JP6681062B2 - METHOD AND DEVICE FOR DETECTION OF MICRO-MAGNETIC MATERIAL AND INSPECTION DEVICE - Google Patents

Description

  The present invention relates to a method and an apparatus capable of detecting the position and concentration of a magnetic substance in an object containing a minute magnetic substance, and in particular, the minute magnetic substance is a magnetic substance marker, and the position of the magnetic substance marker is The present invention relates to a method and an apparatus for detecting a magnetic field, and an inspection apparatus capable of inspecting by detecting the position of a magnetic marker.

  A method of detecting the position of a substance having a magnetic property in a mixture is as follows. A method is known in which a magnetic field induced in a substance having is detected (for example, see Non-Patent Document 1).

  Here, by making the direction of the applied AC magnetic field orthogonal to the direction of the magnetic field detected by the detection coil or the magnetic sensor, the applied AC magnetic field directly enters the detection coil or the magnetic sensor, and Signals other than the magnetic field generated from the substance having magnetic properties are prevented from being output.

  It also describes a method of using a temporary differential coil that detects a signal differentiated along the detection axis as the detection coil and removing signals other than the signal due to the magnetic field to be detected.

  Furthermore, it also describes a method of amplifying the detection signal by matching the frequency of the applied AC magnetic field with the resonance frequency of the detection coil.

  As another method of detecting an object having magnetic characteristics, when an alternating magnetic field is applied, a gradient magnetic field is superimposed and applied to the space in which the object of the subject is present, so that the spatial resolution is desired to be detected. A method has been proposed that realizes a measurement that does not depend on the distance between the substance having the γ and the detection coil, that is, the lift-off distance (for example, see Non-Patent Document 2).

  Here, instead of scanning the detection coil, the third harmonic of the detected signal is acquired while changing the position where the gradient magnetic field becomes zero.

  In a substance having magnetic properties, the third harmonic of the detected signal becomes maximum when the applied DC magnetic field is zero and only the AC magnetic field is applied. Therefore, the maximum value of the third harmonic is The position where the gradient magnetic field when detected is zero is supposed to coincide with the position of the substance having magnetic properties.

  Further, in a mixture in which substances having magnetic properties are mixed, as a method for measuring the concentration of substances having magnetic properties with high sensitivity, a DC magnetic field is applied to a subject and an AC magnetic field is applied to measure the concentration of the measurement sample. A method of measuring a DC bias AC magnetic susceptibility has been proposed (for example, refer to Patent Document 1).

  In particular, a method for improving sensitivity by detecting a harmonic component of the same frequency as the AC magnetic field as a fundamental frequency is also described.

  By combining this method with the method described in Non-Patent Document 1 or Non-Patent Document 2, it is possible to measure the concentration distribution of a substance having magnetic properties in a mixture in which substances having magnetic properties are mixed. However, the above-mentioned problems relating to Non-Patent Document 1 or Non-Patent Document 2 cannot be solved.

  Further, a scanning laser SQUID (Superconducting QUantam Interference Device) microscope is known as an apparatus combining a laser and a magnetic field measuring means (for example, refer to Patent Document 2).

  In a scanning laser SQUID microscope, a semiconductor wafer is irradiated with a laser to induce a current in the semiconductor wafer, and the magnetic field generated by this current is detected by the SQUID.

  In the scanning laser SQUID microscope, the spatial resolution can be determined by the size of the laser beam to be focused, so that a high spatial resolution independent of the lift-off distance can be realized.

JP, 2014-219371, A JP, 2006-258479, A

Takafumi Morishige, Takuro Mihaya, Shi Bai, Takashi Miyazaki, Takashi Yoshida, Masaaki Matsuo, Keiji Enpuku, “Highly Sensitive Magnetic Nanoparticle Imaging Using Cooled-Cu / HTS-Superconductor Pickup Coils”, IEEE Transactions on Applied Superconductivity, Vol. 24, No .4, 1800105 (2014) Shi Bai, Aiki Hirokawa, Kazuhiro Tanabe, Takashi Yoshida, Keiji Enpuku, “Magnetic Particle Imaging Utilizing Orthogonal Gradient Field and Third-Harmonic Signal Detection”, IEEE Transactions on Magnetics, Vol. 50, No. 11, 5101304 (2014)

  In a position detection / visualization method or apparatus capable of measuring the position or concentration distribution of a substance having magnetic properties in a mixture in which substances having magnetic properties are mixed, in the method described in Non-Patent Document 1, the lift-off distance is There is a problem in that the spatial resolution, which is the ability to specify the position in proportion, decreases.

  Therefore, for example, when magnetic nanoparticles are aggregated in a predetermined affected part of the body, such as cancer screening using magnetic markers that have been widely used in recent years, the distance between the magnetic nanoparticles and the detection coil is increased. It is difficult to obtain a high spatial resolution because it is difficult to shorten.

  In addition, in the method described in Non-Patent Document 2, it is possible to improve the spatial resolution by increasing the gradient of the gradient magnetic field, but when measuring a large subject such as a human body, the gradient magnetic field is increased. It is necessary to increase the size of the device that generates the noise, and there is a problem that the device increases in size.

  In addition, when the gradient of the gradient magnetic field is increased, the ratio of the gradient magnetic field directly entering the detection coil is increased, so that signals other than those generated from the substance having the magnetic characteristic to be detected are compared. However, there is a problem that the ratio of the output is large.

  Further, the method described in Patent Document 2 has a problem that it is difficult to evaluate a conductive substance or an insulating substance that cannot induce a current by light.

  Further, there is a problem that it is difficult to specify the position of particles having a diameter of 1 μm or less or a set of particles having a diameter of 1 μm or less, in which it is difficult to generate a large induced current.

  In the method for detecting a minute magnetic substance of the present invention, an external magnetic field having an AC component is applied to a subject, and a fluctuating magnetic field that fluctuates due to this external magnetic field is detected to detect the minute magnetic substance present in the subject. In the method described above, the micro-magnetic material in the subject is irradiated with the laser light by irradiating the subject while scanning the laser light, and the irradiation of the laser light changes the response of the micro-magnetic substance to the external magnetic field. By doing so, the minute magnetic substance is detected.

Further, in the apparatus for detecting a minute magnetic substance according to the present invention, an external magnetic field applying means for applying an external magnetic field having an AC component to a subject, a magnetic field detecting means for detecting a fluctuating magnetic field which fluctuates due to the external magnetic field, and the magnetic field detecting means. In a detection device having an analysis means for detecting a minute magnetic substance existing in a subject based on the detection result of the means, a laser irradiation means for irradiating the subject with laser light being scanned. is there. In particular, the analyzing means detects the first detection value detected by the magnetic field detecting means when the predetermined position of the subject is irradiated with the laser light and the second detection value detected by the magnetic field detecting means when the laser light is not irradiated. It is characterized in that the minute magnetic substance is detected using the detected value of.

Furthermore, the device for detecting a minute magnetic substance of the present invention is also characterized by the following points.
(1) The laser irradiation means has a lens that condenses the laser light and a mirror that reflects the incident laser light in a predetermined direction, and the laser light is scanned by rotating the mirror. The condensing point of the laser light is moved in the optical axis direction by moving the lens in the optical axis direction.
( 2 ) The analysis means lock-in-detects the output signal of the magnetic field detection means with a harmonic whose fundamental frequency is the frequency of the AC component of the external magnetic field.
( 3 ) The laser light must be pulsed laser light with a pulse width of 1 nanosecond or less.
( 4 ) The wavelength of laser light must be 700 nm or longer.

Further, in the inspection device of the present invention, an external magnetic field having an AC component is applied to the subject in the inspection device that performs the inspection by detecting the position of the magnetic marker of the subject to which the magnetic marker including the micromagnetic substance is administered. An external magnetic field applying means, a magnetic field detecting means for detecting a fluctuating magnetic field that fluctuates due to the external magnetic field, an analyzing means for detecting a magnetic marker existing in the body of the subject based on the detection result by the magnetic field detecting means, and a subject Laser irradiation means for irradiating the laser light while scanning it. In particular, the analysis means detects the first detection value detected by the magnetic field detection means when the predetermined position of the subject is irradiated with the laser light and the second detection value which is detected by the magnetic field detection means when not irradiated with the laser light. It is characterized in that the minute magnetic substance is detected using the detected value.

  According to the present invention, the micro magnetic material is irradiated with the laser light in the state where the external magnetic field having the alternating current component is applied to the micro magnetic material, and the micro magnetic material is heated by the irradiation of the laser light. The magnetic characteristics change, and the minute magnetic substance can be detected by detecting the change in the magnetic characteristics.

  In particular, in the method and apparatus for detecting a minute magnetic substance and the inspection apparatus of the present invention, it is sufficient that an external magnetic field acts on the subject, and it is necessary to apply a huge magnetic field such as MRI (nuclear magnetic resonance imaging). The target micro magnetic material or magnetic marker can be detected even with a less expensive device.

It is a schematic diagram of the basic composition of the device concerning the present invention. 6 is a magnetic characteristic graph in which the vertical axis represents the second harmonic component and the horizontal axis represents the magnitude of the applied DC magnetic field. It is a magnetic characteristic graph at the time of detecting the second harmonic component while linearly moving the focus position of the laser light. It is a schematic block diagram of an inspection device which inspects by detecting the position of a magnetic marker of a subject to whom a magnetic marker containing a minute magnetic substance is administered.

  In the method, apparatus, and inspection device for detecting a minute magnetic body of the present invention, the minute magnetic body in the subject is irradiated with laser light, and the minute magnetic body is heated by the laser light and its magnetic characteristics change. By detecting the change in the magnetic characteristics of the minute magnetic substance, not only the position of the minute magnetic substance but also the concentration can be detected.

  In particular, since it is possible to specify the three-dimensional coordinates irradiated with the laser light, it is extremely easy to specify the position of the minute magnetic body. That is, in the conventional case, for example, the position of the minute magnetic body was specified by scanning the detection coil two-dimensionally, whereas the detection coil does not need to be scanned and is fixedly arranged. It suffices to detect only that the magnetic field variation has occurred by irradiating the laser beam while scanning it, and the position of the minute magnetic body can be pinpointed from the irradiation position of the laser beam when the magnetic field variation occurs. Furthermore, the concentration of the minute magnetic substance can be detected from the magnitude of the detected magnetic field fluctuation.

  In order to effectively detect the magnetic field fluctuation caused by irradiating the laser beam while scanning in this way, an external magnetic field having an AC component is applied to the subject, and the variable magnetic field that fluctuates due to this external magnetic field is detected. I have decided.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings.
Further, members having the same use and function are denoted by the same reference numerals and the description thereof will be omitted.

  FIG. 1 is a schematic diagram showing a basic configuration of a device 1 according to an embodiment of the present invention.

  The device 1 includes a pair of opposed first and second electromagnets 1-1 and 1-2 for applying a predetermined magnetic field to the subject 3 and the minute magnetic body 4 included in the subject 3, and the first and second electromagnets 1-2. The electromagnet power source 2 as magnetic field control means for controlling the magnetic fields generated by the electromagnets 1-1 and 1-2, the detection coil 5 for detecting a signal generated by the magnetization of the micro magnetic body 4, and the detection coil 5 A transmission coil 6 that outputs the detected signal as a magnetic field signal, a magnetic sensor 7 that detects the magnetic field signal that is output from the transmission coil 6, a laser 8 that outputs a laser beam that irradiates the subject 3, and a laser beam that receives the laser beam. A lens 9 and a movable mirror 10 for condensing light on an arbitrary position of the sample 3 are provided.

  Here, the first electromagnet 1-1, the second electromagnet 1-2, and the magnetic field control means constitute an external magnetic field application means that applies an external magnetic field having an AC component to the subject 3. The external magnetic field applying means applies not only the AC magnetic field but also a predetermined DC magnetic field to the subject 3.

  Further, the magnetic sensor 7 is a magnetic field detecting means for detecting a fluctuating magnetic field which fluctuates due to an external magnetic field. In the present embodiment, the detection accuracy of the magnetic sensor 7 is improved by using the detecting coil 5 and the transmitting coil 6. I am letting you.

  In the present embodiment, the detection coil 5 has a configuration of a primary differential coil in which a pair of coils whose winding directions are opposite to each other are connected in series on a plane. By using this first-order differential coil configuration, magnetic noise in the environment can be removed. When a primary differential coil is used as the detection coil 5, the center of one side of the pair of coils is preferably aligned with the center of the subject 3.

  The laser 8, the lens 9, and the movable mirror 10 are laser irradiation means for irradiating the subject with laser light while scanning the same. In particular, the movable mirror 10 is incident by an appropriate movable base (not shown). The laser light is reflected in a predetermined direction. Further, the lens 9 condenses the laser light of the parallel rays emitted from the laser 8 to generate a condensing point, and the lens 9 is moved in the optical axis direction by a predetermined moving base (not shown). It is possible to move to. That is, by moving the lens 9 in the optical axis direction, the condensing point of the laser light can be moved in the optical axis direction.

  The laser light emitted from the laser 8 preferably has a wavelength of 700 nm or more. By using a laser beam having a wavelength of 700 nm or more, even when the subject 3 is a human body, the laser beam can efficiently reach a deep position from the surface of the human body. In particular, the laser light is condensed using the lens 9, and in the present invention, “irradiating the laser light” means irradiation of the laser light condensed by the lens 9 at a condensing point portion.

Further, the laser light emitted from the laser 8 is pulsed laser light having a pulse width of 1 nanosecond or less, and damage caused to the subject by the irradiation of the laser light is reduced as much as possible. In the present embodiment, the laser beam output from the laser 8 is a pulse laser having a pulse width of 130 × 10 ⁻¹⁵ seconds and a center wavelength of 1.56 μm.

  The device 1 of the present embodiment is provided with the lock-in amplifier 11 that lock-in-detects the output signal of the magnetic sensor 7 that is the magnetic field detection means, using a harmonic whose fundamental frequency is the frequency of the AC component of the external magnetic field.

  Further, the device 1 of the present embodiment is provided with the analysis device 12 that analyzes the output signal of the lock-in amplifier 11. The analysis device 12 not only executes a predetermined analysis process, but also controls driving of the movable pedestal of the movable mirror 10 and the movable pedestal of the lens 9 to emit a laser beam to a predetermined position of the subject 3. The output of the magnetic sensor 7 at the time of irradiation is obtained. Here, the lock-in amplifier 11 and the analyzing device 12 constitute an analyzing means.

  Hereinafter, the principle of specifying the position and measuring the concentration distribution of the minute magnetic substance contained in the subject by the device 1 of the present invention will be described.

  In FIG. 2, the vertical axis represents the second harmonic component of the detection signal of the magnetic sensor 7 when the minute magnetic body 4 included in the subject 3 is irradiated with laser light and when the minute magnetic body 4 is not irradiated with laser light. 6 is a magnetic characteristic graph in which the horizontal axis represents the magnitude of a DC magnetic field applied by the first electromagnet 1-1 and the second electromagnet 1-2.

  Here, the average intensity of the laser light was 200 mW, and the diameter of the laser light at the focused position was about 3 mm. The magnetic field applied to the measurement sample 3 using the first electromagnet 1-1 and the second electromagnet 1-2 had an alternating magnetic field of 10 mT and its frequency was 10 Hz. The DC magnetic field was changed between 0 and 20 mT.

  It can be seen from FIG. 2 that the second harmonic component of the detection signal changes when the minute magnetic material 4 is irradiated with the laser light. Further, the amount of change is related to the concentration of the minute magnetic substance 4 existing at the condensing point of the laser light. Therefore, the amount of change of the second harmonic is read while changing the position of the focus point of the laser light, and the detected value of the amount of change of the second harmonic when the laser light is irradiated and the laser light is not irradiated. The position or concentration of the minute magnetic substance 4 in the subject 3 can be detected from the detected value of the change amount of the second harmonic in the state. At this time, the DC magnetic field can be set to a magnitude that maximizes the change in the harmonic signal, thereby enabling highly sensitive measurement.

  In the above-described embodiment, the fact that the temperature of the micro magnetic body 4 is changed by irradiating the micro magnetic body 4 with the laser beam is used. However, depending on the type of the micro magnetic body 4, the micro magnetic body 4 may be irradiated with the laser beam. A signal can also be changed by exciting spins inside the minute magnetic body 4. In this case, the signal can be changed at a speed higher than the speed at which the signal is changed by changing the temperature of the minute magnetic body 4.

  Although the alternating magnetic field is 10 mT, it may be operated with only 0 mT, that is, the direct magnetic field. In this case, the output of the magnetic sensor can be directly input to the analysis device 12 without using the lock-in amplifier 11.

FIG. 3 is a magnetic characteristic graph when the second harmonic component is detected while linearly moving the focus position of the laser light with respect to the test body in which the minute magnetic body 4 is present in two places. Is. Here, the fine magnetic material 4 is Fe ₃ O ₄ fine particles, and is set so that the central portion has a low concentration and the peripheral portion has a high concentration.

  It can be seen from FIG. 3 that the harmonic signal is reduced in the portion where the magnetic substance 4 is present. Also, it can be seen that the reduction rate is large in the high density portion.

  FIG. 4 is a schematic configuration when the method for detecting a micromagnetic substance of the present invention is used as an inspection device for inspecting by detecting the position of a magnetic substance marker of a subject to whom a magnetic substance marker containing a minute magnetic substance is administered. It is a figure.

  This test apparatus is configured such that a bed 20 on which a subject to whom a magnetic marker is administered lies down, a first electromagnet 21 and a second electromagnet 22 that generate an external magnetic field in the body axis direction of the subject lying on the bed 20, and an external magnetic field. A detection coil 23 for detecting a fluctuating fluctuating magnetic field, and a laser irradiator 24 for irradiating a subject while scanning the laser beam, and detecting a magnetic marker existing in the subject's body by an analyzer (not shown). I am trying.

  Each of the first electromagnet 21 and the second electromagnet 22 has a hollow central portion, and has a frame shape into which the bed 20 can be inserted. The first electromagnet 21 is attached to the base 25 via the first support frame f1, and the second electromagnet 22 is attached to the base 25 via the second support frame f2 so that the subject can move back and forth in the body axis direction. When getting on and off the bed 20, the first electromagnet 21 is retracted in the overhead direction and the second electromagnet 22 is retracted in the toe direction so that the subject can easily get on and off the bed 20.

  The detection coil 23 is provided inside or on the upper surface of the bed 20.

  The laser irradiator 24 is provided on the upper side of the subject lying on the bed 20 so that the laser beam can be emitted while scanning the laser beam toward the subject. The laser irradiator 24 is attached to the base 25 via the third support frame f3 and can be moved to an appropriate position.

  With the inspection apparatus configured as described above, it is possible to inspect the position and concentration of the magnetic marker of the subject to which the magnetic marker including the minute magnetic substance is administered. In addition to the inspection, it can be used as a therapeutic device by utilizing the fact that the minute magnetic material can be heated by irradiation of laser light.

  In the description of the above-mentioned embodiment, the magnetic marker is assumed as the minute magnetic substance, but the minute magnetic substance is not limited to the case of being used as the magnetic substance marker, and the substance containing the magnetic substance is not limited thereto. It can be widely used for inspection.

1-1 First Electromagnet 1-2 Second Electromagnet 2 Power Supply for Electromagnet 3 Subject 4 Micro Magnetic Material 5 Detection Coil 6 Transfer Coil 7 Magnetic Sensor 8 Laser 9 Lens 10 Movable Mirror 11 Lock-in Amplifier 12 Analysis Device

Claims (7)

An external magnetic field having an AC component is applied to a subject, and a method for detecting a minute magnetic substance existing in the subject by detecting a fluctuating magnetic field that fluctuates due to the external magnetic field,
By irradiating the object while scanning it with laser light, the minute magnetic material in the object is irradiated with the laser light, and the irradiation of this laser light changes the response of the minute magnetic material to the external magnetic field. A method for detecting magnetic substances. An external magnetic field applying means for applying an external magnetic field having an AC component to the subject,
Magnetic field detection means for detecting a fluctuating magnetic field that fluctuates due to an external magnetic field,
In a detection device provided with an analysis means for detecting a minute magnetic substance existing in the subject based on the detection result of the magnetic field detection means,
It has a laser irradiation means for irradiating the subject while scanning the laser beam,
The analysis means detects a first detection value detected by the magnetic field detection means in a state where laser light is applied to a predetermined position of the subject and a magnetic field detection means in a state where no laser light is applied. A detection device for detecting the minute magnetic substance by using a second detection value.   The laser irradiation means has a lens for condensing the laser light and a mirror for reflecting the incident laser light in a predetermined direction. The laser light is scanned by rotating the mirror, and the lens is used. The detection device according to claim 2, wherein the condensing point of the laser light is moved in the optical axis direction by moving the lens in the optical axis direction.   The detection device according to claim 2 or 3, wherein the analysis unit performs lock-in detection of an output signal of the magnetic field detection unit with a harmonic having a frequency of an AC component of the external magnetic field as a fundamental frequency. The detection device according to claim 2, wherein the laser light is pulsed laser light having a pulse width of 1 nanosecond or less. The detection device according to claim 2, wherein the laser light has a wavelength of 700 nm or more. In an inspection device for inspecting by detecting the position of a magnetic marker of a subject to whom a magnetic marker containing a minute magnetic substance is administered,
External magnetic field applying means for applying an external magnetic field having an alternating current component to the subject,
Magnetic field detection means for detecting a fluctuating magnetic field that fluctuates due to an external magnetic field,
An analysis means for detecting a magnetic marker existing in the body of the subject based on the detection result of the magnetic field detection means,
And a laser irradiation means for irradiating the subject while scanning the laser light,
The analyzing means detects, with respect to a predetermined position of the subject, a first detection value detected by the magnetic field detecting means in a state of being irradiated with laser light and a first detection value detected by the magnetic field detecting means in a state of not being irradiated with laser light. An inspection apparatus for detecting the minute magnetic substance by using the detected value of 2.