JP2015004580A - Microparticle and substance detection device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To detect a small amount of detecting object in an inspection solution in which the detecting object and other various materials are mixed.SOLUTION: A microparticle (4a) includes: a selection bond part (41) capable of selectively combining with a detecting object contained in an inspection solution; and a torque application part (42) for applying torque to the microparticle (4a) by receiving force of a field from a magnetic field applied to the inspection solution. The selection bond part and the torque application part are placed at different positions in a surface of the microparticle (4a).

Description

  The present invention relates to microparticles that generate near-field light from the surface when irradiated with light of a specific wavelength, and a substance detection device using the microparticles.

  In recent years, there has been a growing need for methods and devices for detecting trace amounts of harmful components in water and food because of increased awareness of water and food safety and improved hygiene in emerging countries. In particular, among harmful components, there are bacteria that cause lesions in the human body even when about 100 oral intakes are made. For this reason, in the detection methods and apparatuses described above, ultrasensitive detection on the order of ng (nanogram) and pg (picogram) is required.

  In the ultra-sensitive detection as described above, attempts have been made to use the light absorption wavelength peak shift phenomenon caused by the plasmon amplification phenomenon. For example, the following Non-Patent Document 1 uses a phenomenon in which a metal mesh is used as a kind of bandpass filter, and the surface plasmon generation state of the metal mesh is greatly influenced by the refractive index of a substance attached to the surface. , A technique for detecting a minute amount of protein of 500 pg is disclosed. Hereinafter, with reference to FIG. 13, the prior art including Non-Patent Document 1 will be described.

  FIG. 13 is a cross-sectional view showing the occurrence of surface plasmons in the metal mesh 54. A region 543 in FIG. 13 indicates a region (near-field light generation region 543) where near-field light is generated by the generation of surface plasmons. Generally, when a metal nanoparticle is irradiated with light of a specific wavelength, near-field light is generated at the site due to the generation of surface plasmon, which is observed as an increase in the light absorption rate of the metal nanoparticle. The For example, an aqueous colloidal gold solution having a particle size of about 50 nm shows a strong absorption peak around 516 nm.

  In the technique of Non-Patent Document 1, since the plasmon generation state described above depends on the refractive index distribution in the vicinity of the metal mesh 54, a substance having a refractive index different from that of water or the like as a medium is provided in the near-field light generation region 543. In the presence of, a phenomenon in which the wavelength of the absorption peak shifts is observed. That is, by observing the shift of the wavelength of the absorption peak, it can be determined whether or not a substance having a different refractive index exists in the vicinity of the metal mesh 54. In the case of the above-described gold colloid, this absorption peak is observed as an absorption amount that reaches about 10% even at a very low concentration of about 10 to the 10th power per ml. Is possible.

  Furthermore, as employed in the technique of Non-Patent Document 1, an antigen-antibody reaction is used to detect a trace amount of various bacteria. Specifically, the antibody 5411 is modified with a metal mesh, and the property that the detection target 5412 that is an antigen selectively binds to the antibody 5411 is used. In this way, water or food to be inspected is brought into contact with the metal mesh 54, and after the detection target 5412 as an antigen is bound to the antibody 5411 on the metal mesh 54, the substance 5413 other than the detection target 5412 bound by washing. If only the detection object 5412 is washed away, only the detection object 5412 remains in the near-field light generation region 543 of the metal mesh 54, so that a very small amount of the detection object 5412 can be detected.

Yoshida S., Suizu K., Kato E., Nakagomi Y., Ogawa Y., and Kawase K .: A high-sensitivity terahertz sensing method using a metallic mesh with unique transmission properties, Journal of Molecular Spectroscopy, 256 (1) , 146-151 (2009).

  However, the conventional detection method using the plasmon amplification phenomenon as shown in Non-Patent Document 1 detects only a change in the optical constant regardless of whether or not the metal mesh and the substance selectively bind to each other. Therefore, there is a problem that it is vulnerable to noise.

  More specifically, the test object such as water or food contains much more protein than the detection target 5412, and it is not realistic to remove these completely by washing. For example, due to natural adsorption due to hydrogen bonding or intermolecular force, the substance 5413 that does not cause binding to the antibody remains attached to the metal mesh or the like. As described above, since the plasmon amplification phenomenon changes depending only on the change in refractive index, noise is generated by such a remaining substance (substance 5413) other than the detection target 5412, and the detection of the detection target is obstructed. Will be.

  To summarize the above, in the detection of germs in water, foods, etc., there is a problem that noise caused by other substances present in large quantities hinders detection and is substantially impossible to detect.

  The present invention has been made in view of the above problems, and its object is to make a minute amount capable of detecting a very small amount of a detection target in a test solution in which the detection target and various other substances are mixed. To provide particles and the like.

  In order to solve the above-described problem, the microparticle according to one embodiment of the present invention is dispersed in a test solution including at least one detection target, and is irradiated with light of a specific wavelength from a part of the surface. Conductive microparticles that generate near-field light, a selective coupling portion that has an ability to selectively bind to the detection target contained in the test solution, and a magnetic field applied to the test solution from the magnetic field. A torque application unit that receives torque and applies torque to the microparticles, and each of the selective coupling unit and the torque application unit is disposed at a different position on the surface of the microparticles.

  According to one aspect of the present invention, there is an effect that it is possible to detect a trace amount of a detection target in a test solution in which the detection target and various other substances are mixed.

It is a figure which shows schematic structure of the substance detection apparatus and measurement cell which concern on Embodiment 1 of this invention, (a) is a block diagram which shows schematic structure of the said substance detection apparatus, (b) is a detection target object The external appearance of the measurement cell containing the test solution containing is shown. It is the schematic which shows an example of the microparticle which concerns on Embodiment 2 of this invention. It is the schematic which shows another example of the microparticle which concerns on Embodiment 2 of this invention. It is the schematic which shows another example of the microparticle which concerns on Embodiment 2 of this invention. In the microparticle concerning Embodiment 2 of this invention, it is the schematic which shows the perturbation when an external magnetic field is applied, (a) shows the state of the microparticle before an external magnetic field is applied, (b ) Shows the state of the microparticles after the external magnetic field is applied. It is a spectrum which shows the relationship between the wavelength and the transmittance | permeability for demonstrating the concept of the signal processing in the substance detection apparatus which concerns on Embodiment 1-3 of this invention, (a) is an ideal spectrum obtained in a prior art (B) shows the actual spectrum obtained in the prior art, and (c) shows the spectrum obtained by the embodiment of the present invention. In another example of the microparticle which concerns on Embodiment 2 of this invention, it is the schematic which shows the operation | movement when an external magnetic field is applied, (a) shows the state of the microparticle before an external magnetic field is applied. (B) shows the state of the microparticles after the external magnetic field is applied. It is the schematic which shows an example of the microparticle which concerns on Embodiment 3 of this invention. It is a figure which shows schematic structure of the substance detection apparatus which concerns on Embodiment 4 of this invention. It is the schematic which shows an example of the microparticle which concerns on Embodiment 5 of this invention. It is the schematic which shows an example of the microparticle which concerns on Embodiment 6 of this invention. It is a figure which shows schematic structure of the substance detection apparatus which concerns on Embodiment 7 of this invention. It is sectional drawing which shows the generation | occurrence | production state of the surface plasmon in the metal mesh of a prior art.

  The embodiment of the present invention will be described below with reference to FIGS. Descriptions of configurations other than those described in the following specific embodiments may be omitted as necessary, but are the same as those configurations when described in other embodiments. For convenience of explanation, members having the same functions as those shown in each embodiment are given the same reference numerals, and the explanation thereof is omitted as appropriate. Furthermore, the shape of the configuration described in each drawing and the dimensions such as length, size, and width do not reflect the actual shape and dimensions, but are appropriately changed for clarity and simplification of the drawings. doing.

[Substance Detection Apparatus of Embodiment 1 and Fine Particles of Embodiment 2]
Hereinafter, based on FIGS. 1-7, the substance detection apparatus 1a which concerns on Embodiment 1 of this invention, and the microparticles 4a-4e which concern on Embodiment 2 are demonstrated in detail. Hereinafter, for convenience, the substance detection apparatus 1a and the substance detection apparatus 1b and the substance detection apparatus 1c described in Embodiments 4 and 7 to be described later may be collectively referred to as “substance detection apparatus 1”. . Similarly, the microparticles 4a to 4e according to the second embodiment, and the microparticle 4f, the microparticle 4g, and the microparticle 4h according to the third, fifth, and sixth embodiments described below are collectively referred to as “microparticle 4”. May be called.

<Detection of a very small amount of detection target>
First, microparticles according to an embodiment of the present invention will be described with reference to FIGS. 1 and 2. FIG. 1 is a diagram illustrating a schematic configuration of a substance detection device and a measurement cell according to Embodiment 1 of the present invention, and FIG. 1A is a block diagram illustrating a schematic configuration of the substance detection device. 1 (b) shows the appearance of a measurement cell containing a test solution containing a detection target.
FIG. 2 is a schematic diagram showing a schematic configuration of the microparticle 4a. FIG. 2 is a schematic view showing an example of microparticles according to Embodiment 2 of the present invention. As shown in FIG. 2, the microparticle 4 a includes a selective coupling portion 41 and a torque applying portion 42.

  As shown in FIG. 1 (b), the microparticles 4a are dispersed in a test solution 3 containing at least one detection object, and irradiated with light of a specific wavelength as shown in FIGS. 1 (a) and 2. As a result, the conductive fine particles generate near-field light from a part of the surface. The region where the near-field light is generated on a part of the surface of the microparticle 4a is hereinafter referred to as “near-field light generation region” (for example, see the near-field light generation region 43 shown in FIG. 2).

  The selective combining unit 41 is a part having an ability to selectively combine with a detection target contained in the test solution 3.

  The torque applying unit 42 is a part that receives a field force from the magnetic field applied to the test solution 3 and applies torque to the microparticles 4. Each of the selective coupling portion 41 and the torque applying portion 42 is disposed at a different position on the surface of the microparticle 4. The details of the selective coupling unit 41 and the torque applying unit 42 will be described later.

  Due to the configuration of the microparticles 4 described above, the torque applying unit 42 receives a field force from the magnetic field applied to the test solution 3 and applies torque to the microparticles 4 themselves. Here, the “torque” is a moment of force around the center of gravity that works around the center of gravity of the microparticles 4a. For this reason, if a perturbation due to a magnetic field is applied to the test solution 3, the microparticles 4 included in the test solution 3 are perturbed by the above torque. Note that “perturbation of the magnetic field” means fluctuation of the applied magnetic field, and “perturbation of the microparticle” means movement of the microparticle that occurs in synchronization with the perturbation of the applied magnetic field. To do. In the present embodiment, the “perturbation of microparticles” is a reciprocating rotational motion of microparticles. However, in other embodiments, the present invention is not limited to this, and “perturbation of microparticles” may include rotational motion of microparticles.

  Such a perturbation causes a movement such that the selective coupling portion 41 enters and exits the near-field light generation region 43, which is a region where the near-field light is generated, when viewed from the observer on the microparticle 4 (actually Is considered that the relative position of the near-field light generating region 43 in the microparticle 4a with respect to the microparticle 4a changes with the movement of the microparticle 4a). Thereby, when the detection target object is couple | bonded with the selective coupling | bond part 41, the generation | occurrence | production state of near-field light changes synchronizing with the said perturbation. On the other hand, since the impurities in the near-field light generating region 43 do not selectively bind to the selective coupling portion 41 (the binding force is weak), the impurities do not enter or leave the near-field light generating region 43 according to the perturbation. That is, the generation state of near-field light (due to the detection target) does not change according to the perturbation. For example, by using the substance detection device 1 to be described later, by extracting and analyzing the fluctuation component (fluctuation component signal) caused by the change in the generation state of the near-field light, it is possible to detect the detection target and various other objects. In the test solution 3 in which substances are mixed, it is possible to detect a trace amount of a detection object.

<Configuration of microparticle 4>
Subsequently, the configuration of the microparticle 4 will be described in more detail with reference to FIGS. The microparticles 4 are conductive microparticles that emit near-field light from a part of the surface when irradiated with light of a specific wavelength. In other words, the microparticles 4 generate surface plasmons when irradiated with light of a specific wavelength. In general, when the conductive microparticles 4 receive light of a specific wavelength, near-field light is generated from the entire surface of the microparticles 4. On the other hand, when the microparticles 4a are irradiated with polarized light in a specific direction, near-field light is emitted only in the same direction as the polarization direction. Specifically, when the polarization direction is the vertical direction with respect to the paper surface of FIG. 2, near-field light is generated only in the near-field light generation regions 43 located above and below the microparticle 4 as shown in FIG. To do.

  Next, as shown in the figure, the microparticles 4 a are obtained by coating polystyrene nuclei 401 with a gold film 402. Further, the fine particle 4 a includes a selective coupling portion 41 and a torque applying portion 42 on the surface of the gold film 402. As shown in the figure, the selective coupling portion 41 and the torque applying portion 42 are located with respect to the position where the selective coupling portion 41 is arranged with respect to the center O of the microparticle 4a and the center O of the microparticle 4a. It arrange | positions so that angle (theta) made with the position where the torque provision part 42 is distribute | arranged may become a substantially right angle. More specifically, the selective coupling unit 41 and the torque applying unit 42 include a first straight line connecting the center O of the microparticle 4a and the center C1 of the selective coupling unit 41, the center O of the microparticle 4a, and the torque applying unit 42. Is arranged such that the angle θ formed with the second straight line connecting the centers C2 is greater than 85 degrees and less than 95 degrees. Here, the center C1 is the center of the selective coupling portion 41 when viewed from the upper side with respect to the paper surface, and the center C2 is the center of the torque applying portion 42 when viewed from the right side with respect to the paper surface. It is. Thereby, the positional relationship between the torque applying part 42 and the selective coupling part 41 with respect to the fine particles 4a is substantially perpendicular to the center of the fine particles 4a. Thereby, the torque provided to the microparticles 4a can be maximized.

(Selective coupling unit 41)
The selective combining unit 41 has an ability to selectively combine with a detection target in the test solution 3 described later. Specifically, the selective binding portion 41 of the microparticle 4a shown in FIG. 2 is obtained by arranging a plurality of E. coli antibodies 411a of the same type on a gold film 402. For example, E. coli antibody 411a has the ability to selectively bind to E. coli, which is an antigen. That is, as will be described later, by dispersing the microparticles 4a in the test solution 3, it is possible to detect a small amount of E. coli from the test solution 3 in which E. coli to be detected and various other substances are mixed. Become.

  The selective binding portion 41 is not limited to an antibody, and may be a single strand of nucleic acid (hereinafter referred to as “nucleic acid single chain”). The nucleic acid single strand may be a single strand of DNA (deoxyribonucleic acid) or a single strand of RNA (ribonucleic acid).

About the form of the selective coupling | bond part 41, each of the following forms (a)-(f) can mainly be illustrated. That is, the selective binding unit 41 has at least one kind of antibody, at least one kind of nucleic acid single chain, or a combination of at least one antibody and at least one nucleic acid single chain. Also good.
(A) a form having only a single (and therefore one type) antibody (or nucleic acid single chain) in a single microparticle;
(B) a form having a plurality of the same type of antibody (or nucleic acid single chain) in a single microparticle;
(C) a form having a combination of different types of antibodies in a single microparticle,
(D) a form having a combination of different types of nucleic acid single strands in a single microparticle,
(E) a form having a combination of at least one antibody and at least one nucleic acid single chain in a single microparticle;
(F) A form in which each of a plurality of microparticles has a separate antibody (or nucleic acid single chain).

  For example, the microparticle 4a shown in FIG. 2 is an example of the form (b), and the selective binding portion 41 has a plurality of the same type of antibodies 411a.

  Next, the microparticles 4a to 4c shown in FIG. 3 are an example of the above (f) form. In addition to the microparticles 4a, the microparticles 4b having a plurality of types of antibodies 411b different from the antibodies 411a, the same type A microparticle 4c having a single nucleic acid strand 411c is shown.

  Furthermore, the microparticle 4d shown in FIG. 4 is an example of the form (e) described above, and the selective binding portion 41 has an antibody 411a, an antibody 411b, and a nucleic acid single chain 411c.

(Torque imparting section 42)
Next, the torque application unit 42 applies a field force from the magnetic field applied to the test solution 3 and applies torque to the microparticles 4a. That is, perturbation is given to the fine particles 4a by the torque applying unit 42 giving torque to the fine particles 4a.

  In the present embodiment, the torque applying unit 42 is a ferromagnetic perpendicular magnetization film using cobalt platinum, and the surface of the perpendicular magnetization film (the surface opposite to the microparticle 4a side of the selective coupling portion 42). Are all the same in the plurality of microparticles 4 a included in the test solution 3. As a result, the microparticles 4a can be easily perturbed, and repulsion by the same polarity can be used to avoid aggregation of the microparticles 4a.

The magnetic field applied to the test solution 3 is a variable magnetic field having a specific frequency and changing in a sinusoidal shape. When the torque generated by the fluctuating magnetic field is applied to the microparticle 4a, the microparticle 4a performs perturbation synchronized with the specific frequency. Details of the substance detection method using this perturbation will be described later.
<Effect of microparticles 4>
As will be described later, the torque applying unit 42 of the microparticles 4 receives a field force from a magnetic field applied to the test solution 3 and applies torque to the microparticles 4 themselves. For this reason, some of the microparticles 4 perform reciprocating rotational motion (or rotational motion described later). For this reason, when the test solution is irradiated with light of a specific wavelength that generates near-field light in a part of the microparticles 4 and a perturbation due to a magnetic field is applied to the test solution 3, the above-described movement occurs. From the observer on the microparticle 4, the movement of the selective coupling portion 41 moves in and out of the near-field light generation region 43 in which a part of the near-field light of the microparticle 4 is generated (actually). It is considered that the relative position of the near-field light generating region 43 in the microparticle 4 with respect to the microparticle 4 changes with the movement of the microparticle 4).

  However, substances other than the detection target (for example, Escherichia coli) that spontaneously adsorbed or accidentally existed (for example, impurities having a poor ability to bind to the selective binding portion) are more likely to react with the selective binding portion 41 than the detection target. Since the coupling is weak, the relative position with respect to the microparticle 4 is hardly changed, and the relative position of the microparticle 4 with respect to the near-field light generation region 43 is not significantly changed. Therefore, when the perturbation due to the magnetic field is applied to the test solution 3 as described above, and only the detection target coupled to the selective coupling unit 41 causes the movement to enter and exit the near-field light generation region 43, the test solution 3 Due to the difference in refractive index between the solvent in the medium and the object to be detected, the position of the absorption peak spectroscopically measured varies according to the perturbation of the magnetic field. The fluctuation in the position of the absorption peak is a fluctuation component caused only by the detection target coupled to the selective coupling unit 41 in the spectroscopic measurement result.

  For this reason, for example, if the substance detection apparatus 1a described later is used, an inspection in which the detection target and various other substances are mixed by extracting and analyzing such a fluctuation component from the result of the spectroscopic measurement. It is possible to detect a very small amount of the detection target in the solution.

<Basic configuration of the substance detection apparatus 1a>
Next, the basic configuration of the substance detection device 1a will be described with reference to FIG.

  In addition, each form of the microparticles and the substance detection apparatus described above or described below is an example of an aspect that directly shows a difference of the present invention with respect to an existing technology.

  Further, the position between the generation position of near-field light (near-field light generation area) due to plasmon resonance and the position where the selectively adsorbed detection target exists (selective coupling part), which will be described in detail below, The main component of the present invention, that is, detection using a change in the relationship, is a discovery found for the first time by the present inventors, and the present invention can be embodied as long as the main component of the present invention is provided. It goes without saying that the form to be converted is not limited to the above-described embodiment or the embodiment described below. Therefore, in the following description, in addition to the main constituent elements of the present invention, a spectroscopic measurement system (see a spectral characteristic measurement unit 7 described later) and a lock-in amplifier (see a fluctuation component extraction unit 6 described later) of the present invention. Components that have little relation to the essence, and those skilled in the art treat them as black boxes for general-purpose measuring instruments whose properties and usage are established. Shall be omitted.

  Fig.1 (a) is a figure which shows schematic structure of the substance detection apparatus 1a. The substance detection device 1 a includes at least a measurement cell 2, a coil 5, a coil driver 51, a lock-in amplifier 6, a spectral characteristic measurement unit 7, a signal processing unit 14, and a coil driver 51.

(Spectral characteristic measurement unit 7)
The spectral characteristic measuring unit 7 outputs the detection result of the spectral characteristic of the light that has passed through the test solution 3 as a detection signal. As shown in FIG. 1A, the spectral characteristic measuring unit 7 includes at least a light emitting unit 11, a light receiving unit 12, a polarizing plate 111, and a spectroscopic measurement device control unit 10. Further, the spectral characteristic measurement unit 7 measures the amount of light absorption in the substance existing in the optical path 13 between the light emitting unit 11 and the light receiving unit 12 for each wavelength of the light. The light emitting unit 11 irradiates light in the wavelength range set in advance toward the light receiving unit 12 while changing from a short wavelength side to a long wavelength side, for example. In addition, the light receiving unit 12 detects the amount of received light of the transmitted light and inputs the detected amount of received light to the lock-in amplifier 6 as a detection signal. The amount of received light reflects the amount of absorption (absorption rate) of light passing through the optical path 13 in the test solution 3. Here, the absorptance is a value (ratio) represented by a ratio between the intensity of incident light that is light incident on a substance and the intensity of transmitted light that is light transmitted through the substance.

  Further, a polarizing plate 111 is disposed immediately after the light emitting unit 11. When the light from the light emitting unit 11 passes through the polarizing plate 111, for example, light whose polarization direction 132 is the vertical direction shown in FIG. 3 described later enters the test solution 3 (irradiates the detection target substance). The Rukoto.

  In the present invention, it is sufficient that only the measurement function of the spectral characteristic measurement unit can be used. Differences in the measurement method of the spectral characteristic measurement unit do not affect the implementation of the present invention. Therefore, the details of the measurement method and the like are not described.

(Measurement cell 2)
FIG. 1B is a schematic diagram showing details of the measurement cell 2. The measurement cell 2 is a cell for placing a substance on the optical path 13. In the present embodiment, the measurement cell 2 in which the test solution 3 is placed is disposed between the polarizing plate 111 and the light receiving unit 12. In the present embodiment, the test solution 3 is assumed to be food or river water. However, the test solution 3 is not limited to the above example. Further, the above-described microparticles 4 (for example, microparticles 4a) are dispersed in the test solution 3. Furthermore, in order to improve the dispersibility of the microparticles 4, a dispersant (not shown) may be added to the test solution 3.

(Coil 5 and coil driver 51)
The coil (magnetic field application unit) 5 applies a magnetic field to the test solution 3 by a current flowing through the coil 5. For example, in this embodiment, it is assumed that a 100 Hz sine wave current flows through the coil 5 by a coil driver 51 described later. As shown in FIG. 1A, the coil 5 is in contact with the measurement cell 2. Here, when a 100 Hz sinusoidal current flows through the coil 5, a magnetic field that perturbs at a frequency of 100 Hz is applied to the test solution 3 in the measurement cell 2.

  The coil driver 51 allows current to flow through the coil 5. Specifically, the coil driver 51 applies a voltage to the coil 5, thereby causing a current corresponding to the applied voltage to flow through the coil 5. In addition, the coil driver 51 supplies a signal for perturbing the magnetic field, specifically, a signal for causing a 100 Hz sinusoidal current to flow through the coil 5 (hereinafter referred to as a perturbation signal) to the lock-in amplifier 6 described later. input.

(Lock-in amplifier 6)
The lock-in amplifier (variation component extraction unit) 6 detects and amplifies a specific signal. Specifically, the lock-in amplifier 6 receives the detection signal from the light receiving unit 12 and the perturbation signal from the coil driver 51 as a reference signal. The lock-in amplifier 6 generates a near-field signal generated by the signal synchronized with the perturbation signal from the detection signal, that is, the detection object (E. coli) coupled to the selective coupling unit 41 enters and exits the near-field light generation region 43. A signal resulting from a change in the light generation state (hereinafter referred to as a fluctuation component signal) is extracted and output and input to the signal processing unit 14.

  In the present embodiment, the lock-in amplifier is used as an example of the fluctuation component extraction unit. However, the embodiment embodying the present invention is not limited to this. For example, the reference signal from the coil driver 51 is directly input to the signal processing unit 14 together with the detection signal from the light receiving unit 12 (however, the signal after A / D conversion). The fluctuation component signal (or fluctuation component information) may be extracted by processing.

(Signal processing unit 14)
In this embodiment, the signal processing unit (detection processing unit) 14 determines the presence / absence of a detection target or calculates the concentration of the detection target based on the result of the above processing. For example, when the fluctuation component signal is input, the signal processing unit 14 detects the shift amount of the peak of the absorption rate (hereinafter referred to as an absorption peak) using a calibration curve built in advance. It is converted to the concentration of E. coli. Note that the processing performed by the signal processing unit 14 described above is an example, and various types of signal processing may be performed according to the purpose.

  In the present invention, a so-called substance detection system in which a plurality of devices having the functions of the respective members described above are combined is also included in the technical scope.

<Details of substance detection method>
Next, details of the substance detection method using the microparticles 4a will be described with reference to FIGS. FIG. 5 is a schematic diagram showing perturbation when an external magnetic field (magnetic field) is applied to the fine particles 4a. FIG. 5 shows a simulation result using electromagnetic field analysis software.

  As shown in FIG. 5A, for example, when polarized light 131 whose polarization direction 132 is vertical with respect to the paper surface enters the microparticle 4a, the same direction as the polarization direction 132 (see FIG. 5) due to plasmon resonance. 5 (a), the near-field light is generated in the near-field light generation region 43).

  Here, if the selective binding part 41 combined with the detection target 412 (E. coli) is present in the near-field light generation region 43, the position of the absorption peak wavelength caused by the microparticles 4a is shifted to the long wavelength side. However, even when the impurity 413 is naturally adsorbed on the selective coupling portion 41 or when the impurity 413 is accidentally present in the near-field light generation region 43, the position of the absorption peak wavelength caused by the microparticle 4a is also on the long wavelength side. It will shift to.

  Therefore, as shown in FIG. 3B, an external magnetic field 44 whose direction is parallel to the polarization direction 132 and perpendicular to the incident direction of the polarization 131 is applied to the test solution 3. As shown in FIG. 3B, the external magnetic field 44 perturbs at a frequency of 100 Hz in the vertical direction of FIG. Thereby, the microparticle 4a performs perturbation (reciprocating rotational motion) synchronized with the perturbation of the frequency of 100 Hz. As a result, the relative position of the near-field light generating region 43 with respect to the microparticles 4a changes with the perturbation of the microparticles 4a. That is, when the perturbation is viewed from an observer on the microparticle 4a, a part of the microparticle 4a dispersed in the test solution 3 enters and exits the near-field light generation region 43 and the selective coupling portion 41 enters and exits. Cause exercise. Note that the fluctuation direction of the external magnetic field is not limited to the fluctuation direction of the external magnetic field 44 described above. As in a modification described later, an external magnetic field whose variation direction is parallel to the incident direction of the polarized light 131 may be applied according to the positional relationship between the selective coupling unit 41 and the torque applying unit 42, for example.

  On the other hand, the impurity 413 naturally adsorbed to the selective coupling portion 41 is separated from the selective coupling portion 41 by perturbation because the binding to the selective coupling portion 41 is weak. For this reason, the impurities 413 naturally adsorbed on the selective coupling portion 41 and the impurities 413 accidentally present in the near-field light generation region 43 hardly change the relative position with respect to the fine particles. In other words, the impurity 413 does not enter and exit the near-field light generating region 43 together with the selective coupling portion 41.

  As described above, when the external magnetic field 44 is applied to the test solution 3, perturbation of the microparticles 4a occurs. Thereby, the detection object 412 coupled to the selective coupling unit 41 enters and exits the near-field light generation region 43, unlike the impurity 413. When the light receiving unit 12 detects light transmitted through the test solution 3, a detection signal is output in which the position of the absorption peak wavelength changes in synchronization with a specific frequency (100 Hz in the present embodiment). This change in the position of the absorption peak wavelength occurs when the selective coupling unit 41 enters and exits the near-field light generation region 43 due to perturbation of the microparticles 4a at a specific frequency, and the solvent and the detection target in the test solution 3 This is due to the difference in refractive index from 412 (E. coli).

  When the detection signal is input to the lock-in amplifier 6 using the perturbation signal as a reference signal, a component synchronized with the perturbation signal from the detection signal, that is, the detection target 412 (E. coli) coupled to the selective coupling unit 41 The fluctuation component signal to be extracted is extracted.

  FIG. 6 is a spectrum showing the concept of the above signal processing. Specifically, in a substance detection apparatus using plasmon resonance, ideally a spectrum as shown in FIG. 6 (a) is detected. As shown in FIG. 6A, when a shift to the long wavelength side of the absorption peak due to the microparticles 4a is observed, it can be identified that Escherichia coli is bound to the selective binding portion 41. However, in the prior art, a spectrum as shown in FIG. 6B is detected due to the presence of impurities. This makes it difficult to determine the wavelength of the absorption peak. Therefore, by extracting only the component (variation component signal) that changes in synchronization with the perturbation by the substance detection method described above, a spectrum as shown in FIG. 6C is detected. The signal processing unit 14 processes the signal of this spectrum, and converts the shift amount of the absorption peak into the concentration of the detection target, whereby the detection target with reduced noise can be quantified.

<Modification>
In the form described above, the fine particles 4a are arranged as shown in FIG. 2, and the selective coupling portion 41 and the torque applying portion 42 are arranged with the selective coupling portions 41 with respect to the center O of the fine particles 4a as shown in FIG. The angle θ between the position where the torque is applied and the position where the torque applying portion 42 is disposed with respect to the center O of the microparticles 4a is arranged to be substantially perpendicular. This is because the above arrangement is an arrangement that maximizes the perturbation in the microparticles 4a.

  However, in order to solve the problem of the present invention, it is sufficient that the microparticle 4a perturbs the detection target 412 such as E. coli bound to the selective binding unit 41 so as to enter and exit the near-field light generation region 43. It is.

  Therefore, the microparticles according to the embodiment of the present invention may be microparticles 4e arranged so that the selective coupling portion 41 and the torque applying portion 42 face each other as shown in FIG. In this case, in order to give the fine particles 4e a torque such that the normal line of the torque applying unit 42 and the direction of the external magnetic field are parallel to each other, the coil 5 has the right and left sides in FIG. An external magnetic field 45 that perturbs in the direction is applied to the test solution 3. The magnitude of the torque applied to the microparticles 4e is smaller than the magnitude of the torque applied to the microparticles 4a, but perturbs such that the selective coupling portion 41 enters and exits the near-field light generation region 43. It is large enough for this purpose.

Note that the positional relationship between the selective coupling unit 41 and the torque applying unit 42 is not limited to the above-described positional relationship. That is, any positional relationship may be used as long as the selective coupling unit 41 can perturb the microparticles 4 so as to enter and exit the near-field light generation region 43. More specifically, any arrangement may be employed as long as the selective coupling portion 41 and the torque applying portion 42 are not arranged so as to exist at the same position.
[Embodiment 3]
Another embodiment of the present invention will be described below with reference to FIG. FIG. 8 is a schematic view showing an example of microparticles according to Embodiment 3 of the present invention.

  In the fine particles 4a to 4e of the second embodiment described above, the torque application unit 42 is a ferromagnetic perpendicular magnetization film using cobalt platinum. In the present embodiment, the torque application part 42 is different from the fine particles of the second embodiment described above in that it is a ferromagnetic in-plane magnetization film.

  That is, the torque application unit 42 may be any device that rotates the microparticles 4 around the center of gravity of the microparticles according to the external magnetic field. For example, in the embodiment shown in FIG. 8, a ferromagnetic in-plane magnetization film is used as the torque applying unit 642. However, in this case, in order to prevent the aggregation of the microparticles 4f, it is preferable to charge the surface of the microparticles 4f to the same polarity.

[Embodiment 4]
The following will describe still another embodiment of the present invention with reference to FIG. FIG. 9 is a diagram showing a schematic configuration of a substance detection apparatus according to Embodiment 4 of the present invention.

  In Embodiment 1 described above, the fluctuation direction of the external magnetic field is fixed in the vertical direction in FIG. 5 or in the horizontal direction in FIG. In this case, the torque applied to the microparticles 4 gradually decreases because the normal of the torque applying unit 42 changes in parallel with the direction of the external magnetic field according to the perturbation of the microparticles 4. A secondary problem arises.

  In order to solve such a secondary problem, the substance detection device 1b of this embodiment is replaced with a coil driver 51 and a coil 5 in the substance detection device 1a described in Embodiment 1 as shown in FIG. , A coil driver 650, and a coil 651 and a coil 652. The coil 651 and the coil 652 are disposed so as to be in contact with the side surface of the measurement cell 2, and the contact positions thereof are different from each other.

The coil driver 650 applies different voltages to the coil 651 and the coil 652. As an example, in the present embodiment, the coil driver 650 applies a voltage _{VA represented} by the following (Equation 1) to the coil 651 with f ₀ as a frequency and t as a time.

V _A = V ₀ × sin (2π × f ₀ × t) (Formula 1)
The coil driver 650 applies a voltage V _{B represented} by the following (formula 2) to the coil 652.

V _B = V ₀ × cos (2π × f ₀ × t) (Formula 2)
As a result, a magnetic field corresponding to the voltage V _A is generated from the coil 651, and a magnetic field corresponding to the voltage V _B is generated from the coil 652. A synthetic magnetic field obtained by synthesizing these magnetic fields is applied to the test solution 3.

Here, the resultant magnetic field is a rotating magnetic field which rotates at the frequency f _0. Due to this rotating magnetic field, the microparticles 4 a rotate at the frequency f ₀ , and the selective coupling portion 41 enters and exits the near-field light generation region 43. Moreover, since both the synthetic magnetic field and the fine particles 4a rotate at the frequency f ₀ , the normal line of the torque applying unit 42 and the direction of the external magnetic field are prevented from being parallel, and ideally the torque applying unit It is possible to always keep the angle formed by the normal line 42 and the direction of the external magnetic field substantially at a right angle. Thereby, the fine particles 4a can always obtain a large torque as compared with the first embodiment, and as a result, the amplitude of the perturbation can be increased. This means that the arrangement of the detection object with respect to the near-field light generation region 43 changes more greatly, so that the intensity of the detection signal and the fluctuation component signal can be increased.

<Modification>
In the present embodiment, the configuration in which the external magnetic field that causes the microparticles 4a to rotate at a constant rate is applied to the test solution 3 has been described. However, the external magnetic field may cause reciprocal rotation.

Specifically, it is only necessary that the coil driver 650 applies voltages V _C and V _{D represented} by the following (Equation 3) and (Equation 4) to the coil 651 and the coil 652, respectively. In the following (Expression 3) and (Expression 4), φ ₀ is the vibration amplitude.
V _C = V ₀ × sin (φ ₀ × sin (2π × f ₀ × t)) (Formula 3)
V _D = V ₀ × cos (φ ₀ × sin (2π × f ₀ × t)) (Formula 4)
Thereby, the synthetic magnetic field applied to the test solution 3 becomes a reciprocating rotating magnetic field that reciprocally rotates at a vibration amplitude of φ ₀ and a frequency of f ₀ . By using this reciprocating rotating magnetic field, it is possible to obtain information in which the coupling strength between the detection object and the selective coupling unit 41 is reflected.

  The feature of the substance detection device 1b in the present embodiment is that a rotating synthetic magnetic field is applied to the test solution 3 and the microparticles 4 by voltages applied to a plurality of coils. That is, the voltage waveform for generating the synthetic magnetic field is not limited to the voltage waveforms shown in the above (Expression 1) to (Expression 4) as long as the combined magnetic field is rotated.

[Embodiment 5]
The following will describe still another embodiment of the present invention with reference to FIG. FIG. 10 is a schematic view showing an example of fine particles according to Embodiment 5 of the present invention.

  In the fine particles 4 according to Embodiments 2 and 3 described above, the torque applying unit 42 is a ferromagnetic magnetized film. For this reason, there is a concern (secondary problem) that the microparticles 4 are magnetized by the torque application unit 42 and the microparticles 4 aggregate in the test solution 3.

  In order to solve the above-mentioned secondary problem, the fine particles 4g of the present embodiment are fine particles using a conductive film as the torque application unit 742. The conductive film may be made of any material as long as it has conductivity, but in this embodiment, an aluminum film is used as an example. The gold film 402 and the torque applying unit 742 are insulated by an insulating film (not shown).

  Next, the principle that the fine particles 4g perturb by applying a magnetic field to the fine particles 4g using the torque applying unit 742 that is a conductive film will be described.

  When the rotating magnetic field shown in the second embodiment is applied to the test solution 3, an eddy current is generated in the torque applying unit 742, and an induced magnetic field is generated by the eddy current. As a result, torque in a direction following the rotating magnetic field is applied to the fine particles 4g, so that the fine particles 4g perturb. This phenomenon can be explained by the principle of Arago's disk.

  As described above, when the fine particles 4g perturb, the selective coupling unit 41 enters and exits the near-field light generation region 43, so that the detection target 412 coupled to the selective coupling unit 41 can be detected.

  Further, since the conductive film is used for the torque applying unit 742, the fine particles 4g are not magnetized. For this reason, a dispersion process using a dispersant and a process of charging the surface of the microparticle 4 with the same polarity charge are not required. Therefore, the structure is simplified and the number of processes in the manufacturing process is reduced, so that the manufacturing cost can be reduced.

[Embodiment 6]
The following will describe still another embodiment of the present invention with reference to FIG. FIG. 11 is a schematic view showing an example of microparticles according to Embodiment 6 of the present invention.

  The microparticles 4h of the present embodiment are microparticles using a superparamagnetic material as the torque applying unit 842. Here, the superparamagnetic material is a ferromagnetic material or a ferrimagnetic material that exhibits paramagnetism at room temperature. When a magnetic field is applied to a superparamagnetic material, it has a larger magnetic moment than a paramagnetic material. That is, by using the superparamagnetic material as the torque applying unit 842, a torque sufficient to perturb the fine particles 4h can be applied.

The superparamagnetic material may be made of any material as long as it satisfies the above-described magnetic properties, but in the present embodiment, Fe ₃ O ₄ nanoparticles are used as an example. Specifically, the torque applying unit 842 made of Fe ₃ O ₄ nanoparticles is bonded to the fine particles 4h. In order to form such a torque imparting portion 842, an ultrathin film of Fe ₃ O ₄ is partially formed on the surface of the microparticle 4h by using a method such as sputtering, and thereafter, a method such as annealing is used. By aggregation, Fe ₃ O ₄ nanoparticles may be formed from the ultrathin film.

  Next, the principle of perturbing the microparticles 4h by applying a magnetic field to the microparticles 4g using the torque applying unit 842 that is a superparamagnetic material will be described more specifically.

  By applying an external magnetic field to the test solution 3, the torque applying unit 842, that is, the fine particles 4 h are attracted to the magnetic field. This external magnetic field is an external magnetic field that fluctuates at a frequency of 100 Hz described in the first embodiment, for example. The external magnetic field is not limited to a magnetic field that perturbs at a frequency of 100 Hz. Here, since the torque provision part 842 is arrange | positioned asymmetrically with respect to the microparticle 4h, the microparticle 4h perturbs. Due to this perturbation, the selective coupling unit 41 enters and exits the near-field light generation region 43, so that the detection target 412 coupled to the selective coupling unit 41 can be detected.

  Further, since the fine particle 4h uses a superparamagnetic material as the torque applying unit 842, it is not magnetized unless an external magnetic field is applied. For this reason, a dispersion process using a dispersant and a process of charging the surface of the microparticle 4 with the same polarity charge are not required. Therefore, the structure is simplified and the number of processes in the manufacturing process is reduced, so that the manufacturing cost can be reduced.

[Embodiment 7]
The following will describe still another embodiment of the present invention with reference to FIG. FIG. 12 is a diagram showing a schematic configuration of a substance detection apparatus according to Embodiment 7 of the present invention.

  The substance detection apparatus 1c of this embodiment is provided with two coils similarly to the substance detection apparatus 1b of Embodiment 2 mentioned above. However, the substance detection device 1c includes a coil 951 disposed above the test solution 3, instead of the coil 651 disposed at a position in contact with the side surface of the measurement cell 2.

  Below, the substance detection method in this embodiment is demonstrated. In the present embodiment, the microparticles 4a are used as an example.

  First, a magnetic field is applied to the test solution 3 by the coil 951. This magnetic field may be a magnetic field controlled so that the fine particles 4a are attracted to the coil 951. Thereby, the fine particles 4 a dispersed in the test solution 3 are attracted to the coil 951, but cannot be separated from the test solution 3 due to the influence of the surface tension of the test solution 3. As a result, the fine particles 4 a are concentrated on the interface of the test solution 3.

  Subsequently, a magnetic field that perturbs the microparticles 4 a is applied to the test solution 3 using at least one of the coil 951 and the coil 652. For example, the magnetic field that perturbs at the specific frequency described in the first embodiment may be applied using the coil 652, or the rotating synthetic magnetic field described in the fourth embodiment is applied using the coil 951 and the coil 652. May be.

  Thereby, the microparticles 4 a perturb at the interface of the test solution 3. At this time, since the microparticles 4a are exposed at the interface of the test solution 3, the viscous resistance of the test solution 3 is smaller than when the microparticles 4a are completely in the test solution 3. Therefore, even when magnetic fields having the same intensity are applied, the vibration amplitude of the microparticles 4a is increased, and detection with high sensitivity is possible.

  Note that the fine particles used in the present embodiment are not limited to the fine particles 4a as long as they are attracted to the coil 951. For example, the fine particles 4h described in the sixth embodiment may be used.

[Summary]
The fine particles (4) according to the first aspect of the present invention are dispersed in a test solution (3) including at least one detection target (412), and are irradiated with light of a specific wavelength from a part of the surface. A selective coupling part (41) that is a conductive fine particle that generates near-field light and has an ability to selectively bind to the detection target contained in the test solution, and a magnetic field applied to the test solution A torque applying unit (42) that receives a field force from the surface and applies torque to the microparticles, and each of the selective coupling unit and the torque applying unit is disposed at a different position on the surface of the microparticles. .

  According to the above configuration, the torque applying unit for the microparticles receives a field force from the magnetic field applied to the test solution and applies torque to the microparticles themselves. For this reason, some of the fine particles appear to rotate or reciprocate. For this reason, when the test solution is irradiated with light of a specific wavelength that generates near-field light in a part of the microparticles, and the perturbation due to the magnetic field is applied to the test solution, the above-mentioned motion occurs, From the viewpoint of the observer on the particle, the region where the near-field light of a part of the microparticle is generated (hereinafter referred to as the near-field light generation region) moves so that the selective coupling part enters and exits (actually It is considered that the relative position of the near-field light generation region of the microparticle with respect to the microparticle changes with the movement of the microparticle).

  However, substances other than the target to be detected that spontaneously adsorbed or accidentally existed (for example, impurities having a poor ability to bind to the selective binding part) have a weak binding to the selective binding part compared to the target to be detected. The relative position with respect to the particles hardly changes, and the relative position of the microparticles with respect to the near-field light generation region does not change significantly. Therefore, if the perturbation due to the magnetic field is applied to the test solution as described above, and only the detection target coupled to the selective coupling part moves in and out of the near-field light generation region, the solvent in the test solution Due to the difference in refractive index from the detection object, the position of the absorption peak spectroscopically measured varies according to the perturbation of the magnetic field. The fluctuation in the position of the absorption peak becomes a fluctuation component caused only by the detection target coupled to the selective coupling portion in the spectroscopic measurement result.

  For this reason, by extracting and analyzing such a fluctuation component from the result of spectroscopic measurement, in a test solution in which a detection target and various other substances are mixed (for example, a substance detection device described later is used). If used), it is possible to detect a very small amount of detection object.

  The microparticle according to aspect 2 of the present invention is the microparticle according to aspect 1, wherein the position of the selective coupling portion is disposed with respect to the center of the microparticle, and the torque applying portion is disposed with respect to the center of the microparticle. The angle made with the position where it is made may be substantially a right angle.

  According to said structure, the positional relationship with respect to a microparticle of a torque provision part and a selective coupling part becomes a substantially right angle with respect to the center of a microparticle. As a result, the torque applied to the fine particles can be maximized.

  In the microparticle according to aspect 3 of the present invention, in the above aspect 1 or 2, the torque applying unit may include a perpendicular magnetization film of a ferromagnetic material.

  According to the above configuration, since the torque applying unit includes the perpendicular magnetization film of the ferromagnetic material, the detection target coupled with the selective coupling unit and the near-field light are generated by applying a magnetic field to the test solution. A torque large enough to change the positional relationship with the region being applied can be applied to the fine particles. Moreover, since the repulsion by the same polarity can be utilized and aggregation of microparticles can be avoided, a dispersing agent becomes unnecessary.

  In the fine particles according to aspect 4 of the present invention, in the above aspect 1 or 2, the torque applying unit may include a conductive film.

  In the microparticle according to aspect 5 of the present invention, in the above aspect 1 or 2, the torque applying unit may include a superparamagnetic substance.

  According to said structure, a torque provision part contains a electrically conductive film or a superparamagnetic substance. Thereby, since the microparticles themselves do not have magnetism, aggregation of the microparticles can be prevented. In addition, since it is not necessary to perform a dispersion treatment with a dispersant on the fine particles, the configuration is simple and the number of processes in the manufacturing process is reduced, so that the manufacturing cost can be reduced.

  In the microparticles according to aspect 6 of the present invention, in the above aspects 1 to 5, the selective binding portion may have at least one single chain of one or more types of antibodies or one or more types of nucleic acids.

  According to the above configuration, the selective binding portion has at least one single chain of one or more types of antibodies or one or more types of nucleic acids. Accordingly, the selective binding portion selectively binds to the detection target in the test solution that selectively binds to the single chain of the antibody or nucleic acid, and thus the detection target that selectively binds to the single chain of the antibody or nucleic acid. Can be detected.

  The substance detection apparatus 1 according to Aspect 7 of the present invention irradiates a test solution containing at least one fine particle and at least one detection target in the above aspects 1 to 6 with light having a specific wavelength. A substance detection device that detects a detection target contained in the test solution using near-field light generated from particles, and outputs a detection result of a spectral characteristic of light that has passed through the test solution as a detection signal. Spectral characteristic measurement unit (7), at least one magnetic field application unit (coil 5, coil 651, coil 652, coil 951) for applying a magnetic field to the test solution, and the magnetic field application unit applied to the test solution A fluctuation component extraction unit (lock) that extracts and outputs a fluctuation component signal synchronized with the perturbation signal from a detection signal output from the spectral characteristic measurement unit, using a magnetic field perturbation signal as a reference signal And N'anpu 6), detection processing unit for executing a process for detecting the detection object using the fluctuation component signal outputted from the variation component extractor (signal processing section 14) may be provided with a.

  According to the above configuration, by using the perturbation signal of the magnetic field as a reference signal, the fluctuation component synchronized with the perturbation signal from the detection signal that is the detection result of the spectral characteristics of the light that has passed through the test solution to which the magnetic field is applied. Extract and output the signal. And a detection process part detects a detection target object using the said fluctuation | variation component signal.

  Here, the change in the positional relationship between the detection target coupled with the selective coupling unit and the region where the near-field light is generated occurs in synchronization with the perturbation signal. That is, with the above configuration, only the change in the near-field light generation state corresponding to the change in the relative positional relationship with respect to the microparticles of the detection object combined with the selective coupling portion and the near-field light generation region, It can be extracted as a fluctuation component signal. Therefore, it is possible to detect a detection target with a high S / N ratio while suppressing noise caused by impurities.

  A substance detection device according to aspect 8 of the present invention is generated from the fine particles by irradiating a test solution containing at least one fine particle and at least one detection object in aspect 3 with light of a specific wavelength. A substance detection device that detects a detection target contained in the test solution by using near-field light, and outputs a detection result of a spectral characteristic of light that has passed through the test solution as a detection signal And at least one magnetic field applying unit that applies a magnetic field to the test solution, and a perturbation signal of the magnetic field that the magnetic field applying unit applies to the test solution is used as a reference signal, and the detection is output from the spectral characteristic measuring unit A fluctuation component extraction unit that extracts and outputs a fluctuation component signal synchronized with the perturbation signal from a signal; and the detection target object is detected using the fluctuation component signal output from the fluctuation component extraction unit. A detection processing unit that executes a processing to be performed, wherein the test solution includes a plurality of the microparticles, and the surface of the torque application unit of each of the plurality of microparticles on a surface opposite to the microparticle side is provided. The polarities may be the same.

  In the substance detection device according to aspect 9 of the present invention, in the aspect 7 or 8, the torque applying unit may be a perpendicular magnetization film having magnetization in a direction perpendicular to the surface opposite to the microparticle side. Good.

  According to the above configuration, the test solution includes a plurality of microparticles, and each of the plurality of microparticles is on the side opposite to the microparticles side of the torque applying unit (the perpendicular magnetization film of the ferromagnetic material). Since the surface magnetism is the same, the microparticles repel each other. Therefore, aggregation of microparticles can be prevented.

  The substance detection device according to aspect 10 of the present invention may include a plurality of the magnetic field application units in the aspect 7 or 8.

  According to said structure, since the magnetic field application part is provided with two or more, each magnetic field application part can generate a different magnetic field. Thereby, the synthetic | combination magnetic field which synthesize | combined a different magnetic field can be applied to a test solution.

  For example, by controlling the perturbation signal of each magnetic field, a synthetic magnetic field rotating at a specific frequency can be applied. As a result, the microparticles rotate in synchronization with the rotation of the synthetic magnetic field, so the direction of the normal on the surface opposite to the microparticle side and the direction of the synthetic magnetic field have a fixed relationship, ideally these It is possible to maintain such a relationship that the angle formed by the vector is always a right angle. Therefore, a large torque can always be applied to the fine particles, and detection with higher sensitivity is possible.

  In the substance detection device according to aspect 11 of the present invention, in the aspect 8, at least one of the plurality of magnetic field application units may be disposed above the test solution.

  According to the above configuration, at least one of the plurality of magnetic field application units is arranged on the upper part of the test solution. By applying a magnetic field to the test solution by the magnetic field application unit, the fine particles can be exposed at the interface of the test solution. Thereby, the viscosity resistance of the test solution brought to the microparticles can be reduced, and for example, the vibration amplitude of the microparticles with the same magnetic field strength is increased. Therefore, detection with higher sensitivity is possible.

  The present invention is not limited to the above-described embodiments, and various modifications are possible within the scope shown in the claims, and embodiments obtained by appropriately combining technical means disclosed in different embodiments. Is also included in the technical scope of the present invention. Furthermore, a new technical feature can be formed by combining the technical means disclosed in each embodiment.

  The embodiment of the present invention can also be expressed as follows.

  That is, the microparticles of the present invention have a selective binding portion having the ability to selectively bind a magnetic substance to a part of the surface of the conductive microparticle and another part to a detection target.

  According to the above-mentioned microparticles, a perturbation of the microparticles is induced by applying an external magnetic field to the magnetic material, and a minute detection target can be detected by detecting a change corresponding to the perturbations.

  In the fine particles of the present invention, the magnetic substance may be a perpendicular magnetization film, and the polarities of the fine particle surfaces may be the same.

  According to the above microparticles, perturbation can be easily caused and aggregation of the microparticles can be avoided.

  In the fine particle of the present invention, the magnetic substance and the selective coupling portion may be arranged with an angle of 90 degrees with respect to the fine particle center.

  According to the above fine particles, the effect of perturbation can be maximized.

  In addition, the substance detection system of the present invention includes an inspection object including the above-described microparticles, a spectral characteristic measurement unit that detects the spectral characteristics of the inspection object, a magnetic field application unit that magnetically perturbs the microparticles, A lock-in amplifier that uses a perturbation signal in the magnetic perturbation as a reference signal may be included, and a detection target may be detected using a fluctuation component synchronized with the magnetic perturbation.

  According to the above detection system, it is possible to quantify the detection target while suppressing noise.

  The present invention is a substance detection that detects microparticles that generate near-field light from the surface when irradiated with light of a specific wavelength, and minute amounts of bacteria contained in water or food using the microparticles. It can utilize suitably for an apparatus.

DESCRIPTION OF SYMBOLS 1 Substance detection apparatus 1a-1c Substance detection apparatus 3 Test solution 4 Microparticle 4a-4h Microparticle 5 Coil (magnetic field application part)
6 Lock-in amplifier (variable component extraction unit)
7 Spectral Characteristics Measurement Unit 14 Signal Processing Unit (Detection Processing Unit)
41 Selective coupling unit 42, 642, 742, 842 Torque applying unit 412 Object to be detected 651 Coil (magnetic field applying unit)
652 Coil (magnetic field application unit)
951 Coil (magnetic field application unit)

Claims (5)

Conductive fine particles dispersed in a test solution containing at least one detection object and generating near-field light from a part of the surface by being irradiated with light of a specific wavelength,
A selective binding portion having the ability to selectively bind to the detection target contained in the test solution;
A torque applying unit that receives a field force from the magnetic field applied to the test solution and applies torque to the microparticles,
Each of the said selective coupling | bond part and the said torque provision part is arrange | positioned in the position where the surface of the said microparticle differs.   The fine particle according to claim 1, wherein the torque applying unit includes a perpendicular magnetization film of a ferromagnetic material.   The fine particles according to claim 1, wherein the torque applying unit includes a conductive film. Utilizing near-field light generated from the microparticles by irradiating a test solution containing at least one microparticle according to claim 2 and at least one detection object with light of a specific wavelength, A substance detection device for detecting a detection target contained in a test solution,
A spectral characteristic measurement unit that outputs a detection result of the spectral characteristic of light that has passed through the test solution as a detection signal;
At least one magnetic field application unit for applying a magnetic field to the test solution;
A fluctuation component that extracts the fluctuation component signal synchronized with the perturbation signal from the detection signal output from the spectral characteristic measurement section using the perturbation signal of the magnetic field applied to the test solution by the magnetic field application section as a reference signal and outputs the fluctuation component signal An extractor;
A detection processing unit that executes a process of detecting the detection target object using the fluctuation component signal output from the fluctuation component extraction unit, and the test solution includes a plurality of the microparticles,
The substance detection apparatus according to claim 1, wherein the polarities of the surfaces of the torque applying portions of the plurality of microparticles on the side opposite to the microparticles are the same.   5. The substance detection apparatus according to claim 4, wherein the torque application unit is a perpendicular magnetization film having magnetization in a direction perpendicular to the surface opposite to the fine particle side.

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