The present application benefits from Japanese application serial number JP2008-194919, filed on Jul. 29, 2008, the entire content of which is hereby incorporated by reference into this application.
1. Field of the Invention
The present invention relates to a microchip that is adapted to form an emulsion and has first and second glass substrates and a silicon substrate provided between the first and second glass substrates, and to a method for manufacturing the microchip for forming an emulsion.
2. Background Art
In recent years, research has been carried out on cell analysis, chemical reaction, biochemical reaction, biochemical separation, biochemical analysis, etc. using a microchip called a micro total analysis system (μ-TAS), a microchip called a lab-on-a-chip, or a microchip called a micro electro mechanical system (MEMS). Such a microchip includes a plate having sides of several centimeters. The plate has formed therein a flow path of micrometer order and several types of sample introduction holes. The flow path is branched into multiple flow paths, while the branched flow paths join.
The microchip is a system adapted to react, separate and analyze a solution by causing the solution to flow in the flow path (refer to No. JP3402635B). It is known that the system is capable of reacting, separating and analyzing a small amount of a sample and improving the efficiency of the reaction. The microchip has attracted attention.
On the other hand, research has been carried out on a technique for generating a fine emulsion (droplet) in a micro flow path in the fields of chemicals, cosmetics, electronic members or electronic materials (LCD spacer and the like) or drug delivery. The emulsion is formed by using two types of fluids (such as water and oil) that are not mixed with each other due to low affinity with each other and dispersing one of the two types of fluids into the other. Typical emulsions are the following two types: a water-in-oil type emulsion formed by dispersing a water droplet into an oil phase; and an oil-in-water type emulsion formed by dispersing an oil droplet into a water phase.
The emulsion is formed using a flow path having a T-junction, for example. Referring to
When the T-shaped flow path 101 shown in
In a conventional techniques a substrate in which a flow path is provided to form an emulsion is generally made of a synthetic resin material such as polydimethylsiloxane (PDMS) (refer to JP2008-116254A). However, when a fluid flows in a flow path provided in a PDMS substrate at high pressure in order to form an emulsion, the fluid pressure may cause transformation of the flow path and an increase in the width of the flow path. It is, therefore, difficult to form such a fine emulsion as described above using a microchip having the PDMS substrate.
In addition, there is a technique for forming a fine emulsion using an ultrasonic wave. However, there is a problem that the size of an emulsion particle is not constant.
It is, therefore, an object of the present invention to provide a microchip capable of forming a fine emulsion in a stable manner, and a method for manufacturing the microchip for forming an emulsion.
According to the present invention, a microchip for forming an emulsion comprises: a first glass substrate; a second glass substrate; and a silicon substrate provided between the first and second glass substrates, wherein the silicon substrate has formed therein a first fluid flow path through which a first fluid flows and a second fluid flow path through which a second fluid that is not mixed with the first fluid flows; the first fluid flow path has a plurality of branched flow paths that join at a joint portion; the second fluid flow path has an edge portion that communicates with the joint portion; and the silicon substrate has formed therein an emulsion formation flow path to form an emulsion composed of the first fluid and the second fluid that is surrounded by the first fluid, the emulsion formation flow path facing the edge portion of the second fluid flow path.
In the microchip for forming an emulsion according to the present invention, the silicon substrate has a restricting portion formed between the joint portion and the emulsion formation flow path.
In the microchip for forming an emulsion according to the present invention, the restricting portion extends through the silicon substrate in the direction of the thickness of the silicon substrate.
In the microchip for forming an emulsion according to the present invention, the restricting portion has a height smaller than the thickness of the silicon substrate and has an opening facing toward the second glass substrate.
In the microchip for forming an emulsion according to the present invention, the surfaces of the restricting portion is entirely surrounded by the silicon substrate.
In the microchip for forming an emulsion according to the present invention, the first glass substrate or the second glass substrate has formed therein a first fluid inflow hole, the first fluid inflow hole communicating with the first fluid flow path of the silicon substrate and is adapted to introduce the first fluid to the first fluid flow path, the first glass substrate or the second glass substrate has formed therein a second fluid inflow hole, the second fluid inflow hole communicating with the second fluid flow path of the silicon substrate and is adapted to introduce the second fluid to the second fluid flow path, and the first glass substrate or the second glass substrate has formed therein an emulsion outflow hole, the emulsion outflow hole communicating with the emulsion formation flow path of the silicon substrate and allows the emulsion to flow out of the emulsion formation flow path.
According to the present invention, a method for manufacturing a microchip adapted to form an emulsion and having a first glass substrate, a second glass substrate and a silicon substrate provided between the first and second glass substrates, comprises: preparing the first glass substrate and the silicon substrate; bonding the first glass substrate with the silicon substrate; polishing the silicon substrate provided on the first glass substrate to ensure that the silicon substrate has a predetermined thickness; forming flow paths in the silicon substrate having the predetermined thickness by etching; and bonding the second glass substrate with the silicon substrate having the flow paths formed therein, wherein in forming the flow paths in the silicon substrate, a first fluid flow path through which a first fluid flows is formed in the silicon substrate, a second fluid flow path through which a second fluid that is not mixed with the first fluid flows is formed in the silicon substrate, and an emulsion formation flow path is formed in the silicon substrate to form an emulsion composed of the first fluid and the second fluid that is surrounded by the first fluid; the first fluid flow path has a plurality of branched flow paths that join at a joint portion; and the second fluid flow path has an edge portion that communicates with the joint portion.
In the method according to the present invention, in forming the flow paths in the silicon substrate, a restricting portion extending through the silicon substrate in the direction of the thickness of the silicon substrate is formed between the joint portion and the emulsion formation flow path.
In the method according to the present invention, in forming the flow paths in the silicon substrate, a restricting portion is formed between the joint portion and the emulsion formation flow path, the restricting portion having a height smaller than the thickness of the silicon substrate and having an opening facing toward the second glass substrate.
In the method according to the present invention, in forming the flow paths in the silicon substrate, a restricting portion is formed between the joint portion and the emulsion formation flow path, the surfaces of the restricting portion being entirely surrounded by the silicon substrate.
According to the present invention, the silicon substrate has formed therein the first fluid flow path (in which the first fluid flows), the second fluid flow path (in which the second fluid that is not mixed with the first fluid flows) and the emulsion formation flow path (in which an emulsion is formed). This configuration allows a fine emulsion composed of the first fluid and the second fluid (that is surrounded by the first fluid) to be formed in a stable manner.
a) to 6(f) are diagrams showing a method for manufacturing the microchip for forming an emulsion according to the present embodiment.
a) to 9(e) are diagrams showing a method for manufacturing the microchip for forming an emulsion according to the second embodiment.
a) and 12(b) are diagrams showing a method for manufacturing the microchip for forming an emulsion according to the third embodiment.
a) to 13(d) are diagrams showing a modification of a process for forming flow paths by etching in the method for manufacturing the microchip forming an emulsion according to each of the second and third embodiments.
The first embodiment of the present invention is described below with reference to the accompanying drawings.
First, the outline of the microchip for forming an emulsion according to the present embodiment is described with reference to
In
The second glass substrate 12 has a first fluid inflow hole 14, a second fluid inflow hole 15 and an emulsion outflow hole 16. The first fluid inflow hole 14, the second fluid inflow hole 15 and the emulsion outflow hole 16 extend through the second glass substrate 12 in the direction of the thickness of the second glass substrate 12.
The first fluid inflow hole 14 is adapted to introduce a first fluid F1 from the outside of the microchip 10 (for forming an emulsion) to the silicon substrate 20. As described later, the first fluid inflow hole 14 communicates with an inflow portion (first fluid inflow portion 24) of a first fluid flow path 21 provided in the silicon substrate 20. The second fluid inflow hole 15 is adapted to introduce a second fluid F2 from the outside of the microchip 10 (for forming an emulsion) to the silicon substrate 20. As described later, the second fluid inflow hole 15 communicates with an inflow portion (second fluid inflow portion 25) of a second fluid flow path 22 provided in the silicon substrate 20.
The emulsion outflow hole 16 communicates with an outflow portion (emulsion outflow portion 26) of an emulsion formation flow path 23 provided in the silicon substrate 20 as described later. The emulsion outflow hole 16 is adapted to cause an emulsion E formed in the emulsion formation flow path 23 to flow out of the emulsion formation flow path 23 to the outside of the microchip 10 for forming an emulsion.
The second glass substrate 12 is made of Pyrex (registered trademark of Corning Incorporated) glass or the like.
The first glass substrate 11 is entirely flat and has a plate shape. The first glass substrate 11 is configured in substantially the same manner as the second glass substrate 12 except that the first glass substrate 11 does not have the first fluid inflow hole 14, the second fluid inflow hole 15 and the emulsion outflow hole 16. The first glass substrate 11 is made of Pyrex (registered trademark of Corning Incorporated) glass or the like in the same manner as the second glass substrate 12.
The silicon substrate 20 is made of silicon. The silicon substrate 20 has the first fluid flow path 21, the second fluid flow path 22 and the emulsion formation flow path 23. The first fluid F1 flows in the first fluid flow path 21. The second fluid F2 flows in the second fluid flow path 22. The second fluid F2 flowing in the second fluid flow path 22 is not mixed with the first fluid F1. The emulsion E is formed in the emulsion formation flow path 23. The first fluid flow path 21, the second fluid flow path 22 and the emulsion formation flow path 23 extend through the silicon substrate 20 in the direction of the thickness of the silicon substrate 20.
As shown in
The second fluid flow path 22 has a second fluid inflow portion 25 that communicates with the second fluid inflow hole 15 of the second glass substrate 12. The straight flow path 31 extends straight from the second fluid inflow portion 25. The straight flow path 31 has an edge portion 32 on a downstream side thereof. The edge portion 32 communicates with the joint portion 30.
The emulsion formation flow path 23 is adapted to form the emulsion E. The emulsion E is composed of the first fluid F1 (that flows from the first fluid flow path 21) and the second fluid F2 (that flows from the second fluid flow path 22) that is surrounded by the first fluid F1 (as shown in
As shown in
As shown in
The restricting portion 34 has a width w1 smaller than the width of the emulsion formation flow path body 33. The width w1 of the restricting portion 34 is in a range of 1 μm to 30 μm, for example. As shown in
Referring to
Next, an effect of the microchip for forming an emulsion according to the present embodiment is described below with reference to
As shown in
Next, the first fluid F1 introduced from the first fluid inflow hole 14 reaches the branch portion 27 through the first fluid inflow portion 24 as shown in
The first fluid F1 and the second fluid F2 join at the joint portion 30. After that, the first fluid F1 and the second fluid F2 are pushed toward the emulsion formation flow path 23. Thus, the first fluid F1 and the second fluid F2 pass through the narrow restricting portion 34. When the first fluid F1 and the second fluid F2 pass through the narrow restricting portion 34, a large number of fine emulsions E are formed (refer to
After the formation of the emulsions E, the emulsions E pass through the emulsion formation flow path body 33 of the emulsion formation flow path 23 and the emulsion outflow portion 26. Then, the emulsions E flow out of the emulsion outflow hole 16 of the second glass substrate 12.
As a combination of the first fluid F1 and the second fluid F2, a combination of a fluid composed of hexadecane (oil) and a fluid composed of water containing a nonionic surface active agent Span 80 (sorbitan monooleate) may be used. That is, the first fluid F1 may be composed of hexadecane (oil), while the second fluid F2 may be composed of water containing a nonionic surface active agent Span 80 (sorbitan monooleate). Alternatively, the first fluid F1 may be composed of water containing a nonionic surface active agent Span 80 (sorbitan monooleate), while the second fluid F2 may be composed of hexadecane (oil). The combination of the first fluid F1 and the second fluid F2 is not limited to the aforementioned combination. The first fluid F1 and the second fluid F2 may be any fluids as long as the first fluid F1 and the second fluid F2 have low affinities with each other.
Next, the method for manufacturing the microchip for forming an emulsion according to the present embodiment is described below with reference to
First, the first glass substrate 11 and the silicon substrate 20 are prepared (as shown in
The silicon substrate 20 has a thickness of 300 μm to 800 μm. In addition, the silicon substrate 20 is flat and has a plate shape. In the case where the silicon substrate 20 and the first glass substrate 11 are bonded with each other by anodic bonding, at least the surface (to be bonded with the first glass substrate 11 by anodic bonding) of the silicon substrate 20 is preferably subjected to mirror polishing.
Next, the silicon substrate 20 is bonded with the first glass substrate 11 by anodic bonding (as shown in
The first glass substrate 11 and the silicon substrate 20 may be bonded with each other by means of adhesive resin. The adhesive resin may be benzocyclobutene resin. When benzocyclobutene resin is used as the adhesive resin, the first glass substrate 11 and the silicon substrate 20 are heated at a temperature of 250° C. and pressed at a pressure level of 3.5 kN under vacuum for 30 minutes to be bonded with each other. When photosensitive resin such as the benzocyclobutene resin is used as the adhesive resin, a region bonded by means of the adhesive resin can be patterned by a photolithographic method. The pattering allows the first glass substrate 11 and the silicon substrate 20 to be bonded with each other under the condition that the adhesive resin is not present in the first fluid flow path 21, the second fluid flow path 22 and the emulsion formation flow path 23. This suppresses an effect of the adhesive resin on the formation of the emulsions.
The first glass substrate 11 and the silicon substrate 20 may be bonded with each other by eutectic bonding (in which, for example, the substrates 11 and 20 has respective metal (Au, Au—Sn) films, and the metal films contact each other and are heated at a temperature of approximately 400° C. to be alloyed and bonded with each other).
Next, the silicon substrate 20 located on the first glass substrate 11 is polished to have a predetermined thickness (as shown in
Then, the first fluid flow path 21, the second fluid flow path 22 and the emulsion formation flow path 23 are formed in the polished silicon substrate 20 having the predetermined thickness by etching (as shown in
Before the formation of the flow paths 21 to 23, an etching mask 13 having an opening 13a is formed on the silicon substrate 20 (as shown in
Next, etching is performed on a region (of the silicon substrate 20) corresponding to the opening 13a that is not covered with the etching mask 13 to form the first fluid flow path 21, the second fluid flow path 22 and the emulsion formation flow path 23 (as shown in
Then, the second glass substrate 12 is prepared. The second glass substrate 12 has a thickness of 300 μm to 800 μm and a plate shape and is flat, in the same manner as the first glass substrate 11. In the case where the second glass substrate 12 is bonded with the silicon substrate 20 by anodic bonding, the second glass substrate 12 is composed of glass containing a mobile ion such as a sodium (Na) ion. The glass containing a mobile ion may be Pyrex (registered trademark of Corning Incorporated) glass.
Next, the holes 14, 15, and 16 are formed in the second glass substrate 12 by sandblasting, a carbon dioxide gas laser, a drill or the like. Specifically, the first fluid inflow hole 14 (communicating with the first fluid flow path 21 formed in the silicon substrate 20), the second fluid inflow hole 15 and the emulsion outflow hole 16 are formed in the second glass substrate 12.
After that, the second glass substrate 12 is bonded with the silicon substrate 20 by anodic bonding (as shown in
In this way, the microchip 10 (as shown in
According to the present embodiment, the emulsion formation flow path 23 is formed in the silicon substrate 20 and faces the edge portion 32 of the second fluid flow path 22; and each of the emulsions E is composed of the first fluid F1 (that flows from the first fluid flow path 21) and the second fluid F2 (that flows from the second fluid flow path 22) that is surrounded by the first fluid F1. This configuration allows the emulsions E of approximately 1 μm or less to be uniformly sized (particle sized) and stably formed.
According to the present embodiment, each of the flow paths is formed in the silicon substrate 20 made of an inorganic material. Thus, the silicon substrate 20 is not swollen or corroded by an organic solvent, and the shapes of the flow paths are not changed due to the organic solvent. In addition, the shapes of the flow paths are not changed due to pressure of the first fluid F1 and pressure of the second fluid F2.
According to the present embodiment, the restricting portion 34 is provided between the joint portion 30 and the emulsion formation flow path 23. The flow of the first fluid F1 flowing from the first fluid flow path 21 and the flow of the second fluid F2 flowing from the second fluid flow path 22 can be concentrated on the restricting portion 34. Thus, fine emulsions of 1 μm or less can be efficiently, easily formed in a stable manner.
According to the present embodiment, the silicon substrate 20 is sandwiched by the transparent first glass substrate 11 and the transparent second glass substrate 12. This, behaviors of the emulsions in the silicon substrate 20 can be confirmed by transparent observation.
According to the present embodiment, since each of the flow paths are provided in the silicon substrate 20, the flow paths can be easily processed. For example, each of the flow paths can be finely processed with a high aspect ratio and at a submicron level.
According to the present embodiment, after the silicon substrate 20 provided on the first glass substrate 11 is polished to have the predetermined thickness, the first fluid flow path 21, the second fluid flow path 22 and the emulsion formation flow path 23 are formed in the silicon substrate 20 by etching. Since the silicon substrate 20 is polished before the formation of each of the flow paths, the flow paths are not polished. Therefore, any burr and crack are not generated at peripheries of opening portions of the flow paths. This can reduce the likelihood of a failure in processed portions of the flow paths during the manufacturing of the microchip 10 for forming an emulsion.
The second embodiment of the present invention is described below with reference to
In
As shown in
The configuration of the microchip 10 for forming an emulsion according to the second embodiment is substantially the same as that of the microchip 10 for forming an emulsion according to the first embodiment except for the configuration of the restricting portion 35, and detail description thereof is omitted.
The method for manufacturing the microchip according to the present embodiment is described below with reference to
First, the first glass substrate 11 and the silicon substrate 20 are prepared (as shown in
Next, a first etching mask 17 having openings 17a and 17b is formed on the silicon substrate 20 (as shown in
Then, a second etching mask 18 is formed on the first etching mask 17 (as shown in
Then, a portion of the silicon substrate 20 is etched in the direction of the thickness of the silicon substrate 20 by using the second etching mask 18 (first etching:
Then, a portion of the silicon substrate 20 is etched in the direction of the thickness of the silicon substrate 20 by using the first etching mask 17 (second etching:
Then, the second glass substrate 12 is prepared. The second glass substrate 12 has a thickness of 300 μm to 800 μm and a plate shape and is flat, as described in the process shown in
After that, the silicon substrate 20 and the second glass substrate 12 are bonded with each other by anodic bonding (as shown in
Next, a description is made of a modification of the process (shown in
First, a first etching mask 40 is formed in the silicon substrate 20 (as shown in
Next, a portion of the silicon substrate 20 is etched in the direction of the thickness of the silicon substrate 20 by using the first etching mask 40 (first etching:
Then, a second etching mask 41 is formed on the silicon substrate 20 (as shown in
Then, portions of the silicon substrate 20 are etched in the direction of the thickness of the silicon substrate 20 by using the second etching mask 41 (second etching:
According to the present embodiment, the silicon substrate 20 has the restricting portion 35 formed therein. The restricting portion 35 has the height smaller than the thickness of the silicon substrate 20 and is open toward the second glass substrate 12. The flow of the first fluid F1 flowing from the first fluid flow path 21 and the flow of the second fluid F2 flowing from the second fluid flow path 22 can be concentrated on the restricting portion 35. Thus, fine emulsions of 1 μm or less can be efficiently, easily formed in a stable manner.
A method for manufacturing a microchip according to the third embodiment of the present invention is described below with reference to
In
As shown in
The configuration of the microchip 10 for forming an emulsion according to the third embodiment is substantially the same as that of the microchips 10 for forming an emulsion according to the first and second embodiments except for the configuration of the restricting portion 36, and detail description thereof is omitted.
The method for manufacturing the microchip according to the present embodiment is described below with reference to
First, in the same manner as the process shown in
Next, in the same manner as the process shown in
Next, a portion of the silicon substrate portion 20A is etched in the direction of the thickness of the silicon substrate portion 20A by using the second etching mask 18 (first etching:
In this way, a first microchip portion 10A composed of the first glass substrate 11 and the silicon substrate portion 20A is formed (as shown in
Similarly to the first microchip portion 10A, a second microchip portion 10B is formed (as shown in
Next, the first microchip portion 10A and the second microchip portion 10B are bonded with each other (as shown in
In this way, the microchip 10 for forming an emulsion is formed (as shown in
In the present embodiment, the process shown in
According to the present embodiment, the surfaces (which are the side surfaces 36a and 36b, the top surface 36c and the bottom surface 36d) of the restricting portion 36 are surrounded by the silicon substrate 20. Thus, emulsions E can be formed in a stable manner even when the first fluid F1 is composed of water and the second fluid F2 is composed of oil (oil-in-water type) and even when the first fluid F1 is composed of oil and the second fluid F2 is composed of water (water-in-oil type). That is, when water and oil that will flow in the flow paths (first and second fluid flow paths 21, 22) are switched to each other, the type (oil-in-water type or water-in-oil type) of emulsions to be formed can be switched to the other type (water-in-oil type or oil-in-water type).
In the present embodiment, a third fluid flow path may be provided between the first fluid flow path 21 and the emulsion formation flow path 23 to form a water-oil-water double emulsion and an oil-water-oil double emulsion.
The first fluid F1 introduced from the first fluid inflow hole 14 is divided at the branch portion 27 of the first fluid flow path 21, and the divided first fluids F1 flow in the branched flow paths 28a and 28b and join at the joint portion 30, in each of the first to third embodiments. The configuration of the microchip, however, is not limited to this. An inflow hole through which the fluid that will flow in the branched flow path 28a is introduced, and an inflow path through which the fluid that will flow in the branched flow path 28b is introduced, may be separately provided. In this case, the types, components, pressure levels and the like of the fluids flowing in the branched flow paths 28a and 28b may be different from each other.
The first fluid flow path 21 has the pair of branched flow paths 28a and 28b in each of the first to third embodiments. The first fluid flow path 21 may have three or more of branched flow paths.
The first fluid inflow hole 14, the second fluid inflow hole 15 and the emulsion outflow hole 16 are provided in the second glass substrate 12 in each of the first to third embodiments. The configuration of the microchip, however, is not limited to this. A part or all of the first fluid inflow hole 14, the second fluid inflow hole 15 and the emulsion outflow hole 16 may be provided in the first glass substrate 11.
Number | Date | Country | Kind |
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2008-194919 | Jul 2008 | JP | national |