JP2007286069A - Microchemical chip - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a microchemical chip capable of efficiently mixing a plurality of different fluids to be processed without having to enlarge its constitution. <P>SOLUTION: The microchemical chip 1 has a substrate 11 in which a channel 12 for circulating the fluids to be processed and supply parts 13a and 13b connected to the channel 12 for making the fluids to be processed each flow in the channel 12 are formed. The plurality of fluids to be processed are made to flow in the channel 12 from the supply parts 13a and 13b. The plurality of fluids to be processed made to flow in are made confluent and applied with predetermined processings. In the microchemical chip 1, the channel 12 comprises a hydrophilic part (or a hydrophobic part) 12a having hydrophilic (or hydrophobic) wall surfaces and a length L1 on the more downstream side in the direction of the circulation of the fluids to be processed than locations connected to the supply parts 13a and 13b. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a microchemical chip capable of performing a predetermined process such as reaction or analysis on a fluid to be processed such as a substrate or a reagent that circulates through a minute flow path. The present invention relates to a microchemical chip capable of performing a predetermined process by mixing a plurality of different fluids to be processed as in the case of mixing and reacting.

  In recent years, in the field of chemical technology and biotechnology, research for performing reaction to a sample, analysis of a sample, and the like in a minute region has been performed, and a micro electro mechanical system (abbreviation: MEMS). ) Microchemical systems are being researched and developed using technologies to reduce the size of systems such as chemical reactions, biochemical reactions, and sample analysis.

  Reactions and analyzes in a microchemical system are performed using a single chip called a microchemical chip on which a microchannel, a micropump, a microreactor, and the like are formed. For example, a supply port for supplying a fluid such as a sample or a reagent and a sampling port for deriving a processed fluid are formed on a single substrate made of silicon, glass, or resin. There has been proposed a microchemical chip in which a mouth is connected by a microchannel having a small cross-sectional area, and a micropump for feeding a liquid is disposed at an appropriate position in the channel (see Patent Document 1).

  In addition, as a means for feeding liquid, a capillary electrophoresis type using an electroosmosis phenomenon instead of a micropump has been proposed (see Patent Document 2). In these microchemical chips, the flow paths merge at a predetermined position, and fluids are mixed at the merge portion.

  In the microchemical system, since the devices and methods are miniaturized compared to the conventional system, the reaction surface area per unit volume of the sample can be increased, and the reaction time can be greatly reduced. In addition, since the flow rate can be precisely controlled, reaction and analysis can be performed efficiently.

Furthermore, the amount of samples and reagents necessary for reaction and analysis can be reduced.
Japanese Patent Laid-Open No. 2002-214241 (page 4-5, FIG. 1) JP 2001-108619 A (page 4-5, FIG. 1)

  In the above-described microchemical chip, the fluid to be processed flowing through the flow path is a laminar flow. Therefore, when a plurality of different fluids to be processed are supplied from a plurality of supply units to the flow path and mixed, the plurality of fluids to be processed are mixed using a diffusion phenomenon that occurs while flowing through the flow path. Yes. Therefore, in order to sufficiently mix a plurality of fluids to be processed, it is necessary to form a channel on the downstream side longer than a connection position where the supply unit is connected to the channel.

  However, if the flow path is formed long in order to sufficiently mix the fluid to be processed, there arises a problem that the microchemical chip becomes large.

  On the other hand, if the flow path is formed short in order to reduce the size of the microchemical chip, there arises a problem that mixing of the fluid to be processed becomes insufficient. Further, in the state where the fluid to be processed is not sufficiently mixed, there is a problem that the possibility that the processing becomes insufficient even if a predetermined processing such as a reaction is performed.

  An object of the present invention is to provide a microchemical chip capable of efficiently mixing a plurality of different fluids to be processed without increasing the size of the configuration.

  The present invention includes a base body on which a flow path for flowing a fluid to be processed and a plurality of supply portions connected to the flow path and allowing a plurality of fluids to be processed to flow into the flow path are formed. A microchemical chip that allows a plurality of fluids to be processed to flow into the flow path from the supply unit, and combines the plurality of fluids to be processed to perform a predetermined process, wherein the flow path includes the fluid to be processed A microchemical chip having a plurality of regions having different hydrophilicity on a wall surface of a fluid flow path on a downstream side in a flow direction of the fluid to be treated from a position where the supply unit is connected.

  According to the present invention, when fluids to be treated are introduced from a plurality of supply units, the fluids to be treated are merged to flow through the flow path, and a predetermined process is performed. Therefore, if a plurality of different fluids to be treated are introduced from a plurality of supply sections, the plurality of fluids to be treated are merged to flow through the flow path, and a predetermined process is performed. As for the connection between the plurality of supply parts and the flow path, all of them may be connected to the same position of the flow path, for example, the most upstream part, or the positions may be shifted.

  In the present invention, the flow path has a plurality of regions having different hydrophilicities downstream from the position where the supply unit is connected. Therefore, after the plurality of hydrophobic fluids to be treated are joined, When passing through the sex part, turbulence is generated in the joined fluids. This is because the fluid to be processed passes through the flow path portions having different wall characteristics. That is, when the hydrophobic fluids to be treated are merged, by forming the wall surface of the predetermined flow path portion on the downstream side to be more hydrophilic than the wall surface of the flow path portion on the upstream side, A turbulent flow is generated in the fluid to be treated when the fluid to be treated flows from a portion having a low wall surface hydrophilicity to a portion having a high wall surface hydrophilicity.

  A plurality of fluids to be treated can be mixed by generating a turbulent flow in the fluids to be treated that have joined in this way. Thereby, even if it is a short flow path compared with the case where it mixes only by diffusion like the past, a several to-be-processed fluid can fully be mixed.

Further, since the predetermined process is performed in a state where the plurality of fluids to be processed are sufficiently mixed, the predetermined process can be reliably performed as compared with the case where the mixing is insufficient. Furthermore, since the length of the flow path can be shortened compared with the case of mixing only by diffusion, the microchemical chip can be miniaturized.

  In the invention, it is preferable that the base body further includes a collection unit that is connected to the flow path and guides the processed fluid to the outside, and the hydrophilic portion is more than the position to which the supply unit is connected. Provided on the downstream side in the flow direction of the processing fluid, on the upstream side in the flow direction of the fluid to be processed with respect to the position where the sampling unit is connected, and a plurality of fluids to be processed are supplied from the plurality of supply units to the flow path. Each of the fluids to be flowed in is combined, and a plurality of fluids to be treated are joined together to perform a predetermined process, and then the processed fluid is led out from the sampling unit.

  According to the present invention, the plurality of hydrophobic fluids to be flowed respectively into the flow path from the plurality of supply parts are quickly mixed by flowing through the hydrophilic portion of the flow path and predetermined processing. Is applied to the outside from the collection unit. Therefore, for example, it has two supply parts, a hydrophobic compound as a raw material is introduced from one supply part, a reagent is introduced from the other supply part, and the compound and the reagent are sufficiently mixed and reacted. Thereafter, a small microchemical chip capable of taking out the obtained compound from the collecting part can be obtained.

  According to the present invention, the base body performs a predetermined process on the treated fluid that is joined to the downstream side in the flow direction of the treated fluid from a position where the supply unit and the flow path are connected. A treatment section, wherein the hydrophilic portion is downstream in the flow direction of the fluid to be treated with respect to a position where the supply section is connected, and upstream in the flow direction of the fluid to be treated with respect to the treatment section. It is provided.

  According to the present invention, the plurality of hydrophobic fluids to be flowed into the flow path from the plurality of supply sections are mixed and quickly mixed by flowing through the hydrophilic portion of the flow path. A predetermined process is performed. Therefore, for example, two supply units are provided, a hydrophobic compound as a raw material is introduced from one supply unit, a reagent is introduced from the other supply unit, and the compound and the reagent are merged and heated in the processing unit. When the reaction is carried out by heating, since the compound and the reagent can be heated in a sufficiently mixed state, the compound and the reagent can be reacted efficiently and the yield of the reaction product can be improved.

  Further, the present invention includes a base body formed with a flow path for circulating the fluid to be processed, and a plurality of supply portions connected to the flow path and allowing a plurality of fluids to be processed to flow into the flow path, respectively. A microchemical chip that allows a plurality of fluids to be treated to flow into a flow path from a plurality of supply sections, and performs a predetermined process by joining the plurality of fluids to be treated that are flowed in. It is a microchemical chip characterized by having a plurality of regions having different hydrophobicities on the downstream side in the flow direction of the fluid to be treated with respect to the position where the parts are connected.

  According to the present invention, when fluids to be treated are introduced from a plurality of supply units, the fluids to be treated are merged to flow through the flow path, and a predetermined process is performed. Therefore, if a plurality of different fluids to be treated are introduced from a plurality of supply sections, the plurality of fluids to be treated are merged to flow through the flow path, and a predetermined process is performed. As for the connection between the plurality of supply parts and the flow path, all of them may be connected to the same position of the flow path, for example, the most upstream part, or the positions may be shifted.

  In the present invention, the flow path has a plurality of regions having different hydrophobicities downstream from the position where the supply unit is connected. Therefore, after the plurality of hydrophilic fluids to be treated are joined, When passing through the sex part, turbulence is generated in the joined fluids. This is because the fluid to be processed passes through the flow path portions having different wall characteristics. That is, when the hydrophilic fluids to be treated are merged, the wall surface of the predetermined flow path portion on the downstream side is formed so as to be more hydrophobic than the wall surface of the flow path portion on the upstream side, A turbulent flow is generated in the fluid to be treated when the fluid to be treated flows from a portion having a low wall surface hydrophobicity into a portion having a high wall surface hydrophobicity.

  A plurality of fluids to be treated can be mixed by generating a turbulent flow in the fluids to be treated that have joined in this way. Thereby, even if it is a short flow path compared with the case where it mixes only by spreading | diffusion conventionally, a several hydrophilic to-be-processed fluid can fully be mixed. Further, since the predetermined process is performed in a state where the plurality of fluids to be processed are sufficiently mixed, the predetermined process can be reliably performed as compared with the case where the mixing is insufficient. Furthermore, since the length of the flow path can be shortened compared with the case of mixing only by diffusion, the microchemical chip can be miniaturized.

  In the invention, it is preferable that the base body further includes a collection unit that is connected to the flow path and guides the processed fluid to the outside, and the hydrophobic portion is more than the position to which the supply unit is connected. Provided on the downstream side in the flow direction of the processing fluid, on the upstream side in the flow direction of the fluid to be processed with respect to the position where the sampling unit is connected, and a plurality of fluids to be processed are supplied from the plurality of supply units to the flow path. Each of the fluids to be flowed in is combined, and a plurality of fluids to be treated are joined together to perform a predetermined process, and then the processed fluid is led out from the sampling unit.

  According to the present invention, a plurality of hydrophilic fluids to be flowed into a flow path from a plurality of supply parts are quickly mixed by flowing together and flowing through a hydrophobic portion of the flow path, and a predetermined process is performed. Is applied to the outside from the collection unit. Therefore, for example, it has two supply parts, a hydrophilic compound as a raw material is introduced from one supply part, a reagent is introduced from the other supply part, and the compound and the reagent are sufficiently mixed and reacted. Thereafter, a small microchemical chip capable of taking out the obtained compound from the collecting part can be obtained.

  According to the present invention, the base body performs a predetermined process on the treated fluid that is joined to the downstream side in the flow direction of the treated fluid from a position where the supply unit and the flow path are connected. A treatment part, wherein the hydrophobic part is downstream in the flow direction of the fluid to be treated with respect to a position where the supply part is connected, and upstream in the flow direction of the fluid to be treated with respect to the treatment part. It is provided.

  According to the present invention, the plurality of hydrophilic fluids to be flowed into the flow path from the plurality of supply sections are mixed and quickly mixed by flowing through the hydrophobic portion of the flow path. A predetermined process is performed. Therefore, for example, two supply units are provided, a hydrophilic compound as a raw material is introduced from one supply unit, a reagent is introduced from the other supply unit, and the compound and the reagent are merged and heated in the processing unit. When the reaction is carried out by heating, since the compound and the reagent can be heated in a sufficiently mixed state, the compound and the reagent can be reacted efficiently and the yield of the reaction product can be improved.

  In addition, the microchemical chip of the present invention has, for example, the following manufacturing method, that is, a predetermined shape of the mold is pressed on the surface of the ceramic green sheet to form a groove, and the ceramic green sheet on which the groove is formed is When the base body is formed by sintering at a temperature, and the base body is hydrophilic, the target wall surface to be made hydrophilic among the wall surfaces of the groove is covered with a protective film, and then the target wall surface By removing the protective film after applying a hydrophobic treatment to the wall surface except for the above, the target wall surface is made hydrophilic, and when the base body is hydrophobic, the hydrophilicity of the wall surface of the groove is set. The target wall surface has hydrophilicity by covering the portion excluding the target wall surface to be provided with a protective film and then removing the protective film after subjecting the target wall surface to hydrophilic treatment. , It can be produced by a method characterized by forming the substrate by covering the groove on the surface of the substrate main body with a coating member.

  According to the present invention, first, a die is pressed on the surface of the ceramic green sheet to form a groove portion, and the ceramic green sheet having the groove portion is sintered at a predetermined temperature to form a base body.

  Next, the process which gives hydrophilicity to the target wall surface which should give hydrophilicity among the wall surfaces of the said groove part is performed. When the base body is hydrophilic, the target wall surface to be made hydrophilic among the wall surfaces of the groove portion is coated with a protective film, and then the wall surface except the target wall surface is subjected to a hydrophobizing treatment, and then the protection is performed. By peeling the film, the target wall surface is made hydrophilic. When the base body is hydrophobic, a portion of the wall surface of the groove portion excluding the target wall surface to be hydrophilic is covered with a protective film, and then the protection is performed after the target wall surface is subjected to a hydrophilic treatment. By peeling the film, the target wall surface is made hydrophilic.

  Thereafter, the substrate is formed by covering the groove exposed on the surface of the substrate body with a covering member. As a result, a flow path having a hydrophilic portion whose wall surface is hydrophilic is formed inside the substrate.

  By forming the substrate in this manner, a microchemical chip having a flow path having a plurality of regions having different hydrophilicity on the downstream side in the flow direction of the fluid to be processed from the position where the supply unit is connected to the flow path Can be manufactured.

  The microchemical chip of the present invention is, for example, formed by the following manufacturing method, that is, by pressing a mold having a predetermined shape on the surface of the ceramic green sheet to form the groove, and the ceramic green sheet having the groove formed at a predetermined temperature. The base body is formed by sintering with, and when the base body is hydrophilic, the portion of the wall surface of the groove portion excluding the target wall surface to be made hydrophobic is covered with a protective film, By removing the protective film after subjecting the target wall surface to hydrophobic treatment, the target wall surface is made hydrophobic. When the base body is hydrophobic, the groove wall has hydrophobicity. The target wall surface is made hydrophobic by covering the target wall surface with a protective film and then subjecting the wall surface except the target wall surface to a hydrophilic treatment and then peeling off the protective film. It can be produced by a method characterized by forming the substrate by covering the groove on the surface of the substrate main body with a coating member.

  According to the present invention, first, a die is pressed on the surface of the ceramic green sheet to form a groove portion, and the ceramic green sheet having the groove portion is sintered at a predetermined temperature to form a base body.

  Next, the process which gives hydrophobicity to the target wall surface which should give hydrophobicity among the wall surfaces of the said groove part is performed. When the base body is hydrophilic, the portion of the wall surface of the groove portion excluding the target wall surface to be made hydrophobic is covered with a protective film, and then the protection is performed after subjecting the target wall surface to a hydrophobic treatment. By peeling the film, the target wall surface is made hydrophobic. When the base body is hydrophobic, the target wall surface to be made hydrophobic among the wall surfaces of the groove portion is coated with a protective film, and then the wall surface except the target wall surface is subjected to a hydrophilization treatment, and then the protection is performed. By peeling the film, the target wall surface is made hydrophobic.

  Thereafter, the substrate is formed by covering the groove exposed on the surface of the substrate body with a covering member. As a result, a flow path having a plurality of regions having different hydrophobicities is formed inside the substrate.

  By forming the substrate in this manner, a microchemical chip having a flow path having a plurality of regions having different hydrophobicities on the downstream side in the flow direction of the fluid to be processed from the position where the supply unit is connected to the flow path Can be manufactured.

  As described above, according to the present invention, the flow path has a plurality of regions having different hydrophilicity downstream from the position where the supply unit is connected. Even if the flow path is shorter than the case of mixing, a plurality of hydrophobic fluids to be treated can be sufficiently mixed.

Further, since the predetermined process is performed in a state where the plurality of fluids to be processed are sufficiently mixed, the predetermined process can be reliably performed as compared with the case where the mixing is insufficient.

Furthermore, since the length of the channel on the downstream side of the position where the supply unit is connected to the channel can be shortened, the microchemical chip can be miniaturized.

  Further, according to the present invention, the flow path is downstream in the flow direction of the fluid to be processed with respect to the position where the supply unit is connected, and the flow direction of the fluid to be processed with respect to the position where the sampling part is connected to the flow path Since it has a plurality of regions having different hydrophilic properties on the upstream side, for example, it has two supply parts, a hydrophobic compound as a raw material flows from one supply part, and a reagent flows from the other supply part, After the compound and the reagent are sufficiently mixed and reacted, a small microchemical chip capable of taking out the obtained compound from the collection part can be obtained.

  Further, according to the present invention, the flow path has a plurality of different hydrophilicities on the downstream side in the flow direction of the fluid to be processed from the position where the supply unit is connected and on the upstream side in the flow direction of the fluid to be processed than the processing portion. Therefore, for example, two supply parts are provided, a hydrophobic compound as a raw material is introduced from one supply part, a reagent is introduced from the other supply part, and the compound and the reagent are joined together. When the reaction is carried out by heating in the treatment section, the compound and the reagent can be reacted efficiently and the yield of the reaction product can be improved.

  Further, according to the present invention, the flow path has a plurality of regions having different hydrophobicities downstream from the position where the supply unit is connected, and therefore, a plurality of fluids to be processed are mixed only by diffusion. Even if the flow path is shorter than the above, a plurality of hydrophilic treatment fluids can be sufficiently mixed. Further, since the predetermined process is performed in a state where the plurality of fluids to be processed are sufficiently mixed, the predetermined process can be reliably performed as compared with the case where the mixing is insufficient. Furthermore, since the length of the channel on the downstream side of the position where the supply unit is connected to the channel can be shortened, the microchemical chip can be miniaturized.

  Further, according to the present invention, the flow path is downstream in the flow direction of the fluid to be processed from the position where the supply unit is connected, and upstream in the flow direction of the fluid to be processed from the position where the sampling unit is connected. Since it has a plurality of regions having different hydrophobicities, for example, it has two supply parts, a hydrophilic compound as a raw material flows from one supply part, a reagent flows from the other supply part, and the compound and reagent Are sufficiently mixed and reacted, and a small microchemical chip capable of taking out the obtained compound from the collection part can be obtained.

  According to the invention, the flow path has a plurality of different hydrophobicities on the downstream side in the flow direction of the fluid to be processed from the position where the supply unit is connected and upstream in the flow direction of the fluid to be processed than the processing portion. Therefore, for example, two supply units are provided, a hydrophilic compound as a raw material is introduced from one supply unit, a reagent is introduced from the other supply unit, and the compound and the reagent are combined. When the reaction is carried out by heating in the treatment section, the compound and the reagent can be reacted efficiently and the yield of the reaction product can be improved.

  FIG. 1A is a plan view showing a simplified configuration of a microchemical chip 1 according to an embodiment of the present invention. FIG. 1B is a partial cross-sectional view showing a cross-sectional configuration taken along cutting plane lines II, II-II, and III-III of the microchemical chip 1 shown in FIG. In FIG. 1B, cross-sectional configurations along section line II, II-II, and III-III are shown side by side.

  The microchemical chip 1 has a flow channel 12 through which a fluid to be treated is circulated, two supply units 13a and 13b that allow the fluid to be treated to flow into the flow channel 12, a treatment unit 14, and a fluid after treatment to the outside. And a base 11 provided with a collecting portion 15 to be provided.

The base body 11 includes a base body 20 having a groove portion formed on one surface and a lid body 21 that is a covering member. The surface of the base body 20 on which the groove portion 33 is formed is covered with the lid body 21 so that the flow path 12 is formed. Is formed. In this microchemical chip 1, the flow path 12 is located downstream of the position 22 where the supply parts 13 a and 13 b are connected, and the hydrophilic part of the length L 1 whose wall surface is hydrophilic (or hydrophobic, whose wall surface is hydrophobic). Part) 12a.

  The supply section 13a is upstream of the fluid to be processed in the flow direction from the supply flow path 17a connected to the flow path 12, the supply port 16a provided at the end of the supply flow path 17a, and the position 22 connected to the flow path 12. And a micropump 18a provided on the side. Similarly, the supply unit 13b includes a supply channel 17b, a supply port 16b, and a micropump 18b. The supply ports 16a and 16b are opened so that the fluid to be processed can be injected into the supply channels 17a and 17b from the outside. The collection unit 15 is realized with an opening so that the fluid to be processed can be taken out from the flow path 12.

  A heater 19 is provided inside the base body 20 and below the flow path 12 of the processing unit 14. The flow path 12 of the processing unit 14 is formed to be bent so as to pass a plurality of times above the heater 19. A wiring (not shown) for connecting the heater 19 and an external power source is led out from the heater 19 on the surface of the base 11. This wiring is formed of a metal material having a resistance value lower than that of the heater 19.

  In the microchemical chip 1, two kinds of fluids to be processed are respectively introduced into the flow path 12 from the two supply parts 13 a and 13 b and merged, and the flow path 12 is predetermined using the heater 19 in the processing part 14 as necessary. The two types of fluids to be treated are reacted with each other, and the obtained reaction product is led out from the collection unit 15.

The cross-sectional areas of the flow channel 12 and the supply flow channels 17a and 17b are 2.5 × 10 ⁻³ mm in order to efficiently send and mix the specimen, reagent, or cleaning solution flowing from the supply units 13a and 13b. is preferably ² or more 1 mm ² or less. However, the fluid cross-sectional area flows through the 2.5 × ¹⁰ -3 ^{mm 2} ~1mm 2 about the flow path, since generally flows in a laminar flow state, is only allowed to merge two supply passage 17a, the 17b, The two types of fluids to be processed that are respectively flowed into the flow path 12 from the supply units 13a and 13b and mixed together are mixed only by diffusion. Therefore, it is necessary to provide a long flow path in order to completely mix the two types of fluids to be treated, and there is a limit to downsizing the microchemical chip.

  On the other hand, in the present embodiment, the flow path 12 has a hydrophilic portion (or a wall surface having a wall length L1) on the downstream side of the connection position 22 between the flow path 12 and the supply units 13a and 13b. When a plurality of fluids to be treated are merged, the wall surface passes through the hydrophilic portion (or the hydrophobic portion where the wall surface is hydrophobic) 12a. In addition, a turbulent flow is generated in the joined fluids. This is because the fluid to be processed passes through the flow path portions having different wall characteristics. For example, when the hydrophilic fluids to be treated are merged, the wall surface of the downstream channel portion 12a is formed so as to be more hydrophobic than the wall surface of the upstream channel portion. When the fluids to be processed are merged, the wall surface of the downstream channel portion 12a may be formed so as to be more hydrophilic than the wall surface of the upstream channel portion.

  A plurality of fluids to be treated can be mixed by generating a turbulent flow in the fluids to be treated that have joined in this way. Accordingly, it is possible to sufficiently mix a plurality of fluids to be processed in a short flow path as compared with the case of mixing only by diffusion. Therefore, since the length of the flow path 12 can be shortened, the microchemical chip 1 can be miniaturized, and the microchemical system using the microchemical chip 1 can be miniaturized. Further, since the predetermined process is performed in a state where the plurality of fluids to be processed are sufficiently mixed, the predetermined process can be reliably performed as compared with the case where the mixing is insufficient.

  Moreover, in this embodiment, since the flow path 12 has the hydrophilic part (or the hydrophobic part whose wall surface is hydrophobic) 12a between the connection position 22 and the process part 14, it was merged. The fluid to be processed is sufficiently mixed when it reaches the processing unit 14. Therefore, for example, when a compound as a raw material is supplied from the supply unit 13a, a reagent is supplied from the supply unit 13b, the compound and the reagent are combined and heated by the heater 19 of the processing unit 14, the compound and the reagent are reacted. Can be heated in a sufficiently mixed state, so that the compound and the reagent can be reacted efficiently and the yield of the reaction product taken out from the collection unit 15 can be improved.

  The base body 20 can be made of a ceramic material, silicon, glass, resin, or the like, and among these, it is preferable to use a ceramic material. Since the ceramic material is superior in chemical resistance compared to a resin or the like, the base body 20 is made of a ceramic material, thereby obtaining the microchemical chip 1 that is excellent in chemical resistance and can be used under various conditions. it can. As the ceramic material constituting the base body 11, for example, an aluminum oxide sintered body, a mullite sintered body, a glass ceramic sintered body, or the like can be used.

  The lid 21 can be made of glass or ceramic material.

As described above, the cross-sectional areas of the flow channel 12 and the supply flow channels 17a and 17b are 2.5 × in order to efficiently send and mix the specimen, reagent, or cleaning liquid flowing in from the supply units 13a and 13b. it is preferably 10 ^-3 mm ² or more 1 mm ² or less. If the cross-sectional area of the flow channel 12 and the supply flow channels 17a and 17b exceeds 1 mm ² , the amount of the specimen, reagent, or washing solution to be sent becomes too large, so that the reaction surface area per unit volume is increased and the reaction time is increased. The effect of the microchemical chip that can be greatly reduced cannot be obtained sufficiently. Moreover, when the cross-sectional areas of the flow path 12 and the supply flow paths 17a and 17b are less than 2.5 × 10 ⁻³ mm ² , pressure loss due to the micropumps 18a and 18b becomes large, causing a problem in liquid feeding. Thus, the channel 12 and the supply passage 17a, and the cross-sectional area of the 17b 2.5 × ¹⁰ -3 mm ² or more 1 mm ² or less.

  The width w of the flow channel 12 and the supply flow channels 17a and 17b is preferably 50 to 1000 μm, more preferably 100 to 500 μm. The depth d of the flow channel 12 and the supply flow channels 17a and 17b is preferably 50 to 1000 μm, more preferably 100 to 500 μm.

  The external dimensions of the microchemical chip 1 are, for example, a width A of about 40 mm, a depth B of about 70 mm, and a height C of 1 to 2 mm. The dimensions may be used.

  In addition, the used microchemical chip 1 can be used again if it is washed by supplying a cleaning liquid from the supply units 13a and 13b.

  Next, a method for manufacturing the microchemical chip 1 shown in FIG. 1 will be described. In the present embodiment, a case where the base body 20 is made of a ceramic material will be described. FIG. 2 is a plan view showing a processed state of the ceramic green sheets 31 and 32. FIG. 3 is a cross-sectional view showing a laminated state of the ceramic sheets 31 and 32.

  First, mix an appropriate organic binder and solvent into the raw material powder, add a plasticizer or dispersant as necessary to make mud, and form this into a sheet by the doctor blade method or calendar roll method. To form a ceramic green sheet (also called a ceramic raw sheet). As the raw material powder, for example, when the base body 20 is made of an aluminum oxide sintered body, aluminum oxide, silicon oxide, magnesium oxide, calcium oxide, or the like is used.

  In the present embodiment, the base body 20 is formed using two ceramic green sheets formed in this manner. First, as shown in FIG. 2A, the mold is pressed against the surface of the ceramic green sheet 31 to form the groove 33. At this time, a mold having a shape in which the shape of the desired groove 33 is transferred is used as the mold. The pressing force when pressing the mold is adjusted according to the viscosity of the slurry before being formed into the ceramic green sheet. For example, when the viscosity of the slurry is 1 to 4 Pa · s, the slurry is pressed with a pressing force of 2.5 to 7 MPa. The material of the mold is not particularly limited, and may be a mold or a wooden mold.

  Further, as shown in FIG. 2B, a conductive paste is applied to the surface of the ceramic green sheet 32 in a predetermined shape by a screen printing method or the like, thereby forming a wiring that becomes a wiring for connecting the heater 19 and the external power source. A pattern 34 is formed. The conductive paste can be obtained by mixing an appropriate organic binder and a solvent with a metal material powder such as tungsten, molybdenum, manganese, copper, silver, nickel, palladium, or gold. In addition, as the conductive paste for forming the wiring pattern 34 to be the heater 19, a paste obtained by adding 5 to 30% by weight of ceramic powder to the above-described metal material powder is used so that a predetermined resistance value is obtained after firing. .

  Next, as shown in FIG. 3, the ceramic green sheet 31 in which the groove 33 is formed is laminated on the surface of the ceramic green sheet 32 in which the wiring pattern 34 to be the heater 19 is formed. The laminated ceramic green sheets 31 and 32 are sintered at a temperature of about 1600 ° C. As described above, the base body 20 shown in FIG. 1 is formed.

  By performing the following processing on the base body 20 formed in this way, the groove portion 33 having a length L1 serving as the flow path portion 12a downstream of the connection position 22 between the flow path 12 and the supply portions 13a and 13b. This wall surface can be a hydrophilic or hydrophobic wall surface.

  (1) In the case where the wall surface of the flow path portion 12a is made hydrophilic (1-a) When the base body 20 is hydrophilic, the length L1 of the groove portion of the wall surface of the groove portion to be made hydrophilic is set. The target wall surface is made hydrophilic by covering the target wall surface with a protective film and then subjecting the wall surface excluding the target wall surface to a hydrophobic treatment, and then peeling the protective film.

  (1-b) When the base body 20 is hydrophobic, a portion of the wall surface of the groove portion excluding the target wall surface of the groove portion having a length L1 to be hydrophilic is covered with a protective film, and then the target body After the hydrophilic treatment is performed on the wall surface, the protective film is peeled off to make the target wall surface hydrophilic.

  (2) When the wall surface of the flow path portion 12a is made hydrophobic (2-a) When the base body 20 is hydrophilic, the length L1 of the groove portion of the wall surface of the groove portion to be made hydrophobic A portion excluding the target wall surface is covered with a protective film, and then the target wall surface is made hydrophobic by peeling off the protective film after subjecting the target wall surface to a hydrophobic treatment.

  (2-b) When the base body 20 is hydrophobic, the target wall surface of the groove portion having a length L1 to be hydrophobic is covered with a protective film among the wall surfaces of the groove portion, and then the target wall surface is removed. After subjecting the wall surface to a hydrophilic treatment, the protective film is peeled off to make the target wall surface hydrophobic.

  The hydrophilization treatment can be performed by taking out the base body 20 in which the target wall surface or the wall surface excluding the target wall surface is covered with a protective film after being immersed in alcohol for about 30 seconds and washing with water. By dipping in alcohol, hydroxyl groups (—OH) can be introduced into the target wall surface of the base body 20 made of a ceramic material. As the alcohol, for example, isopropyl alcohol (abbreviation: IPA) can be used.

  The hydrophobization treatment is performed by immersing the substrate main body 20 in which the target wall surface or the wall surface excluding the target wall surface is coated with a protective film after being immersed in a surfactant solution for about 30 seconds, and washing with water, preferably warm water. It can be carried out. By dipping in the surfactant solution, the hydroxyl group (—OH) present on the target wall surface of the base body 20 made of a ceramic material can be removed. Examples of the surfactant include alkylene glycol-based nonionic surfactants, alkylphenyl glycol-based nonionic surfactants, fluorine-containing alkylene glycol-based nonionic surfactants, and silicon-containing alkylene glycol-based surfactants. Nonionic surfactants can be used.

  For example, when the wall surface of the flow path portion 12a provided in the hydrophobic base body 20 is made hydrophilic, the portion of the groove portion except the target wall surface to be made hydrophilic is covered with a protective film. Then, after subjecting the target wall surface to hydrophilic treatment, the target wall surface is made hydrophilic by peeling off the protective film.

  In addition, when the wall surface of the flow path portion 12a provided in the hydrophilic base body 20 is made hydrophobic, the whole base body is heated at 200 to 300 ° C. under reduced pressure for 1 to 3 hours. After subjecting to hydrophobic treatment, coating the target wall surface to be made hydrophobic among the wall surfaces of the groove portion with a protective film, and then subjecting the wall surface excluding the target wall surface to hydrophilic treatment, and then peeling the protective film To impart hydrophobicity to the target wall surface.

  The heat treatment of the entire base body needs to be performed when the base body 20 is made of a metal oxide ceramic material such as aluminum oxide, but when the base body 20 is made of another ceramic material. It does not have to be done. For example, when the base body 20 is made of a nitride-based ceramic material such as silicon nitride or silicon carbide, the surface of the base body 20 is already hydrophobic in a fired state, so that it is necessary to perform a heat treatment again. Absent.

  However, after forming the base body 20 by sintering the ceramic green sheet, it is necessary to perform plating on a portion electrically connected to the outside, for example, a power supply terminal for driving the pump. At this time, since there are various treatments, the surface state of the base body 20 changes. Therefore, in this case, it is necessary to heat the entire base body to make the base body hydrophobic.

  FIG. 4 is a plan view showing the configuration of the lid 21 in a simplified manner. As shown in FIG. 4, the supply ports 16 a and 16 b of the substrate 41 made of, for example, glass or a ceramic material, and the sampling portion 15 are positioned in the grooves 33 of the ceramic green sheet 31 shown in FIG. The through holes 42a, 42b, and 43 that communicate with each other are formed to obtain the lid 21.

  The lid 21 is bonded to the surface of the base body 20 where the grooves 33 and 34 are exposed. For example, when the lid 21 is made of glass, the lid 21 and the base body 20 are bonded by heating and pressing, and when the lid 21 is made of a ceramic material, they are bonded by a glass adhesive or the like.

For example, piezoelectric materials 44a and 44b such as lead zirconate titanate (PZT; composition formula: Pb (Zr, Ti) O ₃ ) are attached to predetermined positions on the surface of the lid 21 and the piezoelectric materials 44a and 44b. A wiring (not shown) for applying a voltage is formed. The piezoelectric materials 44a and 44b can vibrate the lid 21 above the supply flow paths 17a and 17b by expanding and contracting according to the applied voltage, so that the piezoelectric materials 44a and 44b are supplied to the supply flow paths 17a and 17b. The micropumps 18a and 18b for feeding liquid can be formed by sticking to the upper lid body 21.

  As described above, the substrate 11 shown in FIG. 1 is formed, and the microchemical chip 1 is obtained.

As described above, the base body 20 and the lid body, in which the wall surface of the groove portion 33 serving as the flow channel portion 12a on the downstream side of the connection position 22 between the flow channel 12 and the supply portions 13a and 13b is made a hydrophilic or hydrophobic wall surface. 21 is bonded to the downstream side in the flow direction of the fluid to be treated from the position 22 where the supply sections 13a and 13b are connected to the flow path 12, and the hydrophilic portion (or the wall surface is hydrophobic). The microchemical chip 1 including the flow path 12 having the hydrophobic portion 12a can be manufactured.

  Further, in the present embodiment, a laminate of the ceramic green sheet 31 with the groove 33 formed on the surface by pressing the mold and the ceramic green sheet 31 with the wiring pattern 34 to be the heater 19 is sintered. After forming the base body 20 by the above-described hydrophilization treatment or hydrophobic treatment, the base body 11 having the flow path 12 is formed by covering the groove portion 33 on the surface of the base body 20 with the lid 21.

Therefore, the microchemical chip 1 can be manufactured by performing simple processing without performing complicated processing such as etching processing required when forming a flow path in a substrate made of silicon, glass, or resin. it can.

  As described above, the microchemical chip 1 of the present embodiment includes the two supply units 13a and 13b, but is not limited thereto, and may include three or more supply units. When two or more supply units are provided, the supply units do not have to be provided to join at one point, and may be provided so as to be connected to different positions of the flow path 12. In this case, the flow path 12 has a hydrophilic part with a hydrophilic wall surface or a hydrophobic part with a hydrophobic wall surface on the downstream side in the flow direction of the fluid to be treated from the position where each supply unit is connected to the flow path 12. It is preferable to have.

  In particular, when a hydrophobic process fluid is introduced from a certain supply unit and a hydrophilic process fluid is supplied from another supply unit, the supply unit into which the hydrophobic process fluid is introduced is a flow path. A hydrophilic portion is provided on the downstream side in the flow direction of the fluid to be treated from the position connected to the fluid 12, and the fluid to be treated is located more than the position where the supply portion into which the fluid to be treated flows is connected to the flow path 12. It is preferable to provide a hydrophobic portion on the downstream side in the flow direction. Thus, when both the hydrophilic part and the hydrophobic part are provided in the flow path 12, for example, the part excluding the target wall surface to be made hydrophilic in the groove 33 of the base body 20 shown in FIG. After the coating, the target wall surface is subjected to a hydrophilization treatment, and then the protective film is peeled off. Then, the portion other than the target wall surface to be made hydrophobic is coated with the protective film, and then the target wall surface is hydrophobic. The protective film is peeled after the crystallization treatment. As a result, a hydrophilic portion and a hydrophobic portion can be separately formed in the flow path 12.

  In addition, the hydrophilic portion (or hydrophobic portion) 12a having a hydrophilic wall surface is illustrated as being provided in a straight portion of the flow path 12, but the present invention is not limited thereto, and a curved portion is provided in the flow path 12. It is possible to provide this portion with a hydrophilic portion (or hydrophobic portion) 12a. In this case, the fluid to be treated can be sufficiently mixed by generating a more effective turbulent flow by the curved portion of the flow path 12 and the hydrophilic portion (or hydrophobic portion) 12a.

  Moreover, although the heater 19 is a structure provided in one place, it is not limited to this, You may provide in two or more places. Thus, a complicated reaction can be controlled by providing three or more supply units and two or more heaters. Note that the heater 19 need not be provided when the reaction proceeds without heating.

  Further, in the microchemical chip 1 of the present embodiment, the collection unit 15 is provided and the reaction product is led out from the collection unit 15, but the detection unit is located upstream of the collection unit 15 or the collection unit 15 in the flow direction of the fluid to be processed. The reaction product of a biochemical reaction such as a chemical reaction, an antigen-antibody reaction, or an enzyme reaction can be detected. In this case, it is preferable that the wall surface of the flow path portion on the upstream side in the flow direction of the fluid to be processed is more hydrophilic or hydrophobic than the detection unit.

  In the present embodiment, the micropumps 18a and 18b are provided as the liquid feeding means, but a configuration in which the micropumps 18a and 18b are not provided is also possible. In this case, when injecting the fluid to be processed from the supply ports 16a and 16b, the fluid to be processed is sent from the supply ports 16a and 16b to the collection unit 15 by pushing the fluid to be processed with a microsyringe or the like. be able to. Moreover, when inject | pouring, liquid can also be sent by injecting, applying pressure to a to-be-processed fluid with the pump etc. which are provided outside. In addition, after injecting the fluid to be processed from the supply ports 16a and 16b, the liquid can be fed by sucking with a microsyringe or the like from the collection unit 15 realized by the opening.

  Further, although the lid body 21 is bonded to the base body 20, the lid body 21 is not limited thereto and may be detachably attached to the base body 20. For example, a configuration in which silicone rubber or the like is sandwiched between the base body 20 and the lid 21 and pressure is applied to the entire microchemical chip may be employed. By allowing the lid 21 to be removed from the base body 20, cleaning when reused becomes easy.

  In the method of manufacturing the microchemical chip 1 of the present embodiment, the base body 20 includes the ceramic green sheet 31 in which the groove portions 33 and 34 are formed, and the ceramic green sheet 32 in which the wiring pattern 34 to be the heater 19 is formed. However, the present invention is not limited to this, and may be formed from three or more ceramic green sheets.

Fig.1 (a) is a top view which simplifies and shows the structure of the microchemical chip 1 which is one Embodiment of this invention, FIG.1 (b) is the microchemical chip 1 shown to Fig.1 (a). It is sectional drawing which shows the cross-sectional structure in cutting surface line II of II, II-II, and III-III. It is a top view which shows the processing state of the ceramic green sheets 31 and 32. FIG. It is a fragmentary sectional view showing the state where ceramic green sheets 31 and 32 were laminated. 3 is a plan view showing a simplified configuration of a lid body 21. FIG.

Explanation of symbols

 DESCRIPTION OF SYMBOLS 1 Microchemical chip 11 Base | substrate 12 Channel 12a Hydrophilic part (hydrophobic part) 13a, 13b Supply part 14 Processing part 15 Sampling part 16a, 16b Supply port 17a, 17b Supply channel 18a, 18b Micro pump 19 Heater 20 Base | substrate main body 21 Lid 22 Connection position 31, 32 Ceramic green sheet 33 Groove 34 Wiring pattern 41 Substrate 42a, 42b, 43 Through hole 44a, 44b Piezoelectric material L1 Length of hydrophilic part (hydrophobic part)

Claims (6)

A substrate having a flow path through which the fluid to be treated is circulated, and a plurality of supply portions connected to the flow path and into which the plurality of fluids to be treated are respectively introduced into the flow paths; A microchemical chip that allows a plurality of fluids to be processed to flow into the flow path and performs a predetermined process by joining the plurality of fluids to be processed,
The flow path has a plurality of regions having different hydrophilicities on the wall surface of the flow path of the fluid to be treated, on the downstream side in the flow direction of the fluid to be treated from the position where the supply unit is connected. Micro chemical chip to do. The base body further includes a collection unit connected to the flow path and leading the processed fluid to the outside,
The plurality of regions having different hydrophilicity are downstream in the flow direction of the fluid to be processed with respect to the position where the supply unit is connected, and the flow direction of the fluid to be processed with respect to the position where the sampling unit is connected Provided on the upstream side, after a plurality of fluids to be processed flow into the flow path from the plurality of supply units, respectively, and a plurality of the fluids to be processed merged to perform a predetermined process, from the sampling unit The microchemical chip according to claim 1, wherein the processed fluid is led out to the outside. The base includes a processing unit that performs a predetermined process on the fluid to be processed that is joined to the downstream side in the flow direction of the fluid to be processed from a position where the supply unit and the flow path are connected. ,
The plurality of regions having different hydrophilicity are provided on the downstream side in the flow direction of the fluid to be processed with respect to a position where the supply unit is connected, and on the upstream side in the flow direction of the fluid to be processed with respect to the processing portion. The microchemical chip according to claim 1 or 2, wherein A substrate having a flow path through which the fluid to be treated is circulated, and a plurality of supply portions connected to the flow path and into which the plurality of fluids to be treated are respectively introduced into the flow paths; A microchemical chip that allows a plurality of fluids to be processed to flow into the flow path and performs a predetermined process by joining the plurality of fluids to be processed,
The flow path has a plurality of regions having different hydrophobicities on the wall surface of the flow path of the fluid to be processed, on the downstream side in the flow direction of the fluid to be processed from the position where the supply unit is connected. Micro chemical chip to do. The base body further includes a collection unit connected to the flow path and leading the processed fluid to the outside,
The plurality of regions having different hydrophobicity are downstream in the flow direction of the fluid to be processed with respect to the position where the supply unit is connected, and the flow direction of the fluid to be processed with respect to the position where the sampling unit is connected Provided upstream,
A plurality of fluids to be processed are respectively introduced into the flow paths from the plurality of supply units, and the plurality of fluids to be processed are combined to perform a predetermined process, and then the processed fluid is externally supplied from the sampling unit. 5. The microchemical chip according to claim 4, wherein the microchemical chip is derived as follows. The base includes a processing unit that performs a predetermined process on the fluid to be processed that is joined to the downstream side in the flow direction of the fluid to be processed from a position where the supply unit and the flow path are connected. ,
The plurality of regions having different hydrophobicities are provided on the downstream side in the flow direction of the fluid to be processed with respect to the position where the supply unit is connected, and on the upstream side in the flow direction of the fluid to be processed with respect to the processing portion. 6. The microchemical chip according to claim 4 or 5, wherein

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