JP5207668B2 - Detection apparatus and detection method - Google Patents

Description

  The present invention relates to a detection apparatus and a detection method for magnetically detecting the presence, quantity or concentration of a substance.

  Several research institutions have reported biosensors that detect magnetic molecules indirectly using magnetic sensor elements with magnetic particles as labels. There are various types of magnetic sensor elements used in this detection method, but many biosensors using magnetoresistive elements have been studied (Non-patent Document 1).

  In biosensors using magnetoresistive elements, many GMR (Giant Magnetistance) elements are used. Some GMR elements are made of Fe / Cr or Co / Cu artificial lattice films, and others have a sandwich structure in which a nonmagnetic metal film such as Cu is formed between two ferromagnetic films. In Non-Patent Document 1, this artificial lattice type GMR element is used. A GMR element having a sandwich structure in which an antiferromagnetic film is exchange-coupled to one ferromagnetic film and the magnetization direction of the ferromagnetic film is not easily rotated is called a spin valve type GMR element.

In addition to the GMR element, a TMR (Tunnel Magnetoresistance) element used as an element of an MRAM (Magnetic Random Access Memory) can be given. This element has a structure in which the nonmagnetic film of a GMR element having a sandwich structure is replaced with a tunnel film made of AlO _x or the like.

  The resistance value of the magnetoresistive effect element changes with application of a magnetic field. However, since the TMR element exhibits a larger resistance change than the GMR element, it is often used in a device that detects an extremely small local magnetic field or drives at a high speed. In addition, in recent years, there has been reported a structure showing a greater resistance change in the TMR element (Patent Document 1).

The configuration disclosed in Patent Document 1 uses an amorphous material such as FeCoB for the magnetic film and an MgO single crystal film for the tunnel film. In this configuration, the resistance change is about 3 to 4 times the resistance change of the TMR element using the AlO _x tunnel film. Further, Patent Documents 2 to 4 can be cited as suggesting sensor applications of TMR elements.

  A method for detecting magnetic particles using a magnetoresistive element will be described with reference to FIGS.

  FIG. 5 shows an example of the detection circuit, and FIG. 6 explains the peripheral portion of the element.

  A sensor element 501 and a reference element 502 are arranged in the magnetic field direction of the coil 504. An alternating current is applied to the coil 504 using the electromagnet power source 505 and the sine wave generator 507. The sensor element 501 and the reference element 502 form a Wheatstone bridge circuit using two fixed resistors. A signal from the Wheatstone bridge circuit is input to the sense amplifier 503. The output of the sense amplifier 503 and a part of the output of the sine wave generation circuit are input to the lock-in amplifier 506 and analyzed using the computer 508 connected to the lock-in amplifier 506.

The magnetic particles 602 are fixed only on the surface of one element (sensor element 501) of the two magnetoresistive elements 501 (sensor element 501 and reference element 502) in the reaction region. At the time of detection, an alternating current is applied to the coil 504 using the electromagnet power source 505 and the sine wave generator 507. As a result, an alternating magnetic field 603 is applied in a direction perpendicular to the magnetoresistive film that is a component of the two magnetoresistive elements, and the magnetic particles 602 are magnetized. As indicated by the magnetization vector 605, a stray magnetic field 604 is generated from the magnetized magnetic particles, and a magnetic field having an in-film direction component is applied to the magnetoresistive element 601 below the magnetic particles. The resistance of the magnetoresistive film changes due to the influence of a magnetic field in the in-plane direction. A Wheatstone bridge circuit is formed using two magnetoresistive elements and two fixed resistors. After the AC component of the signal of the Wheatstone bridge circuit is amplified using the sense amplifier 503, only the frequency component twice the frequency of the applied magnetic field is amplified by the lock-in amplifier 506 to obtain a detection signal indicating the presence of magnetic particles. The computer 508 analyzes (Non-Patent Document 1).

In Patent Document 4, a magnetic field is applied in a direction with high sensitivity to a magnetic field, that is, an in-plane direction of the magnetoresistive film, and magnetization reversal of the magnetoresistive film is caused by the influence of a stray magnetic field from magnetic particles. Detect differences in the magnitude of the magnetic field. A method for detecting the presence of magnetic particles by doing this is described.
David R.D. Baselt, et al, Biosensors & Bioelectronics, 13, 731, (1998) JP 2006-080116 A Japanese translation of PCT publication No. 2003-524781 JP 2005-513475 A US Patent Application Publication No. 2004/0023365

  It is preferable that the magnetic particles have good dispersibility in the sample solution, and from this point of view, the magnetic particles are preferably soft magnetic. In addition, for example, when binding magnetic particles to biomolecules in body fluids, from the viewpoint of reaction efficiency, magnetic particles having a small particle diameter are preferable, and such magnetic particles tend to exhibit a large magnetization saturation magnetic field. .

  Therefore, when using such magnetic particles for detection, it is necessary to apply a magnetic field to the magnetic particles to induce magnetization in a desired direction. In this case, in order to induce sufficiently large magnetization, it is necessary to apply a magnetic field larger than the magnetization reversal field of the magnetoresistive effect film used in the MRAM or the magnetic sensor. If the magnetization of the magnetic particles is small, the stray magnetic field generated from the magnetic particles is also small. In such a case, it is difficult to detect the magnetic particles.

When magnetic particles are detected, the magnetic particles are fixed in the vicinity of the magnetoresistive effect element that is a sensor element, so that the magnetic field applied to the magnetic particles is also applied to the magnetoresistive effect element. Therefore, as disclosed in Patent Document 4, when detecting a magnetic particle by applying a magnetic field in the direction of easy magnetization of the magnetoresistive effect element, the magnetic particle is a soft magnetic material and has a large magnetization saturation magnetic field. To detect
1. If the applied magnetic field is small, the detection signal cannot be obtained because the magnetization of the magnetic particles is small,
2. When a magnetic field that sufficiently increases the magnetization of the magnetic particles is applied, the detection sensitivity of the magnetoresistive effect element is exceeded, making it difficult to detect the magnetic particles.

An object of the present invention is to provide a detection device and a detection method for easily detecting soft magnetic particles by applying a magnetic field in the direction of easy magnetization of a magnetoresistive effect element.

The present invention comprises a magnetoresistive film in which a first magnetic film serving as a detection layer, a nonmagnetic film, and a second magnetic film serving as a magnetization fixed layer are laminated in this order, and for detecting magnetic particles A sensor element; a power source for supplying a current to the sensor element; a voltage detection means for detecting a voltage of the sensor element; and a magnetism generation means for applying a magnetic field in the easy magnetization direction of the detection layer. element a magnetic field is applied from the magnetic generating means, said a detection device for detecting magnetic particles and applied magnetic field strength from the magnitude of the voltage detected by said sensor element,
The magnetization direction of the second magnetic film is parallel to the direction of the magnetic field applied from the magnetism generating means;
The first magnetic film is a magnetic film whose magnetization is reversed at 100 Oe or more;
The detection apparatus according to claim 1, wherein the magnetic field applied from the magnetism generation unit is unidirectionally anisotropic in the second magnetic film.

  Further, using the above-described detection device, the intensity of the applied magnetic field is gradually increased from a magnetic field smaller than the magnetization reversal magnetic field of the detection layer, and the voltage of the sensor element is measured to measure the magnetic field. A method for detecting magnetic particles, comprising detecting particles.

  By using the detection apparatus of the present invention, it is possible to easily detect soft magnetic particles.

  Hereinafter, the best mode for carrying out the present invention will be described in consideration of the case where the substance detection device of the present invention is used for biosensing. The scope of the present invention is defined by each claim. The present invention includes not only the following forms but also various forms within a range that can be understood by those skilled in the art.

  Moreover, the form described as a preferable form or applicable form for one of the substance detection apparatus or substance detection method of the present invention is applicable to the other unless otherwise specified.

  An outline of the detection apparatus and detection method according to the present embodiment will be described.

First, a sensor element including a magnetoresistive film in which a first magnetic film serving as a detection layer, a nonmagnetic film, and a second magnetic film serving as a magnetization fixed layer are stacked in this order is included in the detection device. It is. The power supply further supplies a current to the sensor element, voltage detection means for detecting the voltage of the sensor element, and magnetism generation means for applying a magnetic field in the easy magnetization direction of the detection layer. This detection apparatus is a detection apparatus that detects magnetic particles existing in the vicinity of a sensor element from the intensity of a magnetic field applied to the sensor element and the magnitude of the voltage of the sensor element. Specifically, information on the presence of magnetic particles present on or near the sensor element is detected.

  Using the detection device described above, the intensity of the applied magnetic field is gradually increased from a magnetic field smaller than the magnetization reversal magnetic field of the detection layer, and magnetic particles are detected by measuring the magnitude of the voltage of the sensor element. This is a featured detection method.

  Furthermore, when the magnetoresistive film and the magnetic particles are specifically bound by the substance to be detected, it is possible to indirectly detect the substance to be detected using the magnetic particles as a label.

  Here, the magnetization direction of the second magnetic film is parallel to the direction of the magnetic field applied from the magnetism generating means, and the first magnetic film is a magnetic film whose magnetization is reversed at 100 Oe or more (100 Oersted or more). Preferably there is. Then, the apparatus is configured such that the magnetic field applied from the magnetism generating means has a unidirectional anisotropy direction of the second magnetic film.

  FIG. 1 is a conceptual diagram of the detection apparatus of the present invention. A current source 108 for passing a current and a voltage detection means 109 for detecting a voltage change of the magnetoresistive effect film are connected to the magnetoresistive effect film which is a sensor element.

  In the magnetoresistive film, a nonmagnetic film 102 is formed between a magnetic film that is the detection layer 101 and a magnetic film that is the magnetization fixed layer 103. When the nonmagnetic film 102 is a metal, it is a giant magnetoresistive film (GMR film), and when it is a nonmagnetic dielectric film, it is a spin tunnel film (TMR film).

  Detection is performed by passing an electric current through the TMR film in a direction perpendicular to the film surface. In the GMR film, the current direction is not limited, but a relatively large detection signal can be obtained by flowing in the direction perpendicular to the film surface.

For the nonmagnetic metal film of the GMR film, a metal such as Cu or Cr is preferably used. In addition, an AlO _x film or an MgO film is preferably used as the nonmagnetic dielectric film of the TMR film. Among these, a TMR film using an MgO film is more preferable because a high detection signal can be obtained.

  As the magnetization fixed layer, a ferromagnetic film having a remarkably large coercive force, or a multilayer film in which an antiferromagnetic film having unidirectional anisotropy is exchange-coupled to the ferromagnetic film is used. By using such a magnetic film, it is possible to prevent magnetization reversal even when a magnetic field is applied. Examples of magnetic films having a large coercive force include alloys of Tb and transition metals, artificial lattice films, and the like. An alloy composed of Tb and a transition metal can have a desired coercive force by adjusting the composition.

  In the artificial lattice film, a desired coercive force can be obtained by adjusting the thickness of each magnetic film. MnIr, MnPt, or the like is preferably used for the antiferromagnetic film used for the exchange coupling film of the ferromagnetic film and the antiferromagnetic film. This exchange coupling film can adjust the magnetization reversal field to a desired value by adjusting the film thickness of the ferromagnetic film.

  A sensor used for a memory element (MRAM) using a magnetoresistive effect film, a detection element of a hard disk, or the like uses a magnetic material having a small coercive force so that it operates with a weak magnetic field. They are, for example, NiFeCo, NiFe, FeCoB, GdFe and the like.

  However, when detecting magnetic particles made of a soft magnetic material, such a magnetic film is not preferable because a large magnetic field is applied to the sensor.

Therefore, in the present invention, the magnetization reversal of the detection layer is caused to occur with a relatively large magnetic field. Examples of such a magnetic film are GdTbFe, GdTbCo, GdTbFeCo, and the like. That is, it is an alloy of Gd, Tb, and a transition metal. Alternatively, an alloy of Dy and a transition metal such as DyFe, DyCo, or DyFeCo, or an alloy of Gd, Dy, or a transition metal such as GdDyFe, GdDyCo, or GdDyFeCo can be given. Also, a desired magnetic film can be formed as an artificial lattice film of the rare earth metal and transition metal described above. If these coercive forces are larger than the coercive force of the above-mentioned materials that have been conventionally used, the effects of the present invention will occur. The coercive force of the conventional material is about several Oe to several tens Oe. Further, iron particles are often used as magnetic particles to be detected. For example, the magnetization thereof linearly increases until the applied magnetic field is about 500 Oe. The magnitude of the magnetization at 500 Oe reaches about 70% of the saturation magnetization and reaches about 90% at 1 kOe, and gradually approaches saturation with a magnetic field larger than 1 kOe. Therefore, the coercive force of the detection layer of the magnetoresistive film used in the present invention is preferably 100 Oe or more, and more preferably 500 Oe or more. The upper limit of the coercive force of the detection layer in the present invention is, for example, 5 kOe or less, preferably 1 k Oe or less.

  The coercive force can obtain a desired value by adjusting the composition and the film thickness. Furthermore, it is possible to exchange-couple the antiferromagnetic film to transition metals such as Ni, Fe, and Co and alloys thereof to increase the magnetic field for magnetization reversal.

  A substance 107 to which the biological substance 106 to be detected specifically binds is fixed on the surface of the magnetoresistive film. For this purpose, a fixed film 110 is formed on the magnetoresistive film. In addition, the surface of the magnetic particle 104 used as a label is modified with a substance 105 on which a biological substance to be detected is specifically immobilized. By doing so, the magnetic particles 104 are fixed to the magnetoresistive film surface only when the biological material 106 to be detected is present in the sample solution, and the biological material 106 can be detected. The biological substance 106 to be detected is, for example, an antigen, and the substance 105/107 that specifically binds thereto is, for example, an antibody. Alternatively, the biological substance 106 to be detected is, for example, DNA, and the substance 105/107 that specifically binds to this is complementary DNA.

  At the time of detection, a magnetic field is applied, and the presence or number of biomolecules is detected from the voltage value of the magnetoresistive film. For example, when a magnetic field 111 is applied in the in-plane direction as shown in FIG. 1, the magnetic particles 104 are magnetized in this magnetic field direction, and the stray magnetic field is opposite to the direction of the applied magnetic field 111 with respect to the magnetoresistive film. 112 is applied. Therefore, if the biomolecule 106 to be detected exists in the sample solution and the magnetic particles 104 are specifically fixed, it is difficult to reverse the magnetization of the detection layer 101. That is, the biological material 106 can be indirectly detected from the relationship between the voltage (electric resistance) of the magnetoresistive film and the magnitude of the applied magnetic field.

  FIG. 2 is a diagram for explaining a detection signal when an anti-ferromagnetic film having unidirectional anisotropy and an exchange coupling film of a ferromagnetic film are used as a detection layer. The relationship of electrical resistance is shown. A solid line indicates a case where there is no biological material, and a broken line indicates a case where a biomolecule exists and magnetic particles are fixed on the upper part of the sensor element.

The magnitude of the applied magnetic field, the size and magnetic characteristics of the magnetic particles used is appropriately selected depending on the magnetic characteristics of the magnetoresistance effect film, the magnetization of the magnetic particles to be detected with high sensitivity and higher magnetic field strength to saturate Is possible. Therefore, the magnetization reversal field of the detection layer is preferably about the magnetization saturation field of the magnetic particles. However, if it is possible to detect even a magnetic field smaller than the magnetization saturation magnetic field of the magnetic particles, the magnetization reversal magnetic field of the detection layer may be made smaller than the magnetization saturation magnetic field of the magnetic particles.

Further, although one sensor element is shown in FIG. 1, a plurality of sensors may be provided so that many biomolecules can be detected.

It should be noted that the detection layer is an exchange coupling film of an antiferromagnetic film and a ferromagnetic film having unidirectional anisotropy, and the unidirectional anisotropy is oriented antiparallel to the applied magnetic field when no magnetic field is applied. It is also preferable to configure.

  The detection layer is a ferrimagnetic material made of an alloy of Gd, Tb and a transition metal, an alloy of Dy and a transition metal, or an alloy of Gd, Dy and a transition metal, and the direction of magnetization of the detection layer when no magnetic field is applied A configuration in which is oriented antiparallel to the applied magnetic field is also suitable.

  The above-mentioned magnetic particles are preferably a soft magnetic material. It is preferable that the sensor element and the magnetic particles are specifically bound by a substance to be detected.

  In addition, as a method of detecting magnetic particles using the above-described detection device, it is preferable to carry out as follows. Specifically, the magnetic particles are detected by gradually increasing the strength of the applied magnetic field from a magnetic field smaller than the magnetization reversal magnetic field of the detection layer, and measuring the magnitude of the voltage of the sensor element.

(Example)
Example 1
In this embodiment, an example in which the present invention is applied to a biosensor for detecting prostate specific antigen (PSA) will be described in detail with reference to FIG.

  A selection transistor 311 and a magnetoresistive film electrically connected to the selection transistor 311 are formed on the Si substrate 310 by a semiconductor process. The selection transistor 311 is connected to a current source 308 that supplies current to the sensor element and a voltmeter 309.

  In this example and Example 2 described later, an n-type MOS FET was used as the selection transistor. Since the selection transistor 311 can be manufactured by a normal method, the manufacturing method is not particularly described.

  Ta, MnIr, CoFeB, Ru, CoFeB, MgO, CoFeB, MnIr, and Ta, which are magnetoresistive films, are sequentially formed using a sputtering method.

  Here, MnIr / CoFeB / Ru / CoFeB is the magnetization fixed layer 303, and CoFeB / MnIr formed after MgO which is the nonmagnetic film 302 is the detection layer 301.

  Note that Ta functions to improve the crystallinity of MnIr and prevent deterioration of magnetic properties.

  These magnetic films have unidirectional anisotropy and uniaxial anisotropy in the in-plane direction. The magnetizations of the two CoFeBs in the magnetization fixed layer 303 are antiparallel due to the interaction. The unidirectional anisotropy of MnIr of the magnetization fixed layer 303 and MnIr of the detection layer 301 is antiparallel.

  The formed magnetoresistive film is cut into sensor elements that are insulated from each other and connected to the selection transistor 311 using an etching method. In this embodiment, the size of the sensor element is 3 μm × 9 μm, and the direction of the unidirectional anisotropy and the uniaxial anisotropy is a direction parallel to the long side of the element. On the magnetoresistive film, an upper electrode 315 made of Au serving as an immobilizing film for immobilizing a substance to which a biological substance specifically binds and an SiN film serving as an unimmobilized film 312 are formed. The SiN film that becomes the non-fixed film 312 in the region corresponding to the magnetoresistive effect film is removed, and the upper electrode 315 is exposed.

  An antibody (first antibody) 307 is immobilized on the upper electrode 315 exposed from the SiN film to be the non-immobilized film 312. The non-immobilized film may be a material other than SiN as long as the antibody is not immobilized and the antibody is not immobilized.

  The test protocol is as follows. The sample solution is dropped on the surface of the sensor element and incubated for 5 minutes, and unreacted PSA 306 is washed away with phosphate buffered saline. Next, phosphate buffered saline containing a second antibody (labeled antibody) 305 labeled with magnetic particles 304 is dropped onto the surface of the sensor element and incubated for 5 minutes.

  Thereafter, unreacted labeled antibody is washed away with phosphate buffered saline. If PSA 306 is present in the sample solution, magnetic particles 304 are fixed on the surface of the sensor element.

  After the magnetic particles 304 are fixed, a magnetic field is applied in the direction of unidirectional anisotropy of the magnetization fixed layer 303. The magnetic field can be obtained by passing a current from the electromagnet power source to the coil 313. In FIG. 3, since the direction of unidirectional anisotropy is a direction parallel to the surface of the silicon substrate 310, the coil 313 is arranged so that the generated magnetic field is parallel to the surface of the silicon substrate 310. There is no particular problem as long as the magnetic field is in any direction as long as it is parallel to the substrate.

The magnetization reversal magnetic field of the detection layer 301 of the magnetoresistive effect element used in this embodiment is about 500 Oe. The magnetic particles 304 used in this example have a structure in which the particle diameter is 200 nm and polystyrene contains a plurality of Fe ₂ O ₃ particles having a particle diameter of 20 nm. Fe ₂ O ₃ is a soft magnetic material having a magnetization saturation magnetic field of about 10 kOe and a magnetization magnitude of about 70% of saturation magnetization at 500 Oe. At the time of detection, the applied magnetic field is gradually increased in the range of 400 Oe to 600 Oe. If the magnetic particles 304 are fixed on the element, the magnetization reversal of the sensor element is caused by a relatively large magnetic field, so that it is confirmed that the PSA 306 is present in the sample solution. When about 10 magnetic particles are fixed to one element, a 10 μV signal is detected by the element. However, in this case, the magnitude of the detection current is 20 μA, and it flows from the upper part of the element toward the lower part. It is possible to know the number of magnetic particles fixed on the element by sequentially turning on the selection transistor 311 connected to each element and integrating the detection signals of all the elements.

  When a conventional magnetoresistive element is used, the magnitude of the applied magnetic field is, for example, about 10 Oe, and the stray magnetic field generated from the magnetic particles when such a magnetic field is applied is a floating magnetic field generated by the magnetic particles in this embodiment. It is about 2-3% of the magnitude of the magnetic field. In such a case, the detection signal is lower than the noise level, and magnetic particles cannot be detected.

(Example 2)
In this example, an example in which the present invention is applied to a biosensor that detects prostate specific antigen (PSA) as in Example 1 will be described. However, the magnetoresistive film used in this embodiment is a magnetic material that is a perpendicular magnetization film.

The circuit configuration of the device is the same as in the first embodiment. The magnetoresistive effect film is formed by sputtering Ta, TbFeCo, FeCo, Al ₂ O ₃ , FeCo, GdDyFeCo, and Ta sequentially. TbFeCo / FeCo is the magnetization fixed layer 403, and FeCo / GdDyFeCo is the detection layer 401.

  These magnetic films have uniaxial anisotropy in the direction perpendicular to the film surface. The composition of the ferrimagnetic film used in this example, that is, the TbFeCo film and the GdDyFeCo film, is a composition in which transition metal sublattice magnetization is dominant. However, the present invention can also be implemented as a composition that has a rare earth sublattice magnetization dominant.

  The transition metal sublattice magnetizations of the two films of the fixed magnetization layer 403 are always parallel due to exchange coupling. The same applies to the detection layer 401. In the initial state, the magnetization direction of the detection layer 401 (that is, the transition metal sublattice magnetization direction) and the magnetization direction of the magnetization fixed layer 403 are set to be antiparallel.

  The formed magnetoresistive film is cut into sensor elements that are insulated from each other and connected to the selection transistor 411 using an etching method. The selection transistor 411 is connected to a current source 408 that supplies current to the sensor element and a voltmeter 409.

  On the magnetoresistive film, an upper electrode 415 made of Au serving as an immobilizing film for immobilizing a substance to which a biological substance specifically binds and an SiN film serving as an unimmobilized film 412 are formed. The SiN film that becomes the non-fixed film 412 in the region corresponding to the magnetoresistive effect film is removed, and the upper electrode 415 is exposed.

  An antibody (first antibody) 407 is immobilized on the upper electrode 415 exposed from the SiN film to be the non-immobilized film 412. The non-immobilized film may be a material other than SiN as long as the antibody is not immobilized and the antibody is not immobilized.

  The test protocol is as follows. The sample solution is dropped on the surface of the sensor element and incubated for 5 minutes, and unreacted PSA406 is washed away with phosphate buffered saline. Next, phosphate buffered saline containing a second antibody (labeled antibody) 405 labeled with magnetic particles 404 is dropped on the surface of the sensor element and incubated for 5 minutes.

  Thereafter, unreacted labeled antibody is washed away with phosphate buffered saline. The particle size of the magnetic particles 404 used in this example was 200 nm. If PSA 406 is present in the sample solution, magnetic particles 404 are fixed on the sensor element surface.

  After the magnetic particles 404 are fixed, a magnetic field is applied in the direction of unidirectional anisotropy of the magnetization fixed layer 403. The magnetic field can be obtained by passing a current from the electromagnet power source to the coil 413. In FIG. 4, since the direction of unidirectional anisotropy is a direction perpendicular to the surface of the silicon substrate 410, the coil 413 is arranged so that the generated magnetic field is perpendicular to the surface of the silicon substrate 410. There is no particular problem as long as the magnetic field is in any direction as long as it is perpendicular to the substrate.

The magnetization reversal field of the detection layer 401 of the sensor element using the magnetoresistive film used in this example is about 1 kOe. The particle size of the magnetic particles 404 used in this example is 100 nm, and has a structure containing a plurality of Fe ₂ O ₃ particles having a particle size of 15 nm in polystyrene. Fe ₂ O ₃ is a soft magnetic material having a magnetization saturation magnetic field of about 10 kOe and a magnetization magnitude of about 80% of saturation magnetization at 1 kOe. At the time of detection, the applied magnetic field is gradually increased in the range of 900 Oe to 1100 Oe. If the magnetic particles 404 are fixed on the sensor element, the magnetization reversal of the sensor element is caused by a relatively large magnetic field, so that it is confirmed that PSA is present in the sample solution.

The figure explaining the outline of a structure of the detection apparatus of this invention. The graph explaining the detection signal of the detection apparatus of this invention. The figure explaining the outline | summary of a structure of one Example of the detection apparatus of this invention. The figure explaining the outline | summary of a structure of one Example of the detection apparatus of this invention. The conceptual diagram explaining the conventional detection method. The conceptual diagram of the sensor element periphery for demonstrating the conventional detection method.

Explanation of symbols

101, 301, 401 Detection layer 102, 302, 402 Nonmagnetic layer 103, 303, 403 Magnetization fixed layer 104, 304, 404, 602 Magnetic particle 105, 107 Specific binding substance 106 Biological substance (detection target)
108, 308, 408 Current source 109 Voltage detection means 110 Immobilized film 111 Magnetic field 112, 604 Floating magnetic field 305, 405 Second antibody 306, 406 PSA
307, 407 First antibody 309, 409 Voltmeter 310, 410 Silicon substrate 311, 411 Select transistor 312, 412 Non-immobilized film 313, 413, 504 Coil 314, 414, 505 Electromagnet power supply 315, 415 Upper electrode 501 Sensor Element 502 Reference element 503 Sense amplifier 506 Lock-in amplifier 507 Sine wave generator 508 Computer 601 Magnetoresistive element 603 AC magnetic field 605 Magnetization vector

Claims (7)

A sensor element for detecting magnetic particles, comprising a magnetoresistive film in which a first magnetic film serving as a detection layer, a nonmagnetic film, and a second magnetic film serving as a magnetization fixed layer are laminated in this order; comprising a power source for supplying a current to the sensor element, a voltage detecting means for detecting a voltage of said sensor element, and a magnetism generating means for applying a magnetic field in the easy magnetization direction of the detection layer, the magnetic on the sensor element by applying a magnetic field from the generating means, a detection device for detecting the magnetic particles from the magnitude of the voltage detected at the applied magnetic field strength the sensor element,
The magnetization direction of the second magnetic film is parallel to the direction of the magnetic field applied from the magnetism generating means;
The first magnetic film is a magnetic film whose magnetization is reversed at 100 Oe or more;
The detection apparatus according to claim 1, wherein the magnetic field applied from the magnetism generation unit is unidirectionally anisotropic in the second magnetic film. The detection layer is an exchange coupling film of an antiferromagnetic film and a ferromagnetic film having unidirectional anisotropy,
The detection apparatus according to claim 1, wherein the unidirectional anisotropy is antiparallel to the applied magnetic field when no magnetic field is applied. The detection layer is a ferrimagnetic material composed of an alloy of Gd, Tb, and a transition metal, an alloy of Dy and a transition metal, or an alloy of Gd, Dy, and a transition metal,
The detection device according to claim 1, wherein in a state where no magnetic field is applied, the magnetization direction of the detection layer is antiparallel to the applied magnetic field.   The detection device according to claim 1, wherein the magnetic particle is a soft magnetic material. The sensor element and the magnetic particle are specifically bound by a substance to be detected, and the magnetic particle specifically bound to the sensor element by the substance to be detected is detected, so that the sensor element is specific to the sensor element. The detection apparatus according to any one of claims 1 to 4, wherein the detection target substance to be detected is detected. A method for detecting the magnetic particles using the detection device according to any one of claims 1 to 5,
The strength of the applied magnetic field is gradually increased from a magnetic field smaller than the magnetization reversal magnetic field of the detection layer, and the magnetic particles are detected by measuring the magnitude of the voltage of the sensor element. Detection method.   When the magnetoresistive film and the magnetic particles are specifically bound by a substance to be detected, the substance to be detected is indirectly detected using the magnetic particles as a label. Item 7. The detection method according to Item 6.

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