WO2011108333A1 - Microfluidic detection chip manufacturing method - Google Patents

Microfluidic detection chip manufacturing method Download PDF

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Publication number
WO2011108333A1
WO2011108333A1 PCT/JP2011/052232 JP2011052232W WO2011108333A1 WO 2011108333 A1 WO2011108333 A1 WO 2011108333A1 JP 2011052232 W JP2011052232 W JP 2011052232W WO 2011108333 A1 WO2011108333 A1 WO 2011108333A1
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WIPO (PCT)
Prior art keywords
continuous sheet
flow path
microchannel
inspection
sheet
Prior art date
Application number
PCT/JP2011/052232
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French (fr)
Japanese (ja)
Inventor
細江　秀
Original Assignee
コニカミノルタオプト株式会社
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Publication of WO2011108333A1 publication Critical patent/WO2011108333A1/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
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Definitions

  • the present invention relates to a method for manufacturing a microchannel inspection chip.
  • FIG. 16 shows an example of an immunochromatographic test chip which is a kind of immunological test method. Since the test chip 100 shown in FIG. 16 detects an antigen to be tested for presence or absence in a test liquid by causing an antigen-antibody reaction so that two antibodies arranged on the test chip are sandwiched, a sandwich is used. It is an immunochromatography test chip called the method.
  • the test chip 100 is formed by arranging a sample pad 102, a conjugate pad 103, a test line 104, a control line 105, and an absorption pad 106 in a longitudinal direction on a nitrocellulose membrane.
  • test liquid When the test liquid is dropped on the sample pad 102 of the test chip 100, the test liquid proceeds to the right in the figure by capillary action, and the antibody label bound to the gold colloid or the like in the conjugate pad 103 and the antigen contained in the test liquid The protein binds and travels further through the membrane.
  • the antigen-antibody reaction with the label is sufficiently advanced to reach the test line 104, and the labeled antigen is captured and accumulated by the reagent antibody soaked therein.
  • the test line 104 Since the colloidal gold is brown, when the labeled antigen is captured and accumulated in the test line 104, the test line 104 appears brown, so that the presence of the desired antibody can be confirmed.
  • the test liquid further travels through the membrane, and when it reaches the control line 105, the label is captured regardless of the presence or absence of the desired antigen, and the control line 105 becomes brown.
  • the control line 105 plays a role of displaying that the test liquid is properly immersed in the test line 104 and the test is successful.
  • the absorption pad 106 continues to absorb the test liquid that has finished its role, and continuously advances the test liquid in the membrane.
  • Such an inspection chip is disclosed in, for example, Patent Document 1, Patent Document 2, and the like, and since it can be performed in a short time by a simple method, it is used in clinics and the like.
  • a sample pad In order to manufacture a conventional test chip, it is necessary to have at least four parts: a sample pad, a conjugate pad, a membrane, and an absorption pad, each of which has a function of different absorbability of the test liquid.
  • a sample pad In order to assemble and assemble the components so that the test liquid penetrates without stagnation, there is a great risk that it takes time and is contaminated with dirt. Since the desired amount of antibody to be detected is a very small amount of 10 4 to 10 5 / ml, even if a slight amount of dirt is mixed, it becomes noise and deteriorates the inspection accuracy.
  • an inspection chip using a very narrow channel (microchannel) has been proposed so that it can be used for a wider range of inspections with higher accuracy than the immunochromatography method described above (for example, And Patent Document 3).
  • a microchannel inspection chip is usually provided with a thin channel on a quartz glass substrate, and a dropped test liquid reacts with a reagent or is filtered in the course of flowing through this channel, and is applied to a spectrometer or the like.
  • the desired inspection is performed by measuring the amount of fluorescence.
  • the test liquid flows through the flow path by capillary action or pump suction.
  • the micro flow path inspection chip is made by using quartz glass as the substrate material and exposing and etching using photolithography. Further, a cover glass is joined to cover the flow path. Therefore, it is a very expensive inspection chip. Quartz glass materials can be exposed to strong acids, strong alkalis, and high temperatures, so that they can be kept very clean against the aforementioned contamination, and are suitable for highly sensitive inspections.
  • the reaction time of the test liquid is controlled by the flow rate, the dimensional accuracy of the flow path is strict, and in order to mold this accurately, the injection molding time is lengthened and the molding chip in the mold is gradually cooled over time. Had to open the mold after.
  • the number of molding chips obtained by one molding cannot be increased. Therefore, there is a limit to reducing the price even in the manufacturing method by injection molding using a plastic material.
  • the molded chip thus obtained has to be covered with a plastic plate to close the flow path, and this process is completely different from the above-described injection molding. There was an opportunity for the inspection chip to easily get dirty in the assembly process such as joining of the plates and packing.
  • test chip Once a test chip is contaminated, it is almost impossible to detect dirt, and even if it can be detected, it can only be discarded. If a contaminated test chip is used in a medical setting, it may not only make a mistake in the test decision but also lead to a harmful treatment. That is, the conventional manufacturing process with many opportunities for contamination is basically unsuitable for manufacturing such a high-precision inspection chip. Therefore, the conventional method for producing an inspection chip by injection molding has not only a limit on cost reduction, but also has many problems in terms of quality.
  • An object of the present invention is to solve the above-described problems, that is, to provide a method for manufacturing a microchannel inspection chip that can achieve high productivity and low cost and is free from contamination.
  • the above-mentioned purpose is to supply a reagent to the flow path forming step of transporting the first continuous sheet and forming the flow path by molding, molding, or printing in order in the transport direction of the first continuous sheet.
  • Producing a sheet having a plurality of micro-channel test chips by arranging a reagent supplying step, forming a channel, and a laminating and bonding step of laminating and adhering a second continuous sheet to the first continuous sheet supplied with the reagent Achieved by the manufacturing method.
  • the prepared sheet is then cut into individual microchannel inspection chips, but the cutting step may be arranged after the lamination bonding step.
  • the formation method of the flow path includes “molding”, “molding”, and “printing”, and these are collectively referred to as “formation”.
  • “Molding” refers to a process in which a solid molded object is softened by heating or pressurization and is brought into close contact with the transfer surface of the mold to transfer the shape.
  • “Molding” refers to a liquid molded object. A process in which a shape is transferred by pouring into a mold and curing by heating or UV light irradiation.
  • Print means that a printing material (ink) is attached to a roll-shaped plate and the printing material is transferred to a base film, or ink droplets are used to remove the printing material in fine droplets from a nozzle. A process that is formed by punching out.
  • the present invention further includes a step of forming an optical functional element on the second sheet or on the back surface side of the first sheet corresponding to the inspection portion that is finally inspected by the test liquid reacting with the reagent.
  • an optical functional element is designed so as to be adapted to a single observation device according to the type of microchannel inspection chip, a plurality of different types of inspection can be performed with a single observation device.
  • a movable structure that functions on the flow path of the micro flow path inspection chip can be formed to form a valve or a pump, or an electrode can be formed to perform inspection by an electrical action such as electrophoresis.
  • the term “flow channel” means a flow channel part in which a flow channel in which a liquid flows and a liquid reservoir in which a reagent or the like is fixed, or a movable structure that functions as a valve or a pump, It is used as a term including the flow path portion in which the electrode is formed.
  • test liquid and reagent are used as terms including not only the medical field, but also those in the biochemical field, the agricultural field, and the like.
  • a method of manufacturing a microchannel inspection chip that continuously forms a plurality of microchannel inspection chips The first continuous sheet is conveyed, and sequentially in the conveying direction of the first continuous sheet, A flow path forming step for forming a flow path by molding, molding, or printing; A reagent supplying step of supplying a reagent to the flow path; Forming a flow path, a lamination bonding step of laminating and bonding a second continuous sheet to the first continuous sheet supplied with the reagent, To form a sheet on which a plurality of microchannel inspection chips are formed, and a continuous method of microchannel inspection chips. 2.
  • a method of manufacturing a microchannel inspection chip that continuously forms a plurality of microchannel inspection chips The first continuous sheet is conveyed, and sequentially in the conveying direction of the first continuous sheet, A flow path forming step for forming a flow path by molding, molding, or printing; A reagent supplying step of supplying a reagent to the flow path; An optical functional element forming step of forming an optical functional element of either a diffraction lens, a Fresnel lens, or a diffraction grating on the second continuous sheet; Laminate bonding step of laminating and bonding the second continuous sheet in which the optical functional element is formed to the first continuous sheet supplied with the flow path and the reagent, And producing a sheet on which a plurality of microchannel inspection chips are formed.
  • a method of manufacturing a microchannel inspection chip that continuously forms a plurality of microchannel inspection chips The first continuous sheet is conveyed, and sequentially in the conveying direction of the first continuous sheet, A flow path forming step for forming a flow path by molding, molding, or printing; A reagent supplying step of supplying a reagent to the flow path; An optical functional element forming step of forming an optical functional element of any one of a diffraction lens, a Fresnel lens, and a diffraction grating on the back surface of the first continuous sheet simultaneously with or before and after the flow path forming step, Laminate bonding step of laminating and bonding a second continuous sheet to the first continuous sheet on which flow path formation, reagent supply, and optical functional element are formed, And producing a sheet on which
  • the flow path forming device and the optical functional element forming device are arranged to face each other, and the first continuous sheet is passed between them, and the flow path and the optical functional element are connected to the first continuous sheet. 5.
  • a sacrificial layer forming step is provided before the flow path forming step, a cantilevered flap portion is formed in the flow path in the flow path forming step, and then the sacrificial layer is eluted and removed. 7.
  • microchannel inspection chip according to any one of 1 to 11 above, wherein a cutting step is provided after the laminating and bonding step, wherein the integrated sheet is cut while being continuously fed and separated into individual pieces.
  • Production method 13.
  • 14 14.
  • the present invention can achieve high productivity and low cost, and can produce a micro-channel inspection chip that is free from contamination.
  • Process drawing which shows the manufacturing method of 1st Embodiment of this invention.
  • the schematic diagram which shows the accumulator mechanism used by this invention.
  • the top view and sectional drawing which show the microchannel test
  • Process drawing which shows the manufacturing method of 2nd Embodiment of this invention.
  • Partial process drawing which shows the manufacturing method of the modification of 2nd Embodiment of this invention.
  • the schematic diagram which shows the formation method of the microchannel inspection chip
  • inspection chip of 3rd Embodiment of this invention The partial process figure which shows the manufacturing method of the modification of the microchannel inspection chip
  • the microchannel inspection chip that can be manufactured according to the present invention is designed for inspection applications in various fields such as the medical field, biochemical field, and agricultural field. However, as an embodiment, a test that performs the same function as an immunochromatographic chip. A chip will be described as an example.
  • FIG. 1 is a plan view and a cross-sectional view of the microchannel inspection chip 1 of the first embodiment.
  • a liquid reservoir 2 for supplying a test liquid a channel groove 3a, and a liquid reservoir 4 for a capture antibody.
  • the channel groove 3b, the liquid reservoir 5 for the capture reagent, the channel groove 3c, and the liquid reservoir 6 for storing the liquid after the reaction are formed side by side on the first continuous sheet 7.
  • a mark M for position detection is formed in the lower left part.
  • a second continuous sheet 8 is laminated and adhered so as to cover the first continuous sheet 7 on which these flow paths and marks are formed, and the first continuous sheet 7 corresponds to the liquid reservoir 2 for the test liquid.
  • a hole 9 for supplying a test liquid is formed in a portion of the two continuous sheets 8. At least one of the first continuous sheet 7 and the second continuous sheet 8 is made of a transparent sheet material for inspection observation.
  • a labeled antibody is fixed to the liquid reservoir 2 for supplying the test liquid.
  • the test liquid is dropped into the liquid reservoir 2 from the hole 9, the liquid that has reacted with the labeled antibody is sequentially flown through the flow channel 3a by capillary action. Then, the flow proceeds to the liquid reservoir 4 to which the capture antibody is immobilized, the flow channel 3b, the liquid reservoir 5 to which the capture reagent is immobilized, and the flow channel 3c, and finally accumulates in the liquid reservoir 6. Then, the inspection result is determined at the portion of the liquid reservoir 5.
  • the size of the channel groove to be formed is about 10 to 100 ⁇ m in depth and about 30 to 500 ⁇ m in width, and varies depending on the application.
  • a liquid reservoir for installing a reagent for inspecting the test liquid is arranged in the middle of the flow path, but this liquid reservoir makes it easy to check the color change of the reagent even with the naked eye, and the sensitivity increases even when reading with an apparatus. Thus, it is usually set to a size of about several mm.
  • FIG. 2 is a schematic diagram illustrating a basic process for manufacturing the microchannel inspection chip 1.
  • the basic process for manufacturing the microchannel inspection chip 1 is as follows: -Sheet unloading step A for unloading the first continuous sheet 7, ⁇ Sheet unloading process B to form a flow path, First reagent supply step C for supplying labeled antibody, A second reagent supply step D for supplying the capture antibody, A third reagent supply step E for supplying a capture reagent, A laminating and bonding step F for laminating and bonding the second continuous sheet 8 to the first continuous sheet 7; -Cutting process G for cutting the laminated sheets and cutting the inspection chips into pieces. Consists of.
  • the manufacturing apparatus that performs these processes is installed in a clean room, and is configured so as not to contaminate the inspection chip to be manufactured by supplying air through a filter that cuts dust and bacteria. Further, since the manufacturing process is remotely controlled by a control device (not shown), the manufacturing can be completed without touching human hands, and contamination can be extremely reduced.
  • a roll sheet obtained by winding the first continuous sheet 7 in a roll shape is set in a conveying device, and the first continuous sheet 7 is stretched to a subsequent process.
  • the first continuous sheet 7 is a plastic sheet having a thickness of 500 ⁇ m and a width of 300 mm, and the feeding speed is 1 m / min.
  • the flow path forming step B includes a liquid reservoir 2 for supplying a test liquid, a flow path groove 3a, a liquid reservoir 4 for a test reagent, a flow path groove 3b, a liquid reservoir 5 for a capture reagent, a flow path groove 3c, a reaction liquid
  • the flow path composed of the liquid reservoir 6 and the mark M are formed on the first continuous sheet 7.
  • the negatives of these flow paths are formed on the roll mold B 1, and are formed inside the roll mold B 1.
  • the roll mold B1 is heated by the arranged heating source to thermally transfer the flow path onto the first continuous sheet 7 (so-called molding process).
  • the flow path can be formed by any one of the above-described “molding”, “molding”, and “printing” methods. That is, “molding” is a method in which a flow path pattern formed directly on a roll plate is heat-pressed and the flow path is transferred onto a sheet. “Molding” refers to filling a roll mold with a flow path pattern filled with a fluid material such as thermosetting resin, UV curable resin, or glass material, and curing and transferring onto a sheet by heating or UV irradiation.
  • “printing” is a method in which a resin material is filled in a flow path of a roll plate such as an intaglio and transferred to a sheet as it is.
  • the resin material may be once transferred to the blanket and then transferred onto the sheet in the manner of offset printing. Furthermore, if the viscosity of the resin surface is improved by making the resin surface semi-cured immediately before transferring the resin material onto the sheet, the adhesion with the sheet is greatly improved and the separation from the plate of the resin material is improved, A fine pattern can be transferred onto the sheet with high accuracy. Further, “printing” by micro droplets by ink jet without using a roll plate may be used.
  • the labeled antibody, the capture antibody, and the capture reagent (hereinafter collectively referred to as “reagent”) are stored in the liquid reservoirs 4, 5, and 6, respectively. This is a process of fixing the supply. These reagents are supplied and applied on the liquid reservoir by the printing apparatuses C1, D1, and E1.
  • the printing method uses intaglio etc. if it is about several ⁇ m, and if it is thick to about 10-30 ⁇ m, use letterpress or reversal method. Furthermore, screen printing can be used for thicknesses exceeding 100 ⁇ m.
  • the supplied reagent is dried and fixed on the liquid reservoir. Drying is performed by heating using an infrared lamp (not shown) or the like after each reagent supply step or at the end. .
  • the first reagent supply process C, the second reagent supply process D, and the third reagent supply process E use sensors C2, D2, and E2 that detect the mark M before printing, and the detection signals of these sensors. Based on the above, the rotation of the roll type of each printing apparatus is controlled to accurately supply the reagent to each liquid reservoir.
  • the second continuous sheet 8 is laminated and adhered to the first continuous sheet 7 to which the flow path is formed and each reagent is supplied.
  • the second continuous sheet 8 is formed between the heating and pressurizing roll pair F2 after the hole 9 for supplying the test liquid is formed by the punching device F1 having a die and a punch that reciprocates between the die and the sheet.
  • a scrap basket is disposed under the die to collect perforated scraps.
  • the alignment of the liquid reservoir 2 for the test liquid on the first continuous sheet 7 and the hole 9 is based on the detection of the mark M on the first continuous sheet 7 to control the operation of the punching device F1 at an appropriate timing. This is done by opening 9.
  • an accumulator mechanism in which a hole 9 is formed in the second continuous sheet 8 in advance and is arranged between the second continuous sheet supply roll and the laminating and bonding step F based on the detection of the mark M and the detection of the hole 9. To adjust the conveying speed of the second continuous sheet 8 and align the position. When the mark M is not provided, alignment can be performed by detecting the edge of the liquid reservoir 2 and the hole 9.
  • FIG. 3 is a schematic diagram showing an accumulator mechanism.
  • the accumulator mechanism has a configuration in which a plurality of fixed rollers 10A and dance rollers 10B are alternately arranged, and a sheet material is alternately hung on each roller. By moving 10B as shown by the arrow, the speed on the carry-in side and the carry-out side can be changed or stopped.
  • Adhesion between the first continuous sheet 7 and the second continuous sheet 8 is the same plastic sheet, so that the sheets are brought into close contact with each other while being heated and pressed between the opposed heating and pressing roll pair F2. At this time, if a temperature equal to or higher than the glass transition point of the plastic is applied, the plastic is softened and the cross-sectional shape of the flow path is destroyed.
  • the applied pressure is about 1 to 5 kg / cm 2 .
  • a transparent adhesive can be applied before the lamination bonding step to make the lamination adhesion more complete.
  • the resin is preferably in a semi-cured state and is completely bonded in the lamination bonding step F.
  • the cutting process G is a process of dividing the microchannel inspection chip into individual pieces.
  • the microchannel inspection chip of this embodiment is cut into a chip length of 30 mm and a width of 15 mm.
  • the sheet material is plastic, it is cut into individual pieces by cutting with a blade after lamination.
  • a strip-shaped cutter G2 is installed on the drum surface of the rotary die G1, and the rotary die G1 and the bearer G3 are rotated in synchronization with sheet feeding, so that cutting can be performed with an accurate dimension of the set cutter G2. realizable.
  • the illustrated example is an example in which a blade is provided only in the width direction of the sheet, and the microchannel inspection chips are cut in a line and separated into individual pieces in a separate process.
  • FIG. 2 shows a microchannel inspection chip separated into pieces.
  • each microchannel inspection chip can be separated into individual pieces. In this case, it is also necessary to have a configuration for winding the punched residue.
  • this cutting method is a simple process, it can follow the sheet feeding speed almost without any problem and is very efficient. In addition, you may wind up to a roll and cut into pieces by another process, without cut
  • the material that can be used for the first sheet and the second sheet of the present invention is preferably a plastic material or a glass material.
  • Plastic materials include acrylic, polycarbonate, polystyrene, and COC (cycloolefin copolymer).
  • the thickness of the sheet material is about 1 ⁇ m to 1 mm. Since the microchannel inspection chip is formed in a matrix on the sheet material, the width is preferably about 300 mm, although it depends on the size of the microchannel inspection chip to be manufactured. If the width is too wide, manufacturing equipment for maintaining high accuracy becomes expensive, and if the width is narrowed, the yield decreases.
  • Glass materials include alkali-free or low-alkali glass.
  • As the glass sheet a sheet material having a thickness of 500 ⁇ m or less is already commercially available in roll form, and this can be used.
  • glass materials such as gel glass and low melting point glass paste, thermosetting resins such as bakelite, epoxy resin, acrylic resin, or UV curable resins can be used. It is supplied to a roll mold in which a flow path mold is formed, and is molded or printed.
  • FIG. 4 is a diagram showing the microchannel inspection chip 11 according to the second embodiment of the present invention.
  • the microchannel inspection chip 11 of the second embodiment includes an optical function element.
  • the microchannel inspection chip 11 stores a liquid reservoir 12 for supplying a test liquid, a channel groove 13, and a liquid after reaction.
  • the liquid reservoir 14 is formed on the first continuous sheet 15, and the second continuous sheet 16 is laminated and bonded thereon.
  • On the surface of the second continuous sheet 16 an optical functional element 17 is formed, and In order to protect the optical functional element 17, a third continuous sheet 18 is laminated thereon.
  • the second continuous sheet 16 and the third continuous sheet 18 are formed with holes 19 for supplying the test liquid.
  • the microchannel inspection chip 11 has a reagent fixed to a liquid reservoir 12 for supplying a test liquid.
  • a reagent fixed to a liquid reservoir 12 for supplying a test liquid.
  • the reagent and the test liquid react to react with each other. Move to.
  • the reaction proceeding in the reaction liquid reservoir 14 is observed. However, since the optical functional element 17 is formed, the observation becomes easier.
  • a diffractive lens As the optical functional element 17, a diffractive lens, a Fresnel lens, a diffraction grating, or other diffractive elements can be formed, and a function corresponding to the way of observing the reaction of the test liquid may be provided.
  • the optical function element 17 has an enlargement function, the reaction can be observed sufficiently clearly. Also, when observation at the microscopic level is necessary, if the optical function element 17 is designed to adjust the magnification between the magnification of a single observation device even if the magnification ratio varies depending on the type of the test liquid, the test liquid It is possible to carry out with a single observation device without preparing different observation devices depending on the type. Furthermore, when observing spectral characteristics, if the diffraction grating is appropriately designed, the spectral characteristics of different test liquids can be observed with a single observation device. In this way, it is not necessary to prepare a plurality of observation devices, which is a great merit for small clinics and inspection institutions.
  • FIG. 5 is a schematic diagram showing a process for manufacturing the optical functional element 17.
  • the sheet unloading step A, the flow path forming step B, the reagent supplying step C, and the final cutting step G are the same as in the first embodiment.
  • the second embodiment the case of one type of reagent is shown, but it is needless to say that a microchannel inspection chip that forms a plurality of liquid reservoirs and fixes a plurality of reagents can be used.
  • an optical functional element forming step H for forming an optical functional element on the surface side of the second continuous sheet 16 is provided.
  • the optical functional element forming step H indicates a step by molding a UV curable resin. That is, a UV curable resin is supplied between the second continuous sheet 16 supplied from the roll and the roll mold H1, and formed into a mold of an optical functional element formed on the roll mold H1, and this optical functional element is irradiated with ultraviolet rays. Curing with lamp H2.
  • the second continuous sheet 16 on which the optical functional element is formed proceeds to the lamination adhesion step F with the first continuous sheet 15 and is laminated and adhered so as to cover the flow path formed on the first continuous sheet 15. And it progresses to the process I which carries out the lamination
  • the use of a punching device for forming a test liquid supply hole in the second continuous sheet 16 and the third continuous sheet 18 or a mark detection sensor for alignment is the first implementation. It is the same as the form.
  • FIG. 6 shows a micro-channel inspection chip 21 with an optical function element according to a modification of the above example.
  • the microchannel inspection chip 21 is one in which the optical functional element 22 is formed on the back side of the first continuous sheet 23. Since the flow path (the liquid reservoir 12 for supplying the test liquid, the flow path groove 13, and the liquid reservoir 14 for storing the liquid after the reaction) is formed on the surface of the first continuous sheet 23, and the optical functional element 22 is formed on the back surface, They can be formed simultaneously. The flow path side of the first continuous sheet 23 is covered with the second continuous sheet 24.
  • FIG. 7 shows the flow path and the optical function element forming step J at this time. That is, a UV-curable resin-molded roll mold B2 that forms a flow path is disposed on the front surface side of the first continuous sheet 23, and an optical functional element-formed thermal transfer roll mold B3 is formed on the back surface side (the same as in the first embodiment). Forming method) and forming simultaneously.
  • the UV curable resin transferred from the roll mold B2 is semi-cured by the ultraviolet lamp B4. By forming them simultaneously in this way, the positions of the flow path and the optical function element are not shifted, and the process can be shortened.
  • the microchannel inspection chip 31 of the third embodiment of the present invention has a movable structure that functions on the channel.
  • FIG. 8 schematically shows a method for forming the movable structure portion.
  • the sacrificial layer 33 is formed on the first continuous sheet 32, and then the flow path is formed on the sacrificial layer 33.
  • 34 is formed (FIG. 8B).
  • a cantilevered flap 34f can be formed from the flow path forming material.
  • a second continuous sheet 35 is laminated and bonded onto this structure (FIG. 8D). If the test liquid flows from right to left, the flap 34f allows the liquid to flow in the left direction, but can function as a check valve that blocks the flow in the right direction.
  • the dotted line part of the flow path 34 shows a thin flow path groove.
  • FIG. 9 shows an example in which two such check valves 36 are continuously formed.
  • a simple pump can be configured by providing a configuration for applying and releasing pressure from the second continuous sheet 35 side between the two check valves 36.
  • the pressure may be applied / released with a finger.
  • the plunger 37 abutting against the second continuous sheet 35 between the two check valves 36 is reciprocated by the eccentric cam 38.
  • the microchannel chip having such a pump configuration can move a large amount of liquid as compared to the case where the test liquid moves only by capillary action, and it is easy to control the flow rate stably. It leads to speed, accuracy and high sensitivity.
  • FIG. 10 is a schematic diagram showing a manufacturing process when such a movable mechanism is provided in the flow path.
  • the first continuous sheet 40 fed out from the sheet unloading process proceeds to the lamination bonding process F with the second continuous sheet 41 through the sacrificial layer forming process J, the flow path forming process B ′, and the sacrificial layer elution process K.
  • the sacrificial layer forming step J is a step of forming a sacrificial layer on the first continuous sheet 40.
  • a sacrificial layer can be formed by a molding or printing method.
  • the flow path forming step B ′ is a process of forming a flow path structure in which a cantilever flap valve structure is added between the flow paths, and can be formed by a printing or molding method.
  • the sacrificial layer is eluted by passing the first continuous sheet 40 through the container K1 containing the solvent.
  • the movable structure (cantilever flap structure) formed on the sacrificial layer has a free end portion movable in the flow path.
  • the sacrificial layer is dried with an infrared lamp K2 or the like, and the process proceeds to the next lamination bonding step F.
  • the material and solvent of a sacrificial layer can use a well-known thing in the range which does not affect the 1st continuous sheet 40 or a flow-path formation material.
  • FIG. 11 is a plan view and a cross-sectional view showing an example of a microchannel inspection chip 51 in which a venous valve check valve is formed as a movable structure.
  • the venous valve check valve has a structure in which cantilevered flaps 53 are symmetrically opposed to each other on the first continuous sheet 52, and the free ends of both flaps 53 are close to each other. Accordingly, liquid from the right side of the figure is allowed to pass, but liquid from the left side does not flow with the flap free end closed.
  • the hatched portion is the portion where the sacrificial layer 54 is formed. First, the sacrificial layer 54 is formed, and the flow path including the flap is formed thereon. After that, the sacrificial layer 54 is eluted.
  • the lower end of the movable flap 53 is slightly spaced from the first continuous sheet 52 due to the elution of the sacrificial layer, and the upper end is slightly higher than the channel groove forming portion. Since it is formed low, the movable flap 53 does not come into contact with the first continuous sheet 52 or the second continuous sheet 55, and becomes a movable structure and functions as a valve.
  • Such a venous valve type check valve structure can also be formed by the sacrificial layer forming step J, the flow path forming step B ′, and the sacrificial layer elution step K.
  • FIG. 12 is a partial plan view of the microchannel inspection chip 61 in which electrodes are formed on both sides of the reaction chamber.
  • electrodes are formed on both sides of the reaction chamber.
  • Such electrode formation can also be integrated into the manufacturing method of the present invention.
  • the electrode can be formed in advance on the first continuous sheet, and the first continuous sheet with electrode can be continuously produced by performing flow path formation, reagent supply, and second continuous sheet lamination adhesion of the present invention. Furthermore, the electrode formation itself can be incorporated into the process.
  • FIG. 13 is a schematic diagram showing a process in which the electrode forming process L is incorporated.
  • the first continuous sheet 63 fed out from the sheet unloading process (not shown) proceeds to the lamination bonding process F with the second continuous sheet (not shown) through the electrode forming process L and the flow path forming process B ′.
  • the electrode forming step L shows a step of forming conductive ink by the roll screen printing apparatus L1, and the ink after printing is dried and solidified by the infrared lamp L2.
  • the flow path forming step B ′ following the electrode forming step L is an offset resin molding method in which a resin is supplied to the roll plate B′1, transferred to the blanket B′2, and then transferred onto the first continuous sheet. showed that.
  • the resin in the flow path 64 supplied to the roll plate B ′ 1 is made semi-cured by the infrared lamp B ′ 3 and transferred to the blanket B ′ 2, on the first continuous sheet 63 on which the electrode 62 is formed.
  • a flow path is formed.
  • the resin in the flow path is dried and solidified by the infrared lamp B'4.
  • the electrode forming step L and the flow path forming step B ′ can be formed by other methods such as ink jet printing in addition to the above printing method.
  • the heating process of FIG. 14 is a form in which a pair of stainless steel belts 70, a pressure roll 71 and a heater 72 disposed therein are heated and pressed from both sides of the laminated first continuous sheet and second continuous sheet. is there.
  • this heating method since the sheet is heated while being pulled in a straight line, it is possible to manufacture a micro-channel inspection chip with high dimensional accuracy that is free from bending wrinkles and is completely joined. Even when the first continuous sheet and the second continuous sheet are glass materials, they can be bonded by heating and pressurizing them in close contact with the semi-cured flow path forming material using the heating step of FIG.
  • cutting is performed with a rotary die blade, but in the case of a glass sheet, cutting can also be performed with a laser cutting device (infrared laser and water jet).
  • a laser cutting device infrared laser and water jet.
  • the cutting of the sheet material is performed by irradiating the infrared laser 80 and spraying water on the irradiation position with the water jet device 81.
  • water jet device 81 When water is sprayed on the glass heated locally by the infrared laser 80, the crack grows and progresses, so that the cutting can be performed.
  • a cutting device including the infrared laser 80 and the water jet device 81 is used from the sheet width direction. It is configured to be movable integrally in a slightly diagonal direction, and the sheet is cut while moving in this direction as the sheet is conveyed. Since the sheet is also moving, the sheet and the cutting device are relatively stationary by moving the infrared laser 80 and the water jetting device 81 obliquely in the width direction.
  • the cutting device is configured to be movable in the contact / separation direction with respect to the sheet in order to adjust the focal position of the infrared laser 80 as indicated by an arrow.
  • both the first continuous sheet and the second continuous sheet are made of glass material
  • cutting from the second continuous sheet side propagates to the first continuous sheet side by cutting with infrared laser irradiation and water cooling.
  • one of the sheets or the flow path forming material is a plastic material
  • laser cutting is performed from both sides as indicated by dotted lines in the figure.
  • micro flow path inspection chips are arranged in a matrix, when they are separated, they must be cut in both the width direction and the transport direction. Can not be done at the same time because they intersect and cracks break at the cutting line. Therefore, it is necessary to sequentially perform cutting in the width direction and the conveyance direction.
  • Cutting in the conveyance direction can be performed while carrying the infrared laser beam by the number of semiconductor modules arranged in the width direction, but cutting in the width direction requires maintaining the relative position of the laser cutting device and the sheet stationary. is there.
  • the relatively stationary method is that an accumulator mechanism is installed before the cutting process and an extra sheet is used with a dance roller or the like. There is a method of making time for winding the sheet and stopping the sheet feeding in the laser cutting process during that time.
  • This accumulator mechanism can use the configuration shown in FIG.
  • the manufacturing method of the microchannel inspection chip of the present invention is manufactured in a series of continuous processes, it is possible to perform manufacturing without worrying about contamination by performing these processes in a clean room. it can.
  • Microchannel test chip 2 Liquid reservoir for supply of test liquid 3a, 3b, 3c Channel groove 4 Liquid reservoir for capture antibody 5 Liquid reservoir for capture reagent 6, 14 Reaction Liquid reservoir 7, 15, 23, 32, 40, 52, 63 First sheet, first continuous sheet 8, 16, 24, 35, 41, 55 Second sheet, second continuous sheet 18 Third continuous sheet 9, 19 Hole for supplying test liquid 17 Optical functional element 33, 54 Sacrificial layer 34f, 53 Flap 36 Check valve 62 Electrode A Sheet unloading process B, B 'Sheet unloading process C First reagent supplying process D Second reagent supplying process E Second 3 Reagent Supply Process F Lamination Bonding Process G Cutting Process H Optical Functional Element Formation Process I 3rd Continuous Sheet Lamination Bonding Process J Sacrificial Layer Formation Process K Sacrificial Layer Elution Process L Electrode Formation Process M Mark for Position Detection M

Abstract

The disclosed microfluidic detection chip manufacturing method involves: a channel formation step for conveying a first continuous sheet and for forming channels by means of molding, shaping or printing in order in the conveyance direction of the first continuous sheet; a reagent supply step for supplying a reagent to the channels; and a lamination/adhesion step for laminating and adhering a second continuous sheet to the first continuous sheet in which channels were formed and to which the reagent was supplied. By means of manufacturing sheets forming multiple microfluidic detection chips, microfluidic detection chips can be manufactured with high productivity, low cost, and without fear of contamination.

Description

マイクロ流路検査チップの製造方法Manufacturing method of microchannel inspection chip
　本発明は、マイクロ流路検査チップの製造方法に関する。 The present invention relates to a method for manufacturing a microchannel inspection chip.
　近年、抗原抗体反応などを利用して感染や妊娠の有無など様々な検査を短時間で免疫学的に検査する簡易検査方法が開発されている。例えば、免疫学的検査方法の一種であるイムノクロマト検査チップの例を図１６に示す。図１６に示す検査チップ１００は、被験液体中に有るか無いか検査すべき抗原を、検査チップ上に配された２か所の抗体が挟むようにして抗原抗体反応を起こさせて検出するため、サンドイッチ法と呼ばれるイムノクロマト検査チップである。検査チップ１００は、ニトロセルロース製のメンブレン上に、サンプルパッド１０２、コンジュゲートパッド１０３、テストライン１０４、コントロールライン１０５、吸収パッド１０６を長手方向に並べて形成されている。 In recent years, a simple test method has been developed in which various tests such as the presence or absence of pregnancy or pregnancy using an antigen-antibody reaction are immunologically tested in a short time. For example, FIG. 16 shows an example of an immunochromatographic test chip which is a kind of immunological test method. Since the test chip 100 shown in FIG. 16 detects an antigen to be tested for presence or absence in a test liquid by causing an antigen-antibody reaction so that two antibodies arranged on the test chip are sandwiched, a sandwich is used. It is an immunochromatography test chip called the method. The test chip 100 is formed by arranging a sample pad 102, a conjugate pad 103, a test line 104, a control line 105, and an absorption pad 106 in a longitudinal direction on a nitrocellulose membrane.
　検査チップ１００のサンプルパッド１０２に、被験液体を滴下すると、被験液体は毛細管現象で図中右方向に進み、コンジュゲートパッド１０３において、金コロイドなどと結合した抗体の標識と被験液体に含まれる抗原たんぱく質が結合し、さらにメンブレン中を進む。標識との抗原抗体反応が十分進んだ時間で、テストライン１０４に達し、ここに浸みこませた試薬の抗体により標識の付いた抗原は捕捉され、蓄積される。 When the test liquid is dropped on the sample pad 102 of the test chip 100, the test liquid proceeds to the right in the figure by capillary action, and the antibody label bound to the gold colloid or the like in the conjugate pad 103 and the antigen contained in the test liquid The protein binds and travels further through the membrane. The antigen-antibody reaction with the label is sufficiently advanced to reach the test line 104, and the labeled antigen is captured and accumulated by the reagent antibody soaked therein.
　金コロイドは褐色をしているため、テストライン１０４で標識抗原が捕捉され蓄積されると、テストライン１０４が褐色に呈するため、所望の抗体の存在を確認できる。被験液体はさらにメンブレン中を進行し、コントロールライン１０５に達すると、所望抗原の有無にかかわらず標識が捕捉され、コントロールライン１０５が褐色に呈する。コントロールライン１０５は、被験液体がきちんとテストライン１０４まで浸みこんで、検査が成功したことを表示する役割を成す。吸収パッド１０６は、役割を終えた被験液体を吸収し続け、継続的に被験液体をメンブレン中で進行させる役割をする。 Since the colloidal gold is brown, when the labeled antigen is captured and accumulated in the test line 104, the test line 104 appears brown, so that the presence of the desired antibody can be confirmed. The test liquid further travels through the membrane, and when it reaches the control line 105, the label is captured regardless of the presence or absence of the desired antigen, and the control line 105 becomes brown. The control line 105 plays a role of displaying that the test liquid is properly immersed in the test line 104 and the test is successful. The absorption pad 106 continues to absorb the test liquid that has finished its role, and continuously advances the test liquid in the membrane.
　このような検査チップは、例えば、特許文献１、特許文献２などに開示されており、検査を簡易な方法で短時間に行うことができるので、診療所などで活用されている。 Such an inspection chip is disclosed in, for example, Patent Document 1, Patent Document 2, and the like, and since it can be performed in a short time by a simple method, it is used in clinics and the like.
　しかるに、従来の検査チップを製造するためには、それぞれに被験液体の吸収性が異なる機能を持たせたサンプルパッド、コンジュゲートパッド、メンブレン、吸収パッドの最低４部品が必要であり、そして、これらの構成部品を裁断し結合して、被験液体が滞ることなく浸みこんで進むように組み立てるために、手間がかかりかつ汚れなどが混入する危険が大きかった。検出される所望の抗体量は、１０４～１０５個／ｍｌの濃度と極めて微量のため、わずかな汚れが混入してもノイズとなり、検査精度を劣化させる。 However, in order to manufacture a conventional test chip, it is necessary to have at least four parts: a sample pad, a conjugate pad, a membrane, and an absorption pad, each of which has a function of different absorbability of the test liquid. In order to assemble and assemble the components so that the test liquid penetrates without stagnation, there is a great risk that it takes time and is contaminated with dirt. Since the desired amount of antibody to be detected is a very small amount of 10 4 to 10 5 / ml, even if a slight amount of dirt is mixed, it becomes noise and deteriorates the inspection accuracy.
　また、前述のイムノクロマト法よりもさらに高精度かつより広範な検査に使えるように、非常に細い流路（マイクロ流路）を使った検査チップ（マイクロ流路検査チップ）が提案されている（例えば、特許文献３参照）。 In addition, an inspection chip (microchannel inspection chip) using a very narrow channel (microchannel) has been proposed so that it can be used for a wider range of inspections with higher accuracy than the immunochromatography method described above (for example, And Patent Document 3).
　マイクロ流路検査チップは、通常は石英ガラス基板上に細い流路が設けられ、滴下された被験液体がこの流路を流れる過程で試薬と反応したり濾過されたりして、分光計などにかけられて蛍光量を測ったりすることで所望の検査が行われる。被験液体は、毛細管現象やポンプによる吸引で流路を流れる。 A microchannel inspection chip is usually provided with a thin channel on a quartz glass substrate, and a dropped test liquid reacts with a reagent or is filtered in the course of flowing through this channel, and is applied to a spectrometer or the like. The desired inspection is performed by measuring the amount of fluorescence. The test liquid flows through the flow path by capillary action or pump suction.
　検査精度上、流路の表面状態や寸法精度、清浄度が重要であるため、マイクロ流路検査チップは、石英ガラスを基板材料に用い、フォトリソグラフを使って露光、エッチングして作られており、さらにカバーガラスを接合して流路にふたをする。そのため、非常に高価な検査チップとなっている。石英ガラス材料は、強酸や強アルカリ、高温にさらすことができるので、前述した汚染に対して非常に清浄に保つことができ、感度の高い検査に適している。 Since the surface condition, dimensional accuracy, and cleanliness of the flow path are important for inspection accuracy, the micro flow path inspection chip is made by using quartz glass as the substrate material and exposing and etching using photolithography. Further, a cover glass is joined to cover the flow path. Therefore, it is a very expensive inspection chip. Quartz glass materials can be exposed to strong acids, strong alkalis, and high temperatures, so that they can be kept very clean against the aforementioned contamination, and are suitable for highly sensitive inspections.
特開２００６－７１６３１号公報JP 2006-71631 A 特開２０１０－２５８８７号公報JP 2010-25858 A 特開２００６－１４９３７９号公報JP 2006-149379 A
　一方で、マイクロ流路検査チップを低価格で製作する試みも進んでおり、熱可塑性プラスチックを射出成形して製造する方法が試みられている。 On the other hand, attempts to produce a micro-channel inspection chip at a low price are also progressing, and a method of producing a thermoplastic by injection molding has been attempted.
　しかしながら、被験液体の反応時間を流速で制御するため、流路の寸法精度が厳しく、これを精度よく成形するには射出成形時間を長くして時間をかけて金型内の成形チップを徐冷した後に金型を開かなければならなかった。しかも、高精度な成形のため成形キャビティ間のバラつき誤差を低減するために、一度の成形で得られる成形チップの個数も多くはできなかった。従って、プラスチック材料を用いた射出成形による製造方法においても、低価格化には限界があった。さらに、このようにして得た成形チップに、プラスチック板を貼って流路のふたをしなければならず、この工程は前述射出成形とは全くの別の工程であり、成形チップの移送、プラスチック板の接合、梱包などの組み立て工程で容易に検査チップが汚れる機会があった。 However, since the reaction time of the test liquid is controlled by the flow rate, the dimensional accuracy of the flow path is strict, and in order to mold this accurately, the injection molding time is lengthened and the molding chip in the mold is gradually cooled over time. Had to open the mold after. In addition, in order to reduce the variation error between the molding cavities for high precision molding, the number of molding chips obtained by one molding cannot be increased. Therefore, there is a limit to reducing the price even in the manufacturing method by injection molding using a plastic material. Furthermore, the molded chip thus obtained has to be covered with a plastic plate to close the flow path, and this process is completely different from the above-described injection molding. There was an opportunity for the inspection chip to easily get dirty in the assembly process such as joining of the plates and packing.
　一旦汚染された検査チップは、汚れを検出することはほぼ不可能であり、汚れを検出できたとしても廃棄することしかできない。汚染された検査チップがもし医療現場で使われた場合には、検査の判断を誤って全く用をなさないだけでなく、害のある治療に結びつく可能性がある。つまり、汚染される機会が多い従来の製造工程は、このような高精度検査チップの製造には基本的に不向きなのである。従って、従来の射出成形による検査チップの製造法は、低コスト化に限界があるだけでなく、品質上においても問題が多かった。 • Once a test chip is contaminated, it is almost impossible to detect dirt, and even if it can be detected, it can only be discarded. If a contaminated test chip is used in a medical setting, it may not only make a mistake in the test decision but also lead to a harmful treatment. That is, the conventional manufacturing process with many opportunities for contamination is basically unsuitable for manufacturing such a high-precision inspection chip. Therefore, the conventional method for producing an inspection chip by injection molding has not only a limit on cost reduction, but also has many problems in terms of quality.
　本発明は、以上のような課題を解決すること、すなわち、高い生産性と低コストを達成でき、かつ汚染の恐れのないマイクロ流路検査チップの製造方法を提供することを目的とする。 An object of the present invention is to solve the above-described problems, that is, to provide a method for manufacturing a microchannel inspection chip that can achieve high productivity and low cost and is free from contamination.
　上記の目的は、第１の連続シートを搬送し、該第１の連続シートの搬送方向に順に、成型、成形、あるいは印刷によって流路を形成する流路形成工程、該流路に試薬を供給する試薬供給工程、流路形成および試薬供給された前記第１の連続シートに第２の連続シートを積層接着する積層接着工程を配置して、複数のマイクロ流路検査チップを形成したシートを製造する製造方法によって達成される。作成されたシートは、その後切断して個別のマイクロ流路検査チップとされるが、切断する工程を積層接着工程の後に配置しても良い。 The above-mentioned purpose is to supply a reagent to the flow path forming step of transporting the first continuous sheet and forming the flow path by molding, molding, or printing in order in the transport direction of the first continuous sheet. Producing a sheet having a plurality of micro-channel test chips by arranging a reagent supplying step, forming a channel, and a laminating and bonding step of laminating and adhering a second continuous sheet to the first continuous sheet supplied with the reagent Achieved by the manufacturing method. The prepared sheet is then cut into individual microchannel inspection chips, but the cutting step may be arranged after the lamination bonding step.
　ここで、流路の形成方法としては、「成型」、「成形」、「印刷」を含むものとし、これらを総称して「形成」という。「成型」とは、固体状の被成型物を加熱や加圧によって軟化させ、型の転写面に密着させて形状を転写するプロセスをいい、「成形」とは、液体状の被成形物を型内に流し込み、加熱やＵＶ光照射などで硬化させて形状を転写するプロセスをいう。また、「印刷」とは、ロール状の版型に被印刷材料（インク）を付着させ、この被印刷材料をベースフィルムに転写するプロセス、またはインクジェット印刷により、微細滴の被印刷材料をノズルから打ち出して形成するプロセスをいう。 Here, the formation method of the flow path includes “molding”, “molding”, and “printing”, and these are collectively referred to as “formation”. “Molding” refers to a process in which a solid molded object is softened by heating or pressurization and is brought into close contact with the transfer surface of the mold to transfer the shape. “Molding” refers to a liquid molded object. A process in which a shape is transferred by pouring into a mold and curing by heating or UV light irradiation. “Printing” means that a printing material (ink) is attached to a roll-shaped plate and the printing material is transferred to a base film, or ink droplets are used to remove the printing material in fine droplets from a nozzle. A process that is formed by punching out.
　本発明は、さらに被験液体が試薬と反応して最終的に検査を行う検査部分に対応して光学機能素子を第２のシート上、もしくは、第１のシートの裏面側に形成する工程を配置することによって、製造されたマイクロ流路検査チップで検査を行う際、光学的に拡大や分光などを行うことができる。マイクロ流路検査チップの種類に合わせて単一の観察装置に適合するよう光学機能素子を設計すれば、単一の観察装置で複数の種類の異なる検査を行うことができ便利である。 The present invention further includes a step of forming an optical functional element on the second sheet or on the back surface side of the first sheet corresponding to the inspection portion that is finally inspected by the test liquid reacting with the reagent. By doing so, when inspecting with the manufactured microchannel inspection chip, optical enlargement or spectroscopy can be performed. If an optical functional element is designed so as to be adapted to a single observation device according to the type of microchannel inspection chip, a plurality of different types of inspection can be performed with a single observation device.
　さらに、マイクロ流路検査チップの流路上で機能する可動構造を形成して弁やポンプとする、あるいは電極を形成して電気泳動などの電気的作用で検査を行うこともできる。 Furthermore, a movable structure that functions on the flow path of the micro flow path inspection chip can be formed to form a valve or a pump, or an electrode can be formed to perform inspection by an electrical action such as electrophoresis.
　ここで、本発明では、「流路」という言葉は、液が流れる流路溝と試薬などが固定される液溜り、あるいは弁やポンプとして機能する可動構造を形成した流路部分、さらには、電極を形成した流路部分を含む語として用いている。また、被験液体、試薬なる言葉も医療分野のみならず、生化学分野や農業分野などでの検査を行うものを含む語として用いる。 Here, in the present invention, the term “flow channel” means a flow channel part in which a flow channel in which a liquid flows and a liquid reservoir in which a reagent or the like is fixed, or a movable structure that functions as a valve or a pump, It is used as a term including the flow path portion in which the electrode is formed. In addition, the terms test liquid and reagent are used as terms including not only the medical field, but also those in the biochemical field, the agricultural field, and the like.
　さらに具体的には、本発明の目的は、以下に記載の製造方法によって達成できる。
１．複数のマイクロ流路検査チップを連続して形成するマイクロ流路検査チップの製造方法であって、
　第１連続シートを搬送し、該第１連続シートの搬送方向に順に、
　成型、成形、あるいは印刷によって流路を形成する流路形成工程、
　該流路に試薬を供給する試薬供給工程、
　流路形成、試薬供給された前記第１連続シートに第２連続シートを積層接着する積層接着工程、
　を配置して、複数のマイクロ流路検査チップを形成したシートを作成することを特徴とするマイクロ流路検査チップの連続方法。
２．複数のマイクロ流路検査チップを連続して形成するマイクロ流路検査チップの製造方法であって、
　第１連続シートを搬送し、該第１連続シートの搬送方向に順に、
　成型、成形、あるいは印刷によって流路を形成する流路形成工程、
　該流路に試薬を供給する試薬供給工程、
　第２連続シートに回折レンズ、フレネルレンズ、あるいは回折格子のいずれかの光学機能素子を形成する光学機能素子形成工程、
　流路形成、試薬供給された前記第１連続シートに前記光学機能素子が形成された前記第２連続シートを積層接着する積層接着工程、
　を配置して、複数のマイクロ流路検査チップを形成したシートを作成することを特徴とするマイクロ流路検査チップの製造方法。
３．前記第２連続シートの前記光学機能素子が形成された面を覆う第３連続シートを積層する工程を有することを特徴とする前記２に記載のマイクロ流路検査チップの製造方法。
４．複数のマイクロ流路検査チップを連続して形成するマイクロ流路検査チップの製造方法であって、
　第１連続シートを搬送し、該第１連続シートの搬送方向に順に、
　成型、成形、あるいは印刷によって流路を形成する流路形成工程、
　該流路に試薬を供給する試薬供給工程、
　前記流路形成工程と同時に、あるいはその前後に、前記第１連続シートの裏面に回折レンズ、フレネルレンズ、あるいは回折格子のいずれかの光学機能素子を形成する光学機能素子形成工程、
　流路形成、試薬供給、光学機能素子形成された前記第１連続シートに第２連続シートを積層接着する積層接着工程、
　を配置して、複数のマイクロ流路検査チップを形成したシートを作成することを特徴とするマイクロ流路検査チップの製造方法。
５．前記光学機能素子形成工程が、流路形成装置と光学機能素子形成装置を互いに対向して配置し、この間に前記第１連続シートを通過させて、流路と光学機能素子を前記第１連続シートの両面に同時に形成することを特徴とする前記４に記載のマイクロ流路検査チップの製造方法。
６．前記第１連続シートの前記光学機能素子が形成された面を覆う第３連続シートを積層する工程を有することを特徴とする前記４または５に記載のマイクロ流路検査チップの製造方法。
７．前記流路形成工程の前に、犠牲層を形成する工程を設け、前記流路形成工程で流路とともに片持ち構造のフラップ部を流路中に形成し、次いで前記犠牲層を溶出除去する犠牲層除去工程を設けたことを特徴とする前記１から６のいずれかに記載のマイクロ流路検査チップの製造方法。
８．前記流路形成工程の前に、前記流路形成工程で形成する流路の部分に電極を形成する工程を設け、電気的検査を行えるようにしたことを特徴とする前記１から６のいずれかに記載のマイクロ流路検査チップの製造方法。
９．前記第１連続シート上の被験液体を溜める液溜りに対応する前記第２連続シート上の位置に被験液体供給用の穴を形成する工程を有することを特徴とする前記１から６のいずれかに記載のマイクロ流路検査チップの製造方法。
１０．前記第１連続シート上の前記液溜りと前記第２連続シートの前記穴とを検出するセンサを工程中に配置し、位置合わせを行うことを特徴とする前記９に記載のマイクロ流路検査チップの製造方法。
１１．前記流路形成工程において、流路とともに位置検出用のマークを形成し、該マークを検出することにより位置合わせを行うことを特徴とする前記９に記載のマイクロ流路検査チップの製造方法。
１２．前記積層接着工程の後に、一体となったシートを連続して送りながら切断し個片化する切断工程を設けたことを特徴とする前記１から１１のいずれかに記載のマイクロ流路検査チップの製造方法。
１３．前記第１連続シートに形成した流路部分と、前記第２連続シートの積層接着面に親水処理を行うことを特徴とする前記１から１２のいずれかに記載のマイクロ流路検査チップの製造方法。
１４．前記第１連続シートまたは前記第２連続シートの材料が、プラスチックまたはガラスであることを特徴とする前記１から１３のいずれかに記載のマイクロ流路検査チップの製造方法。 More specifically, the object of the present invention can be achieved by the production method described below.
1. A method of manufacturing a microchannel inspection chip that continuously forms a plurality of microchannel inspection chips,
The first continuous sheet is conveyed, and sequentially in the conveying direction of the first continuous sheet,
A flow path forming step for forming a flow path by molding, molding, or printing;
A reagent supplying step of supplying a reagent to the flow path;
Forming a flow path, a lamination bonding step of laminating and bonding a second continuous sheet to the first continuous sheet supplied with the reagent,
To form a sheet on which a plurality of microchannel inspection chips are formed, and a continuous method of microchannel inspection chips.
2. A method of manufacturing a microchannel inspection chip that continuously forms a plurality of microchannel inspection chips,
The first continuous sheet is conveyed, and sequentially in the conveying direction of the first continuous sheet,
A flow path forming step for forming a flow path by molding, molding, or printing;
A reagent supplying step of supplying a reagent to the flow path;
An optical functional element forming step of forming an optical functional element of either a diffraction lens, a Fresnel lens, or a diffraction grating on the second continuous sheet;
Laminate bonding step of laminating and bonding the second continuous sheet in which the optical functional element is formed to the first continuous sheet supplied with the flow path and the reagent,
And producing a sheet on which a plurality of microchannel inspection chips are formed.
3. 3. The method for manufacturing a micro-channel inspection chip according to 2 above, further comprising a step of laminating a third continuous sheet that covers a surface of the second continuous sheet on which the optical functional element is formed.
4). A method of manufacturing a microchannel inspection chip that continuously forms a plurality of microchannel inspection chips,
The first continuous sheet is conveyed, and sequentially in the conveying direction of the first continuous sheet,
A flow path forming step for forming a flow path by molding, molding, or printing;
A reagent supplying step of supplying a reagent to the flow path;
An optical functional element forming step of forming an optical functional element of any one of a diffraction lens, a Fresnel lens, and a diffraction grating on the back surface of the first continuous sheet simultaneously with or before and after the flow path forming step,
Laminate bonding step of laminating and bonding a second continuous sheet to the first continuous sheet on which flow path formation, reagent supply, and optical functional element are formed,
And producing a sheet on which a plurality of microchannel inspection chips are formed.
5. In the optical functional element forming step, the flow path forming device and the optical functional element forming device are arranged to face each other, and the first continuous sheet is passed between them, and the flow path and the optical functional element are connected to the first continuous sheet. 5. The method for producing a microchannel inspection chip as described in 4 above, wherein the microchannel inspection chip is simultaneously formed on both surfaces of the microchannel inspection chip.
6). 6. The method of manufacturing a microchannel inspection chip according to 4 or 5, further comprising a step of laminating a third continuous sheet that covers a surface of the first continuous sheet on which the optical functional element is formed.
7). A sacrificial layer forming step is provided before the flow path forming step, a cantilevered flap portion is formed in the flow path in the flow path forming step, and then the sacrificial layer is eluted and removed. 7. The method of manufacturing a microchannel inspection chip according to any one of 1 to 6, wherein a layer removing step is provided.
8). Any one of 1 to 6 above, wherein a step of forming an electrode is provided in a portion of the flow path formed in the flow path forming step before the flow path forming step so that electrical inspection can be performed. The manufacturing method of the microchannel test | inspection chip | tip of description.
9. The method according to any one of 1 to 6, further comprising a step of forming a hole for supplying a test liquid at a position on the second continuous sheet corresponding to a liquid reservoir for storing the test liquid on the first continuous sheet. The manufacturing method of the microchannel test | inspection chip of description.
10. 10. The microchannel inspection chip according to 9, wherein a sensor for detecting the liquid pool on the first continuous sheet and the hole of the second continuous sheet is disposed in the process and aligned. Manufacturing method.
11. 10. The method of manufacturing a microchannel inspection chip according to 9, wherein in the channel formation step, a position detection mark is formed together with the channel, and alignment is performed by detecting the mark.
12 12. The microchannel inspection chip according to any one of 1 to 11 above, wherein a cutting step is provided after the laminating and bonding step, wherein the integrated sheet is cut while being continuously fed and separated into individual pieces. Production method.
13. 13. The method of manufacturing a microchannel inspection chip according to any one of 1 to 12, wherein a hydrophilic treatment is performed on a flow path portion formed in the first continuous sheet and a laminated adhesive surface of the second continuous sheet. .
14 14. The method of manufacturing a microchannel inspection chip according to any one of 1 to 13, wherein the material of the first continuous sheet or the second continuous sheet is plastic or glass.
　本発明は、高い生産性と低コスト化が達成でき、かつ汚染の恐れのないマイクロ流路検査チップの製造を実現することができる。 The present invention can achieve high productivity and low cost, and can produce a micro-channel inspection chip that is free from contamination.
本発明の第１実施形態のマイクロ流路検査チップを示す平面図と断面図。The top view and sectional drawing which show the microchannel inspection chip | tip of 1st Embodiment of this invention. 本発明の第１実施形態の製造方法を示す工程図。Process drawing which shows the manufacturing method of 1st Embodiment of this invention. 本発明で用いられるアキュムレータ機構を示す模式図。The schematic diagram which shows the accumulator mechanism used by this invention. 本発明の第２実施形態のマイクロ流路検査チップを示す平面図と断面図。The top view and sectional drawing which show the microchannel test | inspection chip of 2nd Embodiment of this invention. 本発明の第２実施形態の製造方法を示す工程図。Process drawing which shows the manufacturing method of 2nd Embodiment of this invention. 本発明の第２実施形態のマイクロ流路検査チップの変形例を示す平面図と断面図。The top view and sectional drawing which show the modification of the microchannel test | inspection chip of 2nd Embodiment of this invention. 本発明の第２実施形態の変形例の製造方法を示す部分工程図。Partial process drawing which shows the manufacturing method of the modification of 2nd Embodiment of this invention. 本発明の第３実施形態のマイクロ流路検査チップの形成方法を示す模式図。The schematic diagram which shows the formation method of the microchannel inspection chip | tip of 3rd Embodiment of this invention. 本発明の第３実施形態のマイクロ流路検査チップの変形例を示す断面図。Sectional drawing which shows the modification of the microchannel test | inspection chip of 3rd Embodiment of this invention. 本発明の第３実施形態のマイクロ流路検査チップの変形例の製造方法を示す部分工程図。The partial process figure which shows the manufacturing method of the modification of the microchannel inspection chip | tip of 3rd Embodiment of this invention. 本発明の第３実施形態のマイクロ流路検査チップの他の変形例を示す断面図。Sectional drawing which shows the other modification of the microchannel test | inspection chip of 3rd Embodiment of this invention. 本発明の第４実施形態のマイクロ流路検査チップを示す部分平面図。The fragmentary top view which shows the microchannel test | inspection chip of 4th Embodiment of this invention. 本発明の第４実施形態のマイクロ流路検査チップの製造方法を示す部分工程図。The partial process figure which shows the manufacturing method of the microchannel inspection chip | tip of 4th Embodiment of this invention. 本発明の積層接着工程の変形例を示す模式図。The schematic diagram which shows the modification of the lamination | stacking adhesion | attachment process of this invention. 本発明の切断工程の変形例を示す模式図。The schematic diagram which shows the modification of the cutting process of this invention. 従来のイムノクロマト検査チップの構成を示す平面図。The top view which shows the structure of the conventional immunochromatography test chip.
　［第１実施形態］
　本発明によって製造できるマイクロ流路検査チップは、医療分野、生化学分野、農業分野などいろいろな分野の検査用途に合わせて設計されるが、実施形態として、イムノクロマト検査チップと同様の機能を果たす検査チップを例にして説明する。 [First Embodiment]
The microchannel inspection chip that can be manufactured according to the present invention is designed for inspection applications in various fields such as the medical field, biochemical field, and agricultural field. However, as an embodiment, a test that performs the same function as an immunochromatographic chip. A chip will be described as an example.
　図１は、第１実施形態のマイクロ流路検査チップ１の平面図と断面図であり、図において左側から、被験液体供給用の液溜り２、流路溝３ａ、捕捉抗体用の液溜り４、流路溝３ｂ、捕捉試薬用の液溜り５、流路溝３ｃ、反応後の液を溜める液溜り６が第１連続シート７上に並んで形成されている。また、位置検出用のマークＭが左下の部分に形成される。そして、これらの流路、マークが形成された第１連続シート７を覆うように第２連続シート８が積層接着されており、第１連続シート７の被験液体用の液溜り２に対応する第２連続シート８の部分に被験液体供給用の穴９が形成されている。第１連続シート７、第２連続シート８の少なくとも一方は検査観察のため透明シート材料で構成される。 FIG. 1 is a plan view and a cross-sectional view of the microchannel inspection chip 1 of the first embodiment. From the left side in the figure, a liquid reservoir 2 for supplying a test liquid, a channel groove 3a, and a liquid reservoir 4 for a capture antibody. The channel groove 3b, the liquid reservoir 5 for the capture reagent, the channel groove 3c, and the liquid reservoir 6 for storing the liquid after the reaction are formed side by side on the first continuous sheet 7. Further, a mark M for position detection is formed in the lower left part. A second continuous sheet 8 is laminated and adhered so as to cover the first continuous sheet 7 on which these flow paths and marks are formed, and the first continuous sheet 7 corresponds to the liquid reservoir 2 for the test liquid. A hole 9 for supplying a test liquid is formed in a portion of the two continuous sheets 8. At least one of the first continuous sheet 7 and the second continuous sheet 8 is made of a transparent sheet material for inspection observation.
　被験液体供給用の液溜り２には、標識抗体が固定されており、液溜り２に穴９から被験液体が滴下されると、標識抗体と反応した液体は毛細管現象によって順次、流路溝３ａ、捕捉抗体が固定された液溜り４、流路溝３ｂ、捕捉試薬が固定された液溜り５、流路溝３ｃと進み、最後に液溜り６に溜まる。そして、液溜まり５の部分において検査結果を判定する。 A labeled antibody is fixed to the liquid reservoir 2 for supplying the test liquid. When the test liquid is dropped into the liquid reservoir 2 from the hole 9, the liquid that has reacted with the labeled antibody is sequentially flown through the flow channel 3a by capillary action. Then, the flow proceeds to the liquid reservoir 4 to which the capture antibody is immobilized, the flow channel 3b, the liquid reservoir 5 to which the capture reagent is immobilized, and the flow channel 3c, and finally accumulates in the liquid reservoir 6. Then, the inspection result is determined at the portion of the liquid reservoir 5.
　なお、被験液体供給用の穴９に替えて第１連続シート７の左側側面に開口する流路９ａ（図に点線で示す）を形成して、この開口から別体のマイクロポンプなどで被験液体を供給するようにしても良い。 In addition, it replaces with the hole 9 for test liquid supply, and forms the flow path 9a (it shows with a dotted line in the figure) opened on the left side surface of the 1st continuous sheet 7, and test liquid with a separate micropump etc. from this opening May be supplied.
　本発明において、形成する流路溝の大きさは、深さ１０～１００μｍ程度、幅が３０～５００μｍ程度であり、用途によって異なる。また、流路の途中に被験液体を検査する試薬を設置するための液溜まりを配置するが、この液溜まりは、裸眼でも試薬の色変りが確認しやすくし、装置で読み取る場合でも感度が高くなるように、通常は数ｍｍ程度の大きさとする。 In the present invention, the size of the channel groove to be formed is about 10 to 100 μm in depth and about 30 to 500 μm in width, and varies depending on the application. In addition, a liquid reservoir for installing a reagent for inspecting the test liquid is arranged in the middle of the flow path, but this liquid reservoir makes it easy to check the color change of the reagent even with the naked eye, and the sensitivity increases even when reading with an apparatus. Thus, it is usually set to a size of about several mm.
　図２は、マイクロ流路検査チップ１を製造する基本工程を説明する模式図である。マイクロ流路検査チップ１を製造する基本工程は、
・第１連続シート７を搬出するシート搬出工程Ａ、
・流路を形成するシート搬出工程Ｂ、
・標識抗体を供給する第１試薬供給工程Ｃ、
・捕捉抗体を供給する第２試薬供給工程Ｄ、
・捕捉試薬を供給する第３試薬供給工程Ｅ、
・第１連続シート７に第２連続シート８を積層接着する積層接着工程Ｆ、
・積層接着された連続シートを切断し検査チップを個片化する切断工程Ｇ、
からなる。 FIG. 2 is a schematic diagram illustrating a basic process for manufacturing the microchannel inspection chip 1. The basic process for manufacturing the microchannel inspection chip 1 is as follows:
-Sheet unloading step A for unloading the first continuous sheet 7,
・ Sheet unloading process B to form a flow path,
First reagent supply step C for supplying labeled antibody,
A second reagent supply step D for supplying the capture antibody,
A third reagent supply step E for supplying a capture reagent,
A laminating and bonding step F for laminating and bonding the second continuous sheet 8 to the first continuous sheet 7;
-Cutting process G for cutting the laminated sheets and cutting the inspection chips into pieces.
Consists of.
　これらの工程を行う製造装置は、クリーンルーム内に設置され、埃、細菌類をカットするフィルターを通した空気の供給によって、製造する検査チップを汚染しないようにされている。また、製造工程は図示しない制御装置によって遠隔制御されるので、人手に触れることなく製造を完結でき、極めて汚染を少なくできる。 The manufacturing apparatus that performs these processes is installed in a clean room, and is configured so as not to contaminate the inspection chip to be manufactured by supplying air through a filter that cuts dust and bacteria. Further, since the manufacturing process is remotely controlled by a control device (not shown), the manufacturing can be completed without touching human hands, and contamination can be extremely reduced.
　シート搬出工程Ａでは、第１連続シート７をロール状に巻いたロールシートを搬送装置にセットし、第１連続シート７を後工程まで引き伸ばす。第１連続シート７は、厚さ５００μｍ、幅の３００ｍｍのプラスチックシートであり、送り速度は１ｍ／ｍｉｎである。 In the sheet unloading process A, a roll sheet obtained by winding the first continuous sheet 7 in a roll shape is set in a conveying device, and the first continuous sheet 7 is stretched to a subsequent process. The first continuous sheet 7 is a plastic sheet having a thickness of 500 μm and a width of 300 mm, and the feeding speed is 1 m / min.
　流路形成工程Ｂは、被験液体供給用の液溜り２、流路溝３ａ、テスト試薬用の液溜り４、流路溝３ｂ、捕捉試薬用の液溜り５、流路溝３ｃ、反応液の液溜り６からなる流路と、マークＭを第１連続シート７上に形成する工程で、本実施形態では、これらの流路のネガをロール型Ｂ１上に形成し、ロール型Ｂ１の内部に配置された加熱源でロール型Ｂ１を加熱して第１連続シート７上に流路を熱転写している（いわゆる成型工程）。 The flow path forming step B includes a liquid reservoir 2 for supplying a test liquid, a flow path groove 3a, a liquid reservoir 4 for a test reagent, a flow path groove 3b, a liquid reservoir 5 for a capture reagent, a flow path groove 3c, a reaction liquid In this embodiment, the flow path composed of the liquid reservoir 6 and the mark M are formed on the first continuous sheet 7. In this embodiment, the negatives of these flow paths are formed on the roll mold B 1, and are formed inside the roll mold B 1. The roll mold B1 is heated by the arranged heating source to thermally transfer the flow path onto the first continuous sheet 7 (so-called molding process).
　本発明において流路は、先述の「成型」、「成形」、「印刷」のいずれかの方法で形成することができる。すなわち、「成型」は、直接ロール版に形成された流路パターンを加熱圧着して、シート上に流路を転写して形成する方法である。また、「成形」とは、熱硬化性樹脂やＵＶ硬化性樹脂、ガラス材料などの流体状の材料を流路パターンが形成されたロール型に充填し、加熱またはＵＶ照射によってシート上に硬化転写しながら流路を形成する方法であり、「印刷」は凹版などのロール版の流路に樹脂材料を充填し、そのままシート上へ転写して形成する方法である。この時、オフセット印刷の要領で、ブランケットに一旦樹脂材料を移した後にシート上に転写してもよい。さらに、シート上に樹脂材料を転写する直前に樹脂表面を半硬化状態にして粘度を向上させておくと、シートとの密着性が格段に向上して樹脂材料の版からの離れが良くなり、微細なパターンも高精度にシート上に転写することができる。また、ロール版を使わずにインクジェットによる微小液滴による「印刷」であっても良い。 In the present invention, the flow path can be formed by any one of the above-described “molding”, “molding”, and “printing” methods. That is, “molding” is a method in which a flow path pattern formed directly on a roll plate is heat-pressed and the flow path is transferred onto a sheet. “Molding” refers to filling a roll mold with a flow path pattern filled with a fluid material such as thermosetting resin, UV curable resin, or glass material, and curing and transferring onto a sheet by heating or UV irradiation. However, “printing” is a method in which a resin material is filled in a flow path of a roll plate such as an intaglio and transferred to a sheet as it is. At this time, the resin material may be once transferred to the blanket and then transferred onto the sheet in the manner of offset printing. Furthermore, if the viscosity of the resin surface is improved by making the resin surface semi-cured immediately before transferring the resin material onto the sheet, the adhesion with the sheet is greatly improved and the separation from the plate of the resin material is improved, A fine pattern can be transferred onto the sheet with high accuracy. Further, “printing” by micro droplets by ink jet without using a roll plate may be used.
　第１試薬供給工程Ｃ、第２試薬供給工程Ｄ、および第３試薬供給工程Ｅは、それぞれ標識抗体、捕捉抗体、捕捉試薬（以下、まとめて「試薬」という）を液溜り４、５、６に供給固定する工程である。これらの試薬は液溜まり上に印刷装置Ｃ１、Ｄ１、Ｅ１によって供給塗布される。 In the first reagent supply step C, the second reagent supply step D, and the third reagent supply step E, the labeled antibody, the capture antibody, and the capture reagent (hereinafter collectively referred to as “reagent”) are stored in the liquid reservoirs 4, 5, and 6, respectively. This is a process of fixing the supply. These reagents are supplied and applied on the liquid reservoir by the printing apparatuses C1, D1, and E1.
　印刷方式は、数μｍ程度であれば凹版などを使い、１０～３０μｍ程に厚くつけるのであれば凸版や反転法などを使う。さらに１００μｍを超える厚みに対してはスクリーン印刷を使うことができる。 The printing method uses intaglio etc. if it is about several μm, and if it is thick to about 10-30 μm, use letterpress or reversal method. Furthermore, screen printing can be used for thicknesses exceeding 100 μm.
　供給された試薬は、乾燥させて液溜まり上に固定するのであるが、乾燥は、各試薬供給工程の後、または最後にまとめて赤外線ランプ（図示せず）などを用いて加熱することで行う。 The supplied reagent is dried and fixed on the liquid reservoir. Drying is performed by heating using an infrared lamp (not shown) or the like after each reagent supply step or at the end. .
　また、第１試薬供給工程Ｃ、第２試薬供給工程Ｄ、および第３試薬供給工程Ｅは、印刷の前にマークＭを検出するセンサＣ２、Ｄ２、Ｅ２を利用し、これらのセンサの検出信号に基づき、各印刷装置のロール型の回転を制御してそれぞれの液溜まりに正確に試薬を供給する。 The first reagent supply process C, the second reagent supply process D, and the third reagent supply process E use sensors C2, D2, and E2 that detect the mark M before printing, and the detection signals of these sensors. Based on the above, the rotation of the roll type of each printing apparatus is controlled to accurately supply the reagent to each liquid reservoir.
　積層接着工程Ｆでは、流路が形成され各試薬が供給された第１連続シート７に第２連続シート８を積層接着する。ここで、第２連続シート８は、ダイとダイに対してシートを挟んで往復運動するパンチを有する穿孔装置Ｆ１により被験液体供給用の穴９を形成されてから加熱加圧ロール対Ｆ２の間に供給される。なお、ダイの下にはクズかごが配置され、穿孔クズを溜めている。 In the lamination adhesion step F, the second continuous sheet 8 is laminated and adhered to the first continuous sheet 7 to which the flow path is formed and each reagent is supplied. Here, the second continuous sheet 8 is formed between the heating and pressurizing roll pair F2 after the hole 9 for supplying the test liquid is formed by the punching device F1 having a die and a punch that reciprocates between the die and the sheet. To be supplied. A scrap basket is disposed under the die to collect perforated scraps.
　第１連続シート７上の被験液体用液溜まり２と穴９との位置合わせは、第１連続シート７上のマークＭの検出に基づき、穿孔装置Ｆ１の作動を制御して適切なタイミングで穴９を開けることで行う。他の方法としては、第２連続シート８にあらかじめ穴９を開けておき、マークＭの検出と穴９の検出に基づき、第２連続シート供給ロールと積層接着工程Ｆの間に配置したアキュムレータ機構で第２連続シート８の搬送速度を調整して位置合わせする。なお、マークＭを設けない場合は、液溜まり２と穴９の縁を検出して位置合わせを行うことができる。 The alignment of the liquid reservoir 2 for the test liquid on the first continuous sheet 7 and the hole 9 is based on the detection of the mark M on the first continuous sheet 7 to control the operation of the punching device F1 at an appropriate timing. This is done by opening 9. As another method, an accumulator mechanism in which a hole 9 is formed in the second continuous sheet 8 in advance and is arranged between the second continuous sheet supply roll and the laminating and bonding step F based on the detection of the mark M and the detection of the hole 9. To adjust the conveying speed of the second continuous sheet 8 and align the position. When the mark M is not provided, alignment can be performed by detecting the edge of the liquid reservoir 2 and the hole 9.
　図３は、アキュムレータ機構を示す模式図であり、アキュムレータ機構は、複数の固定ローラ１０Ａとダンスローラ１０Ｂとを交互に配置し、それぞれのローラにシート材を交互に掛け合わせる構成であり、ダンスローラ１０Ｂを矢印のように移動させることにより、搬入側と搬出側の速度を変更、あるいは停止することができる。 FIG. 3 is a schematic diagram showing an accumulator mechanism. The accumulator mechanism has a configuration in which a plurality of fixed rollers 10A and dance rollers 10B are alternately arranged, and a sheet material is alternately hung on each roller. By moving 10B as shown by the arrow, the speed on the carry-in side and the carry-out side can be changed or stopped.
　第１連続シート７と第２連続シート８との接着は、両シートとも同じプラスチックシートであるので、対向する加熱加圧ロール対Ｆ２間を加熱加圧しながら通して両シートを密着させ接合する。この時、プラスチックのガラス転位点以上の温度をかけると、プラスチックが軟化して流路断面形状が崩れるので、ガラス転位点よりも１０～３０℃低い温度とする。加圧力は、１～５ｋｇ／ｃｍ２程度とする。また、積層接着工程の前に透明接着剤を塗布して積層接着をより完全にすることもできる。 Adhesion between the first continuous sheet 7 and the second continuous sheet 8 is the same plastic sheet, so that the sheets are brought into close contact with each other while being heated and pressed between the opposed heating and pressing roll pair F2. At this time, if a temperature equal to or higher than the glass transition point of the plastic is applied, the plastic is softened and the cross-sectional shape of the flow path is destroyed. The applied pressure is about 1 to 5 kg / cm 2 . In addition, a transparent adhesive can be applied before the lamination bonding step to make the lamination adhesion more complete.
　流路形成工程Ｂで、流路を樹脂成形または印刷で形成する場合は、樹脂を半硬化状態にしておき、積層接着工程Ｆで完全に接着するとよい。 When the flow path is formed by resin molding or printing in the flow path forming step B, the resin is preferably in a semi-cured state and is completely bonded in the lamination bonding step F.
　切断工程Ｇは、マイクロ流路検査チップを個片化する工程である。本実施形態のマイクロ流路検査チップは、チップ長３０ｍｍ、幅１５ｍｍの大きさに切断される。 The cutting process G is a process of dividing the microchannel inspection chip into individual pieces. The microchannel inspection chip of this embodiment is cut into a chip length of 30 mm and a width of 15 mm.
　本実施形態ではシート材料がプラスチックであるので、積層後に刃物による断裁で個片に切断する。図２において、ロータリーダイＧ１のドラム表面上に帯状の刃物Ｇ２を設置して、ロータリーダイＧ１とベアラＧ３をシート送りに同期して回転することで、設定した刃物Ｇ２の正確な寸法で断裁が実現できる。図示の例は、シートの幅方向にのみ刃物を設けた例で、マイクロ流路検査チップは１列に並んだ形に切断され、別工程で個片化される。ただし、図２では個片化したマイクロ流路検査チップを図示している。 In this embodiment, since the sheet material is plastic, it is cut into individual pieces by cutting with a blade after lamination. In FIG. 2, a strip-shaped cutter G2 is installed on the drum surface of the rotary die G1, and the rotary die G1 and the bearer G3 are rotated in synchronization with sheet feeding, so that cutting can be performed with an accurate dimension of the set cutter G2. realizable. The illustrated example is an example in which a blade is provided only in the width direction of the sheet, and the microchannel inspection chips are cut in a line and separated into individual pieces in a separate process. However, FIG. 2 shows a microchannel inspection chip separated into pieces.
　一方、ロータリーダイＧ１を充分大きくし、刃物を抜き刃とすれば、１つ１つのマイクロ流路検査チップを個片化できる。この場合は抜きカスを巻き取る構成も必要である。 On the other hand, if the rotary die G1 is made sufficiently large and the cutter is used as a cutting blade, each microchannel inspection chip can be separated into individual pieces. In this case, it is also necessary to have a configuration for winding the punched residue.
　この切断方法は、単純な工程のため、シートの送り速度にほとんど問題なく追従することができ、非常に効率が良い。なお、シートを切断することなく、ロールに巻き取り、別工程で個片化してもよい。 Since this cutting method is a simple process, it can follow the sheet feeding speed almost without any problem and is very efficient. In addition, you may wind up to a roll and cut into pieces by another process, without cut | disconnecting a sheet | seat.
　［シート材料］
　本発明の第１シート、第２シートに用いることができる材料は、プラスチック材料、ガラス材料が好適である。プラスチック材料としては、アクリル、ポリカーボネート、ポリスチレン、ＣＯＣ（シクロオレフィンコポリマー）がある。シート材の厚みは、１μｍ～１ｍｍ程度である。幅は、このシート材の上にマトリックス状にマイクロ流路検査チップが形成されていくので、製造するマイクロ流路検査チップの大きさにも依存するが、３００ｍｍ程度が好適である。あまりに幅を広くすると精度を高く保つための製造設備が高価になり、幅を狭くすると、収量が少なくなる。 [Sheet material]
The material that can be used for the first sheet and the second sheet of the present invention is preferably a plastic material or a glass material. Plastic materials include acrylic, polycarbonate, polystyrene, and COC (cycloolefin copolymer). The thickness of the sheet material is about 1 μm to 1 mm. Since the microchannel inspection chip is formed in a matrix on the sheet material, the width is preferably about 300 mm, although it depends on the size of the microchannel inspection chip to be manufactured. If the width is too wide, manufacturing equipment for maintaining high accuracy becomes expensive, and if the width is narrowed, the yield decreases.
　ガラス材料としては無アルカリまたは低アルカリのガラスがある。ガラスシートは、厚みが５００μｍ以下のシート材料がロール形態で既に市販されており、これを使うことができる。 Glass materials include alkali-free or low-alkali glass. As the glass sheet, a sheet material having a thickness of 500 μm or less is already commercially available in roll form, and this can be used.
　［成形、印刷の場合の流路形成材料］
　上記第１実施形態では、流路は成型によって第１連続シート７上に転写したが、成形や印刷によって形成することもできる。 [Flow path forming material for molding and printing]
In the said 1st Embodiment, although the flow path was transcribe | transferred on the 1st continuous sheet 7 by shaping | molding, it can also form by shaping | molding or printing.
　この場合の流路形成材料としては、ゲルガラスや低融点ガラスペーストなどのガラス材料、あるいはベークライトやエポキシ樹脂、アクリル樹脂などの熱硬化性樹脂またはＵＶ硬化性樹脂などを用いることができ、これら材料を流路の型を形成したロール型に供給し、成形または印刷するのである。 As the flow path forming material in this case, glass materials such as gel glass and low melting point glass paste, thermosetting resins such as bakelite, epoxy resin, acrylic resin, or UV curable resins can be used. It is supplied to a roll mold in which a flow path mold is formed, and is molded or printed.
　［第２実施形態］
　図４は、本発明の第２実施形態のマイクロ流路検査チップ１１を示す図である。第２実施形態のマイクロ流路検査チップ１１は、光学機能素子を備えている。 [Second Embodiment]
FIG. 4 is a diagram showing the microchannel inspection chip 11 according to the second embodiment of the present invention. The microchannel inspection chip 11 of the second embodiment includes an optical function element.
　図４（ａ）の平面図、図４（ｂ）の断面図に示すように、マイクロ流路検査チップ１１は、被験液体供給用の液溜り１２、流路溝１３、反応後の液を溜める液溜り１４が第１連続シート１５上に形成されており、この上に第２連続シート１６が積層接着されるが、第２連続シート１６の表面には、光学機能素子１７が形成され、さらに、光学機能素子１７を保護するため、第３連続シート１８がこの上に積層されている。また、第２連続シート１６、第３連続シート１８には、被験液体を供給する穴１９が形成されている。 As shown in the plan view of FIG. 4A and the cross-sectional view of FIG. 4B, the microchannel inspection chip 11 stores a liquid reservoir 12 for supplying a test liquid, a channel groove 13, and a liquid after reaction. The liquid reservoir 14 is formed on the first continuous sheet 15, and the second continuous sheet 16 is laminated and bonded thereon. On the surface of the second continuous sheet 16, an optical functional element 17 is formed, and In order to protect the optical functional element 17, a third continuous sheet 18 is laminated thereon. The second continuous sheet 16 and the third continuous sheet 18 are formed with holes 19 for supplying the test liquid.
　マイクロ流路検査チップ１１は、被験液体供給用の液溜り１２に試薬が固定されており、被験液体供給穴１９から被験液体が滴下されると、試薬と被験液体が反応して反応液溜まり１４に移動する。反応液溜まり１４で進行した反応を観察するわけであるが、光学機能素子１７が形成されているので、観察がより容易になる。 The microchannel inspection chip 11 has a reagent fixed to a liquid reservoir 12 for supplying a test liquid. When the test liquid is dropped from the test liquid supply hole 19, the reagent and the test liquid react to react with each other. Move to. The reaction proceeding in the reaction liquid reservoir 14 is observed. However, since the optical functional element 17 is formed, the observation becomes easier.
　光学機能素子１７としては、回折レンズ、フレネルレンズ、回折格子、あるいはその他の回折素子などを形成することができ、それぞれ被験液体の反応の観察の仕方に応じた機能を設ければよい。 As the optical functional element 17, a diffractive lens, a Fresnel lens, a diffraction grating, or other diffractive elements can be formed, and a function corresponding to the way of observing the reaction of the test liquid may be provided.
　例えば、単純に目視する場合でも、光学機能素子１７が拡大機能を持っておれば、充分明確に反応を観察できる。また、顕微鏡レベルの観察が必要な時、被験液体の種類によって拡大率が異なっても光学機能素子１７が単一の観察装置の倍率との間で倍率調整するよう設計されておれば、被験液体の種類によって異なる観察装置を用意しなくても単一の観察装置で行うことができる。さらに、分光特性を観察する場合、回折格子を適切に設計すれば、単一の観察装置で異なる被験液体の分光特性を観察できる。このように複数の観察装置を用意しなくて済むことは、小規模の診療所や検査機関においては大きなメリットとなる。 For example, even if it is simply visually observed, if the optical function element 17 has an enlargement function, the reaction can be observed sufficiently clearly. Also, when observation at the microscopic level is necessary, if the optical function element 17 is designed to adjust the magnification between the magnification of a single observation device even if the magnification ratio varies depending on the type of the test liquid, the test liquid It is possible to carry out with a single observation device without preparing different observation devices depending on the type. Furthermore, when observing spectral characteristics, if the diffraction grating is appropriately designed, the spectral characteristics of different test liquids can be observed with a single observation device. In this way, it is not necessary to prepare a plurality of observation devices, which is a great merit for small clinics and inspection institutions.
　図５は、光学機能素子１７を製造する工程を示す模式図である。図５の工程のうち、シート搬出工程Ａ、流路形成工程Ｂ、試薬供給工程Ｃ、および最終の切断工程Ｇは第１実施形態と同様である。なお、第２実施形態では、試薬は１種類の場合を示しているが、複数の液溜まりを形成し複数の試薬を固定するマイクロ流路検査チップとすることができるのは勿論である。 FIG. 5 is a schematic diagram showing a process for manufacturing the optical functional element 17. Among the steps of FIG. 5, the sheet unloading step A, the flow path forming step B, the reagent supplying step C, and the final cutting step G are the same as in the first embodiment. In the second embodiment, the case of one type of reagent is shown, but it is needless to say that a microchannel inspection chip that forms a plurality of liquid reservoirs and fixes a plurality of reagents can be used.
　第２実施形態では、第２連続シート１６の表面側に光学機能素子を形成する光学機能素子形成工程Ｈを有している。光学機能素子形成工程Ｈは、ＵＶ硬化樹脂の成形による工程を示している。すなわち、ロールから供給される第２連続シート１６とロール型Ｈ１の間にＵＶ硬化樹脂を供給しロール型Ｈ１上に形成された光学機能素子の型に成形して、この光学機能素子を紫外線照射ランプＨ２で硬化させる。 In the second embodiment, an optical functional element forming step H for forming an optical functional element on the surface side of the second continuous sheet 16 is provided. The optical functional element forming step H indicates a step by molding a UV curable resin. That is, a UV curable resin is supplied between the second continuous sheet 16 supplied from the roll and the roll mold H1, and formed into a mold of an optical functional element formed on the roll mold H1, and this optical functional element is irradiated with ultraviolet rays. Curing with lamp H2.
　光学機能素子が形成された第２連続シート１６は、第１連続シート１５との積層接着工程Ｆに進み、第１連続シート１５上に形成された流路を覆うように積層接着される。そして、光学機能素子を保護する第３連続シート１８を第２連続シート１６上に積層接着する工程Ｉに進み、最後に切断工程Ｇで、個片化される。この際、図示していないが、第２連続シート１６、第３連続シート１８に被験液体供給用の穴を形成する穿孔装置や、位置合わせのためのマーク検出センサを用いることは、第１実施形態と同様である。 The second continuous sheet 16 on which the optical functional element is formed proceeds to the lamination adhesion step F with the first continuous sheet 15 and is laminated and adhered so as to cover the flow path formed on the first continuous sheet 15. And it progresses to the process I which carries out the lamination | stacking adhesion | attachment of the 3rd continuous sheet 18 which protects an optical function element on the 2nd continuous sheet 16, and is cut into pieces by the cutting process G finally. At this time, although not shown, the use of a punching device for forming a test liquid supply hole in the second continuous sheet 16 and the third continuous sheet 18 or a mark detection sensor for alignment is the first implementation. It is the same as the form.
　図６は、上記例の変形例の光学機能素子付きマイクロ流路検査チップ２１を示している。マイクロ流路検査チップ２１は、光学機能素子２２を第１連続シート２３の裏面側に形成するものである。第１連続シート２３の表面に流路（被験液体供給用の液溜り１２、流路溝１３、反応後の液を溜める液溜り１４）を、裏面に光学機能素子２２を形成するので、両者を同時に形成することができる。第１連続シート２３の流路側は、第２連続シート２４で覆われる。 FIG. 6 shows a micro-channel inspection chip 21 with an optical function element according to a modification of the above example. The microchannel inspection chip 21 is one in which the optical functional element 22 is formed on the back side of the first continuous sheet 23. Since the flow path (the liquid reservoir 12 for supplying the test liquid, the flow path groove 13, and the liquid reservoir 14 for storing the liquid after the reaction) is formed on the surface of the first continuous sheet 23, and the optical functional element 22 is formed on the back surface, They can be formed simultaneously. The flow path side of the first continuous sheet 23 is covered with the second continuous sheet 24.
　図７は、このときの流路と光学機能素子の形成工程Ｊを示している。すなわち、第１連続シート２３の搬送路表面側に流路を形成するＵＶ硬化樹脂成形のロール型Ｂ２を配置し、裏面側に光学機能素子形成の熱転写のロール型Ｂ３（第１実施形態と同じ成形方法）を配置して、同時に形成する。ロール型Ｂ２から転写されたＵＶ硬化樹脂は紫外線ランプＢ４によって半硬化される。このように同時に形成することで、流路と光学機能素子の位置がずれることは無く、また工程的にも短縮できる効果がある。なお、光学機能素子を形成した第１連続シート２３の裏面を第３連続シートで覆って光学機能素子を保護するようにしても良い。 FIG. 7 shows the flow path and the optical function element forming step J at this time. That is, a UV-curable resin-molded roll mold B2 that forms a flow path is disposed on the front surface side of the first continuous sheet 23, and an optical functional element-formed thermal transfer roll mold B3 is formed on the back surface side (the same as in the first embodiment). Forming method) and forming simultaneously. The UV curable resin transferred from the roll mold B2 is semi-cured by the ultraviolet lamp B4. By forming them simultaneously in this way, the positions of the flow path and the optical function element are not shifted, and the process can be shortened. In addition, you may make it protect an optical function element by covering the back surface of the 1st continuous sheet 23 in which the optical function element was formed with a 3rd continuous sheet.
　［第３実施形態］
　本発明の第３実施形態のマイクロ流路検査チップ３１は、流路上で機能する可動構造を有するものである。 [Third Embodiment]
The microchannel inspection chip 31 of the third embodiment of the present invention has a movable structure that functions on the channel.
　図８は、可動構造部分の形成方法を模式的に示しており、図８（ａ）で、まず第１連続シート３２上に犠牲層３３を形成し、次に犠牲層３３の上に流路３４を形成する（図８（ｂ））。そして、犠牲層３３を溶剤で溶かして除去（図８（ｃ））すると、流路形成材料によって片持ち構造のフラップ３４ｆを作成できる。この構造の上に第２連続シート３５を積層接着する（図８（ｄ））。被験液体が右から左に流れるとすると、このフラップ３４ｆは左方向への液の流れは許容するが、右方向へは流れを阻止する逆止弁として働くことができる。なお、流路３４の点線部分は細い流路溝を示す。 FIG. 8 schematically shows a method for forming the movable structure portion. In FIG. 8A, first, the sacrificial layer 33 is formed on the first continuous sheet 32, and then the flow path is formed on the sacrificial layer 33. 34 is formed (FIG. 8B). When the sacrificial layer 33 is dissolved and removed with a solvent (FIG. 8C), a cantilevered flap 34f can be formed from the flow path forming material. A second continuous sheet 35 is laminated and bonded onto this structure (FIG. 8D). If the test liquid flows from right to left, the flap 34f allows the liquid to flow in the left direction, but can function as a check valve that blocks the flow in the right direction. In addition, the dotted line part of the flow path 34 shows a thin flow path groove.
　図９は、このような逆止弁３６を２つ連続して形成した例を示す。この場合、２つの逆止弁３６の間で第２連続シート３５側から圧力を印加・解除する構成を設けると、簡単なポンプを構成できる。圧力の印加・解除は、指で印加・解除しても良いが、例えば、２つの逆止弁３６の間の第２連続シート３５に当接するプランジャー３７を偏心カム３８で往復運動させる構成でよく、あるいは圧電素子で圧力を印加・解除することもできる。このようなポンプ構成を持つマイクロ流路チップは、毛細管現象のみで被験液体が移動する場合に比べて大量に液を移動でき、また流速を安定して制御することも容易であるので、検査の迅速化、正確化、高感度化につながる。 FIG. 9 shows an example in which two such check valves 36 are continuously formed. In this case, a simple pump can be configured by providing a configuration for applying and releasing pressure from the second continuous sheet 35 side between the two check valves 36. The pressure may be applied / released with a finger. For example, the plunger 37 abutting against the second continuous sheet 35 between the two check valves 36 is reciprocated by the eccentric cam 38. It is also possible to apply or release pressure with a piezoelectric element. The microchannel chip having such a pump configuration can move a large amount of liquid as compared to the case where the test liquid moves only by capillary action, and it is easy to control the flow rate stably. It leads to speed, accuracy and high sensitivity.
　図１０はこのような可動機構を流路に設ける場合の製造工程を示す模式図である。図示しないシート搬出工程から繰り出された第１連続シート４０は、犠牲層形成工程Ｊ、流路形成工程Ｂ′、犠牲層溶出工程Ｋを経て第２連続シート４１との積層接着工程Ｆに進む。 FIG. 10 is a schematic diagram showing a manufacturing process when such a movable mechanism is provided in the flow path. The first continuous sheet 40 fed out from the sheet unloading process (not shown) proceeds to the lamination bonding process F with the second continuous sheet 41 through the sacrificial layer forming process J, the flow path forming process B ′, and the sacrificial layer elution process K.
　犠牲層形成工程Ｊは、第１連続シート４０上に犠牲層を形成する工程である。この工程も成形や印刷の方法によって犠牲層を形成できる。 The sacrificial layer forming step J is a step of forming a sacrificial layer on the first continuous sheet 40. In this process, a sacrificial layer can be formed by a molding or printing method.
　流路形成工程Ｂ′は、流路の間に片持ちフラップの弁構造を追加した流路構造を形成する工程であり、印刷や成形の方法で形成できる。 The flow path forming step B ′ is a process of forming a flow path structure in which a cantilever flap valve structure is added between the flow paths, and can be formed by a printing or molding method.
　次の犠牲層溶出工程Ｋでは、第１連続シート４０を溶剤が入った容器Ｋ１をくぐらせて犠牲層を溶出する。これにより犠牲層の上に形成された可動構造（片持ちフラップ構造）は自由端部分が流路内で可動になる。犠牲層が溶出した後は赤外線ランプＫ２などで乾燥させて、次の積層接着工程Ｆに進む。なお、犠牲層の材料や溶剤は第１連続シート４０や流路形成材料に影響を与えない範囲で公知のものを使用できる。 In the next sacrificial layer elution step K, the sacrificial layer is eluted by passing the first continuous sheet 40 through the container K1 containing the solvent. As a result, the movable structure (cantilever flap structure) formed on the sacrificial layer has a free end portion movable in the flow path. After the sacrificial layer is eluted, the sacrificial layer is dried with an infrared lamp K2 or the like, and the process proceeds to the next lamination bonding step F. In addition, the material and solvent of a sacrificial layer can use a well-known thing in the range which does not affect the 1st continuous sheet 40 or a flow-path formation material.
　図１１は、可動構造として静脈弁型逆止弁を形成したマイクロ流路検査チップ５１の例を示す平面図と断面図である。静脈弁型逆止弁は、第１連続シート５２の上に片持ち構造のフラップ５３を対称的に向かい合わせた構造で、両フラップ５３の自由端が接近している。従って、図の右側からの液体は通過を許容するが、左側からの液体はフラップ自由端を閉じて流さない。図１１（ａ）の平面図、図１１（ｂ）の側断面図で、ハッチング部分が犠牲層５４を形成する部分で、まず犠牲層５４を形成し、その上にフラップを含む流路を形成し、その後、犠牲層５４を溶出して作成される。 FIG. 11 is a plan view and a cross-sectional view showing an example of a microchannel inspection chip 51 in which a venous valve check valve is formed as a movable structure. The venous valve check valve has a structure in which cantilevered flaps 53 are symmetrically opposed to each other on the first continuous sheet 52, and the free ends of both flaps 53 are close to each other. Accordingly, liquid from the right side of the figure is allowed to pass, but liquid from the left side does not flow with the flap free end closed. In the plan view of FIG. 11A and the side sectional view of FIG. 11B, the hatched portion is the portion where the sacrificial layer 54 is formed. First, the sacrificial layer 54 is formed, and the flow path including the flap is formed thereon. After that, the sacrificial layer 54 is eluted.
　図１１（ｂ）の側断面図において、可動のフラップ５３の下端は犠牲層の溶出により第１連続シート５２とわずかに隙間を開けており、上端は流路溝形成部分よりわずかに高さを低く形成されるので、可動のフラップ５３は、第１連続シート５２とも第２連続シート５５とも接触せず可動構造となって弁の機能を果たす。 11B, the lower end of the movable flap 53 is slightly spaced from the first continuous sheet 52 due to the elution of the sacrificial layer, and the upper end is slightly higher than the channel groove forming portion. Since it is formed low, the movable flap 53 does not come into contact with the first continuous sheet 52 or the second continuous sheet 55, and becomes a movable structure and functions as a valve.
　このような静脈弁型逆止弁の構造も上記の犠牲層形成工程Ｊ、流路形成工程Ｂ′、犠牲層溶出工程Ｋによって形成することができる。 Such a venous valve type check valve structure can also be formed by the sacrificial layer forming step J, the flow path forming step B ′, and the sacrificial layer elution step K.
　［第４実施形態］
　図１２は、反応室の両側に電極を形成したマイクロ流路検査チップ６１の部分平面図である。流路内に電極６２（ドットハッチング部分）を埋め込むことによって、被験液体中の特定物質を電場により分離したり、電気泳動効果でタンパク質の分子量分布を観察したりするなど種々の応用が可能となる。 [Fourth Embodiment]
FIG. 12 is a partial plan view of the microchannel inspection chip 61 in which electrodes are formed on both sides of the reaction chamber. By embedding the electrode 62 (dot hatched portion) in the flow path, various applications such as separation of a specific substance in the test liquid by an electric field and observation of the molecular weight distribution of the protein by the electrophoresis effect are possible. .
　このような電極形成も本発明の製造方法に組み込んで、一貫して製造することができる。電極の形成は、第１連続シートにあらかじめ形成しておき、この電極付き第１連続シートに本発明の流路形成、試薬供給、第２連続シート積層接着を行って、連続して生産できるが、さらに、電極形成そのものも工程に組み込むことができる。 Such electrode formation can also be integrated into the manufacturing method of the present invention. The electrode can be formed in advance on the first continuous sheet, and the first continuous sheet with electrode can be continuously produced by performing flow path formation, reagent supply, and second continuous sheet lamination adhesion of the present invention. Furthermore, the electrode formation itself can be incorporated into the process.
　図１３は、電極形成工程Ｌを組み込んだ工程を示す模式図である。図示しないシート搬出工程から繰り出された第１連続シート６３は、電極形成工程Ｌ、流路形成工程Ｂ′を経て図示しない第２連続シートとの積層接着工程Ｆに進む。 FIG. 13 is a schematic diagram showing a process in which the electrode forming process L is incorporated. The first continuous sheet 63 fed out from the sheet unloading process (not shown) proceeds to the lamination bonding process F with the second continuous sheet (not shown) through the electrode forming process L and the flow path forming process B ′.
　電極形成工程Ｌは、導電性インクをロールスクリーン印刷装置Ｌ１によって形成する工程を示しており、印刷後のインクは、赤外線ランプＬ２で乾燥固化される。 The electrode forming step L shows a step of forming conductive ink by the roll screen printing apparatus L1, and the ink after printing is dried and solidified by the infrared lamp L2.
　また、電極形成工程Ｌに続く流路形成工程Ｂ′は、ロール版Ｂ′１に樹脂を供給し、これをブランケットＢ′２に転写してから第１連続シート上に転写するオフセット樹脂成形法を示した。なおロール版Ｂ′１に供給された流路６４の樹脂は赤外線ランプＢ′３によって半硬化の状態にされてブランケットＢ′２に転写され、電極６２を形成された第１連続シート６３上に流路を形成する。流路の樹脂は赤外線ランプＢ′４で乾燥固化される。 The flow path forming step B ′ following the electrode forming step L is an offset resin molding method in which a resin is supplied to the roll plate B′1, transferred to the blanket B′2, and then transferred onto the first continuous sheet. showed that. The resin in the flow path 64 supplied to the roll plate B ′ 1 is made semi-cured by the infrared lamp B ′ 3 and transferred to the blanket B ′ 2, on the first continuous sheet 63 on which the electrode 62 is formed. A flow path is formed. The resin in the flow path is dried and solidified by the infrared lamp B'4.
　電極形成工程Ｌ、流路形成工程Ｂ′とも上記の印刷方法以外に、インクジェット印刷などのその他の方法で形成することも可能である。 The electrode forming step L and the flow path forming step B ′ can be formed by other methods such as ink jet printing in addition to the above printing method.
　電極の一部は、その上に流路を形成しない部分を作っておき、後工程で第２のシートに電極の端子部と接合する場所に穴をあけて、外部から電極端子に接続することができる。他の方法としては、切断工程での切断面まで電極を形成しておき、切断面に露出した電極端面に導電性インクを塗布・乾燥させ、半田付け面を形成する方法がある。 Make a part of the electrode that does not form a flow path on it, and make a hole in the second sheet where it will be joined to the electrode terminal, and connect it to the electrode terminal from the outside. Can do. As another method, there is a method in which an electrode is formed up to the cut surface in the cutting step, and a conductive ink is applied to the electrode end surface exposed on the cut surface and dried to form a soldering surface.
　［変形例］
　第１実施形態の積層接着工程Ｆでは、第１連続シートと第２連続シートの積層接着を加熱加圧ロール対Ｆ２で行ったが、加圧時間を長くとったほうが完全に接合されるので、図１４に示すステンレスベルトに挟みこみながら、ロールで加圧する工程を通して完全接合を連続して同一工程で行うことができる。 [Modification]
In the laminating and bonding step F of the first embodiment, the laminating and bonding of the first continuous sheet and the second continuous sheet was performed with the heating and pressing roll pair F2, but the longer the pressing time is, the more completely bonded, While being sandwiched between the stainless steel belts shown in FIG. 14, complete joining can be continuously performed in the same process through the process of pressing with a roll.
　図１４の加熱工程は、一対のステンレスベルト７０と、その内部に配置された加圧ロール７１及び加熱ヒータ７２により、積層された第１連続シート、第２連続シートの両側から加熱加圧する形態である。この加熱方法は、シートを直線状に引っ張りながら加熱するので、曲り癖がつかず、接合が完全で寸法精度の高いマイクロ流路検査チップを製造できる。第１連続シート、第２連続シートがガラス材料である場合にも、図１４の加熱工程を用いて半硬化状態の流路形成材料に密着させて加熱加圧を行い接着することができる。 The heating process of FIG. 14 is a form in which a pair of stainless steel belts 70, a pressure roll 71 and a heater 72 disposed therein are heated and pressed from both sides of the laminated first continuous sheet and second continuous sheet. is there. In this heating method, since the sheet is heated while being pulled in a straight line, it is possible to manufacture a micro-channel inspection chip with high dimensional accuracy that is free from bending wrinkles and is completely joined. Even when the first continuous sheet and the second continuous sheet are glass materials, they can be bonded by heating and pressurizing them in close contact with the semi-cured flow path forming material using the heating step of FIG.
　第１実施形態の切断工程では、切断をロータリーダイの刃物によって行ったが、ガラスシートの場合はレーザー切断装置（赤外線レーザーと水噴射）により切断することもできる。これを図１５を用いて説明する。シート材料の切断は、赤外線レーザー８０を照射し、照射位置に水噴射装置８１で水を吹き付けることで行う。赤外線レーザー８０で局所的に加熱されたガラスに水を吹き付けると、割れが成長・進行して切断を行うことができるのである。 In the cutting process of the first embodiment, cutting is performed with a rotary die blade, but in the case of a glass sheet, cutting can also be performed with a laser cutting device (infrared laser and water jet). This will be described with reference to FIG. The cutting of the sheet material is performed by irradiating the infrared laser 80 and spraying water on the irradiation position with the water jet device 81. When water is sprayed on the glass heated locally by the infrared laser 80, the crack grows and progresses, so that the cutting can be performed.
　切断を幅方向のみで行って複数のマイクロ流路検査チップを持つ定寸シートにし、後工程で個片化する場合は、赤外線レーザー８０と水噴射装置８１からなる切断装置を、シート幅方向から少し斜めの方向に一体的に移動可能に構成し、シートの搬送に従い、この方向に移動しながらシートを切断する。これは、シートも移動しているので、赤外線レーザー８０と水噴射装置８１を幅方向に斜めに移動させることで、シートと切断装置とを相対的に静止させるのである。なお、切断装置は、矢印で示すように、赤外線レーザー８０の焦点位置を調整するため、シートに対して接離方向に移動可能に構成される。 When cutting is performed only in the width direction to form a fixed-size sheet having a plurality of micro-channel inspection chips and separated into individual pieces in a subsequent process, a cutting device including the infrared laser 80 and the water jet device 81 is used from the sheet width direction. It is configured to be movable integrally in a slightly diagonal direction, and the sheet is cut while moving in this direction as the sheet is conveyed. Since the sheet is also moving, the sheet and the cutting device are relatively stationary by moving the infrared laser 80 and the water jetting device 81 obliquely in the width direction. The cutting device is configured to be movable in the contact / separation direction with respect to the sheet in order to adjust the focal position of the infrared laser 80 as indicated by an arrow.
　第１連続シートも第２連続シートもガラス材料で構成した場合は、赤外レーザー照射と水冷による切断は、第２連続シート側からの割れが第１連続シート側にも伝搬するので、片側からのみでよいが、一方のシート、あるいは流路形成材料がプラスチック材料の場合は、図に点線で示すように両側からレーザー切断する。 When both the first continuous sheet and the second continuous sheet are made of glass material, cutting from the second continuous sheet side propagates to the first continuous sheet side by cutting with infrared laser irradiation and water cooling. However, when one of the sheets or the flow path forming material is a plastic material, laser cutting is performed from both sides as indicated by dotted lines in the figure.
　また、マイクロ流路検査チップがマトリックス状に並んでいるので、個片化する場合は、幅方向と搬送方向の両方向に切断しなければならないが、同時に赤外線レーザーによる切断を行おうとすると、切断線が交差して割れが切断線で途切れるため同時に行うことはできない。そのため、幅方向と搬送方向の切断を順次行う必要がある。 In addition, since the micro flow path inspection chips are arranged in a matrix, when they are separated, they must be cut in both the width direction and the transport direction. Can not be done at the same time because they intersect and cracks break at the cutting line. Therefore, it is necessary to sequentially perform cutting in the width direction and the conveyance direction.
　搬送方向の切断は、赤外線レーザーのビームを幅方向に半導体モジュールの数だけ並べて搬送を行いながら実行できるが、幅方向の切断は、レーザー切断装置とシートの相対位置を静止状態に維持する必要がある。 Cutting in the conveyance direction can be performed while carrying the infrared laser beam by the number of semiconductor modules arranged in the width direction, but cutting in the width direction requires maintaining the relative position of the laser cutting device and the sheet stationary. is there.
　相対的に静止させる方法は、前述したシート搬送と同期して切断装置を略幅方向に移動させながら行う方法のほかに、切断工程手前に、アキュムレータ機構を設置してダンスローラなどで余分にシートを巻き取る時間を作り、その間、レーザー切断工程のシート送りを止める方法がある。このアキュムレータ機構は、前述の図３に示した構成を用いることができる。 In addition to the method of moving the cutting device substantially in the width direction in synchronism with the sheet conveyance described above, the relatively stationary method is that an accumulator mechanism is installed before the cutting process and an extra sheet is used with a dance roller or the like. There is a method of making time for winding the sheet and stopping the sheet feeding in the laser cutting process during that time. This accumulator mechanism can use the configuration shown in FIG.
　以上説明したように、本発明のマイクロ流路検査チップの製造方法は、製造を連続した一連の工程で行うので、これらの工程をクリーンルーム内で行うことにより汚染の心配のない製造を行うことができる。 As described above, since the manufacturing method of the microchannel inspection chip of the present invention is manufactured in a series of continuous processes, it is possible to perform manufacturing without worrying about contamination by performing these processes in a clean room. it can.
　さらに、従来のようにそれぞれの工程を別々に実施する場合に比べて、連続一貫製造できるので、大幅に生産効率を上げることができる。例えば、幅３００ｍｍのシートを用いて、送り速度１ｍ／ｍｉｎで、チップ長３０ｍｍ×幅１５ｍｍのマイクロ流路検査チップを装置稼働率８０％で製造するとすれば、年間２．７６億個製造できることになる。 Furthermore, compared to the case where each process is performed separately as in the prior art, continuous and consistent manufacturing can be performed, so that the production efficiency can be greatly increased. For example, if a micro flow path inspection chip having a chip length of 30 mm and a width of 15 mm is manufactured at an apparatus operating rate of 80% using a sheet having a width of 300 mm at a feed speed of 1 m / min, 277.6 billion can be manufactured annually. Become.
　１、１１、２１、３１、５１、６１　マイクロ流路検査チップ
　２　被験液体供給用の液溜り
　３ａ、３ｂ、３ｃ　流路溝
　４　捕捉抗体用の液溜り
　５　捕捉試薬用の液溜り
　６、１４　反応液溜り
　７、１５、２３、３２、４０、５２、６３　第１シート、第１連続シート
　８、１６、２４、３５、４１、５５　第２シート、第２連続シート
　１８　第３連続シート
　９、１９　被験液体供給用の穴
　１７　光学機能素子
　３３、５４　犠牲層
　３４ｆ、５３　フラップ
　３６　逆止弁
　６２　電極
　Ａ　シート搬出工程
　Ｂ、Ｂ′　シート搬出工程
　Ｃ　第１試薬供給工程
　Ｄ　第２試薬供給工程
　Ｅ　第３試薬供給工程
　Ｆ　積層接着工程
　Ｇ　切断工程
　Ｈ　光学機能素子形成工程
　Ｉ　第３連続シート積層接着工程
　Ｊ　犠牲層形成工程
　Ｋ　犠牲層溶出工程
　Ｌ　電極形成工程
　Ｍ　位置検出用のマークＭ 1, 11, 21, 31, 51, 61 Microchannel test chip 2 Liquid reservoir for supply of test liquid 3a, 3b, 3c Channel groove 4 Liquid reservoir for capture antibody 5 Liquid reservoir for capture reagent 6, 14 Reaction Liquid reservoir 7, 15, 23, 32, 40, 52, 63 First sheet, first continuous sheet 8, 16, 24, 35, 41, 55 Second sheet, second continuous sheet 18 Third continuous sheet 9, 19 Hole for supplying test liquid 17 Optical functional element 33, 54 Sacrificial layer 34f, 53 Flap 36 Check valve 62 Electrode A Sheet unloading process B, B 'Sheet unloading process C First reagent supplying process D Second reagent supplying process E Second 3 Reagent Supply Process F Lamination Bonding Process G Cutting Process H Optical Functional Element Formation Process I 3rd Continuous Sheet Lamination Bonding Process J Sacrificial Layer Formation Process K Sacrificial Layer Elution Process L Electrode Formation Process M Mark for Position Detection M

Claims (14)

  1. 　複数のマイクロ流路検査チップを連続して形成するマイクロ流路検査チップの製造方法であって、
    　第１連続シートを搬送し、該第１連続シートの搬送方向に順に、
    　成型、成形、あるいは印刷によって流路を形成する流路形成工程、
    　該流路に試薬を供給する試薬供給工程、
    　流路形成、試薬供給された前記第１連続シートに第２連続シートを積層接着する積層接着工程、
    　を配置して、複数のマイクロ流路検査チップを形成したシートを作成することを特徴とするマイクロ流路検査チップの製造方法。     A method of manufacturing a microchannel inspection chip that continuously forms a plurality of microchannel inspection chips,
    The first continuous sheet is conveyed, and sequentially in the conveying direction of the first continuous sheet,
    A flow path forming step for forming a flow path by molding, molding, or printing;
    A reagent supplying step of supplying a reagent to the flow path;
    Forming a flow path, a lamination bonding step of laminating and bonding a second continuous sheet to the first continuous sheet supplied with the reagent,
    And producing a sheet on which a plurality of microchannel inspection chips are formed.
  2. 　複数のマイクロ流路検査チップを連続して形成するマイクロ流路検査チップの製造方法であって、
    　第１連続シートを搬送し、該第１連続シートの搬送方向に順に、
    　成型、成形、あるいは印刷によって流路を形成する流路形成工程、
    　該流路に試薬を供給する試薬供給工程、
    　第２連続シートに回折レンズ、フレネルレンズ、あるいは回折格子のいずれかの光学機能素子を形成する光学機能素子形成工程、
    　流路形成、試薬供給された前記第１連続シートに前記光学機能素子が形成された前記第２連続シートを積層接着する積層接着工程、
    　を配置して、複数のマイクロ流路検査チップを形成したシートを作成することを特徴とするマイクロ流路検査チップの製造方法。     A method of manufacturing a microchannel inspection chip that continuously forms a plurality of microchannel inspection chips,
    The first continuous sheet is conveyed, and sequentially in the conveying direction of the first continuous sheet,
    A flow path forming step for forming a flow path by molding, molding, or printing;
    A reagent supplying step of supplying a reagent to the flow path;
    An optical functional element forming step of forming an optical functional element of either a diffraction lens, a Fresnel lens, or a diffraction grating on the second continuous sheet;
    Laminate bonding step of laminating and bonding the second continuous sheet in which the optical functional element is formed to the first continuous sheet supplied with the flow path and the reagent,
    And producing a sheet on which a plurality of microchannel inspection chips are formed.
  3. 　前記第２連続シートの前記光学機能素子が形成された面を覆う第３連続シートを積層する工程を有することを特徴とする請求項２に記載のマイクロ流路検査チップの製造方法。 3. The method of manufacturing a microchannel inspection chip according to claim 2, further comprising a step of laminating a third continuous sheet that covers a surface of the second continuous sheet on which the optical functional element is formed.
  4. 　複数のマイクロ流路検査チップを連続して形成するマイクロ流路検査チップの製造方法であって、
    　第１連続シートを搬送し、該第１連続シートの搬送方向に順に、
    　成型、成形、あるいは印刷によって流路を形成する流路形成工程、
    　該流路に試薬を供給する試薬供給工程、
    　前記流路形成工程と同時に、あるいはその前後に、前記第１連続シートの裏面に回折レンズ、フレネルレンズ、あるいは回折格子のいずれかの光学機能素子を形成する光学機能素子形成工程、
    　流路形成、試薬供給、光学機能素子形成された前記第１連続シートに第２連続シートを積層接着する積層接着工程、
    　を配置して、複数のマイクロ流路検査チップを形成したシートを作成することを特徴とするマイクロ流路検査チップの製造方法。     A method of manufacturing a microchannel inspection chip that continuously forms a plurality of microchannel inspection chips,
    The first continuous sheet is conveyed, and sequentially in the conveying direction of the first continuous sheet,
    A flow path forming step for forming a flow path by molding, molding, or printing;
    A reagent supplying step of supplying a reagent to the flow path;
    An optical functional element forming step of forming an optical functional element of any one of a diffraction lens, a Fresnel lens, and a diffraction grating on the back surface of the first continuous sheet simultaneously with or before and after the flow path forming step,
    Laminate bonding step of laminating and bonding a second continuous sheet to the first continuous sheet on which flow path formation, reagent supply, and optical functional element are formed,
    And producing a sheet on which a plurality of microchannel inspection chips are formed.
  5. 　前記光学機能素子形成工程が、流路形成装置と光学機能素子形成装置を互いに対向して配置し、この間に前記第１連続シートを通過させて、流路と光学機能素子を前記第１連続シートの両面に同時に形成することを特徴とする請求項４に記載のマイクロ流路検査チップの製造方法。 In the optical functional element forming step, the flow path forming device and the optical functional element forming device are arranged to face each other, and the first continuous sheet is passed between them, and the flow path and the optical functional element are connected to the first continuous sheet. The method for manufacturing a microchannel inspection chip according to claim 4, wherein the microchannel inspection chip is simultaneously formed on both surfaces of the microchannel inspection chip.
  6. 　前記第１連続シートの前記光学機能素子が形成された面を覆う第３連続シートを積層する工程を有することを特徴とする請求項４又は５に記載のマイクロ流路検査チップの製造方法。 6. The method for manufacturing a microchannel inspection chip according to claim 4, further comprising a step of laminating a third continuous sheet covering the surface of the first continuous sheet on which the optical functional element is formed.
  7. 　前記流路形成工程の前に、犠牲層を形成する工程を設け、前記流路形成工程で流路とともに片持ち構造のフラップ部を流路中に形成し、次いで前記犠牲層を溶出除去する犠牲層除去工程を設けたことを特徴とする請求項１から６のいずれかに記載のマイクロ流路検査チップの製造方法。 A sacrificial layer forming step is provided before the flow path forming step, a cantilevered flap portion is formed in the flow path in the flow path forming step, and then the sacrificial layer is eluted and removed. The method for producing a microchannel inspection chip according to claim 1, further comprising a layer removing step.
  8. 　前記流路形成工程の前に、前記流路形成工程で形成する流路の部分に電極を形成する工程を設け、電気的検査を行えるようにしたことを特徴とする請求項１から６のいずれかに記載のマイクロ流路検査チップの製造方法。 7. The method according to claim 1, wherein a step of forming an electrode is provided in the portion of the flow path formed in the flow path forming step before the flow path forming step so that electrical inspection can be performed. A method for producing a microchannel inspection chip according to claim 1.
  9. 　前記第１連続シート上の被験液体を溜める液溜りに対応する前記第２連続シート上の位置に被験液体供給用の穴を形成する工程を有することを特徴とする請求項１から６のいずれかに記載のマイクロ流路検査チップの製造方法。 7. The method according to claim 1, further comprising a step of forming a hole for supplying a test liquid at a position on the second continuous sheet corresponding to a liquid reservoir for storing the test liquid on the first continuous sheet. The manufacturing method of the microchannel test | inspection chip of description.
  10. 　前記第１連続シート上の前記液溜りと前記第２連続シートの前記穴とを検出するセンサを工程中に配置し、位置合わせを行うことを特徴とする請求項９に記載のマイクロ流路検査チップの製造方法。 The microchannel inspection according to claim 9, wherein a sensor for detecting the liquid reservoir on the first continuous sheet and the hole of the second continuous sheet is disposed in the process to perform alignment. Chip manufacturing method.
  11. 　前記流路形成工程において、流路とともに位置検出用のマークを形成し、該マークを検出することにより位置合わせを行うことを特徴とする請求項９に記載のマイクロ流路検査チップの製造方法。 10. The method of manufacturing a microchannel inspection chip according to claim 9, wherein in the channel formation step, a position detection mark is formed together with the channel, and alignment is performed by detecting the mark.
  12. 　前記積層接着工程の後に、一体となったシートを連続して送りながら切断し個片化する切断工程を設けたことを特徴とする請求項１から１１のいずれかに記載のマイクロ流路検査チップの製造方法。 The microchannel inspection chip according to any one of claims 1 to 11, further comprising a cutting step of cutting and separating the integrated sheets while continuously feeding after the laminating and bonding step. Manufacturing method.
  13. 　前記第１連続シートに形成した流路部分と、前記第２連続シートの積層接着面に親水処理を行うことを特徴とする請求項１から１２のいずれかに記載のマイクロ流路検査チップの製造方法。 13. The microchannel inspection chip according to claim 1, wherein a hydrophilic treatment is performed on a flow path portion formed in the first continuous sheet and a laminated adhesive surface of the second continuous sheet. Method.
  14. 　前記第１連続シートまたは前記第２連続シートの材料が、プラスチックまたはガラスであることを特徴とする請求項１から１３のいずれかに記載のマイクロ流路検査チップの製造方法。 The method for manufacturing a microchannel inspection chip according to any one of claims 1 to 13, wherein a material of the first continuous sheet or the second continuous sheet is plastic or glass.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017069139A1 (en) * 2015-10-21 2017-04-27 東洋製罐グループホールディングス株式会社 Immunological measurement device
WO2019002678A1 (en) * 2017-06-30 2019-01-03 Teknologian Tutkimuskeskus Vtt Oy A microfluidic chip and a method for the manufacture of a microfluidic chip

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5411858A (en) * 1989-05-17 1995-05-02 Actimed Laboratories, Inc. Manufacturing process for sample initiated assay device
JPH10158349A (en) * 1996-11-28 1998-06-16 Dainippon Printing Co Ltd Ionizing radiation-curing type resin composition for optical sheet, optical sheet and its production
JP2001520377A (en) * 1997-10-15 2001-10-30 アクレイラ バイオサイエンシズ，インコーポレイティド Laminated micro structural device and method of manufacturing laminated micro structural device
JP2001527637A (en) * 1996-08-26 2001-12-25 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Electrochemical detector integrated on microfabricated capillary electrophoresis chip
JP2003156474A (en) * 2001-11-20 2003-05-30 Brother Ind Ltd Chip for electrophoresis and electrophoresis device using the chip
JP2003217992A (en) * 2002-01-21 2003-07-31 Matsushita Electric Ind Co Ltd Laminate manufacturing device of laminated electronic component
JP2007508542A (en) * 2003-10-09 2007-04-05 スリーエム イノベイティブ プロパティズ カンパニー Multilayer sample processing apparatus and method
JP2008008880A (en) * 2006-06-02 2008-01-17 Sumitomo Bakelite Co Ltd Microchip made from plastic, manufacturing method therefor, and biochip or microanalytical chip using the same
JP2008233002A (en) * 2007-03-23 2008-10-02 Toppan Printing Co Ltd Reaction tip and reaction method using the same

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5411858A (en) * 1989-05-17 1995-05-02 Actimed Laboratories, Inc. Manufacturing process for sample initiated assay device
JP2001527637A (en) * 1996-08-26 2001-12-25 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Electrochemical detector integrated on microfabricated capillary electrophoresis chip
JPH10158349A (en) * 1996-11-28 1998-06-16 Dainippon Printing Co Ltd Ionizing radiation-curing type resin composition for optical sheet, optical sheet and its production
JP2001520377A (en) * 1997-10-15 2001-10-30 アクレイラ バイオサイエンシズ，インコーポレイティド Laminated micro structural device and method of manufacturing laminated micro structural device
JP2003156474A (en) * 2001-11-20 2003-05-30 Brother Ind Ltd Chip for electrophoresis and electrophoresis device using the chip
JP2003217992A (en) * 2002-01-21 2003-07-31 Matsushita Electric Ind Co Ltd Laminate manufacturing device of laminated electronic component
JP2007508542A (en) * 2003-10-09 2007-04-05 スリーエム イノベイティブ プロパティズ カンパニー Multilayer sample processing apparatus and method
JP2008008880A (en) * 2006-06-02 2008-01-17 Sumitomo Bakelite Co Ltd Microchip made from plastic, manufacturing method therefor, and biochip or microanalytical chip using the same
JP2008233002A (en) * 2007-03-23 2008-10-02 Toppan Printing Co Ltd Reaction tip and reaction method using the same

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017069139A1 (en) * 2015-10-21 2017-04-27 東洋製罐グループホールディングス株式会社 Immunological measurement device
CN108139397A (en) * 2015-10-21 2018-06-08 东洋制罐集团控股株式会社 Immunologic assay device
WO2019002678A1 (en) * 2017-06-30 2019-01-03 Teknologian Tutkimuskeskus Vtt Oy A microfluidic chip and a method for the manufacture of a microfluidic chip
US11759782B2 (en) 2017-06-30 2023-09-19 Teknologian Tutkimuskeskus Vtt Oy Microfluidic chip and a method for the manufacture of a microfluidic chip

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