JP2014190915A - Detector and electronic equipment - Google Patents

Detector and electronic equipment Download PDF

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JP2014190915A
JP2014190915A JP2013068261A JP2013068261A JP2014190915A JP 2014190915 A JP2014190915 A JP 2014190915A JP 2013068261 A JP2013068261 A JP 2013068261A JP 2013068261 A JP2013068261 A JP 2013068261A JP 2014190915 A JP2014190915 A JP 2014190915A
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sensor substrate
light
dielectric layer
position
sensor
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JP6248403B2 (en
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Kohei Yamada
耕平 山田
Tetsuo Mano
哲雄 眞野
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Seiko Epson Corp
セイコーエプソン株式会社
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Abstract

PROBLEM TO BE SOLVED: To provide a detector and electronic equipment in which, even when a refractive index of a medium around a metal nanostructure varies by adsorption to the metal nanostructure to shift a plasmon resonance wavelength from a designed value, an optical path length of a resonator can be changed in accordance with the shift amount.SOLUTION: A detector 20A, 20B for detecting a target molecule included in a fluid sample includes: a sensor substrate 10; a moving mechanism 70 which moves the sensor substrate; a light source 30 which irradiates the sensor substrate with light to induce surface enhanced Raman scattering; and a photodetector 50 which detects surface enhanced Raman scattering light. The sensor substrate includes: a mirror layer 14; a dielectric layer 16 which is disposed on the mirror layer and has a thickness t that continuously changes along a direction X where the thickness changes; and a plurality of metal nanostructures 18 disposed on the dielectric layer, which are to be in contact with the fluid sample. The moving mechanism moves the sensor substrate along the direction X where the thickness changes.

Description

  The present invention relates to a detection device, an electronic device, and the like that detect a target molecule.

In recent years, surface-enhanced Raman scattering using surface plasmon resonance (SPR), particularly localized surface plasmon resonance (LSPR), is one of the highly sensitive spectroscopic techniques for detecting low concentrations of target molecules. (SERS: Surface Enhanced Raman Scattering) spectroscopy has attracted attention. SERS is a phenomenon in which an enhanced electric field is formed between metal nanostructures included in a nanometer-scale uneven structure, and Raman scattered light is enhanced by, for example, 10 2 to 10 14 times by the enhanced electric field. A target molecule is irradiated with excitation light of a single wavelength such as a laser. A fingerprint spectrum is obtained by spectroscopic detection of a scattered wavelength (Raman scattered light) slightly shifted from the wavelength of the excitation light by the molecular vibration energy of the target molecule. A very small amount of target molecule can be identified from the fingerprint spectrum.

  Various structures of SERS sensors exhibiting strong enhancement have been proposed. In Patent Document 1, metal nanostructures are arranged on a mirror layer via a dielectric layer. This structural model is reported as a GSP (Gap type Surface Plasmon) model in Non-Patent Document 1.

  When the GSP model sensor is irradiated with light, in the metal nanostructure, the incident light and the light reflected by the mirror layer are strengthened by phase interference, resulting in a strong electric field enhancement by plasmon resonance. When a metal mirror is used for the mirror layer and the arrangement of the metal nanostructures is arranged at a constant period below the incident wavelength, irradiation with light excites localized surface plasmon LSP and propagating surface plasmon PSP (Propagating Surface Plasmon). Bonding occurs between both plasmons, and a very strong electric field appears on the surface of the metal nanostructure.

  In the GSP model sensor, the resonator structure is designed in accordance with the wavelength of the measurement light that matches the target molecule to be detected. When the target molecule to be detected is changed, the wavelength of the measurement light must be changed. If the wavelength of the measuring light is changed, the resonator structure must also be changed to match the wavelength of the measuring light. Patent Document 2 proposes a structure in which a plurality of dielectric layers having different thicknesses are provided in a substrate surface. As described above, since the resonator structure capable of optical resonance with respect to a plurality of wavelengths is provided in one electric field enhanced optical device, the single electric field enhanced optical device can cope with the wavelength change of the measuring light.

Special table 2007-538264 gazette JP 2009-250951 A

OPTICS LETTERS / Vol. 34, No. 3 / February 1, 2009

  When the target molecule is adsorbed on the surface of the metal nanostructure, the medium around the metal nanostructure changes from air to the target molecule. Thus, even when the same target molecule is detected, the refractive index of the medium around the metal nanostructure changes, so that the plasmon resonance wavelength is shifted from the design value. This shift amount differs depending not only on the type of target molecule adsorbed on the metal nanostructure, but also on the amount of adsorption.

  Patent Document 2 is merely provided with a plurality of resonator structures as designed values that match the plasmon resonance wavelength according to the type of target molecule adsorbed on the metal nanostructure, and the plasmon resonance wavelength is shifted from the design value. It becomes impossible to cope with.

  In some embodiments of the present invention, even when the refractive index of the medium around the metal nanostructure is changed by the adsorption to the metal nanostructure and the plasmon resonance wavelength is shifted from the design value, the resonator is adjusted according to the shift amount. It is an object of the present invention to provide a detection device and an electronic apparatus that can change the optical path length of the light.

(1) One aspect of the present invention is
A detection device for detecting a target molecule contained in a fluid sample,
A sensor substrate;
A moving mechanism for moving the sensor substrate;
Illuminating the sensor substrate with light to cause surface enhanced Raman scattering to appear; and
A photodetector for detecting surface enhanced Raman scattered light;
Have
The sensor substrate is
Mirror layer,
A dielectric layer provided on the mirror layer and having a thickness change direction in which the thickness continuously increases or decreases;
A plurality of metal nanostructures provided on the dielectric layer;
Have
The movement mechanism relates to a detection device that moves the sensor substrate along the thickness change direction.

  According to one aspect of the present invention, when the sensor substrate is moved along the thickness change direction of the dielectric layer by the moving mechanism, the thickness of the dielectric on the sensor substrate changes continuously. Therefore, the thickness of the dielectric of the sensor substrate can be selected by the moving mechanism. Moreover, the thickness of the dielectric can be finely adjusted according to the minimum feed pitch of the moving mechanism. On the other hand, since a plurality of metal nanostructures can be regarded as a layer, the optical path length of a resonator formed of a laminated structure of a mirror layer, a dielectric layer, and a plurality of metal nanostructures is determined by the thickness of the dielectric Is done. Even if the refractive index of the medium surrounding the metal nanostructure changes due to adsorption of the target molecule to the metal nanostructure, and the plasmon resonance wavelength shifts from the design value, it moves according to the shifted surface plasmon resonance wavelength. The thickness of the dielectric can be selected by the mechanism.

(2) In one aspect of the present invention, the surface of the dielectric layer can be inclined at a constant angle. Thereby, the thickness continuously changes along the thickness change direction of the dielectric layer. The inclination angle θ (°) for adjusting the optical path length of the resonator may be a very small angle, for example, 1.0 × 10 −5 ≦ θ ≦ 1 × 10 −3 .

  (3) In one aspect of the present invention, the dielectric layer may be formed by laminating a plurality of dielectrics made of different materials. For example, one of the plurality of dielectrics can be an adhesion layer having good adhesion to the mirror layer. For example, the thickness of only one layer of the plurality of dielectrics may be changed as long as the thickness of the plurality of dielectrics continuously changes along the thickness change direction.

  (4) In one aspect of the present invention, the sensor substrate is moved along the thickness change direction by the moving mechanism, and the sensor substrate is irradiated with light at a plurality of positions, and is detected by the photodetector. And a controller that sets a correction position of the sensor substrate based on the result of the surface-enhanced Raman scattering light. The control unit selects the position of the sensor substrate where the signal level of the Raman scattered light is maximum as the correction position, so that the optical path length of the resonator matching the plasmon resonance wavelength can be selected. In this case, the correction position can be detected using the photodetector as it is in the same manner as the original detection operation.

  (5) In one aspect of the present invention, the sensor substrate is moved along the thickness change direction by the moving mechanism, the sensor substrate is irradiated with light at a plurality of positions, and reflected by the sensor substrate. The image processing apparatus may further include a control unit that sets a correction position of the sensor substrate based on the result of the reflected light. The controller can select the optical path length of the resonator that matches the plasmon resonance wavelength by selecting the position of the sensor substrate at which the signal level of the reflected light is minimum as the correction position. The signal level of the reflected light depends on mismatching of the optical path length of the resonator, and is not as sensitive to a minute concentration change of the target molecule in the fluid sample as the signal level of the Raman scattered light. However, most of the reflected light is Rayleigh scattered light having the same wavelength as the light source light, and cannot be detected using a photodetector that detects Raman-shifted Raman scattered light as it is.

(6) In one aspect of the present invention, the photodetector can be set so that a light pass band is different between a detection mode for receiving the Raman scattered light and a correction mode for receiving the reflected light. . Thus, even in the case of (5), the Rayleigh scattered light that occupies most of the reflected light can be detected by the photodetector. In a photodetector in which the correction mode is implemented, for example, a Rayleigh cut filter that cuts Rayleigh light having the same wavelength as the light source light is removed from the optical path, and the spectroscope receives a wavelength band of the light source light (Raman shift = 0 cm). -1 ) to receive reflected light (Rayleigh scattered light).

(7) Still another aspect of the present invention is
The detection device according to any one of (1) to (6);
A calculation unit for calculating health and medical information based on detection information from the detection device;
A storage unit for storing health and medical information;
A display unit for displaying the health care information;
The present invention relates to an electronic device including This electronic device is useful for medical diagnosis and inspection of food and drink.

It is sectional drawing which shows schematically the sensor board | substrate of a detection apparatus. It is a figure explaining the resonator structure of the sensor substrate of FIG. It is a figure for demonstrating wavelength shift. It is sectional drawing of the sensor board | substrate which concerns on one Embodiment of this invention. 5A and 5B are views showing a sputtering apparatus for forming a dielectric of the sensor substrate. FIGS. 6A and 6B are views showing a vapor deposition apparatus for forming a dielectric of the sensor substrate. It is a figure which shows the reflectance measured by shifting the X direction position of the sensor board | substrate shown in FIG. It is a figure which shows the correction | amendment position of the sensor board | substrate from which thickness differs continuously along a X direction. It is a figure which shows the detection apparatus which concerns on 1st Embodiment of this invention. It is a tuning control system block diagram of a detection apparatus. It is a figure which shows the position dependence of the SRES signal strength accompanying a wavelength shift. It is a figure which shows the detection apparatus which concerns on 2nd Embodiment of this invention. 13A to 13C illustrate electronic devices. It is a block diagram of an electronic device.

  Hereinafter, preferred embodiments of the present invention will be described in detail. The present embodiment described below does not unduly limit the contents of the present invention described in the claims, and all the configurations described in the present embodiment are indispensable as means for solving the present invention. Not necessarily.

1. 1. First embodiment 1.1. Resonator of Sensor Substrate FIG. 1 is a cross-sectional view schematically showing a sensor substrate of a detection apparatus according to this embodiment. As shown in FIG. 1, a dielectric layer 17 is provided on the surface of the sensor substrate, and a plurality of metal nanostructures 18 are formed thereon.

  Excitation light (frequency ν) from the light source is applied to the sensor substrate in contact with the fluid sample containing the target molecule 1 with a beam diameter of 1 to 10 μm, for example. As shown in FIG. 1, most of the excitation light (incident light) is scattered as Rayleigh scattered light, and the frequency ν or wavelength of the Rayleigh scattered light does not change with respect to the incident light. A part of the excitation light is scattered as Raman scattered light, and the frequency (ν−ν ′ and ν + ν ′) or wavelength of the Raman scattered light reflects the frequency ν ′ (molecular vibration) of the target molecule. That is, the Raman scattered light is light reflecting the target molecule 1 to be examined. A part of the excitation light loses energy by vibrating the target molecule, but the vibration energy of the target molecule may be added to the vibration energy or light energy of the Raman scattered light. Such a frequency shift (ν ′) is called a Raman shift.

  In the region where the excitation light is incident on the plurality of metal nanostructures 18, the enhanced electric field 2 is formed in the gap between the adjacent metal nanostructures 18. In particular, when the incident light is irradiated onto the metal nanostructure 18 having a wavelength smaller than that of the incident light, the electric field of the incident light acts on free electrons existing on the surface of the metal nanostructure 18 to cause resonance. Thereby, electric dipoles due to free electrons are excited in the metal nanostructure 18, and an enhanced electric field 2 stronger than the electric field of incident light is formed. This is also called Localized Surface Plasmon Resonance (LSPR). This phenomenon is a phenomenon peculiar to an electric conductor such as the metal nanostructure 18 having a size smaller than the wavelength of incident light, for example, 1 to 500 nm in plan view.

  When the sensor substrate is irradiated with incident light, surface enhanced Raman scattering (SERS) occurs. That is, when the target molecule 1 enters the enhanced electric field 2, the Raman scattered light from the target molecule 1 is enhanced by the enhanced electric field 2, and the signal intensity of the Raman scattered light increases. In such surface-enhanced Raman scattering, the detection sensitivity can be increased even if the amount of the target molecule 1 is very small.

  Since the plurality of metal nanostructures 18 can be regarded as layers, the structure shown in FIG. 1 is regarded as a laminated film structure as shown in FIG. In FIG. 2, a resonator is configured by a laminated structure of the mirror layer 14, the dielectric layer 17, and the deemed mirror layer (semi-transparent semi-reflective layer) 18A (GSP model). This resonator is determined by the thickness of the dielectric 18 whose optical path length is a gap portion. For example, the antinodes of standing waves obtained by superimposing the incident waves and the reflected waves generated at the interfaces (between 14-17 and 17-18A) are regarded in FIG. 2 as positions in the mirror layer 18A (broken lines in FIG. 2). ), The plasmon resonance wavelength can be set by setting the film thickness of the dielectric layer 18. At this time, the following equation (1) is approximately given as the relationship between the parameters of the structure shown in FIG. 2 and the plasmon resonance wavelength.

Here, λ is a plasmon resonance wavelength, and m is an integer. Also, n particle and d particle are the refractive index and film thickness of the metal nanostructure 18, n gap and d gap are the refractive index and film thickness of the dielectric layer 17, and φ mirror is the dielectric layer 17 and the mirror layer. This is the amount of phase change [rad] that occurs when reflecting at the 14 interface. When the mirror layer 14 is a single-layer metal film, φ mirror is given by the following equation (2).

Here, n mirror and d mirror are the refractive index and extinction coefficient of the mirror layers 14 and 18A. When the mirror layer 14 is a dielectric mirror, φ mirror = 0 when the refractive index of the dielectric layer 17 in the gap portion is higher than the first layer of the dielectric mirror 14, and φ mirror = π when the refractive index is lower. In addition, when the dielectric layer 17 of the gap layer is composed of a plurality of layers, it is desirable that each dielectric layer of the gap layer satisfies the expression (1). At this time, the second term (2n gap · d gap ) on the right side of the equation (1) is calculated as the sum of the products of the refractive index and the film thickness of each dielectric layer forming the gap layer.

1.2. Wavelength shift When the mirror layer 14 in FIG. 1 is an Au film, the dielectric layer 17 is an SiO 2 layer, and the metal nanostructure 18 is an Ag nanoparticle, the reflectance characteristics of the sensor substrate having the GSP structure in FIG. Shown in In FIG. 3, light exposure due to surface plasmon resonance is observed at 632 nm, which is the wavelength of the light source light incident on the sensor substrate 1, before exposure for supplying the fluid sample to the sensor substrate. This absorption is derived from localized surface plasmons excited by a photoelectric field obtained by superimposing incident light and reflected light generated at each interface.

  Here, when the sensor substrate is exposed to a gas (fluid) and a substance is adsorbed around the metal nanostructure 18, a wavelength shift is caused by a change in refractive index generated at that time. The following formula (3) is a formula related to the polarizability α of the metal nanostructure 18.

As shown in Equation (3), the polarizability α of the metal nanostructure 18 is determined by the complex refractive index N (λ) (N (λ) = n (λ) + ik n of the metal nanostructure 18; (Absorption coefficient) and the complex refractive index N 0 of the medium around the metal nanostructure 18. The resonance condition for the polarizability α to be infinite in equation (3) is 0 in the denominator of equation (3) as in equation (4).

As shown in Formula (4), the localized plasmon resonance wavelength by the metal nanostructure 18 is affected by the complex refractive index N 0 of the medium around the metal nanostructure 18. In a state where nothing is adsorbed on the metal nanostructure 18, the medium around the metal nanostructure 18 is air (N 0 = 1). When the target molecule 1 is adsorbed on the metal nanostructure 18, a part of the medium is changed from the air to the target molecule 1 (N 0 is a value other than 1), so that the refractive index N 0 of the entire medium slightly changes. A minute change in the refractive index N 0 of the medium appears in the form of a shift of the localized plasmon resonance wavelength λ.

  As a result, the wavelength at which the electric field enhancement 2 occurs is also shifted. The wavelength shift amount also varies depending on the refractive index n of the adsorbed substance on the metal nanostructure 18 and the amount of adsorbed substance. FIG. 3 also shows the reflectance characteristics after the adenine solution was exposed and adsorbed by changing the amount to 10 nM and 10 μM. It can be seen that due to the adsorption of adenine molecules, the wavelength shift (red shift) in the red direction is about 5 nm at 10 nM and about 20 nm at 10 μM.

1.3. Sensor substrate with continuously variable optical path length The sensor substrate 10 of the present embodiment shown in FIG. 4 has a dielectric layer 16 instead of the dielectric layer 17 of the sensor substrate of FIG. The thickness t of the dielectric layer 16 continuously changes in the X direction. Since the dielectric layer 16 has a structure in which the thickness of the dielectric layer 16 is continuously changed in the plane of the sensor substrate 10, it can have various resonance wavelengths depending on the position in the X direction in the plane of the substrate 10.

  In the SERS sensor substrate 10 that detects the substance using the enhanced electric field 2 by surface plasmon resonance, the wavelength of the surface plasmon resonance is matched with the wavelength of incident light or the Raman scattering wavelength of the detection target. This is because the SERS enhancement is said to be proportional to the product of the square of the electric field enhancement at the incident wavelength and the square of the electric field enhancement at the scattering wavelength. In the present embodiment, the thickness t of the dielectric layer 16 at which the wavelength of the light source light becomes the surface plasmon resonance wavelength is set at, for example, the center position in the X direction. The thickness t of the dielectric layer 16 continuously and smoothly changes as the distance from the center position in the X direction increases in the X direction. In FIG. 4, the thickness t is uniformly increased or decreased uniformly toward the both sides in the X direction from the center position. In this way, by relatively moving the sensor substrate 10 and the optical axis of the detection device, the optical path length of the resonator (the thickness t of the dielectric layer 16) is set within a predetermined range in response to the wavelength shift described above. Can be selected arbitrarily. In this way, the sensor substrate 10 that is uniformly increased or decreased can predict which direction the optimum position after the wavelength shift is, so that there is an advantage that tuning described later can be easily performed.

As shown in FIG. 4, the sensor substrate 10 was formed by forming, for example, Cr with a thickness of 3 nm on the glass substrate 12 and then forming, for example, Au with a thickness of 250 nm as the mirror layer 14 by sputtering, for example. On the mirror layer 14, alumina Al 2 O 3 as a dielectric is formed as an adhesion layer 16 A with a thickness of 5 nm, for example, by sputtering. For example, SiO 2 is used for the dielectric layer 16B as the main gap layer on the adhesion layer 16A. In the present embodiment, the dielectric layer 16 is formed by laminating two dielectric layers 16A and 16B, and by continuously changing the thickness of the upper dielectric layer 16A along the X direction, The wedge-shaped surface 16C is inclined with respect to the -Y plane. Note that the adhesion layer 16A may be omitted, or a dielectric layer other than the adhesion layer 16A may be laminated.

  FIGS. 5A and 5B and FIGS. 6A and 6B show a method for forming the wedge-shaped dielectric layer 16B. In FIG. 5A showing an example of sputtering, the substrate 10 ′ in the middle of processing in which the mirror layer 14 and the adhesion layer 16 </ b> A are formed on the glass substrate 12 is supported by the rotating drum 3. The rotating drum 3 is rotated about a rotating shaft 3A with a substrate 10 'mounted on each surface of the polyhedron. A correction plate 5 is disposed between the target 4 formed of the material of the dielectric layer 16B and the substrate 10 '. As shown in FIG. 5B, the correction plate 5 has a trapezoidal window 5A, for example. The width W of the window 5A changes continuously along the X direction. Since there is a positive correlation between the width W of the window 5A and the film formation rate, a uniform thickness increase distribution in the X-axis direction can be formed in the plane of the substrate 10 '.

  In the case of vapor deposition, a similar correction plate 7 is installed between the vapor deposition source 6 and the substrate 10 'as shown in FIG. The correction plate 7 also has a trapezoidal window 7A as shown in FIG. The width W of the window 7A changes continuously along the X direction. By depositing the substrate 10 'on the rotary stage 8 and forming the film while rotating, a uniform increase distribution of the thickness in the X-axis direction can be formed in the plane of the substrate 10'. Further, in both sputtering and vapor deposition, the substrate 10 ′ may be tilted to form a film without using the correction plates 5 and 7. In that case, the portion closer to the target 4 and the vapor deposition source 6 has a larger thickness of the thin film.

Thereafter, a metal nanostructure in which a plurality of metal particles 18 are provided at intervals is formed on the dielectric layer 16. The metal nanostructure may be formed by using a photolithography technique, or may be an island-like structure formed by simply depositing a metal by about 10 nm. Further, in FIG. 4, the thickness distribution is given only to the dielectric layer 16B made of SiO 2 , but the thickness distribution may be given to both the dielectric layers 16A and 16B, or only the underlying dielectric layer 16A is thick. It may have a thickness distribution, and further may have a thickness distribution including the upper metal nanostructure.

FIG. 7 shows the reflectance characteristics of the sensor substrate 10 provided with the dielectric layer 16 having the thickness t continuously changing along the X direction. The thicknesses of SiO 2 obtained by fitting from the reflectance characteristics in FIG. 7 were 230 nm, 240 nm, 250 nm, and 260 nm, respectively, at positions 1 to 4 in the X direction shown in FIG. The distance from positions 1 to 4 is 15 mm in the X direction. The inclination angle θ at this time is θ = tan −1 (30 nm / 15 mm) = 1.15 × 10 −4 degrees. The inclination angle θ can be 1.0 × 10 −5 ≦ θ ≦ 1 × 10 −3 . This numerical range is a numerical range that is supported by an appropriate effective area size (for example, 3 mm to 30 mm) that is easy to handle the sensor substrate 10 with the LSPR wavelength shift range being set to 100 nm that can cope with any target molecule adsorption.

  For example, 632 nm is used as the surface-enhanced Raman excitation wavelength for detecting the target molecule 1. At this time, it can be seen from FIG. 7 that the position of the substrate having the maximum enhancement effect with respect to 632 nm is around position 2 where the reflectance is minimum near 632 nm. However, when adenine is exposed, the surface plasmon resonance wavelength is red-shifted as shown in FIG. 3, and when the concentration is high, the wavelength is shifted by about 20 nm. For this reason, position 2 deviates from the surface plasmon resonance wavelength after the shift. For this reason, high enhancement cannot be obtained, resulting in a decrease in sensitivity. In this case, the position corresponding to the surface plasmon resonance wavelength after adenine adsorption always exists by sliding the measurement location to the position 1 (the reflectance is minimum at around 600 nm) side. The maximum detection sensitivity can be obtained by measuring at that location.

1.4. Detection Device FIG. 9 shows a specific configuration example of the detection device 20A of the present embodiment. In the detection apparatus 20A shown in FIG. 9, in addition to the sensor substrate 10 shown in FIG. 4, a light source 30, an optical system 40, and a detection unit 50 are shown.

  In FIG. 9, the light from the light source 30 is collimated by the collimator lens 410 constituting the optical system 40. A polarization control element may be provided downstream of the collimator lens 410 and converted to linearly polarized light. However, if, for example, a surface emitting laser is employed as the light source 30 and light having linearly polarized light can be emitted, the polarization control element can be omitted.

  The light collimated by the collimator lens 410 is guided toward the sensor substrate 10 by a half mirror (dichroic mirror) 420, condensed by the objective lens 430, and incident on the sensor substrate 10. The sensor substrate 10 has the resonator structure shown in FIG.

  The sensor substrate 10 is arranged facing the fluid sample flow path 60. The channel 60 includes a suction channel 62 connected to the suction port 61 and a discharge channel 64 connected to the discharge port 63. The suction port 61 is provided with a dust removal filter 65, and the discharge port 63 is provided with a fan or a pump 66.

  The sensor substrate 10 can be moved in the X direction by a moving mechanism 70 including an X stage movable in the X direction. The moving mechanism 70 can adjust, for example, positions 0 to 4 shown in FIG. 8 to the optical axis by moving the sensor substrate 10 in the X direction with respect to the optical axis of the optical system 40. Thereby, the X direction position of the dielectric layer 16 having a different thickness t along the X direction shown in FIG. 4 is selected, and the optical path length of the resonator is made variable.

  As shown in FIG. 1, the sensor substrate 10 emits Rayleigh scattered light and Raman scattered light due to surface enhanced Raman scattering. Rayleigh scattered light and Raman scattered light from the sensor substrate 10 pass through the objective lens 430, and are guided toward the photodetector 50 by the half mirror 420.

  Rayleigh scattered light and Raman scattered light from the sensor substrate 10 are collected by the condenser lens 440 and input to the photodetector 50. First, the photodetector 50 reaches the optical filter 510. Rayleigh scattered light is cut by an optical filter 510 (for example, a notch filter as a Rayleigh cut filter), and Raman scattered light is extracted. This Raman scattered light is further received by the light receiving element 530 via the spectroscope 520. The spectroscope 520 is formed of, for example, an etalon using Fabry-Perot resonance, and the pass wavelength band can be made variable. The wavelength of the light passing through the spectroscope 520 can be controlled (selected) to the wavelength of the Raman scattered light of the target molecule to be detected. The light receiving element 530 obtains a Raman spectrum peculiar to the target molecule 1, and the signal intensity of the target molecule 1 can be detected by collating the obtained Raman spectrum with previously stored data.

1.5. Tuning of Correction Position for Wavelength Shift FIG. 10 is a control system block diagram for tuning the correction position for wavelength shift. As shown in FIG. 10, the control unit 80 that controls the detection apparatus 20A includes a CPU 81, a ROM 82, a RAM 83, and the like. A light source 30, a light detector 50, a fan 66 and a moving mechanism 70 are connected to the bus line of the CPU 80. The moving mechanism 70 includes an X stage 71 and a drive unit 72 that drives the X stage 71, and the drive unit 72 is connected to the bus line.

  The control unit 80 controls the detection mode for receiving the Raman scattered light and the tuning correction mode for the correction position for the wavelength shift. Hereinafter, the correction mode will be described. In the correction mode, the control unit 80 moves the sensor substrate 10 along the X direction by the moving mechanism 70, and the light source 30 applies the sensor substrate 10 set at each of the positions including the plurality of positions 0 to 4 illustrated in FIG. 8. The correction position of the sensor substrate 10 can be determined on the basis of the Raman scattered light detected by the light detector 50 and irradiated with light.

  Hereinafter, a tuning method in which the control unit 80 automatically obtains a correction position from the SERS signal intensity after exposing the target molecule gas to the sensor substrate 10 as the target molecule 1 will be described with reference to FIG. The direction in which the thickness of the dielectric layer 16 of the sensor substrate 10 shown in FIG. 4 increases (resonance wavelength shifts in red) is defined as right, and the direction in which the thickness decreases (resonance wavelength shifts in blue) is defined as left.

  A position K shown in FIG. 11 is set as an initial position. After driving the fan 66 to expose the target molecule 1 to the sensor substrate 10, the sensor substrate 10 is irradiated with light by the light source 30, and the control unit 70 acquires the SERS signal at the position K via the photodetector 50. To do. The excitation wavelength of the light source 30 was 632 nm, the intensity was 1 mW, and the exposure time was 1 sec. As a result, the SERS signal intensity was 220 counts. Next, in order to determine whether or not the sensitivity at the position K is maximum, the SERS signal intensity is scanned by sending the X stage 71 step by step in the X direction in which the thickness of the dielectric layer 16 continuously changes. To do.

First, the dielectric layer 16 is moved to a position K + 1 away from the initial position K in the right direction, which is the thickness direction, by L mm, and SERS measurement is performed. The value of L is preferably a value of about several mm such as 3 mm. A SERS signal strength of 140 counts was obtained at the K + 1 position. As an algorithm in the control unit 80, the difference (I K + 1 −I K ) between the SERS signal intensity I K at the position K and the intensity I K + 1 at the position K + 1 is calculated. When the sign is ± 0, the position is moved to an intermediate position between the position K and the position K + 1. When the sign is −, the position is moved from the position K to the left by Lmm.
The SERS measurement is performed again at the next new moving location (positions K + 2, K-1, etc.), the calculation is performed based on the signal strength, and the control unit 80 determines the correction position of the sensor substrate 10 by the following method, for example. .

I. When I K <I K + 1 : SERS measurement at position K + 2 moved to the right from position K (i) When I K + 1 > I K + 2 : When position K + 1 is the optimum position (ii) When I K + 1 = I K + 2 : Position K + 1 , K + 2 is at the optimum position (iii) I K + 1 <I K + 2 : SERS measurement is again performed at a position K + 3 moved further L to the right side of the position K + 2. Repeat until I n + 1 ≦ I n is satisfied. The position n at that time is the optimum position (I K <I K + 1 <I K + 2 ... I n ≧ I n + 1 ). When R K-1 = R K-2 : The intermediate position between K-1 and K-2 is the optimum position. When R K-1 <R K-2 : The position K-1 is the optimum position.

II. When I K = I K + 1 : The intermediate position between the positions K and K + 1 is the optimum position III. When I K > I K + 1 : SERS measurement at position K-1 moved from position K to the left (i) When I K <I K-1 <I K-2 : I n ≧ I n-1 is satisfied Repeat until. The position n at that time is the optimum position (I K <I K-1 <I K-2 ... I n ≧ I n-1 )). When I K-1 = I K-2 : The intermediate position between K-1 and K-2 is the optimum position. When I K-1 > I K-2 : The position K-1 is the optimum position.
(Ii) When I K = I K−1 : The intermediate position between the positions K and K−1 is the optimum position. (Iii) When I K > I K−1 : The position K is the optimum position.

In the example shown in FIG. 11, the algorithm III. By executing (i), the correction position K-3 can be determined. Because after I K <I K-1 <I K-2 <I K-3 and when I n = I K-3 and I n-1 = I K-4 , I n ≧ This is because I n-1 is established for the first time.

2. Second Embodiment The second embodiment of the present invention is different from the first embodiment in that the correction position is tuned based on the reflected light intensity, whereas the first embodiment tunes the correction position based on the SERS signal intensity. As in the first embodiment, the detection device 20B having the sensor substrate 10 and the moving mechanism 70 in FIG. 4 can set the notch filter 510 of the photodetector 50 outside the optical path as shown in FIG. Different from one embodiment. The spectroscope 520 can adjust the pass wavelength band as described above, but may be set outside the optical path together with the notch filter 510.

That is, the photodetector 50 is set so that the light pass band is different between the detection mode for receiving the Raman scattered light and the correction mode for receiving the reflected light. In this way, the Rayleigh scattered light that occupies most of the reflected light can be detected by the photodetector 50. When the correction mode is performed, the photodetector 50 has a Rayleigh cut filter 520 that cuts Rayleigh light having the same wavelength as the light source light removed from the optical path as shown in FIG. 12, and the spectroscope 520 has a wavelength band of the light source light. Is set to a band for receiving light (Raman shift = 0 nm −1 ) and receives reflected light (Rayleigh scattered light). The signal level of the reflected light depends on mismatching of the optical path length of the resonator, and is not as sensitive to a minute concentration change of the target molecule in the fluid sample as the signal level of the Raman scattered light. In that respect, the second embodiment is superior to the first embodiment.

The algorithm executed by the control unit 8 in the correction mode in the second embodiment is the same as that in the first embodiment. However, the criterion for determining that the SRES signal intensity is higher is closer to the correction position is that the lower the reflected light intensity is, the correction position is. It is changed to the judgment standard that it is close to. Specifically, the correction mode is executed as follows based on the reflection intensity R.
I. When R K > R K + 1 : SERS measurement at position K + 2 moved to the right from position K + 1 (i) When R K + 1 <R K + 2 : When position K + 1 is the optimum position (ii) When R K + 1 = R K + 2 : Position K + 1 , K + 2 is at the optimum position (iii) R K + 1 > R K + 2 : SERS measurement is again performed at a position K + 3 moved further L to the right side of the position K + 2. Repeat until R n + 1 ≧ R n is satisfied. The position n at that time is the optimum position (R K > R K + 1 > R K + 2 ... R n ≦ R n + 1 ).
II. When R K = R K + 1 : The intermediate position between the positions K and K + 1 is the optimum position III. When R K <R K + 1 : SERS measurement at position K-1 moved to the left from position K (i) When R K > R K-1 > R K-2 : R n ≦ R n-1 is satisfied Repeat until. The position n at that time is the optimum position (R K > R K-1 > R K-2 ... R n ≦ R n-1 ). When R K-1 = R K-2 : The intermediate position between K-1 and K-2 is the optimum position. When R K-1 <R K-2 : The position K-1 is the optimum position.
(Ii) When R K = R K−1 : The intermediate position between the positions K and K−1 is the optimum position (iii) When R K <R K−1 : The position K is the optimum position.

3. Electronic Device An electronic device 100 will be described by taking as an example a substance detection device that detects the concentration of acetone contained in biological gas and detects the amount of burned body fat that correlates with the detected acetone concentration. As shown in FIGS. 13A to 13C, the substance detection apparatus 100 includes a detection sample collection unit 110, a detection unit 130, and a display unit 230 in a space formed by a case 120 and a windshield 121. Stored in The detection sample collection unit 110 is arranged on the side that contacts human skin (the back side of the case 120), the detection unit 130 is inside the case 120, and the display unit 230 is a position where the subject can visually recognize (the surface of the case 120). Side).

  The detection sample collection unit 110 includes a first permeable membrane 111 as a permeable membrane that is in close contact with human skin, and a second permeable membrane 112 that is disposed with a space 113 between the first permeable membrane 111. Yes. The first permeable membrane 111 that is in close contact with the human skin has a water repellency against water so that moisture such as sweat does not directly enter the detection unit 130, and is a biological gas generated from the skin. Gas may be referred to as skin gas). The first permeable membrane 111 is provided to prevent moisture or the like contained in the biological gas from adhering to the sensor unit 131 (described later) when the biological gas is taken into the detection unit 130.

  The second permeable membrane 112 has a function similar to that of the first permeable membrane 111. In order to further enhance the above-described function of the first permeable membrane 111 by forming a double structure with the first permeable membrane 111. Is provided. Therefore, it is not a necessary condition that the permeable membrane has a double structure, and the permeable membrane can be selected according to the amount of perspiration at the site where the substance detection device 100 is attached to the body.

  The first permeable membrane 111 and the second permeable membrane 112 are attached to the human body side of the case 20 and are attached by the mounting belt 220 so that the first permeable membrane 111 is in close contact with the skin. In addition, the substance detection apparatus 100 shown to FIG. 13 (A)-FIG.13 (C) has illustrated the structure in the case of mounting | wearing a wrist part.

  The configuration of the detection unit 130 will be described. As shown in FIGS. 13A and 13B, the detection unit 130 is divided into a sensor chamber 114 and a detection chamber 115. The sensor chamber 114 is a space in which the biological gas diffused from the arm is accommodated, and the sensor unit 131 is disposed therein. The sensor unit 131 includes an optical device 110 that enhances Raman scattered light. The optical device 110 includes the sensor substrate 10 moved by the moving mechanism 70 as shown in FIG.

  In the detection chamber 115, the light source 200, the first lens group that collects the light emitted from the light source 200 on the sensor unit 131, and the enhanced Raman scattered light scattered from the sensor chip 132 (referred to as enhanced Raman scattered light). ).

  The first lens group includes a lens 142 that converts light emitted from the light source 200 into parallel light, a half mirror 143 that reflects the parallel light toward the sensor unit 131, and light reflected by the half mirror 143 as a sensor. And a lens 141 that collects light on the portion 131. The second lens group includes a lens 144 that condenses the Raman light enhanced by the sensor unit 131 via the lens 141 and the half mirror 143, and a lens 145 that converts the condensed Raman light into parallel light. ing.

  Further, the detection chamber 115 includes an optical filter 150 that removes Rayleigh scattered light from the collected scattered light, a spectroscope 160 that splits the enhanced Raman scattered light into a spectrum, and converts the spectrally separated spectrum into an electrical signal. A light receiving element (light detector) 170, a signal processing control circuit unit 180 that converts the spectrally separated spectrum into an electrical signal as fingerprint spectrum information specific to a substance detected from a biological gas, and a power supply unit 190. ing. The fingerprint spectrum is built in the signal processing control circuit unit 180 in advance.

  As the power supply unit 190, a primary battery, a secondary battery, or the like can be used. In the case of a primary battery, if the voltage is lower than a specified voltage, the CPU 181 compares the information stored in the ROM with the voltage information of the obtained primary battery, and if it is lower than the specified voltage, the display unit In the case of a secondary battery that displays a battery replacement instruction in 230, the CPU 181 compares the information stored in the ROM with the voltage information of the obtained secondary battery to confirm that the voltage is lower than the specified voltage. If it is less than the specified value, a charging instruction is displayed on the display unit 230. The test subject can use the battery repeatedly by charging the battery until a predetermined voltage is obtained by connecting a charger to a connection portion (not shown) while viewing the display.

  In addition, the substance detection apparatus 100 according to the present embodiment includes a collected sample discharge unit 210 that discharges the biological gas collected in the sensor chamber 114 to the outside. The collected sample discharge means 210 has an elastic discharge tube 212 having one end communicating with the sensor chamber 114 and the other end communicating with the discharge port 211a, and a plurality of rotating rollers 213. . The collected sample discharge means 210 is a so-called tube pump that can discharge the gas in the sensor chamber 114 to the outside by pressing the discharge tube 212 from the sensor chamber 114 side to the discharge port 211a side with the rotating roller 213. It is.

  The tube pump may be manually rotated or may be driven by a motor. It should be noted that a gas discharge means other than the tube pump can be appropriately selected and used as the collected sample discharge means. In addition, it is more preferable that the discharge ports for discharging the biological gas from the sensor chamber 114 have a structure provided at a plurality of locations in order to quickly discharge the biological gas. In addition, it is more preferable that the discharge ports for discharging the biological gas from the sensor chamber 114 have a structure provided at a plurality of locations in order to quickly discharge the biological gas.

  Next, the display content of the display unit 230 will be described with reference to FIG. The display unit 230 uses an electro-optic display element such as a liquid crystal display element. As the main display contents, as shown in FIG. 13C, the current time, the elapsed time from the start of measurement, the amount of burned fat per minute and the integrated value, the graph display showing these changes, and the like are raised. . In addition, it is necessary to exclude the gas in the sensor chamber 114 after the fat burning amount is measured (that is, the sensor chip 132 is refreshed), and a display for informing the operator of this is also included. For example, when “refresh” is displayed, the collected sample discharging operation is executed.

  Next, the configuration and operation of the substance detection apparatus 100 including the control system will be described with reference to FIG. FIG. 14 is a block diagram showing the main configuration of the substance detection apparatus 100 according to this embodiment. The substance detection apparatus 100 includes a signal processing control circuit unit 180 that controls the entire control system. The signal processing control circuit unit 180 includes a CPU (Central Processing Unit) 181, a RAM (Random Access Memory) 182, and a ROM. (Read Only Memory) 183.

  The sensor chamber 114 includes a sensor chip and a sensor detector (not shown) for detecting the presence / absence of the sensor chip and reading a code, and the information is sent to the CPU 181 via the sensor detection circuit. Sent. The state in which the information is input is a state in which detection can be started, and therefore, input from the CPU 181 that operation is possible is input to the display unit 230 and displayed on the display unit 230.

  When the CPU 181 receives a detection start signal from the operation unit 122, it outputs a light source activation signal from the light source driving circuit 184 to activate the light source 200. The light source 200 incorporates a temperature sensor and a light quantity sensor, so that it can be confirmed that the light source 200 is in a stable state. When the light source 200 is stabilized, the biological gas is collected in the sensor chamber 114. Note that a suction pump (not shown) may be used for collecting biogas.

  The light source 200 is driven by a light source driving circuit 184 by a signal from the CPU 181 and emits light. This light is applied to the sensor chip 132 via the lens 142, the half mirror 143, and the lens 141. Raman scattered light (SERS: surface enhanced Raman scattering) enhanced by the enhanced electric field enters the light receiving element 170 via the lens 141, the half mirror 143, the lens 144, the lens 145, the optical filter 150, and the spectroscope 160. The spectrometer 160 is controlled by a spectrometer driving circuit 185. The light receiving element 170 is controlled by a light receiving circuit 186.

  The optical filter 150 blocks Rayleigh light, and only SERS light enters the spectrometer 160. When a wavelength tunable etalon using Fabry-Perot resonance is adopted as the spectroscope 160, a band of light to be transmitted (λ1 to λ2) and a half-value width are set, and the half-value width is sequentially transmitted starting from λ1. Then, the light receiving element 170 repeatedly converts the intensity of the half-width optical signal into an electric signal. By doing so, the spectrum of the detected SERS light is obtained.

  The SERS light spectrum of the substance to be detected (acetone here) is compared with the fingerprint spectrum stored in the ROM 183 of the signal processing control circuit unit 180 to identify the target substance and detect the concentration of acetone. To do. Then, the signal processing control circuit unit 180 that also functions as a calculation unit calculates the fat burning amount (health medical information) from the acetone concentration and stores it in the RAM 182 that is a storage unit. In order to inform the subject of the calculation result, the CPU 181 displays result information on the display unit 230. An example of the result information is shown in FIG.

  The clock function for measuring the measurement time receives a current time and a fat burning start signal from a preset time by a known clock function circuit 187, and displays the fat burning measurement start time and end time. It also has a clock function for displaying the amount of fat burned per minute, the accumulated amount from the start of fat burning measurement, and the like.

  Those skilled in the art will readily appreciate that many variations are possible without substantially departing from the novel features and advantages of the present invention. Accordingly, all such modifications are intended to be included in the scope of the present invention. For example, a term described with a different term having a broader meaning or the same meaning at least once in the specification or the drawings can be replaced with the different term in any part of the specification or the drawings. In addition, the configuration and operation of the sensor substrate 10, the detection devices 20A and 20B, the electronic device 100, and the like are not limited to those described in this embodiment, and various modifications can be made.

  The present invention can be widely applied to sensing devices used for medical treatment, medical examinations, and food inspections. It can also be used as an affinity sensor for detecting the presence or absence of substance adsorption, such as the presence or absence of antigen adsorption in an antigen-antibody reaction. In the affinity sensor, a white light source is incident on the sensor chip, the wavelength spectrum as shown in FIG. 3 is measured with a spectroscope, and the shift amount of the surface plasmon resonance wavelength due to adsorption is detected. Adsorption is detected with high sensitivity. This requires a white light source, a spectroscope, etc., and the apparatus tends to be upsized. In the detection apparatus according to the present embodiment, for example, the plasmon resonance wavelength shift due to the deposit can be detected with high sensitivity by tuning the optical path length when the reflectance is minimized. The present invention can be applied not only to surface enhanced Raman spectroscopy but also to surface enhanced infrared absorption spectroscopy sensors and the like.

  1 target molecule, 2 enhanced electric field, 10 sensor substrate, 16 dielectric layer, 18 metal nanostructure, 20A, 20B detection device, 30 light source, 40 optical system, 50 photodetector, 70 moving mechanism, 80 control unit, 180 arithmetic Part, 182 storage part, 230 display part, 510 Rayleigh cut filter, 520 spectroscope, X thickness change direction

Claims (7)

  1. A detection device for detecting a target molecule contained in a fluid sample,
    A sensor substrate;
    A moving mechanism for moving the sensor substrate;
    Illuminating the sensor substrate with light to cause surface enhanced Raman scattering to appear; and
    A photodetector for detecting surface enhanced Raman scattered light;
    Have
    The sensor substrate is
    Mirror layer,
    A dielectric layer provided on the mirror layer and having a thickness change direction in which the thickness continuously increases or decreases;
    A plurality of metal nanostructures provided on the dielectric layer;
    Have
    The detecting device, wherein the moving mechanism moves the sensor substrate along the thickness change direction.
  2. In claim 1,
    The detection device, wherein the surface of the dielectric layer is inclined at a constant angle.
  3. In claim 1 or 2,
    The detection device, wherein the dielectric layer includes a plurality of dielectrics made of different materials.
  4. In any one of Claims 1 thru | or 3,
    The sensor substrate is moved along the thickness change direction by the moving mechanism, the sensor substrate is irradiated with light at a plurality of positions, and the result of the surface enhanced Raman scattered light detected by the photodetector is obtained. And a control unit for setting a correction position of the sensor substrate.
  5. In any one of Claims 1 thru | or 3,
    The sensor substrate is moved along the thickness change direction by the moving mechanism, the sensor substrate is irradiated with light at a plurality of positions, and the sensor is based on a result of reflected light reflected by the sensor substrate. A detection apparatus further comprising a control unit for setting a correction position of the substrate.
  6. In claim 5,
    The detection apparatus, wherein the light detector is set so that a light pass band is different between a detection mode for receiving the surface-enhanced Raman scattered light and a correction mode for receiving the reflected light.
  7. The detection device according to any one of claims 1 to 6,
    A calculation unit for calculating health and medical information based on detection information from the detection device;
    A storage unit for storing health and medical information;
    A display unit for displaying the health care information;
    An electronic device characterized by comprising:
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