MICROFLUIDIC CHIP AND METHOD FOR MANUFACTURING MICROFLUIDIC CHIP

BACKGROUND OF THE INVENTION
Field of the Invention

The present invention relates to a microfluidic chip and a method for a manufacturing microfluidic chip.

Description of Background Art

JP 2021-156780 A describes a device for handling a fluid having trapezoid-shaped buffers connected to chambers through channels. The entire contents of this publication are incorporated herein by reference.

SUMMARY OF THE INVENTION

According to one aspect of the present invention, a microfluidic chip includes a chip body having an input section, a channel section and an output section such that a fluid is introduced from the input section, flows in the channel section and discharged or comes into contact with a drug in the output section. The channel section of the chip body has a hydrophobic region in which a contact angle of a surface in contact with the fluid is in a range of 90 degrees to 130 degrees.

According to another aspect of the present invention, a method for manufacturing a microfluidic chip includes forming a floor layer on a substrate, forming a barrier layer above the substrate and the floor layer, and bonding an upper covering layer to the barrier layer. A hydrophobic region is formed on a surface of at least one of the floor layer, the barrier layer, and the upper covering layer.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete appreciation of the invention and many of the attendant advantages thereof will be readily obtained as the same becomes better understood by reference to the following detailed description when considered in connection with the accompanying drawings, wherein:

FIG. 1A is a plan view of an overview of a microfluidic chip according to a first embodiment;

FIG. 1B is a diagram illustrating a cross section of the microfluidic chip taken along a line A-A illustrated in FIG. 1A;

FIG. 1C is a diagram illustrating a cross section of the microfluidic chip taken along a line B-B illustrated in FIG. 1A;

FIG. 1D is a diagram illustrating a cross section of the microfluidic chip taken along a line C-C illustrated in FIG. 1A;

FIG. 2 is a flowchart illustrating an example of a method for manufacturing a microfluidic chip according to the first embodiment;

FIG. 3A is a flowchart illustrating a manufacturing method according to Example 1;

FIG. 3B is a cross-sectional view, taken along a line A-A in FIG. 1B, of a microfluidic chip manufactured in Example 1;

FIG. 3C is a cross-sectional view, taken along a line C-C in FIG. 1D, of the microfluidic chip manufactured in Example 1;

FIG. 4A is a flowchart illustrating a manufacturing method according to Example 2;

FIG. 4B is a cross-sectional view, taken along the line A-A in FIG. 1B, of a microfluidic chip manufactured in Example 2;

FIG. 4C is a cross-sectional view, taken along the line C-C of FIG. 1D, of the microfluidic chip manufactured in Example 2;

FIG. 5A is a flowchart illustrating a manufacturing method according to Example 3.

FIG. 5B is a cross-sectional view, taken along the line A-A in FIG. 1B, of a microfluidic chip manufactured in Example 3;

FIG. 5C is a cross-sectional view, taken along the line C-C in FIG. 1D, of the microfluidic chip manufactured in Example 3;

FIG. 6A is a flowchart illustrating a manufacturing method according to Example 4;

FIG. 6B is a cross-sectional view, taken along the line A-A in FIG. 1B, of a microfluidic chip manufactured in Example 4;

FIG. 6C is a cross-sectional view, taken along the line C-C in FIG. 1D, of the microfluidic chip manufactured in Example 4;

FIG. 7A is a flowchart illustrating a manufacturing method according to Example 5;

FIG. 7B is a cross-sectional view, taken along the line A-A of FIG. 1B, of a microfluidic chip manufactured in Example 5;

FIG. 7C is a cross-sectional view, taken along the line C-C of FIG. 1D, of the microfluidic chip manufactured in Example 5;

FIG. 8A is a flowchart illustrating a manufacturing method according to Example 6;

FIG. 8B is a cross-sectional view, taken along the line A-A of FIG. 1B, of a microfluidic chip manufactured in Example 6;

FIG. 8C is a cross-sectional view, taken along the line C-C in FIG. 1D, of the microfluidic chip manufactured in Example 6;

FIG. 9A is a flowchart illustrating a manufacturing method according to Example 7;

FIG. 9B is a cross-sectional view, taken along the line A-A in FIG. 1B, of a microfluidic chip manufactured in Example 7;

FIG. 9C is a cross-sectional view, taken along the line C-C in FIG. 1D, of the microfluidic chip manufactured in Example 7;

FIG. 10A is a flowchart illustrating a manufacturing method according to Example 8;

FIG. 10B is a cross-sectional view, taken along the line A-A of FIG. 1B, of a microfluidic chip manufactured in Example 8;

FIG. 10C is a cross-sectional view, taken along the line C-C in FIG. 1D, of the microfluidic chip manufactured in Example 8;

FIG. 11A is a flowchart illustrating a manufacturing method according to Example 9;

FIG. 11B is a cross-sectional view, taken along the line A-A in FIG. 1B, of a microfluidic chip manufactured in Example 9;

FIG. 11C is a cross-sectional view, taken along the line C-C in FIG. 1D, of the microfluidic chip manufactured in Example 9;

FIG. 12A is a flowchart illustrating a manufacturing method according to a comparative example 1p;

FIG. 12B is a cross-sectional view, taken along the line A-A in FIG. 1B, of a microfluidic chip manufactured in comparative example 1;

FIG. 12C is a cross-sectional view, taken along the line C-C in FIG. 1D, of the microfluidic chip manufactured in comparative example 1;

FIG. 13 is a cross-sectional view, taken along the line C-C in FIG. 1D, of a microfluidic chip according to a second embodiment; and

FIG. 14 is a cross-sectional view, taken along the line C-C in FIG. 1D, of a microfluidic chip according to a modification example of the second embodiment.

DETAILED DESCRIPTION OF THE EMBODIMENTS

Embodiments will now be described with reference to the accompanying drawings, wherein like reference numerals designate corresponding or identical elements throughout the various drawings.

First Embodiment
Basic Configuration of Microfluidic Chip

FIGS. 1A to 1D are schematic diagrams each for describing a configuration example of a microfluidic chip 1 according to a first embodiment of the present invention. Specifically, FIG. 1A is a plan view of an overview of the microfluidic chip 1 according to the first embodiment. In addition, FIG. 1B is a diagram illustrating a cross section of the microfluidic chip 1 taken along a line A-A illustrated in FIG. 1A. In addition, FIG. 1C is a diagram illustrating a cross section of the microfluidic chip 1 taken along a line B-B illustrated in FIG. 1A. In addition, FIG. 1D is a diagram illustrating a cross section of the microfluidic chip 1 taken along a line C-C illustrated in FIG. 1A.

As illustrated in FIG. 1A, the microfluidic chip 1 includes an input section 2 (may also be referred to simply as an “inlet”) from which a fluid (e.g., liquid) is introduced, a channel section 3 in which the fluid introduced from the input section 2 flows, and output sections 4 and 5 (may also be referred to simply as “outlets”) each of which allows the fluid to be discharged from the channel section 3. In the microfluidic chip 1, the channel section 3 is covered with an upper covering layer 13 described below. The input section 2 and the output sections 4 and 5 are through holes provided in the upper covering layer 13. One channel is divided at a branching section 18 into two channels toward the output sections 4 and 5 as the channel section 3. A trunk channel section 3a is included in the input section 2 to the branching section 18, a branch channel section 3b is included in the branching section 18 to the output section 4, and a branch channel section 3c is included in the branching section 18 to the output section 5. In addition, drug fixation sections (may be referred to as “near the outlets” below for the sake of convenience) that each fix a drug and bring a fluid and the drug introduced from the input section 2 into contact may be provided near the output sections 4 and 5. In a case where the drug fixation sections are provided, the output sections 4 and 5 may not necessarily be provided. Unless otherwise stated, the term output sections 4 and 5 in the narrow sense and the term drug fixation sections will be uniformly referred to as “output sections”. The substances that are tested by using a microfluidic chip are not each limited to drugs or the like.

FIG. 1A illustrates the channel section 3 that is visually recognized through the upper covering layer 13 having transparency. In addition, the microfluidic chip 1 illustrated in FIG. 1A is a microfluidic chip in which a channel branches in the middle from an inlet and has two outlets. This forms simple channels for assessing reactions between a test liquid and two drugs at the same time.

It is sufficient if the microfluidic chip 1 is provided with one or more input sections and two or more output sections. In addition, the channel sections 3 may be provided in the microfluidic chip 1 and the channel sections 3 may be designed to allow fluids introduced from the input sections 2 to merge or be separated.

Here, details of members included in the channel section 3 in the microfluidic chip 1 will be described.

As illustrated in FIG. 1B, the microfluidic chip 1 includes a substrate 10, a floor layer 11 that is provided on the substrate 10, a barrier layer 12 that is provided on the floor layer 11 and forms a channel, and the upper covering layer 13 that is provided on the opposite surface of the barrier layer 12 to the substrate 10. The trunk channel section 3a in which a fluid introduced from the input section 2 flows is a region surrounded by the substrate 10, the floor layer 11, the barrier layer 12, and the upper covering layer 13. A siloxane polymer containing layer 14 is formed on a surface of any of the floor layer 11, the barrier layer 12, and the upper covering layer 13. The siloxane polymer containing layer 14 does not necessarily have to have constant thickness. Details of the siloxane polymer containing layer 14 will be described below. As described above, a fluid is introduced to the trunk channel section 3a from the input section 2 provided in the upper covering layer 13. The floor layer 11 may be provided as a region that increases the adhesion between the substrate 10 and the barrier layer or changes the channel in hydrophobicity as described below.

As illustrated in FIG. 1C, the branch channel section 3b is a region surrounded by the floor layer 11, the barrier layer 12, and the upper covering layer 13 provided to the substrate 10 and has a basic configuration similar to that of FIG. 1B. A fluid flowing in the branch channel section 3b is discharged from the output section 4. The description of the branch channel section 3b also applies to the branch channel section 3c unless otherwise stated in the following description.

The basic configuration in FIG. 1D, that is a cross-sectional view taken along the propagation direction of a channel, is similar to those of FIGS. 1B and 1C.

The substrate 10, the floor layer 11, the barrier layer 12, and the upper covering layer 13 will be further described below.

Substrate

The substrate 10 is a member that serves as the base of the microfluidic chip 1. The barrier layer 12 provided above the substrate 10 forms the shape of a channel of the channel section 3.

It is possible to form the substrate 10 by using any of a light-transmissive material or a non-light-transmissive material. For example, in a case where the state of the inside of the channel section 3 (e.g., the state of a fluid) is detected and observed using light, it is possible to use a material that is excellent in transparency to the light. It is possible to use resin, glass, or the like as the light-transmissive material. The resin used for the light-transmissive material that is used to form the substrate 10 may include an acrylic resin, a methacrylic resin, polypropylene, a polycarbonate resin, a cycloolefin resin, a polystyrene resin, a polyester resin, a urethane resin, a silicone resin, a fluorine-based resin, and the like from the perspective of the suitability for the formation of the main body of the microfluidic chip 1. In addition, a glass substrate having a surface coated with silicone or fluorine may be used.

In addition, for example, in a case where it is unnecessary to detect or observe the state of the inside of the channel section 3 (e.g., the state of a fluid) by using light, a non-light-transmissive material may be used. The non-light-transmissive material may include a silicon wafer, a copper plate, and the like. The thickness of the substrate 10 is not limited in particular, but a certain level of rigidity is necessary in a channel formation process and it is thus preferable that the thickness of the substrate 10 be within a range of 10 μm (0.01 mm) or more and 10 mm or less.

Floor Layer

The floor layer 11 is provided on the substrate 10. It is possible to form the floor layer 11 by using a resin material. It is possible to use, for example, a photosensitive resin as the resin material of the floor layer 11.

It is desirable that the photosensitive resin which is used to form the floor layer 11 have photosensitivity to light having a wavelength of 190 nm or more and 400 nm or less, which is an ultraviolet region. It is possible to use a photoresist such as a liquid resist or a dry film resist as the photosensitive resin. These photosensitive resins may be either positive types in which the photosensitive regions dissolve or negative types in which the photosensitive regions become insoluble. A photosensitive resin composition suitable for the formation of the floor layer 11 in the microfluidic chip 1 includes a radical negative photosensitive resin including an alkali-soluble polymer, an additional polymerizable monomer, and a photopolymerization initiator. It is possible to use, for example, an acryl-based resin, an acrylic urethane-based resin (urethane acrylate-based resin), an epoxy-based resin, a polyamide-based resin, a polyimide-based resin, a polyurethane-based resin, a polyester-based resin, a polyether-based resin, a polyolefin-based resin, a polycarbonate-based resin, a polystyrene-based resin, a norbornene-based resin, a phenolic novolac-based resin, or another resin having photosensitivity alone, or use a mixture of some of the resins or use copolymerized resins as the photosensitive resin material.

In addition, it is more preferable from the perspective for facilitating the deposition of low-molecular weight siloxane volatilizing when polydimethylsiloxane (PDMS) described below is heated that the resin included in the floor layer 11 contain polysiloxane and a silane coupling agent. These are provided to generate a silanol bond to the low-molecular weight siloxane and facilitate the siloxane polymer containing layer 14 to be formed on the surface of the floor layer 11. In addition, the material containing the silane coupling agent is also favorable in itself from the perspective of an increase in the adhesion to the barrier layer 12. This perspective will be described in another embodiment below.

The thickness of the floor layer 11 is not particularly limited. However, the floor layer 11 does not have to be particularly thick but is preferably thin from the perspective of increasing the adhesion between the substrate 10 and the barrier layer 12 or exposing the substrate 10 by patterning. It is preferable that the thickness of the floor layer 11 be within a range of 1 μm or more and 10 μm or less.

Barrier Layer

The barrier layer 12 is one of components that are provided above the substrate and form the channel section 3. It is possible to form the barrier layer 12 by using a resin material. It is possible to use, for example, a photosensitive resin as the resin material of the barrier layer 12.

It is desirable that the photosensitive resin which is used to form the barrier layer 12 have photosensitivity to light having a wavelength of 190 nm or more and 400 nm or less, which is an ultraviolet region. It is possible to use a photoresist such as a liquid resist or a dry film resist as the photosensitive resin. These photosensitive resins may be either positive types in which the photosensitive regions dissolve or negative types in which the photosensitive regions become insoluble. A photosensitive resin composition suitable for the formation of the barrier layer 12 in the microfluidic chip 1 includes a radical negative photosensitive resin including an alkali-soluble polymer, an additional polymerizable monomer, and a photopolymerization initiator. It is possible to use, for example, an acryl-based resin, an acrylic urethane-based resin (urethane acrylate-based resin), an epoxy-based resin, a polyamide-based resin, a polyimide-based resin, a polyurethane-based resin, a polyester-based resin, a polyether-based resin, a polyolefin-based resin, a polycarbonate-based resin, a polystyrene-based resin, a norbornene-based resin, a phenolic novolac-based resin, or another resin having photosensitivity alone, or use a mixture of some of the resins or use copolymerized resins as the photosensitive resin material.

The resin material of the barrier layer 12 is not limited to being a photosensitive resin in the first embodiment. For example, silicone rubber (PDMS: polydimethylsiloxane) or a synthetic resin may be used. It is possible to use, for example, a polymethyl methacrylate resin (PMMA), polycarbonate (PC), a polystyrene resin (PS), polypropylene (PP), a cycloolefin polymer (COP), a cycloolefin copolymer (COC), or the like as the synthetic resin. It is desirable to select the resin material of the barrier layer 12 as appropriate depending on the application.

In addition, the thickness of the barrier layer 12 above the substrate 10, that is, the height of the channel section 3 is not particularly limited, but the height of the channel section 3 is greater than an analysis/test target substance (e.g., a drug, a germ, a cell, a red blood cell, a white blood cell, or the like) included in a fluid introduced to the channel section 3. It is therefore preferable that the thickness of the barrier layer 12, that is, the height (depth) of the channel section 3 be within a range of 1 μm or more and 500 μm or less. It is more preferable that the height (depth) of the channel section 3 be within a range of 10 μm or more and 100 μm or less. It is still more preferable that the height (depth) of the channel section 3 be within a range of 40 μm or more and 60 μm or less. The height (depth) of the channel section is a length in the direction perpendicular to the surfaces of the substrate.

In addition, the width of the channel section 3 similarly is greater than an analysis/test target substance. It is therefore preferable that the width of the channel section 3 defined by the barrier layer 12 be within a range of 1 μm or more and 1000 μm or less. It is more preferable that the width of the channel section 3 defined by the barrier layer 12 be within a range of 10 μm or more and 500 μm or less. It is still more preferable that the width of the channel section 3 defined by the barrier layer 12 be within a range of 10 μm or more and 100 μm or less. The width of the channel is length in the direction parallel with the surfaces of the substrate and perpendicular to the direction of the channel length.

In addition, sufficient reaction time is secured for a reaction solution. It is therefore preferable that the channel length determined by the barrier layer 12 be within a range of 10 mm or more and 100 mm or less. It is more preferable that the channel length determined by the barrier layer 12 be within a range of 30 mm or more and 70 mm or less. It is still more preferable that the channel length determined by the barrier layer 12 be within a range of 40 mm or more and 60 mm or less.

Upper Covering Layer

In the microfluidic chip 1 according to the first embodiment, the upper covering layer 13 is a covering member (the upper covering layer 13 will also be referred to as the “covering member” in some cases for the sake of convenience below) that covers the channel section 3 as illustrated in FIG. 1B. As described above, the upper covering layer 13 is provided on the opposite surface of the barrier layer 12 to the substrate 10 and is opposed to the substrate 10 across the barrier layer 12. More specifically, as illustrated in FIG. 1B, the side end sections of the upper covering layer 13 are supported by the barrier layer 12 and the middle region is opposed to the substrate 10. The middle region defines the upper section of the channel section 3.

It is possible to form the upper covering layer 13 by using any of a light-transmissive material or a non-light-transmissive material. For example, in a case where the state of the inside of the channel section 3 (e.g., the state of a fluid) is detected and observed using light, it is possible to use a material that is excellent in transparency to the light. It is possible to use resin, glass, or the like as the light-transmissive material. The resin that is used to form the upper covering layer 13 may include an acrylic resin, a methacrylic resin, polypropylene, a polycarbonate resin, a cycloolefin resin, a polystyrene resin, a polyester resin, a urethane resin, a silicone resin, a fluorine-based resin, and the like from the perspective of the suitability for the formation of the main body of the microfluidic chip 1.

The resin material of the upper covering layer 13 is not limited to the above in the first embodiment. For example, silicone rubber (PDMS: polydimethylsiloxane) or synthetic resin may be used. It is possible to use, for example, a polymethyl methacrylate resin (PMMA), polycarbonate (PC), a polystyrene resin (PS), polypropylene (PP), polyethylene terephthalate (PET), a cycloolefin polymer (COP), a cycloolefin copolymer (COC), or the like as the synthetic resin. It is desirable to select the resin material of the upper covering layer 13 as appropriate depending on the application. In particular, in the first embodiment, it is, however, desirable to use PDMS from the perspective of the formation of a siloxane polymer containing layer on the surfaces of the inside of the channel section 3.

The thickness of the upper covering layer 13 is not limited in particular, but it is preferable that the thickness of the upper covering layer 13 be within a range of 10 μm or more and 10 mm or less in view of the provision of respective through holes corresponding the input section 2 and the output sections 4 and 5 in the upper covering layer 13. In addition, it is desirable that the upper covering layer 13 have, in advance, respective holes corresponding to the input section 2 from which a fluid is introduced and the output sections 4 and 5 from each of which the fluid is discharged in the upper covering layer 13 before the upper covering layer 13 is bonded to the barrier layer 12.

Manufacturing Method

Next, a method for manufacturing the microfluidic chip 1 according to the first embodiment will be described. FIG. 2 is a flowchart illustrating an example of a method for manufacturing the microfluidic chip 1 according to the first embodiment.

Here, a case where the floor layer 11 and the barrier layer 12 are each formed by using a photosensitive resin will be described as an example.

In FIG. 2, the method for manufacturing the microfluidic chip includes processes of forming the floor layer 11 (S101), forming the barrier layer 12 (S102), conducting surface modification treatment (UV treatment) (S13), and bonding the upper covering layer 13 (S14). The process of forming the floor layer 11 (S101) includes S1 to S6 described below. In addition, the process of forming the barrier layer (S102) includes S7 to S12 described below.

S1. In the method for manufacturing the microfluidic chip 1 according to the first embodiment, a process of coating the substrate 10 with resin is first performed. A resin layer that forms the floor layer 11 is thus provided on the substrate 10.

Examples of a method for forming the floor layer on the substrate 10 include coating the substrate 10 with a photosensitive resin. It is possible to conduct the coating, for example, by spin coating, spray coating, bar coating, or the like. Spin coating is preferable from the perspective of the controllability of the film thickness. It is possible to coat the substrate 10 with, for example, photosensitive resins having a variety of forms such as a liquid photosensitive resin, a solid photosensitive resin, a gel photosensitive resin, and a film photosensitive resin. One of preferable methods includes forming a photosensitive resin layer using a liquid resist.

In addition, it is sufficient if the substrate 10 is coated with resin (e.g., photosensitive resin) to keep the thickness of the resin layer (e.g., photosensitive resin layer), that is, the thickness of the floor layer 11 within a range of 1 μm or more and 10 μm or less. S2. Once the photosensitive resin is formed on the substrate 10, a process of conducting heating treatment (pre-baking treatment) is then performed for the purpose of removing a solvent medium (solvent) included in the resin (e.g., photosensitive resin) with which the substrate 10 is coated. The pre-baking treatment is not an essential process for the method for manufacturing the microfluidic chip 1 according to the first embodiment, and may be carried out as appropriate at the optimum temperature and time depending on the characteristics of the resin. For example, in a case where the resin layer on the substrate 10 is a photosensitive resin, the pre-baking temperature and time are adjusted to optimum conditions as appropriate depending on the characteristics of the photosensitive resin.

S3. Next, a process of exposing the resin (e.g., photosensitive resin) with which the substrate 10 is coated is performed. Specifically, the photosensitive resin with which the substrate 10 is coated is exposed to have a channel pattern drawn thereon. For example, an exposure apparatus or a laser lithography apparatus having a light source producing ultraviolet light can be used for the exposure. For example, one of preferable methods is exposure in which a proximity exposure or contact exposure apparatus having a light source producing ultraviolet light is used. In the case of a proximity exposure apparatus, exposure is performed through a photomask having a channel pattern arrangement in the microfluidic chip 1. A photomask or the like having a two-layer structure of chromium and chromium oxide as a light-shielding film may be used as the photomask.

In addition, as described above, a photosensitive resin having photosensitivity to light having a wavelength of 190 nm or more and 400 nm or less, which is an ultraviolet region, is used for the floor layer 11. It is thus sufficient if the photosensitive resin with which the substrate 10 is coated is sensitized to light having a wavelength of 190 nm or more and 400 nm or less in this process (exposure process).

In a case where the photosensitive resin with which the substrate 10 is coated is a positive resist, the exposure region is dissolved to expose the substrate 10. The photosensitive resin remaining in the non-exposure region serves as the floor layer 11. In addition, in a case where the photosensitive resin with which the substrate 10 is coated is a negative resist, the photosensitive resin remaining in the exposure region serves as the floor layer 11 and the non-exposure region is dissolved to expose the substrate 10. In this way, it is possible to form the floor layer 11 on the substrate 10 by using photolithography in the method for manufacturing the microfluidic chip 1 according to the first embodiment.

S4. Next, a process of developing the exposed photosensitive resin to form a channel pattern is performed.

The development is conducted by reacting a photosensitive resin and a development liquid, for example, in a development apparatus of a spraying type, a dipping type, a puddle type, or the like. It is possible to use, for example, a sodium carbonate aqueous solution, tetramethyl ammonium hydroxide, potassium hydroxide, an organic solvent, or the like for the development liquid. An optimum development liquid depending on the characteristics of the photosensitive resin may be used as appropriate, but the development liquid is not limited to these. In addition, it is possible to adjust the concentration or the development processing time to optimum conditions as appropriate depending on the characteristics of the photosensitive resin.

S5. Next, a process of cleaning the resin layer (photosensitive resin layer) on the substrate 10 of the development liquid used for the development is performed. It is possible to carry out the cleaning, for example, by a cleaning apparatus of a spray type, a shower type, an immersion type, or the like. An optimum cleaning water for removing the development liquid used for the development process may be used as the cleaning water as appropriate, for example, pure water, isopropyl alcohol, or the like. After cleaning, the resin layer is, for example, dried by a spin dryer or an IPA vapor dryer, or naturally dried. (S6)

Next, a process of conducting heating treatment (post-bake) on the floor layer 11 is performed. The residual moisture at the time of development or cleaning is removed through this post-baking treatment. The post-baking treatment is conducted by using, for example, a hot plate, an oven, or the like. In the case of insufficient drying in the cleaning process of S5 above, the development liquid or the moisture at the time of cleaning may remain in the floor layer 11. In addition, solvent that is not removed through the pre-baking treatment may also remain in the floor layer 11. It is possible to remove this by conducting post-baking treatment.

S7. Next, a process of coating the floor layer 11 with resin is performed. A resin layer that forms the barrier layer 12 is thus provided on the floor layer 11. In the method for manufacturing the microfluidic chip 1 according to the first embodiment, for example, a resin layer (photosensitive resin layer) including a photosensitive resin is formed on the floor layer 11.

Examples of a method for forming the photosensitive resin layer on the floor layer 11 include coating the floor layer 11 with a photosensitive resin. It is possible to conduct the coating, for example, by spin coating, spray coating, bar coating, or the like. Spin coating is preferable from the perspective of the controllability of the film thickness. It is possible to coat the floor layer 11 with, for example, photosensitive resins having a variety of forms such as a liquid photosensitive resin, a solid photosensitive resin, a gel photosensitive resin, and a film photosensitive resin. One of preferable methods includes forming a photosensitive resin layer by using a liquid resist.

In addition, the floor layer 11 may be coated with resin (e.g., photosensitive resin) to keep the thickness of the resin layer (e.g., photosensitive resin layer), that is, the thickness of the barrier layer 12 within a range of 5 μm or more and 100 μm or less.

S8. Once the photosensitive resin is formed on the floor layer 11, a process of conducting heating treatment (pre-baking treatment) is then performed for the purpose of removing a solvent medium (solvent) included in the resin (e.g., photosensitive resin) with which the floor layer 11 is coated. The pre-baking treatment is not an essential process for the method for manufacturing the microfluidic chip 1 according to the first embodiment and may be carried out as appropriate at the optimum temperature and time depending on the characteristics of the resin. For example, in a case where the resin layer on the floor layer 11 is a photosensitive resin, the pre-baking temperature and time are adjusted to optimum conditions as appropriate depending on the characteristics of the photosensitive resin.

S9. Next, a process of exposing the resin (e.g., photosensitive resin) with which the floor layer 11 is coated is performed. Specifically, the photosensitive resin with which the floor layer 11 is coated is exposed to have a channel pattern drawn thereon. For example, an exposure apparatus or a laser lithography apparatus having a light source producing ultraviolet light can be used for the exposure. For example, one of preferable methods is exposure in which a proximity exposure or contact exposure apparatus having a light source producing ultraviolet light is used. In the case of a proximity exposure apparatus, exposure is performed through a photomask having a channel pattern arrangement in the microfluidic chip 1. A photomask or the like having a two-layer structure of chromium and chromium oxide as a light-shielding film may be used as the photomask.

In addition, as described above, a photosensitive resin having photosensitivity to light having a wavelength of 190 nm or more and 400 nm or less, which is an ultraviolet region, is used for the barrier layer 12. It is thus sufficient if the photosensitive resin with which the floor layer 11 is coated is sensitized to light having a wavelength of 190 nm or more and 400 nm or less in this process (exposure process).

In a case where the photosensitive resin with which the floor layer 11 is coated is a positive resist, the exposure region is dissolved to serve as the channel section 3. The photosensitive resin remaining in the non-exposure region serves as the barrier layer 12. In addition, in a case where the photosensitive resin with which the floor layer 11 is coated is a negative resist, the photosensitive resin remaining in the exposure region serves as the barrier layer 12 and the non-exposure region is dissolved to serve as the channel section 3. In this way, it is possible to form the barrier layer 12 that configures the channel section 3 on the floor layer 11 by using photolithography in the method for manufacturing the microfluidic chip 1 according to the first embodiment.

In a case where a chemically amplified resist or the like is used to form a resin layer on the floor layer 11, it is favorable to further conduct heating treatment (post-exposure bake: PEB) after exposure to accelerate an acid catalyst reaction caused by the exposure.

S10. Next, a process of developing the exposed photosensitive resin to form a channel pattern is performed.

S11. Next, a process of completely cleaning the resin layer (photosensitive resin layer) on the floor layer 11 of the development liquid used for the development is performed. It is possible to carry out the cleaning, for example, by a cleaning apparatus of a spray type, a shower type, an immersion type, or the like. An optimum cleaning water for removing the development liquid used for the development process may be used as the cleaning water as appropriate, for example, pure water, isopropyl alcohol, or the like. After cleaning, the resin layer is, for example, dried by a spin dryer or an IPA vapor dryer, or naturally dried.

S12. Next, a process of conducting heating treatment (post-bake) on the channel pattern, that is, the barrier layer 12 that forms the channel section 3 is performed. The residual moisture at the time of development or cleaning is removed through this post-baking treatment. The post-baking treatment is conducted by using, for example, a hot plate, an oven, or the like. In the case of insufficient drying in the cleaning process of S11 above, the development liquid or the moisture at the time of cleaning may remain in the barrier layer 12. In addition, the solvent that is not removed through the pre-baking treatment may also remain in the barrier layer 12. It is possible to remove this by conducting post-baking treatment.

S13. After the post-baking treatment, a process of conducting surface modification treatment on the barrier layer 12 and the upper covering layer 13 (covering member) that has not yet been bonded to the barrier layer 12 is performed. As an example of the surface modification treatment, UV treatment is conducted. Additionally, if the surface modification treatment may be performed as appropriate when needed. The surface modification treatment is not an essential process for the method for manufacturing the microfluidic chip 1 according to the first embodiment.

S14. Next, a process of bonding the upper covering layer 13 to the barrier layer 12 that has been subjected to the post-baking treatment is performed. In this process, the upper covering layer 13 is bonded to the opposite surface of the barrier layer 12 to the substrate 10 as illustrated in FIGS. 1B to 1D. This covers the channel section 3 with the upper covering layer 13 to form the microfluidic chip 1.

It is possible to use thermocompression in which, for example, a thermal press machine or a thermal roll machine is used as the method that bonds together the substrates subjected to the surface modification treatment in S13 above. However, in a case where PDMS or the like having flexibility is used as a covering member, it is also possible to bond the substrates with no pressure applied.

It is desirable that the upper covering layer 13 have holes corresponding to the input section 2 and the output sections 4 and 5 for fluids formed therein in advance before the upper covering layer 13 is bonded to the barrier layer 12. This makes it possible to prevent problems with the occurrence of debris and contamination in comparison with a case where holes are made after the barrier layer 12 is bonded.

Additionally, in a case where heat is applied, it is desirable to adjust the conditions depending on the properties of material. For example, it is possible to bond the upper covering layer 13 to the barrier layer 12 by using heating measure such as a hot plate at 40° C. or more for 5 min or more.

The method for bonding the barrier layer 12 and the upper covering layer 13 is not limited to thermocompression as described above. A method in which an adhesive is used or a method for joining and bonding the barrier layer 12 and the upper covering layer 13 without using adhesive by conducting surface modification treatment on the bonding surfaces between the barrier layer 12 and the upper covering layer 13 may be carried out.

In a case where an adhesive is used for bonding, it is possible to determine the adhesive on the basis of the affinity or the like with the materials included in the barrier layer 12 and the upper covering layer 13. The adhesive is not limited in particular as long as the adhesive allows the barrier layer 12 and the upper covering layer 13 to be bonded. For example, it is possible to use an acrylic resin-based adhesive, a urethane resin-based adhesive, an epoxy resin-based adhesive, or the like as the adhesive in the first embodiment.

In addition, the method for bonding with no adhesive by conducting surface modification treatment includes UV treatment, plasma treatment, corona discharge treatment, excimer laser treatment, and the like. In this case, the reactivity of the surface of the barrier layer 12 may be increased and the optimum treatment method be selected as appropriate depending on the affinity and the adhesion compatibility between the barrier layer 12 and the upper covering layer 13. Additionally, in the case of bonding by conducting surface modification treatment, the processes up to S13 of bonding the barrier layer 12 and the upper covering layer 13 may be performed.

An example in which the substrate 10 is coated with a photosensitive resin and the barrier layer 12 that configures the channel section 3 is formed by using photolithography has been described here, but the present invention is not limited to this example. The resin used to form a resin layer serving as the barrier layer 12 above the substrate 10 may be, for example, silicone rubber (PDMS) or synthetic resin (such as a PMMA, PC, a PS, PP, a COP, or a COC). For example, in a case where the barrier layer 12 is formed by using silicone rubber, a channel pattern (the barrier layer 12 that configures the channel section 3) may be formed by forming a channel pattern template with photolithography and transferring the channel pattern template to the silicone rubber.

Example of First Embodiment

Example of the first embodiment will be described below in accordance with a mode in which the siloxane polymer containing layer 14 is provided on a surface of at least any of the floor layer 11, the barrier layer 12, and the upper covering layer 13. For this reason, a siloxane polymer and a contact angle that are each important for achieving hydrophobicity will be first described.

Siloxane Component Volatilized by Heating PDMS

The derivation of the siloxane of the siloxane polymer containing layer 14 will be explained. Siloxanes are generated from familiar silicone products. Siloxane generated as outgas (referred to as “off-gas” below) is a component that easily volatilizes and easily adheres to a substrate or the like. This siloxane has properties of volatilizing in minute amounts even at ordinary temperature and has properties that heating increases the amount of outgassed volatile siloxane and components having a higher level of polymerization volatize with an increase in heating temperature. The present disclosure has focused on hydrophobization brought about by the deposition of this low-molecular weight siloxane on the surface of the substrate. Depending on the quality of PDMS, low-molecular weight siloxane polymers such as cyclic siloxanes D3 to D20 or chain siloxanes M2 to M20 volatilize. To carry out an example of the first embodiment, it is important to confirm in advance the temperature dependence of low-molecular weight siloxanes volatilizing from PDMS.

Method for Measuring Low-Molecular Weight Siloxane

To measure low-molecular weight siloxane volatilizing from PDMS and low-molecular weight siloxane deposited on the surface of the substrate, it is preferable to use thermal extraction gas chromatography-mass spectrometry (GC/MS). The GC/MS is a composite apparatus obtained by coupling a gas chromatograph (GC) that separates a vaporized mixture into single components and a mass spectrometer (MS) that performs qualitative/quantitative analysis by ionizing respective separated components to acquire the mass spectra. A GC/MS is a preferable apparatus for a quantitative analysis of low-molecular weight siloxane. It is possible to measure the temperature dependence of volatilizing siloxane components by changing heating temperature at the time of analyses. In a quantitative method, the cyclic siloxanes are calculated as relative standard concentrations by using decamethylcyclopentasiloxane (D5) as a standard substance. The chain siloxanes are calculated as relative standard concentrations by using octamethyltrisiloxane (M3) as a standard substance.

Change in Contact Angle in Manufacturing Process of Microfluidic Chip

An example of an index indicating whether a predetermined layer exhibits hydrophobicity or hydrophilicity includes a contact angle. A change in the contact angle of a layer in a process of the method for manufacturing the microfluidic chip described above will be described. Roughly speaking, the contact angle changes between a contact angle (referred to as θ1) in a process (S102) of forming the barrier layer 12 that forms the channel section 3, a contact angle (referred to as θ2) after a process (S13) of conducting surface modification treatment on the upper covering layer 13 (covering member) that has not yet been bonded to the barrier layer 12, and a contact angle (referred to θ3) after a process (S14) of bonding the upper covering layer 13 to the barrier layer 12. θ1 represents the contact angle of material itself. It is therefore preferable from the perspective for suppressing backflow of droplets to use a material having a high contact angle. Next, in S13, oxygen radicals (O·) or hydroxy radicals (HO·) produced by the surface modification treatment form a hydrophilic group (—C═O, —OH, or —COOH) on a surface. This hydrophilizes the surface of the material and decreases the contact angle of θ2 (θ1>θ2). There is an effect of decreasing the contact angle (increasing the hydrophilicity) with an increase in irradiation energy or an increase in irradiation time. Next, in S14, heating treatment is conducted during bonding. This deposits low-molecular weight siloxane volatilizing from PDMS on the surface of the material and hydrophobizes the surface of the material to increase the contact angle of θ3 (θ2<θ3). There is an effect of increasing the amount of low-molecular weight siloxane deposited on the surface and increasing the contact angle (increasing the hydrophobicity) with an increase in temperature that is a heating condition or an increase in treatment time that is a heating condition. As a result of studies, it is found that it is possible to optionally control the contact angle of the surface of the material in the channel of the microfluidic chip by controlling the surface modification treatment conditions in S13, and the heating conditions (temperature and time) in S14 described above or heating conditions (temperature and time) using a heating furnace described below. It has been found that the control over the heating conditions in S14 is particularly important. In the present disclosure, the optional contact angle control is achieved by the PDMS heating conditions.

Method for Measuring Contact Angle

As a method for measuring a contact angle, a syringe is filled with water and mounted on a contact angle meter. Parameters are set such as the waiting time [msec] up to a measurement, the measurement time interval [msec], and the number of consecutive measurements [the number of times]. Water is dropped on a surface of a sample from the syringe, an image is captured, and the contact angle of the droplet is measured. As a method for measuring a static contact angle, a sessile drop method is adopted. The sessile drop method is a method for obtaining a contact angle θ from a radius r and height h of a dropped droplet on the premise that the droplet is part of a sphere.

The amount of liquid used for a normal contact angle measurement is typically 1 to 2 μL, but this amount of liquid forms a droplet having a diameter of 1 mm or more on a surface of a solid body. In the microfluidic chip, regions to be measured are micro-regions at a level of several microns in many cases. It is preferable to use, instead of a normal contact angle meter, an apparatus that drops picoliter-order droplets to allow the wettability behavior of the micro-regions to be assessed. For example, droplets in units of picoliters are produced by using a piezo-titrator and a high-powered camera equipped with an objective lens is used to allow a microdroplet to be measured. In addition, microdroplets evaporate extremely quickly and it is thus more preferable to use a high-speed camera.

Next, a main combination of a first photosensitive resin and a second photosensitive resin used in Example and a formation method will be described. The first photosensitive resin serves as the floor layer 11. The second photosensitive resin serves as the barrier layer 12.

Combination 1

Examples of combinations of the first photosensitive resin and the second photosensitive resin will be described in Table 1. The composition (components) of the first photosensitive resin used as the floor layer 11 includes polysiloxane and an acrylic monomer. The contact angle θ1 of the first photosensitive resin is 100°. The composition (components) of the second photosensitive resin used as the barrier layer 12 includes polysiloxane and an acrylic monomer. The contact angle θ1 of the second photosensitive resin is 100°.

The formation of the floor layer 11 (S101) will be described. In a case where the substrate 10 is coated with the first photosensitive resin (S1), spin coating is conducted. A wafer for coating is rotated at a coating rotation speed of 700 rpm for 10 sec. In pre-baking treatment (S2), the wafer is heated to 90° C. for 60 sec. A pattern of the floor layer 11 is exposed (S3) at an exposure value of 70 mJ/cm2. To develop the pattern of the floor layer 11 (S4), a sodium carbonate aqueous solution is used as a development liquid and development time is set to 90 sec. To clean the pattern of the floor layer 11 (S5), the pattern of the floor layer 11 is washed with water for 60 sec. Post-baking treatment (S6) is conducted at 230° C. for 30 min.

The formation of the barrier layer 12 (S102) will be described. In a case where the floor layer 11 is coated with the second photosensitive resin (S7), spin coating is conducted at a coating rotation speed of 500 rpm for 10 sec. Pre-baking treatment (S8) is conducted at 130° C. for 180 sec. A channel pattern is exposed (S9) at an exposure value of 60 mJ/cm2. To develop the channel pattern (S10), a sodium carbonate aqueous solution is used as a development liquid, and the channel pattern is developed for a development time of 180 sec and washed with water for 60 sec. To clean the channel pattern (S11), the channel pattern is washed with water for 60 sec. Post-baking treatment (S12) is conducted at 230° C. for 30 min.

TABLE 1

First
Second

photosensitive resin
photosensitive resin

Floor
Barrier layer

Material characteristics
Negative
Negative

Liquid
Liquid

Composition/components
Polysiloxane
Polysiloxane

Acrylic monomer
Acrylic monomer

Contact angle
100°
100°

Coating rotation speed
700 rpm/10 sec
500 rpm/10 sec

Pre-bake
90° C./60 sec
130° C./180 sec

Exposure
70
mj/cm²
60
mj/cm²

Development liquid
Sodium carbonate
Sodium carbonate

Development time
90
sec
180
sec

Washing with water
60
sec
60
sec

Post-bake
230° C./30 min
230° C./30 min

Combination 2

Other examples of combinations of the first photosensitive resin and the second photosensitive resin will be described in Table 2. The composition (components) of the first photosensitive resin used as the floor layer 11 includes an acrylic resin and an epoxy resin. The contact angle θ1 of the first photosensitive resin is 60°. The composition (components) of the second photosensitive resin used as the barrier layer 12 includes polysiloxane and an acrylic monomer. The contact angle of the second photosensitive resin is 100°.

Conditions for forming the floor layer 11 (S101) and conditions for forming the barrier layer 12 (S102) are the same as those of Table 1.

TABLE 2

First
Second

photosensitive resin
photosensitive resin

Floor
Barrier layer

Material characteristics
Negative
Negative

Liquid
Liquid

Composition/components
Acrylic resin
Polysiloxane

Epoxy resin
Acrylic monomer

Contact angle
60°
100°

Coat rotation speed
700 rpm/10 sec
500 rpm/10 sec

Pre-bake
90° C./60 sec
130° C./180 sec

Exposure
70
mj/cm²
60
mj/cm²

Development liquid
Sodium carbonate
Sodium carbonate

Development time
90
sec
180
sec

Washing with water
60
sec
60
sec

Post-bake
230° C./30 min
230° C./30 min

Combination 3

Other examples of combinations of the first photosensitive resin and the second photosensitive resin will be described in Table 3. The composition (components) of the first photosensitive resin used as the floor layer 11 includes polysiloxane and an acrylic monomer. The contact angle θ1 of the first photosensitive resin is 100°. The composition (components) of the second photosensitive resin used as the barrier layer 12 includes an acrylic resin and an acrylic monomer. The contact angle θ1 of the second photosensitive resin is 70°.

The formation of the floor layer 11 (S101) will be described. In a case where the substrate is coated with the first photosensitive resin (S1 in FIG. 2), spin coating is conducted. A wafer for coating is rotated at a coat rotation speed of 1100 rpm for 30 sec. In pre-baking treatment (S2 in FIG. 2), the wafer is heated to 90° C. for 90 sec. A pattern of the floor layer 11 is exposed (S3 in FIG. 2) at an exposure value of 100 mJ/cm2. To develop the pattern of the floor layer 11 (S4 in FIG. 2), a development liquid of sodium carbonate is used and development time is set to 180 sec. To clean the pattern of the floor layer 11 (S5 in FIG. 2), the pattern of the floor layer 11 is washed with water for 60 sec. Post-baking treatment (S6 in FIG. 2) is conducted at 230° C. for 30 min.

Conditions for forming the barrier layer 12 (S102) are the same as those of Table 1.

TABLE 3

First
Second

photosensitive resin
photosensitive resin

Floor
Barrier layer

Material characteristics
Negative
Negative

Liquid
Liquid

Composition/components
Polysiloxane
Acrylic resin

Acrylic monomer
Acrylic monomer

Contact angle
100°
70°

Coat rotation speed
1100 rpm/30 sec
500 rpm/10 sec

Pre-bake
90° C./90 sec
130° C./180 sec

Exposure
100
mj/cm²
60
mj/cm²

Development liquid
Sodium carbonate
Sodium carbonate

Development time
180
sec
180
sec

Washing with water
60
sec
60
sec

Post-bake
230° C./30 min
230° C./30 min

Combination 4

Other examples of combinations of the first photosensitive resin and the second photosensitive resin will be described in Table 4. The composition (components) of the first photosensitive resin used as the floor layer 11 includes an acrylic resin and an epoxy resin. The contact angle θ1 of the first photosensitive resin is 60°. The composition (components) of the second photosensitive resin used as the barrier layer 12 includes an acrylic resin and an acrylic monomer. The contact angle θ1 of the second photosensitive resin is 70°.

Conditions for forming the floor layer 11 (S101) and conditions for forming the barrier layer 12 (S102) are the same as those of Table 1.

TABLE 4

First
Second

photosensitive resin
photosensitive resin

Floor
Barrier layer

Material characteristics
Negative
Negative

Liquid
Liquid

Composition/components
Acrylic resin
Acrylic resin

Epoxy resin
Acrylic monomer

Contact angle
60°
70°

Coat rotation speed
700 rpm/10 sec
500 rpm/10 sec

Pre-bake
90° C./60 sec
130° C./180 sec

Exposure
70
mj/cm²
60
mj/cm²

Development liquid
Sodium carbonate
Sodium carbonate

Development time
90
sec
180
sec

Washing with water
60
sec
60
sec

Post-bake
230° C./30 min
230° C./30 min

Example 1

In Example 1, the first photosensitive resin of Table 1 was used for a floor layer and PDMS was used for members corresponding to a barrier layer and an upper covering layer to fabricate a microfluidic chip.

FIG. 3A is a flowchart illustrating a manufacturing method according to Example 1. Here, S101a of forming the floor layer corresponds to S101 of FIG. 2. The present disclosure will simplify or will not describe what have relationships similar to the relationships between the configurations and processes of FIGS. 1 and 2 in some cases below.

S102a is different from S102 in that the barrier layer and the upper covering layer are integrally molded by using molds. First, 100 g of two-component potting liquid silicone rubber TSE3032(A) and 10 g of two-component potting liquid silicone rubber TSE3032(B) (both manufactured by MOMENTIVE) were weighed out and stirred at 500 rpm for 15 min by using a stirrer. After that, the silicone rubbers were cast into molds that were cut to have a channel pattern and heated in an oven at 150° C. for 30 min for curing.

In S13a, the bonding surface of the floor layer and the bonding surface of a molding produced by using the molds were irradiated with UV light. The amount of UV irradiation was 1000 mJ/cm2. Additionally, it was confirmed that the contact angle θ2 of the floor layer decreased to 30° after the UV irradiation. In addition, it was confirmed that the contact angle θ2 of PDMS serving as both the barrier layer and the covering member decreased to 60°.

S14a is different from S14 in that the upper covering layer integrally molded with the barrier layer is bonded to the substrate side as a covering member (referred to as a “covering member also serving as the barrier layer” below) 1213. In S14a, the covering member 1213 also serving as the barrier layer was heated on a hot plate at 200° C. for 10 min with the bonding surfaces bonded together, thereby bonding the covering member 1213.

FIG. 3B is a cross-sectional view of a microfluidic chip manufactured in Example 1 corresponding to the cross-sectional view taken along A-A in FIG. 1B. In addition, FIG. 3C is a cross-sectional view of the microfluidic chip manufactured in Example 1 corresponding to the cross-sectional view taken along C-C in FIG. 1D. A cross-sectional view corresponding to the cross-sectional view taken along B-B of FIG. 1C has a configuration similar to the configuration of FIG. 3B and will be thus omitted.

A floor layer 11a was formed on a surface of a substrate 10a. The covering member 1213 also serving as the barrier layer was bonded to the floor layer 11a to surround the channel section 3. Additionally, it was confirmed by GC/MS analysis (gas chromatography-mass spectrometry) that a siloxane polymer containing layer 14a was formed on a surface of the covering member 1213 also serving as the barrier layer and a surface of the floor layer 11a. The contact angle θ3 of the floor layer 11a was 90° and the contact angle θ3 of the covering member 1213 also serving as the barrier layer was 90°.

Additionally, it was confirmed by GC/MS analysis that the siloxane polymer containing layer 14a formed on any of the floor layer 11a and the covering member 1213 also serving as the barrier layer also contained siloxane polymers D3 to D20 (see Table 6 described below).

In addition, FIG. 3C illustrates evaluation of a reaction between drugs 15 and a test liquid 16. In FIG. 3C, the drugs 15 are supplied from an outlet 4 in advance. The test liquid 16 is injected from an inlet 2 and the test liquid is pushed to the region near the outlet by air.

After this state, to promote a reaction between the drugs 15 and the test liquid 16, the microfluidic chip was placed in an incubator having a temperature of 50° C. and a humidity of 80% and left for one hour. The microfluidic chip was taken out one hour later and observation showed that the droplet remained near the outlet and the droplet did not flow back to the branching section 18 of the channel.

As described above, it was possible to carry out a reaction assessment of a test liquid and two types of drugs without contamination between the reaction solutions of the respective drugs.

Example 2

In Example 2, the first photosensitive resin and the second photosensitive resin described in Table 1 were used for a floor layer and a barrier layer. PDMS was used for an upper covering layer. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 1.

FIG. 4A is a flowchart illustrating a manufacturing method according to Example 2.

It was confirmed that the contact angle θ2 of the floor layer decreased to 30° after UV irradiation in S13b. In addition, it was confirmed that the contact angle θ2 of the barrier layer decreased to 40°.

In S14b, the upper covering layer was heated on a hot plate at 200° C. for 10 min with the bonding surfaces bonded together, thereby bonding the upper covering layer.

FIG. 4B is a cross-sectional view of a microfluidic chip manufactured in Example 2 corresponding to the A-A cross-sectional view taken along in FIG. 1B. In addition, FIG. 4C is a cross-sectional view of the microfluidic chip manufactured in Example 2 corresponding to the C-C cross-sectional view taken along in FIG. 1D. A cross-sectional view corresponding to the B-B cross-sectional view of FIG. 1C has a configuration similar to the configuration of FIG. 4B and will be thus omitted.

A floor layer 11b was formed on a surface of a substrate 10b. A barrier layer 12b defines the channel section 3. An upper covering layer 13b is bonded to the barrier layer 12b to surround the channel section 3. Additionally, it was confirmed by GC/MS analysis (gas chromatography-mass spectrometry) that a siloxane polymer containing layer 14b was formed on surfaces of the floor layer 11b, the barrier layer 12b, and the upper covering layer 13b. The contact angle θ3 of the floor layer 11b was 100°, the contact angle of the barrier layer 12b was 90°, and the contact angle of the upper covering layer 13b was 130°.

Additionally, it was confirmed by GC/MS analysis that the siloxane polymer containing layer 14b formed on any of the floor layer 11b, the barrier layer 12b, and the upper covering layer 13b also contained siloxane polymers D3 to D20 (see Table 6 described below).

In addition, FIG. 4C illustrates evaluation of a reaction between drugs 15 and the test liquid 16. In FIG. 4C, the drugs 15 are supplied from the outlet 4 in advance. The test liquid 16 is injected from the inlet 2 and the test liquid 16 is pushed to the region near the outlet by air.

As described above, it was possible to carry out a reaction assessment of a test liquid and two types of drugs without contamination between the reaction solutions of the respective drugs.

Example 3

In Example 3, the first photosensitive resin and the second photosensitive resin described in Table 1 were used for a floor layer and a barrier layer. An acrylic resin was used for an upper covering layer.

FIG. 5A is a flowchart illustrating a manufacturing method according to Example 3. Example 3 includes a process (S103c) of leaving the floor layer and the barrier layer to rest under a siloxane atmosphere. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 1.

It was confirmed that the contact angle θ2 of the floor layer decreased to 30° after UV irradiation in S13c. In addition, it was confirmed that the contact angle θ2 of the barrier layer decreased to 40°.

In S103c, after PDMS was heated to 200° C. in a heating furnace and left to rest for 5 min, a substrate above which the floor layer and the barrier layer were formed was left to rest in the heating furnace for 10 min. The time for which the floor layer and the like are left to rest is not limited to this time. For example, it is possible to leave the floor layer and the like to rest for 5 min or more.

In S14c, the upper covering layer was heated on a hot plate at 200° C. for 10 min with the bonding surfaces bonded together, thereby bonding the upper covering layer.

FIG. 5B is a cross-sectional view of a microfluidic chip manufactured in Example 3 corresponding to the cross-sectional view taken along A-A in FIG. 1B. In addition, FIG. 5C is a cross-sectional view of the microfluidic chip manufactured in Example 3 corresponding to the cross-sectional view taken along C-C in FIG. 1D. A cross-sectional view corresponding to the B-B cross-sectional view of FIG. 1C has a configuration similar to the configuration of FIG. 5B and will be thus omitted.

A floor layer 11c was formed on a surface of a substrate 10c. A barrier layer 12c defines the channel section 3. An upper covering layer 13c is bonded to the barrier layer 12c to surround the channel section 3. Additionally, it was confirmed by GC/MS analysis (gas chromatography-mass spectrometry) that a siloxane polymer containing layer 14c was formed on surfaces of the floor layer 11c and the barrier layer 12c. The contact angle 03 of the floor layer 11c was 110°, the contact angle θ3 of the barrier layer 12c was 90°, and the contact angle θ3 of the upper covering layer 13c was 40°.

Additionally, it was confirmed by GC/MS analysis that the siloxane polymer containing layer 14c formed on any of the floor layer 11c and the barrier layer 12c also contained siloxane polymers D3 to D20 (see Table 6 described below).

In addition, FIG. 5C illustrates evaluation of reaction between the drugs 15 and the test liquid 16. In FIG. 5C, the drugs 15 are supplied from the outlet 4 in advance. The test liquid 16 is injected from the inlet 2 and the test liquid 16 is pushed to the region near the outlet by air.

As described above, it was possible to carry out a reaction assessment of a test liquid and two types of drugs without contamination between the reaction solutions of the respective drugs.

Example 4

In Example 4, the first photosensitive resin and the second photosensitive resin described in Table 2 were used for a floor layer and a barrier layer. PDMS was used for an upper covering layer. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 1.

FIG. 6A is a flowchart illustrating a manufacturing method according to Example 4.

FIG. 6B is a cross-sectional view of a microfluidic chip manufactured in Example 4 corresponding to the cross-sectional view taken along A-A in FIG. 1B. In addition, FIG. 6C is a cross-sectional view of the microfluidic chip manufactured in Example 4 corresponding to the cross-sectional view taken along C-C in FIG. 1D. A cross-sectional view corresponding to the B-B cross-sectional view of FIG. 1C has a configuration similar to the configuration of FIG. 6B and will be thus omitted.

A floor layer 11d was formed on a surface of a substrate 10d. A barrier layer 12d defines the channel section 3. An upper covering layer 13d is bonded to the barrier layer 12b to surround the channel section 3. Additionally, it was confirmed by GC/MS analysis (gas chromatography-mass spectrometry) that a siloxane polymer containing layer 14d was formed on surfaces of the barrier layer 12d and the upper covering layer 13d. The contact angle θ3 of the floor layer 11d was 60°, the contact angle of the barrier layer 12d was 90°, and the contact angle of the upper covering layer 13d was 110°.

Additionally, it was confirmed by GC/MS analysis that the siloxane polymer containing layer 14d formed on any of the barrier layer 12d and the upper covering layer 13d also contained siloxane polymers D3 to D20 (see Table 6 described below).

In addition, FIG. 6C illustrates examination of reaction between the drugs 15 and the test liquid 16. In FIG. 6C, the drugs 15 are supplied from the outlet 4 in advance. The test liquid 16 is injected from the inlet 2 and the test liquid 16 is pushed to the region near the outlet by air.

As described above, it was possible to carry out a reaction assessment of a test liquid and two types of drugs without contamination between the reaction solutions of the respective drugs.

Example 5

In Example 5, the first photosensitive resin and the second photosensitive resin described in Table 3 were used for a floor layer and a barrier layer. PDMS was used for an upper covering layer.

FIG. 7A is a flowchart illustrating a manufacturing method according to Example 5. Example 5 includes a process (S103e) of leaving the floor layer to rest under a siloxane atmosphere. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 1.

In S103e, after PDMS was heated to 200° C. in a heating furnace and left to rest for 5 min, a substrate on which the floor layer was formed was left to rest in the heating furnace for 10 min.

FIG. 7B is a cross-sectional view of a microfluidic chip manufactured in Example 5 corresponding to the cross-sectional view taken along A-A in FIG. 1B. FIG. 7B is a cross-sectional view of a microfluidic chip manufactured in Example 5 corresponding to the cross-sectional view taken along A-A in FIG. 1B. In addition, FIG. 7C is a cross-sectional view of the microfluidic chip manufactured in Example 5 corresponding to the cross-sectional view taken along C-C in FIG. 1D. A cross-sectional view corresponding to the B—B cross-sectional view of FIG. 1C has a configuration similar to the configuration of FIG. 7B and will be thus omitted.

A floor layer 11e was formed on a surface of a substrate 10e. A barrier layer 12e defines the channel section 3. An upper covering layer 13e is bonded to the barrier layer 12e to surround the channel section 3. Additionally, it was confirmed by GC/MS analysis (gas chromatography-mass spectrometry) that a siloxane polymer containing layer 14e was formed on surfaces of the floor layer 11e and the upper covering layer 13e. The contact angle θ3 of the floor layer 11e was 100°, the contact angle θ3 of the barrier layer 12e was 70°, and the contact angle θ3 of the upper covering layer 13e was 110°. Additionally, it was confirmed by GC/MS analysis that the siloxane polymer containing layer 14e formed on any of the floor layer 11e and the upper covering layer 13e also contained siloxane polymers D3 to D20 (see Table 6 described below).

In addition, FIG. 7C illustrates evaluation of a reaction between the drugs 15 and the test liquid 16. In FIG. 7C, the drugs 15 are supplied from the outlet 4 in advance. The test liquid 16 is injected from the inlet 2 and the test liquid 16 is pushed to the region near the outlet by air.

As described above, it was possible to carry out evaluation of a reaction of a test liquid and two types of drugs without contamination between the reaction solutions of the respective drugs.

Example 6

In Example 6, the first photosensitive resin and the second photosensitive resin described in Table 3 were used for a floor layer and a barrier layer. An acrylic resin was used for an upper covering layer.

FIG. 8A is a flowchart illustrating a manufacturing method according to Example 6. Example 6 includes a process (S103f) of leaving the floor layer to rest under a siloxane atmosphere. In addition, to bond the upper covering layer (S14f), heating conditions by a hot plate were set to 50° C. and 10 min. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 1.

In S103f, after PDMS was heated to 200° C. in a heating furnace and left to rest for 5 min, a substrate on which the floor layer was formed was left to rest in the heating furnace for 10 min.

FIG. 8B is a cross-sectional view of a microfluidic chip manufactured in Example 6 corresponding to the cross-sectional view taken along A-A in FIG. 1B. In addition, FIG. 8C is a cross-sectional view of the microfluidic chip manufactured in Example 6 corresponding to the cross-sectional view taken along C-C in FIG. 1D. A cross-sectional view corresponding to the B-B cross-sectional view of FIG. 1C has a configuration similar to the configuration of FIG. 8B and will be thus omitted.

A floor layer 11f was formed on a surface of a substrate 10f. A barrier layer 12f defines the channel section 3. An upper covering layer 13f is bonded to the barrier layer 12f to surround the channel section 3. Additionally, it was confirmed by GC/MS analysis (gas chromatography-mass spectrometry) that a siloxane polymer containing layer 14f was formed on a surface of the floor layer 11f. The contact angle θ3 of the floor layer 11f was 100°, the contact angle θ3 of the barrier layer 12f was 70°, and the contact angle θ3 of the upper covering layer 13f was 40°.

Additionally, it was confirmed by GC/MS analysis that the siloxane polymer containing layer 14f formed on the floor layer 11f contained siloxane polymers D3 to D20 (see Table 6 described below).

In addition, FIG. 8C illustrates evaluation of a reaction between the drugs 15 and the test liquid 16. In FIG. 8C, the drugs 15 are supplied from the outlet 4 in advance. The test liquid is injected from the inlet 2 and the test liquid is pushed to the region near the outlet by air.

As described above, it was possible to carry out evaluation of a reaction of a test liquid and two types of drugs without contamination between the reaction solutions of the respective drugs.

Example 7

In Example 7, the first photosensitive resin and the second photosensitive resin described in Table 2 were used for a floor layer and a barrier layer. An acrylic resin was used for an upper covering layer.

FIG. 9A is a flowchart illustrating a manufacturing method according to Example 7. Example 7 includes a process (S103g) of leaving the floor layer and the barrier layer to rest under a siloxane atmosphere. In addition, to bond the upper covering layer (S14g), heating conditions by a hot plate were set to 50° C. and 10 min. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 1.

In S103g, after PDMS was heated to 200° C. in a heating furnace and left to rest for 5 min, a substrate above which the floor layer and the barrier layer were formed was left to rest in the heating furnace for 10 min.

FIG. 9B is a cross-sectional view of a microfluidic chip manufactured in Example 7 corresponding to the cross-sectional view taken along A-A in FIG. 1B. In addition, FIG. 9B is a cross-sectional view of the microfluidic chip manufactured in Example 7 corresponding to the cross-sectional view taken along C-C in FIG. 1D. A cross-sectional view corresponding to the B-B cross-sectional view of FIG. 1C has a configuration similar to the configuration of FIG. 9B and will be thus omitted.

A floor layer 11g was formed on a surface of a substrate 10g. A barrier layer 12g defines the channel section 3. An upper covering layer 13g is bonded to the barrier layer 12g to surround the channel section 3. Additionally, it was confirmed by GC/MS analysis (gas chromatography-mass spectrometry) that a siloxane polymer containing layer 14g was formed on a surface of the barrier layer 12g. The contact angle θ3 of the floor layer 11g was 60°, the contact angle θ3 of the barrier layer 12g was 90°, and the contact angle θ3 of the upper covering layer 13g was 40°.

Additionally, it was confirmed by GC/MS analysis that the siloxane polymer containing layer 14g formed on the barrier layer 12g contained siloxane polymers D3 to D20 (see Table 6 described below).

In addition, FIG. 9C illustrates evaluation of a reaction between the drugs 15 and the test liquid 16. In FIG. 9C, the drugs 15 are supplied from the outlet 4 in advance. The test liquid is injected from the inlet 2 and the test liquid is pushed to the region near the outlet by air.

As described above, it was possible to carry out evaluation of a reaction of a test liquid and two types of drugs without contamination between the reaction solutions of the respective drugs.

Example 8

In Example 8, the first photosensitive resin and the second photosensitive resin described in Table 4 were used for a floor layer and a barrier layer. An acrylic resin was used for an upper covering layer.

FIG. 10A is a flowchart illustrating a manufacturing method according to Example 8. Example 8 includes a process (S103h) of leaving the upper covering layer to rest under a siloxane atmosphere. In addition, to bond the upper covering layer (S14h), heating conditions by a hot plate were set to 80° C. and 10 min. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 1.

In S103h, after PDMS was heated to 200° C. in a heating furnace and left to rest for 5 min, the upper covering layer was left to rest in the heating furnace for 10 min. FIG. 10B is a cross-sectional view of a microfluidic chip manufactured in Example 8 corresponding to the A-A cross-sectional view taken along in FIG. 1B. In addition, FIG. 10C is a cross-sectional view of the microfluidic chip manufactured in Example 8 corresponding to the cross-sectional view taken along C-C in FIG. 1D. A cross-sectional view corresponding to the B-B cross-sectional view of FIG. 1C has a configuration similar to the configuration of FIG. 10B and will be thus omitted.

A floor layer 11h was formed on a surface of a substrate 10h. A barrier layer 12h defines the channel section 3. An upper covering layer 13h is bonded to the barrier layer 12h to surround the channel section 3. Additionally, it was confirmed by GC/MS analysis (gas chromatography-mass spectrometry) that a siloxane polymer containing layer 14h was formed on a surface of the upper covering layer 13h. The contact angle θ3 of the floor layer 11h was 60°, the contact angle θ3 of the barrier layer 12h was 70°, and the contact angle θ3 of the upper covering layer 13h was 90°.

Additionally, it was confirmed by GC/MS analysis that the siloxane polymer containing layer 14h formed on the upper covering layer 13h contained siloxane polymers D3 to D20 (see Table 6 described below).

In addition, FIG. 10C illustrates evaluation of a reaction between the drugs 15 and the test liquid 16. In FIG. 10C, the drugs 15 are supplied from the outlet 4 in advance. The test liquid is injected from the inlet 2 and the test liquid is pushed to the region near the outlet by air.

As described above, it was possible to carry out a reaction assessment of a test liquid and two types of drugs without contamination between the reaction solutions of the respective drugs.

Example 9

In Example 9, the first photosensitive resin and the second photosensitive resin described in Table 4 were used for a floor layer and a barrier layer. Glass was used for an upper covering layer.

FIG. 11A is a flowchart illustrating a manufacturing method according to Example 9. Example 9 includes a process (S103i) of leaving the upper covering layer to rest under a siloxane atmosphere. In addition, to bond the upper covering layer (S14i), heating conditions by a hot plate were set to 120° C. and 10 min. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 1.

In S103i, after PDMS was heated to 200° C. in a heating furnace and left to rest for 5 min, the upper covering layer was left to rest in the heating furnace for 10 min.

FIG. 11B is a cross-sectional view of a microfluidic chip manufactured in Example 9 corresponding to the cross-sectional view taken along A-A in FIG. 1B. In addition, FIG. 11C is a cross-sectional view of the microfluidic chip manufactured in Example 9 corresponding to the cross-sectional view taken along C-C in FIG. 1D. A cross-sectional view corresponding to the B-B cross-sectional view of FIG. 1C has a configuration similar to the configuration of FIG. 11B and will be thus omitted.

A floor layer 11i was formed on a surface of a substrate 10i. A barrier layer 12i defines the channel section 3. An upper covering layer 13i is bonded to the barrier layer 12i to surround the channel section 3. Additionally, it was confirmed by GC/MS analysis (gas chromatography-mass spectrometry) that a siloxane polymer containing layer 14i was formed on surfaces of the barrier layer 12i and the upper covering layer 13i. The contact angle θ3 of the floor layer 11i was 60°, the contact angle θ3 of the barrier layer 12i was 70°, and the contact angle θ3 of the upper covering layer 13i was 100°.

Additionally, it was confirmed by GC/MS analysis that the siloxane polymer containing layer 14i formed on the upper covering layer 13i contained siloxane polymers D3 to D20 (see Table 6 described below).

In addition, FIG. 11C illustrates evaluation of a reaction between the drugs 15 and the test liquid 16. In FIG. 11C, the drugs 15 are supplied from the outlet 4 in advance. The test liquid is injected from the inlet 2 and the test liquid is pushed to the region near the outlet by air.

As described above, it was possible to evaluate reaction of a test liquid and two types of drugs without contamination between the reaction solutions of the respective drugs.

Comparative Example 1

In a comparative example 1, the first photosensitive resin and the second photosensitive resin described in Table 4 were used for a floor layer and a barrier layer. An acrylic resin was used for an upper covering layer.

FIG. 12A is a flowchart illustrating a manufacturing method according to the comparative example 1. To bond the upper covering layer (S14j), heating conditions by a hot plate were set to 80° C. and 10 min in the comparative example 1. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 1. The manufacturing method illustrated in FIG. 12A includes processes similar to those of the manufacturing method illustrated in FIG. 2.

FIG. 12B is a cross-sectional view of a microfluidic chip manufactured in the comparative example 1 corresponding to the cross-sectional view taken along A-A in FIG. 1B. In addition, FIG. 12C is a cross-sectional view of the microfluidic chip manufactured in the comparative example 1 corresponding to the cross-sectional view taken along C-C in FIG. 1D. A cross-sectional view corresponding to the B-B cross-sectional view of FIG. 1C has a configuration similar to the configuration of FIG. 12B and will be thus omitted.

A floor layer 11j was formed on a surface of a substrate 10j. A barrier layer 12j defines the channel section 3. An upper covering layer 13j is bonded to the barrier layer 12j to surround the channel section 3. Additionally, according to a GC/MS analysis (gas chromatography-mass spectrometry), a siloxane polymer containing layer 14j was not formed on surfaces of any of the floor layer 11j, the barrier layer 12j, and the upper covering layer 13j. The contact angle θ3 of the floor layer 11j was 60°, the contact angle θ3 of the barrier layer 12j was 70°, and the contact angle θ3 of the upper covering layer 13j was 40°.

In addition, FIG. 12C illustrates evaluation of a reaction between the drugs 15 and the test liquid 16. In FIG. 12C, the drugs 15 are supplied from the outlet 4 in advance. The test liquid is injected from the inlet 2 and the test liquid is pushed to the region near the outlet by air.

After this state, to promote a reaction between the drugs 15 and the test liquid 16, the microfluidic chip was placed in an incubator having a temperature of 50° C. and a humidity of 80% and left for one hour. The microfluidic chip was taken out one hour later and it was confirmed by an observation that the droplet flowed back to the inlet and the reaction solutions of respective drugs were contaminated.

Assessment Results

Table 5 illustrates manufacturing conditions and assessment results of Example 1 to the comparative example 1. Table 5 illustrates the compositions/components of the materials of the floor layer, the barrier layer, and the upper covering layer, the targets each left to rest under a siloxane gas atmosphere in the manufacturing process and the bonding conditions of the covering members, the contact angles (the contact angles θ3 after the upper covering layers are bonded), the detected polymers, the detection polymers, and the assessment results. The assessment methods have been described in respective Examples and the respective comparative examples. Contamination between reaction solutions branching in each of the microfluidic chips was assessed in the two levels of “Good” and “Poor” in accordance with the following assessment criterion on the basis of results of observations.

Assessment Criterion

- Good: A reaction solution remaining near the outlet 4 does not flow back to the branching section 18 of the channel, resulting in no contamination between reaction solutions
- Poor: A reaction solution remaining near the outlet 4 flows back to the branching section 18 of the channel, resulting in contamination between reaction solutions

TABLE 5

Composition/components of material

Covering

Flooring
Barrier
member

Example 1
Polysiloxane/acrylic
PDMS
PDMS

monomer

Example 2
Polysiloxane/acrylic
Polysiloxane/acrylic
PDMS

monomer
monomer

Example 3
Polysiloxane/acrylic
Polysiloxane/acrylic
Acrylic

monomer
monomer
resin

Example 4
Acrylic resin/epoxy
Polysiloxane/acrylic
PDMS

resin
monomer

Example 5
Polysiloxane/acrylic
Acrylic resin/acrylic
PDMS

monomer
monomer

Example 6
Polysiloxane/acrylic
Acrylic resin/acrylic
Acrylic

monomer
monomer
resin

Example 7
Acrylic resin/epoxy
Polysiloxane/acrylic
Acrylic

resin
monomer
resin

Example 8
Acrylic resin/epoxy
Acrylic resin/acrylic
Acrylic

resin
monomer
resin

Example 9
Acrylic resin/epoxy
Acrylic resin/acrylic
Glass

resin
monomer

Comparative
Acrylic resin/epoxy
Acrylic resin/acrylic
Acrylic

example 1
resin
monomer
resin

Manufacturing process

Siloxane atmosphere (PDMS

heated at 200° C. for 5 min)

Time for leaving
Bonding conditions

Target left to rest
to rest
of covering member

Example 1
—
—
200° C. - 10 min

Example 2
—
—
200° C. - 10 min

Example 3
Floor and barrier
10 min
200° C. - 10 min

Example 4
—
—
200° C. - 10 min

Example 5
—
—
200° C. - 10 min

Example 6
Floor
10 min
50° C. - 10 min

Example 7
Floor and barrier
10 min
50° C. - 10 min

Example 8
Covering member
10 min
80° C. - 10 min

Example 9
Covering member
10 min
120° C. - 10 min

Comparative
—
—
80° C. - 10 min

example 1

Contact angle θ3[°] after

bonding covering member

((*) . . . In presence

of hydrophobic layer)
Detection

Covering
polymer
Assessment

Floor
Barrier
member
(GC/MS)
result

Example 1
90 (*)
90 (*)
90 (*)
D3 to D20
Good

Example 2
100 (*)
90 (*)
130 (*)
D3 to D20
Good

Example 3
100 (*)
90 (*)
40
D3 to D20
Good

Example 4
60
90 (*)
100 (*)
D3 to D20
Good

Example 5
100 (*)
70
110 (*)
D3 to D20
Good

Example 6
100 (*)
70
40
D3 to D20
Good

Example 7
60
90 (*)
40
D3 to D20
Good

Example 8
60
70
90 (*)
D3 to D20
Good

Example 9
60
70
100 (*)
D3 to D20
Good

Comparative
60
70
40
—
Poor

example 1

Table 6 illustrates the relationships between the types of siloxane polymers included in the siloxane polymer containing layers 14 and the heating conditions. The heating conditions each indicate the temperature and time for bonding a covering member or leaving the covering member to rest in a heating furnace under a siloxane atmosphere. Here, an n-meric low-molecular weight siloxane polymer is abbreviated as Dn.

TABLE 6

Unit: ppm (w/w)

Heating conditions

Sample
100° C. ×
150° C. ×
200° C. ×

Component name
name
10 min
10 min
10 min

Cyclic siloxane
D3
<1.0
2.6
4.6

trimer

Cyclic siloxane
D4
39
50
44

tetramer

Cyclic siloxane
D5
120
150
220

pentamer

Cyclic siloxane
D6
120
200
300

hexamer

Cyclic siloxane
D7
110
180
270

heptamer

Cyclic siloxane
D8
81
160
210

octamer

Cyclic siloxane
D9
22
170
160

nonamer

Cyclic siloxane
D10
1.4
130
180

decamer

Cyclic siloxane
D11
<1.0
120
160

undecamer

Cyclic siloxane
D12
<1.0
70
170

dodecamer

Cyclic siloxane
D13
<1.0
10
130

tridecamer

Cyclic siloxane
D14
<1.0
<1.0
180

tetradecamer

Cyclic siloxane
D15
<1.0
<1.0
210

pentadecamer

Cyclic siloxane
D16
<1.0
<1.0
180

hexadecamer

Cyclic siloxane
D17
<1.0
<1.0
120

heptadecamer

Cyclic siloxane
D18
<1.0
<1.0
46

octadecamer

Cyclic siloxane
D19
<1.0
<1.0
10

nonadecamer

Cyclic siloxane
D20
<1.0
<1.0
1.9

eicosamer

In this way, in a case where a siloxane polymer containing layer (hydrophobic region) having a contact angle of 90 degrees or more and 130 degrees or less was formed on a surface of any of the components of each of the microfluidic chips, it was possible to prevent a backflow of a reaction solution in the microfluidic chip and prevent contamination between reaction solutions.

Second Embodiment
Basic Configuration of Microfluidic Chip

A second embodiment is fundamentally different from the first embodiment in that two types of regions having hydrophobicity and hydrophilicity are formed on a floor layer of a microfluidic chip. The following chiefly describes a configuration different from that of the first embodiment and simplifies or omits the description of configuration similar to that of the first embodiment.

FIG. 13 is a cross-sectional view of a microfluidic chip 101 according to the second embodiment corresponding to the C-C cross-sectional view in FIG. 1D. In the microfluidic chip 101, a floor layer 11k is formed on a substrate 10k from the input section 2 to branching section 18. Further, a configuration is adopted in which the floor layer 11k is provided up to a middle section 19 formed from the branching section 18 to the output section 4, but the floor layer 11k is not provided from the middle section 19 to the output section 4 and the substrate 10k is exposed. As illustrated in FIG. 13, a siloxane polymer containing layer 14k is formed on both an upper covering layer 13k and the floor layer 11k, but the region in which the substrate 10k is exposed exhibits hydrophilicity. Meanwhile, the region in which the floor layer 11k is formed exhibits hydrophobicity.

In this way, the microfluidic chip 101 according to the second embodiment is characterized in that the floor layer 11k on the substrate 10k is patterned to provide a hydrophilic region different from a hydrophobic region in the region near the output section 4.

Modification Example of Second Embodiment

FIG. 14 is a cross-sectional view of the microfluidic chip 101 according to a modification example of the second embodiment corresponding to the C-C cross-sectional view in FIG. 1D. The microfluidic chip 101 is different from that of the second embodiment in that a floor layer 111 is not provided from the input section 2 to the branching section 18 and up to the middle section 19 formed from the branching section 18 to the output section 4 and a substrate 101 is exposed, and the floor layer 111 is provided from the middle section 19 to the output section 4. As illustrated in FIG. 14, a siloxane polymer containing layer 14l is formed on both an upper covering layer 13l and the floor layer 111, but the region in which the floor layer 111 is formed exhibits hydrophilicity. Meanwhile, the region in which the substrate 101 is exposed exhibits hydrophobicity. As described below, a silicon coat 211 is applied to the substrate 101. In this way, the microfluidic chip 101 according to the modification example of the second embodiment is characterized in that the floor layer 111 on the substrate 101 coated with the silicon coat 211 is patterned to provide a hydrophilic region different from a hydrophobic region in the region near the output section 4.

Manufacturing Method

The method for manufacturing the microfluidic chip 101 according to the second embodiment or the modification example is similar to the manufacturing method according to the first embodiment, but different in that a pattern corresponding to the different types of regions of a hydrophobic region and a hydrophilic region is formed when the floor layer is formed (S101). The following description refers to a process corresponding to that of the manufacturing method according to the first embodiment when needed and uses the same reference signs for processes similar to those of the first embodiment to simplify or omit description.

Examples of Second Embodiment or Modification Example

The microfluidic chip according to the second embodiment or the modification example will be described with reference to specific Examples. The present invention is not limited to Examples below.

A first photosensitive resin used as a floor layer and a second photosensitive resin used as a barrier layer in each of Examples will be described. The first photosensitive resin in Table 7 includes polysiloxane and an acrylic monomer and the contact angle θ1 is 100°. The first photosensitive resin in Table 8 includes a silane coupling agent and an acrylic monomer and the contact angle θ1 is 60°. The first photosensitive resin in Table 9 includes an acrylic monomer and an acrylic monomer and the contact angle θ1 is 100°. The first photosensitive resin in Table 10 includes an acrylic resin and an epoxy resin and the contact angle θ1 is 60°.

The second photosensitive resin is illustrated in Table 11, the second photosensitive resin includes an acrylic resin and an acrylic monomer, and the contact angle θ1 is 70°.

TABLE 7

First photosensitive resin

Floor

Material characteristics
Negative

Liquid

Composition/components
Polysiloxane

Acrylic monomer

Contact angle
100°

Coat rotation speed
1100 rpm/10 sec

Pre-bake
90° C./90 sec

Exposure
100
mj/cm²

Development liquid
Sodium carbonate

Development time
180
sec

Washing with water
60
sec

Post-bake
230° C./30 min

Floor A

TABLE 8

First photosensitive resin

Floor

Material characteristics
Negative

Liquid

Composition/components
Silane coupling agent

Acrylic monomer

Contact angle
60°

Coat rotation speed
700 rpm/10 sec

Pre-bake
90° C./60 sec

Exposure
70
mj/cm²

Development liquid
Sodium carbonate

Development time
90
sec

Washing with water
60
sec

Post-bake
230° C./30 min

Floor B

TABLE 9

First photosensitive resin

Floor

Material characteristics
Negative

Liquid

Composition/components
Acrylic monomer

Acrylic monomer

Contact angle
100°

Coat rotation speed
900 rpm/10 sec

Pre-bake
90° C./100 sec

Exposure
100
mj/cm²

Development liquid
Sodium carbonate

Development time
180
sec

Washing with water
60
sec

Post-bake
230° C./30 min

Floor C

TABLE 10

First photosensitive resin

Floor

Material characteristics
Negative

Liquid

Composition/components
Acrylic resin

Epoxy resin

Contact angle
60°

Coat rotation speed
700 rpm/10 sec

Pre-bake
90° C./60 sec

Exposure
70
mj/cm²

Development liquid
Sodium carbonate

Development time
90
sec

Washing with water
60
sec

Post-bake
230° C./30 min

TABLE 11

Second photosensitive resin

Barrier layer

Material characteristics
Negative

Liquid

Composition/components
Acrylic resin

Acrylic monomer

Contact angle
70°

Coat rotation speed
500 rpm/10 sec

Pre-bake
130° C./180 sec

Exposure
60
mj/cm²

Development liquid
Sodium carbonate

Development time
180
sec

Washing with water
60
sec

Post-bake
230° C./30 min

Example 10

In Example 10 of the second embodiment, the first photosensitive resin in Table 7 was used for the floor layer and the second photosensitive resin in Table 11 was used for the barrier layer. A microfluidic chip was fabricated by using PDMS for the upper covering layer.

First, a glass substrate was coated with the first photosensitive resin that was transparent to form the floor layer (S1). The glass substrate was coated with the first photosensitive resin by using a spin coater at a rotation speed of 1100 rpm for 30 seconds. The rotation speed and the time were adjusted to produce a film thickness of 2 μm. Next, heating treatment (pre-bake) (S2) was conducted on a hot plate for the purpose of removing residual solvent medium included in the photosensitive resin. Pre-baking was carried out at a temperature of 90° C. for 90 seconds.

Next, the photosensitive resin layer on the glass substrate was exposed (S3). Specifically, the photosensitive resin was exposed to have a pattern through a photomask having a pattern for providing a hydrophobic region and a hydrophilic region in the microfluidic channel. A photomask having a two-layer structure of chromium and chromium oxide as a light-shielding film was used as the photomask. A proximity exposure apparatus was used for the exposure. The exposure apparatus included a high-pressure mercury lamp as a light source and had a broadband including the g-line, the h-line, and the i-line as the exposure wavelengths. The exposure value was 100 mJ/cm2.

Next, the exposed photosensitive resin layer was developed to form a pattern (S4). Specifically, the photosensitive resin layer was developed for 180 seconds using a sodium carbonate development liquid to dissolve unexposed portions for patterning.

Subsequently, the photosensitive resin layer on the substrate showered off the development liquid with ultrapure water and was dried in a spin dryer (S5).

Next, heating treatment (post-bake) was conducted in an oven at 230° C. for 30 minutes (S6). This formed the pattern of the floor layer corresponding a hydrophobic region and a hydrophilic region on the substrate.

Next, the substrate and the floor layer were coated with the second photosensitive resin that was transparent to form the barrier layer. First, the glass substrate and the floor layer were coated with the second photosensitive resin using a spin coater at a rotation speed of 500 rpm for ten seconds (S7). The rotation speed and the time were adjusted to produce a film thickness of 50 μm. Next, heating treatment (pre-bake) (S8) was conducted on a hot plate for the purpose of removing residual solvent medium included in the photosensitive resin. Pre-baking was carried out at a temperature of 130° C. for 180 seconds.

Next, the photosensitive resin layer above the glass substrate and the floor layer was exposed (S9). Specifically, the photosensitive resin was exposed to have a pattern through a photomask having a channel pattern. A photomask having a two-layer structure of chromium and chromium oxide as a light-shielding film was used as the photomask. A proximity exposure apparatus was used for the exposure. The exposure apparatus included a high-pressure mercury lamp as a light source and had a broadband including the g-line, the h-line, and the i-line as the exposure wavelengths. The exposure value was 60 mJ/cm2.

Next, the exposed photosensitive resin layer was developed to form a channel pattern (S10). Specifically, the photosensitive resin layer was developed for 180 seconds using a sodium carbonate development liquid to dissolve unexposed portions for patterning.

Subsequently, the photosensitive resin layer on the substrate showered off the development liquid with ultrapure water and was dried in a spin dryer (S11).

Next, heating treatment (post-bake) was conducted in an oven at 230° C. for 30 minutes (S12). This formed a channel section (channel pattern) determined by the barrier layer on the substrate. The minimum width of the opposed barrier layer, that is, the minimum width of the channel was 50 μm.

After the channel pattern was formed, the covering member was bonded to fabricate the microfluidic chip. PDMS was used for the covering member. The bonding surfaces of the barrier layer having the channel pattern and the PDMS were both irradiated with UV light (S13) before bonding. The amount of UV irradiation was set to 1000 mJ/cm2. After that, the covering member was heated on a hot plate at 200° C. for 10 min with the bonding surfaces bonded together, thereby bonding the covering member (S14). This produced the microfluidic chip 101.

In addition, a contact angle inside the channel section 3 in the microfluidic chip 101 according to Example 10 was measured by using a micro-titration contact angle meter DSM 100M (manufactured by KRUSS). It was confirmed that the contact angle θ3 of the region (hydrophobic region) illustrated in FIG. 13 in which the floor layer 11k was formed was 110°, the contact angle θ3 of the glass substrate region (hydrophilic region) in which the floor layer 11k was not formed was 70°, and the two types of regions of the hydrophobic region and the hydrophilic region having different contact angles were formed. The contact angle of the barrier layer was 70° and the contact angle of the covering member was 110°.

The initial contact angle θ1 of the floor layer 11k was 100° and the initial contact angle θ1 of the glass substrate was 20° at the time point when the floor layer 11k was formed, and the contact angle θ2 of the floor layer 11k was 60° and the contact angle θ2 of the glass substrate was 5° after a surface modification.

Example 11

In Example 11 of the second embodiment, the first photosensitive resin in Table 7 was used for the floor layer and the second photosensitive resin in Table 11 was used for the barrier layer. A microfluidic chip was fabricated by using PDMS for the upper covering layer.

To bond the upper covering layer (S14), heating conditions by a hot plate were set to 150° C. and 5 min in Example 11. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 10.

It was confirmed by GC/MS analysis that a siloxane polymer containing layer which contained low-molecular weight siloxanes D3 to D20 was formed on both a surface of the floor and a surface of the covering member at this time. In addition, the contact angle θ3 of the region (hydrophobic region) in which the floor layer 11k in FIG. 13 was formed was 100° and the contact angle θ3 of the glass substrate region (hydrophilic region) in which the floor layer 11k was not formed was 20°.

Example 12

In Example 12 of the second embodiment, the first photosensitive resin in Table 8 was used for the floor layer and the second photosensitive resin in Table 11 was used for the barrier layer. PDMS was used for an upper covering layer. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 10.

It was confirmed by GC/MS analysis that a siloxane polymer containing layer which contained low-molecular weight siloxanes D3 to D20 was formed on both a surface of the floor and a surface of the covering member at this time. In addition, the contact angle θ3 of the region (hydrophobic region) in which the floor layer 11k in FIG. 13 was formed was 95° and the contact angle θ3 of the glass substrate region (hydrophilic region) in which the floor layer 11k was not formed was 70°.

The initial contact angle θ1 of the region of the floor layer 11k was 60° and the initial contact angle θ1 of the glass substrate region was 20° at the time point when the floor layer was formed, and the contact angle θ2 of the region of the floor layer 11k was 25° and the contact angle θ2 of the glass substrate region was 5° after a surface modification.

Example 13

In Example 13 according to the modification example of the second embodiment, the first photosensitive resin in Table 8 was used for the floor layer and the second photosensitive resin in Table 11 was used for the barrier layer. PDMS was used for an upper covering layer.

A glass substrate having a surface coated with the silicon coat 211 was used for the glass substrate 101. In addition, in a process of bonding the upper covering layer 13l (S14), heating conditions by a hot plate were set to 100° C. and 10 min. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 10.

It was confirmed by GC/MS analysis that a siloxane polymer containing layer which contained low-molecular weight siloxanes D4 to D10 was formed on both a surface of the floor and a surface of the covering member at this time. In addition, the contact angle θ3 of the glass substrate region (hydrophobic region) in FIG. 14 coated with the silicon coat 211 in which the floor layer 111 was not formed was 90° and the contact angle θ3 of the region (hydrophilic region) in which the floor layer 111 was formed was 55°.

The initial contact angle θ1 of the region of the floor layer 111 was 20° and the initial contact angle θ1 of the glass substrate region was 95° at the time point when the floor layer 111 was formed, and the contact angle θ2 of the region of the floor layer 111 was 25° and the contact angle θ2 of the glass substrate was 80° after a surface modification.

Example 14

In Example 14 of the second embodiment, the first photosensitive resin in Table 7 was used for the floor layer and the second photosensitive resin in Table 11 was used for the barrier layer. A PMMA was used for an upper covering layer. The contact angle θ1 of the PMMA was 80°.

Example 14 includes a process of leaving the floor layer and the barrier layer to rest under a siloxane atmosphere. In addition, to bond the upper covering layer 13k (S14), heating conditions by a hot plate were set to 40° C. and 5 min. Bonding a PMMA under a high-temperature condition remarkably warped a substrate. A PMMA was thus bonded at low temperature within a short time. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 10.

In the process of leaving the PDMS to rest under a siloxane atmosphere, the PDMS was left to rest in a heating furnace at 200° C. for 10 min. A low-molecular weight siloxane atmosphere was formed in the heating furnace and the glass substrate having a channel pattern formed thereon was then exposed to the low-molecular weight siloxane atmosphere.

It was confirmed by GC/MS analysis that a siloxane polymer containing layer which contained low-molecular weight siloxanes D4 to D20 was formed on both a surface of the floor and a surface of the covering member at this time. In addition, the contact angle θ3 of the region (hydrophobic region) in which the floor layer 11k in FIG. 13 was formed was 110° and the contact angle θ3 of the glass substrate region (hydrophilic region) in which the floor layer 11k was not formed was 70°.

The initial contact angle θ1 of the region of the floor layer 11k was 100° and the initial contact angle θ1 of the glass substrate was 20° at the time point when the floor layer 11k was formed, and the contact angle θ2 of the region of the floor layer 11k was 60° and the contact angle θ2 of the glass substrate was 5° after a surface modification.

Example 15

In Example 15 according to the modification example of the second embodiment, the first photosensitive resin in Table 10 was used for the floor layer and the second photosensitive resin in Table 11 was used for the barrier layer. PDMS was used for an upper covering layer.

A glass substrate having a surface coated with the silicon coat 211 was used for the glass substrate 101. In addition, in a process of bonding an upper covering layer (S14), heating conditions by a hot plate were set to 150° C. and 5 min. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 10.

The contact angle θ3 of the glass substrate region (hydrophobic region) in FIG. 14 coated with the silicon coat 211 in which the floor layer 111 was not formed was 95° and the contact angle θ3 of the region (hydrophilic region) in which the floor layer 111 was formed was 60°.

The initial contact angle θ1 of the region of the floor layer 111 at the time point when the floor layer 111 was formed was 60°.

Comparative Example 2

In a comparative example 2 of the second embodiment, the first photosensitive resin in Table 7 was used for the floor layer and the second photosensitive resin in Table 11 was used for the barrier layer. PDMS was used for an upper covering layer.

In a process of bonding an upper covering layer (S14), heating conditions by a hot plate were set to 100° C. and 10 min in the comparative example 2. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 10.

It was confirmed by GC/MS analysis that a siloxane polymer containing layer which contained low-molecular weight siloxanes D4 to D10 was formed on both a surface of the floor and a surface of the covering member at this time. In addition, the contact angle θ3 of the region in which the floor layer was formed was 80° and the contact angle θ3 of the glass substrate region in which the floor layer was not formed was 55°.

Regarding the floor layer, the initial contact angle θ1 of the region of the floor layer was 100° and the initial contact angle θ1 of the glass substrate was 20° at the time when the floor layer was formed, and the contact angle θ2 of the region of the floor layer was 60° and the contact angle θ2 of the glass substrate was 5° after a surface modification.

Comparative Example 3

In a comparative example 3 of the second embodiment, the first photosensitive resin in Table 8 was used for the floor layer and the second photosensitive resin in Table 11 was used for the barrier layer. PDMS was used for an upper covering layer.

In a process of bonding an upper covering layer (S14), heating conditions by a hot plate were set to 100° C. and 10 min in the comparative example 3. Except for them, a microfluidic chip was fabricated under the conditions similar to those of Example 12.

It was confirmed by GC/MS analysis that a siloxane polymer containing layer which contained low-molecular weight siloxanes D4 to D10 was formed on both a surface of the floor and a surface of the covering member at this time. In addition, the contact angle θ3 of the region in which the floor layer was formed was 70° and the contact angle θ3 of the glass substrate region in which the floor layer was not formed was 55°.

Regarding the floor layer 11k, the initial contact angle θ1 of the region of the floor layer 11k was 60° and the initial contact angle θ1 of the glass substrate was 20° at the time when the floor layer was formed, and the contact angle θ2 of the region of the floor layer 11k was 25° and the contact angle θ2 of the glass substrate was 5° after a surface modification.

Comparative Example 4

In a comparative example 4 of the second embodiment, the first photosensitive resin in Table 7 was used for the floor layer and the second photosensitive resin in Table 11 was used for the barrier layer. Synthetic resin including PMMA was used for an upper covering layer.

The comparative example 4 includes a process of leaving the floor layer and the barrier layer to rest under a siloxane atmosphere. Except for them, a microfluidic chip was fabricated under conditions similar to those of Example 14.

In the process of leaving the PDMS to rest under a siloxane atmosphere, the PDMS was left to rest in a heating furnace at 100° C. for 10 min. A low-molecular weight siloxane atmosphere was formed in the heating furnace and the glass substrate having a channel pattern formed thereon was then exposed to the low-molecular weight siloxane atmosphere.

It was confirmed by GC/MS analysis that a siloxane polymer containing layer which contained low-molecular weight siloxanes D4 to D10 was formed on both a surface of the floor and a surface of the covering member at this time. In addition, the contact angle θ3 of the region in which the floor layer was formed was 80° and the contact angle θ3 of the glass substrate region in which the floor layer was not formed was 55°.

Regarding the floor layer, the initial contact angle θ1 of the region of the floor layer was 100° and the initial contact angle θ1 of the glass substrate was 20° at the time point when the floor layer was formed, and the contact angle θ2 of the region of the floor layer was 60° and the contact angle θ2 of the glass substrate was 5° after a surface modification.

Assessment Results

As in the assessment method performed in the first embodiment, drugs were supplied from the outlet 4 of the channel in advance in each of the microfluidic chips according to Examples 10 to 15 and the comparative examples 2 to 4. A test liquid was injected from the inlet 2. After the test liquid was pushed to the region near the outlet 4 by air, the microfluidic chip was put in an incubator having a temperature of 50° C. and a humidity of 80% and left for one hour to promote reaction between the test liquid and the drugs. The microfluidic chip was taken out and observed one hour later. Table 12 illustrates manufacturing conditions and assessment results of Example 10 to the comparative example 4.

TABLE 12

Composition/components of material

Sub-

Covering

strate
Floor
Barrier
member

Example 10
Glass
Polysiloxane/
Acrylic resin/
PDMS

acrylic monomer
acrylic monomer

Example 11
Glass
Polysiloxane/
Acrylic resin/
PDMS

acrylic monomer
acrylic monomer

Example 12
Glass
Silane coupling
Acrylic resin/
PDMS

agent/acrylic
acrylic monomer

monomer

Example 13
Glass/
Silane coupling
Acrylic resin/
PDMS

silicon
agent/acrylic
acrylic monomer

coat
monomer

Example 14
Glass
Polysiloxane/
Acrylic resin/
PMMA

acrylic monomer
acrylic monomer

Example 15
Glass/
Acrylic resin/
Acrylic resin/
PDMS

silicon
epoxy resin
acrylic monomer

coat

Comparative
Glass
Polysiloxane/
Acrylic resin/
PDMS

example 2

acrylic monomer
acrylic monomer

Comparative
Glass
Silane coupling
Acrylic resin/
PDMS

example 3

agent/acrylic
acrylic monomer

monomer

Comparative
Glass
Polysiloxane/
Acrylic resin/
PMMA

example 4

acrylic monomer
acrylic monomer

As illustrated in Table 12, it was confirmed that the contact angle decreased after UV irradiation and the contact angle increased after the PDMS was formed by firing through the process of boding the upper covering layer because a low-molecular weight siloxane containing layer was formed on the surface.

The microfluidic chips according to Example 10 to Example 15 all had satisfactory (“Good”) contamination results. That is, the reaction solution remained near the outlet and the reaction solution did not flow back to the branching section 18 of the channel in each of the microfluidic chips according to Example 10 to Example 15. This made it possible to carry out a reaction assessment of the test liquid and two types of drugs without contamination between the reaction solutions.

In contrast, the microfluidic chips according to the comparative example 2 to the comparative example 4 all had unsatisfactory (“Poor”) contamination results. The reaction solution did not remain near the outlet and the reaction solution flowed back to the branching section 18 of the channel. Reaction solutions thus became contaminated and it was not possible to carry out a reaction assessment of the test liquid and two types of drugs.

Here, the comparative examples 2, 3, and 4 are respectively obtained by carrying out bonding conditions or heating conditions in heating furnaces at low temperature in Example 10, Example 12, and Example 14. The comparative example 2 to the comparative example 4 seemed to fail to offer effects of sufficient hydrophobization because only siloxanes having a lower level of polymerization volatilized. Higher temperature was thus considered more preferable as a firing condition of PDMS in the second embodiment.

Restraint on Backflow of Droplet

In a microfluidic chip, the movement of a droplet in a channel is related to the balance of the Laplace pressure of a liquid interface in the channel. The surface energy of a solidus surface that is a section in contact with the surface of liquid, that is, the contact angle is one of important factors for the Laplace pressure. Therefore, it is possible to prevent a backflow by controlling the contact angle of the surface of the channel. To cause a fluid to smoothly flow, a material having a surface whose contact angle exhibits hydrophilicity is typically used. In addition, in a case where a droplet is retained in a predetermined place as in the present disclosure, a material having a surface whose contact angle exhibits hydrophobicity is used. As the relationship between a droplet and a surface of a solid body, surface tension does not act on a droplet so much with respect to a surface of a solid body that has hydrophilicity. That is, a droplet easily mixes with a hydrophilic surface. In contrast, surface tension easily acts on a droplet with respect to a surface of a solid body that has hydrophobicity. That is, a droplet does not easily mix with a hydrophobic surface. The use of these properties allows a droplet to remain on a hydrophilic surface. As a result of studies, it is found that it is possible to restrain backflow of a droplet by keeping the contact angle of a hydrophobic region at 90 degrees more and 130 degrees or less and the contact angle of a hydrophilic region at less than 90 degrees.

A microfluidic chip and a method for manufacturing the microfluidic chip according to embodiments of the present invention are not limited to the embodiments and Examples described above.

A microfluidic chip and a method for manufacturing a microfluidic chip according to embodiments of the present invention prevent backflow of a reaction solution and prevent contamination between reaction solutions by providing a hydrophobic region and a hydrophilic region in a microfluidic chip for research use, diagnostic use, testing, analysis, incubation, or the like by using material included in a channel.

In addition, it is also possible to control a contact angle in a process such as UV irradiation or bonding that is typically performed to manufacture a microfluidic chip without providing a special process, offering even an effect of increasing the manufacturing efficiency.

Technology has been proposed that forms fine reaction fields by applying lithography processing or thick film processing technology and allows a minute amount of liquid or the like to be tested in units of several microliters to several nanoliters. Such technology that uses fine reaction fields is referred to as μ-TAS (Micro Total Analysis system).

μ-TAS is applied to fields such as genetic testing, chromosome testing, cell testing, and medicament development, biotechnology, testing for minute quantities of substances in the environment, inspection of the breeding environment of agricultural crops or the like, genetic testing of agricultural crops, and the like. The introduction of the μ-TAS technology offers great effects such as automation, acceleration, higher accuracy, lower cost, speed, and reduced environmental impacts.

In μ-TAS, reactions, observations, and the like are made by using micrometer-sized channels (microfluidic channels or microchannels) formed on substrates in many cases. Such devices are each referred to as a microfluidic chip or the like.

Such microfluidic chips have been fabricated by using technology such as injection molding, molding, cutting, and etching. In addition, glass substrates have been chiefly used as substrates of microfluidic chips because the glass substrates are easy to manufacture and also allow for optical detection. Meanwhile, microfluidic chips including light and inexpensive resin materials less prone to breakage than glass substrates also have been under development. Methods for manufacturing microfluidic chips including resin materials include a method for fabricating a microfluidic chip by forming a resin pattern for a channel chiefly by photolithography and bonding a covering member to the resin pattern. This method makes it possible to form even a fine channel pattern that is difficult to form by the conventional technology in some cases.

In addition, a microfluidic chip allows a sensitivity assessment to be carried out in which different types of drugs are fixed in advance in different places in a channel, a test liquid is introduced from an inlet of the channel, and the test liquid and the drugs are reacted. It is advantageous that it is possible to collectively assess the reactions between the test liquid and the multiple drugs at one time. Meanwhile, it is important for such a microfluidic chip to prevent contamination between the respective reaction solutions. This is because, once the respective reaction solutions mix, it is no longer possible to carry out an accurate assessment. A method has been described that defines the shape of a buffer to prevent contamination between chambers. For example, JP 2021-156780 A describes that, in a device for handling a fluid in which trapezoid-shaped buffers connected to chambers are connected through channels, contamination between the chambers is suppressed by setting greater length for the bottom side of each of the trapezoids than the length of a side.

However, for example, in a case where a channel includes a hydrophilic material, the conventional technology having a shape definition may undergo backflow of a reaction solution. In addition, a structure in which a buffer and a chamber are joined by a narrow channel is prone to a backflow of a reaction solution due to a capillary phenomenon. In addition, a portion having a changed shape in the channel is prone to have local air bubbles. An air bubble may cause backflow of reaction solution.

As a result of studies, it found that a hydrophobic region provided in a channel in a microfluidic chip makes it possible to control the movement of droplets and prevent contamination between reaction solutions in the channel. It is possible to form the hydrophobic region by patterning a photosensitive resin and this is an extremely simple method. A microfluidic chip and a method for manufacturing a microfluidic chip according to embodiments of the present invention prevent contamination between reaction solutions in a microfluidic chip.

As a result of studies, it is found that a channel chip provided with a hydrophobic region and a hydrophilic region using material included in a channel makes it possible to stably prevent contamination between reaction solutions.

Accordingly, a microfluidic chip and a method for manufacturing a microfluidic chip according to embodiments of the present invention prevent backflow of reaction solution in a microfluidic chip and prevent contamination between reaction solutions.

A microfluidic chip according to an embodiment of the present invention includes an input section from which a fluid is introduced; a channel section in which the fluid flows; and an output section from which the fluid is discharged or a drug fixation section (uniformly referred to as an “output section”) where the fluid and a drug come into contact. The channel section has a region (referred to as a “hydrophobic region”) in which a contact angle of a surface in contact with the fluid is 90 degrees or more and 130 degrees or less.

A microfluidic chip according to an embodiment of the present invention prevents backflow of reactant in a microfluidic chip and prevents contamination between reaction solutions.

Obviously, numerous modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described herein.

	Number	Date	Country
Parent	PCT/JP2023/007527	Mar 2023	WO
Child	18915571		US

MICROFLUIDIC CHIP AND METHOD FOR MANUFACTURING MICROFLUIDIC CHIP

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