WO2024043160A1 - Fluid device, fluid device manufacturing method, and inspection system - Google Patents

Fluid device, fluid device manufacturing method, and inspection system Download PDF

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Publication number
WO2024043160A1
WO2024043160A1 PCT/JP2023/029681 JP2023029681W WO2024043160A1 WO 2024043160 A1 WO2024043160 A1 WO 2024043160A1 JP 2023029681 W JP2023029681 W JP 2023029681W WO 2024043160 A1 WO2024043160 A1 WO 2024043160A1
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substrate
channel
fluid
tributary
flow path
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PCT/JP2023/029681
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French (fr)
Japanese (ja)
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貴義 大津
正弘 國則
淳憲 一色
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東洋製罐グループホールディングス株式会社
東洋鋼鈑株式会社
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Publication of WO2024043160A1 publication Critical patent/WO2024043160A1/en

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00Apparatus for enzymology or microbiology
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/34Measuring or testing with condition measuring or sensing means, e.g. colony counters
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813Hybridisation assays
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844Nucleic acid amplification reactions
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N37/00Details not covered by any other group of this subclass

Definitions

  • the present invention relates to microfluidic devices used for genetic testing and the like, and particularly to fluidic devices equipped with branch channels.
  • a reaction part is formed in the channel of a microfluidic device, a DNA microarray is placed in this reaction part, and a test object in a reagent sent to the channel is detected. The presence or absence of the test object in the reagent is determined based on the reaction between the reagent and the probe immobilized on the DNA microarray.
  • microfluidic devices allow multiple reagents to be injected through separate inlets. That is, some microfluidic devices are equipped with a plurality of tributary channels (branch channels), and these tributary channels are connected at connecting portions to communicate with the main channel. Such a microfluidic device can be suitably used in tests using a plurality of reagents.
  • a microfluidic device equipped with such a branch channel has a problem in that the reagent does not flow toward the outlet as it is, but flows back into other branch channels. That is, the reagent injected into the tributary channel usually has the property of flowing into the channel where it flows most easily. Therefore, the reagent may not flow from the tributary channel to the outlet provided in the main channel, but may flow back through the connection to the inlet of another tributary channel. In addition, if a part of the reagent remains in other tributary channels due to backflow, it will not be removed unless the liquid is sent or suctioned to the corresponding tributary channel, and as a result, the reagent remains near the connection. There was a problem that it got stuck.
  • Patent Document 1 discloses a microchip having a main channel and a plurality of sub channels. According to this microchip, it is said that a target substance can be detected accurately by sequentially feeding reagents from a plurality of sub-channels to a main channel.
  • this microchip has multiple sub-channels each connected to the main channel individually, there is a problem that reagents injected from one sub-channel flow back into other sub-channels. On the other hand, there was a problem in that backflow in the main flow path could occur. Furthermore, since the structure is such that the reagent injected from the sub-channel is once stored in the main channel, mixing of the reagents may become a problem. For example, in testing applications where the reaction order of reagents and specimens is important, the mixture of reagents and specimens injected into the main channel from one subchannel is discharged once, and a different reagent is injected from the next subchannel. This required a liquid delivery procedure.
  • Patent Document 2 also discloses a microchip having a main channel and a plurality of tributary channels.
  • multiple tributary channels communicate with the main channel through relatively large connections, so there is no backflow from one tributary channel to the other, but reagents may accumulate in the connections. This could occur, and it could not be used in applications where the reagents in the tributary channels and connections were completely replaced and the liquid was sent to the main channel.
  • the present invention has been made in view of the above-mentioned circumstances, and provides a fluid device having a branch flow path in which no backflow or stagnation of fluid occurs, a method for manufacturing the fluid device, and an inspection system. purpose.
  • the fluid device of the present invention is a fluid device including a main channel, a plurality of branch channels, and a connection part communicating with each channel, wherein the main channel, the branch channels, and the The connecting portions are connected to each other such that when fluid is sent from the tributary flow path toward the main flow path, the fluids are fed to the main flow path after converging at the connection portion, and
  • the flow path resistances of the channel, the tributary flow path, and the connection portion satisfy the following relational expression.
  • the fluid device of the present invention is configured such that the flow path cross-sectional area of the main flow path and the tributary flow path satisfies the following relational expression.
  • the fluid device of the present invention may be configured such that at least four substrates are bonded together, the plurality of tributary channels are formed through a second substrate, and a first substrate is formed on one surface side of the second substrate.
  • a third substrate is bonded to the other surface side of the second substrate, and the main flow path is connected to the third substrate on the opposite surface side to the second substrate.
  • a fourth substrate is provided to communicate with the tributary flow path via the connection portion, and is bonded to the side of the third substrate on which the main flow path is provided, and a plurality of substrates are connected to the first substrate.
  • a fluid inlet communicating with the tributary channel is formed to penetrate through the first substrate, the second substrate, and the third substrate, and a fluid outlet communicating with the main channel is formed by penetrating the first substrate, the second substrate, and the third substrate. It is also preferable to have a configuration in which:
  • the fluid device of the present invention is provided with a plurality of tributary channel extension portions each communicating with the tributary channel via a communication portion, and the fluid device is connected to the first substrate, the second substrate, and the third substrate. It is also preferable that the fluid inlet communicating with the tributary channel extension is formed through the fluid inlet. Furthermore, in the fluidic device of the present invention, at least the main flow path is formed through the fourth substrate, and a fifth substrate is provided on the opposite surface side of the fourth substrate to the third substrate. It is also preferable to have a configuration.
  • the fluid device of the present invention may be configured such that at least three substrates are bonded together, a plurality of the tributary channels are formed on one surface of the second substrate, and a first substrate is formed on the surface side of the second substrate. a third substrate is bonded to the other surface side of the second substrate, and the main flow path is connected to the third substrate side of the surface of the second substrate.
  • the first substrate is provided with a fluid inlet communicating with the tributary channel via a connecting portion, and the first substrate is provided with a fluid inlet that communicates with the tributary channel, and the first substrate and the second substrate are provided with: It is also preferable that a fluid outlet communicating with the main flow path is formed through the fluid outlet.
  • the fluid device of the present invention may be configured such that at least a first substrate and a second substrate are bonded, the second substrate is provided with the main flow channel, the branch flow channel, and the connection portion, and the second
  • the first substrate is bonded to a surface side of the substrate on which the main flow channel, the branch flow channel, and the connection portion are provided, and a fluid inlet communicating with the branch flow channel passes through the first substrate. It is also preferable that a fluid outlet communicating with the main flow path is formed through the main flow path.
  • the fluid device of the present invention may be configured such that at least a first substrate and a second substrate are bonded, and the first substrate has a plurality of tributary channels each communicating with the main flow channel and the plurality of tributary flow channels.
  • the second substrate is provided with a plurality of branch channels, the connecting portion communicating with the main channel, and a communication portion communicating with each of the branch channel extensions. It is also preferable to have a configuration in which
  • the fluidic device of the present invention has a configuration in which each substrate is formed of a hydrophobic material. Further, it is also preferable that the fluid device of the present invention has a configuration in which a part of the main flow path is provided with a reaction section.
  • the fluid device of the present invention is configured such that the surface of the reaction section is a surface on which a reaction substance is immobilized. Further, the fluid device of the present invention is configured such that the reaction section is provided with a carrier holding section that is a recess or a through hole, and a carrier on which a reaction substance is immobilized is held in the carrier holding section. It is also preferable. Furthermore, it is also preferable that the fluid device of the present invention is a combination of various configurations of the fluid devices described above.
  • the method for manufacturing a fluidic device of the present invention is a method of forming any of the above fluidic devices using cutting, injection molding, hot embossing, laser processing, etching, or a 3D printer.
  • the inspection system of the present invention includes any one of the above-mentioned fluidic devices, a liquid feeding control unit that feeds a reagent to the flow path, a heating device that heats the fluidic device, and a light that excites fluorescence of the reagent.
  • the configuration includes a light source for irradiation and a detection device having a fluorescence detection section for detecting the generated fluorescence.
  • the inspection system of the present invention includes at least a valve control section that opens/closes, switches, and/or adjusts the flow rate of the tributary channel, the heating device, the detection device, the liquid feeding control section, and the valve control section.
  • the configuration further includes an information processing device to be controlled.
  • the test system of the present invention can be configured to include a nucleic acid extraction mechanism for extracting a test target gene from a specimen, an amplification reaction mechanism for amplifying the extracted nucleic acid, and any one of the above for detecting a test target gene in an amplified product. It is also preferable to have a detection mechanism including a fluid device, and at least these mechanisms are connected in this order by a flow path.
  • a fluid device including a branch flow path in which backflow or stagnation of fluid does not occur, a method for manufacturing the fluid device, and an inspection system.
  • FIG. 1 is a schematic diagram showing the configuration of a fluidic device according to an embodiment of the present invention.
  • FIG. 1 is a schematic diagram showing the configuration of a substrate of a fluidic device according to an embodiment of the present invention.
  • FIG. 2 is an explanatory diagram showing a situation when fluid is sent to a fluid device according to an embodiment of the present invention.
  • FIG. 3 is a schematic diagram showing the configuration of a substrate of Modification Example 1 of the fluidic device according to the embodiment of the present invention.
  • FIG. 7 is a schematic diagram showing the configuration of a substrate of Modification Example 2 of the fluidic device according to the embodiment of the present invention.
  • FIG. 7 is a schematic diagram showing the configuration of a substrate of Modification Example 3 of the fluidic device according to the embodiment of the present invention.
  • FIG. 7 is a schematic diagram showing the configuration of a substrate of Modification Example 4 of the fluidic device according to the embodiment of the present invention.
  • FIG. 7 is a schematic diagram showing the configuration of a substrate of Modification Example 5 of the fluidic device according to the embodiment of the present invention.
  • FIG. 7 is a schematic diagram showing the configuration of a substrate of Modification Example 6 of the fluidic device according to the embodiment of the present invention.
  • FIG. 1 is a schematic diagram showing how fluorescence detection is performed using a fluidic device according to an embodiment of the present invention.
  • 1 is a schematic diagram showing the configuration of an inspection system according to an embodiment of the present invention.
  • FIG. 1 is a schematic diagram showing the configuration of a conventional fluidic device.
  • FIG. 1 is a schematic diagram showing the configuration of a substrate of a conventional fluidic device.
  • FIG. 2 is an explanatory diagram showing a situation when fluid is sent to a conventional fluid device.
  • FIG. 3 is an explanatory diagram showing an example of the arrangement of an inlet and an outlet in a conventional fluid device, and an example of the arrangement of a valve for preventing backflow of fluid.
  • FIG. 1 is a schematic diagram showing the configuration of a fluidic device according to an embodiment of the present invention
  • FIG. 2 is a schematic diagram showing the configuration of a substrate of this fluidic device
  • FIG. 3 is an explanatory diagram showing the situation when fluid is sent to this fluid device.
  • the fluid device of this embodiment is a fluid device that includes a main channel, a plurality of branch channels, and a connecting portion that communicates with each channel.
  • the main channel 10 the tributary channels 20 (21, 2, 23), and the connecting portion 30 are arranged so that the fluid is not sent from the tributary channel 20 toward the main channel 10.
  • the fluids are connected to each other so that the fluids are fed to the main flow path 10 after merging at the connection portion 30 .
  • the main flow path 10, the tributary flow path 20, and the connection portion 30 are characterized in that the flow path resistances satisfy the following relational expression. Flow resistance of main channel ⁇ Flow resistance of connection section ⁇ Flow resistance of tributary channel
  • the tributary channel 21 is connected to the tributary channel extension 41 via the communication section 211, and the tributary channel 22 is connected to the tributary channel extension 42 via the communication section 221.
  • the tributary flow path 23 is connected to the tributary flow path extension 43 via a communication portion 231.
  • Fluid inlets 411, 421, 431 are provided at the ends of the tributary channel extensions 40 (41, 42, 43) opposite to the tributary channel 20, respectively.
  • the tributary channels 21 , 22 , 23 are connected through a connecting portion 30 and communicated with the main channel 10 .
  • a fluid outlet 101 is provided at the end of the main flow path 10 opposite to the connection portion 30 .
  • the flow path resistance of the connecting portion 30 is smaller than the flow path resistance of the tributary flow path 20. Therefore, the fluid flowing into the connecting portion 30 from each tributary flow path does not flow to other tributary flow paths, but instead flows to the connecting portion 30 with lower flow path resistance.
  • the flow path resistance of the connecting portion 30 is the same as or smaller than the flow path resistance of the main flow path 10. Therefore, the fluid that has flowed into the connecting portion 30 flows into the main flow path 10 without flowing back into the tributary flow path 20 having a higher flow resistance. Further, the fluid is prevented from flowing back from the main channel 10 to the connecting portion 30.
  • three branch channels 20 are provided in FIG. 1, the number of branch channels 20 in the fluid device of this embodiment is not particularly limited as long as it is plural.
  • FIG. 2 shows an example of the structure of the substrate of the fluidic device of this embodiment.
  • the fluidic device of this embodiment is composed of five substrates.
  • the first substrate (K1) is a film forming the uppermost surface side, and has fluid inlets 411, 421, 431 and a fluid outlet 101 formed therein.
  • the second substrate (K2) is a double-sided tape (or film) on the upper surface side, and has tributary channels 20 (21, 22, 23) and communication portions 211, 221, 231 formed therein. Further, fluid inlets 411, 421, 431 and a fluid outlet 101 are formed.
  • the third substrate (K3) is a resin substrate, and includes the main channel 10, the fluid outlet 101, the connection part 30, the tributary channel extension 41 and the fluid inlet 411, the tributary channel extension 42 and the fluid inlet 421, and A tributary channel extension 43 and a fluid inlet 431 are formed.
  • the main channel 10 and the tributary channel extensions 41, 42, and 43 are formed as concave-shaped channels on the back side of the substrate. Further, the connecting portion 30, the fluid outlet 101, and the fluid inlets 411, 421, and 431 are formed to penetrate the substrate.
  • the fourth substrate (K4) is a double-sided tape (or film) on the lower surface side, and branch channel extensions 41, 42, 43 and the main channel 10 are formed therein.
  • the fifth substrate (K5) is a film constituting the lowermost side, and nothing is formed thereon, and the tributary channel extensions 41, 42, 43 formed on the fourth substrate (K4) and the main channel are formed on the fifth substrate (K5). 10 is sealed.
  • FIG. 3 shows how colored fluid is injected into the fluidic device of this embodiment.
  • the fluid injected from the fluid inlet 421 is sent to the tributary channel extension 42 and then to the tributary channel 22 via the communication section 221.
  • the fluid sent to the tributary channel 22 flows into the connection part 30, it flows into the main channel 10 without flowing into the other tributary channels 21 and 23 because it satisfies the following relational expression, and then flows into the main channel 10 and passes through the fluid outlet. Reach 101.
  • Flow path resistance of main flow path 10 ⁇ flow path resistance of tributary flow paths 21 and 23 According to the fluid device of this embodiment, even when a plurality of tributary flow paths are provided, one tributary flow path The sent fluid does not flow back into other tributary channels. Further, the fluid sent to the main flow path 10 is prevented from flowing back into the connecting portion 30 or the tributary flow path 20.
  • the flow path cross-sectional area of the main flow path 10 and the tributary flow path 20 satisfy the following relational expression.
  • examples of methods for making the flow path resistance of the main flow path 10 smaller than the flow path resistance of the tributary flow path 20 include the following method. Note that other conditions in the main flow path 10 and the tributary flow path 20 are the same. It is also preferable to configure a combination of these methods. - Make the channel width of the tributary channel 20 smaller than that of the main channel 10. - The depth of the tributary channel 20 is made smaller than that of the main channel 10. - The branching angle between the plurality of tributary channels 20 is made smaller than the branching angle between the tributary channels 20 and the main channel 10. - The length of the tributary flow path 20 is made longer than the main flow path 10. - Raise the horizontal position of the plurality of tributary channels 20 with respect to the main channel 10.
  • Loss in the main flow path and each tributary flow path can be reduced by considering flow path dimensions and flow path shapes such as flow path length, height of the flow path, bending, branching, merging, branching angle of branch flow paths, and valve structure. It is also preferable to design so that the difference is large.
  • various losses occur due to friction loss, changes in cross-sectional area, changes in flow direction, branching, merging, valves, etc., and are affected by the flow path dimensions and shape. In equations expressing flow, this is called the loss head.
  • Pipe friction loss head h which represents the friction loss of a straight pipe, is given by the Darcy-Weisbach equation as follows, regardless of laminar flow, turbulent flow, or roughness of the pipe wall.
  • ⁇ p is the pressure loss
  • is the density of the fluid
  • g is the gravitational acceleration
  • is the pipe friction coefficient
  • L is the length of the flow path
  • d is the diameter of the circular pipe
  • v velocity of the fluid flowing through the flow path.
  • the flow path resistance is the pressure required to flow a fluid into a certain flow path and the resulting flow rate or flow rate of the fluid.
  • the relationship is such that when the flow path resistance increases, the pressure loss increases or the flow velocity decreases.
  • the pressure loss increases as the diameter of the flow path decreases, that is, the cross-sectional area of the flow path decreases, and that the pressure loss also increases as the length of the flow path increases. Therefore, when comparing the pressure losses of branch channels having different cross-sectional areas and lengths, the channel that provides the lowest pressure and the highest flow rate can be designed as the main channel.
  • the loss head can be expressed not only by the pipe friction coefficient but also by the flow path shape as follows.
  • h n ⁇ v n 2 /2g
  • the loss coefficient ⁇ is a coefficient that can be obtained experimentally due to changes in the cross-sectional area of the flow path, changes in flow direction, branching, merging, valves, etc.
  • the loss coefficient of a branch channel is a coefficient that changes depending on the branch angle ⁇ , flow rate ratio, shape of the branch, diameter ratio of the circular pipe, Reynolds number, etc., but for example, the branch angle between the branch channels
  • the branch angle between the branch channels By making the branching angle smaller than the branching angle between the tributary channel and the main channel, more fluid will be distributed to the main channel that is closer to the straight direction. It is possible to further reduce the flow rate of the fluid that can be used, and it is expected that backflow will be greatly reduced.
  • the hydraulic equivalent diameter of a rectangular tube with wetted edges on all four sides can be used.
  • each substrate in the fluid device of this embodiment is not particularly limited, but for example, COP (cycloolefin polymer), PMMA (polymethyl methacrylate), COC (cycloolefin copolymer), etc. can be suitably used.
  • COP cycloolefin polymer
  • PMMA polymethyl methacrylate
  • COC cycloolefin copolymer
  • PDMS polydimethylsiloxane
  • PET polyethylene terephthalate
  • each substrate is preferably formed of a hydrophobic material. If the fluid device of this embodiment is configured in this manner, it becomes possible to use the tributary channel as a hydrophobic passive valve in this fluid device.
  • the hydrophobic passive valve works to keep the liquid in the tributary channel extension. It also becomes possible. Therefore, according to the fluid device of the present embodiment, it is possible to further reduce unintended backflow and retention of liquid in each branch channel.
  • the method for joining each substrate is not particularly limited, and may include thermal fusion, laser, ultrasonic waves, a solvent, an adhesive, a pressure-sensitive adhesive, plasma treatment, and ultraviolet treatment.
  • the main channel 10, the tributary channel 20, the connecting portion 30, the tributary channel extensions 41, 42, 43, the fluid inlets 411, 421, 431, the fluid outlet 101, etc. are processed.
  • the method is not particularly limited, and can be performed using, for example, cutting, injection molding, hot embossing, laser processing, etching, 3D printing, or the like.
  • FIG. 12 is a schematic diagram showing the configuration of a conventional fluidic device
  • FIG. 13 is a schematic diagram showing the configuration of a substrate of the conventional fluidic device.
  • FIG. 14 is an explanatory diagram showing a situation when fluid is delivered to a conventional fluid device.
  • FIG. 15 is an explanatory diagram showing an example of the arrangement of an inlet and an outlet in a conventional fluid device, and an example of the arrangement of valves for preventing backflow of fluid.
  • a conventional general fluid device including a plurality of branch channels includes, for example, a main channel 1000, branch channels 2000 (2100, 2200, 2300), and a connecting portion 3000.
  • the tributary channels 2100, 2200, and 2300 are provided with fluid inlets 2101, 2201, and 2301, respectively, and the main channel 1000 is provided with a fluid outlet 1001.
  • the fluid injected from the fluid inlets 2101, 2201, and 2301 is sent to the main channel 1000 via the connection portion 3000, and is discharged from the fluid outlet 1001.
  • the first substrate (K100) is a resin substrate constituting the uppermost surface side, and includes a main channel 1000 and a fluid outlet 1001, a tributary channel 2100 and a fluid inlet 2101, a tributary channel 2200 and a fluid inlet 2201, and a tributary channel. 2300 and a fluid inlet 2301 are formed.
  • the main channel 1000, the branch channels 2100, 2200, 2300, and the connecting portion 3000 are formed as concave channels on the back side of the substrate.
  • the fluid outlet 1001 and the fluid inlets 2101, 2201, and 2301 are formed to penetrate the substrate.
  • the second substrate (K200) is a double-sided tape (or film), and has a main channel 1000, tributary channels 2100, 2200, 2300, and a connecting portion 3000 formed therein.
  • the third substrate (K300) is a film constituting the lowermost surface side, and has nothing formed thereon, and is connected to the main channel 1000 and the branch channels 2100, 2200, 2300 formed on the second substrate (K200).
  • the connecting portion 3000 is sealed.
  • FIG. 14 shows how colored fluid is injected into the fluidic device of this embodiment.
  • the fluid injected from the fluid inlet 2201 is sent to the branch channel 2200.
  • the fluid that has reached the connecting portion 3000 is sent to the channel where it flows most easily, so it first flows into the tributary channel 2300 in the straight direction instead of the main channel 1000.
  • the fluid also flows into the main flow path 1000 and the tributary flow path 2100 and reaches the fluid outlet 1001.
  • FIG. 15(A) is a schematic diagram showing the arrangement of an inlet and an outlet in such a conventional fluidic device. Since the conventional fluidic device cannot be used properly for testing as it is, it was necessary to arrange a valve to prevent backflow, as shown in FIG. 15(B).
  • a valve is disposed between each inlet and the connection portion.
  • a valve is disposed between each inlet and the connection portion.
  • Modification 1 differs from the fluid device of the present embodiment described above in that it does not have a tributary channel extension, and the tributary channel is provided with a fluid inlet. In other respects, it is similar to the same fluidic device.
  • the fluidic device of Modification 1 is formed by bonding five substrates.
  • the first substrate (K1-1) is a film forming the uppermost surface side, and has fluid inlets 212, 222, 232 and a fluid outlet 101 formed therein.
  • the second substrate (K2-1) is a double-sided tape (or film) on the upper surface side, and has branch channels 20 (21, 22, 23) formed therein. Further, fluid inlets 212, 222, 232 and a fluid outlet 101 are formed.
  • the third substrate (K3-1) is a resin substrate, and has a main channel 10, a fluid outlet 101, and a connecting portion 30 formed therein.
  • the main flow path 10 is formed as a recessed flow path on the back side of the substrate. Further, the connecting portion 30 and the fluid outlet 101 are formed to penetrate the substrate.
  • the fourth substrate (K4-1) is a double-sided tape (or film) on the lower surface side, and has a main flow path 10 formed therein.
  • the fifth substrate (K5-1) is a film constituting the bottom surface side, has nothing formed thereon, and seals the main channel 10 formed on the fourth substrate (K4-1). There is.
  • the fluid injected from the fluid inlets 212, 222, 232 is sent to the tributary channels 21, 22, 23, and then flows into the main channel 10 via the connection part 30.
  • the liquid is fed and discharged from the fluid outlet 101.
  • the flow path resistance of the tributary flow path 20 is greater than the flow path resistance of the connection portion 30, and the flow path resistance of the connection portion 30 is the same as or greater than the flow path resistance of the main flow path 10. It has become. Therefore, fluid does not flow backward from the main channel 10 to the connecting portion 30, and fluid does not flow backward from the connecting portion 30 to the branch channels 21, 22, and 23. Therefore, according to such a fluidic device, a reagent can be appropriately delivered, so that a test using a fluidic device can be suitably carried out.
  • Modification 2 is different from the fluid device of the present embodiment described above in the shape of the tributary channel extension, and is otherwise similar to the same fluid device, but will be described in more detail.
  • the fluidic device of Modification 2 is formed by bonding five substrates.
  • the first substrate (K1-2) is a sealing film or resin substrate.
  • the second substrate (K2-2) is a double-sided tape on which branch channels 20 are formed.
  • the third substrate (K3-2) is a resin substrate on which the main flow path 10, the connecting portion 30, and the branch flow path extension portion are formed.
  • the fourth substrate (K4-2) is a double-sided tape on which the main channel 10 and the branch channel extensions are formed.
  • the fifth substrate (K5-2) is a sealing film or resin substrate.
  • a plurality of branch channels 20 are formed through the second substrate (K2-2).
  • the first substrate (K1-2) is bonded to one surface side of the second substrate (K2-2).
  • a third substrate (K3-2) is bonded to the other surface side of the second substrate (K2-2).
  • the main channel 10 is provided on the opposite surface side to the second substrate (K2-2) so as to communicate with the branch channel 20 via the connecting portion 30. Further, the third substrate (K3-2) is provided with a plurality of tributary channel extensions 41, 42, and 43 that communicate with the tributary channel 20 via communicating portions 211, 221, and 231, respectively.
  • a fourth substrate (K4-2) is bonded to the side of the third substrate (K3-2) on which the main flow path 10 is provided.
  • Fluid inlets are provided in the first substrate (K1-2), the second substrate (K2-2), and the third substrate (K3-2), each communicating with the tributary channel extensions 41, 42, and 43. 411, 421, and 431 are formed to penetrate therethrough, and a fluid outlet 101 communicating with the main flow path 10 is formed to penetrate therethrough.
  • the main flow path 10 and the branch flow path extensions 41, 42, and 43 are formed to penetrate through the fourth substrate (K4-2).
  • a fifth substrate (K5-2) is provided on the opposite surface of the fourth substrate (K4-2) to the third substrate (K3-2).
  • the third substrate (K3-2) and the fifth substrate (K5-2) are bonded using the fourth substrate (K4-2), but the fourth substrate (K4-2) is
  • the structure may be such that the substrate (K4-2) is omitted and the third substrate (K3-2) and the fifth substrate (K5-2) are bonded by another bonding method.
  • the fluid injected from the fluid inlets 411, 421, 431 flows to the tributary channels 21, 22, 23 via the tributary channel extensions 41, 42, 43, respectively.
  • the liquid is sent to the main channel 10 via the connection part 30 and discharged from the fluid outlet 101.
  • the flow path resistance of the tributary flow path 20 is greater than the flow path resistance of the connecting portion 30, and the flow path resistance of the connecting portion 30 is the same as or greater than the flow path resistance of the main flow path 10. Therefore, fluid does not flow backward from the main flow path 10 to the connecting portion 30, and fluid does not flow backward from the connecting portion 30 to the tributary flow paths 21, 22, and 23. Therefore, according to such a fluidic device, a reagent can be appropriately delivered, so that a test using a fluidic device can be suitably carried out.
  • Modification 3 is different from the fluid device of the present embodiment described above in that it is formed by bonding three substrates.
  • the first substrate (K1-3) is a sealing film or resin substrate.
  • the second substrate (K2-3) is a resin substrate on which the main channel 10, the tributary channel 20, the connection part 30, and the tributary channel extension part 40 are formed.
  • the third substrate (K3-3) is a sealing film or resin substrate.
  • a plurality of branch channels 20 are formed on one surface of the second substrate (K2-3). Further, a main channel 10 is formed on the other surface of the second substrate (K2-3).
  • the first substrate (K1-3) is bonded to the surface side of the second substrate (K2-3) on which the tributary channel 20 is formed.
  • the main flow path 10 is provided to communicate with the branch flow path 20 via the connecting portion 30.
  • there are a plurality of tributary flow path extension portions 40 (41, 42, 43) are provided on the surface side of the second substrate (K2-3) where the main flow path is formed.
  • a third substrate (K3-3) is bonded to the side of the second substrate (K2-3) on which the main flow path 10 is provided.
  • Fluid inlets 411, 421, and 431 are formed through the first substrate (K1-3) to communicate with the branch channel extensions 41, 42, and 43, respectively, and to communicate with the main channel 10.
  • a fluid outlet 101 is formed therethrough.
  • the fluid injected from the fluid inlets 411, 421, 431 flows to the tributary channels 21, 22, 23 via the tributary channel extensions 41, 42, 43, respectively.
  • the liquid is sent to the main channel 10 via the connection part 30 and discharged from the fluid outlet 101.
  • the flow path resistance of the tributary flow path 20 is greater than the flow path resistance of the connecting portion 30, and the flow path resistance of the connecting portion 30 is the same as or greater than the flow path resistance of the main flow path 10. Therefore, fluid does not flow backward from the main flow path 10 to the connecting portion 30, and fluid does not flow backward from the connecting portion 30 to the tributary flow paths 21, 22, and 23. Therefore, reagents can be delivered appropriately, and tests using fluidic devices can be suitably carried out.
  • Modification 4 differs from Modification 3 described above in that it does not have a tributary channel extension, and the tributary channel is provided with a fluid inlet. In other respects, it is similar to the same fluidic device.
  • the fluid device of Modification 4 is also formed by bonding three substrates.
  • the first substrate (K1-4) is a sealing film or resin substrate.
  • the second substrate (K2-4) is a resin substrate on which the tributary channel 20, the main channel 10, and the connecting portion 30 are formed.
  • the third substrate (K3-4) is a sealing film or resin substrate.
  • a plurality of branch channels 20 are formed on one surface of the second substrate (K2-4). Further, a main channel 10 is formed on the other surface of the second substrate (K2-4). The first substrate (K1-4) is bonded to the surface side of the second substrate (K2-4) on which the tributary channel 20 is formed.
  • the main flow path 10 is provided to communicate with the branch flow path 20 via the connecting portion 30. Furthermore, a third substrate (K3-4) is bonded to the side of the second substrate (K2-4) on which the main flow path 10 is provided. Fluid inlets 212, 222, and 232 are formed through the first substrate (K1-4) to communicate with the tributary channels 21, 22, and 23, respectively, and fluid inlets that communicate with the main channel 10 are formed through the first substrate (K1-4). An outlet 101 is formed therethrough.
  • the fluid injected from the fluid inlets 212, 222, 232 is sent to the tributary channels 21, 22, 23, and is sent to the main channel 10 via the connection part 30.
  • the liquid is fed and discharged from the fluid outlet 101.
  • the reagent can be appropriately delivered, and the fluid It is possible to suitably carry out an inspection using the device.
  • Modification 5 differs from the above-described embodiment and its modification in that it is formed by bonding two substrates.
  • the first substrate (K1-5) is a sealing film or resin substrate.
  • the second substrate (K2-5) is a resin substrate on which the main channel 10, the tributary channel 20, the connection part 30, and the tributary channel extension part 40 are formed.
  • the main flow path 10, the branch flow paths 20 (21, 22, 23), and the connection portion 30 are provided on one surface side of the second substrate (K2-5). Further, on the same surface side of the second substrate (K2-5), tributary flow path extension portions 40 (41, 42, 43) are connected to the tributary flow paths 21, 22, 23 via communication portions 211, 221, 231, respectively. is provided.
  • the first substrate (K1-5) is bonded to the surface side of the second substrate (K2-5) on which the main flow path 10, the tributary flow path 20, the connecting portion 30, and the tributary flow path extension portion 40 are provided. .
  • fluid inlets 411, 421, 431 communicating with the tributary channel extensions 41, 42, 43 are formed penetratingly, and fluid inlets communicating with the main channel 10 are formed.
  • An outflow port 101 is formed to penetrate therethrough.
  • the fluid injected from the fluid inlets 411, 421, 431 is sent to the tributary channels 21, 22, 23 via the tributary channel extensions 41, 42, 43, respectively.
  • the liquid is sent to the main flow path 10 via the connection part 30 and discharged from the fluid outlet 101. That is, since the fluid does not flow back from the main channel 10 to the connection section 30, and the fluid does not flow back from the connection section 30 to the tributary channels 21, 22, and 23, the reagent can be appropriately delivered, and the fluid It is possible to suitably carry out an inspection using the device.
  • the tributary channel extension part 40 is eliminated, and fluid inlets 212, 222, 232 are provided at the positions of the communication parts 211, 221, 231 in the tributary channels 21, 22, 23, and the fluid inlets 212, It is also possible to adopt a configuration in which the first substrate (K1-5) is provided with the first substrate (K1-5) penetrated therethrough.
  • the fluid injected from the fluid inlets 212, 222, 232 is sent to the tributary channels 21, 22, 23, then to the main channel 10 via the connection part 30, and then discharged from the fluid outlet 101. be done. Even in this case, the fluid does not flow back from the main channel 10 to the connection section 30, and the fluid does not flow back from the connection section 30 to the tributary channels 21, 22, and 23, so that the reagent can be properly delivered. Therefore, it is possible to suitably perform tests using a fluidic device.
  • Modification 6 differs from the above-described embodiment and its modifications in that it includes a tube or cartridge for supplying or mixing reagents.
  • the fluid device of Modification 6 is formed by bonding three substrates.
  • the first substrate (K1-6) is a tube or cartridge for supplying or mixing reagents.
  • the second substrate (K2-6) is a double-sided tape on which the tributary channel 20 and the connecting portion 30 are formed.
  • the third substrate (K3-6) is a sealing film or resin substrate.
  • the first substrate (K1-6) is provided with a plurality of tributary channel extensions 41, 42, 43 penetrating the main channel 10 and communicating with the plurality of tributary channels 21, 22, 23, respectively. It is being
  • the branch channel extensions 41, 42, and 43 correspond to tubes for supplying reagents.
  • the main channel 10 corresponds to a tube for mixing reagents.
  • a plurality of tributary channels 21, 22, 23, a connecting portion 30 communicating with the main channel 10, and a communication portion communicating with the tributary channel extension portions 41, 42, 43, respectively. 211, 221, and 231 are provided.
  • a third substrate (K3-6) is provided on the opposite surface of the second substrate (K2-6) to the first substrate (K1-6).
  • the second substrate (K2-6) is made of a resin substrate, and the tributary flow path 20, the connecting portion 30, and the communication portions 211, 221, 231 are connected to the first substrate (K1) in the second substrate (K2-6). -6), and the third substrate (K3-6) can be omitted.
  • the reagents injected into the tributary channel extensions 41, 42, and 43 through the fluid inlets 411, 421, and 431 are sent to the tributary channels 21, 22, and 23, respectively.
  • the liquid can be sent to the main channel 10 via the connection part 30 and discharged from the fluid outlet 101.
  • the channel resistance of the tributary channel 20 is greater than the channel resistance of the connection section 30, and the channel resistance of the connection section 30 is the same as or greater than the channel resistance of the main channel 10, so that the reagent is There is no backflow from the channel 10 to the connecting portion 30, the tributary channels 21, 22, 23, and the tributary channel extensions 41, 42, 43. Therefore, according to the fluidic device of Modification 6, reagents can be mixed in an appropriate order, and therefore tests using the fluidic device can be appropriately performed.
  • fluid devices of other modifications of the present embodiment by combining all or part of the configurations of the fluid devices of Modifications 1 to 6 described above.
  • the fluid device of this embodiment preferably has a configuration in which a part of the main flow path 10 is provided with a reaction section.
  • a reaction part can also be arrange
  • the reaction part is formed as a recess, and a carrier such as a DNA microarray on which probes are immobilized is placed in this reaction part (the reaction part that holds such a carrier is sometimes referred to as a carrier holding part). , it can also function as an inspection section. Furthermore, it is also preferable to form the carrier holding portion as a perforation (through hole) that penetrates the substrate provided with the main flow path 10.
  • the carrier can be a DNA microarray or a DNA chip.
  • the carrier is not limited to one for detecting DNA, but may also be a microarray, a chip, etc. for detecting other substances.
  • this DNA microarray can be manufactured using a probe using an existing general method.
  • a stick-on DNA chip as this DNA microarray, it can be created by immobilizing probes on a glass substrate using a DNA spotter and forming spots corresponding to each probe.
  • a synthetic DNA chip it can be created by synthesizing single-stranded oligo DNA having the above sequence on a glass substrate using optical lithography technology.
  • the substrate is not limited to glass, and may also be a plastic substrate, a silicon wafer, or the like.
  • the shape of the substrate is not limited to a flat plate, but can also be of various three-dimensional shapes, and substrates with functional groups introduced to the surface to enable chemical reactions can also be used. .
  • the solid support immobilized on the microarray substrate is one for immobilizing nucleic acids (DNA, RNA, etc.) or peptides (oligopeptides, polypeptides, proteins, etc.). and has a functional group that can be covalently bonded to a nucleic acid or peptide.
  • the functional group capable of covalently bonding to a nucleic acid or peptide those known in the art can be used. It is also preferable to use a carrier having a diamond-like carbon layer (DLC) on its surface.
  • DLC diamond-like carbon layer
  • reaction substance biological materials such as nucleic acids, proteins, sugar chains, etc. can be suitably used. Specifically, for example, DNA, RNA, antibodies, lectins, biotin-avidin, etc. can be used. Furthermore, as the reaction substance, it is also possible to use substances other than biological substances, for example, low-molecular compounds (fragrant components, allergens, etc.) that can bind to biological substances such as antibodies and DNA aptamers.
  • the method for manufacturing a fluidic device of this embodiment is characterized in that the fluidic device of this embodiment described above is formed using cutting, injection molding, hot embossing, laser processing, etching, or a 3D printer. do.
  • the fluidic device of this embodiment can be suitably manufactured by such a method.
  • FIG. 10 is a schematic diagram showing how fluorescence detection is performed using the fluidic device of this embodiment.
  • a fluidic device is shown mounted on a heating device 60.
  • a detection device 50 is arranged so as to face the reaction section in this fluidic device.
  • the fluidic device used for testing is prepared by placing a carrier on which a reaction substance is immobilized in the reaction part of the fluidic device, and the reagent is injected from one of the fluid inlets.
  • the liquid is injected and sent to the main channel 10 via the branch channel 20 and the connecting part 30, and brought into contact with the carrier in the reaction section.
  • the reagent contains a substance to be tested bound to a fluorescent substance. Further, the reaction substance in the carrier reacts with the test object to immobilize the test object on the carrier. Therefore, if the test object is contained in the reagent, the test object is captured by the carrier, and the presence or absence of the test object in the reagent is determined by detecting the fluorescent substance of the captured test object. It is now possible to do so.
  • the fluid device is heated by the heating device 60 so that the temperature of the reagent in the reaction section of the fluid device is maintained at a temperature suitable for the reaction between the test object and the reaction substance.
  • the reagent and cleaning liquid are discharged from the fluid outlet 101 while injecting the cleaning liquid from a fluid inlet different from the fluid inlet into which the reagent was input, thereby removing the reagent in the reaction section. Replace with cleaning solution.
  • a laser for excitation of fluorescence is irradiated from the light source 51 onto the carrier disposed in the reaction section, and the fluorescence detection section 52 generates excitation from the fluorescent substance bonded to the test object that has reacted with the reaction substance on the carrier. Detect the emitted fluorescence.
  • FIG. 11 is a schematic diagram showing the configuration of the inspection system of this embodiment.
  • the inspection system 70 of this embodiment includes a fluid device 71, a reagent supply section 72, a waste liquid discharge section 73, a heating device 74, a detection device 75, and a liquid feeding control section 76. are doing.
  • the fluid device 71 is a fluid device according to this embodiment.
  • the reagent supply section 72 is composed of a container, a tube, or the like filled with a reagent.
  • a reagent for example, a hybridization buffer containing DNA, which is the object to be tested, is used.
  • a washing solution is also used to wash away the buffer from the fluidic device 71 after hybridization.
  • the waste liquid discharge section 73 is constituted by a container, a tube, or the like that stores the waste liquid from the fluid device 71 after the reaction in the fluid device 71 .
  • the heating device 74 heats the fluidic device 71 to adjust the temperature of the reagent in the reaction section to a temperature suitable for the reaction.
  • This heating device 74 can be configured using a heater or a metal stage. Specifically, for example, a Peltier type heater can be used. It is also preferable to also include a cooling device such as a cooling fan for cooling as necessary.
  • the detection device 75 corresponds to the detection device 50 in FIG. 10, and includes a light source that irradiates light that excites the fluorescence of the fluorescent substance contained in the reagent, and a fluorescence detection unit that detects the generated fluorescence. . That is, a light source irradiates an excitation laser onto a carrier disposed in a carrier holding section of the fluidic device 71, and a fluorescence detection section detects fluorescence emitted from a fluorescent dye of a reagent bound to a reaction substance immobilized on the carrier. Detect and quantify.
  • the liquid feeding control section 76 controls the feeding of the reagent from the reagent supply section 72 to the fluid device 71.
  • the liquid feeding control unit 76 may be a pneumatic type that uses air pressure as an actuator to flow fluid, a peristaltic type, a thermopneumatic type that uses gas expansion due to heating, an electrostatic attraction type, an electromagnetic type, a piezo type, or a bimetallic type. Types include molds, shape memory alloy types, and voltage-driven types. Specifically, for example, a pump that pressurizes the inside of a flow path, a peristaltic pump, a syringe pump, etc. can be suitably used.
  • the inspection system 70 of this embodiment includes a valve control section 77 and a control device 78.
  • the valve control section 77 can apply external force to the flow path by controlling the valve section to open/close, switch, and adjust the flow rate of the flow path. can.
  • the valve control section 77 can be of an active type, in which a movable part is moved by an actuator to deform or block the flow path, or a passive type, in which the flow direction is defined by the mechanical structure, flow path dimensions, or surface hydrophilicity.
  • Actuators include pneumatic type that uses air pressure, thermopneumatic type that uses gas expansion due to heating, electrostatic attraction type, electromagnetic type, piezo type, bimetal type, shape memory alloy type, and clamp type that uses weights or springs.
  • pneumatic type can be particularly preferably used.
  • the control device 78 can be configured by an information processing device that controls the heating device 74, the detection device 75, the liquid feeding control section 76, and the valve control section 77.
  • an information processing device a computer, a microcomputer, a PLC (programmable logic controller), or the like can be used.
  • the control device 78 can control the operations of each device by transmitting information for controlling each device at a predetermined timing.
  • the testing system of this embodiment includes a nucleic acid extraction mechanism for extracting a gene to be tested from a sample, an amplification reaction mechanism for amplifying the extracted nucleic acid, and the above-mentioned book for detecting a gene to be tested in an amplified product.
  • the detection mechanism includes the fluid device of the embodiment, and that at least these mechanisms are connected in this order by a flow path.
  • a mechanism for performing other processing may be provided between these mechanisms.
  • the nucleic acid extraction mechanism is configured to extract genomic DNA from crushed cells of a specimen.
  • Genomic DNA can be extracted using the CTAB method (Cetyl trimethyl ammonium bromide), a method that uses porous materials to reduce PCR inhibitors, and DNA extraction kits and devices that use filters containing DNA adsorption carriers, magnetic beads, etc. This can be done using general methods such as the method of
  • the amplification reaction mechanism is configured to amplify a target region in extracted genomic DNA. That is, a DNA fragment containing the target region in genomic DNA is amplified.
  • the method for amplifying this target region is not particularly limited, but PCR can be suitably used.
  • a target region is amplified using a PCR reaction solution containing a primer set for amplifying the target region.
  • a general thermal cycler or the like can be used.
  • the detection mechanism is a component of the inspection system described above using FIG. That is, the test system of this embodiment reacts the amplified product with the probe of the DNA microarray placed in the carrier holding part of the fluidic device of this embodiment, and detects the label of the amplified product bound to the probe. Check if there is.
  • the fluid device of this embodiment even if it is provided with a branch flow path, it is possible to prevent backflow or stagnation of fluid. Further, according to the testing system of this embodiment, it is possible to automatically control everything from extraction of the testing object from the sample to detection of the testing object by the fluid device. In addition, it is possible to prevent the reagent from backflowing or stagnation in the fluidic device, making it possible to perform tests appropriately.
  • the present invention can be suitably used as a fluid device that can prevent backflow and stagnation of fluid in testing the presence or absence of an object to be tested using a fluid device.

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Abstract

The objective of the present invention is to make it possible to provide a fluid device which is provided with a branched flow passage and in which backflow and stagnation of fluid does not occur. The fluid device comprises a main flow passage (10), a plurality of branch flow passages (20), and a connecting portion (30) providing communication between the flow passages (20), and is characterized in that: the main flow passage (10), the branch flow passages (20) and the connecting portion (30) are connected to one another such that, when fluid is being delivered from the branch flow passages (20) toward the main flow passage (10), the fluid is delivered to the main flow passage (10) after merging in the connecting portion (30); and flow passage resistances of the main flow passage (10), the branch flow passages (20) and the connecting portion (30) satisfy the following relational expression. Flow passage resistance of main flow passage (10) ≤ flow passage resistance of connecting portion (30)< flow passage resistance of branch flow passages (20)

Description

流体デバイス、流体デバイスの製造方法、及び検査システムFluid device, fluid device manufacturing method, and inspection system
 本発明は、遺伝子検査などに用いるマイクロ流体デバイスなどに関し、特に分岐流路を備えた流体デバイスに関する。 TECHNICAL FIELD The present invention relates to microfluidic devices used for genetic testing and the like, and particularly to fluidic devices equipped with branch channels.
 近年、DNAマイクロアレイを用いた遺伝子検査などにおいて、マイクロ流体デバイスの流路内に反応部を形成し、この反応部にDNAマイクロアレイを配置させて、流路に送液される試薬中の検査対象物と、DNAマイクロアレイに固定化されたプローブとの反応にもとづいて、試薬における検査対象物の有無の判定が行われている。 In recent years, in genetic testing using DNA microarrays, a reaction part is formed in the channel of a microfluidic device, a DNA microarray is placed in this reaction part, and a test object in a reagent sent to the channel is detected. The presence or absence of the test object in the reagent is determined based on the reaction between the reagent and the probe immobilized on the DNA microarray.
 マイクロ流体デバイスには、複数の試薬を個別に備えられた流入口から注入可能なものがある。すなわち、マイクロ流体デバイスに複数の支流路(分岐流路)が備えられ、これらの支流路が接続部で接続されて主流路に連通する構成になっているものがある。このようなマイクロ流体デバイスは、複数の試薬を用いた検査などにおいて、好適に利用することが可能である。 Some microfluidic devices allow multiple reagents to be injected through separate inlets. That is, some microfluidic devices are equipped with a plurality of tributary channels (branch channels), and these tributary channels are connected at connecting portions to communicate with the main channel. Such a microfluidic device can be suitably used in tests using a plurality of reagents.
国際公開第2008/087828号パンフレットInternational Publication No. 2008/087828 pamphlet 国際公開第2008/059718号パンフレットInternational Publication No. 2008/059718 pamphlet
 しかしながら、このような分岐流路を備えたマイクロ流体デバイスには、そのままでは試薬が出口に向かわず、他の支流路に逆流するという問題があった。
 すなわち、支流路に注入された試薬は、通常一番流れやすい流路に流れる性質がある。このため、試薬は支流路から主流路に設けられた流出口に向かうことなく、接続部を経由して他の支流路の流入口へ逆流することがある。また、逆流が発生したことで他の支流路に一部残存した試薬は、該当する支流路に対して送液や吸引操作をしない限り除去されることはなく、結果として接続部付近に試薬が滞留してしまうという問題があった。
However, a microfluidic device equipped with such a branch channel has a problem in that the reagent does not flow toward the outlet as it is, but flows back into other branch channels.
That is, the reagent injected into the tributary channel usually has the property of flowing into the channel where it flows most easily. Therefore, the reagent may not flow from the tributary channel to the outlet provided in the main channel, but may flow back through the connection to the inlet of another tributary channel. In addition, if a part of the reagent remains in other tributary channels due to backflow, it will not be removed unless the liquid is sent or suctioned to the corresponding tributary channel, and as a result, the reagent remains near the connection. There was a problem that it got stuck.
 このような問題を解消する手段として、マイクロ流体デバイスにバルブを配置して、試薬が流れる流路をバルブで制御することにより、逆流を防止する方法がある。
 しかしながら、この方法では、分岐流路ごとにバルブを備える必要があるため、マイクロ流体デバイスの構成が複雑になるという問題があり、このようなバルブによるマイクロ流体デバイスの複雑化は、マイクロ流体デバイスの設計、製造、制御において大きな問題となっていた。
One way to solve this problem is to prevent backflow by arranging a valve in the microfluidic device and controlling the flow path through which the reagent flows.
However, this method has the problem of complicating the configuration of the microfluidic device because it is necessary to provide a valve for each branch channel. This was a major problem in design, manufacturing, and control.
 そこで、本発明者らは鋭意研究して、分岐流路を備えた流体デバイスであって、流体の逆流及び滞留が生じない流体デバイスを開発することに成功して本発明を完成させた。
 ここで、特許文献1には、主流路と複数の副流路を有するマイクロチップが開示されている。このマイクロチップによれば、複数の副流路から試薬を主流路に順次送液して、目的物質を正確に検出できるとされている。
Therefore, the present inventors conducted extensive research and succeeded in developing a fluid device that is equipped with a branch flow path and that does not cause backflow or stagnation of fluid, thereby completing the present invention.
Here, Patent Document 1 discloses a microchip having a main channel and a plurality of sub channels. According to this microchip, it is said that a target substance can be detected accurately by sequentially feeding reagents from a plurality of sub-channels to a main channel.
 しかし、このマイクロチップは、複数の副流路がそれぞれ個別に主流路に接続するものであるため、一つの副流路から注入された試薬が他の副流路に逆流するという問題が生じるものでない一方で主流路の逆流が生じ得るという問題を有するものであった。
 また、副流路から注入された試薬が主流路内で一度貯留される構造であるため、試薬同士の混合が問題となる場合がある。例えば、試薬と検体の反応順序が重要な検査用途では、ある副流路から主流路に注入された試薬と検体の混合物を一度全て排出して、次の副流路から異なる試薬を注入するという送液手順が必要となるものであった。
However, since this microchip has multiple sub-channels each connected to the main channel individually, there is a problem that reagents injected from one sub-channel flow back into other sub-channels. On the other hand, there was a problem in that backflow in the main flow path could occur.
Furthermore, since the structure is such that the reagent injected from the sub-channel is once stored in the main channel, mixing of the reagents may become a problem. For example, in testing applications where the reaction order of reagents and specimens is important, the mixture of reagents and specimens injected into the main channel from one subchannel is discharged once, and a different reagent is injected from the next subchannel. This required a liquid delivery procedure.
 また、特許文献2にも、主流路と複数の支流路を有するマイクロチップが開示されている。このマイクロチップでは、複数の支流路が比較的大きい接続部を介して主流路に連通しているため一方の支流路から他方の支流路へ逆流するものではないが、接続部内での試薬滞留が生じ得るものであり、支流路及び接続部の試薬を完全に置換して主流路に送液するという用途では用いることができないものであった。 Further, Patent Document 2 also discloses a microchip having a main channel and a plurality of tributary channels. In this microchip, multiple tributary channels communicate with the main channel through relatively large connections, so there is no backflow from one tributary channel to the other, but reagents may accumulate in the connections. This could occur, and it could not be used in applications where the reagents in the tributary channels and connections were completely replaced and the liquid was sent to the main channel.
 本発明は、上記事情に鑑みてなされたものであり、分岐流路を備えた流体デバイスであって、流体の逆流や滞留が生じない流体デバイス、流体デバイスの製造方法、及び検査システムの提供を目的とする。 The present invention has been made in view of the above-mentioned circumstances, and provides a fluid device having a branch flow path in which no backflow or stagnation of fluid occurs, a method for manufacturing the fluid device, and an inspection system. purpose.
 上記目的を達成するため、本発明の流体デバイスは、主流路と、複数の支流路と、各流路に連通する接続部を備えた流体デバイスであって、前記主流路と前記支流路と前記接続部が、前記支流路から前記主流路に向かって流体の送液が行われたときに、前記接続部において流体が合流した後に前記主流路に送液されるように互いに接続され、前記主流路と前記支流路と前記接続部の流路抵抗が、以下の関係式を満たす構成としてある。
 主流路の流路抵抗≦接続部の流路抵抗<支流路の流路抵抗
In order to achieve the above object, the fluid device of the present invention is a fluid device including a main channel, a plurality of branch channels, and a connection part communicating with each channel, wherein the main channel, the branch channels, and the The connecting portions are connected to each other such that when fluid is sent from the tributary flow path toward the main flow path, the fluids are fed to the main flow path after converging at the connection portion, and The flow path resistances of the channel, the tributary flow path, and the connection portion satisfy the following relational expression.
Flow resistance of main channel ≦ Flow resistance of connection section < Flow resistance of tributary channel
 また、本発明の流体デバイスを、前記主流路と前記支流路の流路断面積が、以下の関係式を満たす構成とすることも好ましい。
 主流路の流路断面積>支流路の流路断面積
Further, it is also preferable that the fluid device of the present invention is configured such that the flow path cross-sectional area of the main flow path and the tributary flow path satisfies the following relational expression.
Channel cross-sectional area of main channel > Channel cross-sectional area of tributary channel
 また、本発明の流体デバイスを、少なくとも4枚の基板が接合されてなり、第二の基板に複数の前記支流路が貫通して形成され、前記第二の基板の一方の表面側に第一の基板が接合されており、前記第二の基板の他方の表面側に第三の基板が接合されており、前記第三の基板に、前記主流路が前記第二の基板に対する反対表面側に前記接続部を介して前記支流路に連通して備えられ、前記第三の基板の前記主流路が備えられた側に第四の基板が接合されており、前記第一の基板に、複数の前記支流路に連通する流体流入口が貫通して形成され、前記第一の基板、前記第二の基板、及び前記第三の基板に、前記主流路に連通する流体流出口が貫通して形成されている構成とすることも好ましい。 Further, the fluid device of the present invention may be configured such that at least four substrates are bonded together, the plurality of tributary channels are formed through a second substrate, and a first substrate is formed on one surface side of the second substrate. a third substrate is bonded to the other surface side of the second substrate, and the main flow path is connected to the third substrate on the opposite surface side to the second substrate. A fourth substrate is provided to communicate with the tributary flow path via the connection portion, and is bonded to the side of the third substrate on which the main flow path is provided, and a plurality of substrates are connected to the first substrate. A fluid inlet communicating with the tributary channel is formed to penetrate through the first substrate, the second substrate, and the third substrate, and a fluid outlet communicating with the main channel is formed by penetrating the first substrate, the second substrate, and the third substrate. It is also preferable to have a configuration in which:
 また、本発明の流体デバイスを、前記支流路に連通部を介してそれぞれ連通する複数の支流路延長部が備えられ、前記第一の基板、前記第二の基板、及び前記第三の基板に、前記支流路延長部に連通する前記流体流入口が貫通して形成されている構成とすることも好ましい。
 さらに、本発明の流体デバイスを、前記第四の基板に少なくとも前記主流路が貫通して形成され、前記第四の基板における前記第三の基板に対する反対表面側に第五の基板が備えられた構成とすることも好ましい。
Further, the fluid device of the present invention is provided with a plurality of tributary channel extension portions each communicating with the tributary channel via a communication portion, and the fluid device is connected to the first substrate, the second substrate, and the third substrate. It is also preferable that the fluid inlet communicating with the tributary channel extension is formed through the fluid inlet.
Furthermore, in the fluidic device of the present invention, at least the main flow path is formed through the fourth substrate, and a fifth substrate is provided on the opposite surface side of the fourth substrate to the third substrate. It is also preferable to have a configuration.
 また、本発明の流体デバイスを、少なくとも3枚の基板が接合されてなり、第二の基板の一方の表面に複数の前記支流路が形成され、前記第二の基板の当該表面側に第一の基板が接合されており、前記第二の基板の他方の表面側に第三の基板が接合されており、前記第二の基板の表面における前記第三の基板側に、前記主流路が前記接続部を介して前記支流路に連通して備えられ、前記第一の基板に前記支流路に連通する流体流入口が貫通して形成され、前記第一の基板及び前記第二の基板に、前記主流路に連通する流体流出口が貫通して形成されている構成とすることも好ましい。 Further, the fluid device of the present invention may be configured such that at least three substrates are bonded together, a plurality of the tributary channels are formed on one surface of the second substrate, and a first substrate is formed on the surface side of the second substrate. a third substrate is bonded to the other surface side of the second substrate, and the main flow path is connected to the third substrate side of the surface of the second substrate. The first substrate is provided with a fluid inlet communicating with the tributary channel via a connecting portion, and the first substrate is provided with a fluid inlet that communicates with the tributary channel, and the first substrate and the second substrate are provided with: It is also preferable that a fluid outlet communicating with the main flow path is formed through the fluid outlet.
 また、本発明の流体デバイスを、少なくとも第一の基板と第二の基板とが接合されてなり、前記第二の基板に前記主流路と前記支流路と前記接続部が備えられ、前記第二の基板の前記主流路と前記支流路と前記接続部が備えられた表面側に前記第一の基板が接合されており、前記第一の基板に、前記支流路に連通する流体流入口が貫通して形成されていると共に、前記主流路に連通する流体流出口が貫通して形成されている構成とすることも好ましい。 Further, the fluid device of the present invention may be configured such that at least a first substrate and a second substrate are bonded, the second substrate is provided with the main flow channel, the branch flow channel, and the connection portion, and the second The first substrate is bonded to a surface side of the substrate on which the main flow channel, the branch flow channel, and the connection portion are provided, and a fluid inlet communicating with the branch flow channel passes through the first substrate. It is also preferable that a fluid outlet communicating with the main flow path is formed through the main flow path.
 また、本発明の流体デバイスを、少なくとも第一の基板と第二の基板とが接合されてなり、前記第一の基板に、前記主流路と、複数の前記支流路にそれぞれ連通する複数の支流路延長部とが貫通して備えられ、前記第二の基板に、複数の前記支流路と、前記主流路に連通する前記接続部と、前記支流路延長部にそれぞれ連通する連通部とが備えられた構成とすることも好ましい。 Further, the fluid device of the present invention may be configured such that at least a first substrate and a second substrate are bonded, and the first substrate has a plurality of tributary channels each communicating with the main flow channel and the plurality of tributary flow channels. The second substrate is provided with a plurality of branch channels, the connecting portion communicating with the main channel, and a communication portion communicating with each of the branch channel extensions. It is also preferable to have a configuration in which
 また、本発明の流体デバイスを、それぞれの基板が、疎水性材料により形成された構成とすることも好ましい。
 また、本発明の流体デバイスを、前記主流路の一部に反応部が備えられた構成とすることも好ましい。
Further, it is also preferable that the fluidic device of the present invention has a configuration in which each substrate is formed of a hydrophobic material.
Further, it is also preferable that the fluid device of the present invention has a configuration in which a part of the main flow path is provided with a reaction section.
 また、本発明の流体デバイスを、前記反応部の表面が、反応用物質が固定化された表面である構成とすることも好ましい。
 また、本発明の流体デバイスを、前記反応部に、凹部、又は、貫通孔である担体保持部が備えられ、前記担体保持部に反応用物質が固定化された担体が保持された構成とすることも好ましい。
 さらに、本発明の流体デバイスを、上記の流体デバイスにおける各構成を様々に組み合わせたものとすることも好ましい。
Further, it is also preferable that the fluid device of the present invention is configured such that the surface of the reaction section is a surface on which a reaction substance is immobilized.
Further, the fluid device of the present invention is configured such that the reaction section is provided with a carrier holding section that is a recess or a through hole, and a carrier on which a reaction substance is immobilized is held in the carrier holding section. It is also preferable.
Furthermore, it is also preferable that the fluid device of the present invention is a combination of various configurations of the fluid devices described above.
 なお、本発明の流体デバイスの製造方法は、上記のいずれかの流体デバイスを、切削加工、射出成形、ホットエンボス加工、レーザー加工、エッチング加工、又は3Dプリンタ等を用いて形成する方法としてある。 Note that the method for manufacturing a fluidic device of the present invention is a method of forming any of the above fluidic devices using cutting, injection molding, hot embossing, laser processing, etching, or a 3D printer.
 本発明の検査システムは、上記のいずれかの流体デバイスと、試薬を前記流路に送液する送液制御部と、前記流体デバイスを加熱する加熱装置と、前記試薬の蛍光を励起する光を照射する光源及び発生した蛍光を検出する蛍光検出部を有する検出装置とを備えた構成としてある。 The inspection system of the present invention includes any one of the above-mentioned fluidic devices, a liquid feeding control unit that feeds a reagent to the flow path, a heating device that heats the fluidic device, and a light that excites fluorescence of the reagent. The configuration includes a light source for irradiation and a detection device having a fluorescence detection section for detecting the generated fluorescence.
 また、本発明の検査システムを、少なくとも前記支流路の開閉、切替、及び/又は流量調節を行うバルブ制御部と、前記加熱装置、前記検出装置、前記送液制御部、及び前記バルブ制御部を制御する情報処理装置とをさらに備えた構成とすることが好ましい。
 さらに、本発明の検査システムを、検体から検査対象遺伝子を抽出する核酸抽出機構と、抽出された核酸を増幅する増幅反応機構と、増幅産物中の検査対象遺伝子を検出するための上記のいずれかの流体デバイスを備える検出機構とを有し、少なくともこれらの機構が、この順に流路で接続されている構成とすることも好ましい。
Further, the inspection system of the present invention includes at least a valve control section that opens/closes, switches, and/or adjusts the flow rate of the tributary channel, the heating device, the detection device, the liquid feeding control section, and the valve control section. Preferably, the configuration further includes an information processing device to be controlled.
Furthermore, the test system of the present invention can be configured to include a nucleic acid extraction mechanism for extracting a test target gene from a specimen, an amplification reaction mechanism for amplifying the extracted nucleic acid, and any one of the above for detecting a test target gene in an amplified product. It is also preferable to have a detection mechanism including a fluid device, and at least these mechanisms are connected in this order by a flow path.
 本発明によれば、分岐流路を備えた流体デバイスであって、流体の逆流や滞留が生じない流体デバイス、流体デバイスの製造方法、及び検査システムの提供が可能となる。 According to the present invention, it is possible to provide a fluid device including a branch flow path in which backflow or stagnation of fluid does not occur, a method for manufacturing the fluid device, and an inspection system.
本発明の実施形態に係る流体デバイスの構成を示す模式図である。1 is a schematic diagram showing the configuration of a fluidic device according to an embodiment of the present invention. 本発明の実施形態に係る流体デバイスの基板の構成を示す模式図である。FIG. 1 is a schematic diagram showing the configuration of a substrate of a fluidic device according to an embodiment of the present invention. 本発明の実施形態に係る流体デバイスに流体を送液した場合の様子を示す説明図である。FIG. 2 is an explanatory diagram showing a situation when fluid is sent to a fluid device according to an embodiment of the present invention. 本発明の実施形態に係る流体デバイスの変形例1の基板の構成を示す模式図である。FIG. 3 is a schematic diagram showing the configuration of a substrate of Modification Example 1 of the fluidic device according to the embodiment of the present invention. 本発明の実施形態に係る流体デバイスの変形例2の基板の構成を示す模式図である。FIG. 7 is a schematic diagram showing the configuration of a substrate of Modification Example 2 of the fluidic device according to the embodiment of the present invention. 本発明の実施形態に係る流体デバイスの変形例3の基板の構成を示す模式図である。FIG. 7 is a schematic diagram showing the configuration of a substrate of Modification Example 3 of the fluidic device according to the embodiment of the present invention. 本発明の実施形態に係る流体デバイスの変形例4の基板の構成を示す模式図である。FIG. 7 is a schematic diagram showing the configuration of a substrate of Modification Example 4 of the fluidic device according to the embodiment of the present invention. 本発明の実施形態に係る流体デバイスの変形例5の基板の構成を示す模式図である。FIG. 7 is a schematic diagram showing the configuration of a substrate of Modification Example 5 of the fluidic device according to the embodiment of the present invention. 本発明の実施形態に係る流体デバイスの変形例6の基板の構成を示す模式図である。FIG. 7 is a schematic diagram showing the configuration of a substrate of Modification Example 6 of the fluidic device according to the embodiment of the present invention. 本発明の実施形態に係る流体デバイスを用いて蛍光検出を行う様子を示す模式図である。FIG. 1 is a schematic diagram showing how fluorescence detection is performed using a fluidic device according to an embodiment of the present invention. 本発明の実施形態に係る検査システムの構成を示す模式図である。1 is a schematic diagram showing the configuration of an inspection system according to an embodiment of the present invention. 従来の流体デバイスの構成を示す模式図である。FIG. 1 is a schematic diagram showing the configuration of a conventional fluidic device. 従来の流体デバイスの基板の構成を示す模式図である。FIG. 1 is a schematic diagram showing the configuration of a substrate of a conventional fluidic device. 従来の流体デバイスに流体を送液した場合の様子を示す説明図である。FIG. 2 is an explanatory diagram showing a situation when fluid is sent to a conventional fluid device. 従来の流体デバイスにおける流入口と流出口の配置例と流体の逆流を防止するためのバルブの配置例を示す説明図である。FIG. 3 is an explanatory diagram showing an example of the arrangement of an inlet and an outlet in a conventional fluid device, and an example of the arrangement of a valve for preventing backflow of fluid.
 以下、本発明の実施形態に係る流体デバイス、流体デバイスの製造方法、及び検査システムについて詳細に説明する。ただし、本発明は、以下の実施形態の具体的な内容に限定されるものではない。 Hereinafter, a fluid device, a fluid device manufacturing method, and an inspection system according to embodiments of the present invention will be described in detail. However, the present invention is not limited to the specific contents of the embodiments below.
[流体デバイス]
 まず、本発明の実施形態に係る流体デバイスについて、図1~3を参照して説明する。図1は、本発明の実施形態に係る流体デバイスの構成を示す模式図であり、図2は、この流体デバイスの基板の構成を示す模式図である。また、図3は、この流体デバイスに流体を送液した場合の様子を示す説明図である。
[Fluid device]
First, a fluidic device according to an embodiment of the present invention will be described with reference to FIGS. 1 to 3. FIG. 1 is a schematic diagram showing the configuration of a fluidic device according to an embodiment of the present invention, and FIG. 2 is a schematic diagram showing the configuration of a substrate of this fluidic device. Moreover, FIG. 3 is an explanatory diagram showing the situation when fluid is sent to this fluid device.
 本実施形態の流体デバイスは、主流路と、複数の支流路と、各流路に連通する接続部を備えた流体デバイスである。
 図1に示すように、本実施形態の流体デバイスは、主流路10と支流路20(21,2,23)と接続部30が、支流路20から主流路10に向かって流体の送液が行われたときに、接続部30において流体が合流した後に主流路10に送液されるように互いに接続されている。
 そして、主流路10と支流路20と接続部30の流路抵抗が、以下の関係式を満たすことを特徴とする。
 主流路の流路抵抗≦接続部の流路抵抗<支流路の流路抵抗
The fluid device of this embodiment is a fluid device that includes a main channel, a plurality of branch channels, and a connecting portion that communicates with each channel.
As shown in FIG. 1, in the fluid device of the present embodiment, the main channel 10, the tributary channels 20 (21, 2, 23), and the connecting portion 30 are arranged so that the fluid is not sent from the tributary channel 20 toward the main channel 10. When this is done, the fluids are connected to each other so that the fluids are fed to the main flow path 10 after merging at the connection portion 30 .
The main flow path 10, the tributary flow path 20, and the connection portion 30 are characterized in that the flow path resistances satisfy the following relational expression.
Flow resistance of main channel ≦ Flow resistance of connection section < Flow resistance of tributary channel
 すなわち、図1の本実施形態の流体デバイスでは、支流路21が支流路延長部41に連通部211を介して接続され、支流路22が支流路延長部42に連通部221を介して接続され、支流路23が支流路延長部43に連通部231を介して接続されている。
 支流路延長部40(41,42,43)における支流路20に対する反対側の端部には、それぞれ流体流入口411、421,431が備えられている。
That is, in the fluid device of the present embodiment shown in FIG. 1, the tributary channel 21 is connected to the tributary channel extension 41 via the communication section 211, and the tributary channel 22 is connected to the tributary channel extension 42 via the communication section 221. , the tributary flow path 23 is connected to the tributary flow path extension 43 via a communication portion 231.
Fluid inlets 411, 421, 431 are provided at the ends of the tributary channel extensions 40 (41, 42, 43) opposite to the tributary channel 20, respectively.
 また、支流路21,22,23は、接続部30で接続されて主流路10に連通されている。主流路10における接続部30に対する反対側の端部には、流体流出口101が備えられている。
 接続部30の流路抵抗は、支流路20の流路抵抗より小さくなっている。このため、各支流路から接続部30に流入した流体は、他の支流路に流れることなく、より流路抵抗の小さい接続部30に流れるようになっている。
Further, the tributary channels 21 , 22 , 23 are connected through a connecting portion 30 and communicated with the main channel 10 . A fluid outlet 101 is provided at the end of the main flow path 10 opposite to the connection portion 30 .
The flow path resistance of the connecting portion 30 is smaller than the flow path resistance of the tributary flow path 20. Therefore, the fluid flowing into the connecting portion 30 from each tributary flow path does not flow to other tributary flow paths, but instead flows to the connecting portion 30 with lower flow path resistance.
 さらに、接続部30の流路抵抗は、主流路10の流路抵抗と同じであるか、またはそれより小さくなっている。
 このため、接続部30に流入した流体は、より流路抵抗の大きい支流路20に逆流することなく、主流路10に流れるようになっている。また、主流路10から接続部30に流体が逆流することがないようになっている。
 なお、図1において、支流路20は、3つ備えられているが、本実施形態の流体デバイスにおける支流路20の個数は、複数であればよく、特に限定されない。
Furthermore, the flow path resistance of the connecting portion 30 is the same as or smaller than the flow path resistance of the main flow path 10.
Therefore, the fluid that has flowed into the connecting portion 30 flows into the main flow path 10 without flowing back into the tributary flow path 20 having a higher flow resistance. Further, the fluid is prevented from flowing back from the main channel 10 to the connecting portion 30.
Although three branch channels 20 are provided in FIG. 1, the number of branch channels 20 in the fluid device of this embodiment is not particularly limited as long as it is plural.
 本実施形態の流体デバイスの基板の構成例を図2に示す。
 図2に示すように、本実施形態の流体デバイスは、5枚の基板により構成されている。第一の基板(K1)は、最上面側を構成するフィルムであり、流体流入口411,421,431と流体流出口101が形成されている。
FIG. 2 shows an example of the structure of the substrate of the fluidic device of this embodiment.
As shown in FIG. 2, the fluidic device of this embodiment is composed of five substrates. The first substrate (K1) is a film forming the uppermost surface side, and has fluid inlets 411, 421, 431 and a fluid outlet 101 formed therein.
 第二の基板(K2)は、上面側の両面テープ(又はフィルム)であり、支流路20(21,22,23)と連通部211,221,231が形成されている。また、流体流入口411,421,431と流体流出口101が形成されている。
 第三の基板(K3)は、樹脂基板であり、主流路10と流体流出口101、接続部30、支流路延長部41と流体流入口411、支流路延長部42と流体流入口421、及び支流路延長部43と流体流入口431が形成されている。
 主流路10と支流路延長部41,42,43は、基板の裏面側に凹部形状の流路として形成されている。また、接続部30と流体流出口101と流体流入口411,421,431は、基板を貫通して形成されている。
The second substrate (K2) is a double-sided tape (or film) on the upper surface side, and has tributary channels 20 (21, 22, 23) and communication portions 211, 221, 231 formed therein. Further, fluid inlets 411, 421, 431 and a fluid outlet 101 are formed.
The third substrate (K3) is a resin substrate, and includes the main channel 10, the fluid outlet 101, the connection part 30, the tributary channel extension 41 and the fluid inlet 411, the tributary channel extension 42 and the fluid inlet 421, and A tributary channel extension 43 and a fluid inlet 431 are formed.
The main channel 10 and the tributary channel extensions 41, 42, and 43 are formed as concave-shaped channels on the back side of the substrate. Further, the connecting portion 30, the fluid outlet 101, and the fluid inlets 411, 421, and 431 are formed to penetrate the substrate.
 第四の基板(K4)は、下面側の両面テープ(又はフィルム)であり、支流路延長部41,42,43、及び主流路10が形成されている。
 第五の基板(K5)は、最下面側を構成するフィルムであり、何も形成されておらず、第四の基板(K4)に形成された支流路延長部41,42,43と主流路10を封止している。
The fourth substrate (K4) is a double-sided tape (or film) on the lower surface side, and branch channel extensions 41, 42, 43 and the main channel 10 are formed therein.
The fifth substrate (K5) is a film constituting the lowermost side, and nothing is formed thereon, and the tributary channel extensions 41, 42, 43 formed on the fourth substrate (K4) and the main channel are formed on the fifth substrate (K5). 10 is sealed.
 このような本実施形態の流体デバイスを使用した場合の流体の流れについて、図3を参照して説明する。図3は、本実施形態の流体デバイスに着色した流体を注入する様子を示している。
 流体流入口421から注入された流体は、支流路延長部42に送液され、連通部221を経由して支流路22に送液される。
The flow of fluid when using the fluid device of this embodiment will be described with reference to FIG. 3. FIG. 3 shows how colored fluid is injected into the fluidic device of this embodiment.
The fluid injected from the fluid inlet 421 is sent to the tributary channel extension 42 and then to the tributary channel 22 via the communication section 221.
 支流路22に送液された流体は、接続部30に流入した後、以下の関係式を満たすため他の支流路21,23に流入することなく、主流路10に流入して、流体流出口101へ到達する。
 主流路10の流路抵抗<支流路21,23の流路抵抗
 このように本実施形態の流体デバイスによれば、複数の支流路が備えられている場合であっても、1つの支流路に送液された流体が、他の支流路に逆流することがない。また、主流路10に送液された流体が、接続部30や支流路20に逆流することがないようになっている。
After the fluid sent to the tributary channel 22 flows into the connection part 30, it flows into the main channel 10 without flowing into the other tributary channels 21 and 23 because it satisfies the following relational expression, and then flows into the main channel 10 and passes through the fluid outlet. Reach 101.
Flow path resistance of main flow path 10<flow path resistance of tributary flow paths 21 and 23 According to the fluid device of this embodiment, even when a plurality of tributary flow paths are provided, one tributary flow path The sent fluid does not flow back into other tributary channels. Further, the fluid sent to the main flow path 10 is prevented from flowing back into the connecting portion 30 or the tributary flow path 20.
 本実施形態の流体デバイスにおいて、主流路10と支流路20の流路断面積が、以下の関係式を満たすことが好ましい。
 主流路の流路断面積>支流路の流路断面積
 本実施形態の流体デバイスをこのような構成にすれば、主流路10と支流路20における他の条件が同一であれば、主流路10の流路抵抗を、支流路20の流路抵抗より小さくすることができる。このため、支流路20から主流路10に流体を流れ易くすることができ、主流路10から支流路20への流体の逆流を防止することが可能となる。
In the fluid device of this embodiment, it is preferable that the flow path cross-sectional area of the main flow path 10 and the tributary flow path 20 satisfy the following relational expression.
Channel cross-sectional area of main channel>channel cross-sectional area of tributary channel If the fluid device of this embodiment has such a configuration, if other conditions in the main channel 10 and the tributary channel 20 are the same, the main channel 10 The flow path resistance of the tributary flow path 20 can be made smaller than the flow path resistance of the tributary flow path 20. Therefore, the fluid can easily flow from the tributary channel 20 to the main channel 10, and it is possible to prevent the fluid from flowing back from the main channel 10 to the tributary channel 20.
 本実施形態の流体デバイスにおいて、主流路10の流路抵抗を支流路20の流路抵抗より小さくする方法としては、例えば以下の方法を挙げることができる。なお、主流路10と支流路20におけるその他の条件は、同一とする。また、これらの方法を組み合わせて構成することも好ましい。
・支流路20の流路幅を主流路10より小さくする。
・支流路20の流路深さを主流路10より小さくする。
・複数の支流路20間の分岐角度を、支流路20と主流路10の分岐角度より小さくする。
・支流路20の流路長さを主流路10より長くする。
・主流路10に対する複数の支流路20の水平位置を高くする。
In the fluid device of this embodiment, examples of methods for making the flow path resistance of the main flow path 10 smaller than the flow path resistance of the tributary flow path 20 include the following method. Note that other conditions in the main flow path 10 and the tributary flow path 20 are the same. It is also preferable to configure a combination of these methods.
- Make the channel width of the tributary channel 20 smaller than that of the main channel 10.
- The depth of the tributary channel 20 is made smaller than that of the main channel 10.
- The branching angle between the plurality of tributary channels 20 is made smaller than the branching angle between the tributary channels 20 and the main channel 10.
- The length of the tributary flow path 20 is made longer than the main flow path 10.
- Raise the horizontal position of the plurality of tributary channels 20 with respect to the main channel 10.
 ここで、本実施形態の流体デバイスにおける流体の逆流や滞留が生じないという効果を得るために、分岐する各流路に対して流路抵抗と圧力損失に関わる流路幅、流路深さ、流路長さ、流路の高低,曲がり,分岐,合流、分岐流路の分岐角度、バルブの構造などの流路寸法と流路形状を考慮することにより、主流路及び各支流路の損失の差が大きくなるように設計することも好ましい。
 流体デバイスなどの流路では、摩擦損失、断面積の変化、流れの方向変化、分岐や合流、バルブなどの流路寸法と流路形状に影響されて種々の損失を生じ、この損失は流体の流れを表す式において損失ヘッドと呼ばれる。
Here, in order to obtain the effect that backflow or stagnation of fluid does not occur in the fluid device of this embodiment, for each branching channel, the channel width, channel depth, and channel depth related to channel resistance and pressure loss, Loss in the main flow path and each tributary flow path can be reduced by considering flow path dimensions and flow path shapes such as flow path length, height of the flow path, bending, branching, merging, branching angle of branch flow paths, and valve structure. It is also preferable to design so that the difference is large.
In the flow path of fluid devices, various losses occur due to friction loss, changes in cross-sectional area, changes in flow direction, branching, merging, valves, etc., and are affected by the flow path dimensions and shape. In equations expressing flow, this is called the loss head.
 直管の摩擦損失を表す管摩擦損失ヘッドhは、層流、乱流、及び管壁の粗さのいかんに拘わらず、ダルシー・ワイズバッハの式より、以下のように与えられる。
 h=Δp/ρg=λL/d・v2/2g
 Δpは圧力損失、ρは流体の密度、gは重力加速度、λは管摩擦係数、Lは流路の長さ、dは円管直径、vは流路を流れる流体の速度である。
Pipe friction loss head h, which represents the friction loss of a straight pipe, is given by the Darcy-Weisbach equation as follows, regardless of laminar flow, turbulent flow, or roughness of the pipe wall.
h=Δp/ρg=λL/d・v 2 /2g
Δp is the pressure loss, ρ is the density of the fluid, g is the gravitational acceleration, λ is the pipe friction coefficient, L is the length of the flow path, d is the diameter of the circular pipe, and v is the velocity of the fluid flowing through the flow path.
 本式の変形式Δp=λL/d・ρ/2・v2によれば、流路抵抗は、ある流路へ流体を流すために必要な圧力と、その結果確認される流体の流速又は流量との比例定数を示し、流路抵抗が大となる時、圧力損失は大となる、あるいは流速が小となる関係にある。
 また、流路の径が細くなる、つまり流路の断面積が減少することによって圧力損失は増加し、流路の長さが長くなることによっても圧力損失は増加することが示されている。
 したがって、断面積や長さの異なる分岐流路の圧力損失を比較した場合、最も低圧力で最大の流速を得られる流路を主流路として設計することができる。
According to the modified form of this equation Δp=λL/d・ρ/2・v 2 , the flow path resistance is the pressure required to flow a fluid into a certain flow path and the resulting flow rate or flow rate of the fluid. The relationship is such that when the flow path resistance increases, the pressure loss increases or the flow velocity decreases.
Furthermore, it has been shown that the pressure loss increases as the diameter of the flow path decreases, that is, the cross-sectional area of the flow path decreases, and that the pressure loss also increases as the length of the flow path increases.
Therefore, when comparing the pressure losses of branch channels having different cross-sectional areas and lengths, the channel that provides the lowest pressure and the highest flow rate can be designed as the main channel.
 損失ヘッドは、管摩擦係数だけでなく、流路形状に対しても以下のように表すことが可能である。
 h=ζv 2/2g
 損失係数ζは、流路の断面積の変化、流れの方向変化、分岐や合流、バルブなどで実験的に得ることができる係数であり、管路系の総損失ヘッドhは、管摩擦係数と各種損失係数の総和として、h=ΣλL/d・v2/2g+Σζv2/2gと示される。
The loss head can be expressed not only by the pipe friction coefficient but also by the flow path shape as follows.
h n =ζv n 2 /2g
The loss coefficient ζ is a coefficient that can be obtained experimentally due to changes in the cross-sectional area of the flow path, changes in flow direction, branching, merging, valves, etc., and the total loss head hL of the pipe system is the coefficient of pipe friction. and the sum of various loss coefficients is expressed as h L =ΣλL/d·v 2 /2g+Σζv 2 /2g.
 なお、分岐流路の損失係数は、分岐角度θ、流量比、分岐部の形状、円管の直径比、レイノルズ数などに依存して変化する係数であるが、例えば支流路同士がなす分岐角度を、支流路と主流路がなす分岐角度より小さくすることによって、直線方向に近い主流路へより多くの流体が分配されるため、これも加味して流路設計することで、支流路へ分配され得る流体の流速をさらに下げることができ、逆流を大きく低減することが期待できる。
 以上のとおり、流路抵抗に関わる上記式と流路形状を考慮することで圧力損失と流速の大小関係を各流路間で比較し、主流路と各支流路の役割を意図した設計が可能となる。
Note that the loss coefficient of a branch channel is a coefficient that changes depending on the branch angle θ, flow rate ratio, shape of the branch, diameter ratio of the circular pipe, Reynolds number, etc., but for example, the branch angle between the branch channels By making the branching angle smaller than the branching angle between the tributary channel and the main channel, more fluid will be distributed to the main channel that is closer to the straight direction. It is possible to further reduce the flow rate of the fluid that can be used, and it is expected that backflow will be greatly reduced.
As described above, by considering the above formula related to flow path resistance and the flow path shape, it is possible to compare the magnitude relationship between pressure loss and flow velocity between each flow path, and to design a design that takes into account the role of the main flow path and each tributary flow path. becomes.
 なお、本実施形態の流体デバイスにおける流路の断面形状は円管ではなく矩形管であるため、四方全て濡れ縁の矩形管における水力等価直径として換算したものを用いることができる。矩形管の水力等価直径cは、流路幅をa、流路深さをbとしたとき、以下の式によって算出される。
 c=2ab/(a+b)
Note that, since the cross-sectional shape of the flow path in the fluid device of this embodiment is not a circular tube but a rectangular tube, the hydraulic equivalent diameter of a rectangular tube with wetted edges on all four sides can be used. The hydraulic equivalent diameter c of the rectangular pipe is calculated by the following formula, where a is the channel width and b is the channel depth.
c=2ab/(a+b)
 また、ハーゲン・ポアズイユの式から導出される流路抵抗R(N・s/m5)も、本実施形態流体デバイスにおける主流路と支流路を設計する上での指標として用いることができる。
 すなわち、流体が流路内を流れるときの圧力損失Δp、流量Qを用いて、流路抵抗Rは、R=Δp/Qのように示されるが、このハーゲン・ポアズイユの式は、ダルシー・ワイズバッハの式に層流条件で得られる係数λ=64/Reを用いた場合と同一の式であり、同様に用いることができる。
Further, the flow path resistance R (N·s/m 5 ) derived from the Hagen-Poiseuille equation can also be used as an index in designing the main flow path and the tributary flow paths in the fluid device of this embodiment.
That is, using the pressure loss Δp and flow rate Q when fluid flows in the channel, the channel resistance R is expressed as R=Δp/Q, but this Hagen-Poiseuille equation is This is the same equation as when the coefficient λ=64/Re obtained under laminar flow conditions is used in Bach's equation, and can be used in the same way.
 本実施形態の流体デバイスにおける各基板の材料は特に限定されないが、例えば、COP(シクロオレフィンポリマー)、PMMA(ポリメチルメタクリレート)、COC(シクロオレフィンコポリマー)などを好適に用いることが可能である。また、PDMS(ポリジメチルシロキサン)やPET(ポリエチレンテレフタレート)を用いてもよい。 The material of each substrate in the fluid device of this embodiment is not particularly limited, but for example, COP (cycloolefin polymer), PMMA (polymethyl methacrylate), COC (cycloolefin copolymer), etc. can be suitably used. Alternatively, PDMS (polydimethylsiloxane) or PET (polyethylene terephthalate) may be used.
 また、本実施形態の流体デバイスは、各基板が疎水性材料により形成されたものとすることが好ましい。
 本実施形態の流体デバイスをこのような構成にすれば、この流体デバイスにおいて、支流路を疎水性パッシブバルブとして用いることも可能となる。
Further, in the fluid device of this embodiment, each substrate is preferably formed of a hydrophobic material.
If the fluid device of this embodiment is configured in this manner, it becomes possible to use the tributary channel as a hydrophobic passive valve in this fluid device.
 なお、このバルブを通って液体を流すのに必要な圧力を示す圧力差ΔPは、以下の式によって算出することができる。
 ΔP=-2γcosθ(1/w+1/h-1/W+1/H)
 γは単位面積当たりの気-液界面の表面エネルギー、θは接触角、wは支流路の流路幅、hは支流路の流路深さ、Wは支流路延長部の流路幅、Hは支流路延長部の流路深さである。
Note that the pressure difference ΔP indicating the pressure required to flow the liquid through this valve can be calculated using the following formula.
ΔP=-2γcosθ(1/w+1/h-1/W+1/H)
γ is the surface energy of the gas-liquid interface per unit area, θ is the contact angle, w is the channel width of the branch channel, h is the channel depth of the branch channel, W is the channel width of the branch channel extension, H is the channel depth of the tributary channel extension.
 気-液界面が存在する本実施形態のような流体デバイスであれば、流路抵抗にもとづく逆流方向への流速低減に加えて、疎水性パッシブバルブの働きによって、液体を支流路延長部に留めることも可能となる。
 このため、本実施形態の流体デバイスによれば、各支流路への意図しない逆流や液体の滞留をさらに低減することが可能である。
In a fluid device such as this embodiment in which a gas-liquid interface exists, in addition to reducing the flow velocity in the reverse flow direction based on the flow path resistance, the hydrophobic passive valve works to keep the liquid in the tributary channel extension. It also becomes possible.
Therefore, according to the fluid device of the present embodiment, it is possible to further reduce unintended backflow and retention of liquid in each branch channel.
 また、本実施形態の流体デバイスにおいて、各基板の接合方法としては、熱融着、レーザー、超音波、溶剤、接着剤、粘着剤、プラズマ処理、紫外線処理を用いるなど、特に限定されない。 Furthermore, in the fluidic device of the present embodiment, the method for joining each substrate is not particularly limited, and may include thermal fusion, laser, ultrasonic waves, a solvent, an adhesive, a pressure-sensitive adhesive, plasma treatment, and ultraviolet treatment.
 また、本実施形態の流体デバイスにおいて、主流路10、支流路20、接続部30、支流路延長部41,42,43、流体流入口411,421,431、及び流体流出口101等を加工する方法は、特に限定されず、例えば切削加工、射出成形、ホットエンボス加工、レーザー加工、エッチング加工、3Dプリンタなどを用いて行うことが可能である。 In addition, in the fluid device of this embodiment, the main channel 10, the tributary channel 20, the connecting portion 30, the tributary channel extensions 41, 42, 43, the fluid inlets 411, 421, 431, the fluid outlet 101, etc. are processed. The method is not particularly limited, and can be performed using, for example, cutting, injection molding, hot embossing, laser processing, etching, 3D printing, or the like.
 ここで、従来の流体デバイスについて、図12~15を参照して説明する。図12は、従来の流体デバイスの構成を示す模式図であり、図13は、従来の流体デバイスの基板の構成を示す模式図である。図14は、従来の流体デバイスに流体を送液した場合の様子を示す説明図である。図15は、従来の流体デバイスにおける流入口と流出口の配置例と流体の逆流を防止するためのバルブの配置例を示す説明図である。 Here, conventional fluidic devices will be explained with reference to FIGS. 12 to 15. FIG. 12 is a schematic diagram showing the configuration of a conventional fluidic device, and FIG. 13 is a schematic diagram showing the configuration of a substrate of the conventional fluidic device. FIG. 14 is an explanatory diagram showing a situation when fluid is delivered to a conventional fluid device. FIG. 15 is an explanatory diagram showing an example of the arrangement of an inlet and an outlet in a conventional fluid device, and an example of the arrangement of valves for preventing backflow of fluid.
 図12に示すように、複数の支流路を備えた従来の一般的な流体デバイスは、例えば主流路1000と支流路2000(2100,2200,2300)と接続部3000を備えている。
 支流路2100,2200,2300には、それぞれ流体流入口2101,2201,2301が備えられ、主流路1000には流体流出口1001が備えられている。
 そして、流体流入口2101,2201,2301から注入された流体は、接続部3000を経由して主流路1000に送液され、流体流出口1001から排出される構成となっている。
As shown in FIG. 12, a conventional general fluid device including a plurality of branch channels includes, for example, a main channel 1000, branch channels 2000 (2100, 2200, 2300), and a connecting portion 3000.
The tributary channels 2100, 2200, and 2300 are provided with fluid inlets 2101, 2201, and 2301, respectively, and the main channel 1000 is provided with a fluid outlet 1001.
The fluid injected from the fluid inlets 2101, 2201, and 2301 is sent to the main channel 1000 via the connection portion 3000, and is discharged from the fluid outlet 1001.
 従来の流体デバイスの基板の構成例を図13に示す。
 図13に示すように、この従来の流体デバイスは、3つの基板により構成されている。第一の基板(K100)は、最上面側を構成する樹脂基板であり、主流路1000と流体流出口1001、支流路2100と流体流入口2101、支流路2200と流体流入口2201、及び支流路2300と流体流入口2301が形成されている。
 主流路1000と支流路2100,2200,2300と接続部3000は、基板の裏面側に凹部形状の流路として形成されている。また、流体流出口1001と流体流入口2101,2201,2301は、基板を貫通して形成されている。
An example of the structure of a substrate of a conventional fluidic device is shown in FIG.
As shown in FIG. 13, this conventional fluidic device is composed of three substrates. The first substrate (K100) is a resin substrate constituting the uppermost surface side, and includes a main channel 1000 and a fluid outlet 1001, a tributary channel 2100 and a fluid inlet 2101, a tributary channel 2200 and a fluid inlet 2201, and a tributary channel. 2300 and a fluid inlet 2301 are formed.
The main channel 1000, the branch channels 2100, 2200, 2300, and the connecting portion 3000 are formed as concave channels on the back side of the substrate. Furthermore, the fluid outlet 1001 and the fluid inlets 2101, 2201, and 2301 are formed to penetrate the substrate.
 第二の基板(K200)は、両面テープ(又はフィルム)であり、主流路1000と支流路2100,2200,2300と接続部3000が形成されている。
 第三の基板(K300)は、最下面側を構成するフィルムであり、何も形成されておらず、第二の基板(K200)に形成された主流路1000と支流路2100,2200,2300と接続部3000を封止している。
The second substrate (K200) is a double-sided tape (or film), and has a main channel 1000, tributary channels 2100, 2200, 2300, and a connecting portion 3000 formed therein.
The third substrate (K300) is a film constituting the lowermost surface side, and has nothing formed thereon, and is connected to the main channel 1000 and the branch channels 2100, 2200, 2300 formed on the second substrate (K200). The connecting portion 3000 is sealed.
 このような従来の流体デバイスを使用した場合の流体の流れについて、図14を参照して説明する。図14は、本実施形態の流体デバイスに着色した流体を注入する様子を示している。
 流体流入口2201から注入された流体は、支流路2200に送液される。接続部3000に到達した流体は、最も流れやすい流路に送液されるため、主流路1000ではなく、まずは直線方向にある支流路2300に流入する。
 次に、主流路1000と支流路2100にも流入して、流体流出口1001に到達する。
Fluid flow when such a conventional fluid device is used will be explained with reference to FIG. 14. FIG. 14 shows how colored fluid is injected into the fluidic device of this embodiment.
The fluid injected from the fluid inlet 2201 is sent to the branch channel 2200. The fluid that has reached the connecting portion 3000 is sent to the channel where it flows most easily, so it first flows into the tributary channel 2300 in the straight direction instead of the main channel 1000.
Next, the fluid also flows into the main flow path 1000 and the tributary flow path 2100 and reaches the fluid outlet 1001.
 このように、複数の支流路を備えた従来の流体デバイスでは、1つの支流路から注入した流体は、他の支流路に逆流して滞留したり、あるいは主流路から接続部に向けて容易に逆流するようになっている。
 このため、従来の流体デバイスは、このままでは検査に適切に使用できないという問題があった。
As described above, in conventional fluidic devices equipped with a plurality of tributary channels, fluid injected from one tributary channel may flow back into other tributary channels and stagnate there, or easily flow from the main channel toward the connection part. It's starting to flow backwards.
For this reason, there has been a problem in that conventional fluidic devices cannot be used appropriately for testing as they are.
 図15(A)は、このような従来の流体デバイスにおける流入口と流出口の配置を示す模式図である。
 従来の流体デバイスは、このままでは検査に適切に使用できないため、図15(B)に示すように、逆流を防止するためのバルブを配置することが必要であった。
FIG. 15(A) is a schematic diagram showing the arrangement of an inlet and an outlet in such a conventional fluidic device.
Since the conventional fluidic device cannot be used properly for testing as it is, it was necessary to arrange a valve to prevent backflow, as shown in FIG. 15(B).
 図15(B)の例では、各流入口と接続部との間にそれぞれバルブが配置されている。このように従来の流体デバイスであっても、バルブを用いることによって、支流路や接続部への逆流が生じないようにすることは可能である。
 しかしながら、流体デバイスにおけるこのような逆流防止のみを目的とするバルブの設置は、流体デバイスの構成を徒に複雑化する原因となり、流体デバイスの製造においては大きな問題となっていた。
In the example of FIG. 15(B), a valve is disposed between each inlet and the connection portion. In this way, even in conventional fluid devices, by using valves, it is possible to prevent backflow to the tributary channels and connections.
However, installing such a valve in a fluid device solely for the purpose of preventing backflow causes the configuration of the fluid device to become unnecessarily complicated, which has been a major problem in the manufacture of the fluid device.
 次に、本実施形態の流体デバイスの変形例について、図4~9を参照して説明する。
 なお、これらの図において、図1~3を参照して説明した本実施形態の流体デバイスと同様の構成については、同一の符号を付している。
Next, modified examples of the fluidic device of this embodiment will be described with reference to FIGS. 4 to 9.
Note that in these figures, the same reference numerals are given to the same components as those of the fluidic device of this embodiment described with reference to FIGS. 1 to 3.
 まず、図4を参照して、本実施形態の流体デバイスの変形例1について説明する。変形例1は、支流路延長部を有しておらず、支流路に流体流入口が備えられている点で、上述した本実施形態の流体デバイスと相違している。その他の点については、同流体デバイスと同様である。
 変形例1の流体デバイスは、5枚の基板を接合して形成されている。
First, with reference to FIG. 4, a first modification of the fluid device of this embodiment will be described. Modification 1 differs from the fluid device of the present embodiment described above in that it does not have a tributary channel extension, and the tributary channel is provided with a fluid inlet. In other respects, it is similar to the same fluidic device.
The fluidic device of Modification 1 is formed by bonding five substrates.
 第一の基板(K1-1)は、最上面側を構成するフィルムであり、流体流入口212,222,232と流体流出口101が形成されている。
 第二の基板(K2-1)は、上面側の両面テープ(又はフィルム)であり、支流路20(21,22,23)が形成されている。また、流体流入口212,222,232と流体流出口101が形成されている。
The first substrate (K1-1) is a film forming the uppermost surface side, and has fluid inlets 212, 222, 232 and a fluid outlet 101 formed therein.
The second substrate (K2-1) is a double-sided tape (or film) on the upper surface side, and has branch channels 20 (21, 22, 23) formed therein. Further, fluid inlets 212, 222, 232 and a fluid outlet 101 are formed.
 第三の基板(K3-1)は、樹脂基板であり、主流路10と流体流出口101、及び接続部30が形成されている。
 主流路10は、基板の裏面側に凹部形状の流路として形成されている。また、接続部30と流体流出口101は、基板を貫通して形成されている。
The third substrate (K3-1) is a resin substrate, and has a main channel 10, a fluid outlet 101, and a connecting portion 30 formed therein.
The main flow path 10 is formed as a recessed flow path on the back side of the substrate. Further, the connecting portion 30 and the fluid outlet 101 are formed to penetrate the substrate.
 第四の基板(K4-1)は、下面側の両面テープ(又はフィルム)であり、主流路10が形成されている。
 第五の基板(K5-1)は、最下面側を構成するフィルムであり、何も形成されておらず、第四の基板(K4-1)に形成された主流路10を封止している。
The fourth substrate (K4-1) is a double-sided tape (or film) on the lower surface side, and has a main flow path 10 formed therein.
The fifth substrate (K5-1) is a film constituting the bottom surface side, has nothing formed thereon, and seals the main channel 10 formed on the fourth substrate (K4-1). There is.
 このような変形例1の流体デバイスによれば、流体流入口212,222,232から注入された流体は、支流路21,22,23へ送液され、接続部30を介して主流路10に送液されて流体流出口101から排出される。 According to the fluid device of Modification 1, the fluid injected from the fluid inlets 212, 222, 232 is sent to the tributary channels 21, 22, 23, and then flows into the main channel 10 via the connection part 30. The liquid is fed and discharged from the fluid outlet 101.
 ここで、変形例1の流体デバイスは、支流路20の流路抵抗が接続部30の流路抵抗よりも大きく、接続部30の流路抵抗が主流路10の流路抵抗と同一又はより大きくなっている。このため、主流路10から接続部30へ流体が逆流したり、接続部30から支流路21,22,23へ流体が逆流することがない。
 したがって、このような流体デバイスによれば、試薬を適切に送液することができるため、流体デバイスを用いた検査を好適に実施することが可能となる。
Here, in the fluid device of Modification 1, the flow path resistance of the tributary flow path 20 is greater than the flow path resistance of the connection portion 30, and the flow path resistance of the connection portion 30 is the same as or greater than the flow path resistance of the main flow path 10. It has become. Therefore, fluid does not flow backward from the main channel 10 to the connecting portion 30, and fluid does not flow backward from the connecting portion 30 to the branch channels 21, 22, and 23.
Therefore, according to such a fluidic device, a reagent can be appropriately delivered, so that a test using a fluidic device can be suitably carried out.
 次に、図5を参照して、本実施形態の流体デバイスの変形例2について説明する。変形例2は、上述した本実施形態の流体デバイスと支流路延長部の形状が相違しており、その他の点については同流体デバイスと同様のものであるが、より詳細に説明する。
 変形例2の流体デバイスは、5枚の基板を接合して形成されている。
Next, with reference to FIG. 5, a second modification of the fluid device of this embodiment will be described. Modification 2 is different from the fluid device of the present embodiment described above in the shape of the tributary channel extension, and is otherwise similar to the same fluid device, but will be described in more detail.
The fluidic device of Modification 2 is formed by bonding five substrates.
 第一の基板(K1-2)は、封止用のフィルム又は樹脂基板である。第二の基板(K2-2)は、支流路20が形成された両面テープである。第三の基板(K3-2)は、主流路10と接続部30と支流路延長部が形成された樹脂基板である。第四の基板(K4-2)は、主流路10と支流路延長部が形成された両面テープである。第五の基板(K5-2)は、封止用のフィルム又は樹脂基板である。 The first substrate (K1-2) is a sealing film or resin substrate. The second substrate (K2-2) is a double-sided tape on which branch channels 20 are formed. The third substrate (K3-2) is a resin substrate on which the main flow path 10, the connecting portion 30, and the branch flow path extension portion are formed. The fourth substrate (K4-2) is a double-sided tape on which the main channel 10 and the branch channel extensions are formed. The fifth substrate (K5-2) is a sealing film or resin substrate.
 具体的には、第二の基板(K2-2)には、複数の支流路20(21,22,23)が貫通して形成されている。そして、第二の基板(K2-2)の一方の表面側に、第一の基板(K1-2)が接合されている。
 また、第二の基板(K2-2)の他方の表面側に、第三の基板(K3-2)が接合されている。
Specifically, a plurality of branch channels 20 (21, 22, 23) are formed through the second substrate (K2-2). The first substrate (K1-2) is bonded to one surface side of the second substrate (K2-2).
Further, a third substrate (K3-2) is bonded to the other surface side of the second substrate (K2-2).
 第三の基板(K3-2)において、主流路10が、第二の基板(K2-2)に対する反対表面側に接続部30を介して支流路20に連通して備えられている。
 また、第三の基板(K3-2)には、支流路20に連通部211,221,231を介してそれぞれ連通する複数の支流路延長部41,42,43が備えられている。
In the third substrate (K3-2), the main channel 10 is provided on the opposite surface side to the second substrate (K2-2) so as to communicate with the branch channel 20 via the connecting portion 30.
Further, the third substrate (K3-2) is provided with a plurality of tributary channel extensions 41, 42, and 43 that communicate with the tributary channel 20 via communicating portions 211, 221, and 231, respectively.
 さらに、第三の基板(K3-2)の主流路10が備えられた側に第四の基板(K4-2)が接合されている。
 そして、第一の基板(K1-2)、第二の基板(K2-2)、及び第三の基板(K3-2)に、支流路延長部41,42,43にそれぞれ連通する流体流入口411,421,431が貫通して形成されており、また主流路10に連通する流体流出口101が貫通して形成されている。
Furthermore, a fourth substrate (K4-2) is bonded to the side of the third substrate (K3-2) on which the main flow path 10 is provided.
Fluid inlets are provided in the first substrate (K1-2), the second substrate (K2-2), and the third substrate (K3-2), each communicating with the tributary channel extensions 41, 42, and 43. 411, 421, and 431 are formed to penetrate therethrough, and a fluid outlet 101 communicating with the main flow path 10 is formed to penetrate therethrough.
 また、第四の基板(K4-2)には、主流路10、及び支流路延長部41,42,43が貫通して形成されている。
 そして、第四の基板(K4-2)における第三の基板(K3-2)に対する反対表面側に第五の基板(K5-2)が備えられている。
 なお、本変形例1では、第四の基板(K4-2)を用いて第三の基板(K3-2)と第五の基板(K5-2)を接合する構成としているが、第四の基板(K4-2)を省略して、その他の接合方法により、第三の基板(K3-2)と第五の基板(K5-2)を接合する構成としてもよい。
Further, the main flow path 10 and the branch flow path extensions 41, 42, and 43 are formed to penetrate through the fourth substrate (K4-2).
A fifth substrate (K5-2) is provided on the opposite surface of the fourth substrate (K4-2) to the third substrate (K3-2).
In addition, in this modification 1, the third substrate (K3-2) and the fifth substrate (K5-2) are bonded using the fourth substrate (K4-2), but the fourth substrate (K4-2) is The structure may be such that the substrate (K4-2) is omitted and the third substrate (K3-2) and the fifth substrate (K5-2) are bonded by another bonding method.
 このような変形例2の流体デバイスによれば、流体流入口411,421,431から注入された流体は、それぞれ支流路延長部41,42,43を経由して支流路21,22,23へ送液され、接続部30を介して主流路10に送液されて流体流出口101から排出される。 According to the fluid device of Modification 2, the fluid injected from the fluid inlets 411, 421, 431 flows to the tributary channels 21, 22, 23 via the tributary channel extensions 41, 42, 43, respectively. The liquid is sent to the main channel 10 via the connection part 30 and discharged from the fluid outlet 101.
 また、変形例1と同様に、支流路20の流路抵抗が接続部30の流路抵抗よりも大きく、接続部30の流路抵抗が主流路10の流路抵抗と同一又はより大きくなっているため、主流路10から接続部30へ流体が逆流したり、接続部30から支流路21,22,23へ流体が逆流することがない。
 したがって、このような流体デバイスによれば、試薬を適切に送液することができるため、流体デバイスを用いた検査を好適に実施することが可能となる。
Further, similarly to Modification Example 1, the flow path resistance of the tributary flow path 20 is greater than the flow path resistance of the connecting portion 30, and the flow path resistance of the connecting portion 30 is the same as or greater than the flow path resistance of the main flow path 10. Therefore, fluid does not flow backward from the main flow path 10 to the connecting portion 30, and fluid does not flow backward from the connecting portion 30 to the tributary flow paths 21, 22, and 23.
Therefore, according to such a fluidic device, a reagent can be appropriately delivered, so that a test using a fluidic device can be suitably carried out.
 次に、図6を参照して、本実施形態の流体デバイスの変形例3について説明する。変形例3は、3枚の基板を接合して形成されている点で、上述した本実施形態の流体デバイスと相違している。
 第一の基板(K1-3)は、封止用のフィルム又は樹脂基板である。第二の基板(K2-3)は、主流路10と支流路20と接続部30と支流路延長部40が形成された樹脂基板である。第三の基板(K3-3)は、封止用のフィルム又は樹脂基板である。
Next, with reference to FIG. 6, a third modification of the fluidic device of this embodiment will be described. Modification 3 is different from the fluid device of the present embodiment described above in that it is formed by bonding three substrates.
The first substrate (K1-3) is a sealing film or resin substrate. The second substrate (K2-3) is a resin substrate on which the main channel 10, the tributary channel 20, the connection part 30, and the tributary channel extension part 40 are formed. The third substrate (K3-3) is a sealing film or resin substrate.
 具体的には、第二の基板(K2-3)の一方の表面に複数の支流路20(21,22,23)が形成されている。また、第二の基板(K2-3)の他方の表面に主流路10が形成されている。そして、第二の基板(K2-3)の支流路20が形成された表面側に、第一の基板(K1-3)が接合されている。 Specifically, a plurality of branch channels 20 (21, 22, 23) are formed on one surface of the second substrate (K2-3). Further, a main channel 10 is formed on the other surface of the second substrate (K2-3). The first substrate (K1-3) is bonded to the surface side of the second substrate (K2-3) on which the tributary channel 20 is formed.
 第二の基板(K2-3)において、主流路10は接続部30を介して支流路20に連通して備えられている。
 また、第二の基板(K2-3)の主流路が形成された表面側には、支流路20に連通部211,221,231を介してそれぞれ連通する複数の支流路延長部40(41,42,43)が備えられている。
In the second substrate (K2-3), the main flow path 10 is provided to communicate with the branch flow path 20 via the connecting portion 30.
In addition, on the surface side of the second substrate (K2-3) where the main flow path is formed, there are a plurality of tributary flow path extension portions 40 (41, 42, 43) are provided.
 さらに、第二の基板(K2-3)の主流路10が備えられた側に第三の基板(K3-3)が接合されている。
 そして、第一の基板(K1-3)に、支流路延長部41,42,43にそれぞれ連通する流体流入口411,421,431が貫通して形成されており、また主流路10に連通する流体流出口101が貫通して形成されている。
Further, a third substrate (K3-3) is bonded to the side of the second substrate (K2-3) on which the main flow path 10 is provided.
Fluid inlets 411, 421, and 431 are formed through the first substrate (K1-3) to communicate with the branch channel extensions 41, 42, and 43, respectively, and to communicate with the main channel 10. A fluid outlet 101 is formed therethrough.
 このような変形例3の流体デバイスによれば、流体流入口411,421,431から注入された流体は、それぞれ支流路延長部41,42,43を経由して支流路21,22,23へ送液され、接続部30を介して主流路10に送液されて流体流出口101から排出される。 According to the fluid device of Modification 3, the fluid injected from the fluid inlets 411, 421, 431 flows to the tributary channels 21, 22, 23 via the tributary channel extensions 41, 42, 43, respectively. The liquid is sent to the main channel 10 via the connection part 30 and discharged from the fluid outlet 101.
 また、変形例1と同様に、支流路20の流路抵抗が接続部30の流路抵抗よりも大きく、接続部30の流路抵抗が主流路10の流路抵抗と同一又はより大きくなっているため、主流路10から接続部30へ流体が逆流したり、接続部30から支流路21,22,23へ流体が逆流することがない。このため、試薬を適切に送液することができ、流体デバイスを用いた検査を好適に実施することが可能になっている。 Further, similarly to Modification Example 1, the flow path resistance of the tributary flow path 20 is greater than the flow path resistance of the connecting portion 30, and the flow path resistance of the connecting portion 30 is the same as or greater than the flow path resistance of the main flow path 10. Therefore, fluid does not flow backward from the main flow path 10 to the connecting portion 30, and fluid does not flow backward from the connecting portion 30 to the tributary flow paths 21, 22, and 23. Therefore, reagents can be delivered appropriately, and tests using fluidic devices can be suitably carried out.
 次に、図7を参照して、本実施形態の流体デバイスの変形例4について説明する。変形例4は、支流路延長部を有しておらず、支流路に流体流入口が備えられている点で、上述した変形例3と相違する。その他の点については、同流体デバイスと同様である。
 変形例4の流体デバイスも、3枚の基板を接合して形成されている。
 第一の基板(K1-4)は、封止用のフィルム又は樹脂基板である。第二の基板(K2-4)は、支流路20と主流路10と接続部30が形成された樹脂基板である。第三の基板(K3-4)は、封止用のフィルム又は樹脂基板である。
Next, with reference to FIG. 7, a fourth modification of the fluidic device of this embodiment will be described. Modification 4 differs from Modification 3 described above in that it does not have a tributary channel extension, and the tributary channel is provided with a fluid inlet. In other respects, it is similar to the same fluidic device.
The fluid device of Modification 4 is also formed by bonding three substrates.
The first substrate (K1-4) is a sealing film or resin substrate. The second substrate (K2-4) is a resin substrate on which the tributary channel 20, the main channel 10, and the connecting portion 30 are formed. The third substrate (K3-4) is a sealing film or resin substrate.
 具体的には、第二の基板(K2-4)の一方の表面に複数の支流路20(21,22,23)が形成されている。また、第二の基板(K2-4)の他方の表面に主流路10が形成されている。そして、第二の基板(K2-4)の支流路20が形成された表面側に、第一の基板(K1-4)が接合されている。 Specifically, a plurality of branch channels 20 (21, 22, 23) are formed on one surface of the second substrate (K2-4). Further, a main channel 10 is formed on the other surface of the second substrate (K2-4). The first substrate (K1-4) is bonded to the surface side of the second substrate (K2-4) on which the tributary channel 20 is formed.
 第二の基板(K2-4)において、主流路10は接続部30を介して支流路20に連通して備えられている。
 また、第二の基板(K2-4)の主流路10が備えられた側に第三の基板(K3-4)が接合されている。
 そして、第一の基板(K1-4)に、支流路21,22,23にそれぞれ連通する流体流入口212,222,232が貫通して形成されており、また主流路10に連通する流体流出口101が貫通して形成されている。
In the second substrate (K2-4), the main flow path 10 is provided to communicate with the branch flow path 20 via the connecting portion 30.
Furthermore, a third substrate (K3-4) is bonded to the side of the second substrate (K2-4) on which the main flow path 10 is provided.
Fluid inlets 212, 222, and 232 are formed through the first substrate (K1-4) to communicate with the tributary channels 21, 22, and 23, respectively, and fluid inlets that communicate with the main channel 10 are formed through the first substrate (K1-4). An outlet 101 is formed therethrough.
 このような変形例4の流体デバイスによれば、流体流入口212,222,232から注入された流体は、支流路21,22,23へ送液され、接続部30を介して主流路10に送液されて流体流出口101から排出される。
 このとき、主流路10から接続部30へ流体が逆流したり、接続部30から支流路21,22,23へ流体が逆流することがないため、試薬を適切に送液することができ、流体デバイスを用いた検査を好適に実施することが可能である。
According to the fluid device of Modification 4, the fluid injected from the fluid inlets 212, 222, 232 is sent to the tributary channels 21, 22, 23, and is sent to the main channel 10 via the connection part 30. The liquid is fed and discharged from the fluid outlet 101.
At this time, since the fluid does not flow backward from the main channel 10 to the connection section 30 or from the connection section 30 to the tributary channels 21, 22, 23, the reagent can be appropriately delivered, and the fluid It is possible to suitably carry out an inspection using the device.
 次に、図8を参照して、本実施形態の流体デバイスの変形例5について説明する。変形例5は、2枚の基板を接合して形成されている点で、上述した実施形態及びその変形例と相違する。
 第一の基板(K1-5)は、封止用のフィルム又は樹脂基板である。第二の基板(K2-5)は、主流路10と支流路20と接続部30と支流路延長部40が形成された樹脂基板である。
Next, with reference to FIG. 8, a fifth modification of the fluid device of this embodiment will be described. Modification 5 differs from the above-described embodiment and its modification in that it is formed by bonding two substrates.
The first substrate (K1-5) is a sealing film or resin substrate. The second substrate (K2-5) is a resin substrate on which the main channel 10, the tributary channel 20, the connection part 30, and the tributary channel extension part 40 are formed.
 具体的には、第二の基板(K2-5)の一方の表面側に、主流路10と支流路20(21,22,23)と接続部30が備えられている。また、第二の基板(K2-5)の同表面側に、支流路21,22,23に連通部211,221,231を介してそれぞれ連通する支流路延長部40(41,42,43)が備えられている。
 そして、第二の基板(K2-5)の主流路10と支流路20と接続部30と支流路延長部40が備えられた表面側に第一の基板(K1-5)が接合されている。
 また、第一の基板(K1-5)において、支流路延長部41,42,43に連通する流体流入口411,421,431が貫通して形成されており、また主流路10に連通する流体流出口101が貫通して形成されている。
Specifically, the main flow path 10, the branch flow paths 20 (21, 22, 23), and the connection portion 30 are provided on one surface side of the second substrate (K2-5). Further, on the same surface side of the second substrate (K2-5), tributary flow path extension portions 40 (41, 42, 43) are connected to the tributary flow paths 21, 22, 23 via communication portions 211, 221, 231, respectively. is provided.
The first substrate (K1-5) is bonded to the surface side of the second substrate (K2-5) on which the main flow path 10, the tributary flow path 20, the connecting portion 30, and the tributary flow path extension portion 40 are provided. .
Further, in the first substrate (K1-5), fluid inlets 411, 421, 431 communicating with the tributary channel extensions 41, 42, 43 are formed penetratingly, and fluid inlets communicating with the main channel 10 are formed. An outflow port 101 is formed to penetrate therethrough.
 このような変形例5の流体デバイスにおいても、流体流入口411,421,431から注入した流体は、それぞれ支流路延長部41,42,43を経由して支流路21,22,23へ送液され、接続部30を介して主流路10に送液されて流体流出口101から排出される。
 すなわち、主流路10から接続部30へ流体が逆流せず、また接続部30から支流路21,22,23へ流体が逆流することがないため、試薬を適切に送液することができ、流体デバイスを用いた検査を好適に実施することが可能である。
Also in the fluid device of Modification 5, the fluid injected from the fluid inlets 411, 421, 431 is sent to the tributary channels 21, 22, 23 via the tributary channel extensions 41, 42, 43, respectively. The liquid is sent to the main flow path 10 via the connection part 30 and discharged from the fluid outlet 101.
That is, since the fluid does not flow back from the main channel 10 to the connection section 30, and the fluid does not flow back from the connection section 30 to the tributary channels 21, 22, and 23, the reagent can be appropriately delivered, and the fluid It is possible to suitably carry out an inspection using the device.
 なお、変形例5において、支流路延長部40を無くし、支流路21,22,23における連通部211,221,231の位置に流体流入口212,222,232を設けると共に、流体流入口212,222,232が第一の基板(K1-5)を貫通して備えられた構成にすることも可能である。 In addition, in modification 5, the tributary channel extension part 40 is eliminated, and fluid inlets 212, 222, 232 are provided at the positions of the communication parts 211, 221, 231 in the tributary channels 21, 22, 23, and the fluid inlets 212, It is also possible to adopt a configuration in which the first substrate (K1-5) is provided with the first substrate (K1-5) penetrated therethrough.
 この場合は、流体流入口212,222,232から注入した流体は、支流路21,22,23へ送液され、接続部30を介して主流路10に送液されて流体流出口101から排出される。
 このようにしても、主流路10から接続部30へ流体が逆流せず、また接続部30から支流路21,22,23へ流体が逆流することがないため、試薬を適切に送液することができ、流体デバイスを用いた検査を好適に実施することが可能である。
In this case, the fluid injected from the fluid inlets 212, 222, 232 is sent to the tributary channels 21, 22, 23, then to the main channel 10 via the connection part 30, and then discharged from the fluid outlet 101. be done.
Even in this case, the fluid does not flow back from the main channel 10 to the connection section 30, and the fluid does not flow back from the connection section 30 to the tributary channels 21, 22, and 23, so that the reagent can be properly delivered. Therefore, it is possible to suitably perform tests using a fluidic device.
 次に、図9を参照して、本実施形態の流体デバイスの変形例6について説明する。変形例6は、試薬供給用又は混合用のチューブ又はカートリッジを備えている点で、上述した実施形態及びその変形例と相違する。
 変形例6の流体デバイスは、3枚の基板を接合して形成されている。
 図9において、第一の基板(K1-6)は、試薬供給用又は混合用のチューブ又はカートリッジである。第二の基板(K2-6)は、支流路20と接続部30が形成された両面テープである。第三の基板(K3-6)は、封止用のフィルム又は樹脂基板である。
Next, with reference to FIG. 9, a sixth modification of the fluid device of this embodiment will be described. Modification 6 differs from the above-described embodiment and its modifications in that it includes a tube or cartridge for supplying or mixing reagents.
The fluid device of Modification 6 is formed by bonding three substrates.
In FIG. 9, the first substrate (K1-6) is a tube or cartridge for supplying or mixing reagents. The second substrate (K2-6) is a double-sided tape on which the tributary channel 20 and the connecting portion 30 are formed. The third substrate (K3-6) is a sealing film or resin substrate.
 具体的には、第一の基板(K1-6)において、主流路10と、複数の支流路21,22,23にそれぞれ連通する複数の支流路延長部41,42,43が貫通して備えられている。支流路延長部41,42,43は、試薬供給用のチューブに相当する。また、主流路10は、試薬混合用のチューブに相当する。 Specifically, the first substrate (K1-6) is provided with a plurality of tributary channel extensions 41, 42, 43 penetrating the main channel 10 and communicating with the plurality of tributary channels 21, 22, 23, respectively. It is being The branch channel extensions 41, 42, and 43 correspond to tubes for supplying reagents. Further, the main channel 10 corresponds to a tube for mixing reagents.
 また、第二の基板(K2-6)において、複数の支流路21,22,23と、主流路10に連通する接続部30と、支流路延長部41,42,43にそれぞれ連通する連通部211,221,231が備えられている。
 そして、第二の基板(K2-6)における第一の基板(K1-6)に対する反対表面側に第三の基板(K3-6)が備えられている。
 なお、第二の基板(K2-6)を樹脂基板により構成し、支流路20と接続部30と連通部211,221,231を第二の基板(K2-6)における第一の基板(K1-6)の表面側に形成して、第三の基板(K3-6)を省略することもできる。
Further, in the second substrate (K2-6), a plurality of tributary channels 21, 22, 23, a connecting portion 30 communicating with the main channel 10, and a communication portion communicating with the tributary channel extension portions 41, 42, 43, respectively. 211, 221, and 231 are provided.
A third substrate (K3-6) is provided on the opposite surface of the second substrate (K2-6) to the first substrate (K1-6).
The second substrate (K2-6) is made of a resin substrate, and the tributary flow path 20, the connecting portion 30, and the communication portions 211, 221, 231 are connected to the first substrate (K1) in the second substrate (K2-6). -6), and the third substrate (K3-6) can be omitted.
 このような変形例6の流体デバイスによれば、流体流入口411,421,431を介して支流路延長部41,42,43にそれぞれ注入された試薬は、支流路21,22,23へ送液され、接続部30を介して主流路10に送液され、流体流出口101から排出させることができる。 According to the fluid device of Modification 6, the reagents injected into the tributary channel extensions 41, 42, and 43 through the fluid inlets 411, 421, and 431 are sent to the tributary channels 21, 22, and 23, respectively. The liquid can be sent to the main channel 10 via the connection part 30 and discharged from the fluid outlet 101.
 このとき、支流路20の流路抵抗が接続部30の流路抵抗よりも大きく、接続部30の流路抵抗が主流路10の流路抵抗と同一又はより大きくなっているため、試薬が主流路10から接続部30や支流路21,22,23、及び支流路延長部41,42,43へ逆流することがない。
 したがって、変形例6の流体デバイスによれば、試薬を適切な順序で混合することなどができるため、流体デバイスを用いた検査を適切に行うことが可能になっている。
At this time, the channel resistance of the tributary channel 20 is greater than the channel resistance of the connection section 30, and the channel resistance of the connection section 30 is the same as or greater than the channel resistance of the main channel 10, so that the reagent is There is no backflow from the channel 10 to the connecting portion 30, the tributary channels 21, 22, 23, and the tributary channel extensions 41, 42, 43.
Therefore, according to the fluidic device of Modification 6, reagents can be mixed in an appropriate order, and therefore tests using the fluidic device can be appropriately performed.
 さらに、以上説明した変形例1~変形例6の流体デバイスの全部又は一部の構成を組み合わせることによって、本実施形態における他の変形例の流体デバイスを構成することも好ましい。 Furthermore, it is also preferable to configure fluid devices of other modifications of the present embodiment by combining all or part of the configurations of the fluid devices of Modifications 1 to 6 described above.
 また、本実施形態の流体デバイスは、図示しないが、主流路10の一部に反応部が備えられた構成とすることが好ましい。なお、支流路延長部41,42,43の一部に反応部を配置させることもできる。
 このとき、本実施形態の流体デバイスにおける反応部の表面自体にプローブなど(反応用物質)を固定化して、検査部として機能させることが可能である。
Further, although not shown in the drawings, the fluid device of this embodiment preferably has a configuration in which a part of the main flow path 10 is provided with a reaction section. In addition, a reaction part can also be arrange|positioned in a part of branch channel extension part 41,42,43.
At this time, it is possible to immobilize a probe or the like (substance for reaction) on the surface of the reaction section itself in the fluidic device of this embodiment to function as an inspection section.
 また、反応部を凹部として形成して、この反応部にプローブが固定化されたDNAマイクロアレイなどの担体を配置し(このような担体を保持する反応部を担体保持部と称する場合がある。)、検査部として機能させることもできる。
 さらに、担体保持部を、主流路10が備えられた基板を貫通する穿孔(貫通孔)として形成することも好ましい。
Further, the reaction part is formed as a recess, and a carrier such as a DNA microarray on which probes are immobilized is placed in this reaction part (the reaction part that holds such a carrier is sometimes referred to as a carrier holding part). , it can also function as an inspection section.
Furthermore, it is also preferable to form the carrier holding portion as a perforation (through hole) that penetrates the substrate provided with the main flow path 10.
 さらに、担体としては、DNAマイクロアレイやDNAチップとすることができる。また、担体は、DNAを検出するものに限られず、その他の物質を検出するためのマイクロアレイやチップなどであってもよい。
 本実施形態において、担体としてDNAマイクロアレイを用いる場合、このDNAマイクロアレイは、プローブを用いて、既存の一般的な方法で製造することができる。
Furthermore, the carrier can be a DNA microarray or a DNA chip. Further, the carrier is not limited to one for detecting DNA, but may also be a microarray, a chip, etc. for detecting other substances.
In this embodiment, when a DNA microarray is used as a carrier, this DNA microarray can be manufactured using a probe using an existing general method.
 例えば、このDNAマイクロアレイとして、貼り付け型のDNAチップを作成する場合は、DNAスポッターによりプローブをガラス基板上に固定化して、各プローブに対応するスポットを形成することにより作成することができる。また、合成型DNAチップを作成する場合は、光リソグラフィ技術により、ガラス基板上で上記配列を備えた一本鎖オリゴDNAを合成することにより作成することができる。さらに、基板はガラス製に限定されず、プラスチック基板やシリコンウエハー等を用いることもできる。また、基板の形状は平板状のものに限定されず、様々な立体形状のものとすることもでき、その表面に化学反応が可能となるように官能基を導入したものなどを用いることもできる。 For example, when creating a stick-on DNA chip as this DNA microarray, it can be created by immobilizing probes on a glass substrate using a DNA spotter and forming spots corresponding to each probe. Furthermore, when creating a synthetic DNA chip, it can be created by synthesizing single-stranded oligo DNA having the above sequence on a glass substrate using optical lithography technology. Furthermore, the substrate is not limited to glass, and may also be a plastic substrate, a silicon wafer, or the like. In addition, the shape of the substrate is not limited to a flat plate, but can also be of various three-dimensional shapes, and substrates with functional groups introduced to the surface to enable chemical reactions can also be used. .
 また、担体としてDNAマイクロアレイを用いる場合、マイクロアレイ用基板に固定化される固体支持体は、核酸(DNA,RNA等)、又はペプチド(オリゴペプチド、ポリペプチド、タンパク質等)を固定化するためのもので、核酸又はペプチドと共有結合し得る官能基を有する。核酸又はペプチドと共有結合し得る官能基としては、当技術分野で公知のものを使用できる。また担体として、表面にダイヤモンドライクカーボン層(DLC)を有するものを用いることも好ましい。 In addition, when using a DNA microarray as a carrier, the solid support immobilized on the microarray substrate is one for immobilizing nucleic acids (DNA, RNA, etc.) or peptides (oligopeptides, polypeptides, proteins, etc.). and has a functional group that can be covalently bonded to a nucleic acid or peptide. As the functional group capable of covalently bonding to a nucleic acid or peptide, those known in the art can be used. It is also preferable to use a carrier having a diamond-like carbon layer (DLC) on its surface.
 反応用物質としては、核酸、タンパク質、糖鎖などの生体物質を好適に用いることができる。具体的には、例えば、DNA、RNA、抗体、レクチン、ビオチン-アビジン等を用いることができる。また、反応用物質として、生体物質以外のもの、例えば、抗体やDNAアプタマーなどの生体物質と結合することが可能な低分子化合物(香気成分、アレルゲンなど)を用いることも可能である。 As the reaction substance, biological materials such as nucleic acids, proteins, sugar chains, etc. can be suitably used. Specifically, for example, DNA, RNA, antibodies, lectins, biotin-avidin, etc. can be used. Furthermore, as the reaction substance, it is also possible to use substances other than biological substances, for example, low-molecular compounds (fragrant components, allergens, etc.) that can bind to biological substances such as antibodies and DNA aptamers.
[流体デバイスの製造方法]
 本実施形態の流体デバイスの製造方法は、上述した本実施形態の流体デバイスを、切削加工、射出成形、ホットエンボス加工、レーザー加工、エッチング加工、又は3Dプリンタ等を用いて形成することを特徴とする。
 本実施形態の流体デバイスは、このような方法により、好適に製造することが可能である。
[Fluid device manufacturing method]
The method for manufacturing a fluidic device of this embodiment is characterized in that the fluidic device of this embodiment described above is formed using cutting, injection molding, hot embossing, laser processing, etching, or a 3D printer. do.
The fluidic device of this embodiment can be suitably manufactured by such a method.
[検査方法]
 次に、図10を参照して、本実施形態の流体デバイスを用いた検査方法について説明する。図10は、本実施形態の流体デバイスを用いて蛍光検出を行う様子を示す模式図である。図10には、加熱装置60に載置された流体デバイスが示されている。この流体デバイスにおける反応部に対面するように、検出装置50が配置されている。
[Inspection method]
Next, with reference to FIG. 10, an inspection method using the fluidic device of this embodiment will be described. FIG. 10 is a schematic diagram showing how fluorescence detection is performed using the fluidic device of this embodiment. In FIG. 10, a fluidic device is shown mounted on a heating device 60. A detection device 50 is arranged so as to face the reaction section in this fluidic device.
 本実施形態の流体デバイスを用いた検査方法では、流体デバイスの反応部に反応用物質が固定化された担体を配置して検査に用いる流体デバイスを準備し、いずれかの流体流入口から試薬を注入して、支流路20と接続部30を経由して主流路10へ送液し、反応部における担体と接触させる。 In the testing method using the fluidic device of this embodiment, the fluidic device used for testing is prepared by placing a carrier on which a reaction substance is immobilized in the reaction part of the fluidic device, and the reagent is injected from one of the fluid inlets. The liquid is injected and sent to the main channel 10 via the branch channel 20 and the connecting part 30, and brought into contact with the carrier in the reaction section.
 試薬には、被検査物質に蛍光物質を結合したものが含まれている。また、担体における反応用物質は、検査対象物と反応することによって、検査対象物を担体に固定する。
 したがって、試薬に検査対象物が含まれていると、検査対象物は担体に捕捉されるため、捕捉された検査対象物の蛍光物質を検出することによって、試薬における検査対象物の有無を判定することができるようになっている。
The reagent contains a substance to be tested bound to a fluorescent substance. Further, the reaction substance in the carrier reacts with the test object to immobilize the test object on the carrier.
Therefore, if the test object is contained in the reagent, the test object is captured by the carrier, and the presence or absence of the test object in the reagent is determined by detecting the fluorescent substance of the captured test object. It is now possible to do so.
 このとき、流体デバイスの反応部における試薬の温度が、検査対象物と反応用物質との反応に適した温度に保たれるように、加熱装置60によって流体デバイスを加熱する。
 検査対象物と反応用物質の反応完了後、試薬を投入した流体流入口とは別の流体流入口から洗浄液を注入しつつ、流体流出口101から試薬と洗浄液を排出して、反応部内における試薬を洗浄液に置換する。
 そして、反応部に配置された担体に対して、光源51から蛍光の励起用のレーザーを照射し、蛍光検出部52によって、担体における反応用物質と反応した検査対象物に結合する蛍光物質から励起された蛍光を検出する。
At this time, the fluid device is heated by the heating device 60 so that the temperature of the reagent in the reaction section of the fluid device is maintained at a temperature suitable for the reaction between the test object and the reaction substance.
After the reaction between the test object and the reaction substance is completed, the reagent and cleaning liquid are discharged from the fluid outlet 101 while injecting the cleaning liquid from a fluid inlet different from the fluid inlet into which the reagent was input, thereby removing the reagent in the reaction section. Replace with cleaning solution.
Then, a laser for excitation of fluorescence is irradiated from the light source 51 onto the carrier disposed in the reaction section, and the fluorescence detection section 52 generates excitation from the fluorescent substance bonded to the test object that has reacted with the reaction substance on the carrier. Detect the emitted fluorescence.
 このような本実施形態の検査方法によれば、本実施形態の流体デバイスにおいて流体の逆流が生じないため、検査を好適に行うことが可能である。 According to the testing method of this embodiment, no backflow of fluid occurs in the fluidic device of this embodiment, so that testing can be suitably performed.
[検査システム]
 次に、図11を参照して、本実施形態の検査システムについて説明する。図11は、本実施形態の検査システムの構成を示す模式図である。
 図11に示すように、本実施形態の検査システム70は、流体デバイス71と、試薬供給部72と、廃液排出部73と、加熱装置74と、検出装置75と、送液制御部76を有している。
[Inspection system]
Next, referring to FIG. 11, the inspection system of this embodiment will be described. FIG. 11 is a schematic diagram showing the configuration of the inspection system of this embodiment.
As shown in FIG. 11, the inspection system 70 of this embodiment includes a fluid device 71, a reagent supply section 72, a waste liquid discharge section 73, a heating device 74, a detection device 75, and a liquid feeding control section 76. are doing.
 流体デバイス71は、本実施形態に係る流体デバイスである。
 試薬供給部72は、試薬が充填された容器やチューブなどにより構成される。試薬としては、例えば検査対象物であるDNAを含むハイブリダイゼーションバッファーなどが用いられる。また、ハイブリダイゼーション後、流体デバイス71からバッファーを洗い流すための洗浄液も用いられる。
 廃液排出部73は、流体デバイス71における反応後、流体デバイス71からの廃液を貯留する容器やチューブなどにより構成される。
The fluid device 71 is a fluid device according to this embodiment.
The reagent supply section 72 is composed of a container, a tube, or the like filled with a reagent. As the reagent, for example, a hybridization buffer containing DNA, which is the object to be tested, is used. A washing solution is also used to wash away the buffer from the fluidic device 71 after hybridization.
The waste liquid discharge section 73 is constituted by a container, a tube, or the like that stores the waste liquid from the fluid device 71 after the reaction in the fluid device 71 .
 加熱装置74は、流体デバイス71を加熱して、反応部における試薬の温度を反応に適した温度に調節する。この加熱装置74としては、ヒーターや金属製のステージを用いて構成することができる。具体的には、例えばペルチェ式ヒーターを用いることができる。また、必要に応じて冷却させるために、冷却ファンなどの冷却装置を併せて備えることも好ましい。 The heating device 74 heats the fluidic device 71 to adjust the temperature of the reagent in the reaction section to a temperature suitable for the reaction. This heating device 74 can be configured using a heater or a metal stage. Specifically, for example, a Peltier type heater can be used. It is also preferable to also include a cooling device such as a cooling fan for cooling as necessary.
 検出装置75は、図10の検出装置50に相当するものであり、試薬に含まれる蛍光物質の蛍光を励起する光を照射する光源と、発生した蛍光を検出する蛍光検出部とを備えている。
 すなわち、光源が流体デバイス71の担体保持部に配置された担体に励起レーザーを照射して、蛍光検出部が担体に固定化された反応用物質に結合した試薬の蛍光色素から放出される蛍光を検出して数値化する。
The detection device 75 corresponds to the detection device 50 in FIG. 10, and includes a light source that irradiates light that excites the fluorescence of the fluorescent substance contained in the reagent, and a fluorescence detection unit that detects the generated fluorescence. .
That is, a light source irradiates an excitation laser onto a carrier disposed in a carrier holding section of the fluidic device 71, and a fluorescence detection section detects fluorescence emitted from a fluorescent dye of a reagent bound to a reaction substance immobilized on the carrier. Detect and quantify.
 送液制御部76は、試薬供給部72から流体デバイス71への試薬の送液を制御する。送液制御部76は、流体を流すためにアクチュエータとして空気圧を用いるニューマチック型、蠕動運動型、加熱による気体の膨張を利用するサーモニューマチック型、静電引力型、電磁石型、ピエゾ型、バイメタル型、形状記憶合金型、電圧駆動型などがあげられる。具体的には、例えば流路内を加圧するポンプ、ペリスタポンプ、シリンジポンプ等を好適に用いることができる。 The liquid feeding control section 76 controls the feeding of the reagent from the reagent supply section 72 to the fluid device 71. The liquid feeding control unit 76 may be a pneumatic type that uses air pressure as an actuator to flow fluid, a peristaltic type, a thermopneumatic type that uses gas expansion due to heating, an electrostatic attraction type, an electromagnetic type, a piezo type, or a bimetallic type. Types include molds, shape memory alloy types, and voltage-driven types. Specifically, for example, a pump that pressurizes the inside of a flow path, a peristaltic pump, a syringe pump, etc. can be suitably used.
 また、本実施形態の検査システム70において、バルブ制御部77と制御装置78を備えることも好ましい。
 バルブ制御部77は、流体デバイス71にバルブ部が備えられている場合、バルブ部を制御することによって流路に対して外部から力を与え、流路の開閉、切替、流量調節を行うことができる。バルブ制御部77は、アクチュエータにより可動部を動かして流路を変形・遮断する能動型と、機械的構造や流路寸法、表面親水性により流れの方向を規定する受動型のものがあげられる。アクチュエータとしては、空気圧を用いるニューマチック型、加熱による気体の膨張を利用するサーモニューマチック型、静電引力型、電磁石型、ピエゾ型、バイメタル型、形状記憶合金型、おもりやバネを用いる挟持型などがあげられ、特にニューマチック型を特に好適に用いることができる。
Further, it is also preferable that the inspection system 70 of this embodiment includes a valve control section 77 and a control device 78.
When the fluid device 71 is equipped with a valve section, the valve control section 77 can apply external force to the flow path by controlling the valve section to open/close, switch, and adjust the flow rate of the flow path. can. The valve control section 77 can be of an active type, in which a movable part is moved by an actuator to deform or block the flow path, or a passive type, in which the flow direction is defined by the mechanical structure, flow path dimensions, or surface hydrophilicity. Actuators include pneumatic type that uses air pressure, thermopneumatic type that uses gas expansion due to heating, electrostatic attraction type, electromagnetic type, piezo type, bimetal type, shape memory alloy type, and clamp type that uses weights or springs. Among them, pneumatic type can be particularly preferably used.
 制御装置78は、加熱装置74、検出装置75、送液制御部76、及びバルブ制御部77を制御する情報処理装置などにより構成することができる。この情報処理装置としては、コンピュータやマイコン、PLC(programmable logic controller,プログラマブルロジックコントローラ)などを用いることができる。制御装置78は、各装置を制御するための情報を所定のタイミングで送信することによりそれらの動作を制御することができる。 The control device 78 can be configured by an information processing device that controls the heating device 74, the detection device 75, the liquid feeding control section 76, and the valve control section 77. As this information processing device, a computer, a microcomputer, a PLC (programmable logic controller), or the like can be used. The control device 78 can control the operations of each device by transmitting information for controlling each device at a predetermined timing.
 また、本実施形態の検査システムを、検体から検査対象遺伝子を抽出する核酸抽出機構と、抽出された核酸を増幅する増幅反応機構と、増幅産物中の検査対象遺伝子を検出するための上述した本実施形態の流体デバイスを備える検出機構とを有し、少なくともこれらの機構が、この順に流路で接続された構成とすることも好ましい。
 勿論、これらの機構の間に、その他の処理を行う機構を有するものとすることができることは言うまでもない。
In addition, the testing system of this embodiment includes a nucleic acid extraction mechanism for extracting a gene to be tested from a sample, an amplification reaction mechanism for amplifying the extracted nucleic acid, and the above-mentioned book for detecting a gene to be tested in an amplified product. It is also preferable that the detection mechanism includes the fluid device of the embodiment, and that at least these mechanisms are connected in this order by a flow path.
Of course, it goes without saying that a mechanism for performing other processing may be provided between these mechanisms.
 核酸抽出機構は、検体の細胞の破砕物からゲノムDNAを抽出する構成である。ゲノムDNAの抽出は、CTAB法(Cetyl trimethyl ammonium bromide)や多孔質材料を使ってPCR阻害物質を低減する方法や、DNA吸着担体を含むフィルター、磁性ビーズなどを用いるDNA抽出キット・装置によって分離精製する方法など、一般的な手法により行うことができる。
 増幅反応機構は、抽出したゲノムDNAにおける標的領域を増幅させる構成である。すなわち、ゲノムDNAにおける標的領域を含むDNA断片を増幅させる。この標的領域の増幅方法は、特に限定されないが、PCR法を好適に用いることができる。PCR法では、標的領域を増幅させるためのプライマーセットを含有するPCR反応液を用いて、標的領域を増幅させる。PCR装置としては、一般的なサーマルサイクラーなどを用いることができる。
The nucleic acid extraction mechanism is configured to extract genomic DNA from crushed cells of a specimen. Genomic DNA can be extracted using the CTAB method (Cetyl trimethyl ammonium bromide), a method that uses porous materials to reduce PCR inhibitors, and DNA extraction kits and devices that use filters containing DNA adsorption carriers, magnetic beads, etc. This can be done using general methods such as the method of
The amplification reaction mechanism is configured to amplify a target region in extracted genomic DNA. That is, a DNA fragment containing the target region in genomic DNA is amplified. The method for amplifying this target region is not particularly limited, but PCR can be suitably used. In the PCR method, a target region is amplified using a PCR reaction solution containing a primer set for amplifying the target region. As a PCR device, a general thermal cycler or the like can be used.
 検出機構は、図11を用いて上述した検査システムの構成部分である。すなわち、本実施形態の検査システムによって、増幅産物を本実施形態の流体デバイスの担体保持部に配置したDNAマイクロアレイのプローブと反応させ、プローブと結合した増幅産物の標識を検出することで、増幅産物の有無を確認する。 The detection mechanism is a component of the inspection system described above using FIG. That is, the test system of this embodiment reacts the amplified product with the probe of the DNA microarray placed in the carrier holding part of the fluidic device of this embodiment, and detects the label of the amplified product bound to the probe. Check if there is.
 以上説明したように、本実施形態の流体デバイスによれば、分岐流路を備えていても、流体の逆流や滞留が生じることを防止することが可能である。
 また、本実施形態の検査システムによれば、検体からの検査対象物の抽出から、流体デバイスによる検査対象物の検出までを自動的に制御することが可能である。また、流体デバイスにおいて試薬の逆流や滞留が生じることを防止することができるため、検査を適切に行うことが可能となっている。
As explained above, according to the fluid device of this embodiment, even if it is provided with a branch flow path, it is possible to prevent backflow or stagnation of fluid.
Further, according to the testing system of this embodiment, it is possible to automatically control everything from extraction of the testing object from the sample to detection of the testing object by the fluid device. In addition, it is possible to prevent the reagent from backflowing or stagnation in the fluidic device, making it possible to perform tests appropriately.
 本発明は、以上の実施形態に限定されるものではなく、本発明の範囲内において、種々の変更実施が可能であることは言うまでもない。
 例えば、流路を一直線状ではなく、1つ又は複数の曲がり角を備えたものとしたりするなど適宜変更することが可能である。
It goes without saying that the present invention is not limited to the above-described embodiments, and that various modifications can be made within the scope of the present invention.
For example, it is possible to make appropriate changes such as making the flow path not a straight line but having one or more curved corners.
 本発明は、流体デバイスを用いた検査対象物の存否の検査などにおいて、流体の逆流や滞留を防止可能な流体デバイスとして、好適に利用することが可能である。 The present invention can be suitably used as a fluid device that can prevent backflow and stagnation of fluid in testing the presence or absence of an object to be tested using a fluid device.
 この明細書に記載の文献及び本願のパリ優先の基礎となる日本出願明細書の内容を全てここに援用する。 The contents of the documents mentioned in this specification and the specification of the Japanese application, which is the basis of the Paris priority of this application, are all incorporated herein by reference.
 10 主流路
 101 流体流出口
 20(21,22,23) 支流路
 211,221,231 連通部
 212,222,232 流体流入口
 30 接続部
 40(41,42,43) 支流路延長部
 411,421,431 流体流入口
 50 検出装置
 51 光源
 52 蛍光検出部
 60 加熱装置
 70 検査システム
 71 流体デバイス
 72 試薬供給部
 73 廃液排出部
 74 加熱装置
 75 検出装置
 76 送液制御部
 77 バルブ制御部
 78 制御装置
10 Main channel 101 Fluid outlet 20 (21, 22, 23) Branch channel 211, 221, 231 Communication section 212, 222, 232 Fluid inlet 30 Connection section 40 (41, 42, 43) Branch channel extension section 411, 421 , 431 fluid inlet 50 detection device 51 light source 52 fluorescence detection section 60 heating device 70 inspection system 71 fluid device 72 reagent supply section 73 waste liquid discharge section 74 heating device 75 detection device 76 liquid feeding control section 77 valve control section 78 control device

Claims (15)

  1.  主流路と、複数の支流路と、各流路に連通する接続部を備えた流体デバイスであって、
     前記主流路と前記支流路と前記接続部が、前記支流路から前記主流路に向かって流体の送液が行われたときに、前記接続部において流体が合流した後に前記主流路に送液されるように互いに接続され、
     前記主流路と前記支流路と前記接続部の流路抵抗が、以下の関係式を満たすことを特徴とする流体デバイス。
     主流路の流路抵抗≦接続部の流路抵抗<支流路の流路抵抗
    A fluid device comprising a main channel, a plurality of tributary channels, and a connection part communicating with each channel,
    The main flow path, the tributary flow path, and the connection portion are arranged such that when fluid is sent from the tributary flow path toward the main flow path, the fluid is fed to the main flow path after converging at the connection portion. connected to each other so that
    A fluid device characterized in that flow path resistances of the main flow path, the tributary flow path, and the connection portion satisfy the following relational expression.
    Flow resistance of main channel ≦ Flow resistance of connection section < Flow resistance of tributary channel
  2.  前記主流路と前記支流路の流路断面積が、以下の関係式を満たすことを特徴とする請求項1記載の流体デバイス。
     主流路の流路断面積>支流路の流路断面積
    2. The fluid device according to claim 1, wherein a cross-sectional area of the main flow path and the branch flow path satisfies the following relational expression.
    Channel cross-sectional area of main channel > Channel cross-sectional area of tributary channel
  3.  少なくとも4枚の基板が接合されてなり、
     第二の基板に複数の前記支流路が貫通して形成され、前記第二の基板の一方の表面側に第一の基板が接合されており、
     前記第二の基板の他方の表面側に第三の基板が接合されており、前記第三の基板に、前記主流路が前記第二の基板に対する反対表面側に前記接続部を介して前記支流路に連通して備えられ、
     前記第三の基板の前記主流路が備えられた側に第四の基板が接合されており、
     前記第一の基板に、複数の前記支流路に連通する流体流入口が貫通して形成され、
     前記第一の基板、前記第二の基板、及び前記第三の基板に、前記主流路に連通する流体流出口が貫通して形成されている
     ことを特徴とする請求項1記載の流体デバイス。
    At least four boards are bonded together,
    A plurality of tributary channels are formed through the second substrate, and the first substrate is bonded to one surface side of the second substrate,
    A third substrate is bonded to the other surface side of the second substrate, and the main flow path is connected to the third substrate through the connecting portion to the opposite surface side to the second substrate. connected to the road,
    a fourth substrate is bonded to a side of the third substrate on which the main flow path is provided;
    A fluid inlet communicating with the plurality of tributary channels is formed through the first substrate,
    The fluid device according to claim 1, wherein a fluid outlet communicating with the main flow path is formed to penetrate through the first substrate, the second substrate, and the third substrate.
  4.  前記支流路に連通部を介してそれぞれ連通する複数の支流路延長部が備えられ、
     前記第一の基板、前記第二の基板、及び前記第三の基板に、前記支流路延長部に連通する前記流体流入口が貫通して形成されている
     ことを特徴とする請求項3記載の流体デバイス。
    A plurality of tributary channel extensions each communicating with the tributary channel via a communication portion are provided,
    4. The fluid inlet port communicating with the tributary channel extension portion is formed to penetrate through the first substrate, the second substrate, and the third substrate. Fluid device.
  5.  前記第四の基板に少なくとも前記主流路が貫通して形成され、
     前記第四の基板における前記第三の基板に対する反対表面側に第五の基板が備えられた
     ことを特徴とする請求項3又は4記載の流体デバイス。
    At least the main channel is formed to penetrate through the fourth substrate,
    5. The fluidic device according to claim 3, wherein a fifth substrate is provided on a surface of the fourth substrate opposite to the third substrate.
  6.  少なくとも3枚の基板が接合されてなり、
     第二の基板の一方の表面に複数の前記支流路が形成され、前記第二の基板の当該表面側に第一の基板が接合されており、
     前記第二の基板の他方の表面側に第三の基板が接合されており、
     前記第二の基板の表面における前記第三の基板側に、前記主流路が前記接続部を介して前記支流路に連通して備えられ、
     前記第一の基板に前記支流路に連通する流体流入口が貫通して形成され、前記第一の基板及び前記第二の基板に、前記主流路に連通する流体流出口が貫通して形成されている
     ことを特徴とする請求項1記載の流体デバイス。
    At least three boards are bonded together,
    A plurality of branch channels are formed on one surface of the second substrate, and the first substrate is bonded to the surface side of the second substrate,
    A third substrate is bonded to the other surface side of the second substrate,
    The main flow channel is provided on the third substrate side of the surface of the second substrate and communicates with the tributary flow channel via the connection part,
    A fluid inlet communicating with the tributary channel is formed to penetrate the first substrate, and a fluid outlet communicating with the main channel is formed penetrating the first substrate and the second substrate. The fluidic device according to claim 1, characterized in that:
  7.  少なくとも第一の基板と第二の基板とが接合されてなり、
     前記第二の基板に前記主流路と前記支流路と前記接続部が備えられ、
     前記第二の基板の前記主流路と前記支流路と前記接続部が備えられた表面側に前記第一の基板が接合されており、
     前記第一の基板に、前記支流路に連通する流体流入口が貫通して形成されていると共に、前記主流路に連通する流体流出口が貫通して形成されている
     ことを特徴とする請求項1記載の流体デバイス。
    at least a first substrate and a second substrate are bonded,
    The second substrate is provided with the main flow channel, the branch flow channel, and the connection part,
    the first substrate is bonded to a surface side of the second substrate where the main flow path, the branch flow path, and the connection portion are provided;
    A fluid inlet communicating with the tributary channel is formed to penetrate the first substrate, and a fluid outlet communicating with the main channel is formed penetrating the first substrate. 1. The fluidic device according to 1.
  8.  少なくとも第一の基板と第二の基板とが接合されてなり、
     前記第一の基板に、前記主流路と、複数の前記支流路にそれぞれ連通する複数の支流路延長部とが貫通して備えられ、
     前記第二の基板に、複数の前記支流路と、前記主流路に連通する前記接続部と、前記支流路延長部にそれぞれ連通する連通部とが備えられた
     ことを特徴とする請求項1記載の流体デバイス。
    at least a first substrate and a second substrate are bonded,
    The first substrate is provided with a plurality of tributary channel extensions penetrating the main channel and communicating with the plurality of tributary channels, respectively,
    2. The second substrate is provided with a plurality of the tributary channels, the connecting portion communicating with the main channel, and communication portions communicating with the tributary channel extensions, respectively. fluidic devices.
  9.  それぞれの基板が、疎水性材料により形成されたことを特徴とする請求項1又は2記載の流体デバイス。 The fluidic device according to claim 1 or 2, wherein each substrate is formed of a hydrophobic material.
  10.  前記主流路の一部に反応部が備えられたことを特徴とする請求項1又は2記載の流体デバイス。 The fluid device according to claim 1 or 2, wherein a reaction section is provided in a part of the main flow path.
  11.  前記反応部の表面が、反応用物質が固定化された表面であることを特徴とする請求項10記載の流体デバイス。 11. The fluidic device according to claim 10, wherein the surface of the reaction section is a surface on which a reaction substance is immobilized.
  12.  前記反応部に、凹部、又は、貫通孔である担体保持部が備えられ、前記担体保持部に反応用物質が固定化された担体が保持されたことを特徴とする請求項10記載の流体デバイス。 11. The fluid device according to claim 10, wherein the reaction section is provided with a carrier holding section that is a recess or a through hole, and the carrier holding section holds a carrier on which a reaction substance is immobilized. .
  13.  請求項1又は2記載の流体デバイスと、試薬を前記支流路に送液する送液制御部と、前記流体デバイスを加熱する加熱装置と、前記試薬の蛍光を励起する光を照射する光源及び発生した蛍光を検出する蛍光検出部を有する検出装置と、を備えた
     ことを特徴とする検査システム。
    The fluid device according to claim 1 or 2, a liquid feeding control unit that feeds a reagent to the branch channel, a heating device that heats the fluid device, and a light source and generator that irradiates light that excites fluorescence of the reagent. An inspection system comprising: a detection device having a fluorescence detection section that detects fluorescence.
  14.  少なくとも前記支流路の開閉、切替、及び/又は流量調節を行うバルブ制御部と、前記加熱装置、前記検出装置、前記送液制御部、及び前記バルブ制御部を制御する情報処理装置と、をさらに備えたことを特徴とする請求項13記載の検査システム。 further comprising: a valve control unit that opens/closes, switches, and/or adjusts the flow rate of at least the tributary channel; and an information processing device that controls the heating device, the detection device, the liquid feeding control unit, and the valve control unit. 14. The inspection system according to claim 13, further comprising:
  15.  検体から検査対象遺伝子を抽出する核酸抽出機構と、
     抽出された核酸を増幅する増幅反応機構と、
     増幅産物中の検査対象遺伝子を検出するための請求項1又は2記載の流体デバイスを備える検出機構と、を有し、
     少なくともこれらの機構が、この順に流路で接続されている
     ことを特徴とする検査システム。
    a nucleic acid extraction mechanism that extracts the gene to be tested from the sample;
    an amplification reaction mechanism for amplifying the extracted nucleic acid;
    A detection mechanism comprising the fluidic device according to claim 1 or 2 for detecting the gene to be tested in the amplification product,
    An inspection system characterized in that at least these mechanisms are connected in this order through a flow path.
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Publication number Priority date Publication date Assignee Title
WO2005108571A1 (en) * 2004-05-07 2005-11-17 Konica Minolta Medical & Graphic, Inc. Micro-reactor for testing, genetic testing apparatus, and genetic testing method
US20080312104A1 (en) * 2007-06-15 2008-12-18 Yasuhiko Sasaki Biological material preparation chip and preparation chip system
JP2009109249A (en) * 2007-10-26 2009-05-21 National Institute Of Advanced Industrial & Technology Microchip and master chip
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