JP2005099011A - Antigen measurement apparatus and method, pallet, and antibody chip package - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an antigen measurement apparatus and an antigen measurement method that can analyze a trace substance in a sample solution with high sensitiveness and high precision, and provide a pallet and an antibody chip package that facilitate mounting and removal of an antibody chip. <P>SOLUTION: The antigen measurement apparatus consists of: the antibody chip 1 comprising a substrate 16, an incoming grating 13a and an outgoing grating 13b disposed at both ends on the surface of the substrate 16, an antibody immobilizing layer 14 positioned between the incoming grating 13a and the outgoing grating 13b, and a cell wall 12 enclosing the antibody immobilizing layer 14 to form a cell 11; of a light emitting element 109 for emitting light to the incoming grating 13a; and of a light receiving element 110 for receiving light emerging from the outgoing grating 13b through the substrate 16 under the antibody immobilizing layer 14. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to analysis of substances using antibodies, and more particularly to an antibody chip, an antigen measuring apparatus, an antigen measuring method, a palette, and an antibody chip package for analyzing a very small amount of substance in a sample solution with high sensitivity.

  Conventionally, an enzyme immunoassay (ELISA method) is known as a method for measuring trace components using a specific reaction between an antigen and an antibody. An antigen measurement method using an optical waveguide by applying this method has been proposed. In this immunosensor, a pair of gratings are formed on the light incident portion and light emitting portion on the substrate surface, a single optical waveguide layer is formed on the substrate surface located between the gratings, and an antibody is further formed on the optical waveguide layer. It has a structure in which an immobilization film is formed.

In the immunosensor having such a structure, when a specimen solution containing a measurement target antigen is brought into contact with the antibody-immobilized membrane, the antibody and the measurement target antigen are bound. Furthermore, when a fluorescently labeled antibody is added, an immune complex composed of antibody / antigen to be measured / fluorescently labeled antibody is formed on the substrate surface. In this state, laser light is incident on the optical waveguide layer through the grating, an evanescent wave is generated, and the light amount of the fluorescence of the sample solution resulting from the reaction between the evanescent wave and the immune complex is detected by the light receiving element. The biomolecular weight in the sample solution is analyzed (see, for example, Patent Document 1).
JP-A-8-285851

  However, in the conventional antigen measurement method, it is necessary to detect the amount of surface-emitting fluorescence, the detection sensitivity is limited, and it is not suitable for biomolecule analysis in a very small amount of a sample solution. Therefore, the present invention provides an antibody chip, an antigen measuring device, an antigen measuring method, and a palette and an antibody that can easily handle a substance in a very small amount of sample solution with high sensitivity and high accuracy. It is intended to provide a chip package.

  The first feature of the present invention is (a) a substrate, an incident-side optical element and an exit-side optical element installed on both ends of the substrate, and an antibody positioned between the incident-side optical element and the exit-side optical element An antibody chip comprising an immobilization layer and a cell wall surrounding the antibody immobilization layer to form a cell; (b) a light-emitting element that impinges light toward the incident-side optical element; and (c) an antibody in the substrate. The gist of the present invention is an antigen measuring device including a light receiving element that receives light that is transmitted to pass through the region below the immobilization layer and that is emitted from the emission side optical element.

  The second feature of the present invention is that (a) a specimen solution is dropped on an antibody immobilization layer of an antibody chip to form a primary antibody-antigen complex, and (b) an enzyme label is formed on the antibody immobilization layer. The added secondary antibody solution is dropped to form a primary antibody-antigen-secondary antibody complex, and (c) light is emitted to the incident-side optical element of the antibody chip while injecting a buffer solution onto the antibody immobilization layer. Light is emitted from the element, the light emitted from the optical element on the emission side is received by the light receiving element, the reference light intensity is measured, and (d) a coloring reagent solution is dropped on the antibody immobilization layer to react with the labeling enzyme. (E) irradiating the incident optical element of the antibody chip with light from the light emitting element, and receiving the emitted light from the emitting optical element with the light receiving element, and measuring the light intensity after color development And (f) anti-calculation of the concentration of the antigen in the sample solution from the difference between the reference light intensity and the light intensity after color development. And summarized in that a measuring method.

  A third feature of the present invention is a pallet including a recess for mounting a plurality of antibody chips so that the center distance between the antibody chips is 9 millimeters, and an identification terminal indicating the type of the antibody chip. This is the gist.

  A fourth feature of the present invention is that a packaging container that stores a plurality of antibody chips so that the distance between the centers of the antibody chips is constant, a desiccant for keeping the antibody chips dry, a packaging container, and a heat The gist is that the antibody chip package includes a packing cover to be crimped.

  According to the antigen measuring apparatus and the antigen measuring method of the present invention, it is possible to analyze a substance in a very small amount of a sample solution with high sensitivity and high accuracy. Moreover, according to the pallet and the antibody chip package of the present invention, the antibody chip can be easily attached and detached.

  Next, embodiments of the present invention will be described with reference to the drawings. In the following description of the drawings, the same or similar parts are denoted by the same or similar reference numerals. However, it should be noted that the drawings are schematic and ratios of dimensions and the like are different from actual ones. Accordingly, specific dimensions and the like should be determined in consideration of the following description. Moreover, it is a matter of course that portions having different dimensional relationships and ratios are included between the drawings.

(Antigen measuring device)
As shown in FIG. 1, the antigen measuring apparatus according to the embodiment of the present invention includes (a) a translucent substrate 16, an antibody immobilization layer 14 formed on one main surface of the substrate 16, and An entrance side grating 13a and an exit side grating 13b arranged so as to sandwich the antibody immobilization layer 14 on one main surface of the substrate 16 and a cell wall 12 forming the cell 11 by surrounding the antibody immobilization layer 14 are formed. And (b) a light emitting element 109 that emits light from the other main surface side of the substrate 16 toward the incident side grating 13a disposed on the one main surface side. And (c) a light receiving element 110 that receives the light transmitted through the region under the antibody immobilization layer 14 in the substrate 16 and emitted from the emission side grating 13b.

  It is preferable that the incident side grating 13a and the emission side grating 13b of the antibody chip 1 and the substrate 16 other than the antibody immobilization layer 14 are covered with a fluororesin film 15 to form the reaction hole 10 on the antibody immobilization layer 14.

  In addition, the antigen measurement apparatus is configured to inject the solution from the cell 11 and the injection tube 105 connected to the injection pump 104 as injection means for injecting the solution into the cell 11 which is a space formed by the opening formed by the cell wall 12. A discharge tube 106 connected to a discharge pump 107 is further included as discharge means for discharging. The position of the end portion serving as the spout of the injection tube 105 is preferably located in the cell 11 and immediately above the antibody immobilization layer 14, and the position of the end portion serving as the suction port of the discharge tube 106 is as follows. It is preferably located in the vicinity of the cell wall 12. By doing so, the solution to be injected is surely dropped on the antibody immobilization layer 14, and the solution overflowing from the reaction hole 10 flows toward the cell wall 12 because the fluororesin film 15 is water repellent. . And it discharges | emits reliably from the discharge tube 106 of the cell wall 12 side. The position of the injection tube 105 and the discharge tube 106 can be kept stable by being fixed to the container lid 112 that covers the antibody chip 1. A syringe pump or the like is preferably used as the infusion pump 104, and a bimorph pump or the like is preferably used as the discharge pump.

  Furthermore, the antigen measuring apparatus further includes a solution selection valve 103 connected to the first solution tank 101 and the second solution tank 102 and the injection pump 104 in order to select a solution to be injected. For example, a cleaning solution containing a surfactant is placed in the first solution tank 101, a buffer solution is placed in the second solution tank 102, and which solution is injected into the reaction hole 10 as required by the measurement procedure. Can be selected. Here, the injection pump 104 is operated only when the antibody chip 1 is installed, and the solution is not injected into the measurement container 111 without the antibody chip 1 installed.

Since the light incident from the light emitting element 109 of the antigen measuring apparatus is laser light or the like, it is dangerous when irradiated to the eyeball. Therefore, the light emitting element 109 is operated only when the container lid 112 is closed. In addition, a light shielding plate 108 is provided on the antibody chip 1 side of the container lid 112 so that only light transmitted through the substrate 16 reaches the light receiving element 110, thereby preventing light from entering from unnecessary paths.
The laser light incident on the incident-side grating 13a is reflected and diffracted by the incident-side grating 13a and remains on the substrate 16, and most of the laser light passes through the incident grating 13a and is emitted from the substrate 16 to the container lid 112 side. For this reason, the container lid 112 shields the laser beam from leaking outside. The light incident on the container lid 112 is absorbed by the container lid 112, but there is also a component that reflects. It is necessary to prevent the reflected component from entering the substrate 16 again. Therefore, the surface of the container lid 112 facing the antibody chip is elongated in a direction intersecting with the arrangement direction of the gratings 13a and 13b so as to be positioned between the gratings 13a and 13b provided on the antibody chip 1. A partition-like light shielding plate 108 is disposed. The protruding end of the light shielding plate 108 is disposed at a position where it does not come into contact with the antibody chip 1 when the container lid 112 is closed. At this time, the position closer to the antibody chip 1 is more preferable. A plurality of the gratings 13a and 13b may be arranged side by side along the arrangement direction of the gratings 13a and 13b. Since eight antibody chips 1 are arranged in parallel in a direction perpendicular to the arrangement direction of the gratings 13a and 13b, the light shielding plate 112 is arranged in the extending direction so as to function with respect to the plurality of antibody chips 1. It is good to comprise with one continuous board. At this time, notches and slits may be provided so as to avoid the frame constituting the cell wall 12.
When the container lid 112 is closed, a switch (not shown) provided on the measurement container 111 is pressed by the container lid 112. This switch is electrically connected to the power supply circuit of the light emitting element 109, and is configured not to emit laser light when the switch is not closed.

(palette)
The pallet 113 according to the embodiment of the present invention is provided with a recess into which the antibody chip 1 is fitted. As shown in FIG. 2, one unit is constituted by one pallet 113 on which a plurality of antibody chips 1 are mounted. Specifically, the pallet 113 includes eight recesses for mounting the eight antibody chips 1 so that the center distance is 9 millimeters. A plurality of pallets 113 such as the first unit 200a, the second unit 200b, the third unit 200c, and the fourth unit 200d can be connected and attached to the antigen measuring apparatus. When a plurality of pallets 113 are connected in this way, it is preferable that the type of antibody chip 1 mounted on the pallet 113 can be identified. For this purpose, the pallet 113 is provided with an identification terminal (not shown) on the other main surface different from the main surface on which the antibody chip 1 is arranged, that is, the surface facing the measurement container 111. The identification terminal is connected to an IC chip embedded in the pallet 113 and set to allow writing and reading. Identification information indicating the type of the antibody chip 1 is recorded on the IC chip. The identification information is appropriately rewritten according to the type of the antibody chip 1.
The antigen measurement apparatus has a probe (not shown) that contacts the identification terminal at a portion facing each pallet in the measurement container 111. The probe contacts the identification terminal, reads identification information in the IC chip, recognizes the type of the antibody chip, and automatically selects an appropriate antigen measurement procedure.
The combination of the identification terminal and the IC chip can be wireless. At this time, a transmission / reception circuit capable of communicating with the wireless IC chip is provided on the measurement container 111 side instead of the probe.

(Antibody chip package)
As shown in FIGS. 3 and 4, the antibody chip package according to the embodiment of the present invention is (a) a package that stores a plurality of antibody chips 1 so that the distance between the centers of the antibody chips 1 is constant. It includes a container 202, (b) a desiccant 201 for keeping the antibody chip 1 in a dry state, and (c) a packing cover 203 for thermocompression bonding with the packing container 202.

  The packaging container 202 is made of polystyrene or the like. As the desiccant 201, silica gel or the like is used. The packing cover 203 is made of polyethylene terephthalate (PET), polystyrene, laminate film, or the like.

  Multipipettes and microwell plate operation instruments that are currently commercially available and widely used are 8 series and the distance between them is 9 mm. In view of compatibility with such an instrument, the antibody chip package can accommodate eight antibody chips 1 and the center distance is preferably 9 mm.

  In addition, since the mounting arrangement of the antibody chip 1 on the pallet 113 conforms to this, the mounting operation from the antibody chip package to the pallet 113 becomes easy. On the other hand, when the used antibody chip 1 is thrown away from the pallet 113, it can be thrown away without dirtying the hand if it is returned to the antibody chip package.

(Antibody chip)
The antibody chip of the present invention includes a substrate 16 constituting an optical waveguide layer in which light can propagate through total reflection, and an antibody immobilization layer 14 formed on at least a part of the surface of the optical waveguide layer that totally reflects. The antibody chip | tip which comprises these. Preferably, the lyophobic liquid repellent is formed on the surface of the substrate 16 and opens so that at least a part of the antibody-immobilized layer 14 is exposed so that the surface is higher than the antibody-immobilized layer. The antibody chip is provided with a film 15 having a property, and is fixed to the surface of the optical waveguide layer. The tip is higher than the film having liquid repellency and is formed so as to surround the reaction hole to constitute the cell 11. An antibody chip having a frame body.
The antibody chip preferably includes a cell wall 12 that forms a cell surrounding the antibody immobilization layer, and a reaction hole 10 is preferably formed in the cell 11. By using such an antibody chip, it becomes possible to analyze a measurement target substance in a very small amount of a sample solution with high sensitivity and high accuracy.

The antibody chip includes, for example, a substrate 16 made of borosilicate glass, an incident side grating 13a and an output side grating 13b, which are optical elements disposed on both end surfaces of the substrate 16, and an antibody immobilization layer 14 positioned therebetween. It comprises. Furthermore, a cell wall 12 that surrounds the antibody immobilization layer 14 and forms the cell 11 is provided on the substrate 16. Further, a liquid repellent resin film 15 having the reaction hole 10 on the antibody immobilization layer 14 is provided on the upper side of the incident side grating 13 a and the emission side grating 13 b and on the bottom surface of the cell 11 excluding the antibody immobilization layer 14.
The thickness of the antibody immobilization layer 14 (distance from the surface of the optical waveguide layer to the surface of the antibody immobilization layer) is preferably 30 nm to 500 nm, more preferably 100 nm or less, and particularly preferably 80 nm or less.

The cell wall 12 is a frame and is preferably formed of a colored resin such as black. The resin material is not particularly limited as long as it has no reactivity and compatibility with reagents, solvents, etc., and has good moldability, and acrylic resin, ABS resin, etc. are selected and used according to the kit configuration. be able to.
The frame constituting the cell wall 12 is directly bonded to the surface of the main surface constituting the total reflection surface of the substrate 16 forming the optical waveguide layer by a UV curable adhesive so as to close one end of the opening. ing. The cell wall 12 surrounds the measurement area so that a chemical solution such as a reagent, a specimen solution, and a washing solution that is put into the reaction hole 10 does not leak outside at an unintended time. Therefore, the height from the substrate surface defined by the frame end is formed higher than the height of the liquid repellent resin film 15.
The antibody chip is used in combination with a laser transmitter, a photoelectric conversion element that receives reflected light, or the like. By providing such a cell wall, it becomes possible to prevent erosion by the chemical liquid of various apparatuses due to the chemical liquid operation on the apparatus. As long as the cell wall 12 does not react with the chemicals contained in the measurement kit, the size and height, the shape of the opening of the frame, the material, and the like may be freely determined according to ease of use.

The liquid repellent resin film 15 covers all portions of the surface of the main surface constituting the total reflection surface of the substrate 16 other than at least a part of the antibody immobilization layer 14 and the region where the cell wall 12 is provided. It arrange | positions so that it may cover. For the liquid repellent resin film 15, it is preferable to use a colored resin such as black which has a light shielding property so that light incident from below the substrate 16 is not leaked to the outside. The liquid repellent resin is not particularly limited as long as it has no reactivity and compatibility with the kit and has good liquid repellency and water repellency, but a fluororesin is particularly preferable.
The incident side grating 13a and the emission side grating 13b are made of, for example, titanium oxide (TiO2), tin oxide (SnO2), zinc oxide, lithium niobate, gallium arsenide (GaAs), indium tin oxide (ITO), polyimide, or the like. It is preferable.
The gratings 13a and 13b have an optical function for introducing and emitting a laser beam to the antibody chip. However, the gratings 13a and 13b do not need to be particularly provided if the same function can be realized by using other members. . Further, other optical elements such as a prism may be arranged as long as the same function can be realized.
The antibody immobilization layer 14 has a structure in which, for example, an antibody is immobilized with a cross-linked polymer. Examples of the crosslinked polymer used in the antibody immobilizing layer 14 include a polymer containing a hydrogen bonding functional group such as photocrosslinkable polyvinyl alcohol. Since antibodies are generally hydrophilic, it is preferable that the antibody immobilization layer also has hydrophilicity.

(Method for producing antibody chip)
Next, an example of the manufacturing process of the antibody chip 1 described above will be described with reference to FIGS. 7, 8 and 9;
S10: First, as shown in FIG. 8A, for example, TiO 2 is sputtered on the surface of the substrate 16 made of, for example, borosilicate glass to form the thin film 13.
S11: Next, as shown in FIG. 8B, the thin film 13 is patterned by a photo-etching technique to form the incident-side grating 13a and the emission-side grating 13b on both end surfaces.
S12: Next, as shown in FIG. 8C, for example, on the incident side grating 13a and the emission side grating 13b and on the surface of the substrate 16 other than the reaction hole 10 and the cell wall 12 adhesion portion, for example, light-shielding colored fluorine. Resin is printed to form the fluororesin film 15.
S13: Next, as shown in FIG. 9 (d), for example, a cell wall 12 made of black acrylic is placed so as to surround the reaction hole 10, and is adhered to the substrate 16 using an ultraviolet curing adhesive. The cell 11 is formed.
S14: Next, as shown in FIG. 9E, the antibody immobilization layer 14 is formed in the reaction hole 10. Specifically, (i) silane coupling treatment is performed using aminosilane as a silane coupling agent, and the surface of the substrate 16 is modified with an amino group. (B) Next, glutaraldehyde treatment is performed, and the antibody is immobilized on the substrate 16 by crosslinking. (C) Finally, an excess amino group is blocked with bovine serum albumin (BSA) or the like to form the antibody immobilization layer 14.

(Antigen measurement method using antibody chip)
Next, a method for measuring an antigen of a specific substance in a sample solution by the antibody chip 1 according to the embodiment of the present invention will be described with reference to FIGS.
S20: The surface of the substrate 16 of the reaction hole 10 of the antibody chip 1 is composed of a primary antibody 14a that specifically recognizes an antigen 20a to be measured such as protein or gene, as shown in FIG. 11 (a). An antibody immobilization layer 14 is formed. When the specimen solution 20 containing the antigen 20a is dropped onto the antibody immobilization layer 14 in the reaction hole 10, the antigen 20a binds to the primary antibody 14a as shown in FIG. Form a complex.
S21: Next, the sample solution 20 other than the antigen 20a bound to the primary antibody 14a is washed with a washing solution such as a phosphate buffer (PBS) containing a surfactant.
S22: Next, the enzyme-labeled secondary antibody solution 21 is dropped. Then, as shown in FIG. 11C, the secondary antibody 21a further binds to the antigen 20a at a site different from the primary antibody 14a. As a result, a primary antibody-antigen-secondary antibody complex is formed. As a labeling enzyme that labels the secondary antibody 21a, for example, peroxidase (POD) can be used as an oxidoreductase.
S23: Next, the secondary antibody solution 21 containing the secondary antibody 21a that has not formed a complex is rewashed with a washing solution such as PBS containing a surfactant.
S24: Next, the surfactant used for washing is removed, and only PBS or the like is injected as a buffer solution for stabilization.
S25: At this time, laser light or the like is irradiated from the light emitting element toward the incident side grating 13a of the antibody chip, and the emitted light from the emission side grating 13b is received by the light receiving element and measured as the reference light intensity.
S26: Next, as shown in FIG. 11D, the coloring reagent solution 22 is dropped into the cell 11. Examples of the color reagent solution 22 include 80 mmol of acetic acid, 1.13 mmol of tetramethylbenzidine (TMBZ), 1.91 mmol of hydrogen peroxide (H 2 O 2), dimethyl sulfoxide (1 liter of pH = 4.9 buffer). It is preferred to use those containing less than 1% DMSO). Then, a radical oxygen atom (O *) is generated by an oxidoreductase reaction between a labeling enzyme such as POD and H2O2 which is a substrate of the labeling enzyme. O * produced by the enzyme reaction generates an enzyme reaction product that the coloring reagent 22a develops color.
S27: In such a state, a laser beam or the like is irradiated from the light emitting element toward the incident side grating 13a of the antibody chip, the reflected light from the emission side grating 13b is received by the light receiving element, and the light intensity after color development is measured. To do.
S28: The concentration of the antigen 20a to be measured in the sample solution 20 is calculated from the difference between the reference light intensity measured in S25 and the post-color light intensity measured in S27.

  When the light intensity is continuously measured using this measurement method, the value at a predetermined time A between S24 and S25 is adopted as the reference light intensity, and the value at a predetermined time B after S26 is adopted as the light intensity after coloring. Concentration can be calculated. Therefore, it is not necessary to measure the reference light intensity by performing a target experiment using an antigen-free solution.

  Since the antibody chip 1 of the present invention causes an antigen-antibody reaction and a color development reaction in the reaction hole 10, a sample solution 20 of about 1 microliter can be sufficiently measured.

  It goes without saying that the present invention includes various embodiments not described herein. The technical scope of the present invention is determined only by the invention specifying matters according to the scope of claims reasonable from the above description.

  In the measurement using the antigen-antibody reaction, the concentration of the sample is measured by increasing or decreasing the reference light instead of the fluorescence, so that it can be used when it is difficult to secure a large amount of the sample, such as in the case of testing for newborns and small animals.

1 is a schematic diagram of an antigen measuring apparatus according to an embodiment of the present invention. It is a top view of the measurement container of the antigen measurement apparatus which concerns on embodiment of this invention. It is a top view of the antibody chip package according to the embodiment of the present invention. It is a side view of the antibody chip package which concerns on embodiment of this invention. 1 is a top view showing an antibody chip according to an embodiment of the present invention. FIG. 6 is a cross-sectional view taken along the line II of FIG. 5 showing the antibody chip according to the embodiment of the present invention. It is a flowchart which shows the manufacturing process of the antibody chip which concerns on embodiment of this invention. It is process sectional drawing which shows the manufacturing process of the antibody chip which concerns on embodiment of this invention (the 1). It is process sectional drawing which shows the manufacturing process of the antibody chip which concerns on embodiment of this invention (the 2). It is a flowchart which shows the process of the antigen measuring method by the antibody chip concerning embodiment of this invention. It is a figure explaining the antigen measuring method by the antibody chip concerning an embodiment of the invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Antibody chip, 10 ... Reaction hole, 11 ... Cell, 12 ... Cell wall, 13 ... Thin film, 13a ... Incident side grating, 13b ... Outgoing side grating, 14 ... Antibody fixed layer, 14a ... Primary antibody, 15 ... Fluororesin film, 16 ... substrate, 20 ... specimen solution, 20a ... antigen, 21 ... secondary antibody solution, 21a ... secondary antibody, 22 ... coloring reagent solution, 22a ... enzyme reaction product, 101 ... first solution tank, 102 DESCRIPTION OF SYMBOLS 2nd solution tank, 103 ... Solution selection valve, 104 ... Injection pump, 105 ... Injection tube, 106 ... Discharge tube, 107 ... Discharge pump, 108 ... Light-shielding plate, 109 ... Light emitting element, 110 ... Light receiving element, 111 ... Measurement Container, 112 ... Container lid, 113 ... Pallet, 200a ... First unit, 200b ... Second unit, 200c ... Third unit, 200d ... Fourth unit, 201 Desiccant, 202 ... packing container, 203 ... packing cover

Claims (15)

A substrate having translucency, an antibody-immobilized layer formed on one main surface of the substrate, an incident-side optical element and an output-side optical element disposed so as to sandwich the antibody-immobilized layer, and one end thereof An antibody chip comprising a frame that is fixed to one main surface of the substrate and forms a cell by surrounding the antibody immobilization layer;
A light emitting element that allows light to enter from the other principal surface of the substrate toward the incident side optical element;
A light receiving element that receives the light transmitted through the antibody immobilization layer lower region in the substrate and emitted from the other main surface by the emission side optical element;
An antigen measuring apparatus comprising:   The antigen measuring apparatus according to claim 1, further comprising an injection tube connected to an injection pump for injecting the solution into the cell.   The antigen measuring apparatus according to claim 2, further comprising a discharge tube connected to a discharge pump for discharging the solution from the cell.   The antigen measurement apparatus according to claim 3, further comprising a container lid that covers the antibody chip and fixes the injection tube and the discharge tube.   5. The antigen measuring apparatus according to claim 4, further comprising a solution selection valve connected to a plurality of solution tanks and the injection pump for selecting the solution to be injected.   6. The antigen measurement apparatus according to claim 5, wherein the infusion pump operates only when the antibody chip is installed.   The antigen measuring apparatus according to claim 6, wherein light is incident from the light emitting element only when the container lid is closed.   The light-shielding plate extended in the direction which crosses the arrangement direction of the said incident side optical element and the said output side optical element, and was installed in the said antibody chip side of the said container lid, It has characterized by the above-mentioned. Antigen measuring device.   The antigen measuring apparatus according to claim 1, further comprising a pallet on which a plurality of the antibody chips can be mounted.   The antigen measuring apparatus according to claim 9, wherein a plurality of the pallets can be connected and mounted.   The antigen measurement apparatus according to claim 10, wherein the pallet includes an identification terminal of a type of the mounted antibody chip. A specimen solution is dropped on the antibody immobilization layer of the antibody chip to form a primary antibody-antigen complex,
An enzyme-labeled secondary antibody solution is dropped on the antibody immobilization layer to form a primary antibody-antigen-secondary antibody complex,
A buffer solution is injected onto the antibody immobilization layer, the incident optical element of the antibody chip is irradiated with light from the light emitting element, and the emitted light from the emitting optical element is received by the light receiving element to obtain the reference light intensity. Measure and
A coloring reagent solution is dropped on the antibody immobilization layer to produce an enzyme reaction product that develops color by reaction with the labeling enzyme,
Irradiating the incident-side optical element of the antibody chip with the light from the light-emitting element, receiving the emitted light from the emission-side optical element with the light-receiving element, and measuring the light intensity after color development;
An antigen measurement method, wherein the concentration of the antigen in the sample solution is calculated from the difference light intensity between the reference light intensity and the post-coloring light intensity. A recess for mounting a plurality of antibody chips such that the center distance of each of the antibody chips is 9 mm;
A pallet comprising an identification terminal indicating a type of the antibody chip. A plurality of antibody chips, a packaging container for storing the antibody chips so that the center intervals of the antibody chips are constant; and
A desiccant for keeping the antibody chip dry;
An antibody chip package comprising the packaging container and a thermocompression-bonding cover.   The antibody chip package according to claim 14, wherein an interval between centers of the antibody chips is 9 mm.

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