JP2010071675A - Microchemical system and microchemical system apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a microchemical system, capable of sending a fluid in a two-dimensional direction and a three-dimensional direction, and capable of precisely performing the treatment, such as the reaction, stirring, detection of the fluid by one apparatus by using a single device, and to provide a microchemical system apparatus. <P>SOLUTION: In the microchemical system 1, there are provided two or more layers of disks 11, 21, 31 and 41 are stacked, the flow channels formed to the disks have the flow channels in the surface directions, formed in the surface directions of the disks and the connection flow channel for connecting the flow channels in the surface directions, formed in the disks of different layers, and a sample accumulating tank 12; a reagent accumulating tank 32; a stirring adjusting tank 22 for stirring the sample of the sample accumulating tank and the reagent of the reagent accumulating tank; and a detection tank 34 for detecting the sample adjusted in the stirring adjusting tank. The sample accumulation tank and the stirring adjusting tank, the reagent accumulation tank and the stirring-adjusting tank, and the stirring-adjusting tank and the detection tank are, respectively connected via flow channels 13, 23 and 33. The microchemical system apparatus which is equipped with the microchemical system is also disclosed. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention includes biochemical analysis and environmental conservation in the medical and pharmaceutical fields, analysis by enzyme immunoassay (ELISA method) known as a simple and local sensitivity method among analysis methods in the quarantine field of food and organisms, and The present invention relates to a microchemical system capable of performing unit operations such as sample mixing and reaction performed before analysis with a single apparatus, and a microchemical system apparatus including the microchemical system.

Conventionally, a microchemical chip has attracted attention as a high-speed and high-sensitivity analysis system. With a microchemical chip, a micro flow path is formed on a single chip, and fluid is fed in a planar direction. Then, operations such as mixing, reaction, and analysis can be performed on the chip (for example, Patent Documents 1 and 2 below (FIG. 7)).
JP 2002-340911 A JP 2007-155484 A

  However, since the analyzers of Patent Document 1 and Patent Document 2 (FIG. 7) are operated on the plane of the microchip, mixing is not sufficient or the optical path length for analysis is not sufficient. The detection sensitivity may be reduced. In addition, since operations that cannot be performed on the chip are performed by a separate apparatus, it often takes time to analyze the sample or requires another apparatus. Furthermore, since each operation is performed manually, there may be a difference in accuracy.

  Therefore, the present invention provides a microchemical system capable of performing analysis and unit operations necessary for analysis in a single device with high accuracy and in a short time, and capable of downsizing the device and processing multiple samples. An object of the present invention is to provide a microchemical system apparatus using the same.

Means and effects for solving the problems

  The microchemical system of the present invention is a microchemical system for transferring a fluid to a flow path formed in a disk by centrifugal force generated by the rotation of the disk, comprising a laminate in which two or more layers of the disk are stacked, The path has a surface-direction flow path formed in the surface direction of the disk and a connection flow path for connecting the surface-direction flow paths formed in the disk of different layers.

  According to the above configuration, fluid such as a liquid or a gas in the liquid can be transferred not only in a two-dimensional (planar) direction but also in a three-dimensional direction, so that processing such as reaction, stirring, and detection in the flow path can be performed with high accuracy.

  Further, the microchemical system according to the present invention has a convex portion on the surface of the uppermost disk of the laminated body, penetrates the convex portion in the convex direction, and is formed on the disk. It is preferable to have a hole connected to the path. According to this, the fluid is accelerated and more easily transferred in the three-dimensional direction due to the centrifugal force and the venturi effect generated by the convex portion and the hole. Therefore, it becomes easy to transfer the fluid to the upper layer in the direction opposite to the gravity.

  In the microchemical system of the present invention, it is preferable that at least a part of the flow path formed in the disk is a bundle of a plurality of pores, and the maximum length of the cross section of the pores is 3 mm or less. According to this, since the surface area of the flow path can be greatly increased, the efficiency of each processing such as fluid feeding, stirring, and reaction can be greatly improved. In addition, since the said effect is hard to be exhibited when the maximum length of the cross section of a pore exceeds 3 mm, it is preferable that it is 3 mm or less.

In the microchemical system of the present invention, it is preferable that a thin film is coated on the inner wall surface of the flow path formed in the disk, and the thin film is made of a material different from the material of the disk. According to this, the coated material can be immobilized on the inner wall surface as an antigen or an antibody. Therefore, antigens, antibodies, and the like can be stably fixed at a high density on the inner wall surface of the flow path, so that accuracy, speed, and efficiency of processing such as stirring and reaction can be further improved. Here, for example, a resin or a metal can be used for the disk, and a biopolymer or a catalyst of a protein such as Pt, Au, Ti, TiO ₂ , SiO ₂ , Ag, avidin or the like is coated on the thin film. Thus, the thin film can be coated.

  In the microchemical system of the present invention, the flow path formed in the disk includes a sample accumulation tank, a reagent accumulation tank, a sample in the sample accumulation tank, and an agitation adjustment tank that agitates the reagent in the reagent accumulation tank, A detection tank for detecting the sample adjusted in the stirring adjustment tank, between the sample accumulation tank and the stirring adjustment tank, between the reagent accumulation tank and the stirring adjustment tank, and It is preferable that the stirring adjustment tank and the detection tank are connected to each other via a flow path.

  According to this, operations such as sample pretreatment, mixing, reaction, separation, extraction, and detection can be integrated in one apparatus. Thereby, size reduction and weight reduction of an apparatus can be achieved, and a sample and a reagent are restrained in a small quantity than before. Moreover, a stirring adjustment tank and a detection tank can be provided in the three-dimensional flow path. As a result, a place necessary for stirring, a volume and a surface area necessary for reaction, and a light path necessary for light detection can be sufficiently obtained as compared with the prior art, and the accuracy and analytical sensitivity of each operation can be improved. Therefore, a single apparatus can simultaneously detect and process a large number of samples (specimens) and can perform each operation in a short time. In addition, since a small time change in the reaction process of the specimen can be detected in the detection tank, the detection range can be expanded.

  In the microchemical system of the present invention, a reaction tank is provided in the middle of a flow path connecting the stirring adjustment tank and the detection tank, and between the stirring adjustment layer and the reaction tank, and The reaction tank and the detection tank are preferably connected to each other via a flow path. According to this, in the reaction tank, the reaction can be promoted, or the reaction of only a specific sample or a specific part of the sample can be caused, so that the selectivity of the sample can be improved.

  In the microchemical system of the present invention, it is preferable that the disk on which the reaction layer is located contains metal fine particles having a particle size of 10 μm or less. As the metal fine particles, for example, gold or silver fine particles can be used. According to this, metal fine particles appear on the surface of the flow path or the reaction layer and are immobilized as an antigen or an antibody. Therefore, the reaction is further promoted and the accuracy of the reaction is further improved. In addition, when fine particles having a particle size larger than 10 μm are contained, the fine metal particles are hardly immobilized as antigens or antibodies on the surface of the flow path or the reaction layer.

  Further, in the microchemical system of the present invention, the disk on which the reaction vessel is located is an enzyme immunoassay element having a large number of holes having flow paths therein, and the flow paths inside the holes are connected to each other. It is preferable that a predetermined antibody or antigen is immobilized on the inner wall surface of the flow path inside the hole while intersecting inside.

  According to this, the surface area of the flow path can be greatly improved as compared with the conventional case, and the mixing (mixing) effect generated when the sample or reagent liquid passes can be further improved. As a result, it is possible to provide a microchemical system capable of performing enzyme immunoassay that can be performed at a higher speed and with higher sensitivity than before. In addition, the sample solution and the reagent solution are fed into the disk where the stirring tank is located by balancing with the surface tension of the solution at the end of the hole of the disk where the stirring tank is located and the centrifugal force by the rotating device. It can be deterred and has the effect of a valve. Furthermore, since it has a bundle structure of capillaries (capillaries), it has an effect as a capillary.

  In the microchemical system of the present invention, the inner wall surface of the flow path of the enzyme immunoassay element is coated with a thin film, and the antibody or the antigen is immobilized on the surface of the thin film. Is preferred. As the thin film, for example, a thin film containing a metal such as nickel or platinum, diamond-like carbon, a compound, or a biocompatible polymer (such as avidin) can be used. According to this, since the predetermined antibody or antigen is stably fixed at a high density on the channel surface, the sensitivity in detection can be further improved.

Further, the microchemical system of the present invention includes a space between the sample accumulation tank and the stirring adjustment tank, a gap between the reagent accumulation tank and the stirring adjustment tank, and a gap between the stirring adjustment tank and the detection tank. It is preferable to have a valve provided in the middle of each of the connected flow paths. According to this, since the liquid supply of the sample and the reagent can be suppressed by opening and closing the valve, the inflow and outflow of the reagent and the sample are suppressed during each processing performed in the stirring adjustment tank, the reaction tank, the detection tank, and the like. And the accuracy of each operation can be improved.
In particular, the valve preferably includes a phase-change material. For example, as the phase-change material, for example, a paraffin-based material or a pluronic polymer of a polymer copolymer can be used. According to this, it is possible to easily open and close the valve (the width of the flow path) by changing the phase (for example, changing to a sol or gel) by temperature, electromagnetic waves (light), or the like.

  In the microchemical system of the present invention, it is preferable that an antigen or an antibody is immobilized on the inner wall surface of the stirring adjustment tank. According to this, since the predetermined antibody or antigen is stably fixed at a high density on the inner wall surface of the stirring adjustment tank, the pretreatment of the reaction can be performed efficiently. A catalyst may be immobilized instead of the antigen or antibody.

  In the microchemical system of the present invention, it is preferable that the convex portion of the disk is formed at a position coaxial with the detection tank, and the hole and the detection tank are connected. According to this, it becomes easy to send a sample to a detection tank by the venturi effect which arises by a convex part and a hole. In particular, even when the flow path position connected to the reaction layer or the stirring adjustment tank is at the bottom of the detection tank, the fluid can be fed to the high position of the detection tank by the venturi effect to fill the detection tank.

  Moreover, it is preferable that the microchemical system apparatus of this invention is equipped with the microchemical system mentioned above and the rotation apparatus which rotates the said laminated body. According to this, each operation such as stirring, reaction, and detection of the sample can be automatically performed by the centrifugal force generated by rotating the microchemical system by the rotating device. Therefore, the operation can be performed easily and in a short time, and the amount of reagents and samples can be suppressed to a small amount. In addition, it is possible to suppress the occurrence of variations in human operation accuracy that have conventionally occurred, and it is possible to improve reproducibility, reliability, and analysis sensitivity.

  Moreover, it is preferable that the microchemical system apparatus of this invention is equipped with the irradiation means to irradiate an electromagnetic wave to the said laminated body. According to this, it is possible to irradiate electromagnetic waves such as fluorescence and laser light to a stirring adjustment tank, a reaction tank, a detection tank, a valve and the like. This makes it possible to promote agitation, acceleration of reactions that are difficult to thermally react, reaction of a specific part of a sample or a specific sample, reaction at room temperature, improved selectivity, high speed reaction, high yield. A microchemical system apparatus can be provided. Also, light detection is possible. The irradiating means is not limited to irradiating light, but may be irradiating electromagnetic waves such as microwaves, surface acoustic waves, and ultrasonic waves. For example, metal nanoparticles and organometallic complexes can be synthesized by irradiating the reaction vessel with microwaves, and the accuracy of stirring the sample can be further improved by irradiating surface acoustic waves to the stirring adjustment vessel.

  Preferred embodiments will be described below.

<First Embodiment>
Hereinafter, embodiments of a microchemical system and a microchemical system apparatus using the same according to the present invention will be described. FIG. 1 is a schematic configuration diagram of a microchemical system apparatus according to the first embodiment of the present invention. FIG. 2 is a perspective view of the microchemical system constituting the microchemical system apparatus of FIG. 3 is a top view of four disks constituting the microchemical system of FIG. 4 is a schematic cross-sectional view taken along the line AA of FIG.

  In FIG. 1, a microchemical system device 100 includes a microchemical system 1, a rotating device 2 that rotates the microchemical system 1, and a first irradiation device (irradiation means) that irradiates the microchemical system 1 with light (electromagnetic waves). ) 3 and a second irradiation device (irradiation means) 8. And the optical fiber 4a which transmits the fluorescence which generate | occur | produces with the light irradiated to the microchemical system 1 from the 1st irradiation apparatus 3, and the absorption light generated with the light irradiated to the microchemical system 1 from the 1st irradiation apparatus 3 are received. Transmitting optical fiber 4b, spectroscope 5 that receives the light transmitted through the optical fibers 4a and 4b, detector 6 that detects the light beam split by the spectroscope 5, and the results detected by the detector 6 are analyzed. In addition, it further includes a personal computer 7 for instructing the rotation device 2 of the number of rotations. Here, the optical fiber 4 a is provided close to the side surface of the microchemical system 1, and the optical fiber 4 b is provided close to the top surface of the microchemical system 1.

  The microchemical system 1 is a stacked body in which a first disk 11, a second disk 21, a third disk 31, and a fourth disk 41 are stacked concentrically in order from the top. 3, (a) is the first disk 11, (b) is the second disk 21, (c) is the third disk 31, and (d) is the fourth disk. In FIG. 3, for convenience of explanation, flow paths and tanks located on other disks are indicated by dotted lines. A flow path is formed in the first disk 11, the second disk 21, the third disk 31, and the fourth disk 41. This flow path is a surface-direction flow path formed in the surface direction of the disk. And a connecting flow path for connecting the flow paths in the surface direction formed on the disks of different layers. Note that the connection flow path is not limited to the direction perpendicular to the surface direction, and may be formed in an oblique direction or the like. The material of the first disk 11, the second disk 21, the third disk 31, and the fourth disk 41 is, for example, polymethyl methacrylate (PMMA) or SU-8 as a material that can be processed by X-rays. Fluorine resins such as epoxy negative resist and polytetrafluoroethylene (PTFE) are used. Further, when nickel, copper, gold, or the like is used as a mold material, a fine structure can be manufactured. In addition, thermoplastic resins, ceramics, and the like can be used.

  In the middle of the channel in the surface direction and the connection channel, the sample accumulation tank 12, the reagent accumulation tank 32, the stirring adjustment tank 22 for stirring the sample in the sample accumulation tank 12 and the reagent in the reagent accumulation tank 32, and stirring A detection tank 34 for detecting the sample adjusted in the adjustment tank 22 is provided. The sample storage tank 12 and the stirring adjustment tank 22 are connected via the first flow path 13, and the reagent storage tank 32 and the stirring adjustment tank 22 are connected via the second flow path 33. The agitation adjustment tank 22 and the detection tank 34 are connected via the third flow path 23. Further, a reaction tank 35 is provided in the middle of the third flow path 23 connecting the stirring adjustment tank 22 and the detection tank 34, and between the stirring adjustment tank 22 and the reaction tank 35, and the reaction tank 35. And the detection tank 34 are connected to each other via a flow path. Furthermore, the first valve 15 provided in the middle of the first flow path 13, the second valve 37 provided in the middle of the second flow path 33, and the third valve provided in the middle of the third flow path 23. 25, a fourth valve 38 and a fifth valve 39 are provided. Here, the third valve 25 is located between the stirring adjustment tank 22 and the reaction tank 35, and the fourth valve 38 and the fifth valve 39 are located between the reaction tank 35 and the detection tank 34. The first valve 15, the second valve 37, the third valve 25, the fourth valve 38, and the fifth valve 39 include a material that changes phase. In the present embodiment, the phase changes due to light (electromagnetic waves). Contains material. Furthermore, the detection tanks 34 are provided on the circle at regular intervals, and the pulse generation markers 40 are described at regular intervals between the detection tanks 34.

  The sample accumulation tank 12 is located on the first disk 11 and accumulates a sample to be a sample injected from a sample injection port (not shown), and can perform sample pretreatment and the like. An antigen or an antibody can be used for the sample. For example, when blood is used for the sample, it can be used as a blood cell separation tank for separating blood into blood cells and serum. At this time, in the sample storage tank 12, blood cells move outside the center of the first disk 11, and serum moves to the center side of the first disk 11. This pretreatment is performed by centrifugal force generated by rotating the microchemical system 1 by the rotating device 2. And the 1st flow path 13 is connected to the center side to which the serum of the sample storage tank 12 moved.

  The stirring adjustment tank 22 is located on the second disk 21. In the stirring adjustment tank 22, stirring, adjustment, and the like of the sample sent from the sample accumulation tank 12 and the reagent sent from the reagent accumulation tank 32 are performed.

  The reagent accumulation tank 32 is a tank that communicates with the first disk 11 and the second disk 21, and accumulates reagents injected from a reagent injection port (not shown). As the reagent, an antigen or an antibody that reacts with an antigen or antibody used in a sample can be used.

  The detection tank 34 is a substantially cylindrical tank communicating with part of the second disk 21, the third disk 31, and the fourth disk 41. The detection tank 34 also communicates with the thin hole 16 formed in the first disk 11 in the thickness direction. The detection tank 34 is provided with a film 24 from the upper surface of the second disk 21 to the lower surface of the third disk 31, and the light irradiated from the second irradiation device 8 to the detection tank 34 by this film 24 is condensed as fluorescence. Then, it is guided to the detector 6 through the optical fiber 4a. Here, for the film 24, for example, polydimethylsiloxane (PDMS), paraxylylene resin, or a surface coated with platinum can be used. And light other than fluorescence among the lights irradiated to the detection tank 34 from the 2nd irradiation apparatus 8 is guide | induced to the detector 6 through the optical fiber 4b as absorption light. In addition, although the electromagnetic wave is irradiated to the detection tank 34 in the thickness direction of the disk from the second irradiation device 8 and light detection is performed, the detection tank 34 communicates with the second disk 21, the third disk 31, and the fourth disk 41. As a result, the optical path necessary for light detection can be sufficiently secured. Further, the sample and the reagent sent from the reaction tank 35 are filled up to the upper surface of the second disk 21 of the detection tank 34 by the centrifugal force generated by the rotation of the laminate and the capillary phenomenon generated by the hole 16 communicating with the detection tank 34.

  The reaction tank 35 has a structure in which a plurality of pores having flow paths inside are bundled. Here, the cross section of the pore can be various shapes such as a round shape, an oval shape, and a quadrilateral shape, and the maximum length of the cross section is 3 mm or less. Moreover, it is preferable that an antigen or an antibody is immobilized on the surface of the pore or a catalyst is coated. In the present embodiment, an antigen is immobilized, and the fluid (A) fed from the stirring adjustment tank 22 by this antigen is changed to a different fluid (B). If metal fine particles having a particle diameter of 10 μm or less are contained in the third disk in which the reaction tank 35 is located, the metal fine particles appear on the surface of the reaction layer and can be immobilized as antigens or antibodies. As the metal fine particles, gold or silver fine particles can be used.

The method for immobilizing the antigen or antibody to the reaction tank 35 is a known method (for example, a two-antibody solid phase method, a single antibody solid phase method, a competitive method using a solid phased antigen and an enzyme-labeled antibody, a sandwich method, an immunoassay Techniques defined in the ELISA method such as the enzymometric method) can be used, but are not limited thereto. Examples of antibodies include monoclonal antibodies and polyclonal antibodies. Examples of the antigen include low molecular compounds such as nonylphenol and dioxin, proteins such as tumor markers, virus particles, and cells. In addition, you may fix a catalyst instead of an antibody or an antigen. Moreover, you may use what the antigen, antibody, or catalyst is not fixed to the inner wall surface of the reaction tank 35. As another method, the inner wall surface of the stirring adjustment tank 22 may be coated with a thin film. By using this thin film as a material different from the material of the third disk 31, the thin film can be immobilized on the surface of the inner wall as an antigen or an antibody. The disk can be made of, for example, resin or metal, and the thin film is coated with a protein biopolymer such as Pt, Au, Ti, TiO ₂ , SiO ₂ , Ag, avidin or a catalyst. The thin film can be coated.

  As shown in FIGS. 2 and 3, the first flow path 13 is branched in the middle, and is a flow path that guides a sample from one sample accumulation tank 12 to a plurality of stirring adjustment tanks 22. Similarly, the second flow path 33 is branched in the middle, and is a flow path that guides the reagent from one reagent accumulation tank 32 to the plurality of stirring adjustment tanks 22. And as shown in FIG. 4, the 1st flow path 13 and the 2nd flow path 33 are connected on the way. The third flow path 23 guides the fluid sent to the stirring adjustment tank 22 to the reaction tank 35 and the detection tank 34. Here, the fluid is a liquid or a liquid containing a gas. A plurality of third flow paths 23 connected to the stirring adjustment tank 22 may be connected to one reaction tank 35. Moreover, in this embodiment, the 1st flow path 13 is connected to the center side where the serum of the sample storage tank 12 is located.

  The first valve 15, the second valve 37, the third valve 25, the fourth valve 38 and the fifth valve 39 open when receiving light irradiated from the irradiation device 8 and are stopped when irradiation is not performed. Then the valve closes. A check valve or an automatic valve may be used for the first valve 15, the second valve 37, the third valve 25, the fourth valve 38, and the fifth valve 39. A disk provided with a sample injection port communicating with the sample storage tank 12 may be laminated on the upper surface of the first disk 11.

  The rotating device 2 is a device that rotates the laminate 1 based on the number of rotations or the rotation speed commanded from the computer (control device) 7. At this time, the first disk 11, the second disk 21, the third disk 31, and the fourth disk 41 rotate simultaneously. The rotation axis is the central axis of the first disk 11, the second disk 21, the third disk 31, and the fourth disk 41. In addition, the rotation speed of the laminated body by the rotation apparatus 2 is controlled according to each operation, such as pre-processing, stirring, reaction, and detection, for rotation speed and rotation speed.

  The first irradiation device 3 (irradiation means) irradiates the detection tank 34 with light (electromagnetic waves) in the axial direction of the laminate. The second irradiation device 8 irradiates the first bulb 15, the second bulb 37, the third bulb 25, the fourth bulb 38 and the fifth bulb 39 with light (electromagnetic waves). The first irradiation device 3 and the second irradiation device 8 may be one device. Moreover, what is irradiated from the 1st irradiation apparatus 3 and the 2nd irradiation apparatus is not restricted to light, You may irradiate a wave (for example, a microwave, Rayleigh wave), a laser beam, etc. Furthermore, the 1st irradiation apparatus 3 and the 2nd irradiation apparatus 8 are movable things, and what can irradiate light, a microwave, a Rayleigh wave, etc. with respect to the reaction tank 35 may be used.

  The optical fibers 4 a and 4 b are for transmitting the light applied to the detection tank 34 to the spectrometer 5. The spectroscope 5 is provided so as to be connected to the optical fibers 4a and 4b. The spectroscope 5 is a device that receives light transmitted from the optical fiber 4 and spectrums the received light by spectroscopic measurement. . Further, the detector 6 is an apparatus that is connected to the spectroscope 5 and measures the measurement results spectralized in the spectroscope 5. Then, the computer (control device) 7 performs processing such as storage and organization of the results measured by the detector 6. The computer (control device) 7 is a device that instructs the rotation device 2 to control the rotation speed, and instructs the rotation device 2 to determine the rotation speed of the laminate according to each operation.

  Next, a method for stacking the disks 1 will be specifically described with reference to FIGS. Here, each of (a) to (f) of FIG. 5 is a diagram showing a manufacturing process of a structure in which a plurality of pores having a flow path of the reaction tank 35 inside are bundled. Each of (a) to (d) of FIG. 6 is an example of a joining process in which the first disk 11, the second disk 21, the third disk 31, and the fourth disk 41 are stacked and joined. FIG. Further, each of FIGS. 7A to 7C is a diagram showing an example of a process for producing a flow path in the surface direction of the disk, and each of FIGS. 7D to 7F is a disk of a different layer. It is a figure which shows an example of the process of producing the connection flow path which connects the flow path of the surface direction formed in this, (g) is sectional drawing of the disk which joined the disk produced by these processes.

  First, a method for manufacturing the second disk 21 will be described with reference to FIG. A resist structure (b) is produced by X-ray lithography shown in (a). The resist structure is electroformed, and the reverse structure is transferred to the electroformed film to produce a molding die for the structure (c). A structure is manufactured by a molding process shown in (d) using a molding die (e). Note that (f) is obtained by inverting the molding die shown in (c) upside down. This series of manufacturing methods includes three steps: X-ray lithography using X-rays, electroforming which is a kind of electroplating technique, and molding. Note that not only the final molded (e) but also the structure (b) and molding die (f) produced by X-ray lithography can be used in the reaction tank 35, the flow path, or the stirring adjustment tank 22. .

  Next, a process of stacking and joining the first disk 11, the second disk 21, the third disk 31, and the fourth disk 41 made of resin will be described with reference to FIG. First, the third disk 31 and the fourth disk 41 manufactured by the method shown in FIG. 5 ((b), (e)) are stacked so as to be positioned concentrically in order from the top, and heated. -Joining with no adhesive by pressurization (Fig. 6 (a)). Next, the second disk 21 and the joined third disk 31 and fourth disk 41 are aligned so as to be positioned concentrically, and stacked so that the second disk 21 comes to the top. Then, they are joined with no adhesive by heating and pressing (FIG. 6B). Then, the first disk 11 and the joined second disk 21, third disk 31, and fourth disk 41 are aligned so as to be positioned concentrically, and the first disk 11 comes to the top. Then, they are laminated and joined with no adhesive by heating and pressing (FIGS. 6C and 6D). In the present embodiment, since the first disk 11, the second disk 21, the third disk 31, and the fourth disk 41 are made of resin, the first disk 11 and the second disk 21 are used without using an adhesive. The third disk 31 and the fourth disk 41 can be joined. Thereby, there is no worry about the thickness of the adhesive layer generated when an adhesive is used, and a fine laminated structure can be formed.

  Next, another example of a method for producing a reagent or sample flow path in the disk 1 will be described with reference to FIG. First, an example of a process for producing a planar flow path in the disk 1 (a process for producing the first disk 11, the third disk 31, and the fourth disk 41) will be described. Place SU-8 having a size to be a flow path on the substrate (a), place silicon rubber (PDMS) on the substrate and SU-8 (b), and place silicon rubber (PDMS) on which the flow path is formed. Peel from the substrate and SU-8 (c). Next, an example of a flow path manufacturing process (second disk 21) in a direction perpendicular to the plane of the disk 1 will be described. A mask in which holes are formed at positions to be flow paths is prepared (d), the mask is placed on the photosensitive resin, and patterning is performed by irradiating the photosensitive resin with UV or X-rays from above the mask (e ). By this irradiation, a flow path is formed in the photosensitive resin (f). Then, the produced silicon rubber (PDMS) and the photosensitive resin are laminated and joined in the order of silicon rubber, photosensitive resin, and silicon rubber (g). In addition, according to this manufacturing process, since silicon rubber (PDMS) has self-adhesiveness, it can be joined and sealed without the need for heating / pressurizing treatment as shown in FIG.

  Next, the operation method of the microchemical system apparatus 100 and the microchemical system 1 and the fluid feeding will be specifically described with reference to FIGS. FIG. 8 is a diagram showing the relationship between the rotational speed of the disk 1 and time when blood is used as a sample, and the first valve 15, the second valve 37, the third valve 25, the fourth valve 38, and the fifth valve. It is a figure which shows the relationship between opening and closing of 39, and time. Each of (a) to (d) of FIG. 9 is a diagram showing a process of feeding a sample and liquid in the disk 1. In addition, the range of the dashed-dotted line of FIG.8 (b) may open or close a valve | bulb.

  First, a sample is injected from a sample injection port (not shown), and the sample is stored in the sample storage tank 12. Then, the disk 1 is rotated by the rotating device 2 at the number of rotations shown in FIG. 8A, and the sample is pretreated in the sample storage tank 12. Here, the first valve 15 is closed while the pretreatment operation is performed. Then, the closed first valve 15 can prevent the sample from moving to the stirring adjustment tank 22. The pretreatment includes, for example, a process of centrifuging blood cells and serum when the sample is blood. In this case, as shown in FIG. 3A, the blood cell moves to the center side of the circle of the microchemical system 1, and the serum moves to the outside in the radial direction of the circle of the microchemical system 1 to be separated. When this operation is finished, the rotation of the microchemical system 1 is stopped. In addition, according to the content of pre-processing. The rotation of the microchemical system 1 after the pretreatment may be continued.

  Next, a reagent is injected from a reagent injection port (not shown), and the reagent is stored in the reagent storage tank 32. Here, the second valve 37 is closed while the reagent is being accumulated in the reagent accumulation tank 32. And it can suppress that a reagent moves to the stirring adjustment tank 22 by this closed 2nd valve | bulb 37 (Fig.9 (a)).

  Then, the irradiation device 8 irradiates the first valve 15 and the second valve 37 with electromagnetic waves (laser light), opens the first valve 15 and the second valve 37, and increases the rotation speed of the disk 1 with the rotating device 2. The microchemical system 1 is rotated at a rotational speed different from the rotational speed of the pretreatment shown in FIG. 8B (a rotational speed less than the rotational speed of the pretreatment). As a result, the sample (serum) and the reagent move to the stirring adjustment tank 22, and the sample (serum) and the reagent are stirred in the stirring adjustment tank 22. In addition, since the 1st valve | bulb 15 and the 2nd valve | bulb 37 will close if irradiation of electromagnetic waves (laser light) is stopped, it can adjust with the quantity of a sample and a reagent by adjusting the time to irradiate electromagnetic waves (laser light). Further, the third valve 25 is closed while stirring and mixing are performed. The closed third valve 25 can prevent the sample from being sent to the third flow path 23 on the downstream side of the reaction tank 35 and the third valve 25 (FIG. 9B). For example, as shown in FIG. 4, when the antigen or antibody is immobilized on the inner wall surface of the mixing tank, the concentration of the sample can be changed or changed to another substance. Further, if the catalyst is fixed on the inner wall surface of the mixing tank, a catalytic reaction occurs and the sample can be made different.

  Next, the number of rotations is further increased by the rotating device 2, and the number of rotations different from the number of rotations of stirring and mixing shown in FIG. 8C (less than the number of rotations of stirring and mixing and higher than the number of rotations of pretreatment) The microchemical system 1 is rotated at the rotation speed), and the third valve 25 is opened. As a result, the sample (serum) and the reagent are sent from the stirring adjustment tank 22 through the third flow path 23 to the reaction tank 35 (FIG. 9C). And if the electromagnetic wave (laser light) is irradiated to the reaction tank 35 from the 2nd irradiation apparatus 8, excitation and acceleration | stimulation of the reaction of the sample in the reaction tank 35 can be improved. Since the fourth valve 38 is closed while the sample is being reacted, the reaction product generated in the reaction tank 35 is prevented from moving to the detection tank 34.

  After completion of the reaction of the sample, the electromagnetic wave (laser light) is irradiated to open the fourth valve 38 and the fifth valve 39, and the number of rotations is further increased. The chemical system 1 is rotated. Due to the centrifugal force generated by this rotation, the reaction product passes from the reaction tank 35 through the second flow path 23 to the detection tank 34, and the entire detection tank 34 is filled with the sample. Here, since the hole 16 is thin, the reaction product sent from the fourth disk 41 by the inter-capillary phenomenon flows to the second disk 21, and the entire detection tank 34 is filled with the reaction product. Thereafter, the rotation device 2 changes the rotation speed to the rotation speed indicated by E in FIG. 8 so that the reaction product does not flow backward to the fourth disk 41 side, and the irradiation of the electromagnetic wave (laser light) to the fifth valve 39 is stopped. Thus, the fifth valve 39 is closed to maintain the state in which the detection tank 34 is filled with the reaction product (FIG. 9D). The rotational speed is not limited to the rotational speed shown in FIG. 8 and may be adjusted to a preferable rotational speed at which each process can be performed.

  Next, the microchemical system 1 is rotated at a rotation speed suitable for detection shown in F of FIG. 8, and electromagnetic waves (light) are irradiated from the first irradiation device 3 to the detection tank 34 in the stacking direction of the stacked body. The light irradiated to the reaction product becomes transmitted light or fluorescence. Then, the fluorescence is collected by the film 24, guided in the radial direction of the disk 1 (the arrow direction in FIG. 8D), and transmitted to the spectrometer. Then, the change in absorbance due to the enzyme reaction from each of the plurality of samples or the transmitted light or fluorescence from the sample is dispersed, and the peak position and intensity of the obtained spectrum are measured to measure the reaction product. Specifically, the detection tank 34 is irradiated with light from the first irradiation device 3, and the absorbance change due to the enzyme reaction or the fluorescence from the reaction product is transmitted to the spectroscope 5 by the optical fiber 4a. Absorbed light from the reaction product is transmitted to the spectroscope 5 through the optical fiber 4b. Then, the transmitted light or fluorescence transmitted is received by the spectroscope 5 and spectrally separated. Then, the peak position and intensity of the obtained spectrum are measured by the detector 6, and the measured data is stored and organized in a computer (control device) 7.

  In the present embodiment, the microchemical system 1 is rotated at the rotational speed shown in FIG. 8, but is not limited to the rotational speed shown in FIG. 8. For example, instead of the microchemical system according to the present embodiment, when a microchemical system without the reaction tank 35 is used, when the disk 1 is rotated at a high speed rotation as shown by a one-dot chain line in FIG. It is possible to analyze minute changes in the reaction process of the specimen.

  According to this embodiment, since fluid such as a liquid or a gas in the liquid can be transferred not only in a two-dimensional (planar) direction but also in a three-dimensional direction by centrifugal force, processing such as reaction, stirring, and detection in the flow path is accurate. Can do well. In addition, operations such as sample pretreatment, mixing, reaction, separation, extraction, and detection can be integrated in one apparatus. Thereby, size reduction and weight reduction of an apparatus can be achieved, and a sample and a reagent are restrained in a small quantity than before. Moreover, since a tank formed in a direction perpendicular to the plane of the disk of the microchemical system 1 is used, a place necessary for stirring, a capacity and a surface area required for reaction, and further, a light detection are required. A sufficient optical path can be obtained, and the accuracy and analytical sensitivity of each operation can be improved. As a result, a single apparatus can simultaneously detect and process a large number of samples (specimens) and can perform each operation in a short time. Furthermore, since a small change in the reaction process of the specimen can be detected in the detection tank, the detection range can be expanded.

  In addition, since the agitation adjustment tank 22 is bundled with a plurality of pores, the surface area of the flow path can be greatly increased, and the efficiency of each treatment such as fluid feeding, agitation, and reaction can be greatly improved. Can do.

  Further, in the reaction tank 35, the reaction can be promoted, or the reaction of only a specific sample or a specific part of the sample can be caused, so that the selectivity of the sample can be improved. In the present embodiment, the microchemical system 1 including the reaction tank 35 is used. However, if a reaction apparatus without the reaction tank 35 is used, the reaction process of the specimen can be detected by the detection tank 34, so that the detection range can be expanded. Can be planned. In addition, since antigens and antibodies can be stably fixed at a high density on the inner wall surface of the reaction tank 35, the accuracy of processing such as stirring and reaction can be further improved.

  In addition, since the first valve 15, the second valve 37, the third valve 25, the fourth valve 38, and the fifth valve 39 provided in the middle of the flow path are opened and closed, the liquid feeding of the sample can be suppressed. The accuracy of each operation in the sample accumulation tank, the stirring adjustment tank, and the detection tank can be improved. In addition, since the first valve 15, the second valve 37, the third valve 25, the fourth valve 38, and the fifth valve 39 contain a phase change material, the valve can be easily opened and closed (the flow path is wide or narrow). Can be operated.

  In addition, since the predetermined antibody or antigen and the catalyst are stably fixed at a high density on the inner wall surface of the stirring adjustment tank 22, the pretreatment of the reaction can be performed efficiently.

  In addition, each operation such as stirring, reaction, and detection of the sample can be automatically performed by the centrifugal force generated by rotating the microchemical system 1 by the rotating device 2. Thus, the operation can be performed easily and in a short time, and the amount of reagents and samples can be reduced to a small amount. In addition, it is possible to suppress the occurrence of variations in human operation accuracy that have conventionally occurred, and it is possible to improve reproducibility, reliability, and analysis sensitivity.

  Further, the first irradiation device 3 and the second irradiation device 8 can irradiate the stirring adjustment tank, the reaction tank, the detection tank, the light valve, etc. with fluorescence or laser light. This makes it possible to promote agitation, acceleration of reactions that are difficult to thermally react, reaction of a specific part of a sample or a specific sample, reaction at room temperature, improved selectivity, high speed reaction, high yield. A microchemical system apparatus can be provided. Also, light detection is possible. The irradiation device is not limited to the one that irradiates light, but may be one that irradiates microwaves or surface acoustic waves. For example, metal nanoparticles and organometallic complexes can be synthesized by irradiating the reaction vessel with microwaves, and the accuracy of stirring the sample can be further improved by irradiating surface acoustic waves to the stirring adjustment vessel.

  In the present embodiment, a third irradiation device (not shown) for irradiating the stirring adjustment tank 22 with electromagnetic waves such as surface acoustic waves may be provided above the disk or at a position near the disk. The third irradiation device can irradiate the agitation adjustment tank 22 with surface acoustic waves and ultrasonic waves, so that the mixing and agitation in the agitation adjustment tank 22 can be promoted, and the reaction sensitivity and detection sensitivity can be further improved. In addition, what is irradiated from a 2nd irradiation apparatus will not be restricted to a surface acoustic wave or an ultrasonic wave, if the mixing and stirring in a stirring adjustment tank are accelerated | stimulated.

  In the present embodiment, the inner walls of the first flow path 13, the second flow path 33, the third flow path 23, the stirring adjustment tank 22, and the reaction tank 35 are covered with a thin film, and the thin film is the first disk 11. The second disk 21, the third disk 31, and the fourth disk 41 may be made of a different material. By adopting such a configuration, antigens, antibodies, and the like can be stably fixed at a high density on the inner wall surface of the flow path, so that accuracy, speed, and efficiency of processing such as stirring and reaction can be further improved.

<Second Embodiment>
Next, another embodiment of the third disk in the first embodiment of the present invention will be described. FIG. 10 is a scanning electron micrograph (SEM photograph) of the main body of the third disc (enzyme immunoassay element) according to the second embodiment of the present invention, where (a) is a perspective photograph and (b) is a perspective photograph. It is a cross-sectional photograph. FIG. 11 is a diagram sequentially illustrating a manufacturing process of the main body of the enzyme immunoassay element shown in FIG. FIG. 12A shows a part of the microchemical system (the lower surface of the second disk and the upper surface of the fourth disk when the third disk according to the present embodiment is used in the microchemical system according to the first embodiment. (B) and (c) are diagrams showing a part of the liquid feeding process of the sample in (a).

  As shown in FIGS. 10A and 10B, the main body of the third disk 231 (enzyme immunoassay element) according to the present embodiment has a hole (diameter of 50 μm or less) having a flow path therein. A large number of holes are formed, and the flow paths intersect each other inside. And this hole becomes the reaction tank 35 and the 2nd flow path 23 in 1st Embodiment. And although not shown in figure, it becomes an element for enzyme immunoassay by fixing a predetermined antibody or antigen to the inner wall surface of this flow path. In addition, you may fix a catalyst instead of an antibody or an antigen. For immobilization of the predetermined antibody or antigen, a known method (for example, a two-antibody solid phase method, a one-antibody solid phase method, a competitive method using a solid-phased antigen and an enzyme-labeled antibody, a sandwich method, an immunoenzymatic method) However, the present invention is not limited to these.

  The main body of the third disk (enzyme immunoassay element) 231 according to the present embodiment is formed using a photosensitive resin such as polymethyl methacrylate, an epoxy photosensitive resin, or polytetrafluoroethylene.

  Examples of antibodies used in the present embodiment include monoclonal antibodies and polyclonal antibodies. Examples of the antigen include low molecular compounds such as nonylphenol and dioxin, proteins such as tumor markers, virus particles, and cells.

  Next, a method for manufacturing the main body of the second disk (enzyme immunoassay element) 231 according to this embodiment will be described with reference to FIG. Here, a lithography process technique of a photosensitive resin using soft X-rays or hard X-rays having a photon energy of 70 eV or more is used.

  First, an X-ray mask 251 in which a predetermined number of holes are formed is placed on the surface of the photosensitive resin 252 on the X-ray 253 irradiation side. Subsequently, the X-ray mask 251 and the photosensitive resin 252 are tilted by a predetermined angle with respect to the X-ray 253 irradiation direction, and then the X-ray 253 is irradiated toward the X-ray mask 251 so that a predetermined portion of the photosensitive resin 252 is irradiated. The photosensitive portion 252a is formed by exposure (see FIG. 11A). Next, once the irradiation of the X-ray 253 is stopped, the X-ray mask 251 and the photosensitive resin 252 are inclined at a predetermined angle, and the X-ray 253 is irradiated again toward the X-ray mask 251 to be photosensitive. A predetermined portion of the resin 252 is exposed to form a photosensitive portion 252b (see FIG. 11B). The body of the third disk (enzyme immunoassay element) 231 according to this embodiment is formed by dissolving the photosensitive portions 252a and 252b using a developer and molding (developing) the intersecting flow path 254. Completed (see FIG. 11C). Further, by fixing a predetermined antibody or antigen to the main body of the second disk (enzyme immunoassay element) 231, the third disk (enzyme immunoassay element) 231 according to the present embodiment is completed.

  In addition, although the case where only one main body was manufactured was demonstrated in the said manufacturing method, the following methods can be used in mass production. That is, first, after carrying out to the manufacturing method of FIG. 11A, the photosensitive portion 252a is dissolved using a developer. Then, this is electroformed to produce a mold for manufacturing a main body of a third disk (enzyme immunoassay element) 231 having a protrusion having the same shape as the photosensitive portion 252a. Using this mold, the resin is once punched diagonally to form a hole having the same shape as that of the photosensitive portion 252a, and then inserted into this hole again, so that the hole having the same shape as that of the photosensitive portion 252b in FIG. The main body of the third disc (enzyme immunoassay element) 231 shown in FIG. 11C can be manufactured (so-called embossing) by punching the resin again obliquely so as to form. Therefore, the main body of the third disk (enzyme immunoassay element) 231 can be mass-produced by the mold. Examples of the mold material include metals such as nickel, gold, platinum, copper, molybdenum, tungsten, cobalt, and alloys thereof.

  Next, the third chemistry (element for enzyme immunoassay) 231 according to the present embodiment is used in place of the third disk 31 of the micro chemistry system 100 according to the first embodiment, and the micro chemistry shown in FIG. A sample liquid feeding process when the system is used will be described. The liquid feeding process in the first disk, the second disk, and the fourth disk in the first embodiment is the same as the liquid feeding process in the first disk, the second disk, and the fourth disk (not shown) in the present embodiment. Since it is a thing, description may be abbreviate | omitted.

  When a sample processed in a sample storage tank (not shown) is sent to the third disk 231, the sample is sent to the third disk 231 by the filter effect of the third disk 231 as shown in FIG. Without being maintained on the surface of the third disk 231. Then, a pressure by centrifugal force is applied in the direction indicated by the arrow in FIG. 12B, and the sample (reaction product) is fed into the third disk 231 and below the third disk 231.

  Here, an example of the state of the sample when the sample is fed into the third disk (enzyme immunoassay element) 231 according to the present embodiment will be described. A sample solution in which “a test substance to be an antigen and a complex in which the test substance and the enzyme or a fluorescently labeled antibody are bound” is mixed into the hole of the third disk (enzyme immunoassay element) 231 is sent. Then, the antigen-antibody reaction is performed competitively while being held in the flow path of the third disk (element for enzyme immunoassay) 231.

  Subsequently, after the antigen-antibody reaction and the catalytic reaction as described above are completed in the third disk 231, the sample is held in the space between the third disk 231 and the fourth disk by the applied pressure, as shown in the figure. No liquid is fed to the fourth disc. In the fourth disk, when the rotation speed is further changed by the rotating device, the sample is fed to the detection tank.

  Then, the identification and concentration of the test substance are measured in a detection tank (not shown). In addition, the identification of the test substance and the measurement of the concentration were carried out using the above-mentioned complex eluted from the third disk (enzyme immunoassay element) 231 according to the present embodiment, as in the first embodiment, the absorbance by the enzyme reaction. The change or the transmitted light or fluorescence from the complex is dispersed, and the peak position and intensity of the obtained spectrum are measured. Here, examples of “a test substance to be an antigen and a complex in which the test substance and an enzyme or a fluorescently labeled antibody are combined” include the above-described complex of an antigen and peroxidase, the above-described antibody, and Examples include complexes with peroxidase. Also, instead of peroxidase, it is a complex that uses either an enzyme whose reaction product can be detected by fluorescence or absorption, such as phosphatase or β-galactosidase, or an enzyme that catalyzes a luminescence reaction, such as luciferase. There may be. Another example is a complex of a low-molecular compound that emits fluorescence and an antigen (or antibody). Moreover, water or / and an organic solvent are used for the solvent of a solution.

  When the third disk (element for enzyme immunoassay) 231 configured as described above is used in the microchemical system according to the first embodiment, the same effects as those of the microchemical system according to the first embodiment can be obtained. In addition, the surface area of the flow path can be greatly improved as compared with the conventional one, and the mixing effect generated when the liquid passes can be achieved. As a result, it is possible to provide a microchemical system capable of performing enzyme immunoassay that can be performed at a higher speed and with higher sensitivity than before.

  As a modification, the inner wall surface of the channel is coated with a thin film containing, for example, a metal such as nickel or platinum, diamond-like carbon, a compound, or a biocompatible polymer (such as avidin). Alternatively, a predetermined antibody, antigen or catalyst may be immobilized on the surface of the thin film. Thereby, since the predetermined antibody or antigen is stably fixed at a high density on the surface of the flow path, the sensitivity in enzyme immunoassay can be further improved and the measurement can be performed at high speed.

<Third Embodiment>
Next, another embodiment of the microchemical system in the first embodiment of the present invention will be described. FIG. 13 is a schematic configuration diagram of a microchemical system apparatus according to a third embodiment of the present invention. 14 is a schematic cross-sectional view taken along the line BB of the microchemical system 301 in FIG. FIG. 15A is a perspective view of the first disk according to the third embodiment of the present invention, and FIG. 15B is a schematic cross-sectional view of the convex portion of FIG. FIG. 16A is a perspective view of a modified example of the first disk of FIG. 15, and FIG. 16B is a schematic cross-sectional view of the convex portion of FIG. In addition, each part to which the code | symbol 1-41 in 1st Embodiment is touched, each part to which the code | symbol 301-341 is given in this embodiment, and code | symbol 411-413, 415,434 in this modification are touched. Since the components are the same in order, the description may be omitted.

  Differences between the first embodiment and the third embodiment will be described with reference to FIGS. In the third embodiment, (1) the first disc 301 has a convex portion 317 on the surface opposite to the second disc 321, and a hole communicating with the detection tank is formed in the convex portion 317. (2) The detection tank 334 is not provided with a film. (3) The optical fiber 304 is provided close to the detection tank 334 on the bottom surface of the microchemical system 300 on the same axis as the first irradiation device 303. In the first embodiment, the optical fiber 304 receives the absorption light of the electromagnetic wave irradiated to the detection tank 334 from (4), and (4) the third disk 31 contains metal fine particles having a particle size of 10 μm or less. And different. In addition, this convex part is formed coaxially with the detection tank. As the metal fine particles, gold or silver fine particles can be used.

  As shown in FIG. 15, the first disk has a rectangular parallelepiped convex portion 317 at a position coaxial with the detection tank 334 on the surface opposite to the second disk. A hole 316 that penetrates the convex portion 317 in the convex direction is formed in the fourth disk 341, and the hole 316 communicates with the detection tank 334. The convex portion 317 is not limited to a rectangular parallelepiped shape, and may be a semicircular convex portion 417 or a triangular convex portion as shown in FIG.

  According to the microchemical system apparatus according to the present embodiment, the same effects as those of the microchemical system apparatus according to the first embodiment can be obtained. Further, due to the Venturi effect generated by the rotating device 302, the centrifugal force convex portion 317, and the hole 316, the fluid sent from the fourth disk 341 to the position of the second disk 321 in the detection tank 334 is detected. Tank 334 can be filled. Further, due to the pressure difference between the channel inlet (detection tank 334 inlet) and the channel outlet (hole 316 outlet) generated by the venturi effect, a force for transporting the liquid in the channel is added to the centrifugal force. As a result, the number of rotations of each step (separation, mixing, reaction, liquid feeding, detection, etc.) shown in FIG. 8 can be reduced. Thereby, generation | occurrence | production of the turbulent flow accompanying a liquid feeding and the production | generation of the bubble by a turbulent flow can be suppressed, and the precision of the liquid feeding for every step can be improved.

  In the present embodiment, the third disk 31 may contain metal fine particles having a particle size of 10 μm or less. As a result, the metal fine particles appear on the inner wall surface of the reaction tank and are immobilized as antigens or antibodies. As a result, the reaction of the sample can be further promoted and the accuracy of the reaction can be further improved.

  The microchemical system and the microchemical system apparatus according to the embodiments of the present invention have been described above. However, the present invention is not limited to the above-described embodiments, and various modifications are possible as long as they are described in the claims. It is a thing. For example, although the stirring adjustment tank is located on the second disk and the reaction tank is located on the third disk, the position of each tank is not limited to the disk shown in the present embodiment. Further, the change in the rotational speed is not limited to the rotational speed shown in the first embodiment.

  Moreover, in this embodiment, although the microchemical system which provided the reaction tank in the middle of the 2nd flow path was used, you may react in a detection tank, without providing a reaction tank. Thereby, since the fine time change of the reaction process of a sample can be detected in a detection tank, a detection range becomes wider. At this time, the reaction process can be detected more accurately by rotating the disk at a high speed such as the number of rotations indicated by the two-dot chain line shown in FIG. Moreover, you may perform stirring and reaction in a stirring adjustment tank, without providing a reaction tank.

  In addition, the sample used in the microchemical system according to the present embodiment is not limited to blood. For example, food poisoning bacteria (O157, Salmonella), environmental hormones, cancer cells, and the like can be used. Etc., and can be used in various fields.

  Moreover, in this embodiment, although the tank is provided in the middle of the flow path, mixing, reaction, and detection may be performed in the middle of the flow path without providing the tank. Furthermore, the positions of the tanks and the flow paths are not limited to being located on the disk shown in the present embodiment, and may be located on different disks.

  Moreover, in 1st Embodiment, what bundled the several pore which has a flow path inside is used for the reaction tank, However, It is not restricted to a reaction tank, You may use for a stirring adjustment tank and a 3rd flow path.

1 is a schematic configuration diagram of a microchemical system apparatus according to a first embodiment of the present invention. It is a perspective view of the microchemical system which comprises the microchemical system apparatus of FIG. FIG. 3 is a top view of four disks constituting the microchemical system of FIG. 2. It is a cross-sectional schematic diagram of AA of FIG. Each of (a)-(f) is a figure which shows the manufacturing process of the reaction tank of FIG. (A)-(d) is a figure which shows the joining process which laminates | stacks and joins the 1st disk of FIG. 3, a 2nd disk, a 3rd disk, and a 4th disk. (A)-(c) is a figure which shows the process of producing the plane flow path of the disk of FIG. 2, and each of (d)-(f) is a disk of a different layer of the disk of FIG. It is a figure which shows an example of the process of producing the connection flow path which connects the formed surface direction flow path, and (g) is sectional drawing of the disk which joined the disk produced by these processes. It is a figure which shows the relationship between the rotation speed of a disk at the time of using the blood as a sample for the microchemical system of FIG. 1, and time. (A)-(d) is a figure which shows the process of a sample and liquid feeding in the disc of FIG. It is a scanning electron micrograph (SEM photograph) of the main body of the 2nd disc (element for enzyme immunoassay) concerning 2nd Embodiment of this invention, (a) is a perspective photograph, (b) is a cross-sectional photograph. . It is a figure which shows the manufacturing process of the main body of the element for enzyme immunoassay of FIG. 10 in order. (A) is a perspective view which shows a part of microchemical system at the time of using the 2nd disc concerning this embodiment for the microchemical system which concerns on 1st Embodiment, (b), (c) is It is a figure which shows a part of liquid feeding process in (a). It is a schematic block diagram of the micro chemical system apparatus which concerns on 3rd Embodiment of this invention. It is a cross-sectional schematic diagram of A'-A 'of the microchemical system of FIG. (A) is a perspective view of the 1st disc concerning a 3rd embodiment of the present invention, and (b) is a section schematic diagram of a convex part of (a). (A) is a perspective view of the modification of the 1st disk of FIG. 15, (b) is a cross-sectional schematic diagram of the convex part of (a).

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Microchemical system 2 Rotating apparatus 3 1st irradiation apparatus 4a, 4b Optical fiber 5 Spectrometer 6 Detector 7 Computer (control apparatus)
8 Second irradiation device 11, 211, 311 First disk 12 Sample storage tank 13 First flow path 34,334 Detection tank 15 First valve 16,316 hole 21,231 Second disk 22 Stirring adjustment tank 23 Third flow path 24 Membrane 25 3rd valve 31 3rd disk 32 Reagent accumulation tank 33 2nd flow path 35 Reaction tank 37 2nd valve 38 4th valve 39 5th valve 40 Pulse generation marker 41 4th disk 100 Micro chemical system apparatus 251 X-ray Mask 252 Photosensitive resin 252a, 252b Photosensitive portion 253 X-ray 254 Channel 317, 417 Protruding portion

Claims (16)

A microchemical system for transferring a fluid to a flow path formed in a disk by centrifugal force generated by the rotation of the disk,
Comprising a laminate in which two or more layers of the disk are laminated;
The flow path has a surface-direction flow path formed in the surface direction of the disk and a connection flow path for connecting the surface-direction flow paths formed in the disk of different layers. Characteristic microchemical system. It has a convex part on the surface of the uppermost disk of the laminate,
2. The microchemical system according to claim 1, further comprising a hole penetrating the convex portion in the convex direction and connected to a flow path formed in the disk. At least a part of the flow path formed in the disk is a bundle of a plurality of pores,
The microchemical system according to claim 1 or 2, wherein the maximum length of the cross section of the pore is 3 mm or less. The inner wall surface of the flow path formed in the disk is coated with a thin film,
The microchemical system according to any one of claims 1 to 3, wherein the thin film is made of a material different from a material of the disk. Provided in the middle of the flow path formed in the disk,
A sample storage tank;
A reagent storage tank;
A stirring adjustment tank for stirring the sample in the sample storage tank and the reagent in the reagent storage tank;
A detection tank for detecting the sample adjusted in the stirring adjustment tank;
Between the sample accumulation tank and the stirring adjustment tank, between the reagent accumulation tank and the stirring adjustment tank, and between the stirring adjustment tank and the detection tank are respectively connected via flow paths. The microchemical system according to any one of claims 1 to 4, wherein: A reaction tank is provided in the middle of the flow path connecting the stirring adjustment tank and the detection tank,
The microchemical system according to claim 5, wherein the stirring adjustment tank and the reaction tank, and the reaction tank and the detection tank are connected to each other through a flow path.   The microchemical system according to claim 5 or 6, wherein the disk on which the reaction layer is located contains fine metal particles having a particle diameter of 10 µm or less. The disk in which the reaction vessel is located is an enzyme immunoassay element in which a large number of holes having flow paths are formed,
The flow paths inside the hole intersect with each other inside, and a predetermined antibody or antigen is immobilized on the inner wall surface of the flow path inside the hole. The microchemical system according to any one of the above. The inner wall surface of the flow path of the enzyme immunoassay element is coated with a thin film,
The microchemical system according to claim 8, wherein the antibody or the antigen is immobilized on the surface of the thin film.   Each of the flow paths connecting between the sample accumulation tank and the stirring adjustment tank, between the reagent accumulation tank and the stirring adjustment tank, and between the stirring adjustment tank and the detection tank The microchemical system according to any one of claims 5 to 9, wherein the microchemical system has a valve provided on the surface.   It has a valve provided in the middle of each of the channel which connects between the stirring adjustment layer and the reaction tank, and between the reaction tank and the detection tank. Item 11. The microchemical system according to any one of Items 6 to 10.   The microchemical system according to claim 10 or 11, wherein the valve includes a phase-changing material.   The microchemical system according to any one of claims 5 to 12, wherein an antigen or an antibody is fixed to an inner wall surface of the stirring adjustment tank. The convex part is formed at a position coaxial with the detection tank,
The microchemical system according to claim 5, wherein the hole and the detection tank are connected.   A microchemical system device comprising: the microchemical system according to claim 1; and a rotating device that rotates the laminate.   The microchemical system apparatus according to claim 16, comprising irradiation means for irradiating the laminate with electromagnetic waves.