Detection unit and detection system

Abstract

To improve incidence efficiency of a light wave and a microwave to an NV center of a diamond crystal.SOLUTION: A detection unit including a first substrate and a second substrate abutting on the first substrate, irradiates the first substrate with a microwave that generates an electron spin resonance and excitation light. The first substrate comprises a layer including a diamond crystal in which an NV center is arranged. The second substrate comprises: magnetic beads that is arranged on one end of a surface opposed to the first substrate to move in the other end direction by dropping specimen liquid, and to which a secondary antibody is immobilized; and a binding part which is a portion of the surface opposed to the first substrate, and in which a primary antibody that binds to an antigen contained in the specimen liquid binding to the magnetic beads, is arranged.SELECTED DRAWING: Figure 8

Description

Technical Field

[0001] This disclosure relates to a detection unit and detection system Mu .

Background Art

[0002] Patent Document 1 discloses a magnetic sensor that utilizes the quantum effect of NV (Nitrogen Vacancy) centers present in diamond crystals.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] The NV center is a complex defect in a diamond crystal where nitrogen replaces carbon at a position where carbon should originally be present, and there is a vacancy at an adjacent position.The NV center has a part of the degenerate shared electron pair missing.The NV center has electrons with orbital angular momentum in two energy levels of m = 0 and m = ±1 in a zero magnetic field.The electrons with m = ±1 have a magnetic moment and are affected by an external magnetic field, and the degeneracy of m = ±1 is also lifted, and it further has two energy levels.By detecting the electron spin resonance caused by these using light waves and microwaves, the strength of the external magnetic field can be detected.<000s030>

[0005] Electrons in an NV center are excited by light with a wavelength of 532 nm and emit fluorescence at 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, it is possible to observe the electron state at m=±1. In a diamond NV center, the electron spin resonance frequency at zero magnetic field is known to be approximately 2.87 GHz. When microwaves at the frequency of this resonance point (resonance frequency) are irradiated, the fluorescence at a wavelength of 638 nm is extinguished. Furthermore, the microwave resonance frequency changes due to changes in the electron state at m=±1 depending on the magnitude of the external magnetic field, etc. By detecting this change as a frequency change in fluorescence intensity, it is possible to detect the magnetic field.

[0006] In the technology described in Patent Document 1, the input and output of microwaves and light waves to the NV centers of a diamond crystal is performed by spatial propagation. Therefore, there is room for improvement in the incidence efficiency of light waves and microwaves to the NV centers of a diamond crystal. [Means for solving the problem]

[0007] A detection unit according to one embodiment includes a first substrate and a second substrate in contact with the first substrate, and irradiates the first substrate with microwaves that generate electron spin resonance and excitation light, wherein the first substrate comprises a layer including a diamond crystal on which NV centers are arranged, and the second substrate comprises magnetic beads on which secondary antibodies are immobilized, arranged at one end of the surface facing the first substrate and moving toward the other end when a sample solution is dropped, and a binding portion which is part of the surface corresponding to the first substrate and on which primary antibodies that bind to antigens contained in the sample solution bound to the magnetic beads are arranged.

[0008] A detection system according to one embodiment comprises the above-mentioned detection unit, a signal generator that generates and outputs a microwave signal, a light-emitting element that generates excitation light, a photodetector that receives fluorescence from the NV center, and a signal processing control unit that processes the signals from the signal generator, the light-emitting element and the photodetector and outputs the result.

[0009] A detection substrate for a detection unit according to one embodiment includes a magnetic bead on which a secondary antibody is immobilized, which is disposed at one end of a surface facing a probe substrate having a first layer containing a diamond crystal on which an NV center is arranged, and which moves toward the other end when a sample solution is dropped onto it, and a binding portion which is part of the surface corresponding to the probe substrate and on which a primary antibody that binds to the antigen contained in the sample solution bound to the magnetic bead is arranged. [Effects of the Invention]

[0010] Detection unit relating to one aspect of this disclosure and Detection system Mu According to this, the incidence efficiency of light waves and microwaves into the NV centers of a diamond crystal can be improved. [Brief explanation of the drawing]

[0011] [Figure 1] Figure 1 is a front view of a magnetic sensor according to the first embodiment. [Figure 2] Figure 2 is an exploded perspective view of the magnetic sensor according to the first embodiment. [Figure 3] Figure 3 is a schematic diagram illustrating the magnetic sensor according to the first embodiment. [Figure 4] Figure 4 is a plan view of the waveguide of the magnetic sensor according to the first embodiment. [Figure 5] Figure 5 is a schematic block diagram of a detection system using a magnetic sensor according to the first embodiment. [Figure 6] Figure 6 is an exploded perspective view of the magnetic sensor according to the second embodiment. [Figure 7] Figure 7 is a cross-sectional view of the magnetic sensor according to the second embodiment. [Figure 8] Figure 8 is a schematic diagram of the detection unit according to the third embodiment. [Figure 9] Figure 9 is a diagram illustrating the detection process using the detection unit according to the third embodiment. [Figure 10] Figure 10 is a diagram illustrating the detection process using the detection unit according to the third embodiment.

Mode for Carrying Out the Invention

[0012] The magnetic sensor 10 according to the first embodiment will be described below.

[0013] [First Embodiment] (Magnetic Sensor) FIG. 1 is a front view of the magnetic sensor 10 according to the first embodiment. FIG. 2 is an exploded perspective view of the magnetic sensor 10 according to the first embodiment. As shown in FIGS. 1 and 2, the magnetic sensor 10 includes a diamond substrate (substrate) 11 and a waveguide 14 that abuts on the diamond substrate 11. In the present embodiment, abutting on the diamond substrate 11 includes a state in which a matching material 17 and solder 18 described later are sandwiched therebetween. In the present embodiment, the diamond substrate 11 and the waveguide 14 are joined by the matching material 17 and the solder 18.

[0014] The diamond substrate 11 is a so-called diamond sensor. The diamond substrate 11 has a surface 11a that does not abut on the waveguide 14 and a surface 11b that abuts on the waveguide 14. The surface 11a and the surface 11b are arranged to face each other. The diamond substrate 11 includes a first layer 11La and a second layer 11Lb. More specifically, the diamond substrate 11 has a first layer 11La containing a diamond crystal in which the NV centers 12 are arranged on the surface 11a. The diamond substrate 11 has a second layer 11Lb in which conductor patterns 13 are arranged on the surface 11b.

[0015] The NV centers 12 may be arranged singly or in a plurality. In the present embodiment, in FIGS. 1 and the like, a state in which a plurality of NV centers are arranged is illustrated.

[0016] Figure 3 is a schematic diagram illustrating a magnetic sensor 10 according to the first embodiment. As shown in Figure 3, the conductor pattern 13 is arranged in the second layer 11Lb of the diamond substrate 11. The conductor pattern 13 includes a conductor pattern (first conductor pattern) 13S through which microwave signals are transmitted, and a grounded conductor pattern (second conductor pattern) 13G. Microwaves transmitted by the transmission line 15 are transmitted through the conductor pattern 13.

[0017] The conductor pattern 13S is formed in an annular shape in the center of the second layer 11Lb. A circular opening 131 is located in the center of the conductor pattern 13S. The surface 11b of the diamond substrate 11 is exposed through the opening 131. The conductor pattern 13G is arranged around the conductor pattern 13S of the second layer 11Lb. An annular opening 132 is located between the conductor pattern 13S and the conductor pattern 13G. The surface 11b of the diamond substrate 11 is exposed through the opening 132.

[0018] Conductor pattern 13S is connected to conductor 15S, which is a signal line for transmitting signals, via solder 18S. Conductor pattern 13G is connected to conductor 15G, which is a ground line, via solder 18G. Multiple solder 18G may be arranged in the width direction of conductor 15G. In an axial view, the optical waveguide 16 is located in the opening 131. Excitation light that irradiates the diamond substrate 11 and fluorescence emitted by the excitation light in the first layer 11La of the diamond substrate 11 are transmitted through the opening 131. A matching material 17 is interposed between the opening 131 and the optical waveguide 16.

[0019] Figure 4 is a plan view of the waveguide 14 of the magnetic sensor 10 according to the first embodiment. As shown in Figure 4, the waveguide 14 comprises a line 15 and an optical waveguide 16. The waveguide 14 is formed of a resin material such as SiO2, glass material, or polymer. In this embodiment, the waveguide 14 is formed in a columnar shape with a rectangular cross-section in the axial direction. The waveguide 14 includes a side surface 14a and a side surface 14b arranged opposite to side surface 14a.

[0020] The transmission line 15 is a microstrip transmission line that transmits microwaves that generate electron spin resonance to the conductor pattern 13. The characteristic impedance of the transmission line 15 is tuned. The transmission line 15 includes a conductor 15S, which is a signal line, and a conductor 15G, which is a ground pattern. Conductor 15S is located on side 14a. Conductor 15G is located on side 14b. The transmission line 15 is arranged along the axial direction of the waveguide 14. The transmission line 15 is arranged parallel to the core 161 of the optical waveguide 16.

[0021] The optical waveguide 16 is either single-mode or multi-mode. The optical waveguide 16 transmits excitation light irradiating the diamond substrate 11 and fluorescence emitted by the excitation light in the first layer 11La of the diamond substrate 11. The optical waveguide 16 includes a core 161 located in the center and a cladding 162 arranged around the core 161. The core 161 has a higher refractive index than the cladding 162. The core 161 is transparent to excitation light and fluorescence. The core 161 is arranged along the axial direction of the waveguide 14. In this embodiment, the core 161 and cladding 162 are formed in a rectangular columnar shape with a rectangular cross-section in the axial direction. The core 161 is arranged along the axial direction of the waveguide 14. The core 161 is arranged parallel to the transmission line 15.

[0022] The diamond substrate 11 and the waveguide 14 are connected via a matching material 17. More specifically, the surface 11b of the diamond substrate 11 and the surface 12c of the waveguide 14 are connected via the matching material 17. The matching material 17 is a material that adjusts and matches the refractive index of the diamond substrate 11 and the optical waveguide 16. The matching material 17 has a refractive index similar to that of the diamond substrate 11. As the matching material 17, for example, a material such as a resin having a refractive index similar to that of the core 161 of the optical waveguide 16 may be used. The refractive index of the matching material 17 is, for example, about 1.7 to 2.5. In an axial view, the matching material 17 has the same shape as the surface 12c of the waveguide 14.

[0023] The magnetic sensor 10 configured in this way can be used as a probe for a detection system.

[0024] (Control device) Figure 5 is a schematic block diagram of a detection system using a magnetic sensor 10 according to the first embodiment. The detection system comprises a magnetic sensor 10 and a control device 50. The magnetic sensor 10 is controlled by the control device 50. The control device 50 includes a signal generator 51, a light-emitting element 52, a light-receiving element 53, an optical isolator 54, and a signal processing control unit 55.

[0025] The signal generator 51 generates a microwave signal and outputs it to the transmission line 15 based on the control of the signal processing control unit 55. The signal generator 51 generates microwaves, for example, between 2.7 GHz and 2.9 GHz. The light-emitting element 52 is a laser diode. Based on the control of the signal processing control unit 55, the light-emitting element 52 emits laser light, for example, with a wavelength of 527 nm, into the optical waveguide 16. The light-emitting element 52 emits green excitation light into the optical waveguide 16. The light-receiving element 53 is a photodiode. Based on the control of the signal processing control unit 55, the light-receiving element 53 receives fluorescence from the NV center 12 of the diamond substrate 11. The light-receiving element 53 receives fluorescence via the optical waveguide 16. The optical isolator 54 is placed between the optical waveguide 16, the light-emitting element 52, and the light-receiving element 53. The optical isolator 54 outputs the light wave output from the light-emitting element 52 to the optical waveguide 16. The optical isolator 54 receives the optical wave from the optical waveguide 16 and outputs the optical wave to the photodetector 53.

[0026] The signal processing control unit 55 processes the signals from the signal generator 51, the light-emitting element 52, and the photodetector 53, and outputs the result. More specifically, the signal processing control unit 55 controls the generation of signals in the signal generator 51. The signal processing control unit 55 controls the emission of light in the light-emitting element 52. The signal processing control unit 55 controls the reception of light in the photodetector 53. The signal processing control unit 55 processes the red fluorescence signal received by the photodetector 53. As a result, the signal processing control unit 55 outputs the magnetic field strength.

[0027] (effect) As described above, in this embodiment, light waves and microwaves propagate through the waveguide 14 in a substantially coaxial manner. In this embodiment, a diamond substrate 11 having minute NV centers 12 is arranged in a probe-like manner at the tip of the waveguide 14. In this embodiment, the diamond substrate 11 having NV centers 12 can irradiate light waves and microwaves with low loss and receive almost all of the reflected light. According to this embodiment, signal access with multiple minute NV centers 12 can be performed without loss. Thus, according to this embodiment, the incidence efficiency of light waves and microwaves to the NV centers 12 of the diamond substrate 11 can be improved.

[0028] In this embodiment, light waves and microwaves can be aligned and connected simultaneously to the region on the diamond substrate 11 where the NV center 12 is located. This embodiment enables stable propagation of light waves and microwaves without loss.

[0029] In this embodiment, no obstacles such as cover glass are required on the surface 11a side of the diamond substrate 11. According to this embodiment, the magnetic sensor 10 can measure while in close proximity to the object to be measured. According to this embodiment, the magnetic sensor 10 can detect the magnetic charge of the object to be measured with high sensitivity.

[0030] According to this embodiment, the diamond substrate 11 having a minute-sized NV center 12 can be brought into close proximity to a minute magnetic charge and detect the minute magnetic charge with high sensitivity. For example, when a minute magnetic charge is brought within 1 μm of the NV center 12, 1 × 10⁻¹⁶ -23 It can detect magnetic moments of approximately Wb·m or less. The region in which the NV center 12 can detect magnetic moments is, for example, 1 μm or a narrower region.

[0031] According to this embodiment, the magnetic sensor 10 can be configured with robust and compact optical and microwave transmission paths. Therefore, this embodiment can stabilize the incidence efficiency of optical and microwaves without readjustment. Furthermore, this embodiment allows for the miniaturization of sensors, units, systems, etc. Moreover, this embodiment can be used for sensing in very narrow areas.

[0032] In contrast, conventional sensors have a large detection unit. As a result, conventional sensors may not be able to adequately capture the spatial distribution fluctuations of magnetic charges due to the large distance between the magnetic charge and the detection unit.

[0033] [Second Embodiment] Figure 6 is an exploded perspective view of the magnetic sensor 20 according to the second embodiment. Figure 7 is a cross-sectional view of the magnetic sensor 20 according to the second embodiment. In this embodiment, the magnetic sensor 20 includes a plurality of diamond substrates 21 and one photoelectric mixed substrate 24 that contacts each of the diamond substrates 21. In this embodiment, contact with each of the diamond substrates 21 includes a state in which solder 28S and solder 28G, which will be described later, and matching material (not shown) are sandwiched between them.

[0034] In this embodiment, the magnetic sensor 20 has multiple diamond substrates 21 arranged on a photoelectric mixed substrate 24. In this embodiment, four diamond substrates 211, 212, 213, and 214 are arranged on the photoelectric mixed substrate 24. When it is not necessary to distinguish between diamond substrates 211, 212, 213, and 214, the four diamond substrates 211, 212, 213, and 214 are referred to as diamond substrate 21. Each diamond substrate 21 is configured similarly to the diamond substrate 11 in the first embodiment.

[0035] The diamond substrate 21 has a first layer 21La containing a diamond crystal on a surface 21a that does not contact the photoelectric substrate 24, on which NV centers 22 are arranged. The diamond substrate 21 has a second layer 21Lb on a surface 21b that contacts the photoelectric substrate 24, on which an electrode pattern 23 is arranged. The electrode pattern 23 includes an electrode pattern (first electrode pattern) 23S through which microwave signals are transmitted, a grounded electrode pattern (second electrode pattern) 23G, and an opening (not shown) that transmits fluorescence emitted by excitation light.

[0036] The photoelectric mixed-signal substrate 24 has a line layer (line) 25 that functions as a line and an optical waveguide layer (optical waveguide) 26 that functions as an optical waveguide stacked on top of each other. In this embodiment, the line layer 25 is stacked on top of the optical waveguide layer 26. The photoelectric mixed-signal substrate 24 has the line layer 25 facing the diamond substrate 21. The photoelectric mixed-signal substrate 24 and the diamond substrate 21 are connected via solder 28S and solder 28G. The photoelectric mixed-signal substrate 24 has a first recess 24a and a second recess 24b at the placement position of each diamond substrate 21. The first recess 24a and the second recess 24b are formed in a recess shape from the surface of the photoelectric mixed-signal substrate 24, in other words, from the surface 252a of the second substrate 252 of the line layer 25. The first recess 24a is a deeper recess than the second recess 24b. The surface 241a of the first recess 24a is arranged parallel to the surface 21b of the diamond substrate 21. In the first recess 24a, the mirror surface 26a provided at the tip of the optical waveguide layer 26, which will be described later, is exposed. In the second recess 24b, the conductor 25G of the line layer 25, which will be described later, is exposed.

[0037] The transmission line layer 25 includes microstrip lines that transmit microwaves that generate electron spin resonance to electrode patterns 23 on each of the diamond substrates 21. The transmission line layer 25 includes a first substrate 251 and a second substrate 252. The second substrate 252 is laminated on top of the first substrate 251. The transmission line layer 25 includes conductors (lines) 25S which are signal lines and conductors (lines) 25G which are ground patterns. Conductors 25S are arranged on the surface 252a of the second substrate 252. Conductors 25S include conductors 25S1, 25S2, 25S3 and 25S4. Conductor 25S1 transmits microwaves to electrode patterns 23S on the diamond substrate 211. Conductor 25S2 transmits microwaves to electrode patterns 23S on the diamond substrate 212. Conductor 25S3 transmits microwaves to the electrode pattern 23S of the diamond substrate 213. Conductor 25S4 transmits microwaves to the electrode pattern 23S of the diamond substrate 214. When it is not necessary to distinguish between conductors 25S1, 25S2, 25S3, and 25S4, they are all referred to as conductor 25S. Conductor 25G is located between the lower surface of the first substrate 251 and the optical waveguide layer 26. Conductor 25G transmits microwaves to the electrode patterns 23G of the diamond substrates 211, 212, 213, and 214.

[0038] The conductor 25S has a width w1 in the direction perpendicular to the microwave transmission direction, for example, 30 μm to 60 μm. The width w2 in the lamination direction between conductor 25S and conductor 25G is, for example, 30 μm to 60 μm.

[0039] The optical waveguide layer 26 is either single-mode or multi-mode guiding. The optical waveguide layer 26 has optical waveguides 261, 262, 263, and 264. The optical waveguide layer 26 transmits excitation light irradiating the diamond substrate 21 and fluorescence emitted by the excitation light in the first layer 21La of the diamond substrate 21 to each of the diamond substrates 21. More specifically, optical waveguide 261 transmits excitation light irradiating the diamond substrate 211 and fluorescence emitted by the excitation light in the first layer 211La of the diamond substrate 211. Optical waveguide 262 transmits excitation light irradiating the diamond substrate 212 and fluorescence emitted by the excitation light in the first layer 212La of the diamond substrate 212. Optical waveguide 263 transmits excitation light irradiating the diamond substrate 213 and fluorescence caused by the excitation light in the first layer 213La of the diamond substrate 213. Optical waveguide 264 transmits excitation light irradiating the diamond substrate 214 and fluorescence caused by the excitation light in the first layer 214La of the diamond substrate 214.

[0040] The optical waveguide layer 26 is configured in a coaxial structure with a lower cladding 261, a core 262, and upper and side cladding 263. Because the refractive index of the core 262 is several percent higher than that of the lower cladding 261 and the upper and side cladding 263, optical signals can be confined to the core and transmitted with low loss.

[0041] The lower cladding 261 has a width w3 in the stacking direction of, for example, 15 μm or more and 25 μm or less. The core 262 has a width w4 in the stacking direction of, for example, 35 μm or more and 100 μm or less. The upper cladding 263 has a width w5 in the stacking direction of, for example, 15 μm or more and 25 μm or less.

[0042] The mirror surface 26a has an optical path conversion surface that is inclined with respect to the optical axis direction of the core 262. For example, the mirror surface 26a is an optical path conversion surface that is inclined at 45° with respect to the optical axis direction. This optical path conversion surface converts the optical path direction of the light traveling through the core 262 by 90°, changing the optical path to a direction normal to the surface 251a of the first substrate 251. In the second recess 24b, a portion of the conductor 25G is exposed.

[0043] To further reduce the occurrence of light transmission loss, a matching material such as resin may be filled into the space A where the mirror surface 26a is exposed. This can reduce the light transmission loss between the optical waveguide layer 26 and the diamond substrate 11. As the matching material, for example, a resin having the same refractive index as the core 262 of the optical waveguide layer 26 may be used.

[0044] The mirror surface 26a of the optical waveguide layer 26 is inclined with respect to the surface 241a of the first recess 24a. The inclination angle θ is, for example, 45°. The inclination of the mirror surface 26a of the optical waveguide layer 26 allows for efficient propagation of light between the optical waveguide layer 26 and the diamond substrate 21.

[0045] The photoelectric mixed-signal substrate 24 and the diamond substrate 21, configured in this way, are connected via solder 28S and solder 28G. More specifically, solder 28S connects the electrode pattern 23S of the diamond substrate 21 to the conductor 25S of the line layer 25. Solder 28G connects the electrode pattern 23G of the diamond substrate 21 to the conductor 25G of the line layer 25.

[0046] The magnetic sensor 20 configured in this way can be used as a probe for a detection system, similar to the first embodiment, by including a control device 50.

[0047] As described above, this embodiment allows for the arrangement of multiple minute-sized NV centers 12 by arranging multiple diamond substrates 21 on the photoelectric mixed-signal substrate 24. According to this embodiment, the magnetic sensor 20 can be integrated more highly than the magnetic sensor 10. According to this embodiment, the magnetic sensor 20 can capture spatial distribution fluctuations of minute-sized magnetic charges with high resolution. According to this embodiment, the magnetic sensor 20 can dynamically image the movement of specific proteins or biomolecules by combining it with phenomena such as nuclear magnetic resonance.

[0048] [Third Embodiment] Figure 8 is a schematic diagram of the detection unit 40 according to the third embodiment. Figure 9 is a diagram illustrating the detection process using the detection unit 40 according to the third embodiment. Figure 10 is a diagram illustrating the detection process using the detection unit 40 according to the third embodiment. The detection unit 40 detects antigen Y contained in the sample solution X. As shown in Figure 8, the detection unit 40 comprises a magnetic sensor 10 and a substrate (second substrate, detection substrate for detection unit) 30. In this embodiment, as an example, the magnetic sensor 10 is described as being configured in the same way as in the first embodiment. In this embodiment, the first substrate is the diamond substrate 11 of the magnetic sensor 10.

[0049] The substrate 30 includes a strip substrate 31, a primary antibody 32 immobilized on a test line 311 provided on the strip substrate 31, magnetic beads 33 movably arranged on the surface 31a of the strip substrate 31, and a secondary antibody 34 immobilized on the magnetic beads 33.

[0050] The strip substrate 31 functions as a slide in the detection unit 40. The strip substrate 31 is formed in a plate shape. The test line 311 is located in the center of the surface 31a of the strip substrate 31.

[0051] The primary antibody 32 is a primary antibody against antigen Y. The magnetic beads 33 are positioned at one end of the surface 31a of the strip substrate 31, which faces the diamond substrate 11. The magnetic beads 33 have a secondary antibody 34 immobilized on them, which moves toward the other end when the sample solution X is dropped onto them. The secondary antibody 34 is a secondary antibody against antigen Y. The primary antibody 32 is positioned separately from the magnetic beads 33 and the secondary antibody 34.

[0052] The substrate 30 further includes a binding portion 35 which is part of the surface 31a of the strip substrate 31 corresponding to the diamond substrate 11, and on which a primary antibody 32 that binds to antigen Y contained in the sample solution X bound to magnetic beads 33 is arranged.

[0053] A method for detecting antigen Y such as a virus using the detection unit 40 will be described. As shown in FIG. 9, a test liquid X containing antigen Y such as a virus is dropped onto the magnetic beads 33 and the secondary antibody 34. The dropped test liquid X diffuses on the strip substrate 31 while a part of the antigen Y binds to the secondary antibody 34.

[0054] As shown in FIG. 10, the antigen Y bound to the secondary antibody 34 binds to the primary antibody 32 in a sandwich manner to form a binding part 35. The binding part 35 has the antigen Y sandwiched between the primary antibody 32 and the secondary antibody 34. The binding part 35 is arranged in the order of the primary antibody 32, the antigen Y, the secondary antibody 34, and the magnetic beads 33 in this order from the closest to the strip substrate 31. In the binding part 35, the number of magnetic beads 33 corresponding to the concentration of the antigen Y in the test liquid X binds. The magnetic beads 33 are located at the position farthest from the strip substrate 31 in the binding part 35.

[0055] Half of the width w6 of the binding part 35 is narrower than the width w7 from the center of the binding part 35 to the region where the unbound magnetic beads 33 do not distribute. The relationship of w6 and w7 is w6 / 2 < w7. w6 is, for example, 0.5 mm or more and 1.5 mm or less. w7 is, for example, 0.3 mm or more, preferably about 3 mm or more and 15 mm or less.

[0056] In the magnetic sensor 10, the width w8 of the NV center 12 is narrower than the width w6 of the binding part 35. The relationship between w6 and w8 is w6 > w8.

[0057] The magnetic beads 33 that did not bind to the antigen Y move to the end on the opposite side of the position where the test liquid X was dropped on the strip substrate 31 instead of staying at the test line 311.

[0058] The strip substrate 31 may be provided with a control line on the downstream side of the test line 311 so as to specifically adsorb the unbound magnetic beads 33. In that case, w7 is the width from the center of the binding part 35 to the upstream end of the control line.

[0059] The magnetic sensor 10, which is a detection probe, is brought close to or in contact with the position where the primary antibody 32 was fixed. Prior to this, the magnetic beads 33 have been magnetized by the application of a magnetic field. As a result, the magnetic sensor 10 strongly detects the magnetic charge of the magnetic beads 33 in the binding portion 35, which is the object to be measured. The concentration is detected by the magnetic sensor 10 according to the number of magnetic beads 33. The signal processing control unit 55 of the control device 50 calculates the strength of the magnetic field from the signal detected by the magnetic sensor 10 and outputs it as a result.

[0060] The detection unit 40 configured in this way can be used as a detection system by including a control device 50.

[0061] As described above, this embodiment allows the magnetic beads 33 to be detected by the magnetic sensor 10 at a distance from the unbound magnetic beads 33. The influence of the magnetic charge of the unbound magnetic beads 33 on the magnetic sensor 10 decreases inversely proportional to the cube of the distance. According to this embodiment, the signal-to-noise ratio (S / N) of the signal due to antigen-antibody binding can be improved.

[0062] In the above description, the first substrate was assumed to be the diamond substrate 11 of the magnetic sensor 10, but it is not limited to this. The first substrate can be any substrate that has a layer (magnetic detection layer) having a detection accuracy equivalent to that of the diamond substrate 11. For example, when a minute magnetic charge is brought within 1 μm of the detection part of the magnetic sensor 10, the magnetic detection layer of the first substrate can detect 1 × 10⁻¹⁶ magnetic charges. -23 It is sufficient that the magnetic moment is detectable on or less than Wb·m. Furthermore, the magnetic detection layer of the first substrate only needs to be able to detect magnetic charges present in a region of, for example, 1 μm or smaller. The first substrate may be, for example, a substrate on which a magnetoresistive element, a magnetoimpedance element, or a superconducting quantum interference element is arranged on the surface layer.

[0063] Conventional detection units have low and insufficient sensitivity, or the detection unit is several millimeters or larger, and the thickness of the sealing layer covering the surface of the detection unit is several hundred micrometers or more. Therefore, when the detection unit is brought close to the binding portion 35, which is the object to be measured, in order to ensure that the distance between the detection unit and the unbound magnetic beads 33 is sufficiently large relative to the distance between the detection unit and the binding portion 35, it is necessary to enlarge the substrate 30 to widen the distance between the binding portion 35 and the area where the unbound magnetic beads 33 are distributed. As a result, in addition to the large size of the detection unit, the size of the substrate 30 also increases, and the detection unit becomes larger. Furthermore, if detection is performed without enlarging the substrate 30, the detection accuracy of the signal-to-noise ratio of the antigen-antibody binding signal is reduced due to the influence of the magnetic charge of the unbound magnetic beads 33.

[0064] This embodiment solves the problems of conventional detection units as described above, enabling miniaturization of the entire unit and improving detection accuracy.

[0065] 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.

[0066] Characteristic embodiments have been described in order to fully and clearly disclose the technology relating to the appended claims. However, the appended claims should not be limited to the above embodiments, but should be configured to embody all modifications and alternative configurations that a person skilled in the art may create within the scope of the fundamental matters presented herein. [Explanation of Symbols]

[0067] 10 Magnetic Sensors 11. Diamond substrate (substrate, first substrate) 11a Surface (the surface that does not come into contact with the waveguide) 11b Surface (the surface in contact with the waveguide) 11La 1st layer 11Lb 2nd layer 12 NV Center 13, 13S, 13G Conductor Patterns 14 Waveguides 15 railroad tracks 15S, 15G conductor 16 Optical waveguide 17 Matching material 18S, 18G solder 20 Magnetic Sensors 21 Diamond substrate (substrate) 21a Surface (the side that does not come into contact with the photoelectric mixed-signal substrate) 21b Surface (the surface that contacts the photoelectric mixed-signal substrate) 21La 1st layer 21Lb 2nd layer 22 NV Center 23, 23S, 23G electrode patterns 24. Photoelectric mixed-signal substrate 25 Track Layer (Tracks) 25S, 25G conductors 26 Optical waveguide layer (optical waveguide) 28S, 28G solder 30 substrates (second substrate, detection substrate for detection unit) 31 Strip substrates 311 Test Line 32 Primary antibodies 33 Magnetic Beads 34 Secondary antibody 35 Joint 40 detection units 50 Control device 51 Signal Generator 52 Light-emitting element 53 Light-receiving element 54 Optical Isolators 55 Signal Processing Control Unit X Sample Solution Y antigen

Claims

1. A detection unit comprising a first substrate and a second substrate in contact with the first substrate, wherein the first substrate is irradiated with microwaves that generate electron spin resonance and excitation light, The first substrate is, The device comprises a layer containing a diamond crystal on which an NV center is located, and a layer on which a conductor pattern on which the microwaves are transmitted is located. The aforementioned second substrate is A magnetic bead on which a secondary antibody is immobilized is positioned at one end of the surface facing the first substrate and moves toward the other end when a sample solution is dropped onto it, A detection unit comprising a binding portion which is a part of the surface facing the first substrate and on which a primary antibody that binds to the antigen contained in the sample solution bound to the magnetic beads is arranged.

2. The detection unit according to claim 1, wherein the conductor pattern has an opening in the center, and the microwave and the excitation light are irradiated onto the first substrate through the opening to generate the electron spin resonance.

3. The detection unit according to claim 2, wherein excitation light irradiating the first substrate and fluorescence emitted by the excitation light in the diamond crystal layer of the first substrate where the NV center is located are transmitted through the opening.

4. A waveguide that contacts the layer on which the conductor pattern of the first substrate is arranged, The aforementioned waveguide is A line for transmitting the microwaves to the conductor pattern, The detection unit according to claim 2, comprising: an excitation light for irradiating the first substrate; and an optical waveguide for transmitting fluorescence emitted by the excitation light in a layer of the first substrate containing a diamond crystal in which the NV center is located.

5. The optical waveguide is a columnar shape with a rectangular cross-section in the axial direction, The detection unit according to claim 4, wherein the line is arranged along the side surface of the optical waveguide.

6. The optical waveguide is A core located in the center, The core includes a cladding disposed around the core, The detection unit according to claim 5, wherein the core is located at the opening of the conductor pattern in an axial view of the optical waveguide.

7. The railway line is A conductor which is a signal line, Includes a conductor which is the ground pattern, The detection unit according to claim 5, wherein the conductor which is the signal line is located on the conductor pattern in an axial view of the optical waveguide.

8. The detection unit according to claim 1, wherein half the width of the coupling portion is narrower than the width from the coupling portion to the region where uncoated magnetic beads are not distributed.

9. The detection unit according to claim 1 or claim 8, wherein the width of the NV center on the first substrate is narrower than the width of the coupling portion.

10. The detection unit according to claim 1, A signal generator that generates and outputs microwave signals, A light-emitting element that generates excitation light, A light-receiving element that receives fluorescence from the NV center, The system comprises a signal processing control unit that processes the signals from the signal generator, the light-emitting element, and the light-receiving element and outputs the result. Detection system.

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