JP7540970B2 - DETECTION APPARATUS AND DETECTION METHOD - Google Patents

Description

The present disclosure relates to a detection apparatus and a detection method .

Patent Document 1 discloses a technique in which an aqueous solution containing a specimen and a secondary antibody is dropped onto a substrate on which a primary antibody is immobilized, and the specimen sandwiched between the primary and secondary antibodies is detected by a dye or fluorescent substance bound to the secondary antibody.

JP 2015-230221 A

With the technology described in Patent Document 1, if the amount of sample is insufficient, it is difficult to confirm the change in the pigment, and there is a risk of incorrect detection. As such, there is room for improvement in detection accuracy.

The detection substrate according to one embodiment comprises a dielectric substrate, a waveguide covering a portion of the surface of the dielectric substrate and irradiating microwaves, a diamond crystal located on the surface side of the dielectric substrate where the waveguide is located and having an NV center formed on the surface opposite to the surface in contact with the waveguide, and a thin film covering the surface of the diamond crystal where the NV center is formed and having a primary antibody immobilized on the surface, and detects magnetic beads to which a secondary antibody is immobilized that bind to a sample bound to the primary antibody on the surface of the diamond crystal where the NV center is formed.

The detection unit according to one embodiment has the above-mentioned detection substrate, a second dielectric substrate, and magnetic beads on which the secondary antibody is immobilized, and the second dielectric substrate has a recess in which the detection substrate is fitted, and the upper surface of the second dielectric substrate is connected so as to be flat with the upper surface of the detection substrate, and the magnetic beads on which the secondary antibody is immobilized are placed on the upper surface of the second dielectric substrate and are moved by dripping of a sample liquid.

A detection device according to one embodiment has the above-mentioned detection unit and an optical pickup, and the optical pickup has a light source that irradiates light onto the detection substrate provided in the detection unit, and a detector that detects the fluorescence of the detection substrate.

The detection substrate according to one embodiment comprises a dielectric substrate and a thin film covering a portion of the surface of the dielectric substrate and having a primary antibody immobilized thereon. Magnetic beads having a secondary antibody immobilized thereon that bind to the analyte bound to the primary antibody are detected on the surface of the dielectric substrate where the thin film is located by placing the magnetic beads facing a diamond crystal that forms an NV center.

The detection unit according to one embodiment has the above-mentioned detection substrate and magnetic beads on which the secondary antibody is immobilized, and the magnetic beads on which the secondary antibody is immobilized are located at one end of the surface of the dielectric substrate on which the thin film is located, and are moved by the dropping of the sample liquid.

The detection device according to one embodiment is a detection device having the above-mentioned detection unit, the diamond crystal, a waveguide, and an optical pickup, in which the diamond crystal forms an NV center on one surface, the waveguide is located on the surface of the diamond crystal opposite the surface on which the NV center is formed, and the optical pickup includes a light source that irradiates light onto the detection substrate provided in the detection unit, and a detector that detects fluorescence from the detection substrate.

According to a detection device and a detection method according to an aspect of the present disclosure, detection can be performed with high accuracy regardless of the amount of a sample.

FIG. 1 is a cross-sectional view of a detection substrate according to the first embodiment. FIG. 2 is a schematic diagram illustrating an example of the arrangement of thin films on the detection substrate according to the first embodiment. FIG. 3 is a cross-sectional view of the detection unit according to the first embodiment. FIG. 4 is a diagram illustrating a detection process using the detection device according to the first embodiment. FIG. 5 is a diagram illustrating a detection process using the detection device according to the first embodiment. FIG. 6 is a diagram illustrating a detection process using the detection device according to the first embodiment. FIG. 7 is a cross-sectional view of the detection device according to the second embodiment. FIG. 8 is a cross-sectional view of a detection device according to a modified example of the second embodiment.

A detection device and a detection method according to a first embodiment will be described below. The detection device and the detection method are for detecting a specimen.

[First embodiment]
(Detection board)
Fig. 1 is a cross-sectional view of a detection substrate 10 according to the first embodiment. As shown in Fig. 1, the detection substrate 10 is a substrate on which a primary antibody 17 for an antigen Y contained in a specimen liquid X, which is a specimen, is arranged. The detection substrate 10 constitutes a test line. The detection substrate 10 includes a dielectric substrate 11, an antenna conductor 12, a waveguide 13, a diamond crystal 14, and a thin film 16.

The dielectric substrate 11 has an antenna conductor 12 and a waveguide 13 formed on a surface 11a. The dielectric substrate 11 is made of, for example, SiO ₂ , a glass material, a ceramic material, or a resin-based material such as glass epoxy. The dielectric substrate 11 is formed in a plate shape.

The antenna conductor 12 transmits microwaves to be irradiated to the NV center 15 of the diamond crystal 14. The antenna conductor 12 is interposed between the surface 11a of the dielectric substrate 11 and the face 14b of the diamond crystal 14. The antenna conductor 12 is, for example, ring-shaped when viewed in the normal direction of the surface 11a of the dielectric substrate 11 (hereinafter referred to as "planar view").

The waveguide 13 is a high-frequency line conductor. The waveguide 13 covers a portion of the surface 11a of the dielectric substrate 11, and irradiates microwaves to the NV center 15 of the diamond crystal 14. The waveguide 13 is interposed between the surface 11a of the dielectric substrate 11 and a face 14b of the diamond crystal 14. The waveguide 13 transmits the microwaves transmitted by the antenna conductor 12. The waveguide 13 is formed of, for example, _SiO2 , a glass material, a ceramic material, or a resin-based material such as glass epoxy.

The diamond crystal 14 is a so-called diamond sensor. The diamond crystal 14 is located on the surface 11a side of the dielectric substrate 11 where the waveguide 13 is located. The diamond crystal 14 has an NV center 15 formed on the surface 14a side opposite the surface 14b that contacts the waveguide 13. A primary antibody 17 is immobilized on the surface 14a.

The diamond crystal 14 has a side length d11 of, for example, 200 μm. The diamond crystal 14 has a thickness d12 of, for example, 100 μm.

The NV center 15 may be arranged singly or in multiples on the surface 14a side of the diamond crystal 14. In this embodiment, Figure 1 etc. illustrates an arrangement of multiple NV centers 15.

The NV centre 15 is a complex defect in the diamond crystal 14 where carbon would normally be, replaced by nitrogen, with a vacancy at an adjacent position. The NV centre 15 is missing a portion of the degenerate shared electron pair. The NV centre 15 has electrons with orbital angular momentum at two levels, m = 0 and m = ±1, in zero magnetic field. The m = ±1 electrons have a magnetic moment and are therefore affected by an external magnetic field, which removes the m = ±1 degeneracy and gives them two more energy levels. The strength of the external magnetic field can be detected by detecting the electron spin resonance caused by these using light waves and microwaves.

The electrons in the NV center 15 are excited by light with a wavelength of 532 nm, and emit fluorescence with a wavelength of 638 nm during the relaxation process. This fluorescence process is unlikely to occur at the electron spin resonance frequency. Therefore, by using this property, the state of the m = ±1 electrons can be observed. In the NV center 15 of the diamond crystal 14, the electron spin resonance frequency in zero magnetic field is known to be about 2.87 GHz. When microwaves with the frequency of this resonance point (resonance frequency) are irradiated, the fluorescence with a wavelength of 638 nm is quenched. In addition, the resonant frequency of the microwave changes due to the change in the state of the m = ±1 electrons depending on the magnitude of the external magnetic field, etc. Then, by capturing this change as a frequency change in the fluorescence intensity, the magnetic field can be detected.

The thin film 16 covers the surface 14a of the diamond crystal 14 on which the NV center 15 is formed. At least a portion of the periphery of the thin film 16 is adjacent to the surface 14a of the diamond crystal 14. The thin film 16 can be formed into various shapes, for example, rectangular, circular, and polygonal. The thin film 16 is formed of a hydrophilic polymer, for example, Au, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, vinyl acetate and vinylamine copolymer, cellulose and its derivatives, polysaccharides, collagen, polyamino acids, etc.

Figure 2 is a schematic diagram illustrating an example of the arrangement of the thin film 16 in the detection substrate 10 according to the first embodiment. Figure 2 is a plan view of the detection substrate 10. As shown in Figure 2, one or more thin films 16 are arranged on the surface 14a of the diamond crystal 14. The thin films 16 may be arranged periodically on the surface 14a. In this embodiment, the thin films 16 are arranged in a lattice pattern on the surface 14a. In the direction of each side of the detection substrate 10, the surface 14a of the diamond crystal 14 and the thin films 16 are alternately exposed. In this embodiment, 10 x 10 thin films 16 are arranged on the surface 14a. The length d21 of one side of the thin film 16 is, for example, 1 μm. The interval between adjacent thin films 16 in the direction of each side of the detection substrate 10 is, for example, 1 μm.

The primary antibody 17 is a primary antibody for antigen Y. Between 1 and 1000 primary antibodies 17 are arranged on one thin film 16. The primary antibodies 17 may cover the entire surface of the thin film 16. The primary antibodies 17 are arranged away from the magnetic beads 23 and secondary antibodies 22 described below.

The detection substrate 10 thus formed detects magnetic beads 23 to which secondary antibodies 22 are immobilized, which bind to a specimen bound to a primary antibody 17 (antigen Y in specimen liquid X, as shown in FIG. 3) on the surface 14a where the NV center 15 of the diamond crystal 14 is formed.

(Detection unit)
3 is a cross-sectional view of the detection unit 20 according to the first embodiment. The detection unit 20 functions as a preparation for a detection device 40 described below. The detection unit 20 has a detection substrate 10, a second dielectric substrate 21, and magnetic beads 23 having secondary antibodies 22 immobilized thereon. The second dielectric substrate 21 has a recess 24 in which the detection substrate 10 is positioned. A surface 21a, which is the upper surface of the second dielectric substrate 21, is connected to the upper surface of the detection substrate 10 so as to be flat.

The second dielectric substrate 21 is a support substrate that supports the detection substrate 10. The second dielectric substrate 21 includes a waveguide that transmits a microwave signal to the detection substrate 10 and an antenna conductor connected to the waveguide. The second dielectric substrate 21 is formed in a plate shape. The detection substrate 10 is disposed in the center of a surface 21a of the second dielectric substrate 21. The second dielectric substrate 21 is formed of a resin-based material such as SiO ₂ , a glass material, a ceramic material, or glass epoxy. The second dielectric substrate 21 is formed in a plate shape. The second dielectric substrate 21 may be formed integrally with the dielectric substrate 11.

A secondary antibody 22 is located on one end side of the surface 21a of the second dielectric substrate 21. The secondary antibody 22 is a secondary antibody for antigen Y. The secondary antibody 22 is immobilized on magnetic beads 23 arranged on the surface 21a of the second dielectric substrate 21.

The magnetic beads 23 are disposed at one end of the surface 21a of the second dielectric substrate 21. Secondary antibodies 22 that migrate toward the other end when sample liquid X is dropped onto the magnetic beads 23 are immobilized on the surface of each magnetic bead 23. The magnetic beads 23 have a particle size of, for example, 30 nm or more and ₆₀ nm or less. The magnetic beads 23 are made of iron oxide such as _Fe2O3 or _Fe3O4 , the surface of which is coated with a _hydrophilic polymer.

The recess 24 is formed in a concave shape on the surface 21a of the second dielectric substrate 21. The detection substrate 10 fits into the recess 24. The recess 24 is disposed in the middle of the surface 21a of the second dielectric substrate 21. The recess 24 is separated from the position where the secondary antibody 22 and the magnetic beads 23 are disposed.

The absorbent pad 25 is disposed at the other end of the surface 21a of the second dielectric substrate 21. The absorbent pad 25 absorbs the specimen liquid X and the secondary antibodies 22 immobilized on the magnetic beads 23 that have flowed onto the surface 21a of the second dielectric substrate 21. The absorbent pad 25 absorbs the specimen liquid X and the secondary antibodies 22 immobilized on the magnetic beads 23 that have not bound to the primary antibodies 17 of the detection substrate 10. The absorbent pad 25 is disposed away from the recess 24.

A secondary antibody 22 immobilized on a magnetic bead 23 and an absorbent pad 25 are arranged on the surface 21a of the second dielectric substrate 21, sandwiching a recess 24. The magnetic bead 23 on which the secondary antibody 22 is immobilized is arranged on the surface 21a of the second dielectric substrate 21, and moves when the sample liquid X is dripped on it.

(Detection device)
The detection device 40 detects an antigen Y contained in a sample liquid X. As shown in FIG.

The optical pickup 30 is disposed facing the detection substrate 10. The optical pickup 30 inputs and outputs light to the NV center 15 of the diamond crystal 14. The optical pickup 30 detects the magnetism of the detection substrate 10. In this embodiment, the optical pickup 30 performs detection while scanning the detection substrate 10. The optical pickup 30 has a light-emitting element 31 that is a light source and a light-receiving element 32 that is a detector. The optical pickup 30 is controlled by a control circuit (not shown). The control circuit controls the light emission of the light-emitting element 31. The control circuit controls the light reception of the light-receiving element 32. The control circuit processes the red fluorescent light signal received by the light-receiving element 32. The control circuit outputs the magnetic field strength as a result.

The light-emitting element 31 irradiates light to the detection substrate 10 provided in the detection unit 20. The light-emitting element 31 is a laser diode. The light-emitting element 31 emits laser light, for example, with a wavelength of 527 nm, based on the control of the control circuit. The light-emitting element 31 emits green excitation light. The light-emitting element 31 emits excitation light that irradiates the diamond crystal 14.

The light receiving element 32 detects the fluorescence from the detection substrate 10. The light receiving element 32 is a photodiode. The light receiving element 32 receives the fluorescence from the NV center 15 of the diamond crystal 14 based on the control of the control circuit. The light receiving element 32 receives the fluorescence. The light receiving element 32 receives the fluorescence emitted from the diamond crystal 14 in response to the excitation light.

(Detection Method)
A method for detecting an antigen Y such as a virus using the detection unit 20 will be described with reference to Fig. 4 to Fig. 6. Fig. 4 is a diagram for explaining a detection process using the detection device 40 according to the first embodiment. Fig. 5 is a diagram for explaining a detection process using the detection device 40 according to the first embodiment. Fig. 6 is a diagram for explaining a detection process using the detection device 40 according to the first embodiment. First, as shown in Fig. 4, a sample liquid X of an antigen Y such as a virus is dropped onto the magnetic beads 23 and the secondary antibody 22 on the second dielectric substrate 21.

As shown in FIG. 5, in the specimen liquid X, a part of the antigen Y binds to the secondary antibody 22. The dropped specimen liquid X spreads on the second dielectric substrate 21 with a part of the antigen Y still bound to the secondary antibody 22. This causes the magnetic beads 23 to adhere to the multiple thin films 16 of the detection substrate 10. The specimen liquid X flows through the detection substrate 10 toward the absorption pad 25.

As shown in FIG. 6, the antigen Y bound to the secondary antibody 22 is bound to the primary antibody 17 in a sandwich-like manner, forming a binding portion Q. In the binding portion Q, the antigen Y is sandwiched between the primary antibody 17 and the secondary antibody 22. In the binding portion Q, the primary antibody 17, the antigen Y, the secondary antibody 22, and the magnetic beads 23 are arranged in that order, in order of proximity to the second dielectric substrate 21. In the binding portion Q, the magnetic beads 23 are located at the position furthest from the second dielectric substrate 21. In the binding portion Q, the number of magnetic beads 23 that corresponds to the concentration of the antigen Y in the sample liquid X is bound.

The magnetic beads 23 that do not bind to the antigen Y do not remain on the thin film 16 of the second dielectric substrate 21, but move toward the absorption pad 25 located at the end opposite the position where the sample liquid X was dropped.

The optical pickup 30, which is a detection probe, is brought close to or into contact with the position where the primary antibody 17 was fixed. Prior to this, a magnetic field is applied to the magnetic beads 23. The magnetic beads 23 are magnetic. The magnetic field of the magnetic beads 23 acts on the NV center 15. More specifically, the magnetic field of the magnetic beads 23 acts on the NV center 15 in the portion where the surface 14a of the diamond crystal 14 is exposed, which is arranged adjacent to the thin film 16. The optical pickup 30 receives the electron spin resonance signal of the NV center 15 in the portion where the surface 14a of the diamond crystal 14 is exposed, as fluorescence. As a result, the optical pickup 30 detects the magnetic charge of the magnetic beads 23 in the bond Q, which is the object to be measured. The optical pickup 30 detects the concentration according to the number of magnetic beads 23. The control device calculates the strength of the magnetic field from the signal that is the detection result of the optical pickup 30 and outputs the result.

(effect)
As described above, in this embodiment, the primary antibody 17 is disposed on the thin film 16 disposed on the surface 14a of the diamond crystal 14. In this embodiment, the magnetic beads 23 to which the secondary antibody 22 is immobilized, which binds to the specimen bound to the primary antibody 17, are detected on the surface 14a of the diamond crystal 14. According to this embodiment, a weak magnetic field can be detected by using the NV center 15. Thus, this embodiment can detect a specimen with high accuracy even if the amount of the specimen is small.

In this embodiment, the diamond crystal 14 is integrated into the detection substrate 10. This embodiment can simplify the configuration of the detection device 40.

In this embodiment, the detection substrate 10 fits into the recess 24 of the second dielectric substrate 21. In this embodiment, the magnetic beads 23 and the secondary antibody 22 are immobilized on the second dielectric substrate 21. According to this embodiment, the area in which the diamond crystal 14 is used can be reduced.

In this embodiment, the optical pickup 30 irradiates light onto the detection substrate 10 and detects the fluorescence from the detection substrate 10. This embodiment can detect with high accuracy even if the amount of sample is small.

In this embodiment, a plurality of thin films 16 are arranged on the surface 14a of the diamond crystal 14. In this embodiment, the thin films 16 are arranged, for example, periodically on the surface 14a of the diamond crystal 14. According to this embodiment, even when the amount of the specimen is small, the possibility that the antigen Y binds to the primary antibody 17 and the secondary antibody 22 in a sandwich-like manner on any of the thin films 16 can be increased. As a result, this embodiment can detect with high accuracy even when the amount of the specimen is small. In addition, in this embodiment, the detection results of the amount of antigen Y attached to the binding portion Q in the plurality of thin films 16 are averaged, so that the amount can be quantified stably with good reproducibility. This embodiment can easily and accurately quantify the number of antigens Y contained in the specimen liquid X attached to the binding portion Q.

In this embodiment, the thin film 16 is arranged in a lattice pattern on the surface 14a of the diamond crystal 14. In this embodiment, the surface 14a of the diamond crystal 14 is exposed adjacent to the thin film 16. In other words, in this embodiment, the surface 14a of the diamond crystal 14 is exposed adjacent to the bonding portion Q. In this embodiment, the distance between the bonding portion Q and the NV center 15 can be reduced. In this embodiment, the magnetic field of the magnetic bead 23 contained in the bonding portion Q can be efficiently applied to the NV center 15. In this embodiment, light can be input and output from the exposed surface 14a of the diamond crystal 14 to the NV center 15. In this embodiment, since the bonding portion Q is adjacent to the NV center 15, even a weak magnetic field such as the magnetic field from one magnetic bead 23 can be detected. According to this embodiment, detection can be performed with high accuracy.

[Second embodiment]
Fig. 7 is a cross-sectional view of a detection device 40 according to a second embodiment. Fig. 7 illustrates the middle part of the dielectric substrate 11. This embodiment differs from the first embodiment in that it does not have a second dielectric substrate 21 and in the arrangement of the diamond crystals 14.

(Detection board)
The detection substrate 10 includes a dielectric substrate 11 and a thin film 16. The detection substrate 10 does not include diamond crystals 14.

The dielectric substrate 11 comprises a lower dielectric substrate 11A and an upper dielectric substrate 11B. In this embodiment, the dielectric substrate 11 functions as the dielectric substrate 11 and the second dielectric substrate 21 of the first embodiment. More specifically, a thin film 16 is disposed in the middle of the dielectric substrate 11, magnetic beads 23 with secondary antibodies 22 immobilized thereon are disposed at one end, and an absorbent pad 25 is disposed at the other end.

The lower dielectric substrate 11A is configured similarly to the dielectric substrate 11 of the first embodiment.

The upper dielectric substrate 11B faces the lower dielectric substrate 11A with the antenna conductor 12 interposed therebetween. The upper dielectric substrate 11B is disposed in place of the diamond crystal 14 of the first embodiment. The upper dielectric substrate 11B is formed of, for example, SiO ₂ , a glass material, a ceramic material, or a resin-based material such as glass epoxy. The upper dielectric substrate 11B is formed in a plate shape.

The antenna conductor 12 is located between the lower dielectric substrate 11A and the upper dielectric substrate 11B.

The waveguide 13 is located between the lower dielectric substrate 11A and the upper dielectric substrate 11B.

The thin film 16 covers a part of the middle part of the surface 11Ba of the upper dielectric substrate 11B. The thin film 16 has a primary antibody 17 immobilized on the surface 11Ba. One or more thin films 16 are arranged on the surface 11Ba of the upper dielectric substrate 11B. The thin films 16 are arranged periodically on the surface 11Ba of the upper dielectric substrate 11B.

(Detection unit)
The detection unit 20 has a detection substrate 10 and magnetic beads 23 on which secondary antibodies 22 are immobilized.

A secondary antibody 22 is located on one end side of the surface 11Ba of the upper dielectric substrate 11B. The secondary antibody 22 is fixed to magnetic beads 23 arranged on the surface 11Ba of the upper dielectric substrate 11B.

The magnetic beads 23 are arranged at one end of the surface 11Ba of the upper dielectric substrate 11B.

The absorption pad 25 is disposed at the other end of the surface 11Ba of the upper dielectric substrate 11B. The absorption pad 25 absorbs the sample liquid X and the secondary antibodies 22 immobilized on the magnetic beads 23 that have flowed onto the surface 11Ba of the upper dielectric substrate 11B.

(Detection device)
The detection device 40 includes a detection unit 20 , a diamond crystal 14 , and an optical pickup 30 .

The diamond crystal 14 faces the thin film 16. The diamond crystal 14 is placed close to or in close contact with the thin film 16. In this embodiment, a bond Q is formed between the diamond crystal 14 and the thin film 16. The diamond crystal 14 has an NV center 15 disposed on the surface 14b side facing the thin film 16.

The optical pickup 30 inputs light from directly above the NV center 15 of the diamond crystal 14. The optical pickup 30 includes a light-emitting element 31, which is a light source that irradiates light onto the detection substrate 10 included in the detection unit 20, and a light-receiving element 33, which is a detector that detects the fluorescence from the detection substrate 10.

(Detection Method)
A specimen liquid X containing an antigen Y such as a virus is dropped onto the magnetic beads 23 and the secondary antibody 22 on the surface 11Ba of the upper dielectric substrate 11B of the detection substrate 10 included in the detection unit 20 configured as described above. Then, the magnetic beads 23 to which the secondary antibody 22 is immobilized, which binds to the specimen bound to the primary antibody 17, are detected by facing the diamond crystal 14 forming the NV center 15 on the surface 11Ba where the thin film 16 of the upper dielectric substrate 11B is located.

(effect)
As a result, in this embodiment, the diamond crystal 14 is close to or in close contact with the thin film 16. As a result, in this embodiment, the magnetic bead 23 at the bond Q is located closer to the NV center 15 than in the first embodiment. This embodiment makes it easier to detect even weak magnetic fields. This embodiment allows for more accurate detection.

In this embodiment, the specimen liquid X is dropped onto the surface 11Ba of the upper dielectric substrate 11B of the detection substrate 10. In this embodiment, the specimen liquid X does not adhere to the diamond crystal 14. According to this embodiment, the diamond crystal 14 can be reused in magnetic field detection.

[Modification]
8 is a cross-sectional view of a modified example of the detection device 40 according to the modified example of the second embodiment. The basic configuration of the detection device 40 is similar to that of the second embodiment. This embodiment differs from the second embodiment in the configuration of the dielectric substrate 11 and in that the antenna conductor 12 is disposed in the diamond crystal 14.

The dielectric substrate 11 is a single plate.

The antenna conductor 12 is located on the surface 14a of the diamond crystal 14, opposite the surface 14b on which the NV center 15 is formed. In this embodiment, the antenna conductor 12 is formed in a ring shape.

The waveguide 13 is located on the surface 14a of the diamond crystal 14, opposite the surface 14b on which the NV center 15 is formed.

As described above, in the modified example, as in the first embodiment, microwaves can be irradiated to the NV center 15 of the diamond crystal 14 from the waveguide 13 located near the NV center 15. According to the modified example, the detection substrate 10 and the detection unit 20 can be simplified.

The embodiments disclosed in this application may be modified without departing from the spirit and scope of the invention. Furthermore, the embodiments disclosed in this application and their modifications may be combined as appropriate.

The appended claims have been described with respect to specific embodiments in order to fully and clearly disclose the technology to which they relate. However, the appended claims should not be limited to the above-described embodiments, but should be construed to embody all modifications and alternative configurations that may be conceived by those skilled in the art within the scope of the basic matters set forth in this specification.

REFERENCE SIGNS LIST 10 detection substrate 11 dielectric substrate 11a surface 12 antenna conductor 13 waveguide 14 diamond crystal 14a surface 14b face 15 NV center 16 thin film 17 primary antibody 20 detection unit 21 second dielectric substrate 21a surface 22 secondary antibody 23 magnetic beads 24 recess 25 absorption pad 30 optical pickup 31 light emitting element 32 light receiving element 40 detection device X specimen liquid Y antigen

Claims (3)

A dielectric substrate;
a detection substrate having a thin film covering a portion of the surface of the dielectric substrate and having a primary antibody immobilized on the surface;
a detection unit having the detection substrate and magnetic beads having a secondary antibody immobilized thereon;
Diamond crystals and
A waveguide;
An optical pickup;
Equipped with
The diamond crystal forms an NV center on one surface,
the waveguide is located on a surface of the diamond crystal opposite to a surface on which the NV center is formed;
The optical pickup includes a light source that irradiates the detection substrate of the detection unit with light that has passed through the diamond crystal, and a detector that detects fluorescence from the detection substrate,
a diamond crystal forming an NV center is placed opposite a magnetic bead having a secondary antibody immobilized thereon, the secondary antibody binding to the sample bound to the primary antibody, on the surface of the dielectric substrate where the thin film is located, and the magnetic bead is detected;
the magnetic beads on which the secondary antibodies are immobilized are located at one end of the surface of the dielectric substrate on which the thin film is located, and are moved by dropping a sample liquid;
Detection device. The detection device according to claim 1 , wherein a plurality of the thin films are disposed on the surface of the dielectric substrate. A dielectric substrate;
a detection substrate having a thin film covering a portion of the surface of the dielectric substrate and having a primary antibody immobilized on the surface;
a detection unit having the detection substrate and magnetic beads having a secondary antibody immobilized thereon;
Diamond crystals and
A waveguide;
An optical pickup;
A detection method using a detection device comprising:
The diamond crystal forms an NV center on one surface,
the waveguide is located on a surface of the diamond crystal opposite to a surface on which the NV center is formed;
The optical pickup includes a light source that irradiates the detection substrate of the detection unit with light that has passed through the diamond crystal, and a detector that detects fluorescence from the detection substrate,
a diamond crystal forming an NV center is placed opposite a magnetic bead having a secondary antibody immobilized thereon, the secondary antibody binding to the sample bound to the primary antibody, on the surface of the dielectric substrate where the thin film is located, and the magnetic bead is detected;
the magnetic beads on which the secondary antibodies are immobilized are located at one end of the surface of the dielectric substrate on which the thin film is located, and are moved by dropping a sample liquid;
Detection methods.

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