KR101224326B1 - Sensor chip, sensor cartridge, and analysis apparatus - Google Patents

Abstract

A sensor chip comprising: a substrate having a planar portion; A plurality of substrates positioned between the plurality of first protrusions periodically arranged in a period of 100 nm or more and 1000 nm or less in a first direction parallel to the planar portion and adjacent two first protrusions to constitute a base of the substrate; And a diffraction grating comprising a portion and a plurality of second protrusions formed on upper surfaces of the plurality of first protrusions, the surface having a metal surface, formed on the planar portion, and having a target material disposed thereon.

Description

Sensor Chips, Sensor Cartridges, and Analysis Devices {SENSOR CHIP, SENSOR CARTRIDGE, AND ANALYSIS APPARATUS}

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

This application claims priority with respect to Japanese Patent Application No. 2009-263706 for which it applied on November 19, 2009, and Japanese Patent Application No. 2010-192839 for which it applied on August 30, 2010, The content here Quote on.

In recent years, the demand of the sensor used for the medical diagnosis, the inspection of food products, etc. is increasing, and the development of the sensor technology which can sense small size and high speed is calculated | required. In order to respond to these demands, various types of sensors have been studied, including electrochemical techniques. Among these, interest in sensors using Surface Plasmon Resonance (SPR) is increasing because of the possibility of integration, low cost, and obscuring the measurement environment.

Here, surface plasmon is a vibration mode of the electromagnetic wave which causes coupling with light by surface-specific boundary conditions. As a method of exciting surface plasmons, a diffraction grating is inscribed on a metal surface, a method of combining light and plasmon, or a method of using evanescent waves. For example, as a structure of the sensor using SPR, the structure provided with the total reflection prism and the metal film which contacts the target substance formed in the surface of the prism is known. With this configuration, the presence or absence of adsorption of the target substance, such as the presence or absence of the adsorption of the antigen in the antigen antibody reaction, is detected.

By the way, a propagation type surface plasmon exists in a metal surface, and a local type surface plasmon exists in metal fine particles. When localized surface plasmons, ie, surface plasmons localized on the surface microstructure, are excited, it is known that remarkably enhanced electric field is induced.

Here, for the purpose of improving the sensor sensitivity, a sensor using localized surface plasmon resonance (LSPR) using metal fine particles or metal nanostructures has been proposed. For example, Patent Document 1 (Japanese Patent Laid-Open No. 2000-356587) discloses light on a transparent substrate having metal fine particles fixed on the surface thereof in a film form, and thus absorbance of light transmitted through the metal fine particles. By measuring, the change of the medium in the vicinity of metal fine particles is detected, and the adsorption and deposition of a target substance are detected.

However, in Patent Document 1, it was difficult to uniformly prepare the size (size and shape) of the metal fine particles and to arrange the metal fine particles regularly. If the size and arrangement of the metal fine particles cannot be controlled, variations occur in absorption and resonance wavelengths caused by resonance. As a result, the width of the absorbance spectrum becomes wider and the peak intensity decreases. For this reason, the signal change which detects the change of the medium near metal fine particles is low, and there existed a limit in improving sensor sensitivity. Therefore, the sensitivity of the sensor was insufficient for applications such as specifying a substance from the absorbance spectrum.

Japanese Unexamined Patent Publication No. 2000-356587

In view of the above circumstances, an object of the present invention is to provide a sensor chip, a sensor cartridge, and an analysis apparatus capable of improving sensor sensitivity and specifying a target substance from a Raman spectral spectrum.

In order to solve the said subject, this invention adopts the following structures.

According to a first aspect of the present invention, there is provided a sensor chip comprising: a substrate having a planar portion; A base is formed between a plurality of first protrusions periodically arranged in a period of 100 nm or more and 1000 nm or less in a first direction parallel to the planar portion, and between two neighboring first protrusions. A diffraction grating having a plurality of skeleton portions and a plurality of second protrusions formed on the upper surfaces of the plurality of first protrusions, having a surface formed of metal, formed on the planar portion, and having a target material disposed thereon; do.

According to the first aspect of the present invention, the surface-enhanced Raman having high reinforcement by excitation of the near electric field enhanced through surface plasmon resonance by the first protrusion on the surface of the same shape and by the metal microstructure of the second protrusion. SER (Surface Enhanced Raman Scattering) can be expressed. Specifically, when light enters a surface on which a plurality of first projections and a plurality of second projections are formed, a vibration mode (surface plasmon) inherent to the surface caused by the plurality of first projections is generated. Then, the free electrons resonate oscillate in response to the vibration of light, and the vibration of the electromagnetic waves is excited in accordance with the vibration of the free electrons. Since the vibration of the electromagnetic wave affects the vibration of the free electrons, the system combines the vibrations of the free electrons, creating a so-called surface plasmon polariton (SPP). Thereby, Localized Surface Plasmon Resonance (LSPR) is excited in the vicinity of the plurality of second protrusions. In this structure, since the distance between two neighboring 2nd protrusions is small, the extremely strong reinforcement electric field arises in the vicinity of the contact. Then, when one to several target substances are adsorbed at the contact point, SERS is generated there. For this reason, the sharp SERS spectrum unique to a target substance can be acquired. Therefore, the sensor chip which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided. In addition, by appropriately changing the period, the height of the first projections, and the height of the second projections, the position of the resonance peak can be adjusted to any wavelength. For this reason, when specifying a target substance, the wavelength of the light to irradiate can be selected suitably, and the width | variety of a measurement range becomes wide.

In the sensor chip of the present invention, the plurality of first protrusions are preferably arranged periodically in a second direction crossing the first direction and parallel to the planar portion. Thereby, sensing can be performed under plasmon resonance conditions wider than when the first projection is formed with periodicity only in the direction parallel to the planar portion of the substrate (first direction). Therefore, the sensor chip which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided. Moreover, in addition to the period of a 1st direction in a 1st protrusion, you may change suitably the period of a 2nd direction. For this reason, when specifying a target substance, the wavelength of the light to irradiate can be selected suitably, and the width | variety of a measurement range becomes wide.

In the sensor chip of the present invention, the plurality of second protrusions are preferably arranged periodically in a third direction parallel to the planar portion. Thereby, the period of a 2nd protrusion can be changed suitably. For this reason, when specifying a target substance, the wavelength of the light to irradiate can be selected suitably, and the width | variety of a measurement range becomes wide.

In the sensor chip of the present invention, the plurality of second protrusions are preferably arranged periodically in a fourth direction crossing the third direction and parallel to the planar portion. Thereby, sensing can be performed under plasmon resonance conditions wider than when the 2nd protrusion is formed only in the direction parallel to the planar part of a base material (3rd direction). Therefore, the sensor chip which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided. Moreover, in addition to the period of a 3rd direction in a 2nd protrusion, you may change suitably the period of a 4th direction. For this reason, when specifying a target substance, the wavelength of the light to irradiate can be selected suitably, and the width | variety of a measurement range becomes wide.

In the sensor chip of the present invention, the plurality of second protrusions preferably comprise fine particles. Thereby, the sensor chip which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided.

In the sensor chip of the present invention, when the width of the first projection in the first direction is W1 and the distance between two adjacent first projections in the first direction is W2, W1> W2 It is desirable to satisfy the relationship. Thereby, since the space filling rate of the 1st protrusion in which LSPR is excited increases, sensing can be performed under the wider plasmon resonance condition than when the relationship of W1 <W2 is satisfied. In addition, when specifying a target substance, the energy of light to irradiate can be utilized effectively.

In the sensor chip of the present invention, the ratio of the distance W2 between the width W1 of the first protrusion in the first direction and two adjacent first protrusions in the first direction is determined. It is desirable to satisfy the relationship of W1: W2 = 9: 1. Thereby, the sensing can be performed under a wide plasmon resonance condition. In addition, when specifying a target substance, the energy of light to irradiate can be utilized effectively.

In the sensor chip of the present invention, the metal constituting the surface of the diffraction grating is preferably gold or silver. Thereby, since gold or silver has the characteristic to express SPP, LSPR, and SERS, SPP, LSPR, and SERS are easy to express, and it becomes possible to detect a target substance with high sensitivity.

According to a second aspect of the present invention, there is provided a sensor cartridge comprising: the sensor chip described above; A conveying unit for conveying the target substance to the surface of the sensor chip; A mounting part to mount the sensor chip; A housing accommodating the sensor chip, the transfer unit, and the mounting unit; And an irradiation window provided at a position facing the surface of the sensor chip of the housing.

According to the second aspect of the present invention, since the sensor chip described above is provided, the Raman scattered light can be selectively spectroscopically detected to detect the target molecule. Therefore, the sensor cartridge which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided.

According to a third aspect of the present invention, there is provided an analysis apparatus comprising: the sensor chip described above; A light source for irradiating light to the sensor chip; And a photo detector for detecting the light obtained by the sensor chip.

According to the third aspect of the present invention, since the sensor chip described above is provided, the Raman scattered light can be selectively spectroscopically detected to detect the target molecule. Therefore, the analysis apparatus which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided.

According to a fourth aspect of the present invention, there is provided a sensor chip comprising: a substrate having a planar portion; A plurality of first concave-convex shapes in which a plurality of first convex shapes are periodically arranged at intervals of 100 nm or more and 1000 nm or less, and a plurality of second convex shapes in a period shorter than a period of the first concave-convex shape in the plurality of first convex shapes. It includes a diffraction grating having a composite pattern formed in the planar portion, having a surface formed of a metal, and having a target material disposed by the overlapping of the second irregularities arranged periodically.

According to the fourth aspect of the present invention, a surface having a high degree of reinforcement by excitation of a near electric field enhanced by surface plasmon resonance by a first convex shape to a surface of the same shape and by a metal microstructure by a second convex shape It can express Surface Enhanced Raman Scattering (SERS). Specifically, when light enters the surface on which the first uneven shape and the second uneven shape are formed, a vibration mode (surface plasmon) inherent in the surface due to the first uneven shape is generated. Then, the free electrons resonate oscillate in response to the vibration of light, and the vibration of the electromagnetic waves is excited in accordance with the vibration of the free electrons. Since the vibration of the electromagnetic wave affects the vibration of the free electrons, the system combines the vibrations of the free electrons, creating a so-called surface plasmon polariton (SPP). 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, the extremely strong reinforcement electric field arises in the vicinity of the contact. Then, when one to several target substances are adsorbed at the contact point, SERS is generated there. For this reason, the sharp SERS spectrum unique to a target substance can be acquired. Therefore, the sensor chip which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided. Moreover, the position of a resonance peak can be matched to arbitrary wavelengths by changing suitably the period, height of a 1st convex shape, and the height of a 2nd convex shape. For this reason, when specifying a target substance, the wavelength of the light to irradiate can be selected suitably, and the width | variety of a measurement range becomes wide.

In the sensor chip of the present invention, the plurality of first convex shapes are periodically arranged in a first direction parallel to the planar portion, and in a second direction crossing the first direction and parallel to the planar portion. It is preferable to arrange periodically. Thereby, sensing can be performed under plasmon resonance conditions wider than the case where the first convex shape is formed with periodicity only in the direction parallel to the planar portion of the substrate (first direction). Therefore, the sensor chip which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided. Moreover, in addition to the period of a 1st direction in a 1st convex shape, the period of a 2nd direction can also be changed suitably. For this reason, when specifying a target substance, the wavelength of the light to irradiate can be selected suitably, and the width | variety of a measurement range becomes wide.

In the sensor chip of this invention, it is preferable that the said 2nd convex shape is arrange | positioned periodically in the 3rd direction parallel to the said planar part. Thereby, the period of a 2nd convex shape can be changed suitably. For this reason, when specifying a target substance, the wavelength of the light to irradiate can be selected suitably, and the width | variety of a measurement range becomes wide.

In the sensor chip of the present invention, the plurality of second convex shapes are preferably arranged periodically in a fourth direction crossing the third direction and parallel to the planar portion. Thereby, sensing can be performed under plasmon resonance conditions wider than when the 2nd convex shape is formed only in the direction parallel to the planar part of a base material (3rd direction). Therefore, the sensor chip which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided. Moreover, in addition to the period of a 3rd direction in a 2nd convex shape, the period of a 4th direction can also be changed suitably. For this reason, when specifying a target substance, the wavelength of the light to irradiate can be selected suitably, and the width | variety of a measurement range becomes wide.

In the sensor chip of this invention, it is preferable that the said 2nd convex shape consists of microparticles | fine-particles. Thereby, the sensor chip which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided.

In the sensor chip of the present invention, 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, W1 It is desirable to satisfy the relationship of> W2. As a result, since the space filling rate of the first convex shape in which the LSPR is excited increases, the sensing can be performed under a wider plasmon resonance condition than when the relationship W1 < W2 is satisfied. In addition, when specifying a target substance, the energy of light to irradiate can be utilized effectively.

In the sensor chip of the present invention, the distance W2 between the width W1 of the first convex shape in the first direction and two adjacent first convex shapes in the first direction. It is desirable that the ratio satisfy the relationship W1: W2 = 9: 1. Thereby, the sensing can be performed under a wide plasmon resonance condition. In addition, when specifying a target substance, the energy of light to irradiate can be utilized effectively.

In the sensor chip of the present invention, the metal constituting the surface of the diffraction grating is preferably gold or silver. Thereby, since gold or silver has the characteristic to express SPP, LSPR, and SERS, SPP, LSPR, and SERS are easy to express, and it becomes possible to detect a target substance with high sensitivity.

According to a fifth aspect of the present invention, there is provided a sensor cartridge comprising: the sensor chip described above; A conveying unit for conveying the target substance to the surface of the sensor chip; A mounting part to mount the sensor chip; A housing accommodating the sensor chip, the transfer unit, and the mounting unit; And an irradiation window provided at a position facing the surface of the sensor chip of the housing.

According to the fifth aspect of the present invention, since the sensor chip described above is provided, the Raman scattered light can be selectively spectroscopically detected to detect the target molecule. Therefore, the sensor cartridge which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided.

According to a sixth aspect of the present invention, there is provided an analysis apparatus comprising: the sensor chip described above; A light source for irradiating light to the sensor chip; And a photo detector for detecting the light obtained by the sensor chip.

According to the sixth aspect of the present invention, since the sensor chip described above is provided, the Raman scattered light can be selectively spectrated to detect the target molecule. Therefore, the analysis apparatus which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided.

1A and 1B are schematic diagrams showing a schematic configuration of a sensor chip of one embodiment according to the present invention;
2A and 2B show Raman scattering spectroscopy,
3A and 3B show the mechanism of full length enhancement by LSPR;
4 shows SERS spectroscopy,
5 is a graph showing the reflected light intensity of the first projection unit;
6 is a graph showing a dispersion curve of an SPP;
7 is a graph showing the reflected light intensity of the first projection unit;
8A and 8B are graphs showing the reflected light intensities of the first protrusions;
9A and 9B are graphs showing the reflected light intensity of the first projection alone;
10 is a graph showing the reflected light intensity of the sensor chip of one embodiment according to the present invention;
11A to 11C are graphs showing the reflected light intensity of the structure in which the second projection is superposed on the planar portion of the substrate;
12 is a schematic view of a sensor chip in which a plurality of second protrusions are formed on a plane portion of a base material;
FIG. 13 is a graph showing the reflected light intensity of the sensor chip in FIG. 12;
14A to 14F illustrate a manufacturing process of a sensor chip;
15 is a schematic configuration diagram showing a modification of the sensor chip having the first protrusion of the form;
16A and 16B are schematic configuration diagrams showing a modification of the sensor chip having the second protrusions;
17A and 17B are schematic configuration diagrams showing a modification of the sensor chip having the second projections;
18 is a schematic diagram illustrating an example of an analysis apparatus;
19 is a schematic diagram showing a schematic configuration of a sensor chip of one embodiment according to the present invention;
It is a schematic diagram which shows schematic structure of the sensor chip of one Embodiment which concerns on this invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, embodiments of the present invention will be described with reference to the drawings. Such 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. In addition, in the following drawings, in order to make each structure easy to understand, the scale, number, etc. in an actual structure and each structure differ.

1: A and 1B is a schematic diagram which shows schematic structure of the sensor chip of one Embodiment which concerns on this invention. 1A is a schematic configuration perspective view of a sensor chip, and FIG. 1B is a schematic configuration sectional view of a sensor chip. In Fig. 1B, reference numeral P1 denotes a period of the first projection (first convex shape), reference numeral P2 denotes a period of the second projection (second convex shape), and reference numeral W1 denotes the first projection. Width, reference numeral W2 is the distance between two neighboring first protrusions, reference numeral T1 is the height of the first protrusion (depth of the groove), reference numeral T2 is the height of the second protrusion (groove) Depth).

19 and 20 are schematic diagrams showing a schematic configuration of a sensor chip of an embodiment according to the present invention corresponding to FIG. 1B. 19 and 20, reference numeral P1 denotes a period of the first protrusion (first convex shape), reference numeral P2 denotes a period of the second protrusion (second convex shape), and reference numeral W1 denotes The width of the first projection, reference W2 is the distance between two neighboring first projections, T1 is the height of the first projection (depth of the groove), and T2 is the width of the second projection. Height (depth of the groove)

The sensor chip 1 arranges a target material on a diffraction grating 9 formed on a substrate 10 including a metal, and localized surface plasmon resonance (LSPR) and surface enhanced Raman scattering (SERS: Surface). Enhanced Raman Scattering) is used to detect the target material.

The sensor chip 1 is used to arrange the target material on the diffraction grating 9 formed on the substrate 10 and to detect the target material using LSPR and SERS. The diffraction grating 9 includes a plurality of first projections 11 arranged in a period P1 of 100 nm or more and 1000 nm or less in a first direction parallel to the planar portion of the substrate 10, and two adjacent ones. A plurality of skeletal portions 10a disposed between the first protrusions 11 and constituting the skeleton of the base 10 and a plurality of agents formed on the respective upper surfaces 11a of the plurality of first protrusions 11. 2 protrusions 12 are provided. The diffraction grating 9 has a surface formed of metal and is formed on the planar portion 10s of the substrate 10.

In other words, the diffraction grating 9 has a first convex shape (first projection) 11 at a period P1 of 100 nm or more and 1000 nm or less in a direction perpendicular to the plane portion 10s of the substrate 10. The second convex shape (second protrusion) 12 is arranged in each of the first concave-convex shape in which the c) is arranged and the period P2 shorter than the period of the first concave-convex shape in each of the plurality of first convex shapes 11. It has a composite pattern obtained by superimposing the 2nd uneven shape, and has the surface formed from the metal.

In addition, the term "diffraction grating" as used herein means a structure in which a plurality of irregularities (plural protrusions) are periodically arranged.

In addition, the "plane part" as used here means the upper surface part of description. That is, a "plane part" means the surface part of the one side of the base material in which a target substance is arrange | positioned. In addition, the composite pattern formed by overlapping a 1st uneven shape and a 2nd uneven shape is formed in the upper surface part of a base material at least. In addition, the shape is not specifically limited about 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 of the substrate to the flat portion (upper surface portion) and the like, it is preferable that the lower surface portion of the substrate is a plane parallel to and flat with respect to the skeleton portion of the flat portion.

As a structure of the diffraction grating 9, as shown in FIG. 1B, the structure in which the base material 10, the 1st convex shape 11, and the 2nd convex shape 12 all consist of metal is mentioned. 19, the base material 10 and the 1st convex shape 11 are formed of insulating members, such as glass and resin, the whole exposed part of an insulating member is covered with a metal film, and it consists of a metal on a metal film. The structure in which the 2nd convex shape 12 was formed is mentioned. Moreover, as shown in FIG. 20, the base material 10, the 1st convex shape 11, and the 2nd convex shape 12 were all formed by the insulating member, and the whole exposed part of the insulating member was covered with the metal film. Can be mentioned. That is, the diffraction grating 9 has the structure in which at least the surface of the skeletal part 10a, the 1st convex shape 11, and the 2nd convex shape 12 of the base material 10 was formed with the metal.

The base material 10 has a structure in which a metal film is formed in 150 nm or more on the glass substrate, for example. This metal film turns into the 1st protrusion 11 and the 2nd protrusion 12 by the manufacturing process mentioned later. In addition, in this embodiment, although the base material in which the metal film was formed on the glass substrate as the base material 10 is used, it is not limited to this. For example, a substrate on which a metal film is formed on a quartz substrate or a sapphire substrate may be used as the substrate 10. Moreover, you may use the flat plate which consists of metal as a base material.

The 1st protrusion 11 is formed in the flat part 10s of the base material 10, and has predetermined height T1. The first projections 11 are arranged in a period P1 shorter than the wavelength of light in a direction (first direction) parallel to the plane portion 10s of the substrate 10. In the period P1, the width W1 of the single width | variety W1 of the 1st protrusion 11 single body in a 1st direction (left-right direction of FIG. 1B), and the distance W2 between two adjacent 1st protrusions 11 Are summed together (P1 = W1 + W2). In addition, the 1st protrusion 11 is rectangular convex from a cross section, and the some 1st protrusion 11 is formed in line and space (stripe shape) by planar view.

In the 1st protrusion 11, it is preferable that period P1 is set to the range of 100 nm-1000 nm, for example, and height T1 is set to the range of 10 nm-100 nm. Thereby, the 1st protrusion 11 can function as a structure for expressing LSPR.

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

Two or more 2nd protrusions 12 are formed in each upper surface 11a of the some 1st protrusion 11, and have predetermined height T2. Specifically, the second projection 12 is formed on the skeleton portion 10a of the substrate 10 (the flat portion 10s of the substrate 10 in the region between two neighboring first projections 11). It is not formed, but is formed only on the upper surface 11a of the first convex shape 11.

These second protrusions 12 are arranged at a period P2 shorter than the wavelength of light in a direction (third direction) parallel to the plane portion 10s of the substrate 10. In the period P2, the width | variety of the 2nd protrusion 12 single body in a 3rd direction (left-right direction of FIG. 1B), and the distance between two adjacent 2nd protrusions 12 are mutually added. As a result, the period P2 of the second projection 12 is sufficiently shorter than the period P1 of the first projection 11.

In the second projection 12, for example, the period P2 is preferably set to a value smaller than 500 nm, and the height T2 is preferably set to a value smaller than 200 nm. Thereby, the 2nd protrusion 12 can function as a structure for expressing SERS.

In addition, in this embodiment, the arrangement direction (first direction) of the 1st protrusion 11 and the arrangement direction (third direction) of the 2nd protrusion 12 are the same. Similarly to the first projection, the second projection 12 is formed in a rectangular convex shape in cross section, and the plurality of second projections 12 are formed in a line and space (stripe shape) in plan view.

As a metal of the surface of the diffraction grating 9, gold (Au), silver (Ag), copper (Cu), aluminum (A1), or these alloys are used, for example. In this embodiment, gold or silver which has the characteristics which express SPP, LSPR, and SERS is used. Thereby, SPP, LSPR, and SERS become easy to express, and it becomes possible to detect a target substance with high sensitivity.

Here, the 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 plurality of first protrusions 11 and the plurality of second protrusions 12 are formed, the vibration mode inherent in the surface by the plurality of first protrusions 11. (Surface plasmon) 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 the electromagnetic wave is excited in accordance with the vibration of the free electrons. Since the vibration of the electromagnetic wave affects the vibration of the free electrons, a system in which the vibrations of both are combined, so-called surface plasmon polariton (SPP), is generated. Incidentally, in this embodiment, the incident angle of light is substantially perpendicular to the chip surface, but the incident angle is not limited to this angle (vertical) as long as it is a condition for exciting the SPP.

This SPP propagates along the surface of the sensor chip 1, specifically, along the interface between air and the second projection 12, and excites a strong local electric field in the vicinity of the second projection 12. The coupling of SPP is sensitive to the wavelength of light, and the coupling efficiency is high. In this way, 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) can be used from the relationship between LSPR and Raman scattered light.

2A and 2B are diagrams showing Raman scattering spectroscopy. 2A illustrates the principle of Raman scattering spectroscopy. 2B shows the Raman spectrum (raman shift and Raman scattering intensity). In FIG. 2A, reference numeral L denotes incident light (light having a single wavelength), reference numeral Ra denotes Raman scattered light, reference Ray denotes Rayleigh scattered light, reference numeral X denotes target molecule (target). Substance). In FIG. 2B, the horizontal axis represents Raman shift. In addition, a Raman shift is a difference between the frequency of the Raman scattered light Ram and the frequency of the incident light L, and says a value peculiar to the structure of the target molecule X.

As shown in Fig. 2A, when the light L having a single wavelength is irradiated onto the target molecule X, light having a wavelength different from that of the incident light in the scattered light is generated (Raman scattered light Ram). The energy difference between the Raman scattered light Ram and the incident light L corresponds to the energy of the vibration level, rotational level, or electron level of the target molecule X. Since the target molecule X has a unique vibration energy according to its structure, the target molecule X can be specified by using light L of 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. In addition, most of the incident light L has the same amount of energy as before the impact even after the collision with the target molecule X. This elastic scattered light is called Rayleigh scattered light. For example, when the vibration energy of Rayleigh scattered light Ray is V4, V4 = V1.

From the Raman spectrum shown in FIG. 2B, when the scattering intensity (spectral peak) of Raman scattered light (Ram) is compared with the scattering intensity of Rayleigh scattered light (Ray), it turns out that Raman scattered light (Ram) is weak. As described above, the Raman scattering spectroscopy is excellent in the identification ability of the target molecule (X), but the sensitivity itself of sensing the target molecule (X) is a low measurement method. In this embodiment, in order to achieve high sensitivity, spectroscopy (SERS spectroscopy) using surface-enhanced Raman scattering is used (see FIG. 4).

3A and 3B show the mechanism of full-field enhancement by LSPR. 3A is a schematic diagram when light is incident on metal nanoparticles. 3B is a diagram illustrating LSPR enhanced full length. In FIG. 3A, reference numeral 100 denotes a light source, reference numeral 101 denotes metal nanoparticles, and reference numeral 102 denotes light emitted from the light source. In Fig. 3B, reference numeral 103 is a surface localization full length.

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

Then, in accordance with the resonance oscillation of the free electrons, the surface localization electric field 103 that is strong near the metal nanoparticles 101 is excited (see FIG. 3B). In this way, the light 102 is incident on the metal nanoparticle 101, thereby allowing LSPR to be excited.

4 is a diagram illustrating SERS spectroscopy. In Fig. 4, reference numeral 200 denotes a substrate (corresponding to the first projection of one embodiment according to the present invention), and reference numeral 201 denotes a metal nanostructure (second projection of one embodiment according to the present invention). Equivalent reference numeral 202 denotes a selective adsorption membrane, reference numeral 203 denotes an augmented electric field, reference numeral 204 denotes a target molecule, reference numeral 211 denotes an incident laser light, reference numeral 212 denotes a Raman scattered light, Reference numeral 213 denotes Rayleigh scattered light. In addition, the selective adsorption membrane 202 adsorbs the target molecules 204.

As shown in FIG. 4, when the laser light 211 enters the metal nanostructure 201, free electrons resonate oscillate in response to 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, in accordance with the resonance vibration of the free electrons, a strong surface localization electric field near the metal nanostructure 201 is excited. Thereby, LSPR is excited. When the distance between neighboring metal nanostructures 201 becomes small, an extremely strong enhanced electric field 203 is generated near the contact point. When one to several target molecules 204 adsorb to the contact point, SERS is generated there. This point has also been confirmed in the results of the enhanced electric field generated between two adjacent silver nanoparticles calculated using the Finite Difference Time Domain (FDTD) method. Thus, Raman scattered light can be selectively spectroscopy to detect the target molecule with high sensitivity.

As described above, the present embodiment has a structure in which the LSPR is excited by arranging the first protrusions 11 at a period P1 shorter than the wavelength of light in a direction parallel to the planar portion of the substrate 10. Moreover, this embodiment has a structure which expresses SERS by forming two or more 2nd protrusions 12 only in the upper surface 11a of the 1st protrusion 11. Specifically, based on the principle that when a single wavelength of light is irradiated to a target molecule, a Raman scattered light is generated, the target molecule is disposed between two neighboring second protrusions 12 and an augmented magnetic field is generated near this contact point. SERS is generated by doing. Thereby, it becomes possible to use SERS spectroscopy which can detect a target substance with high sensitivity compared with Raman scattering spectroscopy.

Fig. 5 is a graph showing the reflected light intensity of the first protrusions alone. In FIG. 5, the horizontal axis represents wavelength of light and the vertical axis represents 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 (to be 1.0) is the absorbance.

Light is incident perpendicularly to the first projection 11. The polarization direction of light is TM polarization. The period of the first protrusion 11 is 580 nm, and the resonance peak of the reflected light intensity exists near the wavelength of 630 nm. This resonance peak is derived from SPP, and when the height T1 of the first protrusion 11 is increased, the resonance peak shifts to the long wavelength side (long wavelength region). When the height T1 of the first protrusion 11 is 30 nm, the reflected light intensity is the strongest and it can be seen that the absorption is the strongest.

6 is a graph showing the dispersion curve of the SPP. In Fig. 6, reference numeral C1 denotes a dispersion curve of the SPP (for example, a value at the interface between air and Au), and reference numeral C2 denotes a light line. The period of the first protrusion 11 is 580 nm. The position of the grating vector of the 1st protrusion 11 is shown on the horizontal axis (it corresponds to 2 (pi) / P on the horizontal axis in FIG. 6). Extending the line upwards from this position intersects the SPP's dispersion curve. The wavelength corresponding to this intersection is calculated | required from following formula (1).

[Equation 1]

In Equation 1, P1 is a period of the first protrusion 11, E1 is a complex dielectric constant of air, and E2 is a complex dielectric constant of Au. Substituting P1, E1, E2 into Equation 1 yields λ = 620 nm (corresponding to ω 0 on the vertical axis in FIG. 6).

The height T1 of the 1st protrusion 11 becomes large, and the hub part in the wave number of SPP becomes large. Thereby, the real part in the wavenumber of SPP becomes small, and the intersection of the line extended from the position of a lattice vector, and the dispersion curve of SPP moves from upper right to 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 projection alone. FIG. 7, the horizontal axis represents the wavelength of light and the vertical axis represents the reflected light intensity. The ratio (hereinafter, referred to as duty ratio) of the width W1 between the width W1 of the first protrusion 11 in the first direction and two adjacent first protrusions is taken as a parameter (W1: W2). = 5: 5, 8: 2). In addition, the graph of the parameters W1: W2 = 5: 5 in this figure is the same as the graph of the parameter T1 = 30 in FIG.

Light of TM polarized light is incident perpendicularly to the first projection 11. 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 near the wavelength of 630 nm. In addition, when the duty ratio is W1: W2 = 8: 2, the resonance peak of the reflected light intensity exists near the wavelength of 660 nm. If the duty ratio is increased, the gradient of the resonance peak is sharpened, and the resonance peak is shifted to the long wavelength side.

8A to 9B are graphs showing the reflected light intensity of the first projection alone. 8A is a graph when the duty ratio is W1: W2 = 7: 3. 8B is a graph when the duty ratio is W1: W2 = 3: 7. 9A is a graph when the duty ratio is W1: W2 = 9: 1. 9B is a graph when the duty ratio is W1: W2 = 1: 9. 8A to 9B, the horizontal axis represents wavelength of light and the vertical axis represents 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).

Light of TM polarized light is incident perpendicularly to the first projection 11. 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 near 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 near 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 shifts to the long 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 near the wavelength 730 nm, and the gradient of the resonance peak is wide (see FIG. 9B). 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 shifts to the long 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 reflected light intensity of the structure in which the second protrusion 12 is superimposed on the first protrusion 11, that is, the sensor chip 1 of the embodiment according to the present invention. In FIG. 10, the horizontal axis represents wavelength of light and the vertical axis represents reflected light intensity. The height T2 of the second projection 12 is taken as a parameter (T2 = 0 nm, 30 nm). In addition, the graph of parameter T2 = 0 in this figure is the same as the graph of parameter W1: W2 = 8: 2 in FIG.

Light of TM polarized light is incident perpendicularly to the first projection 11. 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. In addition, the period P2 of the second protrusion 12 is 116 nm. The plurality of second projections 12 are formed only on the upper surface 11a of the first projection 11, whereby 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 the SERS described above. When the height T2 of the second protrusion 12 is 30 nm, a local electric field strong in the vicinity of the surface of the second protrusion 12 can be excited by irradiating light having a wavelength of 710 nm. In addition, by appropriately changing the periods P1 and P2 and the heights T1 and T2 of the first projections 11 and the second projections 12, the position of the resonance peak can be adjusted to an arbitrary wavelength.

11A to 11C are graphs showing the reflected light intensities of the structure in which the second protrusions 12 are superposed on the substrate 10. FIG. 11A is a graph when a plurality of second projections are formed (not shown) in a plurality of plane portions (skeletal portions of the substrate) of the substrate in the upper surface of the first projection and the region between two adjacent first projections. . 11B is a graph of the case where a plurality of second projections are formed only on the upper surface of the first projection (the structure of the sensor chip of one embodiment according to the present invention). FIG. 11C is a graph of the case where a plurality of second projections are formed only on the planar portion (skeletal portion of the substrate) in the region between two adjacent first projections (not shown). 11A to 11C, the horizontal axis represents wavelength of light and the vertical axis represents reflected light intensity. The height T2 of the second projection 12 is taken as a parameter (T2 = 0 nm, 40 nm). In addition, the graph of parameter T2 = 0 in this figure is the same as the graph of parameter T1 = 30 in FIG.

Light of TM polarized light is incident perpendicularly to the first projection 11. 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. In addition, the period P2 of the second projection 12 is 97 nm, and the height T2 is 40 nm.

By forming a plurality of second projections on each of the upper surface of the first projection and the skeleton portion of the substrate, it can be seen that the position of the resonance peak of the reflected light intensity is shifted from the wavelength 640 nm to the wavelength 730 nm vicinity (see FIG. 11A). ). In addition, it is understood that 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 by forming a plurality of second protrusions 12 only on the upper surface 11a of the first protrusion 11. (See FIG. 11B). 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 projections are formed only in the skeleton portion of the substrate.

From these results, it is thought that SPP propagates mainly along the interface of air and the upper surface of a 1st protrusion. Therefore, forming two or more second projections only on the upper surface of the first projection without forming the second projections is effective as a structure for exciting LSPR and expressing SERS. Further, by increasing the duty ratio of the first projections (W1> W2), the space filling rate of the first projections that excite the LSPR increases, so that the energy of the light to be irradiated when specifying the target substance can be effectively used. .

12 shows the case where only the second projection 12 is formed in the flat portion 10s of the substrate 10 without forming the first projection 11 in the flat portion 10s of the substrate 10, that is, the substrate ( It is a figure which shows typically the sensor chip 2 when the some 2nd protrusion 12 is formed in planar part 10s of 10. 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 planar portion 10s of the substrate 10. In Fig. 13, the horizontal axis represents wavelength of light and the vertical axis represents reflected light intensity. The height T2 of the second projection 12 is taken as a parameter (T2 = 0 nm, 40 nm, 80 nm). Light of the TM polarized light is incident perpendicularly to the second projection 12. Even in this figure, the resonance peak of the 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 it does not go through the SPP, it is hardly possible to couple light energy to the second protrusion 12.

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

Next, a resist pattern 32a having a period of 580 nm is formed by a method such as imprint (see FIG. 14B). Next, using the 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 first protrusion 31a is formed by removing the resist pattern 32a (see FIG. 14C).

Next, the resist 33 is applied onto the Au film 31 on which the first protrusion 31a is formed by spin coating or the like (see FIG. 14D). Next, by a method such as imprint, a resist pattern 33a having a period Pb of 116 nm is formed only on the upper surface of the first protrusion 31a (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 second protrusion 31b is formed by removing the resist pattern 33a (see FIG. 14F). By the above process, the sensor chip 3 of one Embodiment which concerns on this invention can be manufactured.

According to the sensor chip 1 of the embodiment according to the present invention, LSPR is excited through the SPP to the metal microstructure by the first protrusion 11, and SERS to the metal microstructure by the second protrusion 12. Can be expressed. Specifically, when light is incident on the surface on which the plurality of first protrusions 11 and the plurality of second protrusions 12 are formed, the vibration mode (surface plasmon) inherent to the surface by the plurality of first protrusions 11 is generated. Occurs. Then, free electrons resonate and vibrate with the vibration of light, and SPP is excited, and the surface local electric field strong in the vicinity of the some 2nd protrusion 12 is excited. As a result, the LSPR is excited. In this structure, since the distance between two adjacent 2nd protrusions 12 is small, the extremely strong reinforcement electric field arises in the vicinity of the contact. Then, when one to several target substances are adsorbed at the contact point, SERS is generated there. For this reason, the intensity | strength characteristic of a narrow reflection light intensity spectrum and a sharp resonance peak can be obtained, and a sensor sensitivity can be improved. Therefore, the sensor chip 1 which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided. In addition, by suitably changing the period P1 of the 1st protrusion 11, the height T1, and the height T2 of the 2nd protrusion 12, the position of a resonance peak can be matched to arbitrary wavelengths. For this reason, when specifying a target substance, the wavelength of the light to irradiate can be selected suitably, and the width | variety of a measurement range becomes wide.

According to this configuration, since the second projections 12 are arranged with periodicity in the third direction parallel to the planar portion of the substrate 10, the period P2 of the second projections 12 may be appropriately changed. Can be. For this reason, when specifying a target substance, the wavelength of the light to irradiate can be selected suitably, and the width | variety of a measurement range becomes wide.

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

According to this configuration, since the duty ratio of the first protrusion 11 satisfies the relationship of W1> W2, and the space filling rate of the first protrusion 11 to which LSPR is excited increases, the relationship of W1 <W2 is changed. Sensing can be performed under wider plasmon resonance conditions than satisfactory. In addition, when specifying a target substance, the energy of light to irradiate can be utilized effectively.

Further, even when the duty ratio of the first protrusion 11 satisfies the relationship of W1: W2 = 9: 1, the sensing can be performed under a wide plasmon resonance condition, and the energy of the light to be irradiated can be effectively used. .

In addition, in this embodiment, although the 1st protrusion 11 showed the structure arranged in the period P1 shorter than the wavelength of light in the direction parallel to the planar part of the base material 10 (1st direction), It is not limited. The sensor chip 4 which has a structure different from the 1st protrusion 11 of this embodiment is demonstrated using FIG.

FIG. 15 is a schematic configuration perspective view of the sensor chip 4 having the first protrusions 41 different from the first protrusions 11 described above. In addition, in this figure, illustration of a 2nd protrusion is abbreviate | omitted for convenience.

As shown in FIG. 15, the 1st protrusion 41 is formed in the flat part 40s of the base material 40. As shown in FIG. These first projections 41 are arranged at a period P3 shorter than the wavelength of light in a direction (first direction) parallel to the planar portion of the substrate 40. The first protrusion 41 is arranged at a period P4 shorter than the wavelength of light in the second direction perpendicular to the first direction and parallel to the planar portion of the substrate 40. The second direction is not limited to the direction orthogonal to the first direction and parallel to the planar portion of the base 40, but may be a direction intersecting the first direction and parallel to the planar portion of the base 40.

According to this structure, sensing can be performed under plasmon resonance conditions wider than when the first projection is formed only in a direction parallel to the planar portion of the substrate 10 (first direction). Therefore, the sensor chip 4 which can aim at the improvement of a sensor sensitivity and can specify a target substance from a SERS spectrum can be provided. In addition to the period P3 in the first direction in the first projection, the period P4 in the second direction may be appropriately changed. For this reason, when specifying a target substance, the wavelength of the light to irradiate can be selected suitably, and the width | variety of a measurement range becomes wide.

In addition, in this embodiment, the structure in which the 2nd protrusion 12 is arrange | positioned by the period P2 shorter than the wavelength of light in the direction parallel to the planar part of the base material 10 (third direction), specifically, Although the structure in which the arrangement direction (first direction) of the first protrusion 11 and the arrangement direction (third direction) of the second protrusion 12 are in the same direction is shown, the present invention is not limited thereto. The sensor chips 5, 6, 7, and 8 having a structure different from the second protrusions 12 of the present embodiment will be described with reference to Figs. 16A to 17B.

16A and 16B are schematic configuration perspective views of a sensor chip having a second protrusion different from the above-described second protrusion 12. FIG. 16A shows the sensor chip 5 with the second protrusion 52, and FIG. 16B shows the sensor chip 6 with the second protrusion 62.

As shown to FIG. 16A, two or more 2nd protrusions 52 are formed only in each upper surface 51a of the some 1st protrusion 51 formed in the flat part 50s of the base material 50. As shown in FIG. That is, the 2nd protrusion 52 is not formed in the frame | skeleton part 50a of the base material 50. As shown in FIG. In this figure, as an example, the structure where the angle | corner of the arrangement direction (1st direction) of the 1st protrusion 51 and the arrangement direction (3rd direction) of the 2nd protrusion 52 is 45 degrees is shown, have.

As shown in FIG. 16B, two or more second projections 62 are formed only on the upper surfaces 61a of the plurality of first projections 61 formed on the planar portion 60s of the substrate 60. That is, the 2nd protrusion 62 is not formed in the frame | skeleton part 60a of the base material 60. As shown in FIG. In this drawing, as an example, a structure in which the angle at which the arrangement direction (first direction) of the first protrusion 61 intersects with the arrangement direction (third direction) of the second protrusion 62 is 90 °, have.

Also in such a configuration, it is possible to provide a sensor chip capable of improving sensor sensitivity and specifying a target material from the SERS spectrum under a wide plasmon resonance condition.

17A and 17B are enlarged plan views of a sensor chip having a second protrusion different from the above-described second protrusion 12. 17A shows a sensor chip 7 with a second protrusion 72, and FIG. 17B shows a sensor chip 8 with a second protrusion 82.

As shown in FIG. 17A, two or more second projections 72 are formed only on the upper surfaces 71a of the plurality of first projections (not shown). Further, the second projections 72 are arranged with periodicity in the fourth direction crossing the third direction and parallel to the plane portion of the substrate. In this figure, as an example, the second projection 72 shows a circular structure in plan view. In addition, the second projections 72 may be arranged randomly without having periodicity.

As shown in FIG. 17B, two or more second projections 82 are formed only on the upper surfaces 81a of the plurality of first projections (not shown). The second projection 82 is arranged with periodicity in a fourth direction crossing the third direction and parallel to the planar portion of the substrate. In this figure, as an example, the second projection 82 shows an elliptical structure in plan view. In addition, the 2nd protrusion 82 may be arrange | positioned at random without having periodicity.

According to this structure, sensing can be performed under plasmon resonance conditions wider than when the second projection is formed only in the direction parallel to the planar portion of the substrate (third direction). Therefore, the sensor chip which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided. Moreover, in addition to the period of a 3rd direction in a 2nd protrusion, you may change suitably the period of a 4th direction. For this reason, when specifying a target substance, the wavelength of the light to irradiate can be selected suitably, and the width | variety of a measurement range becomes wide.

In addition, in this embodiment, although the 2nd protrusion is formed by patterning the Au film formed in the upper surface of a glass substrate, it is not limited to this. For example, the second projection may be fine particles. Also in such a structure, the sensor chip which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided.

In addition, in this embodiment, although the same metals (gold or silver) are used as a metal contained in a base material, the metal contained in a 1st protrusion, and a metal contained in a 2nd protrusion, it is not limited to this. For example, another metal (gold, silver, copper, aluminum or These alloys) may be used in combination.

(Analysis device)

It is a schematic diagram which shows an example of the analysis apparatus provided with the sensor chip of one Embodiment which concerns on this invention. In addition, the arrow in FIGS. 14A-14F shows the conveyance direction of a target substance (not shown).

As shown in FIG. 18, the analysis apparatus 1000 includes a sensor chip 1001, a light source 1002, a photo detector 1003, a collimator lens 100, and a polarization control element 1005. ), A dichroic mirror (1006), an objective lens (1007), an objective lens (1008), and a conveying unit (1010). The light source 1002 and the photodetector 1003 are electrically connected to a control apparatus (not shown) via wiring, respectively.

The light source 1002 generates laser light that excites SPP, LSPR, and SERS. The laser light irradiated from the light source 1002 becomes parallel light by the collimator lens 1004, passes through the polarization control element 1005, and is in the direction of the sensor chip 1001 by the dichroic mirror 1006. The light is guided and collected by the objective lens 1007, and enters the sensor chip 1001. At this time, the target substance (not shown) is arrange | positioned at the surface (for example, the surface in which the metal nanostructure and the detection substance selection mechanism were formed) of the sensor chip 1001. In addition, by controlling the driving of a fan (not shown), the target substance is introduced into the conveyance section 1010 from the delivery port 1011 and is discharged from the discharge port 1012 to the exterior of the conveyance section 1010. In addition, the size of the metal nanostructure is smaller than the wavelength of the laser light.

When a laser beam enters a metal nanostructure, free electrons resonate and vibrate in response to the vibration of a laser beam, and a strong surface localization electric field in the vicinity of the metal nanostructure is excited, thereby LSPR is excited. When the distance between neighboring metal nanostructures becomes small, an extremely strong enhancement electric field is generated near the contact point, and SERS is generated therefrom when one to several target substances are adsorbed at the contact point.

The light (Raman scattered light or Rayleigh scattered light) obtained by the sensor chip 1001 passes through the objective lens 1007, is guided by the dichroic mirror 1006 in the direction of the photo detector 1003, and the objective lens 1007. ) Is focused on and incident on the photodetector 1003. Then, the photodetector 1003 is used for spectral decomposition to obtain spectral information.

According to such a structure, since the sensor chip of one Embodiment which concerns on this invention mentioned above is provided, the target molecule can be detected by selectively spectroscopy Raman scattered light. Therefore, the analysis apparatus 1000 which can aim at the improvement of a sensor sensitivity and can specify a target substance from SERS spectrum can be provided.

The analyzing apparatus 1000 includes a sensor cartridge 1100. The sensor cartridge 1100 accommodates a sensor chip 1001, a conveying unit 1010 for conveying a target substance to the surface of the sensor chip 1001, a mounting unit 1101 for mounting the sensor chip 1001, and these The housing 1110 is provided. An irradiation window 1111 is provided at a position facing the sensor chip 1001 of the housing 1110. The laser light irradiated from the light source 1002 passes through the irradiation window 1111 and is irradiated onto the surface of the sensor chip 1001. The sensor cartridge 1100 is located above the analysis device 1000, and is provided to be detachable from the main body of the analysis device 1000.

According to such a structure, since the sensor chip of one Embodiment which concerns on this invention mentioned above is provided, the target molecule can be detected by selectively spectroscopy Raman scattered light. Therefore, the sensor cartridge 1100 which can aim at the improvement of a sensor sensitivity and can specify a target substance from a SERS spectrum can be provided.

The analysis device of one embodiment according to the present invention can be widely applied to a sensing device used for medical or medical examination, detection of drugs or explosives, and inspection of food. It can also be used as an affinity sensor that detects the presence or absence of adsorption of a substance, such as the presence or absence of adsorption of an antigen in an antigen-antibody reaction.

1: sensor chip 9: diffraction grating
10: base material 10a: skeleton portion
10s: planar portion 11: first projection (first convex shape)
12: 2nd protrusion (2nd convex shape)

Claims (20)

In the sensor chip,
A substrate having a planar portion;
A plurality of skeletons which are arranged between a plurality of first protrusions periodically arranged in a period of 100 nm or more and 1000 nm or less in a first direction parallel to the planar portion and adjacent two first protrusions to constitute a skeleton of the substrate; And a diffraction grating comprising a portion and second projections formed on at least two upper surfaces of each of the plurality of first projections, the diffraction grating having a surface formed of metal, formed on the planar portion, and having a target material disposed thereon. doing
Sensor chip. The method of claim 1,
The plurality of first protrusions are periodically arranged in a second direction crossing the first direction and parallel to the planar portion.
Sensor chip. The method of claim 1,
Two or more of the second protrusions are periodically arranged in a third direction parallel to the planar portion.
Sensor chip. The method of claim 3, wherein
Two or more of the second protrusions are periodically arranged in a fourth direction crossing the third direction and parallel to the planar portion;
Sensor chip. The method of claim 1,
At least two of the second protrusions are composed of fine particles
Sensor chip. The method of claim 1,
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, the relationship of W1> W2 is satisfied.
Sensor chip. The method according to claim 6,
The ratio of the distance W2 between the width W1 of the first protrusion in the first direction and two adjacent first protrusions in the first direction is W1: W2 = 9: 1. Satisfying relationship
Sensor chip. The method of claim 1,
The metal constituting the surface of the diffraction grating is gold or silver
Sensor chip. In the sensor cartridge,
A sensor chip according to claim 1;
A conveying unit for conveying the target substance to the surface of the sensor chip;
A mounting part to mount the sensor chip;
A housing accommodating the sensor chip, the transfer unit, and the mounting unit;
An irradiation window provided at a position opposite to a surface of the sensor chip of the housing;
Sensor cartridge. In the analysis device,
A sensor chip according to claim 1;
A light source for irradiating light to the sensor chip;
A photo detector for detecting light obtained by the sensor chip.
Analysis device. In the sensor chip,
A substrate having a planar portion;
A plurality of first concave-convex shapes in which a plurality of first convex shapes are periodically arranged at intervals of 100 nm or more and 1000 nm or less, and a plurality of second convex shapes in a period shorter than a period of the first concave-convex shape in the plurality of first convex shapes. The second concave-convex shapes arranged periodically have a composite pattern formed in the planar portion, have a surface formed of metal, and includes a diffraction grating in which a target material is disposed.
Sensor chip. The method of claim 11,
The plurality of first convex shapes are periodically arranged in a first direction parallel to the planar portion, and are periodically arranged in a second direction crossing the first direction and parallel to the planar portion.
Sensor chip. The method of claim 11,
The plurality of second convex shapes are periodically arranged in a third direction parallel to the planar portion.
Sensor chip. The method of claim 13,
The plurality of second convex shapes are periodically arranged in a fourth direction crossing the third direction and parallel to the planar portion.
Sensor chip. The method of claim 11,
The plurality of second convex shapes are made of fine particles
Sensor chip. The method of claim 15,
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.
Sensor chip. 17. The method of claim 16,
The ratio of the distance W2 between the width W1 of the first convex shape in the first direction and two adjacent first convex shapes in the first direction is W1: W2 = 9: 1, satisfy the relationship
Sensor chip. The method of claim 11,
The metal constituting the surface of the diffraction grating is gold or silver
Sensor chip. In the sensor cartridge,
A sensor chip according to claim 11;
A conveying unit for conveying the target substance to the surface of the sensor chip;
A mounting part to mount the sensor chip;
A housing accommodating the sensor chip, the transfer unit, and the mounting unit;
An irradiation window provided at a position opposite to a surface of the sensor chip of the housing;
Sensor cartridge. In the analysis device,
A sensor chip according to claim 11;
A light source for irradiating light to the sensor chip;
A photo detector for detecting light obtained by the sensor chip.
Analysis device.

Images