sodium hydroxide and potassium hydroxide. Water is used when the linear material is formed of a water-soluble substance. By dissolving and removing the linear material of the template, a flow path having a three-dimensional structure, a two-dimensional structure, or a one-dimensional structure corresponding to the shape of the template can be formed in the chip.

<Second embodiment of the present invention>
The method for producing a chip having a flow channel inside the second aspect of the present invention is a method including the following steps (11) to (13).
(11) A step of producing a channel template using a hollow linear material,
(12) a step of embedding the template in a curable chip forming material and then curing the chip forming material;
(13) A method comprising a step of injecting a solution for dissolving the linear material into the hollow portion of the template to dissolve the linear material to form a chip having a flow path therein (second embodiment of the present invention). Embodiment).

Process (11)
A channel template is prepared using a hollow linear material.
If the linear material is hollow, it can be at least one material selected from the group consisting of metal materials, inorganic materials, and organic materials. Furthermore, the metal material can be a pure metal or an alloy material, and the inorganic material can be a glass or a ceramic material (eg, alumina). Examples of pure metals include iron, aluminum, copper, magnesium, zinc, tin, silicon, silver, lead, manganese, nickel, chromium and titanium. Examples of alloys include iron alloys (stainless steel, chromium molybdenum steel, manganese molybdenum steel, 42 alloy, invar, kovar, sendust, permendur, silicon steel, KS steel, Spiegel Eisen), copper alloys (brass, red copper) , Tomback, white, bronze, bronze, bronze, bronze, constantan, kunife), aluminum alloy (duralumin, silmine), nickel alloy (nichrome, inconel, hastelloy, monel, permalloy), others (magnesium alloy, amalgam, solder) Can be mentioned. Examples of organic materials include DNA, polysaccharides (starch, cellulose, chitin, chitosan, pullulan, curdlan, alginic acid, hyaluronic acid, dextran, xanthan), peptides (gluten, zein), collagen, gelatin, fibroin, sericin, Examples thereof include keratin, casein, albumin, and polyamino acid (cyanophycin, polyglutamic acid, polylysine, polyaspartic acid).

  In the hollow linear material, the hollow is formed by injecting a solution for dissolving the linear material into the hollow in the step (13) to promote the dissolution of the linear material. The outer diameter of the material), the ease of injection of the dissolution solution (hollow inner diameter), and the ease of production of the linear material can be determined as appropriate. However, from the viewpoint of ease of injection of the dissolved solution, the hollow inner diameter is preferably 0.01 mm or more, more preferably 0.1 mm or more, still more preferably 0.5 mm or more, 1 mm or more Even more preferably. The linear material may have a circular cross section or a square shape (for example, a triangle, a square, a rectangle, or a pentagon or more polygon).

  The shape of the template can be determined as appropriate according to the structure of the flow channel desired to be formed in the chip. The shape of the template can be a three-dimensional structure, a two-dimensional structure or a one-dimensional structure. Depending on the structure of the flow path, a plurality of templates can be used. The linear material may have a uniform diameter in the length direction, or may have a partially changed diameter or a changed sectional shape.

Process (12)
The template is embedded in a curable chip forming material, and then the chip forming material is cured. This step can be performed in the same manner as the step (2) of the first aspect. However, in the second aspect, since the template does not have a coating layer, it is not necessary to consider melting of the coating material due to heating during curing at the time of embedding. The curable chip-forming material can be at least one material selected from the group consisting of organic materials and inorganic materials.

Examples of organic materials are shown below.
Epoxide: Epoxy (EP), Melamine-formaldehyde (MF), Polyamide (nylon) (PA), Polyamide / imide (PAI), Polybutylene terephthalate (PBT), Polycarbonate (PC), Polyallyl diallyl (PDAP), Polyethylene ( PE), polyether ether ketone (PEEK), polyether imide (PEI), polyether sulfone (PES), polyethylene terephthalate (PET), phenol formaldehyde (PF), polyimide (PI), polymethyl methacrylate (PMMA), Polypropylene (PP), polyphenylene ether (PPE), polyphenylene sulfide (PPS), polystyrene (PS), polysulfone (PSU), polyurethane (PUR), polyvinyl alcohol (PVAL), polyvinyl acetate (PVAC), polyvinyl chloride (PVC) ), Polyvinylidene chloride (PVDC), Rear - formaldehyde (UF), unsaturated polyester (UP), fluorine resin, silicone resin

Copolymer material Acrylonitrile / Butadiene / Styrene (ABS)
Styrene / Acrylonitrile (SAN)

Bioplastic material polyhydroxyalkanoate (PHA)
Polylactic acid (PLA)
Polyglycolic acid (PGA)
Polycaprolactone (PCL)
Polybutylene succinate (PBSA)
Polybutylene succinate adipate (PBAT)
Polypropylene terephthalate (PPT)

  Examples of the inorganic material include glass, quartz, silicon, and the like.

Process (13)
A solution for dissolving the linear material is injected into the hollow portion of the template to dissolve the linear material, thereby forming a chip having a flow path therein. In the step (13), a solution for dissolving the linear material is injected into the hollow portion of the template. The dissolving solution can be, for example, an acid aqueous solution, an acid and hydrogen peroxide mixed solution, a base aqueous solution, or water, and can be appropriately selected according to the material of the linear material. Examples of the acid include hydrochloric acid, sulfuric acid, nitric acid, perchloric acid, hydrofluoric acid, oxalic acid and the like. Examples of the acid and hydrogen peroxide mixed aqueous solution include an aqueous solution obtained by mixing the acid and hydrogen peroxide solution. Examples of the base include sodium hydroxide and potassium hydroxide. Water is used when the linear material is formed of a water-soluble substance. By dissolving and removing the linear material of the template, a flow path having a three-dimensional structure, a two-dimensional structure, or a one-dimensional structure corresponding to the shape of the template can be formed in the chip.

Process (5)
The method may further include a step (5) of providing a coating layer on the inner wall of the flow channel of the chip having the flow channel inside formed in the step (4) in the first mode and the step (13) in the second mode. . Formation of the coating layer in the step (5) can be performed, for example, by applying a photocurable material to the inner wall of the flow path and then photocuring. Application of the photocurable material to the inner wall of the flow path is, for example, by introducing the photocurable material into the flow path, and then circulating a gas such as nitrogen gas through the flow path, and photocuring while maintaining the flow. It can be carried out. The photocurable material for forming the coating layer can be, for example, a fluorine-based epoxy resin.

  In the step (5), a chip having a coating layer on the inner wall of the flow path is provided. As a method other than the step (5), in the second embodiment of the present invention, a linear material having a coating layer on the surface is used as the template in the step (12), and the template linear shape in the step (13) By dissolving the material and leaving the coating layer remaining, it is possible to form a channel having the coating layer inside the chip. Also by this method, a chip having a channel having a coating layer inside can be obtained.

  Examples of the material for forming the coating layer on the surface of the template in the step (12) include resins, glasses, metals and ceramics. Examples of the resin include polyethylene, polypropylene, Teflon, and a fluorine-based epoxy resin. Examples of the metal include all metals that can be coated by electrolytic plating or chemical plating (gold, silver, copper, iron, nickel, chromium, tin, lead, platinum, etc.). Examples of ceramics include alumina, zirconia, titanium oxide, silicon carbide, silicon nitride, aluminum nitride, boron nitride, and sialon. In particular, when the material constituting the chip is a resin, from the viewpoint of improving the solvent resistance of the flow path, the material constituting the coating layer is suitably a material having high solvent resistance. Examples include Teflon, fluorine-based epoxy resin, polyethylene, polypropylene, glass, gold, platinum, zirconia, and titanium oxide.

  Examples of the method for forming the coating layer on the surface of the hollow linear material used as the template include the methods shown on the left and right sides of FIG. In the method (1) shown on the left side of FIG. 9, a plastic covering material (polyethylene, polypropylene, etc.) is applied to the surface of a linear material, and then deformed into the shape of a flow path to obtain a template. In this method, the coating material to be used is limited to a plastic material, but since the coating layer is formed before the flow path shape processing, coating is easy and a coating layer with a uniform thickness can be easily formed. . In the method (2) shown on the right side of FIG. 9, a linear material is deformed into the shape of a flow path, and then a coating material is applied to the surface to form a coating layer to obtain a template. This method can be applied regardless of whether the covering material is plastic. Therefore, although the application range is wide, when the template shape is complicated, coating becomes difficult, and formation of a coating layer having a uniform thickness tends to be difficult.

  In step (13), the linear material of the template is dissolved as in step (13) described above. By dissolving the linear material and leaving the coating layer formed on the surface of the linear material, it is possible to form a channel having the coating layer inside the chip. From the viewpoint of dissolving the linear material and leaving the coating layer formed on the surface of the linear material, the coating layer is a material that is not soluble in the linear material solution, or the solubility is linear. It is preferable to select a material lower than the shape material from the viewpoint that the coating layer remains.

  Hereinafter, the present invention will be described in more detail with reference to examples.

Example 1
Embodiment 1 will be described with reference to FIGS. FIG. 1 is a perspective explanatory view, and FIG. 2 is a schematic cross-sectional explanatory view.

  As shown in (1A) of FIG. 1 and (2A) of FIG. 2, an iron wire (diameter 0.3 mm) was deformed into the shape of a flow path. Next, as shown in FIG. 1 (1B) and FIG. 2 (2B), a template was prepared by applying polyethylene glycol (PEO) 2000 (manufactured by Wako Pure Chemical Industries, Ltd.) (average molecular weight 2000) to an iron wire having a channel shape. At the time of application, PEO was heated to a liquid state, applied to a template using a brush, and then cooled at room temperature to solidify the PEO. The coating amount of PEO was about 0.18 mm in thickness. Next, as shown in (1C) of FIG. 1 and (2C) of FIG. 2, this template is placed in an uncured silicone resin (PDMS: polydimethylsiloxane) filled in a container and allowed to stand at room temperature. The silicone resin was cured. As for the silicone resin, a mixture of a base of SILPOT184 (manufactured by Dow Corning Toray) and a curing agent in a ratio of 10: 1 was used. After that, as shown in (1D) of FIG. 1, PEO is made liquid with hot water (90-100 ° C.) ((2D) of FIG. 2), and then hot water is injected into the chip, so that the PEO on the surface of the iron wire is obtained. Is then eluted from the silicone resin ((2E) in FIG. 2), and then a 40% aqueous phosphoric acid solution is poured into the void formed by the dissolution of PEO ((2F) in FIG. 2). Dissolved to form a flow path. Finally, the silicone resin was taken out of the container to complete the chip ((1E) in FIG. 1 and (2G) in FIG. 2).

Example 2
As shown in (3A) of FIG. 3 and (4A) of FIG. 4, an aluminum tube (inner diameter 2 mm, outer diameter 3 mm) was deformed to produce a template. Next, the template was placed in an uncured silicone resin (PDMS: polydimethylsiloxane) filled in a container, and then the silicone resin was cured by heating at 80 ° C. As for the silicone resin, a mixture of a base of SILPOT184 (manufactured by Dow Corning Toray) and a curing agent in a ratio of 10: 1 was used. Next, a solution was poured into the template tube to dissolve the aluminum tube at room temperature to form a flow path. The solution used was a mixture of concentrated hydrochloric acid (35-37%) and 30% hydrogen peroxide in a ratio of 1: 1. Finally, the silicone resin was taken out of the container to complete the chip ((3D) in FIG. 3 and (4D) in FIG. 4).

Example 3
As shown in FIG. 5, a chip having a channel inside was manufactured in the same manner as in Example 1. Titanium oxide was applied to the inner wall of the channel of this chip by the following method.
A small amount of uncured silicone resin was allowed to flow through the channel, and the uncured silicone resin was applied to the channel wall. A commercially available titanium oxide powder (titanium dioxide, anatase type) (manufactured by Wako Pure Chemical Industries, Ltd.) is placed in a syringe, and this syringe is connected to the inlet of the chip channel. Then, the titanium oxide powder in the syringe was blown into the flow path by air pressure, and the titanium oxide powder was adhered to the uncured silicone resin on the flow path wall surface. Thereafter, the titanium oxide was fixed by curing the silicone resin on the wall surface by flowing nitrogen into the flow path at room temperature.
Using a chip in which titanium oxide was applied to the inner wall of the channel, a photoreaction experiment was performed using the apparatus shown in FIG. The chip is irradiated with 365 nm ultraviolet light while a methylene blue aqueous solution is being fed into the chip at a constant flow rate (0.15 mL / min). The photoreaction by titanium oxide was evaluated by measuring the absorbance (664 nm) of the solution coming out of the chip.
The results are shown in FIG.
When the chip is irradiated with ultraviolet light, methylene blue photoreduction occurs on the titanium oxide surface, and the absorbance decreases. When light irradiation was stopped, the photoreaction stopped and the absorbance returned to its original value.

Example 4
Making the chip channel solvent-resistant A chip having a channel inside was prepared in the same manner as in Example 1, and then the inner wall of the channel was covered with an ultraviolet curable fluorine-based epoxy resin (see FIG. 8).
A small amount of UV-curable fluorine-based epoxy resin (Optodyne UV-1000) (manufactured by Daikin Industries) was allowed to flow through the channel, and the resin was applied to the channel wall. Next, the epoxy resin on the channel wall was cured by irradiating the chip with ultraviolet light (365 nm) while flowing nitrogen through the channel to prevent the channel from becoming blocked.
The flow path of this chip is superior in resistance to organic solvents compared to the case where the inner wall is made of silicone resin.

Example 5
Making the chip channel solvent-resistant (Part 2, method on the left side of Fig. 9 (1))
A photograph of the operation of this example is shown in FIG.
A template was prepared by introducing a hollow aluminum tube with an inner diameter of 0.4 mm and an outer diameter of 0.8 mm into a polyethylene tube with an inner diameter of 0.8 mm and an outer diameter of 1.3 mm. However, at this time, the polyethylene thin tube is not introduced at the branch point of the flow path, and the aluminum tube is directly connected with polyvinyl alcohol glue.
Next, the circumference of this branching point was wrapped with a polyethylene sheet, and a polyethylene thin tube, the polyethylene sheet and the sheet were fused together using a heating tool such as a soldering iron to cover the circumference of the branching point. The polyethylene-coated template produced in this way was bent into the shape of the flow path in the chip.
Next, the template was placed in an uncured silicone resin (PDMS: polydimethylsiloxane) filled in a container, and then the silicone resin was cured by heating at 80 ° C. As for the silicone resin, a mixture of a base of SILPOT184 (manufactured by Dow Corning Toray) and a curing agent in a ratio of 10: 1 was used.
Next, a solution was poured into the template tube to dissolve the aluminum tube at room temperature to form a flow path. The solution used was a mixture of concentrated hydrochloric acid (35-37%) and water at a ratio of approximately 1: 1. Finally, the silicone resin was taken out of the container to complete the chip.

Example 6 (Method (2) on the right side of FIG. 9)
A photograph of the operation of this example is shown in FIG.
A hollow aluminum tube with an inner diameter of 0.4 mm and an outer diameter of 0.8 mm was prepared as a template, and this aluminum tube was bent to form a flow path. Next, an ultraviolet curable fluorine-based epoxy resin (Optodyne UV-1000) (manufactured by Daikin Industries) was applied to the outside of the aluminum tube. Then, the epoxy resin on the surface of the aluminum tube was cured by irradiating the aluminum tube with ultraviolet light (365 nm). The thus prepared fluorine-based epoxy resin-coated template was put into an uncured silicone resin (PDMS: polydimethylsiloxane) filled in a container, and then the silicone resin was cured by heating at 80 ° C. As for the silicone resin, a mixture of a base of SILPOT184 (manufactured by Dow Corning Toray) and a curing agent in a ratio of 10: 1 was used.
Next, a solution was poured into the template tube to dissolve the aluminum tube at room temperature to form a flow path. The solution used was a mixture of concentrated hydrochloric acid (35-37%) and water at a ratio of approximately 1: 1. Finally, the silicone resin was taken out of the container to complete the chip.

  The present invention is useful in all fields related to a chip having a channel inside.

Claims (15)

A method of manufacturing a chip having a flow path therein,
(1) A coating material having a melting point at a temperature in the range of 0 to 150 ° C. is applied to the surface of a linear material that is solid at the melting point of the coating material and has a solubility, thereby producing a channel template. Process,
(2) a step of embedding the template in a curable chip forming material and then curing the chip forming material;
(3) A step of heating the cured material in which the template is embedded to a temperature equal to or higher than the melting point of the coating material applied to the template surface, melting the coating material on the template surface, and causing the cured material to flow out of the cured material;
(4) A solution that dissolves the linear material is injected into a gap formed between the template and the cured product to dissolve the linear material, thereby forming a chip having a flow path therein. A method comprising the steps. The coating material is at least one material selected from the group consisting of polyethylene glycol, paraffin, low temperature solder (low melting point alloy), ionic liquid, petrolatum, wax (lipid), caprolactone, stearic acid, and palmitic acid. Item 2. The production method according to Item 1. 3. The production method according to claim 2, wherein the polyethylene glycol has a molecular weight in the range of 600 to 200,000. 4. The manufacturing method according to claim 1, wherein the linear material is a solid material or a hollow material. The linear material is a hollow material, and in the step (4), the solution for dissolving the linear material is injected into a hollow portion of the hollow material to dissolve the linear material. Described in A method of manufacturing a chip having a flow path therein,
(11) A step of producing a channel template using a hollow linear material,
(12) a step of embedding the template in a curable chip forming material and then curing the chip forming material;
(13) A method comprising a step of injecting a solution for dissolving the linear material into a hollow portion of the template to dissolve the linear material to form a chip having a flow path therein. 7. The manufacturing method according to claim 1, wherein the linear material is at least one material selected from the group consisting of a metal material, an inorganic material, and an organic material. 8. The manufacturing method according to claim 7, wherein the metal material is a pure metal or an alloy material. 8. The production method according to claim 7, wherein the inorganic material is a glass or a ceramic material. 10. The manufacturing method according to claim 1, wherein the curable chip forming material is at least one material selected from the group consisting of an organic material and an inorganic material. 11. The production method according to claim 1, wherein the solution for dissolving the linear material is an acid aqueous solution, an acid and hydrogen peroxide mixed aqueous solution, a basic aqueous solution, or water. The production according to any one of claims 1 to 11, further comprising a step (5) of providing a coating layer on the inner wall of the flow channel of the chip having a flow channel inside formed in the step (4) or the step (13). Method. 13. The production method according to claim 12, wherein the formation of the coating layer in the step (5) is performed by applying a photocurable material to the inner wall of the flow path and then photocuring. The template in the step (12) has a coating layer on the surface,
In the step (13), the linear material of the template is dissolved, and the coating layer is left to form a channel having a coating layer inside the chip, and a channel having a coating layer inside is formed. 7. The manufacturing method according to claim 6, wherein a chip having the same is obtained. 15. The manufacturing method according to claim 14, wherein the coating layer is made of at least one material selected from the group consisting of resin, glass, metal, or ceramics.