JP5655435B2 - Sensor chip, sensor cartridge and analyzer - Google Patents

Description

  The present invention relates to a sensor chip, a sensor cartridge, and an analyzer.

  In recent years, there has been an increasing demand for sensors used for medical diagnosis and inspection of food and drink, and the development of sensor technology that is small and capable of sensing at high speed is demanded. In order to meet such a demand, various types of sensors including an electrochemical method are being studied. Among these, because of the fact that integration is possible, the cost is low, and the measurement environment is not selected, interest in sensors using surface plasmon resonance (SPR) 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 microstructure is excited, a significantly enhanced electric field is induced.

  Therefore, for the purpose of improving sensor sensitivity, a sensor using localized surface plasmon resonance (LSPR) using metal fine particles or metal nanostructures has been proposed. For example, in Patent Document 1, light is applied to a transparent substrate having metal fine particles fixed on the surface thereof, and the absorbance of the light transmitted through the metal fine particles is measured to thereby change the medium in the vicinity of the metal fine particles. It detects and detects adsorption and deposition of the target substance.

Japanese Unexamined Patent Publication No. 2000-356587

  However, in Patent Document 1, it is difficult to uniformly produce metal fine particles (size and shape) and to regularly arrange the metal fine particles. If the size and arrangement of the metal microparticles cannot be controlled, the absorption caused by resonance and the resonance wavelength will also vary. As a result, the width of the absorbance spectrum becomes broad and the peak intensity decreases. For this reason, the signal change for detecting the change of the medium in the vicinity of the metal fine particles is low, and there is a limit in improving the sensor sensitivity. Accordingly, the sensitivity of the sensor is insufficient for applications in which substances are identified from the absorbance spectrum.

  The present invention has been made in view of such circumstances, and provides a sensor chip, a sensor cartridge, and an analyzer that can improve the sensitivity of a sensor and can identify a target substance from a Raman spectrum. Objective.

In order to solve the above-described problem, one sensor chip according to the present invention includes a base material having a flat surface portion, and a diffraction grating formed on the flat surface portion and on which a target substance is disposed, and the diffraction grating Are arranged periodically in a first direction parallel to the plane portion with a period of 100 nm or more and 1000 nm or less, and a plurality of first protrusions whose surfaces are made of metal and two adjacent first protrusions And a plurality of base portions constituting the base of the base material and a plurality of second protrusions formed on the top surface of the plurality of first protrusions and having a surface made of metal. It is characterized by this.
In order to solve the above-described problem, one sensor chip according to the present invention includes a base material having a plane portion and a diffraction grating on which a target substance is disposed, and the diffraction grating is parallel to the plane portion. A first concavo-convex shape in which a plurality of first convex shapes whose surfaces are made of metal are periodically arranged in a first direction with a period of 100 nm to 1000 nm; and the plurality of first convex shapes And the second concavo-convex shape in which a plurality of second convex shapes whose surfaces are made of metal with a cycle shorter than the cycle of the first concavo-convex shape are periodically arranged, It has the synthetic pattern formed in the plane part, and has the surface formed with the metal.
In order to solve the above-described problem, one sensor chip according to the present invention includes a base material having a flat surface portion, and a diffraction grating formed on the flat surface portion and on which a target substance is disposed, and the diffraction grating Is configured between the plurality of first protrusions periodically arranged in the first direction with a period of 100 nm or more and 1000 nm or less and the two adjacent first protrusions to form the base of the base material A plurality of base portions and a plurality of second protrusions formed on the top surfaces of the plurality of first protrusions, and having a surface made of metal.
In order to solve the above-described problem, one sensor chip according to the present invention includes a base material having a flat portion and a diffraction grating on which a target substance is disposed, and the diffraction grating has a period of 100 nm to 1000 nm. The first concavo-convex shape in which a plurality of first convex shapes are periodically arranged, and the plurality of second convex shapes in the plurality of first convex shapes with a cycle shorter than the cycle of the first concavo-convex shape. It has a synthetic pattern formed on the plane portion by overlapping with a second concavo-convex shape in which convex shapes are periodically arranged, and has a surface made of metal.
In order to solve the above problems, the sensor chip of the present invention arranges a target substance on a diffraction grating formed on a substrate containing a metal, and utilizes the surface plasmon resonance and surface enhanced Raman scattering to cause the target substance to be disposed. A sensor chip for detection, wherein the diffraction grating is formed on a flat surface portion of the base material, and a cross-sectional shape in a direction perpendicularly cutting the flat surface portion is a rectangular convex shape, and the base material A first protrusion group including a metal arranged in a first direction parallel to the plane of the light at a period shorter than the wavelength of light, and two adjacent first protrusions in the first protrusion group A group of base portions of the substrate located between and a group of a plurality of second protrusions including a metal formed on the upper surface of each of the first protrusions in the group of the first protrusions; It is characterized by having.

  According to this configuration, the near electric field enhanced by the first protrusion via the surface plasmon resonance is excited to the surface of the same shape, and further, the surface enhanced Raman scattering (intensity enhancement by the metal fine structure by the second protrusion ( SERS: Surface Enhanced Raman Scattering) can be expressed. Specifically, when light is incident on the surface on which the first protrusion group and the second protrusion group are formed, a surface-specific vibration mode (surface plasmon) is generated by the first protrusion group. Then, free electrons resonate with the vibration of light, and the vibration of the electromagnetic wave is excited with the vibration of the free electrons. Since the vibration of the electromagnetic wave affects the vibration of free electrons, a system in which both vibrations are combined, that is, a so-called surface plasmon polariton (SPP) is formed. As a result, localized surface plasmon resonance (LSPR) is excited in the vicinity of the second group of protrusions. In this structure, since the distance between two adjacent second protrusions is small, an extremely strong electric field is generated near the contact point. When one to several target substances are adsorbed on the contact, SERS is generated therefrom. For this reason, the sharp SERS spectrum intrinsic | native to a target substance is acquirable. Therefore, it is possible to provide a sensor chip capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. Moreover, the position of the resonance peak can be adjusted to an arbitrary wavelength by appropriately changing the period and height of the first protrusion and the height of the second protrusion. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

The sensor chip may be arranged with periodicity in a second direction in which the first protrusion intersects the first direction and is parallel to the plane of the substrate.
According to this configuration, sensing is performed under a wider plasmon resonance condition than when the first protrusion is formed with periodicity only in a direction parallel to the plane of the substrate (first direction). be able to. Therefore, it is possible to provide a sensor chip capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. In addition to the period in the first direction of the first protrusion, the period in the second direction can be changed as appropriate. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

In the sensor chip, the second protrusions may be arranged with periodicity in a third direction parallel to the plane of the substrate.
According to this configuration, the period of the second protrusion can be changed as appropriate. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

The sensor chip may be arranged with periodicity in a fourth direction in which the second protrusion intersects the third direction and is parallel to the plane of the substrate.
According to this configuration, sensing can be performed under a wider plasmon resonance condition than when the second protrusion is formed only in the direction parallel to the plane of the substrate (third direction). Therefore, it is possible to provide a sensor chip capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. In addition to the period in the third direction of the second protrusion, the period in the fourth direction can be changed as appropriate. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

In the sensor chip, the second protrusion may be made of fine particles.
Even in this configuration, it is possible to provide a sensor chip capable of improving the sensor sensitivity and specifying the target substance from the SERS spectrum.

The sensor chip has a width W1 when the width of the first protrusion in the first direction is W1, and the distance between two adjacent first protrusions in the first direction is W2. It is desirable to satisfy the relationship> W2.
According to this configuration, since the space filling rate of the first protrusions where LSPR is excited increases, sensing can be performed under a wider plasmon resonance condition than when the relationship of W1 <W2 is satisfied. Moreover, the energy of the light irradiated when specifying a target substance can be used effectively.

In the sensor chip, the ratio between the width W1 of the first protrusion in the first direction and the distance W2 between the two adjacent first protrusions in the first direction is W1: W2 = It is desirable to satisfy the 9: 1 relationship.
Even in this configuration, sensing can be performed under a wide range of plasmon resonance conditions. Moreover, the energy of the light irradiated when specifying a target substance can be used effectively.

In the sensor chip, the metal contained in the base material, the metal contained in the first projection, and the metal contained in the second projection are preferably gold or silver.
According to this configuration, since gold or silver has a property of expressing SPP, LSPR, and SERS, SPP, LSPR, and SERS are easily expressed, and a target substance can be detected with high sensitivity. .

  The sensor chip of the present invention is a sensor chip for detecting a target substance by using surface plasmon resonance and surface enhanced Raman scattering by arranging the target substance on a diffraction grating formed on a base material containing metal. The diffraction grating includes a metal, and the first convex shape is arranged with a period shorter than the wavelength of light as a cross-sectional shape of the diffraction grating in a direction in which the planar portion of the base material is cut vertically. The first concavo-convex shape and the second concavo-convex shape in which the second convex shape is arranged in a cycle shorter than the cycle of the first concavo-convex shape in each of the first convex shapes in the first concavo-convex shape And a composite pattern obtained by superimposing and.

  According to this structure, the near electric field enhanced by the first convex shape through the surface plasmon resonance is excited to the surface of the same shape, and the surface enhanced Raman having a high strength is obtained by the metal microstructure by the second convex shape. Scatter (SERS: Surface Enhanced Raman Scattering) can be expressed. Specifically, when light enters the surface on which the first concavo-convex shape and the second concavo-convex shape are formed, a surface-specific vibration mode (surface plasmon) is generated by the first concavo-convex shape. Then, free electrons resonate with the vibration of light, and the vibration of the electromagnetic wave is excited with the vibration of the free electrons. Since the vibration of the electromagnetic wave affects the vibration of free electrons, a system in which both vibrations are combined, that is, a so-called surface plasmon polariton (SPP) is formed. Thereby, localized surface plasmon resonance (LSPR) is excited in the vicinity of the second uneven shape. In this structure, since the distance between two adjacent second convex shapes is small, an extremely strong enhanced electric field is generated near the contact point. When one to several target substances are adsorbed on the contact, SERS is generated therefrom. For this reason, the sharp SERS spectrum intrinsic | native to a target substance is acquirable. Therefore, it is possible to provide a sensor chip capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. In addition, by appropriately changing the period and height of the first convex shape and the height of the second convex shape, the position of the resonance peak can be adjusted to an arbitrary wavelength. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

In the sensor chip, the first convex shape has periodicity in a first direction parallel to the plane of the base material, and intersects the first direction and is parallel to the plane of the base material. They may be arranged with periodicity in the two directions.
According to this configuration, sensing is performed under a wider plasmon resonance condition than when the first convex shape is formed with periodicity only in the direction parallel to the plane of the substrate (first direction). It can be carried out. Therefore, it is possible to provide a sensor chip capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. In addition to the period in the first direction in the first convex shape, the period in the second direction can be changed as appropriate. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

In the sensor chip, the second convex shape may be arranged with periodicity in a third direction parallel to the plane of the substrate.
According to this configuration, the period of the second convex shape can be changed as appropriate. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

The sensor chip may be arranged with periodicity in a fourth direction in which the second convex shape intersects the third direction and is parallel to the plane of the substrate.
According to this configuration, sensing can be performed under a wider plasmon resonance condition than when the second convex shape is formed only in the direction parallel to the plane of the substrate (third direction). Therefore, it is possible to provide a sensor chip capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. Moreover, in addition to the period of the 3rd direction in a 2nd convex shape, the period of a 4th direction can also be changed suitably. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

In the sensor chip, the second convex shape may be made of fine particles.
Even in this configuration, it is possible to provide a sensor chip capable of improving the sensor sensitivity and specifying the target substance from the SERS spectrum.

In the sensor chip, the width of the first convex shape in the first direction is W1, and the distance between two adjacent first convex shapes in the first direction is W2. , W1> W2 is preferably satisfied.
According to this configuration, since the space filling rate of the first convex shape in which LSPR is excited increases, sensing can be performed under a wider plasmon resonance condition than when the relationship of W1 <W2 is satisfied. Moreover, the energy of the light irradiated when specifying a target substance can be used effectively.

In the sensor chip, the ratio of the first convex width W1 in the first direction to the distance W2 between two adjacent first convex shapes in the first direction is W1: It is desirable to satisfy the relationship of W2 = 9: 1.
Even in this configuration, sensing can be performed under a wide range of plasmon resonance conditions. Moreover, the energy of the light irradiated when specifying a target substance can be used effectively.

Moreover, as for the said sensor chip, it is desirable that the metal contained in the said base material, the metal contained in the said 1st convex shape, and the metal contained in the said 2nd convex shape are gold or silver.
According to this configuration, since gold or silver has a property of expressing SPP, LSPR, and SERS, SPP, LSPR, and SERS are easily expressed, and a target substance can be detected with high sensitivity. .

The analysis device of the present invention includes the above-described sensor chip of the present invention, a light source that irradiates light to the sensor chip, and a photodetector that detects light from the sensor chip.
According to this configuration, since the sensor chip according to the present invention described above is provided, it is possible to selectively disperse Raman scattered light and detect a target molecule. Therefore, it is possible to provide an analyzer capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum.

  The sensor chip of the present invention is a sensor chip for detecting a target substance by arranging a target substance on a diffraction grating formed on a substrate and utilizing surface plasmon resonance and surface enhanced Raman scattering. The diffraction grating is formed on the planar portion of the base material, and has a group of first protrusions arranged in a first direction parallel to the plane of the base material with a period of 100 nm or more and 1000 nm or less. In the group of one protrusion, the base part group of the base material positioned between two adjacent first protrusions, and in the first protrusion group, formed on the upper surface of the first protrusion. A plurality of second protrusion groups, and a surface of the diffraction grating is made of metal.

  According to this configuration, the near electric field enhanced by the first protrusion via the surface plasmon resonance is excited to the surface of the same shape, and further, the surface enhanced Raman scattering (intensity enhancement by the metal fine structure by the second protrusion ( SERS: Surface Enhanced Raman Scattering) can be expressed. Specifically, when light is incident on the surface on which the first protrusion group and the second protrusion group are formed, a surface-specific vibration mode (surface plasmon) is generated by the first protrusion group. Then, free electrons resonate with the vibration of light, and the vibration of the electromagnetic wave is excited with the vibration of the free electrons. Since the vibration of the electromagnetic wave affects the vibration of free electrons, a system in which both vibrations are combined, that is, a so-called surface plasmon polariton (SPP) is formed. As a result, localized surface plasmon resonance (LSPR) is excited in the vicinity of the second group of protrusions. In this structure, since the distance between two adjacent second protrusions is small, an extremely strong electric field is generated near the contact point. When one to several target substances are adsorbed on the contact, SERS is generated therefrom. For this reason, the sharp SERS spectrum intrinsic | native to a target substance is acquirable. Therefore, it is possible to provide a sensor chip capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. Moreover, the position of the resonance peak can be adjusted to an arbitrary wavelength by appropriately changing the period and height of the first protrusion and the height of the second protrusion. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

The sensor chip may be arranged with periodicity in a second direction in which the first protrusion intersects the first direction and is parallel to the plane of the substrate.
According to this configuration, sensing is performed under a wider plasmon resonance condition than when the first protrusion is formed with periodicity only in a direction parallel to the plane of the substrate (first direction). be able to. Therefore, it is possible to provide a sensor chip capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. In addition to the period in the first direction of the first protrusion, the period in the second direction can be changed as appropriate. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

In the sensor chip, the second protrusions may be arranged with periodicity in a third direction parallel to the plane of the substrate.
According to this configuration, the period of the second protrusion can be changed as appropriate. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

The sensor chip may be arranged with periodicity in a fourth direction in which the second protrusion intersects the third direction and is parallel to the plane of the substrate.
According to this configuration, sensing can be performed under a wider plasmon resonance condition than when the second protrusion is formed only in the direction parallel to the plane of the substrate (third direction). Therefore, it is possible to provide a sensor chip capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. In addition to the period in the third direction of the second protrusion, the period in the fourth direction can be changed as appropriate. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

In the sensor chip, the second protrusion may be made of fine particles.
Even in this configuration, it is possible to provide a sensor chip capable of improving the sensor sensitivity and specifying the target substance from the SERS spectrum.

The sensor chip has a width W1 when the width of the first protrusion in the first direction is W1, and the distance between two adjacent first protrusions in the first direction is W2. It is desirable to satisfy the relationship> W2.
According to this configuration, since the space filling rate of the first protrusions where LSPR is excited increases, sensing can be performed under a wider plasmon resonance condition than when the relationship of W1 <W2 is satisfied. Moreover, the energy of the light irradiated when specifying a target substance can be used effectively.

In the sensor chip, the ratio between the width W1 of the first protrusion in the first direction and the distance W2 between the two adjacent first protrusions in the first direction is W1: W2 = It is desirable to satisfy the 9: 1 relationship.
Even in this configuration, sensing can be performed under a wide range of plasmon resonance conditions. Moreover, the energy of the light irradiated when specifying a target substance can be used effectively.

In the sensor chip, the metal on the surface of the diffraction grating is preferably gold or silver.
According to this configuration, since gold or silver has a property of expressing SPP, LSPR, and SERS, SPP, LSPR, and SERS are easily expressed, and a target substance can be detected with high sensitivity. .

  The sensor chip of the present invention is a sensor chip for detecting a target substance by arranging a target substance on a diffraction grating formed on a substrate and utilizing surface plasmon resonance and surface enhanced Raman scattering. The diffraction grating has a surface formed of a metal, and a cross-sectional shape of the diffraction grating in a direction in which the planar portion of the base material is cut vertically is arranged such that a first convex shape is arranged with a period of 100 nm to 1000 nm. A first concavo-convex shape, and a second concavo-convex shape in which the second convex shape is arranged in a cycle shorter than the cycle of the first concavo-convex shape in the first convex shape in the first concavo-convex shape, It is a composite pattern obtained by superposition.

  According to this structure, the near electric field enhanced by the first convex shape through the surface plasmon resonance is excited to the surface of the same shape, and the surface enhanced Raman having a high strength is obtained by the metal microstructure by the second convex shape. Scatter (SERS: Surface Enhanced Raman Scattering) can be expressed. Specifically, when light enters the surface on which the first concavo-convex shape and the second concavo-convex shape are formed, a surface-specific vibration mode (surface plasmon) is generated by the first concavo-convex shape. Then, free electrons resonate with the vibration of light, and the vibration of the electromagnetic wave is excited with the vibration of the free electrons. Since the vibration of the electromagnetic wave affects the vibration of free electrons, a system in which both vibrations are combined, that is, a so-called surface plasmon polariton (SPP) is formed. Thereby, localized surface plasmon resonance (LSPR) is excited in the vicinity of the second uneven shape. In this structure, since the distance between two adjacent second convex shapes is small, an extremely strong enhanced electric field is generated near the contact point. When one to several target substances are adsorbed on the contact, SERS is generated therefrom. For this reason, the sharp SERS spectrum intrinsic | native to a target substance is acquirable. Therefore, it is possible to provide a sensor chip capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. In addition, by appropriately changing the period and height of the first convex shape and the height of the second convex shape, the position of the resonance peak can be adjusted to an arbitrary wavelength. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

In the sensor chip, the first convex shape has periodicity in a first direction parallel to the plane of the base material, and intersects the first direction and is parallel to the plane of the base material. They may be arranged with periodicity in the two directions.
According to this configuration, sensing is performed under a wider plasmon resonance condition than when the first convex shape is formed with periodicity only in the direction parallel to the plane of the substrate (first direction). It can be carried out. Therefore, it is possible to provide a sensor chip capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. In addition to the period in the first direction in the first convex shape, the period in the second direction can be changed as appropriate. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

In the sensor chip, the second convex shape may be arranged with periodicity in a third direction parallel to the plane of the substrate.
According to this configuration, the period of the second convex shape can be changed as appropriate. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

The sensor chip may be arranged with periodicity in a fourth direction in which the second convex shape intersects the third direction and is parallel to the plane of the substrate.
According to this configuration, sensing can be performed under a wider plasmon resonance condition than when the second convex shape is formed only in the direction parallel to the plane of the substrate (third direction). Therefore, it is possible to provide a sensor chip capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. Moreover, in addition to the period of the 3rd direction in a 2nd convex shape, the period of a 4th direction can also be changed suitably. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

In the sensor chip, the second convex shape may be made of fine particles.
Even in this configuration, it is possible to provide a sensor chip capable of improving the sensor sensitivity and specifying the target substance from the SERS spectrum.

In the sensor chip, the width of the first convex shape in the first direction is W1, and the distance between two adjacent first convex shapes in the first direction is W2. , W1> W2 is preferably satisfied.
According to this configuration, since the space filling rate of the first convex shape in which LSPR is excited increases, sensing can be performed under a wider plasmon resonance condition than when the relationship of W1 <W2 is satisfied. Moreover, the energy of the light irradiated when specifying a target substance can be used effectively.

In the sensor chip, the ratio of the first convex width W1 in the first direction to the distance W2 between two adjacent first convex shapes in the first direction is W1: It is desirable to satisfy the relationship of W2 = 9: 1.
Even in this configuration, sensing can be performed under a wide range of plasmon resonance conditions. Moreover, the energy of the light irradiated when specifying a target substance can be used effectively.

In the sensor chip, the metal on the surface of the diffraction grating is preferably gold or silver.
According to this configuration, since gold or silver has a property of expressing SPP, LSPR, and SERS, SPP, LSPR, and SERS are easily expressed, and a target substance can be detected with high sensitivity. .

The sensor cartridge of the present invention includes the above-described sensor chip of the present invention, a transport unit that transports the target substance to the surface of the sensor chip, a mounting unit that mounts the sensor chip, the sensor chip, and the transport And a housing for housing the mounting portion, and an irradiation window provided at a position facing the surface of the sensor chip of the housing.
According to this configuration, since the sensor chip according to the present invention described above is provided, it is possible to selectively disperse Raman scattered light and detect a target molecule. Therefore, it is possible to provide a sensor cartridge capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum.

The analysis device of the present invention includes the above-described sensor chip of the present invention, a light source that irradiates light to the sensor chip, and a photodetector that detects light from the sensor chip.
According to this configuration, since the sensor chip according to the present invention described above is provided, it is possible to selectively disperse Raman scattered light and detect a target molecule. Therefore, it is possible to provide an analyzer capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum.

It is a mimetic diagram showing a schematic structure of a sensor chip concerning the present invention. It is a figure which shows a Raman scattering spectroscopy. It is a figure which shows the mechanism of the electric field enhancement by LSPR. It is a figure which shows SERS spectroscopy. It is a graph which shows the reflected light intensity of the 1st protrusion single-piece | unit. It is a graph which shows the dispersion | distribution curve of SPP. It is a graph which shows the reflected light intensity of the 1st protrusion single-piece | unit. It is a graph which shows the reflected light intensity of the 1st protrusion single-piece | unit. It is a graph which shows the reflected light intensity of the 1st protrusion single-piece | unit. It is a graph which shows the reflected light intensity of the sensor chip based on this invention. It is a graph which shows the reflected light intensity | strength of the structure which accumulated the 2nd protrusion on the plane part of the base material. It is a mimetic diagram of a sensor chip which formed a plurality of 2nd projections in a plane part of a substrate. It is a graph which shows the reflected light intensity of the sensor chip in FIG. It is a figure which shows the preparation processes of a sensor chip. It is a schematic block diagram of the sensor chip which has the 1st protrusion of another form. It is a schematic block diagram of the sensor chip which has the 2nd protrusion of another form. It is a schematic block diagram of the sensor chip which has the 2nd protrusion of another form. It is a schematic diagram which shows an example of an analyzer. It is a mimetic diagram showing a schematic structure of a sensor chip concerning the present invention. It is a mimetic diagram showing a schematic structure of a sensor chip concerning the present invention.

  Embodiments of the present invention will be described below with reference to the drawings. This embodiment shows one aspect of the present invention, and does not limit the present invention, and can be arbitrarily changed within the scope of the technical idea of the present invention. Moreover, in the following drawings, in order to make each structure easy to understand, an actual structure and a scale, a number, and the like in each structure are different.

  FIG. 1 is a schematic diagram showing a schematic configuration of a sensor chip according to the present invention. FIG. 1A is a schematic configuration perspective view of a sensor chip, and FIG. 1B is a schematic configuration cross-sectional view of the sensor chip. In FIG. 1B, reference numeral P1 is the period of the first protrusion (first convex shape), reference numeral P2 is the period of the second protrusion (second convex shape), and reference numeral W1 is the width of the first protrusion. , W2 is the distance between two adjacent first protrusions, T1 is the height of the first protrusion (groove depth), and T2 is the height of the second protrusion (groove depth). It is.

  19 and 20 are schematic views showing a schematic configuration of the sensor chip according to the present invention, corresponding to FIG. 19 and 20, reference numeral P1 is a period of the first protrusion (first convex shape), reference numeral P2 is a period of the second protrusion (second convex shape), and reference numeral W1 is a width of the first protrusion. , W2 is the distance between two adjacent first protrusions, T1 is the height of the first protrusion (groove depth), and T2 is the height of the second protrusion (groove depth). It is.

  The sensor chip 1 arranges a target substance on a diffraction grating 9 formed on a base material 10 containing a metal, a localized surface plasmon resonance (LSPR) and a surface enhanced Raman scattering (SERS). ) To detect the target substance. The diffraction grating 9 is formed on the flat surface portion 10 s of the base material 10, has a convex shape with a rectangular cross section in the direction of cutting the flat surface portion 10 s vertically, and is parallel to the plane of the base material 10. A base member positioned between two first protrusions 11 adjacent to each other in the group of first protrusions 11 including a metal arranged in a direction with a period P1 shorter than the wavelength of light. And a group of second protrusions 12 including a metal formed on the upper surface 11a of each of the first protrusions 11 in the group of first protrusions 11. Yes.

  Specifically, the sensor chip 1 is for disposing the target substance on the diffraction grating 9 formed on the base material 10 and detecting the target substance using LSPR and SERS. The diffraction grating 9 is formed on the planar portion 10 s of the base material 10, and is a group of first protrusions 11 arranged in a first direction parallel to the plane of the base material 10 with a period P1 of 100 nm or more and 1000 nm or less. And a group of base portions 10a of the base material 10 located between two adjacent first protrusions 11 in the group of first protrusions 11, and each first protrusion 11 in the group of first protrusions 11 And a group of a plurality of second protrusions 12 formed on the upper surface 11a. The surface of the diffraction grating 9 is made of metal.

  In other words, the diffraction grating 9 includes a metal, and the cross-sectional shape of the diffraction grating 9 in the direction in which the planar portion 10s of the base material 10 is cut vertically is a first convex shape (first first) with a period P1 shorter than the wavelength of light. Of the first protrusions and protrusions 11 and the first protrusions 11 in the first protrusions and protrusions 11 and the second protrusions (first protrusions) with a period P2 shorter than the period of the first protrusions and recesses. (2 projections) 12 is a composite pattern obtained by superimposing the second concavo-convex shape on which 12 are arranged. That is, the sensor chip 1 includes a first convex shape 11 for expressing LSPR and a second convex shape 12 for expressing SERS. Details of LSPR and SERS will be described later.

  Specifically, the surface of the diffraction grating 9 is formed of a metal, and the cross-sectional shape of the diffraction grating 9 in the direction in which the planar portion 10s of the base material 10 is cut vertically is a first convex with a period P1 of 100 nm to 1000 nm. The first concavo-convex shape in which the shapes (first protrusions) 11 are arranged, and the first concavo-convex shape of each of the first concavo-convex shapes 11 in the first concavo-convex shape 11 is shorter than the period of the first concavo-convex shape, This is a composite pattern obtained by superimposing the second concavo-convex shape in which the convex shapes (second protrusions) 12 are arranged.

  Here, the “diffraction grating” refers to a structure in which a plurality of irregular shapes (groups of protrusions) are periodically arranged.

  Further, the “planar portion” here refers to the upper surface portion of the substrate. That is, the “planar portion” refers to a surface portion on one side of the base material on which the target substance is disposed. The composite pattern formed by overlapping the first uneven shape and the second uneven shape is formed at least on the upper surface portion of the substrate. Moreover, the shape is not specifically limited regarding the surface part of the other one side of a base material, ie, the lower surface part of a base material. However, in consideration of the processing step for the flat portion (upper surface portion) of the base material, the lower surface portion of the base material is preferably a flat surface parallel to the base portion of the flat surface portion.

  As a structure of the diffraction grating 9, as shown in FIG.1 (b), the base material 10, the 1st convex shape 11, and the 2nd convex shape 12 all consist of a metal. In addition, as shown in FIG. 19, the base material 10 and the first convex shape 11 are formed of an insulating member such as glass or resin, and the entire exposed portion of the insulating member is covered with a metal film, and the metal is formed on the metal film. What formed the 2nd convex shape 12 which consists of these is mentioned. Furthermore, as shown in FIG. 20, the base material 10, the first convex shape 11 and the second convex shape 12 are all formed of an insulating member, and the entire exposed portion of the insulating member is covered with a metal film. It is done. That is, the diffraction grating 9 can be configured such that at least the surfaces of the base portion 10a, the first convex shape 11 and the second convex shape 12 of the base material 10 are made of metal.

  The base material 10 is formed by, for example, forming a metal film of 150 nm or more on a glass substrate. This metal film becomes the first protrusion 11 and the second protrusion 12 by a manufacturing process described later. In the present embodiment, the substrate 10 is formed by forming a metal film on a glass substrate, but is not limited thereto. For example, a metal film formed on a quartz substrate or a sapphire substrate may be used. Moreover, you may use the flat plate which consists of metals as a base material.

  The first projection 11 is formed on the flat surface portion 10 s of the base material 10 with a predetermined height T1. The first protrusions 11 are arranged in a direction (first direction) parallel to the plane of the substrate 10 with a period P1 shorter than the wavelength of light. The period P1 is the sum of the width W1 of the first protrusion 11 alone and the distance W2 between the two adjacent first protrusions 11 in the first direction (left-right direction in FIG. 1B). (P1 = W1 + W2). The first protrusion 11 has a convex shape with a rectangular shape in cross section, and the group of the first protrusions 11 has a line-and-space (striped shape) in plan view.

  As for the 1st protrusion 11, it is desirable to set the period P1 to the range of 100-1000 nm, for example, and the height T1 to the range of 10-100 nm. Thereby, the 1st processus | protrusion 11 can be made into the structure for expressing LSPR.

  The width W1 of the first protrusion 11 in the first direction is larger than the distance W2 between two adjacent first protrusions 11 (W1> W2). Thereby, the space filling rate of the 1st protrusion 11 in which LSPR is excited increases.

  Two or more second protrusions 12 are formed on the upper surface 11a of the first protrusion 11 with a predetermined height T2. Specifically, the second protrusion 12 is not formed on the base portion 10a of the base material 10 (the flat portion 10s of the base material 10 in the region between the two adjacent first protrusions 11). It is formed only on the upper surface 11 a of the convex shape 11.

  The second protrusions 12 are arranged in a direction (third direction) parallel to the plane of the substrate 10 with a period P2 shorter than the wavelength of light. The period P2 is the sum of the width of the second protrusion 12 alone in the third direction (the left-right direction in FIG. 1B) and the distance between two adjacent second protrusions 12. is there. Accordingly, the period P2 of the second protrusion 12 is sufficiently shorter than the period P1 of the first protrusion 11.

  As for the 2nd processus | protrusion 12, it is desirable to set the period P2 to a value smaller than 500 nm, for example, and to set the height T2 to a value smaller than 200 nm. Thereby, the 2nd protrusion 12 can be made into the structure for expressing SERS.

  In the present embodiment, the arrangement direction of the first protrusions 11 (first direction) and the arrangement direction of the second protrusions 12 (third direction) are the same direction. Similarly to the first protrusion, the second protrusion 12 has a convex shape with a rectangular shape in cross section, and the group of the second protrusions 12 has a line-and-space (striped shape) in plan view.

  As the metal on the surface of the diffraction grating 9, for example, gold (Au), silver (Ag), copper (Cu), aluminum (Al), or an alloy thereof is used. In the present embodiment, gold or silver having the characteristic of expressing SPP, LSPR, and SERS is used. Thereby, SPP, LSPR, and SERS are easily expressed, and the target substance can be detected with high sensitivity.

  Here, SPP, LSPR, and SERS will be described. When light is incident on the surface of the sensor chip 1, that is, the surface on which the group of the first protrusions 11 and the group of the second protrusions 12 are formed, the vibration mode (surface plasmon) inherent to the surface by the group of the first protrusions 11 Occurs. However, the polarization state of incident light is TM (Transverse Electric) polarization orthogonal to the groove direction of the first protrusion 11. Then, the vibration of electromagnetic waves is excited with the vibration of free electrons. Since the vibration of the electromagnetic wave affects the vibration of free electrons, a system in which both vibrations are combined, that is, a so-called surface plasmon polariton (SPP) is formed. In this embodiment, the incident angle of light is substantially perpendicular to the chip surface. However, the present invention is not limited to this as long as the SPP is excited.

  The SPP propagates along the surface of the sensor chip 1, specifically along the interface between air and the second protrusion 12, and excites a strong local electric field in the vicinity of the second protrusion 12. SPP coupling is sensitive to the wavelength of light and its coupling efficiency is high. As described above, localized surface plasmon resonance (LSPR) can be excited from the incident light in the air propagation mode via the SPP. And surface enhanced Raman scattering (SERS: Surface Enhanced Raman Scattering) can be utilized from the relationship between LSPR and Raman scattered light.

  FIG. 2 is a diagram showing Raman scattering spectroscopy. FIG. 2A shows the principle of Raman scattering spectroscopy. FIG. 2B shows a Raman spectrum (relation between Raman shift and Raman scattering intensity). In FIG. 2 (a), symbol L indicates incident light (light having a single wavelength), symbol Ram indicates Raman scattered light, symbol Ray indicates Rayleigh scattered light, and symbol X indicates a target molecule (target substance). In FIG. 2B, the horizontal axis represents the Raman shift. The Raman shift is the difference between the frequency of the Raman scattered light Ram and the frequency of the incident light L, and takes a value specific to the structure of the target molecule X.

  As shown in FIG. 2A, when the target molecule X is irradiated with light L having a single wavelength, light having a wavelength different from that of the incident light is generated in the scattered light (Raman scattered light Ram). ). The energy difference between the Raman scattered light Ram and the incident light L corresponds to the vibration level, rotational level, or electron level energy of the target molecule X. Since the target molecule X has a specific vibration energy corresponding to its structure, the target molecule X can be specified by using the light L having a single wavelength.

  For example, if the vibration energy of the incident light L is V1, the vibration energy consumed by the target molecule X is V2, and the vibration energy of the Raman scattered light Ram is V3, then V3 = V1−V2. Most of the incident light L has the same amount of energy after collision with the target molecule X as before the collision. This elastic scattered light is called Rayleigh scattered light Ray. For example, when the vibration energy of Rayleigh scattered light Ray is V4, V4 = V1.

  From the Raman spectrum shown in FIG. 2B, it can be seen that the Raman scattered light Ram is weak when comparing the scattered intensity (spectrum peak) of the Raman scattered light Ram and the scattered intensity of the Rayleigh scattered light Ray. Thus, although the Raman scattering spectroscopy is excellent in the discrimination ability of the target molecule X, it is a measurement method with low sensitivity itself for sensing the target molecule X. Therefore, in the present invention, in order to achieve high sensitivity, a spectroscopy using surface enhanced Raman scattering (SERS spectroscopy) is used (see FIG. 4).

  FIG. 3 is a diagram showing a mechanism of electric field enhancement by LSPR. FIG. 3A is a schematic diagram when light is incident on the metal nanoparticles. FIG. 3B is a diagram showing an LSPR enhanced electric field. In FIG. 3A, reference numeral 100 denotes a light source, reference numeral 101 denotes metal nanoparticles, and reference numeral 102 denotes light from the light source. In FIG.3 (b), the code | symbol 103 is a surface local electric field.

  As shown in FIG. 3A, when light 102 is incident on the metal nanoparticles 101, free electrons resonate with the vibration of the light 102. The metal nanoparticle diameter is smaller than the wavelength of incident light. For example, the wavelength of light is 400 to 800 nm, and the metal nanoparticle diameter is 10 to 100 nm. Further, Ag and Au are used as the metal nanoparticles.

  Then, along with the resonance vibration of free electrons, a strong surface localized electric field 103 is excited in the vicinity of the metal nanoparticles 101 (see FIG. 3B). Thus, the LSPR can be excited by the light 102 entering the metal nanoparticles 101.

  FIG. 4 is a diagram showing SERS spectroscopy. In FIG. 4, reference numeral 200 is a substrate (corresponding to a first protrusion according to the present invention), reference numeral 201 is a metal nanostructure (corresponding to a second protrusion according to the present invention), reference numeral 202 is a selective adsorption film, and reference numeral 203 is Reference numeral 204 denotes a target molecule, reference numeral 211 denotes incident laser light, reference numeral 212 denotes Raman scattered light, and reference numeral 213 denotes Rayleigh scattered light. The selective adsorption film 202 adsorbs the target molecule 204.

  As shown in FIG. 4, when laser light 211 is incident on the metal nanostructure 201, free electrons resonate and vibrate with the vibration of the laser light 211. The size of the metal nanostructure 201 is smaller than the wavelength of the incident laser light. Then, a strong surface localized electric field is excited in the vicinity of the metal nanostructure 201 with the resonance vibration of free electrons. Thereby, LSPR is excited. When the distance between adjacent metal nanostructures 201 is reduced, an extremely strong enhanced electric field 203 is generated in the vicinity of the contact. When one to several target molecules 204 are adsorbed to the contact, SERS is generated therefrom. This is also confirmed from the result of the enhanced electric field generated between two adjacent silver nanoparticles calculated using the time domain difference (FDTD) method. Therefore, the Raman scattered light can be selectively dispersed and the target molecule can be detected with high sensitivity.

  In the present invention, as described above, the LSPR is excited by arranging the first protrusions 11 in a direction parallel to the plane of the substrate 10 with a period P1 shorter than the wavelength of light. Further, two or more second protrusions 12 are formed only on the upper surface 11a of the first protrusion 11 so that SERS is expressed. Specifically, based on the principle that when the target molecule is irradiated with light of a single wavelength, Raman scattered light is generated, the target molecule is disposed between two adjacent second protrusions 12 and in the vicinity of this contact point. SERS is generated by generating an enhanced magnetic field. This makes it possible to use SERS spectroscopy that can detect a target substance with higher sensitivity than Raman scattering spectroscopy.

  FIG. 5 is a graph showing the reflected light intensity of the first protrusion alone. In FIG. 5, the horizontal axis represents the light wavelength, and the vertical axis represents the reflected light intensity. The height T1 of the first protrusion 11 is taken as a parameter (T1 = 20 nm, 30 nm, 40 nm). In the structure of the sensor chip 1 of the present embodiment, the value obtained by subtracting the reflected light intensity from the incident light intensity (1.0) is the absorbance.

  The light is incident on the first protrusion 11 perpendicularly. The polarization direction of light is TM polarized light. The period of the first protrusion 11 is 580 nm, and the resonance peak of reflected light intensity exists in the vicinity of a wavelength of 630 nm. This resonance peak is derived from SPP, and as the height T1 of the first protrusion 11 is increased, the resonance peak shifts to the long wavelength side. It can be seen that when the height T1 of the first protrusion 11 is 30 nm, the reflected light intensity is the strongest and the absorption is the strongest.

  FIG. 6 is a graph showing a dispersion curve of SPP. In FIG. 6, reference C <b> 1 is an SPP dispersion curve (for example, a value at the interface between air and Au), and reference C <b> 2 is a light line. The period of the first protrusion 11 is 580 nm. The position of the lattice vector of the first protrusion 11 is shown on the horizontal axis (corresponding to 2π / P on the horizontal axis in FIG. 6). If the line is extended upward from this position, it intersects with the dispersion curve of SPP. The wavelength corresponding to this intersection is obtained from the following equation.

  In Equation (1), P1 is the period of the first protrusion 11, E1 is the complex permittivity of air, and E2 is the complex permittivity of Au. Substituting P1, E1, and E2 into equation (1) yields λ = 620 nm (corresponding to w0 on the vertical axis in FIG. 6).

  As the height T1 of the first protrusion 11 increases, the imaginary part in the wave number of the SPP increases. As a result, the real part in the wave number of the SPP is reduced, and the intersection of the line extending from the position of the lattice vector and the dispersion curve of the SPP moves from the upper right to the lower left. That is, the resonance peak shifts to the long wavelength side.

  FIG. 7 is a graph showing the reflected light intensity of the first protrusion alone. In FIG. 7, the horizontal axis represents the wavelength of light, and the vertical axis represents the reflected light intensity. The ratio of the width W1 of the first protrusion 11 in the first direction to the distance W2 between two adjacent first protrusions (hereinafter referred to as the duty ratio) is used as a parameter (W1: W2 = 5: 5, 8: 2). The graph of parameters W1: W2 = 5: 5 in this figure is the same as the graph of parameters T1 = 30 in FIG.

  The TM polarized light is incident on the first protrusion 11 perpendicularly. When the period of the first protrusion 11 is 580 nm and the duty ratio is W1: W2 = 5: 5, the resonance peak of the reflected light intensity exists in the vicinity of the wavelength of 630 nm. When the duty ratio is W1: W2 = 8: 2, the resonance peak of the reflected light intensity exists in the vicinity of the wavelength of 660 nm. When the duty ratio is increased, the gradient of the resonance peak becomes sharp, and the resonance peak shifts to the longer wavelength side.

  8 and 9 are graphs showing the reflected light intensity of the first protrusion alone. FIG. 8A shows a case where the duty ratio is W1: W2 = 7: 3. FIG. 8B shows a case where the duty ratio is W1: W2 = 3: 7. FIG. 9A shows a duty ratio of W1: W2 = 9: 1. FIG. 9B shows a case where the duty ratio is W1: W2 = 1: 9. 8 and 9, the horizontal axis represents the wavelength of light, and the vertical axis represents the reflected light intensity. The height T1 of the first protrusion 11 is taken as a parameter (T1 = 20 nm, 30 nm, 40 nm, 50 nm).

  The TM polarized light is incident on the first protrusion 11 perpendicularly. When the duty ratio of the first protrusion 11 is W1: W2 = 7: 3 and the height T1 is 30 nm, the resonance peak of the reflected light intensity exists in the vicinity of the wavelength of 660 nm (see FIG. 8A). On the other hand, when the duty ratio is W1: W2 = 3: 7 and the height T1 is 40 nm, the resonance peak of the reflected light intensity exists in the vicinity of the wavelength of 600 nm (see FIG. 8B). When the duty ratio of the first protrusion 11 is W1: W2 = 7: 3, it can be seen that when the height T1 is increased, the position of the resonance peak of the reflected light intensity is shifted to the longer wavelength side. However, when the duty ratio of the first protrusion 11 is W1: W2 = 3: 7, it can be seen that the position of the resonance peak of the reflected light intensity hardly changes.

  When the duty ratio of the first protrusion 11 is W1: W2 = 9: 1 and the height T1 is 40 nm, the resonance peak of the reflected light intensity exists near the wavelength of 670 nm (see FIG. 9A). On the other hand, when the duty ratio is W1: W2 = 1: 9 and the height T1 is 20 nm, the resonance peak of the reflected light intensity exists in the vicinity of the wavelength of 730 nm, and the gradient of the resonance peak is broad (FIG. 9B). reference). When the duty ratio of the first protrusion 11 is W1: W2 = 9: 1, it can be seen that when the height T1 is increased, the position of the resonance peak of the reflected light intensity is shifted to the longer wavelength side. However, when the duty ratio of the first protrusion 11 is W1: W2 = 1: 9, the resonance peak of the reflected light intensity is small.

  FIG. 10 is a graph showing the structure in which the second protrusion 12 is overlapped with the first protrusion 11, that is, the reflected light intensity of the sensor chip 1 according to the present invention. In FIG. 10, the horizontal axis represents the wavelength of light, and the vertical axis represents the reflected light intensity. The height T2 of the second protrusion 12 is taken as a parameter (T2 = 0 nm, 30 nm). The graph of the parameter T2 = 0 in this figure is the same as the graph of the parameters W1: W2 = 8: 2 in FIG.

  The TM polarized light is incident on the first protrusion 11 perpendicularly. The duty ratio of the first protrusion 11 is W1: W2 = 8: 2, and the height T1 of the first protrusion 11 is 30 nm. Further, the period P2 of the second protrusion 12 is 116 nm. By forming a plurality of second protrusions 12 only on the upper surface 11a of the first protrusion 11, the position of the resonance peak of the reflected light intensity is shifted from the wavelength of 660 nm to the vicinity of the wavelength of 710 nm. In addition, the sharpness and gradient of the resonance peak are maintained. This resonance peak is derived from SERS described above. When the height T2 of the second protrusion 12 is 30 nm, a strong local electric field can be excited near the surface of the second protrusion 12 by irradiating light with a wavelength of 710 nm. Note that the position of the resonance peak can be adjusted to an arbitrary wavelength by appropriately changing the periods P1 and P2 and the heights T1 and T2 of the first protrusion 11 and the second protrusion 12.

  FIG. 11 is a graph showing the reflected light intensity of the structure in which the second protrusion 12 is superimposed on the base material 10. FIG. 11A shows the second protrusion on each of the upper surface of the first protrusion and the flat portion of the base material (the base portion of the base material) in the region between the two adjacent first protrusions. A plurality are formed (not shown). FIG. 11B shows a structure in which a plurality of second protrusions are formed only on the upper surface of the first protrusion (the structure of the sensor chip according to the present invention). FIG. 11C shows a case where a plurality of second protrusions are formed (not shown) only on the flat portion of the base material (the base portion of the base material) in the region between the two adjacent first protrusions. In FIG. 11, the horizontal axis represents the wavelength of light, and the vertical axis represents the reflected light intensity. The height T2 of the second protrusion 12 is taken as a parameter (T2 = 0 nm, 40 nm). Note that the graph of the parameter T2 = 0 in this drawing is the same as the graph of the parameter T1 = 30 in FIG.

  The TM polarized light is incident on the first protrusion 11 perpendicularly. The period of the first protrusion 11 is 580 nm, the duty ratio is W1: W2 = 5: 5, and the height T1 is 30 nm. The period P2 of the second protrusion 12 is 97 nm, and the height T2 is 40 nm.

  It can be seen that by forming a plurality of second protrusions on each of the upper surface of the first protrusion and the base portion of the base material, the position of the resonance peak of the reflected light intensity shifts from the wavelength of 640 nm to the vicinity of the wavelength of 730 nm. 11 (a)). Further, it can be seen that by forming a plurality of second protrusions 12 only on the upper surface 11a of the first protrusion 11, the position of the resonance peak of the reflected light intensity shifts from the wavelength of 640 nm to the vicinity of the wavelength of 710 nm (FIG. 11B )reference). However, it can be seen that the position of the resonance peak of the reflected light intensity hardly changes even when a plurality of second protrusions are formed only on the base portion of the substrate.

  From these results, it is considered that the SPP propagates mainly along the interface between air and the upper surface of the first protrusion. Therefore, forming two or more second protrusions only on the upper surface of the first protrusion without forming the second protrusion on the base portion of the substrate is effective as a structure for exciting LSPR and developing SERS. It is. In addition, by increasing the duty ratio of the first protrusion (W1> W2), the space filling rate of the first protrusion that excites the LSPR increases, so that the energy of the light irradiated when specifying the target substance is effective. Can be used.

  FIG. 12 shows the case where only the second protrusion 12 is formed on the flat surface portion 10a of the base material 10 without forming the first protrusion 11 on the flat surface portion 10a of the base material 10, that is, the flat surface portion 10a of the base material 10. It is a figure which shows typically the sensor chip 2 at the time of forming the several 2nd protrusion 12 in FIG.

  FIG. 13 is a graph showing the reflected light intensity of the sensor chip 2 when a plurality of second protrusions are formed on the flat surface portion 10 a of the substrate 10. In FIG. 13, the horizontal axis represents the wavelength of light, and the vertical axis represents the reflected light intensity. The height T2 of the second protrusion 12 is used as a parameter (T2 = 0 nm, 40 nm, 80 nm). The TM-polarized light is incident on the second protrusion 12 perpendicularly. Even if this figure is seen, the resonance peak of reflected light intensity is not recognized. From this result, it can be seen that when the first protrusion 11 does not exist, that is, when the SPP is not interposed, the light energy cannot be coupled to the second protrusion 12.

  FIG. 14 is a diagram illustrating a manufacturing process of the sensor chip. First, the Au film 31 is formed on the glass substrate 30 by a method such as vapor deposition or sputtering. Next, a resist 32 is applied on the Au film 31 by a method such as spin coating (see FIG. 14A). At this time, the film thickness Ta of the Au film 31 is formed so thick that it does not transmit incident light (for example, 200 nm).

  Next, a resist pattern 32a having a period Pa of 580 nm is formed by a method such as imprinting (see FIG. 14B). Next, using this resist pattern 32a as a mask, the Au film 31 is etched by a predetermined depth D1 (for example, 70 nm) by dry etching. Thereafter, the resist pattern 32a is removed to form the first protrusion 31a (see FIG. 14C).

  Next, a resist 33 is applied on the Au film 31 on which the first protrusions 31a are formed by a method such as spin coating (see FIG. 14D). Next, a resist pattern 33a having a period Pb of 116 nm is formed only on the upper surface of the first protrusion 31a by a method such as imprinting (see FIG. 14E). Next, using the resist pattern 33a as a mask, only the first protrusion 31a is etched by a predetermined depth D2 (for example, 40 nm) by dry etching. Thereafter, the resist pattern 33a is removed to form the second protrusion 31b (see FIG. 14F). Through the above steps, the sensor chip 3 according to the present invention can be manufactured.

  According to the sensor chip 1 of the present invention, it is possible to excite LSPR via the SPP with the metal microstructure formed by the first protrusions 11 and to cause SERS to be expressed by the metal microstructure formed by the second protrusions 12. Specifically, when light is incident on the surface on which the first projection 11 group and the second projection 12 group are formed, a surface-specific vibration mode (surface plasmon) is generated by the first projection 11 group. . Then, free electrons resonate with the vibration of the light to excite the SPP, and a strong surface localized electric field is excited in the vicinity of the second protrusion 12 group. Thereby, LSPR is excited. In this structure, since the distance between two adjacent second protrusions 12 is small, an extremely strong electric field is generated near the contact point. When one to several target substances are adsorbed on the contact, SERS is generated therefrom. For this reason, the width of the reflected light intensity spectrum is narrow and the resonance peak is sharp, and the sensor sensitivity can be improved. Therefore, it is possible to provide the sensor chip 1 capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. Further, by appropriately changing the period P1, the height T1 of the first protrusion 11 and the T2 of the second protrusion 12, the position of the resonance peak can be adjusted to an arbitrary wavelength. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

  Further, according to this configuration, since the second protrusion 12 is arranged with periodicity in the third direction parallel to the plane of the base material 10, the period P2 of the second protrusion 12 is changed as appropriate. can do. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

  Further, according to this configuration, since gold or silver is used as the metal on the surface of the diffraction grating 9, LSPR and SERS are easily expressed, and the target substance can be detected with high sensitivity.

  In addition, according to this configuration, the duty ratio of the first protrusion 11 satisfies the relationship of W1> W2, and the space filling rate of the first protrusion 11 in which LSPR is excited increases, so the relationship of W1 <W2 Sensing can be performed under a wider plasmon resonance condition than when satisfying the above condition. Moreover, the energy of the light irradiated when specifying a target substance can be used effectively.

  Even when the duty ratio of the first protrusion 11 satisfies the relationship of W1: W2 = 9: 1, sensing can be performed under a wide range of plasmon resonance conditions, and the energy of the irradiated light is effective. Can be used.

  In the present embodiment, the structure in which the first protrusions 11 are arranged in the direction parallel to the plane of the base material 10 (first direction) with a period P1 shorter than the wavelength of light is shown. Not limited to. A sensor chip 4 having a structure different from that of the first protrusion 11 of this embodiment will be described with reference to FIG.

  FIG. 15 is a schematic configuration perspective view of the sensor chip 4 having the first protrusion 41 having a different form from the first protrusion 11 described above. In the drawing, the second protrusion is not shown for convenience.

  As shown in FIG. 15, the first protrusion 41 is formed on the flat surface portion 40 s of the base material 40. The first protrusions 41 are arranged in a direction (first direction) parallel to the plane of the substrate 40 with a period P3 shorter than the wavelength of light. The first protrusions 41 are arranged in a second direction perpendicular to the first direction and parallel to the plane of the base material 40 with a period P4 shorter than the wavelength of light. Note that the second direction is not limited to a direction orthogonal to the first direction and parallel to the plane of the base material 40, but may be a direction intersecting the first direction and parallel to the plane of the base material 40. Good.

  According to this structure, sensing can be performed under a wider plasmon resonance condition than when the first protrusions are formed only in the direction parallel to the plane of the substrate 10 (first direction). Therefore, it is possible to provide the sensor chip 4 capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. In addition to the period P3 in the first direction of the first protrusion, the period P4 in the second direction can be appropriately changed. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

  In the present embodiment, the structure in which the second protrusions 12 are arranged in a direction parallel to the plane of the base material 10 (third direction) with a period P2 shorter than the wavelength of light, specifically, Although the structure in which the arrangement direction of the first protrusions 11 (first direction) and the arrangement direction of the second protrusions 12 (third direction) are the same is shown, the present invention is not limited to this. The sensor chips 5, 6, 7, and 8 having a structure different from that of the second protrusion 12 of this embodiment will be described with reference to FIGS.

  FIG. 16 is a schematic configuration perspective view of a sensor chip having a second protrusion different in form from the second protrusion 12 described above. 16A shows the sensor chip 5 having the second protrusion 52, and FIG. 16B shows the sensor chip 6 having the second protrusion 62.

  As shown in FIG. 16A, two or more second protrusions 52 are formed only on the upper surface 51 a of the first protrusion 51 in the group of the first protrusions 51 formed on the flat surface portion 50 s of the base material 50. Has been. That is, the second protrusion 52 is not formed on the base portion 50 a of the substrate 50. In this figure, as an example, a structure in which the angle at which the arrangement direction of the first protrusions 51 (first direction) intersects the arrangement direction of the second protrusions 52 (third direction) is 45 degrees is shown. Yes.

  As shown in FIG. 16B, two or more second protrusions 62 are formed only on the upper surface 61a of the first protrusion 61 in the group of the first protrusions 61 formed on the flat surface portion 60s of the substrate 60. Has been. That is, the second protrusion 62 is not formed on the base portion 60 a of the substrate 60. In this drawing, as an example, a structure in which the angle at which the arrangement direction of the first protrusions 61 (first direction) intersects the arrangement direction of the second protrusions 62 (third direction) is 90 degrees is shown. Yes.

  Even in such a configuration, it is possible to provide a sensor chip that can improve sensor sensitivity and can identify a target substance from a SERS spectrum under a wide range of plasmon resonance conditions.

  FIG. 17 is an enlarged plan view of a sensor chip having a second protrusion of a form different from the second protrusion 12 described above. 17A shows the sensor chip 7 having the second protrusion 72, and FIG. 17B shows the sensor chip 8 having the second protrusion 82. FIG.

  As shown in FIG. 17A, two or more second protrusions 72 are formed only on the upper surface 71a of each first protrusion in the first protrusion group (not shown). The second protrusions 72 are arranged with periodicity in a fourth direction that intersects the third direction and is parallel to the plane of the substrate. In this figure, the 2nd protrusion 72 has shown the structure of planar view circular shape as an example. In addition, the 2nd protrusion 72 may be arrange | positioned at random, without having periodicity.

  As shown in FIG. 17B, two or more second protrusions 82 are formed only on the upper surface 81a of each first protrusion in the first protrusion group (not shown). The second protrusions 82 are arranged with periodicity in a fourth direction that intersects the third direction and is parallel to the plane of the substrate. In this figure, the 2nd protrusion 82 has shown the structure of planar view ellipse shape as an example. Note that the second protrusions 82 may be randomly arranged without periodicity.

  According to this configuration, sensing can be performed under a wider plasmon resonance condition than when the second protrusion is formed only in the direction parallel to the plane of the substrate (third direction). Therefore, it is possible to provide a sensor chip capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum. In addition to the period in the third direction of the second protrusion, the period in the fourth direction can be changed as appropriate. For this reason, it becomes possible to select the wavelength of the light irradiated when specifying a target substance suitably, and the width of a measurement range spreads.

  In the present embodiment, the second protrusion is formed by patterning the Au film formed on the upper surface of the glass substrate. However, the present invention is not limited to this. For example, the second protrusion may be a fine particle. Even in such a configuration, it is possible to provide a sensor chip capable of improving the sensor sensitivity and identifying the target substance from the SERS spectrum.

  In the present embodiment, the same metal (gold or silver) is used as the metal contained in the base material, the metal contained in the first projection, and the metal contained in the second projection, but this is not limitative. Absent. For example, the metal contained in the base material is gold, the metal contained in the first protrusion is silver, the metal contained in the second protrusion is an alloy of gold and silver, and the like (gold, silver, copper, aluminum, etc.) Or an alloy thereof may be used in combination.

(Analysis equipment)
FIG. 18 is a schematic diagram showing an example of an analyzer equipped with a sensor chip according to the present invention.
In addition, the arrow in FIG. 14 has shown the conveyance direction of the target substance (not shown).

  As shown in FIG. 18, the analysis apparatus 1000 includes a sensor chip 1001, a light source 1002, a photodetector 1003, a collimator lens 1004, a polarization control element 1005, a dichroic mirror 1006, an objective lens 1007, and an objective lens. 1008 and the conveyance part 1010 are comprised. The light source 1002 and the photodetector 1003 are each electrically connected to a control device (not shown) via wiring.

  The light source 1002 emits laser light that excites SPP, LSPR, and SERS. The laser light emitted from the light source 1002 is collimated by the collimator lens 1004, passes through the polarization control element 1005, is guided in the direction of the sensor chip 1001 by the dichroic mirror 1006, is condensed by the objective lens 1007, and is sensor chip. 1001 is incident. At this time, a target substance (not shown) is arranged on the surface of the sensor chip 1001 (for example, a surface on which a metal nanostructure or a detection substance selection mechanism is formed). The target substance is introduced into the transport unit 1010 from the carry-in port 1011 and discharged from the discharge port 1012 to the outside of the transport unit 1010 by controlling driving of a fan (not shown). The size of the metal nanostructure is smaller than the wavelength of the laser beam.

  When laser light is incident on the metal nanostructure, free electrons resonate with the vibration of the laser light, and a strong surface localized electric field is excited in the vicinity of the metal nanostructure, thereby exciting LSPR. When the distance between adjacent metal nanostructures is reduced, an extremely strong electric field is generated in the vicinity of the contact. When one to several target substances are adsorbed at the contact, SERS is generated therefrom.

  Light from the sensor chip 1001 (Raman scattered light or Rayleigh scattered light) passes through the objective lens 1007, is guided toward the photodetector 1003 by the dichroic mirror 1006, is collected by the objective lens 1007, and is detected by the photodetector 1003. Is incident on. Then, the spectrum is decomposed by the photodetector 1003 to obtain spectrum information.

  According to this configuration, since the sensor chip according to the present invention described above is provided, it is possible to selectively disperse Raman scattered light and detect a target molecule. Therefore, it is possible to provide the analyzer 1000 that can improve the sensor sensitivity and can identify the target substance from the SERS spectrum.

  The analysis apparatus 1000 includes a sensor cartridge 1100. The sensor cartridge 1100 includes a sensor chip 1001, a transport unit 1010 that transports a target substance to the surface of the sensor chip 1001, a mounting unit 1101 on which the sensor chip 1001 is mounted, and a housing 1110 that stores these. Configured. An irradiation window 1111 is provided at a position facing the sensor chip 1001 of the housing 1110. The laser light emitted from the light source 1002 passes through the irradiation window 1111 and is irradiated on the surface of the sensor chip 1001. The sensor cartridge 1100 is located in the upper part of the analyzer 1000 and is provided so as to be detachable from the main body of the analyzer 1000.

  According to this configuration, since the sensor chip according to the present invention described above is provided, it is possible to selectively disperse Raman scattered light and detect a target molecule. Therefore, it is possible to provide the sensor cartridge 1100 that can improve the sensor sensitivity and can identify the target substance from the SERS spectrum.

  The analysis device according to the present invention can be widely applied to a sensing device used for medical treatment and medical examination, detection of narcotics and explosives, and food inspection. Further, it can 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.

DESCRIPTION OF SYMBOLS 1, 3, 4, 5, 6, 7, 8, 1001 ... Sensor chip, 9 ... Diffraction grating, 10, 40, 50, 60 ... Base material, 10a, 50a, 60a ... Base part, 10s, 40s, 50s, 60s: flat portion of base material, 11, 31a, 41, 51, 61 ... first projection (first convex shape), 11a, 51a, 61a, 71a, 81a ... upper surface of first projection, 12, 31b , 52, 62, 72, 82 ... second projection (second convex shape), 1000 ... analyzer, 1002 ... light source, 1003 ... light detector, 1100 ... sensor cartridge, 1101 ... mounting section, 1110 ... housing Body, 1111, ... Irradiation window, P1, P2, P3, P4 ... Period, W1 ... Width of first protrusion (convex shape), W2 ... Distance between adjacent first protrusions (convex shape)

Claims (20)

A base material having a planar portion;
A diffraction grating formed on the planar portion and on which a target substance is disposed,
The diffraction grating is periodically arranged in a first direction parallel to the planar portion with a period of 100 nm or more and 1000 nm or less, and a plurality of first protrusions whose surfaces are made of metal and two adjacent second projections. A plurality of base portions constituting the base of the base material positioned between one protrusion and a plurality of second protrusions formed on the upper surface of the plurality of first protrusions and having a surface made of metal door to including it,
Features a sensor chip. Wherein the plurality of first protrusions, the a first direction, said first intersecting the direction the second direction parallel to the planar portion and is periodically arranged in, claim 1 Sensor chip.   The sensor chip according to claim 1, wherein the plurality of second protrusions are periodically arranged in a third direction parallel to the planar portion. The plurality of second protrusions are periodically arranged in the third direction and a fourth direction that intersects the third direction and is parallel to the planar portion. Sensor chip. It said plurality of second protrusions is formed of a fine particle, a sensor chip according to any one of claims 1, 2 or 4.   The relationship of W1> W2 is satisfied, where W1 is a width of the first protrusion in the first direction and W2 is a distance between two adjacent first protrusions in the first direction. Item 6. The sensor chip according to any one of Items 1 to 5.   The ratio between the width W1 of the first protrusion in the first direction and the distance W2 between two adjacent first protrusions in the first direction is W1: W2 = 9: 1. The sensor chip according to claim 6, satisfying the relationship.   The sensor chip according to any one of claims 1 to 7, wherein a metal constituting the surface of the diffraction grating is gold or silver. The sensor chip according to any one of claims 1 to 8,
A transport unit for transporting the target substance to the surface of the sensor chip;
A mounting section for mounting the sensor chip;
A housing for housing the sensor chip, the transfer unit, and the mounting unit;
An irradiation window provided at a position facing the surface of the sensor chip of the housing;
Including a sensor cartridge. The sensor chip according to any one of claims 1 to 8,
A light source for irradiating light to the sensor chip;
A photodetector for detecting the light obtained by the sensor chip;
Including an analytical device. A base material having a planar portion;
A diffraction grating on which a target substance is disposed,
The diffraction grating has a first concavo-convex structure in which a plurality of first convex shapes whose surfaces are made of metal are periodically arranged in a first direction parallel to the planar portion with a period of 100 nm to 1000 nm. And a plurality of second convex shapes whose surfaces are made of metal with a cycle shorter than the cycle of the first concave and convex shapes on the plurality of first convex shapes. and irregularities of having a composite pattern that is formed on the flat portion by the superimposed, that has a surface with a metal,
Features a sensor chip. Said plurality of first convex shape, said first direction and are periodically arranged in a second direction parallel to the plane portion intersecting the first direction, claim 11 The sensor chip described in 1.   The sensor chip according to claim 11 or 12, wherein the plurality of second convex shapes are periodically arranged in a third direction parallel to the planar portion. Said plurality of second convex shape, and the third direction are periodically arranged in a fourth direction parallel to the plane portion intersecting said third direction, claim 13 The sensor chip described in 1. The sensor chip according to claim 11 , wherein the plurality of second convex shapes are made of fine particles.   When the width of the first convex shape in the first direction is W1, and the distance between two adjacent first convex shapes in the first direction is W2, the relationship of W1> W2 is satisfied. The sensor chip according to any one of claims 11 to 15.   The ratio between the width W1 of the first convex shape in the first direction and the distance W2 between two adjacent first convex shapes in the first direction is W1: W2 = 9: The sensor chip according to claim 16, satisfying the relationship of 1.   The sensor chip according to any one of claims 11 to 17, wherein the metal constituting the surface of the diffraction grating is gold or silver. A sensor chip according to any one of claims 11 to 18,
A transport unit for transporting the target substance to the surface of the sensor chip;
A mounting section for mounting the sensor chip;
A housing for housing the sensor chip, the transfer unit, and the mounting unit;
An irradiation window provided at a position facing the surface of the sensor chip of the housing;
Including a sensor cartridge. A sensor chip according to any one of claims 11 to 18,
A light source for irradiating light to the sensor chip;
A photodetector for detecting the light obtained by the sensor chip;
Including an analytical device.