JP2016003858A - Detector, method for detection, and electric field enhancement element - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a detector that can exchange electric field enhancement elements according to need while suppressing the frequency of exchanges of electric field enhancement elements.SOLUTION: A detector 100 according to the present invention includes: an electric field enhancement element 20; a light source 10 irradiating the electric field enhancement element 20 with first light L1; a light detecting unit 70 detecting second light L2 emitted from the electric field enhancement element 20 when the first light L1 reaches the electric field enhancement element 20; a filter 40 allowing lights with the same wavelength as that of the first light L1 to reflect from the filter and allowing the lights with a wavelength different from that of the first light L1 to pass through the filter; and a first moving unit 50 relatively moving the filter 40 to a first position where the second light L2 does not enter and a second position where the second light L2 enters with respect to the second light L2.

Description

  The present invention relates to a detection device, a detection method, and an electric field enhancement element.

  In recent years, there has been an increasing demand for sensor chips used for medical diagnosis, food and beverage inspection, and the development of highly sensitive and small sensor chips is required. In order to meet such demands, various types of sensor chips including an electrochemical method have been studied. Among these, spectroscopic analysis using surface plasmon resonance (SPR), particularly surface-enhanced Raman scattering (SERS), for reasons such as integration, low cost, and choice of measurement environment. : Interest in sensor chips using Surface Enhanced Raman Scattering is increasing.

  Here, the surface plasmon is a vibration mode of an electron wave that causes coupling with light due to boundary conditions unique to the surface. As a method of exciting surface plasmons, there are a method of engraving a diffraction grating on a metal surface and combining light and plasmons and a method of using evanescent waves. For example, a sensor using SPR includes a total reflection prism and a metal film that contacts a target substance formed on the surface of the prism. With such a configuration, the presence or absence of target substance adsorption, such as the presence or absence of antigen adsorption in an antigen-antibody reaction, is detected.

  By the way, while propagation-type surface plasmons exist on the metal surface, localized surface plasmons exist on the metal fine particles. It is known that when a localized surface plasmon, that is, a surface plasmon localized on the surface metal microstructure is excited, a significantly enhanced electric field is induced.

  Further, when the Raman scattered light is irradiated to the enhanced electric field formed by localized surface plasmon resonance (LSPR) using metal nanoparticles, the Raman scattered light is enhanced by the surface enhanced Raman scattering phenomenon. Is known, and a highly sensitive sensor (detection device) has been proposed. By using this principle, various trace amounts of substances can be detected.

  In the detection apparatus including the sensor chip as described above, the sensor chip may be deteriorated due to, for example, molecules adsorbed on the surface of the sensor chip and the molecules cannot be removed. For example, in Patent Document 1, the flow rate of a fluid sample is increased or a light source is used, compared to a case where a substance (molecule) to be inspected in a fluid sample is adsorbed to a sensor chip and scattered light is detected by a light detection unit. It is described that the molecules adsorbed on the sensor chip can be released by increasing the light intensity.

JP 2012-230042 A

  However, in the method described in Patent Document 1, there are cases where it cannot be sufficiently detached by molecules adsorbed on the sensor chip (electric field enhancing element). Furthermore, the deterioration of the electric field enhancing element is caused by the fact that molecules are adsorbed on the surface of the electric field enhancing element and cannot be removed, and may also be caused by the structural change of the electric field enhancing element. In the method described in Patent Document 1, deterioration due to the structural change of the electric field enhancing element may not be prevented.

  For this reason, in the detection device including the electric field enhancement element, when the electric field enhancement element deteriorates, it is preferable to replace the electric field enhancement element. However, if the electric field enhancing element is replaced each time the target substance that is the detection target is detected, the cost increases and the replacement work is troublesome. Therefore, it is desired to replace the electric field enhancing element as necessary while suppressing the number of times the electric field enhancing element is replaced.

  One of the objects according to some aspects of the present invention is to provide a detection device that can replace an electric field enhancing element as needed while suppressing the number of times the electric field enhancing element is replaced. Moreover, one of the objects according to some aspects of the present invention is to provide a detection method capable of exchanging the electric field enhancement element as necessary while suppressing the number of exchanges of the electric field enhancement element.

The detection device according to the present invention is:
An electric field enhancing element;
A light source for irradiating the electric field enhancing element with first light;
A photodetector for detecting second light emitted by the electric field enhancing element when the electric field enhancing element is irradiated with the first light;
A filter that reflects light having the same wavelength as the wavelength of the first light and transmits light having a wavelength different from the wavelength of the first light;
A first moving unit that moves the filter relative to the second light relative to a first position where the second light is not incident and a second position where the second light is incident;
including.

  In such a detection device, it is possible to determine whether or not to replace the electric field enhancement element based on the detection result of the photodetector in a state where the filter is in the first position, and further, the filter is in the second position. Based on the detection result of the photodetector in a certain state, it can be determined whether or not to replace the electric field enhancement element. Thereby, it is possible to determine whether or not to replace the electric field enhancement element based on the reflected light in the electric field enhancement element, and further to determine whether or not to replace the electric field enhancement element based on the Raman spectrum. can do. Therefore, in such a detection device, the deterioration of the electric field enhancement element caused by the structural change of the electric field enhancement element over time and the target substance (molecule) adsorbed on the surface of the electric field enhancement element cannot remove the molecule. It is possible to detect the deterioration of the electric field enhancement element that occurs. Therefore, in such a detection apparatus, the electric field enhancing element can be replaced as necessary while suppressing the number of times the electric field enhancing element is replaced.

In the detection apparatus according to the present invention,
A first determination unit that determines whether to replace the electric field enhancement element based on a detection result of the photodetector in a state where the filter is in the first position;
A second determination unit that determines whether to replace the electric field enhancement element based on a detection result of the photodetector in a state where the filter is in the second position;
May be included.

  In such a detection device, the electric field enhancement element can be exchanged as necessary while suppressing the number of exchanges of the electric field enhancement element.

In the detection apparatus according to the present invention,
The electric field enhancing element is
A substrate,
A metal microstructure provided in a first region of the substrate;
A metal layer provided in a second region of the substrate;
You may have.

  In such a detection device, the intensity of the reflected light in the metal microstructure (second reflected light intensity) is divided by the intensity of the reflected light in the metal layer (first reflected light intensity), thereby obtaining the metal of the metal microstructure. The influence of absorption in itself can be reduced, and the intensity ratio of reflected light based on the absorption in SPR can be obtained more accurately. Furthermore, in such a detection apparatus, since the metal fine structure and the metal layer are provided in one electric field enhancing element, in order to obtain the first reflected light intensity and the second reflected light intensity, the element ( It is not necessary to replace the substrate, and man-hours can be reduced.

In the detection apparatus according to the present invention,
The electric field enhancing element is relative to the first light at a third position where the first light is incident on the metal layer and a fourth position where the first light is incident on the metal microstructure. A second moving part to be moved to,
Based on the detection result of the photodetector in a state where the filter is in the first position and the electric field enhancing element is in the third position, the intensity of the first reflected light is obtained,
Based on the detection result of the photodetector in a state where the filter is in the first position and the electric field enhancing element is in the fourth position, the intensity of the second reflected light is obtained,
An intensity ratio calculation unit for obtaining an intensity ratio of reflected light from the intensity of the first reflected light and the intensity of the second reflected light;
Including
The first determination unit may determine whether to replace the electric field enhancing element based on the intensity ratio.

  In such a detection device, the electric field enhancement element can be exchanged as necessary while suppressing the number of exchanges of the electric field enhancement element.

In the detection apparatus according to the present invention,
A Raman spectrum acquisition unit that acquires a Raman spectrum based on a detection result of the photodetector in a state where the filter is in the second position;
The second determination unit may determine whether to replace the electric field enhancing element based on the Raman spectrum.

  In such a detection device, the electric field enhancement element can be exchanged as necessary while suppressing the number of exchanges of the electric field enhancement element.

In the detection apparatus according to the present invention,
The second determination unit obtains a difference between an intensity at a predetermined Raman shift of the Raman spectrum and an average intensity of the baseline of the Raman spectrum, and the difference is equal to or greater than a noise intensity of the baseline of the Raman spectrum. In this case, it may be determined that the electric field enhancing element is replaced.

  In such a detection device, the second determination unit can determine to replace the electric field enhancement element even when a very small amount of molecules are attached to the electric field enhancement element.

In the detection apparatus according to the present invention,
You may include the output part which outputs the determination result of the said 1st determination part, and the determination result of the said 2nd determination part.

  In such a detection device, the electric field enhancement element can be exchanged as necessary while suppressing the number of exchanges of the electric field enhancement element.

The detection method according to the present invention includes:
Irradiating the electric field enhancing element with the first light, detecting the second light from the electric field enhancing element, and determining whether to replace the electric field enhancing element based on the detected intensity of the second light Process,
Irradiating the electric field enhancing element with the first light to detect the second light from the electric field enhancing element through a filter, and based on the intensity of the second light detected through the filter, Determining whether to replace the electric field enhancing element; and
Including
The filter reflects light having the same wavelength as the wavelength of the first light and transmits light having a wavelength different from the wavelength of the first light.

  In such a detection method, in the first step (the step of determining whether or not to replace the electric field enhancement element based on the intensity of the second light detected without passing through the filter), the reflected light from the electric field enhancement element. In the second step (step of determining whether to replace the electric field enhancement element based on the intensity of the second light detected by the filter). Based on the Raman spectrum, it can be determined whether or not to replace the electric field enhancing element. Therefore, in such a detection method, the electric field enhancement element caused by the deterioration of the electric field enhancement element caused by the structural change of the electric field enhancement element over time and the fact that the molecules cannot be adsorbed on the surface of the electric field enhancement element and cannot be removed. Can be detected. Therefore, in the detection method according to the present embodiment, the electric field enhancement element can be exchanged as necessary while suppressing the number of exchanges of the electric field enhancement element.

The electric field enhancing element according to the present invention is
A substrate,
A metal microstructure provided in a first region of the substrate;
A metal layer provided in a second region of the substrate;
including.

The functional block diagram of the detection apparatus which concerns on this embodiment. The top view which shows typically the electric field enhancement element which concerns on this embodiment. Sectional drawing which shows typically the electric field enhancement element which concerns on this embodiment. The functional block diagram of the detection apparatus which concerns on this embodiment. The functional block diagram of the detection apparatus which concerns on this embodiment. The graph which shows an example of a Raman spectrum. The flowchart for demonstrating the detection method which concerns on this embodiment. The flowchart for demonstrating the detection method which concerns on the modification of this embodiment. The figure which shows typically the specific structure of the detection apparatus which concerns on this embodiment. The SEM photograph of the sample board | substrate used for the experiment example. The graph which shows a reflected light intensity ratio spectrum. The table | surface which shows the reflectance ratio of wavelength 632.8nm. The graph which shows a Raman spectrum. A table showing intensity differences and baseline noise intensity.

  DESCRIPTION OF EMBODIMENTS Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the drawings. The embodiments described below do not unduly limit the contents of the present invention described in the claims. In addition, not all of the configurations described below are essential constituent requirements of the present invention.

1. Detection Device First, the detection device according to the present embodiment will be described with reference to the drawings. FIG. 1 is a functional block diagram of a detection apparatus 100 according to this embodiment. As shown in FIG. 1, the detection apparatus 100 includes a light source 10, an electric field enhancement element 20, moving units 30 and 50, a filter 40, a control unit 60, a photodetector 70, an operation unit 80, and an output. Unit 82, storage unit 84, storage medium 86, and processing unit 90.

  The light source 10 irradiates the electric field enhancing element 20 with the first light L1. In the illustrated example, the first light L1 enters the electric field enhancing element 20 through the half mirror 12 and the lens 14. The light source 10 is, for example, a semiconductor laser or a gas laser, and the first light L1 is laser light. The wavelength of the first light L1 is, for example, not less than 350 nm and not more than 1000 mn, and specifically 632.8 nm.

  The electric field enhancing element 20 receives the first light L1 and emits the second light L2. The second light L2 is scattered light emitted from the electric field enhancing element 20 by the first light L1. The second light L2 includes, for example, reflected light reflected by the electric field enhancing element 20. Here, FIG. 2 is a plan view schematically showing the electric field enhancing element 20. FIG. 3 is a cross-sectional view taken along the line III-III of FIG. 2 schematically showing the electric field enhancing element 20. 2 and 3, the X axis, the Y axis, and the Z axis are illustrated as three axes orthogonal to each other.

  As shown in FIGS. 2 and 3, the electric field enhancing element 20 includes a substrate 21, a metal microstructure 25, and a metal layer 26. The substrate 21 includes a support substrate 22, a metal layer 23, and a dielectric layer 24.

  The support substrate 22 is, for example, a glass substrate, a silicon substrate, or a resin substrate.

  The metal layer 23 is provided on the support substrate 22. The thickness of the metal layer 23 is, for example, not less than 10 nm and not more than 100 μm. The material of the metal layer 23 is, for example, gold, silver, aluminum, or copper. The metal layer 23 is formed by, for example, a vacuum deposition method or a sputtering method. The metal layer 23 may have a function of exciting a propagation surface plasmon (PSP) in the electric field enhancing element 20. Specifically, PSP may be excited at the interface between the metal layer 23 and the dielectric layer 24 (in the vicinity of the interface) by making light (excitation light) incident on the electric field enhancing element 20.

The dielectric layer 24 is provided on the metal layer 23. The thickness of the dielectric layer 24 includes PSP excited at the interface between the metal layer 23 and the dielectric layer 24, and localized surface plasmon (LSP) excited by the metal microstructure 25. It may be set so that it can interact. The thickness of the dielectric layer 24 is, for example, 10 μm or more and 1 μm or less. The material of the dielectric layer 24 is, for example, silicon oxide (SiO ₂ ), aluminum oxide (Al ₂ O ₃ ), tantalum oxide (Ta ₂ O ₅ ), silicon nitride (Si ₃ N ₄ ), titanium oxide (TiO ₂ ). , Polymers such as PMMA (Polymethylmethacrylate), ITO (Indium Tin Oxide). The dielectric layer 24 is formed by, for example, a vacuum deposition method, a sputtering method, or a CVD (Chemical Vapor Deposition) method.

  The metal microstructure 25 is provided in the first region 21 a of the substrate 21. The first region 21 a is a region on the upper surface of the dielectric layer 24. The shape of the metal microstructure 25 is not particularly limited, and is, for example, a particle shape, a prism, a sphere, or a spheroid, but in the illustrated example, a cylinder. The size of the metal microstructure 25 (for example, the size in the X-axis direction and the size in the Y-axis direction) is less than or equal to the wavelength of the first light L1 emitted from the light source 10. The size of the metal microstructure 25 is 10 nm or more and 1 μm or less, and preferably 40 nm or more and 700 nm or less. The thickness of the metal microstructure 25 is, for example, not less than 1 nm and not more than 500 nm, preferably not less than 10 nm and not more than 100 nm. As shown in the figure, the metal microstructure 25 need not be provided over the entire first region 21a, and may be provided only in a part of the first region 21a.

  A plurality of metal microstructures 25 are provided. The number of metal microstructures 25 is not particularly limited. In the illustrated example, the shapes of the plurality of metal microstructures 25 are the same as each other, but may be different from each other. In the illustrated example, the plurality of metal microstructures 25 are provided periodically, but may not be provided periodically. The pitch in the X-axis direction of the metal microstructures 25 is, for example, 1 nm or more and 500 nm or less. The pitch in the Y-axis direction of the metal microstructures 25 is, for example, 1 nm or more and 500 nm or less. In the illustrated example, the pitch in the X-axis direction of the metal microstructures 25 is different from the pitch in the Y-axis direction, but may be the same as the pitch in the Y-axis direction.

  The pitch in the X-axis direction of the metal microstructures 25 is the distance between the centers of gravity of the metal microstructures 25 adjacent in the X-axis direction, and the pitch in the Y-axis direction of the metal microstructures 25 is Y This is the distance between the centers of gravity of adjacent metal microstructures 25 in the axial direction.

  The material of the metal microstructure 25 is gold, silver, aluminum, or copper. Gold, silver, aluminum, and copper are metals having a small imaginary part of dielectric constant in the ultraviolet to visible light region, and can enhance the electric field enhancement effect (details will be described later). The metal microstructure 25 is formed by, for example, a patterning method after forming a thin film by a vacuum deposition method, a sputtering method, or the like, a microcontact printing method, a nanoimprinting method, or the like.

  Although not shown, a target substance (target molecule) to be detected is adsorbed to the metal microstructure 25. When the target substance adsorbed on the metal microstructure 25 is irradiated with the first light L1, Rayleigh scattered light having the same wavelength as the first light L1, and Raman scattered light having a wavelength different from the first light L1, Will occur. The energy of the Raman scattered light corresponds to a specific vibration energy corresponding to the structure of the target substance. Therefore, the target substance can be specified by obtaining the Raman shift that is the difference between the wave number (frequency) of the Raman scattered light and the wave number of the first light L1. Furthermore, the concentration of the target substance can be known from the Raman shift and the intensity.

  The metal microstructure 25 generates surface plasmon resonance (SPR: Surface Plasmon Resonance) by the first light L1. Specifically, the metal microstructure 25 generates localized plasmon resonance (LSPR) by the first light L1. LSPR is a phenomenon in which, when light is incident on a metal structure having a wavelength equal to or less than the wavelength of light, free electrons existing in the metal collectively vibrate due to the electric field component of the light and induce a localized electric field outside. This localized electric field can enhance Raman scattered light. The enhancement of Raman scattered light by the electric field induced by SPR is referred to as an electric field enhancement effect. The intensity of Raman scattered light (SERS light) enhanced by SPR is proportional to the fourth power of the electric field enhanced by SPR. When PSP is excited at the interface between the metal layer 23 and the dielectric layer 24, the electric field enhancement effect can be further enhanced by the PSP.

  The metal layer 26 is provided in the second region 21 b of the substrate 21. The second region 21b is a region on the upper surface of the dielectric layer 24, and is a region different from the first region 21a. In the illustrated example, the planar shape of the metal layer 26 is a quadrangle. The metal layer 26 has a shape having a size (for example, a size in the X-axis direction and a size in the Y-axis direction) in plan view larger than the thickness. The metal layer 26 is, for example, a member made of metal having a size in plan view that is 100 times or more the thickness. The size of the metal layer 26 in plan view is larger than the size of the metal microstructure 25 in plan view. The size of the metal layer 26 in the X-axis direction is, for example, 1000 times or more and 100000 times or less than that of the metal microstructure 25, and the size of the metal layer 26 in the Y-axis direction is, for example, 1000 times or more and 100000 times. It is as follows. The thickness of the metal layer 26 is, for example, 1 nm or more and 10 μm or less. The thickness of the metal layer 26 may be the same as the thickness of the metal microstructure 25. As shown in the figure, the metal layer 26 does not need to be provided over the entire second region 21b, and may be provided only in a part of the second region 21b.

  The material of the metal layer 26 is the same as the material of the metal microstructure 25, for example. The metal layer 26 is formed by the same method as the metal microstructure 25, for example.

  The second moving unit 30 includes the electric field enhancing element 20 with respect to the first light L1, the position where the first light L1 is incident on the metal layer 26 (third position), and the first light L1 on the metal microstructure 25. It moves relatively to the incident position (fourth position). For example, the second moving unit 30 moves the electric field enhancing element 20 into the third position where the first light L1 is incident on the metal layer 26 (see FIG. 1) and the first position where the first light L1 is incident on the metal microstructure 25. 4 positions (see FIG. 4).

  Note that the second moving unit 30 moves the mirror (not shown) without moving the electric field enhancing element 20, thereby moving the electric field enhancing element 20 to the third position and the fourth position with respect to the first light L1. You may move relatively. That is, the second moving unit 30 moves the mirror (not shown) without moving the electric field enhancing element 20, thereby changing the irradiation position of the first light L1 to the electric field enhancing element 20 to the third position and the fourth position. You may move relatively. Thus, “moving the electric field enhancing element 20 relative to the first light L1 to the third position and the fourth position” means that the electric field enhancing element 20 is directly moved to the third position and the fourth position. And a case where the electric field enhancing element 20 is moved relative to the third position and the fourth position with respect to the first light L1 by moving a mirror (not shown). FIG. 4 is a functional block diagram illustrating a state in which the filter 40 is in the first position and the electric field enhancing element 20 is in the third position in the detection apparatus 100.

  Although not shown, the second moving unit 30 includes, for example, a support unit that supports the electric field enhancing element 20 and a drive unit that moves the support unit, and receives a signal from the processing unit 90 and receives the signal from the processing unit 90. By driving, the support part moves, and the electric field enhancing element 20 can be moved. The drive part of the 2nd moving part 30 is a motor, for example. In addition, the 2nd moving part 30 has a knob, and you may move the support part which supports the electric field enhancement element 20 manually by pinching this knob.

  The filter 40 reflects light having the same wavelength as that of the first light L1, and transmits light having a wavelength different from that of the first light L1. Specifically, the filter 40 reflects light (Rayleigh scattered light) having the same wavelength as the first light L1 in the second light L2, and other scattered light (Raman scattered light) in the second light L2. Permeate. The filter 40 may be a notch filter.

  The first moving unit 50 places the filter 40 with respect to the second light L2 at a position where the second light L2 does not enter the filter 40 (first position) and a position where the second light L2 enters the filter 40 (second position). Position). For example, the first moving unit 50 moves the filter 40 into a first position where the second light L2 does not enter the filter 40 (see FIG. 4) and a second position where the second light L2 enters the filter 40 (see FIG. 5). ) And move to. The filter 40 in the second position is located between the electric field enhancing element 20 and the photodetector 70, for example. When the filter 40 is in the second position, light having a wavelength different from the wavelength of the first light L1 in the second light L2 passes through the filter 40 and reaches the photodetector 70. FIG. 5 is a functional block diagram showing a state where the filter 40 is in the second position and the electric field enhancing element 20 is in the fourth position in the detection apparatus 100.

  The first moving unit 50 moves the mirror (not shown) without moving the filter 40, thereby moving the filter 40 relative to the first position and the second position with respect to the second light L2. It may be moved. That is, the first moving unit 50 moves the mirror (not shown) without moving the filter 40, so that the irradiation position of the second light L <b> 2 with respect to the filter 40 is relative to the first position and the second position. It may be moved to. Thus, “relatively move the filter 40 to the first position and the second position with respect to the second light L2” means that the filter 40 is moved directly to the first position and the second position. And a case where the filter 40 is moved relative to the first light L1 between the first position and the second position by moving a mirror (not shown).

  Although not shown, the first moving unit 50 includes, for example, a support unit that supports the filter 40 and a drive unit that moves the support unit, and the drive unit is driven by receiving a signal from the processing unit 90. By doing so, the support part moves and the filter 40 can be moved. The drive unit of the first moving unit 50 is, for example, a motor. In addition, the 1st moving part 50 has a knob, and you may move the support part which supports the filter 40 manually by pinching this knob.

  The control unit 60 receives a signal from the processing unit 90 and outputs a signal to the second moving unit 30. The signal output from the control unit 60 to the second moving unit 30 is, for example, a signal for moving the electric field enhancing element 20 from the third position to the fourth position, or the electric field enhancing element 20 from the fourth position to the third position. It is a signal for moving to.

  The control unit 60 receives the signal from the processing unit 90 and outputs a signal to the first moving unit 50. The signal output from the control unit 60 to the first moving unit 50 is, for example, a signal for moving the filter 40 from the first position to the second position, or for moving the filter 40 from the second position to the first position. Signal.

  The control unit 60 receives a signal from the processing unit 90 and outputs a signal to the light source 10. The signal output from the control unit 60 to the light source 10 is a signal for irradiating the first light L1 from the light source 10 or a signal for stopping the irradiation of the first light L1 from the light source 10.

  The control unit 60 receives a signal from the photodetector 70 and outputs a signal to the processing unit 90. The signal output from the control unit 60 to the photodetector 70 is a signal including information on the intensity of the second light L2 detected by the photodetector 70. The control unit 60 includes, for example, an IC and the like.

  The photodetector 70 detects the second light L2 emitted by the electric field enhancing element 20 when the electric field enhancing element 20 is irradiated with the first light L1. The photodetector 70 may include a CCD (Charge Coupled Device), a photomultiplier tube, a photodiode, an imaging plate, and the like.

  The operation unit 80 performs a process of acquiring an operation signal corresponding to an operation by the user and sending the signal to the processing unit 90. The operation unit 80 is, for example, a button, a key, a touch panel display, a microphone, or the like.

  The output unit 82 outputs the processing result of the processing unit 90 based on the display signal input from the processing unit 90. Specifically, the output unit 82 outputs the determination result of the first determination unit 95 and the determination result of the second determination unit 98. The output unit 82 outputs a determination result when the first determination unit 95 determines to replace the electric field enhancement element 20, and outputs a determination result when the first determination unit 95 determines not to replace the electric field enhancement element 20. You don't have to. Similarly, the output unit 82 outputs a determination result when the second determination unit 98 determines to replace the electric field enhancement element 20, and determines when the second determination unit 98 determines not to replace the electric field enhancement element 20. The result need not be output. The output unit 82 may display the processing result of the processing unit 90 as characters or may output it as sound. When displaying the processing result of the processing unit 90 in characters, the output unit 82 is, for example, an LCD (Liquid Crystal Display), a CRT (Cathode Ray Tube), a touch panel display, or the like.

  The storage unit 84 stores programs, data, and the like for the processing unit 90 to perform various calculation processes and control processes. The storage unit 84 is further used as a work area of the processing unit 90. The operation signal input from the operation unit 80, the program and data read from the storage medium 86, and the calculation result executed by the processing unit 90 according to various programs. Etc. are temporarily stored. A database 85 is stored in the storage unit 84.

  In the database 85, data related to the target substance to be analyzed is registered. Specifically, the database 85 includes data for specifying (qualifying) the target substance from the Raman shift and data for specifying (quantifying) the concentration of the target substance from the intensity of the Raman spectrum. Is registered. The database 85 may be stored in the storage medium 86.

  The storage medium 86 is a computer-readable storage medium for storing various application programs and data. Note that the program may be distributed from an information storage medium included in the host device (server) to the storage medium 86 (storage unit 84) via a network or the like.

  The storage medium 86 may also function as a storage unit that stores data that needs to be stored for a long time among the data generated by the processing of the processing unit 90. The storage medium 86 is realized by, for example, an optical disk (CD, DVD), a magneto-optical disk (MO), a magnetic disk, a hard disk, a magnetic tape, or a memory (ROM, flash memory, etc.).

  The processing unit 90 performs various types of calculation processing in accordance with programs stored in the storage unit 84 and programs stored in the storage medium 86. In the present embodiment, the processing unit 90 executes a program stored in the storage unit 84 to thereby execute an intensity ratio calculation unit 91, a second moving unit control unit 92, a first determination unit 95, and a first determination unit 95. It functions as a moving unit control unit 96, a Raman spectrum acquisition unit 97, and a second determination unit 98. The functions of the processing unit 90 can be realized by hardware such as various processors (CPU, DSP, etc.), ASIC (gate array, etc.), and programs. Note that at least a part of the processing unit 90 may be realized by hardware (dedicated circuit).

  In the intensity ratio calculation unit 91, the filter 40 is in the first position (the position where the second light L2 is not incident on the filter 40), and the electric field enhancing element 20 is the third position (the first light L1 is incident on the metal layer 26). The intensity of the first reflected light (the intensity of the first reflected light) is acquired based on the detection result of the photodetector 70 in the position (see FIG. 1). The first reflected light intensity is the intensity of the second light L2 detected by the photodetector 70 in a state where the filter 40 is in the first position and the electric field enhancing element 20 is in the third position. Specifically, in a state where the filter 40 is in the first position and the electric field enhancement element 20 is in the third position, the signal output from the photodetector 70 is received via the control unit 60, and the first reflected light is received. Get strength.

  The second moving unit control unit 92 sends a signal for driving the second moving unit 30 to the second moving unit 30 via the control unit 60 after the intensity ratio calculating unit 91 acquires the first reflected light intensity. Output to. The signal output from the second moving unit control unit 92 is, for example, a signal for moving the electric field enhancing element 20 from the third position (see FIG. 1) to the fourth position (see FIG. 4) or the electric field enhancing element 20. Is a signal for moving from the fourth position to the third position. The second moving unit control unit 92 can control the position of the electric field enhancing element 20 by controlling the second moving unit 30.

  When the electric field enhancing element 20 is moved relatively to the third position and the fourth position with respect to the second light L2 by moving a mirror (not shown), the second moving unit control unit 92 is By controlling the second moving unit 30, the position of the mirror can be controlled.

  In the intensity ratio calculation unit 91, the filter 40 is in the first position (the position where the second light L2 is not incident on the filter 40), and the electric field enhancing element 20 is in the fourth position (the first light L1 is in the metal microstructure 25). The intensity of the second reflected light (second reflected light intensity) is acquired based on the detection result of the photodetector 70 in the state (see FIG. 4) in the incident position. The second reflected light intensity is the intensity of the second light L2 detected by the photodetector 70 in a state where the filter 40 is in the first position and the electric field enhancing element 20 is in the fourth position. Specifically, the intensity ratio calculation unit 91 outputs the intensity of the second light L2 detected by the photodetector 70 after the signal is output from the second moving unit control unit 92 to the second moving unit 30 (second Get reflected light intensity).

  The intensity ratio calculator 91 divides the second reflected light intensity by the acquired first reflected light intensity to obtain the reflected light intensity ratio (second reflected light intensity / first reflected light intensity).

  The first determination unit 95 determines whether or not to replace the electric field enhancement element 20 based on the detection result of the photodetector 70 in a state where the filter 40 is in the first position (see FIGS. 1 and 4). Specifically, the first determination unit 95 determines whether or not to replace the electric field enhancing element 20 based on the intensity ratio of reflected light (reflected light intensity ratio) obtained by the intensity ratio calculation unit 91.

More specifically, the first determination unit 95 is used for detecting the first reflected light intensity ratio r ₁ (once detected by the Raman spectroscopy once only after replacing the electric field enhancing element 20. If the difference Δr between the reflected light intensity ratio in the electric field enhancing element 20 and the reflected light intensity ratio r obtained by the intensity ratio calculation unit 91 is equal to or larger than r ₂ , the electric field enhancing element 20 is replaced. If the difference Δr is less than r ₂ , it is determined that the electric field enhancing element 20 is not replaced. The initial reflected light intensity ratio r ₁ is stored in the storage unit 84, for example. r ₂ is, for example, 0.1 or more and 0.2 or less when the maximum of the reflected light intensity ratio r is 1. For example, as shown in an experimental example described later, when the first reflected light intensity ratio r ₁ = 0.035 and the reflected light intensity ratio r (reflected light intensity ratio obtained this time) = 0.031, the difference Δr Since 0.004 and the difference Δr is less than r ₂ , the first determination unit 95 determines not to replace the electric field enhancing element 20. On the other hand, when the initial reflected light intensity ratio r ₁ = 0.035 and the reflected light intensity ratio r = 0.773, the difference Δr = 0.338, and the difference Δr is greater than or equal to r ₂ . The determination unit 95 determines to replace the electric field enhancing element 20.

  For example, when the first determination unit 95 determines not to replace the electric field enhancing element 20, the first movement unit control unit 96 sends a signal for driving the first movement unit 50 via the control unit 60. Output to the first moving unit 50. The signal output from the first moving unit control unit 96 is, for example, a signal for moving the filter 40 from the first position (see FIG. 4) to the second position (see FIG. 5) or the filter 40 in the second position. It is a signal for moving to 1st position. The first moving unit control unit 96 can control the position of the filter 40 by controlling the first moving unit 50.

  When the filter 40 is moved relative to the second position with respect to the second light L2 by moving a mirror (not shown), the first moving unit control unit 96 By controlling one moving unit 50, the position of the mirror can be controlled.

  The Raman spectrum acquisition unit 97 determines the Raman spectrum (SERS spectrum) based on the detection result of the photodetector 70 in the state where the filter 40 is in the second position and the electric field enhancing element 20 is in the fourth position (see FIG. 5). ) To get. Specifically, the Raman spectrum acquisition unit 97 transmits the signal output from the photodetector 70 via the control unit 60 in a state where the filter 40 is in the second position and the electric field enhancing element 20 is in the fourth position. And get a Raman spectrum. For example, the Raman spectrum acquisition unit 97 acquires a Raman spectrum after a signal is output from the first movement unit control unit 96 to the first movement unit 50. Here, FIG. 6 is a graph showing an example of a Raman spectrum acquired by the Raman spectrum acquisition unit 97. As shown in FIG. 6, the Raman spectrum is expressed as a Raman shift on the horizontal axis and an intensity on the vertical axis.

  The second determination unit 98 determines the electric field enhancement element 20 based on the detection result of the photodetector 70 in a state where the filter 40 is in the second position and the electric field enhancement element 20 is in the fourth position (see FIG. 5). Determine whether to replace. Specifically, the second determination unit 98 determines whether or not to replace the electric field enhancing element 20 based on the Raman spectrum acquired by the Raman spectrum acquisition unit 97.

  More specifically, the second determination unit 98 obtains an intensity difference between the intensity at a predetermined Raman shift of the Raman spectrum acquired by the Raman spectrum acquisition unit 97 and the average intensity of the baseline of the Raman spectrum, and When the intensity difference is equal to or higher than the baseline noise intensity of the Raman spectrum, it is determined to replace the electric field enhancement element 20, and when the intensity difference is less than the baseline noise intensity, it is determined not to replace the electric field enhancement element 20. Hereinafter, the process of the 2nd determination part 98 is demonstrated concretely.

First, the second determination unit 98 acquires the intensity I _MAX at a predetermined Raman shift ν. Specifically, the user through the operation unit 80 is displayed on the output section 82 material (e.g., pyridine, toluene, adenine, etc.) is selected, the second judging unit 98 during the first range S ₁ The maximum intensity I _MAX at and the Raman shift ν at which the intensity becomes I _MAX are acquired. The first range S ₁ is set in advance according to the target substance to be detected and is stored in the storage unit 84. When the user selects pyridine, for example, the first range S ₁ is 1008 cm ^{−1 to} 1012 cm ⁻¹ . In the example shown in FIG. 6, I _MAX = 1425 counts (ν = 1009.9 cm ⁻¹ ).

Incidentally, for example, if the user selects the toluene, the first range _{S 1} ^is 1000cm ^-1 ~1004cm -1, if you choose adenine, first range _{S 1} ^{is, 718cm -1 ~722cm} -1 It is.

Next, the second determination unit 98 obtains the average intensity of the baseline around the Raman shift ν. Specifically, the second determination unit 98, the average intensity of the second range S _2, and the average intensity of the third range S _3, the acquired determines the average intensity I _AVE of two values. Raman shift of the second range S ₂ is smaller than the Raman shift [nu _1, the Raman shift of the third range S ₃ is greater than the Raman shift [nu _1. The second range S ₂ and the third range S ₃ are set in advance according to the target substance to be detected and are stored in the storage unit 84. If the user selects a pyridine, eg, second range _{S 2} ^is a 990cm ^-1 ~1000cm -1, third range _{S 3} ^is 1020cm ^-1 ~1030cm -1. In the example shown in FIG. 6, the average intensity of the second range S2 is 842 counts, the average intensity of the third range S3 is 843 counts, and the average intensity I _AVE of both values is 842.5 counts.

Next, the second determination unit 98 subtracts the baseline average intensity I _AVE from the intensity I _MAX to obtain the intensity difference ΔI. In the example shown in FIG. 6, the intensity difference ΔI is expressed by the following formula (1).

Next, the second determination unit 98 calculates the baseline noise intensity. The baseline noise intensity is the value of the baseline standard deviation. The second determination unit 98, the following equation (2), the standard deviation sigma ₂ of the second range _{S 2,} and the standard deviation sigma ₃ of the third range _{S 3,} the determined, the sigma ₂ squared and sigma ₃ The square root is obtained by adding the squares to obtain the standard deviation σ (noise intensity) of the baseline.

In the example shown in FIG. 6, the standard deviation sigma ₂ = 49.5 for the second range _{S 2,} since the standard deviation sigma ₃ = 17.8 in the third range _{S 3,} the standard deviation of the baseline, the following formula ( It becomes like 3). The standard deviation of the baseline varies depending on the laser intensity and irradiation time from the light source 10 and the structure and material of the electric field enhancing element 20.

  Next, the second determination unit 98 compares the intensity difference ΔI with the baseline noise intensity σ. Then, the second determination unit 98 determines to replace the electric field enhancement element 20 when the intensity difference ΔI is greater than or equal to the intensity σ, and determines not to replace the electric field enhancement element 20 when the intensity difference ΔI is less than the intensity σ. To do. In the example shown in FIG. 6, since the intensity difference ΔI is equal to or greater than the intensity σ, the second determination unit 98 determines to replace the electric field enhancing element 20.

  The second determination unit 98 determines to replace the electric field enhancement element 20 when the intensity difference ΔI is equal to or greater than a preset value, and replaces the electric field enhancement element 20 when the intensity difference ΔI is less than the preset value. You may decide not to. Further, the second determination unit 98 may determine whether or not to replace the electric field enhancing element 20 based on a predetermined Raman shift peak value of the Raman spectrum.

  The detection apparatus 100 has the following features, for example.

  In the detection apparatus 100, the filter 40 that reflects light having the same wavelength as the wavelength of the first light L1 and transmits light having a wavelength different from the wavelength of the first light L1, and the filter 40 with respect to the second light L2, The 1st moving part 50 moved relatively to the 1st position where 2 light L2 does not enter, and the 2nd position where 2nd light L2 injects is included. Therefore, in the detection apparatus 100, the first determination unit 95 determines whether to replace the electric field enhancement element 20 based on the detection result of the photodetector 70 in a state where the filter 40 is in the first position. The second determination unit 98 can determine whether or not to replace the electric field enhancing element 20 based on the detection result of the photodetector 70 in a state where the filter 40 is in the second position. Thereby, the 1st determination part 95 can determine whether the electric field enhancement element 20 is replaced | exchanged based on the reflected light in the electric field enhancement element 20, and the 2nd determination part 98 is based on a Raman spectrum. Thus, it can be determined whether or not to replace the electric field enhancing element 20. Therefore, in the detection apparatus 100, the electric field enhancement element 20 is deteriorated due to the structural change of the electric field enhancement element 20 with time, and the target substance (molecule) is adsorbed on the surface of the electric field enhancement element 20 and the molecule cannot be removed. It is possible to detect the deterioration of the electric field enhancement element 20 caused by the above (see the experimental example described later for details). Therefore, in the detection apparatus 100, it is possible to replace the electric field enhancing element 20 as necessary while suppressing the number of times the electric field enhancing element 20 is replaced.

  For example, the light transmitted through the filter has a low intensity of light detected by the photodetector, and the intensity of the reflected light from the electric field enhancing element 20 may not be obtained accurately. In addition, light that does not pass through the filter has strong Rayleigh scattered light, cannot detect Raman scattered light having a wavelength close to the wavelength of Rayleigh scattered light, and may not be able to acquire an accurate Raman spectrum.

  In the detection apparatus 100, the electric field enhancing element 20 includes a metal microstructure 25 provided in the first region 21 a of the substrate 21 and a metal layer 26 provided in the second region 21 b of the substrate 21. Therefore, in the detection apparatus 100, the intensity of the reflected light (second reflected light intensity) in the metal microstructure 25 is divided by the intensity of the reflected light (first reflected light intensity) in the metal layer 26, thereby obtaining the metal microstructure. The influence of absorption in the 25 metal itself can be reduced, and the intensity ratio of reflected light based on the absorption in SPR can be obtained more accurately. Therefore, the first determination unit 81 can more accurately detect the deterioration of the electric field enhancement element 20 caused by the structural change of the electric field enhancement element 20 over time. Further, in the detection device 100, since the metal microstructure 25 and the metal layer 26 are provided in one electric field enhancing element 20, in order to obtain the first reflected light intensity and the second reflected light intensity, the element There is no need to replace the (substrate), and man-hours can be reduced.

  In the detection apparatus 100, the second determination unit 98 obtains an intensity difference ΔI between the intensity at a predetermined Raman shift of the Raman spectrum and the average intensity of the baseline of the Raman spectrum, and the intensity difference ΔI is calculated based on the baseline of the Raman spectrum. When it is larger than the noise, it is determined that the electric field enhancing element 20 is replaced. Therefore, in the detection apparatus 100, the second determination unit 98 can determine that the electric field enhancement element 20 is replaced even when a very small amount of molecules are attached to the electric field enhancement element 20.

2. Detection Method Next, a detection method according to the present embodiment will be described with reference to the drawings. FIG. 7 is a flowchart for explaining the detection method according to the present embodiment. Below, the detection method using the detection apparatus 100 is demonstrated as a detection method which concerns on this embodiment.

  For example, when the user requests processing for obtaining the concentration of the target substance via the operation unit 80, the processing unit 90 receives the operation signal from the operation unit 80 and starts processing. For example, when requesting processing, the user inputs the type of target substance to be analyzed (target of detection).

  First, the processing unit 90 performs a process for irradiating the light source 10 with the first light L1 (step S102). Specifically, the processing unit 90 outputs a signal for irradiating the first light L <b> 1 to the light source 10 via the control unit 60. The light source 10 receives the signal from the processing unit 90 and irradiates the electric field enhancing element 20 with the first light L1.

  Next, in the intensity ratio calculation unit 91, the filter 40 is in the first position (the position where the second light L2 is not incident on the filter 40), and the electric field enhancing element 20 is in the third position (the first light L1 on the metal layer 26). The first reflected light intensity is acquired based on the detection result of the photodetector 70 in the state (see FIG. 1) at the position where the light is incident (step S104). Specifically, the intensity ratio calculation unit 91 transmits the signal output from the photodetector 70 via the control unit 60 in a state where the filter 40 is in the first position and the electric field enhancing element 20 is in the third position. And receiving the first reflected light intensity.

  Next, after the intensity ratio calculation unit 91 obtains the first reflected light intensity, the second moving unit control unit 92 outputs a signal for driving the second moving unit 30 to the second moving unit 30. The electric field enhancing element 20 is moved from the third position (position where the first light L1 is incident on the metal layer 26) to the fourth position (position where the first light L1 is incident on the metal microstructure 25) (step S106).

  Next, based on the detection result of the photodetector 70 in the state where the filter 40 is in the first position and the electric field enhancing element 20 is in the fourth position (see FIG. 4), the intensity ratio calculation unit 91 The reflected light intensity is acquired (step S108). Specifically, the intensity ratio calculation unit 91 outputs the intensity of the second light L2 detected by the photodetector 70 after the signal is output from the second movement unit control unit 92 to the second movement unit 30 in step S106. (Second reflected light intensity) is acquired.

  Next, the intensity ratio calculation unit 91 obtains a reflected light intensity ratio (second reflected light intensity / first reflected light intensity ratio) by dividing the second reflected light intensity by the acquired first reflected light intensity (step S110). ).

Next, the first determination unit 95 determines whether or not to replace the electric field enhancing element 20 based on the reflected light intensity ratio r obtained by the intensity ratio calculation unit 91 (step S112). The first determination unit 95 is, for example, the first reflected light intensity ratio r ₁ obtained by the intensity ratio calculating unit 91 for the first time after replacing the electric field enhancing element 20 and the reflected light intensity obtained by the intensity ratio calculating unit 91 this time. When the difference Δr with respect to the ratio r is equal to or greater than r ₂ , it is determined that the electric field enhancement element 20 is replaced. When the difference Δr is less than r ₂ , it is determined that the electric field enhancement element 20 is not replaced.

  As described above, whether the electric field enhancing element 20 is irradiated with the first light L1 to detect the second light from the electric field enhancing element 20, and the electric field enhancing element 20 is exchanged based on the detected intensity of the second light L2. It can be determined whether or not.

  When the first determination unit 95 determines to replace the electric field enhancement element 20 (Yes in step S112), the first determination unit 95 displays an instruction to replace the electric field enhancement element 20 on the output unit 82. A signal is output (step S114). Furthermore, the first determination unit 95 outputs a signal for stopping the irradiation of the first light L <b> 1 in the light source 10 via the control unit 60. Then, the user replaces the electric field enhancing element 20 according to the display on the output unit 82.

  Next, after the first determination unit 95 outputs a signal to the output unit 82, the second moving unit control unit 92 outputs a signal for driving the second moving unit 30 to the second moving unit 30. The electric field enhancing element 20 is moved from the fourth position to the third position (step S116). Note that the order of step S114 and step S116 is not particularly limited.

Next, the process of step S102 to step S112 is performed on the replaced electric field enhancing element 20. In the replaced electric field enhancing element 20, the reflected light intensity ratio r obtained in step S110 is the first reflected light intensity ratio r ₁ obtained for the first time after replacing the electric field enhancing element 20, and the processing unit 90 stores the The value of the initial reflected light intensity ratio r ₁ stored in the unit 84 is overwritten with the obtained reflected light intensity ratio r. Therefore, the electric field enhancement device 20 is replaced, since the reflected light intensity ratio r = first reflected light intensity ratio r _1, the first determination unit 95 in step S112, it is determined not to replace the electric field enhancement device 20.

  When the first determination unit 95 determines not to replace the electric field enhancing element 20 (No in step S112), the first moving unit control unit 96 outputs a signal for driving the first moving unit 50 as the first signal. Output to the moving unit 50 to move the filter 40 from the first position (position where the second light L2 does not enter the filter 40) to the second position (position where the second light L2 enters the filter 40) (step S118). ).

  Next, the Raman spectrum acquisition unit 97 determines the Raman spectrum based on the detection result of the photodetector 70 in a state where the filter 40 is in the second position and the electric field enhancing element 20 is in the fourth position (see FIG. 5). Is acquired (step S120). Specifically, the Raman spectrum acquisition unit 97 has the filter 40 in the second position after the signal is output from the first moving unit control unit 96 to the first moving unit 50 in step S118, and the electric field enhancing element 20. Is in the fourth position, the signal output from the photodetector 70 is received via the control unit 60, and the Raman spectrum is acquired.

Next, the second determination unit 98 determines whether or not to replace the electric field enhancing element 20 based on the Raman spectrum (step S122). For example, the second determination unit 98 obtains an intensity difference ΔI between the intensity I _MAX in a predetermined Raman shift of the Raman spectrum and the average intensity I _AVE of the Raman spectrum baseline, and the intensity difference ΔI is the baseline of the Raman spectrum. It is determined that the electric field enhancement element 20 is to be replaced when the noise intensity σ is greater than or equal to the noise intensity σ, and it is determined that the electric field enhancement element 20 is not to be replaced when the intensity difference ΔI is less than the baseline noise intensity σ of the Raman spectrum.

  As described above, the electric field enhancing element 20 is irradiated with the first light L1, the second light L2 from the electric field enhancing element 20 is detected through the filter 40, and the intensity of the second light L2 detected through the filter 40 is increased. Based on this, it can be determined whether or not to replace the electric field enhancing element 20.

  When the second determination unit 98 determines to replace the electric field enhancement element 20 (Yes in step S122), the second determination unit 98 displays an instruction to replace the electric field enhancement element 20 on the output unit 82. A signal is output (step S124). Furthermore, the second determination unit 98 outputs a signal for stopping the irradiation of the first light L <b> 1 in the light source 10 via the control unit 60. Then, the user replaces the electric field enhancing element 20 according to the display on the output unit 82.

  Next, after the second determination unit 98 outputs a signal to the output unit 82, the second moving unit control unit 92 outputs a signal for driving the second moving unit 30 to the second moving unit 30, The electric field enhancing element 20 is moved from the fourth position to the third position (step S126).

  Next, the first moving unit control unit 96 outputs a signal for driving the first moving unit 50 after the second moving unit control unit 92 outputs a signal to the second moving unit 30 in step S116. The output is made to the moving unit 50, and the filter 40 is moved from the second position to the first position (step S128). The order of step S124, step S126, and step S128 is not particularly limited.

Next, the process of step S102 to step S112 and the process of step S118 to step S122 are performed on the replaced electric field enhancing element 20. In the replaced electric field enhancing element 20, the intensity I _MAX is smaller than the average intensity I _AVE and the intensity difference ΔI is less than the intensity σ. Therefore, in step S122, the second determination unit 98 determines not to replace the electric field enhancing element 20.

  When the second determination unit 98 determines not to replace the electric field enhancing element 20 (No in step S122), the processing unit 90 obtains, for example, the concentration of the target substance (step S130). Specifically, after the target substance is attached to the metal microstructure 25 of the electric field enhancing element 20 and the Raman scattered light is detected by the photodetector 70, the processing unit 90 displays the detection result of the photodetector 70. Based on this, the concentration of the target substance is determined. Then, the processing unit 90 outputs a signal for displaying the concentration of the target substance to the output unit 82, and ends the processing.

  The detection method according to the present embodiment has the following features, for example.

  In the detection method according to the present embodiment, the electric field enhancing element 20 is irradiated with the first light L1 to detect the second light L2 from the electric field enhancing element 20, and the electric field is determined based on the detected intensity of the second light L2. A step of determining whether to replace the enhancement element 20 (first step), and irradiating the electric field enhancement element 20 with the first light L1 and detecting the second light L2 from the electric field enhancement element 20 through the filter 40 And a step of determining whether or not to replace the electric field enhancing element 20 based on the intensity of the second light detected through the filter 40 (second step). Therefore, in the detection method according to the present embodiment, in the first step, it can be determined whether or not to replace the electric field enhancement element 20 based on the reflected light from the electric field enhancement element 20, and in the second step, the Raman spectrum is converted into the Raman spectrum. Based on this, it can be determined whether or not to replace the electric field enhancing element 20. Therefore, in the detection method according to the present embodiment, the electric field enhancement element 20 is deteriorated due to the structural change of the electric field enhancement element 20 with time, and the molecules cannot be adsorbed on the surface of the electric field enhancement element 20 to be removed. It is possible to detect the deterioration of the electric field enhancement element 20 caused by the above (see the experimental example described later for details). Therefore, in the detection method according to the present embodiment, the electric field enhancing element 20 can be exchanged as necessary while suppressing the number of exchanges of the electric field enhancing element 20.

3. Next, a detection method according to a modification of the present embodiment will be described with reference to the drawings. FIG. 8 is a flowchart for explaining a detection method according to a modification of the present embodiment. Hereinafter, in the detection method according to the modified example of the present embodiment, differences from the detection method according to the present embodiment will be described, and description of similar points will be omitted.

  In the detection method according to the present embodiment described above, as shown in FIG. 7, first, the first determination unit 95 determines whether or not to replace the electric field enhancement element 20 (step S112), and then the second determination unit. In 98, it was determined whether or not to replace the electric field enhancing element 20 (step S122). On the other hand, in the detection method according to the modification of the present embodiment, as shown in FIG. 8, first, the second determination unit 98 determines whether or not to replace the electric field enhancing element 20, and then the first determination. In section 95, it is determined whether or not to replace electric field enhancing element 20.

  In the detection method according to the modification of the present embodiment, the Raman spectrum acquisition unit 97 includes the photodetector 70 in a state where the filter 40 is in the second position and the electric field enhancing element 20 is in the fourth position (see FIG. 5). Based on the detection result, a Raman spectrum is acquired (step S120).

  Next, the second determination unit 98 determines whether or not to replace the electric field enhancing element 20 based on the Raman spectrum (step S122).

  When the second determination unit 98 determines to replace the electric field enhancement element 20 (Yes in step S122), the second determination unit 98 displays an instruction to replace the electric field enhancement element 20 on the output unit 82. A signal is output (step S124). Furthermore, the second determination unit 98 outputs a signal for stopping the irradiation of the first light L <b> 1 in the light source 10 via the control unit 60. Then, after the user replaces the electric field enhancing element 20, the processing unit 90 performs the processes of steps S102, S120, and S122 in the replaced electric field enhancing element 20.

  When the second determination unit 98 determines not to replace the electric field enhancing element 20 (No in step S122), the second moving unit control unit 92 outputs a signal for driving the second moving unit 30 to the second The electric field enhancing element 20 is output to the moving unit 30 and moved from the fourth position to the third position (step S132).

  Next, the first moving unit control unit 96 outputs a signal for driving the first moving unit 50 after the signal is output from the second moving unit control unit 92 to the second moving unit 30 in step S132. 1 is output to the moving unit 50, and the filter 40 is moved from the second position to the first position (step S134). Note that the order of step S132 and step S134 is not particularly limited.

  Next, based on the detection result of the photodetector 70 in the state where the filter 40 is in the first position and the electric field enhancing element 20 is in the third position (see FIG. 1), the intensity ratio calculation unit 91 The reflected light intensity is acquired (step S104).

  Next, the processing unit 90 performs the processes of S106, S108, S110, and S112.

  When the first determination unit 95 determines to replace the electric field enhancement element 20 (Yes in step S112), the first determination unit 95 displays an instruction to replace the electric field enhancement element 20 on the output unit 82. A signal is output (step S114). Furthermore, the second determination unit 98 outputs a signal for stopping the irradiation of the first light L <b> 1 in the light source 10 via the control unit 60. Then, after the user replaces the electric field enhancing element 20, the processing unit 90 performs the processes of steps S120, S120, S122, S202, S204, S104, S106, S108, and S112 in the replaced electric field enhancing element 20.

  When the first determination unit 95 determines not to replace the electric field enhancing element 20 (No in step S112), the first moving unit control unit 96 outputs a signal for driving the first moving unit 50 as the first signal. The output is made to the moving unit 50, and the filter 40 is moved from the first position to the second position (step S134).

Next, the processing unit 90 obtains the concentration of the target substance, for example, after the first moving unit control unit 96 outputs a signal to the first moving unit 50 in step S134 (step S130).
In the detection method according to the modified example of the present embodiment, the electric field enhancement element 20 can be replaced as necessary while suppressing the number of replacements of the electric field enhancement element 20 as in the detection method according to the present embodiment.

  Note that the detection method according to the present invention is not limited to the examples of the flowcharts shown in FIGS.

4). Specific Configuration of Detection Device Next, a specific configuration of the detection device according to the present embodiment will be described with reference to the drawings. Below, the specific structure of the detection apparatus 100 is demonstrated as a specific structure of the detection apparatus which concerns on this embodiment. FIG. 9 is a diagram for explaining a specific configuration of the detection apparatus 100. For the sake of convenience, the operation unit 80, the output unit 82, the storage unit 84, the storage medium 86, and the processing unit 90 are not shown in FIG.

  As shown in FIG. 9, the detection device 100 includes a control unit 60, a gas sample holding unit 210, a detection unit 220, and a housing 230 that houses the detection unit 220 and the control unit 60.

  The gas sample holding unit 210 includes an electric field enhancing element 20, a second moving unit 30, a cover 212 that covers the electric field enhancing element 20, a suction channel 214, and a discharge channel 216. When the user replaces the electric field enhancing element 20, the user opens the cover 212 and replaces the electric field enhancing element 20.

  The detection unit 220 includes the light source 10, the half mirror 12, lenses 14 a, 14 b, 14 c, 14 d, a filter 40, a first moving unit 50, and a photodetector 70.

  As shown in FIG. 9, the control unit 60 may be electrically connected to a connection unit 62 for connection to the outside.

  In the detection apparatus 100, when the suction mechanism 217 provided in the discharge flow channel 216 is operated, the suction flow channel 214 and the discharge flow channel 216 have negative pressure, and contain the target substance to be detected from the suction port 213. A gas sample is aspirated. The suction port 213 is provided with a dust removal filter 215, which can remove relatively large dust, some water vapor, and the like. The gas sample passes through the suction channel 214, the vicinity of the surface of the electric field enhancing element 20, and the discharge channel 216, and is discharged from the discharge port 218. When the gas sample passes near the surface of the electric field enhancing element 20, the target substance is adsorbed on the surface of the electric field enhancing element 20.

  The shapes of the suction channel 214 and the discharge channel 216 are such that light from the outside does not enter the electric field enhancing element 20. Thereby, the S / N ratio of the signal based on the intensity of the light detected by the photodetector 70 can be improved. The material constituting the channels 214 and 216 is, for example, a material or a color that hardly reflects light.

  The shapes of the suction channel 214 and the discharge channel 216 are such that the fluid resistance to the gas sample is reduced. Thereby, highly sensitive detection becomes possible. For example, retention of the gas sample in the corners can be eliminated by making the shapes of the channels 214 and 216 as smooth as possible by eliminating the corners. As the suction mechanism 217, for example, a fan motor or a pump having a static pressure and an air volume corresponding to the flow path resistance is used.

  In the detection device 100, the first light L1 emitted from the light source 10 is collected by the lens 14a, and then enters the electric field enhancement element 20 via the half mirror 12 and the lens 14b. The second light L2 is emitted from the electric field enhancing element 20, and the second light L2 reaches the photodetector 70 via the lens 14b, the half mirror 12, and the lenses 14c and 14d. The second light L2 includes Rayleigh scattered light having the same wavelength as the first light L1, and when it is desired to remove the Rayleigh scattered light, before the second light L2 reaches the photodetector 70, the second light L2 is incident on the filter 40. The second light L2 is received by the light receiving element 74 via the spectroscope 72 of the photodetector 70, for example.

  The spectroscope 72 of the photodetector 70 is formed of, for example, an etalon using Fabry-Perot resonance, and the pass wavelength band can be made variable. For example, a Raman spectrum peculiar to the target substance is obtained by the light receiving element 74 of the photodetector 70, and the signal intensity of the target substance is detected by comparing the obtained Raman spectrum with previously stored data (target The concentration of the substance can be determined).

5. Experimental Example An experimental example is shown below to describe the present invention more specifically. The present invention is not limited by the following experimental examples.

5.1. Sample substrate As a sample substrate used in the experimental example, an Ag layer (metal layer) having a thickness of 100 nm, an SiO ₂ layer (dielectric layer) having a thickness of 30 nm, and Ag particles (metal microstructures) on a glass substrate, They were formed in this order. Ag particles had a diameter (diameter in plan view) of 80 nm, a thickness of 30 nm, a pitch in the X-axis direction of 140 nm, and a pitch in the Y-axis direction of 400 nm. The sample substrate is designed so that a strong electric field enhancement effect can be obtained by SPR when a laser beam of 632.8 nm is irradiated.

5.2. First Experimental Example Ag particles on a sample substrate were irradiated with light using a white light source, and the intensity of reflected light was measured. Here, FIG. 10 is a SEM photograph of the sample substrate used in the experimental example. In this experimental example, as shown in FIG. 10, three types of sample substrates were used. The sample substrate A is a sample substrate that has never been used for detecting a target substance by Raman spectroscopy (a sample substrate in which no structural change of Ag particles has occurred) (see FIG. 10A). The sample substrate B was previously used to detect the target substance by Raman spectroscopy, but the structural change of Ag particles is not confirmed by SEM observation (see FIG. 10B). The sample substrate C is a sample substrate that was previously used for detecting a target substance by Raman spectroscopy, and in which the structural change of Ag particles was confirmed by SEM observation (see FIG. 10C).

  In this experimental example, an Ag layer (metal layer) having a thickness of 200 nm is further formed on a glass substrate to form a reference substrate, and the reference substrate is irradiated with light using a white light source, and the intensity of reflected light. Was measured. Then, in the sample substrates A, B, and C, the reflected light intensity ratio (the intensity of the reflected light on the sample substrate / the intensity of the reflected light on the reference substrate) was obtained.

  FIG. 11 is a graph showing reflected light intensity ratio spectra of sample substrates A, B, and C. FIG. 11 shows that the sample substrates A and B have relatively the same spectral shape, but the sample substrate C in which the structural change of the Ag particles is confirmed is significantly different from the sample substrates A and B. It was. Here, when SPR occurs, the light is confined around the Ag particles, and the reflected light intensity ratio becomes low. Therefore, the lower the reflected light intensity ratio, the stronger the electric field enhancement effect of the sample substrate. That is, the sample substrates A and B have a strong electric field enhancing effect and can increase the intensity of Raman scattered light, but the sample substrate C has a weaker electric field enhancing effect than the sample substrates A and B, and Raman scattering. It can be said that the intensity of light cannot be increased.

  FIG. 12 is a table (table showing the reflectance ratio of the wavelength 632.8 nm) obtained by extracting the value of the reflected light intensity ratio of the wavelength 632.8 nm shown in FIG. From FIG. 12, the difference between the reflected light intensity ratio of the sample substrate A and the reflected light intensity ratio of the sample substrate B is small, but the difference between the reflected light intensity ratio of the sample substrate A and the reflected light intensity ratio of the sample substrate C is I found it big.

  As described above, it is possible to detect deterioration of the sample substrate due to the structural change of Ag particles by examining the reflected light intensity ratio at a single wavelength using a laser light source without measuring a wide wavelength region using a white light source. I found out that

5.3. Second Experimental Example A Raman spectrum was obtained by irradiating Ag particles on a sample substrate with 632.8 nm laser light. In this experimental example, the sample substrate D that has never been used to detect the target substance by Raman spectroscopy, the sample substrates E and F that were previously used to detect the target substance by Raman spectroscopy, Raman spectra were obtained for the sample substrate G exposed to (exposed to) pyridine gas having a concentration of 20 ppm and the sample substrate H exposed to pyridine gas having a concentration of 3%.

FIG. 13 is a graph showing Raman spectra of the sample substrates D, E, F, G, and H. In the sample substrate F, a peak is confirmed in the vicinity of 1010 cm ⁻¹ . This is because when a Raman spectroscopy method was previously performed using the sample substrate F, molecules (pyridine) adhered to the surface of the Ag particles, and the molecules remained as they were without leaving.

As can be seen from the Raman spectra of the sample substrates G and H in FIG. 13, peaks with different intensities can be obtained according to the concentration of the target substance, and the concentration of the target substance (target molecule) can be quantified. Since the peak Raman shift value (position where the peak appears) differs depending on the molecule, the molecular species can also be specified from the Raman spectrum. Here, for example, when it is desired to quantify the pyridine concentration, the sample substrate was exposed to a sample when a peak was confirmed in the vicinity of 1010 cm ^{−1 in} the sample substrate before exposing (exposing) pyridine to the sample substrate as in the sample substrate F. The later peak intensity cannot be correctly determined. In particular, when a low concentration measurement is performed as in the case of the sample substrate G, if a peak exists before the pyridine is exposed to the sample substrate, the error becomes large. For example, the detection apparatus 100 can output an instruction to replace such a sample substrate G. Note that FIG. 6 described above is a Raman spectrum of the sample substrate H.

FIG. 14 is a table showing the intensity difference ΔI of the sample substrates D, E, F, G, and H and the baseline noise intensity σ. As described above, the intensity difference ΔI is a value obtained by subtracting the baseline average intensity I _AVE from the intensity I ₁ , and the baseline noise intensity σ is the value of the baseline standard deviation. As described above, when it is determined that the electric field enhancing element 20 is to be replaced when the intensity difference ΔI is greater than or equal to the intensity σ, the sample substrate D is replaced.

  As described above, it was found from the Raman spectrum that the degradation of the sample substrate caused by the target substance adsorbed on the surface of the sample substrate and the removal of the molecule cannot be detected.

  The above-described embodiments and modifications are merely examples, and the present invention is not limited to these. For example, it is possible to appropriately combine each embodiment and each modification.

  The present invention includes configurations that are substantially the same as the configurations described in the embodiments (for example, configurations that have the same functions, methods, and results, or configurations that have the same objects and effects). In addition, the invention includes a configuration in which a non-essential part of the configuration described in the embodiment is replaced. In addition, the present invention includes a configuration that exhibits the same operational effects as the configuration described in the embodiment or a configuration that can achieve the same object. Further, the invention includes a configuration in which a known technique is added to the configuration described in the embodiment.

DESCRIPTION OF SYMBOLS 10 ... Light source, 12 ... Half mirror, 14, 14a, 14b, 14c, 14d ... Lens, 20 ... Electric field enhancement element, 21 ... Substrate, 21a ... First region, 21b ... Second region, 22 ... Support substrate, 23 ... Metal layer, 24 ... Dielectric layer, 25 ... Metal microstructure, 26 ... Metal layer, 30 ... Second moving part, 40 ... Filter, 50 ... First moving part, 60 ... Control part, 62 ... Connecting part, 70 DESCRIPTION OF SYMBOLS ... Photodetector, 72 ... Spectroscope, 74 ... Light receiving element, 80 ... Operation part, 82 ... Output part, 84 ... Memory | storage part, 85 ... Database, 86 ... Storage medium, 90 ... Processing part, 91 ... Intensity ratio calculating part , 92 ... 2nd moving part control part, 95 ... 1st determination part, 96 ... 1st moving part control part, 97 ... Raman spectrum acquisition part, 98 ... 2nd determination part, 100 ... Detection apparatus, 210 ... Gas sample holding | maintenance Part 212 ... cover 213 ... suction port 214 ... suction Passage, 215 ... dust filter, 216 ... discharge passage, 217 ... suction mechanism, 218 ... discharge port, 220 ... detector

Claims (9)

An electric field enhancing element;
A light source for irradiating the electric field enhancing element with first light;
A photodetector for detecting second light emitted by the electric field enhancing element when the electric field enhancing element is irradiated with the first light;
A filter that reflects light having the same wavelength as the wavelength of the first light and transmits light having a wavelength different from the wavelength of the first light;
A first moving unit that moves the filter relative to the second light relative to a first position where the second light is not incident and a second position where the second light is incident;
Including a detection device. In claim 1,
A first determination unit that determines whether to replace the electric field enhancement element based on a detection result of the photodetector in a state where the filter is in the first position;
A second determination unit that determines whether to replace the electric field enhancement element based on a detection result of the photodetector in a state where the filter is in the second position;
Including a detection device. In claim 2,
The electric field enhancing element is
A substrate,
A metal microstructure provided in a first region of the substrate;
A metal layer provided in a second region of the substrate;
A detection device. In claim 3,
The electric field enhancing element is relative to the first light at a third position where the first light is incident on the metal layer and a fourth position where the first light is incident on the metal microstructure. A second moving part to be moved to,
Based on the detection result of the photodetector in a state where the filter is in the first position and the electric field enhancing element is in the third position, the intensity of the first reflected light is obtained,
Based on the detection result of the photodetector in a state where the filter is in the first position and the electric field enhancing element is in the fourth position, the intensity of the second reflected light is obtained,
An intensity ratio calculation unit for obtaining an intensity ratio of reflected light from the intensity of the first reflected light and the intensity of the second reflected light;
Including
The first determination unit is a detection device that determines whether to replace the electric field enhancement element based on the intensity ratio. In any one of Claims 2 thru | or 4,
A Raman spectrum acquisition unit that acquires a Raman spectrum based on a detection result of the photodetector in a state where the filter is in the second position;
The detection device, wherein the second determination unit determines whether or not to replace the electric field enhancement element based on the Raman spectrum. In claim 5,
The second determination unit obtains a difference between an intensity at a predetermined Raman shift of the Raman spectrum and an average intensity of the baseline of the Raman spectrum, and the difference is equal to or greater than a noise intensity of the baseline of the Raman spectrum. And a detection device that determines to replace the electric field enhancement element. In any one of Claims 2 thru | or 6,
An inspection apparatus including an output unit that outputs a determination result of the first determination unit and a determination result of the second determination unit. Irradiating the electric field enhancing element with the first light, detecting the second light from the electric field enhancing element, and determining whether to replace the electric field enhancing element based on the detected intensity of the second light Process,
Irradiating the electric field enhancing element with the first light to detect the second light from the electric field enhancing element through a filter, and based on the intensity of the second light detected through the filter, Determining whether to replace the electric field enhancing element; and
Including
The detection method, wherein the filter reflects light having the same wavelength as the wavelength of the first light and transmits light having a wavelength different from the wavelength of the first light. A substrate,
A metal microstructure provided in a first region of the substrate;
A metal layer provided in a second region of the substrate;
Including an electric field enhancement element.