JP4883424B2 - Micro magnetic two-dimensional distribution detector - Google Patents

Description

  The present invention relates to a minute magnetic two-dimensional distribution detection device, and more particularly to a minute magnetic two-dimensional distribution detection device capable of detecting a minute magnetic two-dimensional distribution of pT or less.

  Conventionally, a SQUID immunoassay system that detects how much antigen bound to an antibody labeled with magnetic nanoparticles is present in a sample by moving the sample with an electric slider and passing directly under the SQUID magnetic sensor is known. (For example, see Non-Patent Document 1).

Keiji Enfuku, “Development of SQUID immunoassay system using magnetic nanoparticles”, Internet <URL: http://www.sc.kyushu-u.ac.jp/publication/vol1/enpuku.pdf>

In the conventional SQUID immunoassay system, it was possible to detect a minute magnetism of pT or less.
However, there is a problem that a two-dimensional distribution cannot be detected.
Accordingly, an object of the present invention is to provide a minute magnetic two-dimensional distribution detection device capable of detecting a minute magnetic two-dimensional distribution of pT or less.

In a first aspect, the present invention provides a sample stage (S) having a SQUID (1) and a sample (S) having an inspection surface (A) so that the inspection surface (A) faces the SQUID (1). 8), vibration means (7) for vibrating the sample table (8), and relative to the SQUID (1), the sample table (8) is two-dimensionally relative to the inspection surface (A). A micro magnetic two-dimensional device characterized by comprising scanning means (5) for movement and an electronic circuit (10, 11, 12) for detecting a magnetic signal component of the vibration frequency via the SQUID (1). A distribution detection device (100) is provided.
In the micro magnetic two-dimensional distribution detection apparatus (100) according to the first aspect, the sample (S) is vibrated while facing the inspection surface (A) of the sample (S) to the SQUID (1), thereby reducing the pT or less. Can detect minute magnetism. Further, the inspection surface (A) can be scanned two-dimensionally by moving the sample table (2) relative to the SQUID (1) two-dimensionally in the direction of the inspection surface (A). Therefore, it is possible to detect a minute two-dimensional magnetic distribution of pT or less. Further, since the magnetic signal component of the vibration frequency is detected, the influence of magnetic noise having a frequency away from the vibration frequency can be suppressed.

In a second aspect, the present invention provides a sample (S) having a plurality of one-dimensionally arranged SQUIDs (1) and an inspection surface (A), and the inspection surface (A) faces the SQUID (1). The sample stage (8) to be held in this manner, the vibration means (7) for vibrating the sample stage (8), and the sample stage (8) with respect to the SQUID (1) Scanning means (5) capable of relative movement in a direction and at least in a direction orthogonal to the arrangement of the SQUID (1), and an electronic circuit (10) for detecting a magnetic signal component of the vibration frequency via the SQUID (1) , 11, 12). A micromagnetic two-dimensional distribution detector (200) is provided.
In the micro magnetic two-dimensional distribution detection apparatus (200) according to the second aspect, the sample (S) is vibrated while facing the inspection surface (A) of the sample (S) to the SQUID (1), thereby reducing the pT or less. Can detect minute magnetism. Further, by moving the sample table (2) relative to the SQUID (1) arranged one-dimensionally in the direction of the inspection surface (A) and in the direction orthogonal to the arrangement of the SQUID (1), the inspection surface (A ) Can be scanned two-dimensionally. Therefore, it is possible to detect a minute two-dimensional magnetic distribution of pT or less. Further, since the magnetic signal component of the vibration frequency is detected, the influence of magnetic noise having a frequency away from the vibration frequency can be suppressed.

In a third aspect, the present invention provides the micromagnetic two-dimensional distribution detection apparatus according to the first or second aspect, wherein the SQUID (1), the sample stage (8), the excitation means (7), and the Provided is a micromagnetic two-dimensional distribution detecting device characterized in that the scanning means (5) is accommodated in a magnetic shielding box (31).
In the micro magnetic two-dimensional distribution detection device according to the third aspect, the influence of external magnetic noise can be suppressed by the magnetic shielding box (31).

In a fourth aspect, the present invention relates to a sample (S) having a plurality of two-dimensionally arranged SQUIDs (1) and an inspection surface (A), and the inspection surface (A) faces the SQUID (1). A sample stage (8) to be held in this way, vibration means (7) for vibrating the sample stage (8), and an electronic circuit for detecting a magnetic signal component of the vibration frequency via the SQUID (1) ( 10, 11, 12), and a micromagnetic two-dimensional distribution detector (300).
In the micro magnetic two-dimensional distribution detection apparatus (300) according to the fourth aspect, the sample (S) is vibrated while the inspection surface (A) of the sample (S) faces the SQUID (1), so that the pT or less is reduced. Can detect minute magnetism. In addition, since the plurality of SQUIDs (1) are two-dimensionally arranged, the inspection surface (A) can be scanned two-dimensionally. Therefore, it is possible to detect a minute two-dimensional magnetic distribution of pT or less. Further, since the magnetic signal component of the vibration frequency is detected, the influence of magnetic noise having a frequency away from the vibration frequency can be suppressed.

In a fifth aspect, the present invention provides the micromagnetic two-dimensional distribution detection apparatus (300) according to the fourth aspect, wherein the SQUID (1), the sample stage (8), and the vibration means (7) are provided. Provided is a micromagnetic two-dimensional distribution detection device (300) characterized by being housed in a magnetic shielding box (31).
In the micro magnetic two-dimensional distribution detection device according to the third aspect, the influence of external magnetic noise can be suppressed by the magnetic shielding box (31).

In a sixth aspect, the present invention provides the minute magnetic two-dimensional distribution detection device according to any one of the first to fifth aspects, wherein the excitation means (7) is housed in a dedicated magnetic shielding box (32). A micromagnetic two-dimensional distribution detection device characterized by the above is provided.
In the micromagnetic two-dimensional distribution detection apparatus according to the sixth aspect, the magnetic shielding box (32) can suppress the influence of magnetic noise generated by the vibration means (7).

  According to the minute magnetic two-dimensional distribution detection device of the present invention, it is possible to detect a minute magnetic two-dimensional distribution of pT or less. Further, it is possible to suppress the influence of magnetic noise having a frequency away from the vibration frequency of the sample stage.

1 is a partially broken front view showing a minute magnetic two-dimensional distribution detection device according to Embodiment 1. FIG. FIG. 3 is a top view in which a part of the micromagnetic two-dimensional distribution detector according to the first embodiment is omitted. It is the top view which abbreviate | omitted further one part of the micro magnetic two-dimensional distribution detection apparatus which concerns on Example 1. FIG. It is explanatory drawing which shows a detection point. It is a schematic diagram which shows the detected minute magnetic two-dimensional distribution. It is a partially broken front view which shows the micro magnetic two-dimensional distribution detection apparatus which concerns on Example 2. FIG. FIG. 6 is a top view in which a part of the micromagnetic two-dimensional distribution detector according to the second embodiment is omitted. FIG. 6 is a top view in which a part of the micromagnetic two-dimensional distribution detector according to the second embodiment is omitted. FIG. 6 is a top view in which a part of the micromagnetic two-dimensional distribution detector according to the second embodiment is omitted. It is an illustration figure which shows the test | inspection result by the micro magnetic two-dimensional distribution detection apparatus which concerns on Example 2. FIG. It is a top view which shows the division of a sample. It is explanatory drawing which shows the selective coupling | bonding of biopolymer. It is a partially broken front view which shows the micro magnetic two-dimensional distribution detection apparatus which concerns on Example 3. FIG. FIG. 10 is a top view in which a part of the micromagnetic two-dimensional distribution detection device according to the third embodiment is omitted.

  Hereinafter, the present invention will be described in more detail with reference to embodiments shown in the drawings. Note that the present invention is not limited thereby.

Example 1
FIG. 1 is an explanatory diagram of a configuration of a minute magnetic two-dimensional distribution detection apparatus 100 according to the first embodiment.
This micromagnetic two-dimensional distribution detection apparatus 100 includes a SQUID 1, a cryostat 2 that cools the SQUID 1, a magnetizing coil 4 that is mounted on the outer periphery of the tip of the cryostat 2 that houses the SQUID 1, and the x direction, the y direction, and the z direction. XYZ stage 5 movable in three directions; rail 6 fixed on the upper surface of XYZ stage 5; vibrator 7 generating vibration in x direction; and sample movable on rail 6 in x direction A base 8, a connecting member 9 that connects the vibrator 7 and the sample base 8, an oscillator 10 that applies an excitation frequency to the vibrator 7, and a SQUID that drives the SQUID 1 and outputs an output signal corresponding to the detected magnetism Drive circuit 11, lock-in amplifier 12 that extracts the signal component of the excitation frequency, analyzer 13 that analyzes the signal component of the excitation frequency, SQUID 1, and cryostat A magnetic shielding box 31 that surrounds the tip of the magnet, the XYZ stage 5, the rail 6, the vibrator 7, the sample stage 8, and the connecting member 9, and a magnetic shielding box 32 that surrounds only the vibrator 7. It comprises.

  The sample S having the inspection surface A is held on the upper surface of the sample table 8.

  The SQUID 1 has a diameter of 2 mm, for example.

  The magnetizing coil 4 is formed, for example, by winding an enameled wire having a wire diameter of 0.1 mm around the outer periphery of the tip of the cryostat 2 for 10,000 turns.

FIG. 2 is a top view showing the inside of the magnetic shielding box 31.
FIG. 3 is a top view showing the XYZ stage 5, the rail 6, the vibrator 7, the sample stage 8, the connecting member 9, and the magnetic shielding box 32 with the ceiling removed.

The vibration exciter 7 applies vibration in the x direction with an amplitude of 0.1 mm to 10 mm and an excitation frequency of 1 Hz to 100 kHz, for example, to the sample stage 8 via the connecting member 9.
A specific example of the vibrator 7 is, for example, an ultrasonic vibrator (piezoelectric element).

  The XYZ stage 5 moves in the z direction so that the distance between the SQUID 1 and the sample S in the z direction is 1 mm, for example. Then, as shown in FIG. 4, it moves in the x direction and the y direction so that one of a plurality of detection points d (x, y) assumed on the sample S is directly below SQUID1. In FIG. 4, the detection point d (x, y) is assumed on a lattice point with a pitch of 3 mm.

  The sample S is, for example, a two-dimensional thin layer chromatography carrier of a solution containing a substance labeled with magnetic nanoparticles.

When detecting a two-dimensional distribution of magnetic susceptibility, a magnetic signal component of an excitation frequency is detected via SQUID1 in a state where a direct current is applied to the magnetizing coil and a magnetic field of, for example, 1 μT is applied to the sample S. Repeat at each detection point d (x, y). Then, a two-dimensional distribution of magnetic susceptibility is obtained based on the obtained result.
FIG. 5 illustrates the obtained two-dimensional distribution of magnetic susceptibility.

  When detecting a two-dimensional distribution of magnetic relaxation, a magnetic signal component of an excitation frequency is detected via SQUID 1 in a state where a pulse current is applied to the magnetizing coil and a magnetic field of, for example, 1 mT is applied to the sample S. In a state where no magnetic field is applied to the sample S, the magnetic signal component of the excitation frequency is detected via the SQUID 1 and the difference is obtained at each detection point d (x, y). Then, based on the obtained result, a two-dimensional distribution of magnetic relaxation is obtained.

  When detecting a two-dimensional distribution of residual magnetism, a pulse current is applied to the magnetizing coil to apply a magnetic field of, for example, 1 mT to the sample S. Is detected at each detection point d (x, y). Then, a two-dimensional distribution of remanence is obtained based on the obtained result.

  According to the minute magnetic two-dimensional distribution detection apparatus 100 of the first embodiment, it is possible to detect a minute two-dimensional magnetic distribution of pT or less. In addition, the influence of magnetic noise having a frequency away from the vibration frequency of the sample stage 8 can be suppressed. Moreover, the influence of external magnetic noise can be suppressed. Furthermore, the influence of magnetic noise generated by the vibration exciter 7 can be suppressed.

-Example 2-
FIG. 6 is an explanatory diagram of a configuration of a minute magnetic two-dimensional distribution detection apparatus 200 according to the second embodiment.
This micromagnetic two-dimensional distribution detection device 200 includes three SQUIDs 1 arranged in a one-dimensional manner, a cryostat 2 that cools SQUID 1, a magnetizing coil 4 that is attached to the outer periphery of the tip of the cryostat 2 that houses SQUID 1, An XYZ stage 5 movable in three directions of x direction, y direction, and z direction, a rail 6 fixed on the upper surface of the XYZ stage 5, a vibration exciter 7 that generates vibration in the x direction, and on the rail 6 A sample base 8 capable of moving in the x direction, a connecting member 9 for connecting the vibrator 7 and the sample base 8, an oscillator 10 for applying an excitation frequency to the vibrator 7, and a magnetism detected by driving the SQUID 1. A SQUID driving circuit 11 for outputting a corresponding output signal, a lock-in amplifier 12 for extracting the signal component of the excitation frequency, an analysis device 13 for analyzing the signal component of the excitation frequency, and the SQUI 1, the tip of the cryostat 2, the magnetizing coil 4, the XYZ stage 5, the rail 6, the shaker 7, the sample stage 8 and the connecting member 9, and the magnetic shielding box 31 surrounding only the shaker 7. And a shielding box 32.

  The sample S having the inspection surface A is held on the upper surface of the sample table 8.

FIG. 7 is a top view showing the inside of the magnetic shielding box 31.
The sample S is a gel-like substrate whose inspection surface A is divided into 3 rows and 3 columns of sections A1 to A9.

First, as shown in FIG. 7, the XYZ stage 5 moves the sections A1 to A3 directly below the three SQUIDs 1 that are one-dimensionally arranged. And the magnetic susceptibility of division A1-A3 is detected.
Next, as shown in FIG. 8, the XYZ stage 5 moves the sections A4 to A6 immediately below the three SQUIDs 1 that are one-dimensionally arranged. And the magnetic susceptibility of division A4-A6 is detected.
Next, as shown in FIG. 9, the XYZ stage 5 moves the sections A7 to A9 immediately below the three SQUIDs 1 that are one-dimensionally arranged. And the magnetic susceptibility of division A7-A9 is detected.

FIG. 10 is an exemplary diagram illustrating a detection result of magnetic susceptibility.
It can be seen that the magnetic susceptibility is the highest in the section A1, the magnetic susceptibility is slightly higher in the section A2, and the magnetic susceptibility is almost zero in the sections A3 to A9.

As shown in FIG. 11, polymer films containing different types of biopolymers G1,..., G9 are arranged in the sections A1,.
As shown in FIG. 12, only the biopolymer B1 can selectively bind to the biopolymer G1. Further, only the biopolymer B2 can selectively bind to the biopolymer G2. Similarly, only different types of biopolymers B3,..., B9 can selectively bind to the biopolymers G3,.

Therefore, when it is desired to check whether or not a certain solution contains biopolymers B1 to B9, as shown in FIG. 12, a biopolymer C that can be bonded in common to the biopolymers B1 to B9 is used as a magnet. Nanoparticles m are bound to biopolymers B1 to B9. Next, this solution is poured into each of the compartments A1 to A9 of the sample S and washed away after a certain time. Then, if, for example, the biopolymer B1 is included in the solution, the biopolymer B1 selectively binds only to the biopolymer G1 in the section A1, and therefore remains in the section A1, and in the sections A2 to A9. Does not remain. Further, if the solution contains, for example, biopolymer B2, the biopolymer B2 selectively binds only to the biopolymer G2 in the section A2, and therefore remains in the section A2, and the sections A1, A3 to A3. It does not remain in A9. Similarly, if the solution contains, for example, biopolymers B3,..., B9, the biopolymers B3,..., B9 selectively bind only to the biopolymer G2 in the sections A3,. , Remain in the sections A3,..., A9, respectively, and do not remain in other sections.
Therefore, if the detection result of the magnetic susceptibility as shown in FIG. 10 is obtained, the solution contains the biopolymer B1 at a high concentration and the biopolymer B2 at a medium concentration. It turns out that B3-B9 is hardly contained.

  According to the minute magnetic two-dimensional distribution detection apparatus 200 of the second embodiment, a minute magnetic two-dimensional distribution of pT or less can be detected. In addition, the influence of magnetic noise having a frequency away from the vibration frequency of the sample stage 8 can be suppressed. Moreover, the influence of external magnetic noise can be suppressed. Furthermore, the influence of magnetic noise generated by the vibration exciter 7 can be suppressed.

Example 3
FIG. 13 is an explanatory diagram of a configuration of a minute magnetic two-dimensional distribution detection apparatus 300 according to the third embodiment.
This micromagnetic two-dimensional distribution detection device 300 is mounted on the outer periphery of nine SQUIDs 1 that are two-dimensionally arranged in three rows and three columns, a cryostat 2 that cools SQUID 1, and a cryostat 2 that houses SQUID 1. Magnetization coil 4, rail 6, sample stage 8 movable on the rail 6 in the x direction, magnetic shield box 31 surrounding SQUID 1, the tip of cryostat 2, magnetization coil 4, rail 6, and sample stage 8. A vibrator 7 installed outside the magnetic shielding box 31 and generating vibration in the x direction, a magnetic shielding box 32 surrounding the vibrator 7, and a connection connecting the vibrator 7 and the sample stage 8. A member 9, an oscillator 10 that applies an excitation frequency to the vibrator 7, a SQUID driving circuit 11 that drives the SQUID 1 and outputs an output signal corresponding to the detected magnetism, and a signal component of the excitation frequency are collected. A lock-in amplifier 12 to issue comprises an analyzing device 13 for analyzing the signal component of the vibration frequency.

  The sample S having the inspection surface A is held on the upper surface of the sample table 8.

FIG. 14 is a top view showing the inside of the magnetic shielding box 31.
The sample S is the same as in Example 2, and is a gel-like substrate in which the inspection surface A is divided into 3 rows and 3 columns of sections A1 to A9.

  As shown in FIG. 14, sections A1 to A9 are placed immediately below nine SQUID1 two-dimensionally arranged in three rows and three columns, and the magnetic susceptibility of the sections A1 to A9 is detected.

  According to the minute magnetic two-dimensional distribution detection apparatus 300 of the third embodiment, a minute magnetic two-dimensional distribution of pT or less can be detected. In addition, the influence of magnetic noise having a frequency away from the vibration frequency of the sample stage 8 can be suppressed. Moreover, the influence of external magnetic noise can be suppressed. Moreover, the influence of the magnetic noise which the vibrator 7 generate | occur | produces can be suppressed. Furthermore, the XYZ stage 5 becomes unnecessary.

Example 4
Two-dimensional scanning may be performed by fixing the sample S and moving the SQUID 1 side.

-Example 5
A bandpass filter whose center frequency is the vibration frequency of the sample stage 8 may be used instead of the lock-in amplifier 12.

  The micromagnetic two-dimensional distribution detection apparatus of the present invention can be used in the field of molecular biology such as immune reaction analysis using magnetic nanoparticles as an index, drug tests, and the like.

1 SQUID
DESCRIPTION OF SYMBOLS 2 Cryostat 3 Stand 4 Magnetization coil 5 XYZ stage 6 Rail 7 Exciter 8 Specimen base 9 Connecting member 10 Oscillator 11 SQUID drive circuit 12 Lock-in amplifier 13 Analysis apparatus 100-300 Micro magnetic two-dimensional distribution detection apparatus A Inspection surface A1- A9 Section S Sample

Claims (6)

A sample (S) having a SQUID (1), a magnetizing coil (4) mounted on the outer periphery of the tip of a cryostat (2) that accommodates the SQUID (1), and an inspection surface (A) is attached to the inspection surface ( A) a sample stage (8) held so as to face the SQUID (1), a vibration means (7) for vibrating the sample stage (8), and the sample stage with respect to the SQUID (1) Scanning means (5) for relatively moving (8) two-dimensionally in the direction of the inspection surface (A), and an electronic circuit (10) for detecting a magnetic signal component of the vibration frequency via the SQUID (1). , 11, 12) and an analysis device (13). The analysis device (13) applies a pulse current to the magnetization coil (4) and applies a magnetic field to the sample (S) (SQUID ( 1) to detect the magnetic signal component of the excitation frequency via In the state where no magnetic field is applied to the sample (S), the magnetic signal component of the excitation frequency is detected via the SQUID (1), and the difference is obtained repeatedly at each detection point d (x, y). A two-dimensional distribution of magnetic relaxation is obtained based on the result of the measurement, or a pulse current is applied to the magnetizing coil (4) to apply a magnetic field to the sample (S), and then no magnetic field is applied to the sample (S). Whether to detect the magnetic signal component of the excitation frequency via the SQUID (1) at each detection point d (x, y) and whether to obtain a two-dimensional distribution of residual magnetism based on the obtained result A micro magnetic two-dimensional distribution detection device (100) characterized by performing at least one of A sample having a plurality of one-dimensionally arranged SQUIDs (1), a magnetizing coil (4) mounted on the outer periphery of the tip of a cryostat (2) that accommodates the SQUID (1), and a test surface (A) ( S) holds the inspection surface (A) so that the inspection surface (A) faces the SQUID (1), vibration means (7) for vibrating the sample table (8), and the SQUID (1) Scanning means (5) capable of relatively moving the sample stage (8) in the direction of the inspection surface (A) and at least in the direction orthogonal to the arrangement of the SQUID (1), and the SQUID (1) An electronic circuit (10, 11, 12) for detecting a magnetic signal component of the frequency of vibration via an analysis device (13), and the analysis device (13) is connected to the magnetizing coil (4). Apply a pulse current to apply magnetic field to the sample (S) In this state, the magnetic signal component of the excitation frequency is detected via the SQUID (1), and then the magnetic signal component of the excitation frequency is detected via the SQUID (1) without applying a magnetic field to the sample (S). Obtaining the difference is repeated at each detection point d (x, y), and a two-dimensional distribution of magnetic relaxation is obtained based on the obtained result, or a pulse current is passed through the magnetizing coil (4). The magnetic signal component of the excitation frequency is detected via the SQUID (1) in a state where the magnetic field is applied to the sample (S) and then the magnetic field is not applied to the sample (S). ), And a two-dimensional distribution of residual magnetism is obtained based on the obtained result, or at least one of the two is performed . 3. The micromagnetic two-dimensional distribution detection apparatus according to claim 1, wherein the SQUID (1), the sample stage (8), the excitation means (7), and the scanning means (5) are magnetically shielded. A micromagnetic two-dimensional distribution detection device characterized by being housed in a box (31). A sample having a plurality of SQUIDs (1) arranged two-dimensionally, a magnetizing coil (4) mounted on the outer periphery of the tip of a cryostat (2) that accommodates the SQUID (1), and an inspection surface (A) ( S) holds the inspection surface (A) so that the inspection surface (A) faces the SQUID (1), vibration means (7) for vibrating the sample table (8), and the SQUID (1) ) Through the electronic circuit (10, 11, 12) for detecting the magnetic signal component of the frequency of the vibration and the analysis device (13), and the analysis device (13) includes the magnetizing coil (4). The magnetic signal component of the excitation frequency is detected via the SQUID (1) in a state where a pulse current is applied to the sample (S) and then the SQUID (1) is applied in the state where no magnetic field is applied to the sample (S). ) To detect the magnetic signal component of the excitation frequency Then, obtaining the difference is repeated at each detection point d (x, y), and a two-dimensional distribution of magnetic relaxation is obtained based on the obtained result, or a pulse current is applied to the magnetizing coil (4). The magnetic signal component of the excitation frequency is detected via the SQUID (1) without applying a magnetic field to the sample (S) and then applying a magnetic field to the sample (S). A micromagnetic two-dimensional distribution detection apparatus (300), characterized in that it comprises repeating the step y) and obtaining at least one of the two-dimensional distribution of remanence based on the obtained result.
5. The micromagnetic two-dimensional distribution detection device (300) according to claim 4, wherein the SQUID (1), the sample stage (8), and the excitation means (7) are accommodated in a magnetic shielding box (31). A micromagnetic two-dimensional distribution detector (300) characterized by the following.
6. The micromagnetic two-dimensional distribution detection apparatus according to claim 1, wherein the excitation means (7) is housed in a dedicated magnetic shielding box (32). Distribution detector.

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