JP5438106B2 - Structure, localized surface plasmon resonance sensor chip, and localized surface plasmon resonance sensor - Google Patents

Description

  The present invention can provide a highly sensitive localized surface plasmon resonance sensor, a chip for localized surface plasmon resonance sensor, a localized surface plasmon resonance sensor obtained therefrom, and a method for manufacturing the same About. More specifically, the present invention relates to a novel fine structure, an optical processing method, and a manufacturing method that have been developed by paying attention to mass transfer of a photoresponsive material based on near-field light existing near the surface of a fine particle under light irradiation.

  In addition, the present invention provides: (i) after applying a suspension in which a solid is dispersed on a photoresponsive material, or (ii) refracting between a substrate having an uneven structure on at least one surface and the photoresponsive material. A novel manufacturing method characterized by forming a structure having a concave portion and a convex portion on the surface of a photoresponsive material by irradiating light after filling an intermediate material having a rate higher than 1, and the manufacturing method The present invention relates to a structure formed using

  60% of the human body is made up of moisture, and half of the remaining 40% is made up of protein, and most of the cells, muscles, and skin of the human body are made of protein. For this reason, diseases are often correlated with protein mutations. In cancer, influenza and other diseases, specific proteins increase in the body (in the blood, etc.) as the disease progresses.

  Therefore, by monitoring the state of a specific protein (presence / absence, amount, etc. of a specific protein), it is possible to know the morbidity and progress of the disease. Currently, dozens of proteins are correlated with the disease. ing. For example, a biomolecule that increases with the progression of a tumor (cancer) is called a tumor marker, and different tumor markers are specified depending on the site of tumor occurrence.

  In addition, biomolecules such as proteins, DNA, and sugar chains in living organisms are often directly related to the occurrence of diseases, so the mechanism of disease is elucidated by analyzing the interactions between these biomolecules. However, it is becoming possible to develop a magic bullet.

  There is a biosensor as a tool for easily and accurately measuring the presence or amount of a specific protein including the above tumor marker, and is expected to be applied to misdiagnosis prevention, early diagnosis, preventive medicine and the like in the future.

  Here, as a method for detecting the interaction of biomolecules such as proteins, surface plasmon resonance (SPR) is used. Surface plasmon resonance is a resonance phenomenon caused by the interaction between free electrons on the metal surface and electromagnetic waves (light). Compared to the fluorescence detection method, the sample does not need to be labeled with a fluorescent substance, and is a simple technique. Attention has been paid. Sensors using surface plasmon resonance include a propagation surface plasmon resonance sensor and a localized surface plasmon resonance sensor.

  The principle of the propagation surface plasmon resonance sensor will be briefly described with reference to FIGS. As shown in FIGS. 8A and 8C, the propagation surface plasmon resonance sensor 11 is formed by forming a metal film 13 such as Au or Ag having a thickness of about 50 nm on the surface of a glass substrate 12. is there.

  The propagation surface plasmon resonance sensor 11 irradiates light from the glass substrate 12 side and totally reflects light at the interface between the glass substrate 12 and the metal film 13. Biomolecules are sensed by receiving the totally reflected light and measuring the reflectance of the light.

  That is, when this reflectance measurement is performed by changing the incident angle θ of light, the reflected angle is greatly attenuated at a certain incident angle (resonance incident angle) θ1, as shown in FIG. This is because when light incident on the interface between the glass substrate 12 and the metal film 13 is totally reflected at the interface, the evanescent light (near-field light) generated at the interface interacts with the surface plasmon wave of the metal. It is. Specifically, at a specific wavelength and a specific incident angle, light energy is absorbed into the metal film 13 and is changed to vibrational energy of free electrons in the metal film 13 so that the light reflectance is significantly reduced. Because it does.

  Since this resonance condition depends on the dielectric constant (refractive index) of the surrounding material of the metal film 13, such a phenomenon is used as a technique for detecting a change in physical properties of the surrounding material with high sensitivity. In particular, when used as a biosensor, an antibody 14 (probe) that specifically binds to a specific protein (antigen) is immobilized on the surface of the metal film 13 in advance as shown in FIG. . If the target antigen 16 is present in the introduced test sample, the antigen 16 specifically binds to the antibody 14 as shown in FIG. Then, when the antigen 16 binds to the antibody 14, the refractive index around the metal film 13 changes, and the resonance wavelength and the resonance incident angle change.

  Therefore, whether or not the antigen 16 is contained in the test sample is measured by measuring the change in the resonance wavelength before and after the test sample is introduced, the change in the resonance incident angle, or the temporal change in the resonance wavelength and the resonance incident angle. Can be inspected. It is also possible to examine the concentration of the antigen 16 contained.

  (D) of FIG. 8 represents an example of the result of measuring the dependence of the reflectance on the incident angle θ. In FIG. 8D, the broken line indicates the reflectance spectrum 17a before the test sample is introduced, and the solid line indicates the reflectance spectrum 17b after the test sample is introduced and the antigen 16 is bound to the antibody 14.

  Thus, by measuring the change Δθ in the resonance incident angle before and after introducing the test sample, it can be checked whether the test sample contains the antigen 16 or not. In addition, the concentration of the antigen 16 can be examined, and the presence or absence of a specific pathogen or the presence or absence of a disease can be examined.

  Note that a general propagation type surface plasmon resonance sensor uses a prism to introduce light into a glass substrate. For this reason, the optical system of the sensor is complicated and large, and the sensor chip (glass substrate) and the prism must be brought into close contact with the matching oil.

  However, in the propagation type surface plasmon resonance sensor, the sensing area is several hundred nm from the glass substrate surface, which is larger than the protein size (around 10 nm). Therefore, this sensor is easily affected by temperature changes in the test sample and contaminants in the test sample (for example, proteins other than the test target). In the biosensor, the antigen that is not bound to the antibody and is suspended in the test sample. Will also have sensitivity.

  Since these cause noise, it is difficult to produce a highly sensitive sensor with a small S / N ratio. In addition, in order to produce a highly sensitive sensor, a process for removing impurities that cause noise and a strict temperature control means for keeping the temperature of the inspection sample constant are required. The equipment cost becomes expensive.

  On the other hand, in the localized surface plasmon resonance sensor, the near field generated on the surface of the metal fine particle (metal nanoparticle) becomes the sensing region, and therefore, a sensitivity region of several tens of nm below the diffraction limit can be realized. As a result, the localized surface plasmon resonance sensor has no sensitivity to the inspection object floating in the region away from the metal fine particles, and only the inspection object attached to a very narrow region on the surface of the metal fine particles. There is a possibility that a sensor with higher sensitivity can be realized.

  A localized surface plasmon resonance sensor using metal fine particles has no sensitivity to the test object floating away from the metal fine particles, and therefore has less noise components. In that sense, compared to a propagation type surface plasmon resonance sensor. High sensitivity. However, in a sensor using surface plasmon resonance generated in metal fine particles such as Au and Ag, the intensity of the signal obtained from the inspection object attached to the surface of the metal fine particles is small, and in that sense, the sensitivity is still low. Or the sensitivity was not enough.

  In order to eliminate such difficulty in handling, a localized surface plasmon resonance sensor similar to a diffraction grating having a plurality of recesses has been disclosed (for example, see Patent Document 1).

  As shown in FIG. 9, the localized surface plasmon resonance sensor has a substrate 19 having a structure in which depressions (recesses) formed by nanoimprinting are regularly arranged, and is deposited or sputtered from above the recesses. The metal layer 20 obtained by laminating the metal materials by reflecting the shape below. As shown in FIG. 10, in this localized surface plasmon resonance sensor 18, when linearly polarized light is irradiated from the metal layer 20 side of the substrate 19, a strong electric field 22 is concentrated in the concave portion.

Japanese Patent Publication “Japanese Patent Laid-Open No. 2008-216055 (published on September 18, 2008)”

  However, in the localized surface plasmon resonance sensor described in Patent Document 1, the distance d between adjacent recesses is preferably 400 nm or less, but if the distance d between recesses (see FIG. 10) is too close, the gap between the recesses is reduced. The flat part is recognized as a convex part by light, and the produced concave part loses its function. In other words, in the localized surface plasmon resonance sensor described in Patent Document 1, as the distance d between the recesses is reduced to increase the density of the recesses and increase the sensitivity, the recesses themselves will not function. There was a problem.

  The present invention has been made in view of the above problems, and an object thereof is to provide a structure, a localized surface plasmon resonance sensor chip, and a localized surface plasmon resonance sensor chip capable of providing a higher sensitivity localized surface plasmon resonance sensor. An object is to provide a localized surface plasmon resonance sensor composed of these.

  In order to solve the above problems, the present inventor has conducted extensive studies on a highly sensitive localized surface plasmon resonance sensor, and as a result, not only a concave portion but also a flat portion and a flat portion on the surface of the metal layer. It has been found that a localized surface plasmon resonance sensor with higher sensitivity can be realized by using a chip for a localized surface plasmon resonance sensor having a recessed portion recessed with respect to the flat portion and a protruding portion protruding from the flat portion. It was.

  At the same time, the present inventor has made extensive studies on the manufacturing method for forming a concavo-convex structure on the surface of the photoresponsive material, and as a result, (i) applied a suspension in which a solid is dispersed on the photoresponsive material. Or (ii) using a substrate having a concavo-convex structure on at least one surface, and contacting the substrate on the photoresponsive material with an intermediate material having a refractive index larger than 1, followed by light irradiation Thus, the inventors have found that a predetermined structure can be manufactured, and that a highly sensitive localized surface plasmon resonance sensor can be realized by forming a metal layer on the structure, and the present invention has been completed.

  That is, the structure according to the present invention is a structure formed by irradiating the photoresponsive material with light in order to solve the above-described problem, and includes a flat portion, a concave portion recessed with respect to the flat portion, A convex portion projecting from the flat portion, the convex portion projecting continuously along the outer periphery of the concave portion, and the convex projecting continuously along the outer periphery of the concave portion. The diameter of the shape formed by the apex of the part is in the range of 5 nm to 1,000 nm.

  According to the above configuration, for example, the structure is used for a localized surface plasmon resonance sensor substrate, and a metal layer is formed on the surface along the shape of the substrate, whereby a flat portion and a flat surface are formed on the surface of the metal layer. A localized surface plasmon resonance sensor chip having a recessed portion that is recessed with respect to the portion and a protruding portion that protrudes with respect to the flat portion can be manufactured.

  In the localized surface plasmon resonance sensor chip thus obtained, coupling occurs between free electrons and incident light in the metal inside the region surrounded by the convex portions and the concave portions, and the inner and convex portions are strong. The electric field concentrates and extremely strong localized surface plasmon resonance occurs. Therefore, by using the chip, it is possible to provide a highly sensitive localized surface plasmon resonance sensor.

  In order to solve the above problems, a localized surface plasmon resonance sensor chip according to the present invention includes a substrate and a metal layer formed so as to cover at least a part of the surface of the substrate. On the surface of the layer, a flat portion, a concave portion recessed with respect to the flat portion, and a convex portion protruding with respect to the flat portion are formed, and the convex portion extends along an outer periphery of the concave portion. The diameter of the shape which protrudes continuously and the vertex of the said convex part which protruded continuously along the outer periphery of the said recessed part is in the range of 5 nm or more and 1,000 nm or less is characterized by the above-mentioned.

  According to the above configuration, coupling occurs between free electrons and incident light in the metal inside the region surrounded by the convex portion and the concave portion, and a strong electric field concentrates on the inside and the convex portion, so that the localized surface is extremely strong. Plasmon resonance occurs. Therefore, it is possible to provide a highly sensitive localized surface plasmon resonance sensor.

  In order to solve the above problems, a localized surface plasmon resonance sensor according to the present invention emits light to the localized surface plasmon resonance sensor chip and the localized surface plasmon resonance sensor chip according to the present invention. It is characterized by comprising a light source for irradiating and a photodetector for receiving light reflected or transmitted by the above-mentioned localized surface plasmon resonance sensor chip.

  According to the above configuration, since the localized surface plasmon resonance sensor chip according to the present invention is provided, a local resonance electric field is generated inside the region surrounded by the convex portion and the concave portion of the chip. be able to. Then, the light from the light source is irradiated onto the region, and the light reflected or transmitted by the region is received by the photodetector, so that the reflectance or transmittance of the sensor chip or the light detector receives the light. The measured light intensity can be measured. Therefore, according to the said structure, there exists an effect that a highly sensitive localized surface plasmon resonance sensor can be provided.

  In order to solve the above problems, the method for producing a structure according to the present invention applies a suspension in which a solid having an average diameter in the range of 1 nm to 100 μm is dispersed on a photoresponsive material. It includes a liquid coating step and a light irradiation step of irradiating light to the photoresponsive material coated with the suspension.

  According to the above method, the photoresponsive material located under the solid is recessed to irradiate light to the photoresponsive material to which the suspension is applied, and the photoresponsiveness around the recess is formed. The material rises and protrudes. In addition, since the photoresponsive material is irradiated with light without drying the solvent of the suspension, the solid is not fixed to the photoresponsive material, and only the suspension is removed. A structure can be obtained.

  Then, the structure manufactured by the above method is used for a substrate for a localized surface plasmon resonance sensor, and a metal layer is formed on the surface along the shape of the substrate, whereby a flat portion and a flat portion are formed on the surface of the metal layer. Thus, a localized surface plasmon resonance sensor chip having a recessed portion recessed with respect to the flat portion and a protruding portion protruding with respect to the flat portion can be produced.

  In the localized surface plasmon resonance sensor chip thus obtained, coupling occurs between free electrons and incident light in the metal inside the region surrounded by the convex portions and the concave portions, and the inner and convex portions are strong. The electric field concentrates and extremely strong localized surface plasmon resonance occurs.

  Therefore, it is possible to produce a structure that can provide a localized surface plasmon resonance sensor that is simple, stable, low-cost, and more sensitive.

  In order to solve the above-described problem, the structure manufacturing method according to the present invention has a step of applying an intermediate material having a refractive index greater than 1 on a photoresponsive material, and at least one surface has an uneven structure. Place the template substrate on the intermediate material applied on the photoresponsive material so that the uneven surface of the template substrate faces the applied intermediate material, and place the template substrate across the intermediate material A light irradiation step of irradiating the photoresponsive material with light.

  According to the said method, the photoresponsive material located under the said convex body in a template board | substrate dents, and the photoresponsive material in the circumference | surroundings of the said dent rises and protrudes. In addition, since the template substrate is used, the convex body is not fixed to the photoresponsive material, and the structure can be obtained simply by removing the template substrate.

  The method for manufacturing a structure according to the present invention is a method for manufacturing a structure to be a mold of the structure obtained by the above manufacturing method according to the present invention, and the first structure is manufactured by the above manufacturing method according to the present invention. Applying a thermosetting resin or a photocurable resin to the surface of the first structure, and peeling it after curing, thereby forming a second structure that becomes the mold of the first structure. And a step of obtaining.

  According to the above method, for example, the structure according to the present invention described above can be easily replicated by applying a thermosetting resin or a photocurable resin to the mold and peeling it after curing. Therefore, by using the replicated structure for a localized surface plasmon resonance sensor substrate and forming a metal layer on the surface along the shape of the substrate, the surface of the metal layer is flat and flat. A localized surface plasmon resonance sensor chip having a recessed portion and a protruding portion protruding with respect to the flat portion can be manufactured.

  In the localized surface plasmon resonance sensor chip thus obtained, coupling occurs between free electrons and incident light in the metal inside the region surrounded by the convex portions and the concave portions, and the inner and convex portions are strong. The electric field concentrates and extremely strong localized surface plasmon resonance occurs.

  Therefore, it is possible to produce a structure that can provide a localized surface plasmon resonance sensor that is simple, stable, low-cost, and more sensitive.

  The method for producing a structure according to the present invention is obtained by applying a thermosetting resin or a photocurable resin to the surface of the second structure to be a mold obtained by the above method according to the present invention, and peeling after curing. Thus, the third structure is obtained.

  According to the above method, since the structure according to the present invention described above can be easily replicated, the structure replicated by the above method is used as a substrate for a localized surface plasmon resonance sensor, and the surface of the structure conforms to the shape of the substrate. By forming the metal layer in this manner, a localized surface plasmon resonance sensor chip having a flat portion, a concave portion recessed with respect to the flat portion, and a convex portion protruding with respect to the flat portion on the surface of the metal layer is manufactured. can do.

  In the localized surface plasmon resonance sensor chip thus obtained, coupling occurs between free electrons and incident light in the metal inside the region surrounded by the convex portions and the concave portions, and the inner and convex portions are strong. The electric field concentrates and extremely strong localized surface plasmon resonance occurs.

  Therefore, it is possible to produce a structure that can provide a localized surface plasmon resonance sensor that is simple, stable, low-cost, and more sensitive.

  In order to solve the above-described problem, a method for manufacturing a localized surface plasmon resonance sensor chip according to the present invention includes a step of manufacturing a structure by any one of the methods for manufacturing a structure according to the present invention, and Forming a metal layer having a shape reflecting the shape of the structure by depositing metal on the surface of the structure.

  According to the above method, there is an effect that it is possible to manufacture a localized surface plasmon resonance sensor chip that can provide a localized surface plasmon resonance sensor more easily and stably at low cost and with higher sensitivity. .

  As described above, the structure according to the present invention is a structure formed by irradiating the light-responsive material with light, and the flat portion, the concave portion recessed with respect to the flat portion, and the flat portion. And projecting continuously along the outer periphery of the recess, and the apex of the projecting portion protruding continuously along the outer periphery of the recess is formed. It is characterized in that the shape has a diameter in the range of 5 nm to 1,000 nm.

  For this reason, there exists an effect that a highly sensitive localized surface plasmon resonance sensor can be provided.

  In addition, as described above, the method for producing a structure according to the present invention is a suspension in which a suspension in which a solid having an average diameter in the range of 1 nm to 100 μm is dispersed on a photoresponsive material. It is characterized by including an application | coating process and the light irradiation process of irradiating light with respect to the said photoresponsive material with which suspension was apply | coated.

  For this reason, there is an effect that it is possible to manufacture a structure that can provide a localized surface plasmon resonance sensor more easily and stably at low cost and with higher sensitivity.

  That is, according to the present invention, it is possible to manufacture a structure having a concave portion and a convex portion with respect to a reference surface before light irradiation, and local surface plasmon resonance is performed by laminating a metal on the structure. A sensor can be manufactured.

It is a top view which shows an example of the fundamental structure of the reflective optical system of the localized surface plasmon resonance sensor which concerns on this Embodiment. It is a top view which shows an example of the fundamental structure of the transmission optical system of the localized surface plasmon resonance sensor which concerns on this Embodiment. The schematic structure which expanded the measurement area | region in the localized surface plasmon resonance sensor which concerns on this Embodiment is shown, (a) is a top view, (b) is the AA arrow line view in (a) of FIG. It is sectional drawing. It is sectional drawing which shows an example of the manufacturing method of the chip | tip for localized type surface plasmon resonance sensors concerning this Embodiment. 2 is an AFM photograph of the surface structure of the substrate portion of the sensor chip obtained in Example 1. FIG. FIG. 3 is a cross-sectional view showing a schematic configuration of a structure used for a simulation result of the intensity of electric field concentration in a localized surface plasmon resonance sensor chip, where (a) shows a one-dimensional groove structure and (b) shows the present invention. Such a structure is shown. It is drawing which shows the simulation result of the intensity | strength of the electric field concentration in the chip | tip for localized surface plasmon resonance sensors, (a) shows the result of a one-dimensional groove structure, (b) shows the result of the structure based on this invention. . It is drawing which shows typically the principle of the conventional propagation type surface plasmon resonance sensor. It is sectional drawing which shows schematic structure of the conventional localized surface plasmon resonance sensor. It is sectional drawing which shows that a strong electric field concentrates on a recessed part in the conventional localized surface plasmon resonance sensor. 6 is a drawing showing an AFM photograph of a surface structure of a substrate portion of a sensor chip obtained in Example 3. FIG. 6 is a drawing showing a transmission spectrum of an LSPR chip obtained in Example 3. FIG. 6 is a side view schematically showing a template substrate produced in Example 4. 6 is a drawing showing an AFM photograph of a surface structure in a structure obtained in Example 4. FIG.

  An embodiment of the present invention will be described as follows.

  In the present specification, “A to B” indicating a range means A or more and B or less, and various physical properties mentioned in the present specification are described in Examples described later unless otherwise specified. Means the value measured by the method.

(I) Structure The structure according to the present embodiment is a structure formed by irradiating a photoresponsive material with light, and includes a flat portion, a concave portion recessed with respect to the flat portion, and the flat portion. And a projecting portion protruding relative to the surface.

[Photo-responsive material]
The photoresponsive material is a material that causes mass transfer by light irradiation, and more specifically, is a material that causes a mass transfer phenomenon along the bright and dark portions of the light of the irradiated portion.

  The photoresponsive material is not particularly limited as long as it is a material capable of causing photodeformation and exhibits mass transfer according to the light and dark part of the light irradiation part.For example, ablation, photochromism, Examples include organic or inorganic materials that contain a component (photoreactive component) that causes photo-induced alignment of molecules in the matrix material, and whose volume, density, free volume, and the like are changed by light irradiation. The photoresponsive material has a structure in which any element selected from the group consisting of sulfur, selenium, and tellurium is bonded to any element selected from the group consisting of germanium, arsenic, and antimony. Examples thereof include inorganic materials generically called chalcogenite glass.

  Examples of the photoreactive component include a photoisomerization component and a photopolymerizable component, which are components capable of causing an anisotropic photoreaction accompanied by a change in the shape of the material.

  Examples of the photoisomerization component include a component that causes trans-cis photoisomerization, particularly typically a dye structure having an azo group (—N═N—), particularly a chemical structure of azobenzene or a derivative thereof. Ingredients.

  In the case where the isomerization component is a material containing a dye structure having an azo group, the dye structure has one or more electron-withdrawing functional groups (electron-withdrawing substituents) and / or one or two or more. These electron donating functional groups (electron donating substituents) are preferably provided, and it is particularly preferred to have both of these electron withdrawing functional groups and electron donating functional groups.

  The electron-withdrawing functional group is preferably a functional group having a positive value for the substituent constant σ in Hammett's rule, and the electron-donating functional group is a functional group having a negative value for the substituent constant σ in Hammett's rule. preferable.

That is, the isomerization component is represented by the following formula (1)
Σ | σ | ≦ | σ1 | + | σ2 | (1)
(In the above formula, σ is a substituent constant in Hammett's rule, σ 1 is a cyano group substituent constant, and σ 2 is an amino group substituent constant.)
It is preferable that the above-mentioned electron donating substituent and electron withdrawing substituent are provided under the condition that is established. Thereby, the dye structure controlled so that the cut-off wavelength on the long wavelength side of the light absorption wavelength is in the wavelength range shorter than the fluorescence peak wavelength in the fluorescent dye for fluorescence analysis can be included. Thereby, an accurate measurement can be performed.

  The type of the dye structure is not particularly limited. For example, a dye structure having an azo group, particularly a chemical structure of azobenzene or a derivative thereof is preferable. That is, the photoresponsive material preferably contains an azopolymer derivative, and more preferably an azopolymer derivative having an azobenzene group in the main chain or side chain.

  In the matrix material of the photoresponsive material, the photoresponsive component may be simply dispersed or may be chemically bonded to the constituent molecules of the matrix material. From the point of view that the distribution density of the photoreactive component in the matrix material can be almost completely controlled and the heat resistance or stability over time of the material, the photoresponsive component is chemically connected to the molecules constituting the matrix material. It is particularly preferred that they are bonded together.

  As said matrix material, organic materials, such as a normal polymer material, and inorganic materials, such as glass, can be used. In consideration of the uniform dispersibility or binding property of the photoresponsive component to the matrix material, it is more preferable to use an organic material, particularly a polymer material.

  The type of the polymer material constituting the matrix material is not particularly limited, but it is preferable that the repeating structural unit of the polymer has a urethane group, a urea group, or an amide group, and further the main chain of the polymer. It preferably has a ring structure such as a phenylene group from the viewpoint of heat resistance.

  The polymer material constituting the matrix material is not particularly limited in molecular weight and degree of polymerization as long as it can be molded into a required shape. Further, the polymerization form may be any form such as linear, branched, ladder, or star shape, and may be a homopolymer or a copolymer.

  For the stability of photodeformation over time, the glass transition temperature of the polymer material is preferably high, for example, 100 ° C. or higher, but it can be used even when the glass transition temperature is about room temperature or lower. is there.

〔Structure〕
The structure includes a flat portion, a concave portion recessed with respect to the flat portion, and a convex portion protruding with respect to the flat portion.

  Here, the convex portion in the structure projects continuously along the outer periphery of the concave portion. In other words, the structure has both a convex portion protruding above the flat portion and a concave portion recessed below the flat portion, and the convex portion has a closed shape such as a circle. It preferably has a shape similar to the barnacle of marine organisms.

  In the present specification, a portion having a shape like a barnacle formed by the concave portion and a convex portion continuously projecting along the outer periphery of the concave portion may be referred to as a “barnacle body”. .

  The diameter of the shape formed by the vertices of the convex portions continuously projecting along the outer periphery of the concave portion is in the range of 5 nm to 1,000 nm.

  In the present specification, the “diameter” means the length of the longest line segment having both ends on the line constituting the harmful shape regardless of the target shape.

  Moreover, it is preferable that the diameter of the most depressed part in the said recessed part exists in the range of 0 nm or more and 1,000 nm or less. In addition, as a case where the diameter of the most depressed part in a recessed part is 0 nm, the shape where the recessed part is tapering toward the depth direction is mentioned, for example.

  In the structure, a ratio (A / B) of a depth B of the concave portion to the flat portion and a height A of the convex portion to the flat portion is in a range of 0.01 to 100. Is more preferable, and it is more preferably within a range of 0.1 to 10.

  The ratio C / D between the inner diameter C of the shape formed by the convex portion continuously projecting along the outer periphery of the concave portion and the sum D of the height of the convex portion and the depth of the concave portion is 0.01 or more and 100 It is preferably within the following range, more preferably within the range of 0.1 or more and 10 or less.

Further, the dispersion density of the barnacle body, one / 100 [mu] m is preferably ² or more is 10,000 / 100 [mu] m ² within the following range, 1/100 [mu] m ² or more 1,000 / 100 [mu] m ² within the following ranges It is more preferable that Moreover, it may be in the range of 1 piece / μm ² or more and 10,000 pieces / μm ² or may be in the range of 10 pieces / μm ² or more and 500 pieces / μm ² or less.

  As described above, in the structure according to the present invention, the ratio (A / B) between the depth B of the concave portion with respect to the flat portion and the height A of the convex portion with respect to the flat portion is 0.01 or more. It is preferable to be within the range of 100 or less.

  According to the above configuration, since a stronger localized surface plasmon resonance can be generated when a localized surface plasmon resonance sensor chip is manufactured, a more sensitive localized surface plasmon resonance sensor is provided. can do.

  In the structure according to the present invention, the ratio (A / B) of the depth B of the concave portion to the flat portion and the height A of the convex portion to the flat portion is 0.1 or more and 10 or less. It is preferable to be within the range.

  According to the above configuration, since a stronger localized surface plasmon resonance can be generated when a localized surface plasmon resonance sensor chip is manufactured, a more sensitive localized surface plasmon resonance sensor is provided. can do.

  Furthermore, in the structure according to the present invention, the inner diameter C of the shape formed by the convex portion continuously projecting along the outer periphery of the concave portion, and the sum D of the height of the convex portion and the depth of the concave portion, The ratio C / D is preferably in the range of 0.01 to 100.

  According to the above configuration, since a stronger localized surface plasmon resonance can be generated when a localized surface plasmon resonance sensor chip is manufactured, a more sensitive localized surface plasmon resonance sensor is provided. can do.

  Further, in the structure according to the present invention, the inner diameter C of the shape formed by the convex portion continuously projecting along the outer periphery of the concave portion, and the sum D of the height of the convex portion and the depth of the concave portion The ratio C / D is preferably in the range of 0.1 to 10.

  According to the above configuration, since a stronger localized surface plasmon resonance can be generated when a localized surface plasmon resonance sensor chip is manufactured, a more sensitive localized surface plasmon resonance sensor is provided. can do.

Furthermore, in the structure according to the present invention, the dispersion density of the structure composed of the concave portions and the convex portions continuously protruding along the outer periphery thereof is 1/100 μm ² or more and 10,000 / 100 μm ² or less. It is preferable to be within the range.

  According to the above configuration, since a stronger localized surface plasmon resonance can be generated when a localized surface plasmon resonance sensor chip is manufactured, a more sensitive localized surface plasmon resonance sensor is provided. can do.

Further, in the structure according to the present invention, the dispersion density of the structure consisting of the recess and the continuous protrusions and convex portions along its circumference, one / 100 [mu] m ² or more 1,000 / 100 [mu] m ² or less of the range It is preferable to be within.

  According to the above configuration, since a stronger localized surface plasmon resonance can be generated when a localized surface plasmon resonance sensor chip is manufactured, a more sensitive localized surface plasmon resonance sensor is provided. can do.

  Furthermore, in the structure according to the present invention, the photoresponsive material preferably contains an azopolymer derivative.

  According to the said structure, a structure can be obtained more easily.

  In the structure according to the present invention, the photoresponsive material is preferably an azopolymer derivative having an azobenzene group in the main chain and / or side chain.

  According to the said structure, a structure can be obtained more easily.

(II) Localized surface plasmon resonance sensor chip The localized surface plasmon resonance sensor chip according to the present embodiment includes a substrate and a metal layer formed so as to cover at least a part of the surface of the substrate. The surface of the metal layer is formed with a flat portion, a concave portion recessed with respect to the flat portion, and a convex portion protruding with respect to the flat portion, and the convex portion is formed with the concave portion. The diameter of the shape formed by the vertices of the protrusions protruding continuously along the outer periphery of the recess is in the range of 5 nm to 1,000 nm.

  Since the localized surface plasmon resonance sensor chip according to the present embodiment has the above-described shape, it is coupled between free electrons and incident light in the metal inside the region surrounded by the convex and concave portions. As a result, a strong electric field concentrates inside and on the convex portion, and extremely strong localized surface plasmon resonance is generated.

  Here, the local resonance electric field means an electric field in which the resonance electric field does not propagate along the metal surface and the region of the electric field enhanced by resonance is smaller than the diffraction limit of incident light.

  In the localized surface plasmon resonance sensor chip according to the present embodiment, the convex portion continuously protrudes along the outer periphery of the concave portion, that is, the “barnacle body” described above. If it is the said structure, a coupling | bonding will occur more easily between the free electron and incident light in the metal of the inside enclosed by the convex part and the recessed part, and a stronger localized surface plasmon resonance will be concentrated because a strong electric field concentrates inside. Occur.

  In the localized surface plasmon resonance sensor chip according to the present embodiment, the diameter formed by the apex of the convex portion of the barnacle form is in the range of 5 nm to 1,000 nm. In addition, when used as a biosensor, since the size of a general protein is around 10 nm, the diameter formed by the apex of the convex portion of the barnacle body is preferably in the range of 20 nm to 1,000 nm. preferable.

  In the localized surface plasmon resonance sensor chip according to the present embodiment, the depth of the barnacle body composed of the convex portion and the concave portion (the sum of the height of the convex portion and the depth of the concave portion) is 5 nm or more and 10 μm or less. It is preferably within the range, and more preferably within the range of 10 nm to 500 nm. If the depth of the barnacle is within the above range, the localized surface plasmon resonance phenomenon can be satisfactorily generated with high sensor sensitivity.

In the localized surface plasmon resonance sensor chip according to the present embodiment, the distance between barnacle bodies is not limited, but the dispersion density of the barnacle bodies is 1/100 μm ² or more and 1,000 / 100 μm ² or less. Preferably, it is in the range of 10/100 μm ² or more and 1,000 / 100 μm ² or less. Further, it may be in the range of 10 / μm ² or more and 1,000 / μm ² or less, or in the range of 10 / μm ² or more and 500 / μm ² or less.

  In the localized surface plasmon resonance sensor chip according to the present embodiment, the surface of the substrate includes a flat portion, a concave portion recessed with respect to the flat portion, and a convex portion protruding with respect to the flat portion. The shape of the metal layer is preferably formed in accordance with the shape of the substrate surface.

  That is, in the localized surface plasmon resonance sensor chip according to the present embodiment, the substrate has a plurality of barnacle bodies on the surface, and the metal layer has the shape of the barnacle body provided on the substrate surface. It is preferably formed on the surface of the substrate so as to reflect and form a barnacle body. In such an embodiment, a fine barnacle can be formed on the metal layer by a simple process.

  In the localized surface plasmon resonance sensor chip according to the present embodiment, the thickness of the metal layer may be 10 nm or more in the case of reflected light. Although an upper limit is not specifically limited, For example, it can be 500 nm.

  In the case of transmitted light, the thickness of the metal layer can be in the range of 10 nm to 200 nm, and more preferably in the range of 20 nm to 125 nm. If the thickness of the metal layer is within this range, the plasmon resonance phenomenon can be sufficiently detected by transmitted light.

  In the localized surface plasmon resonance sensor chip according to the present embodiment, the thickness of the metal layer may be in the range of 10 nm to 100 nm. If the thickness of the metal layer is within the range, a sufficient amount of light can be secured for the reflected light, and a sufficient amount of light can be secured for the transmitted light amount, resulting in high measurement accuracy.

  In the localized surface plasmon resonance sensor chip according to the present embodiment, the metal layer preferably contains Au or Ag. Specifically, the material is Au, Ag, or an Au—Pd alloy. Preferably there is. That is, the material of the metal layer may be Au or Ag alone, or an alloy containing Au and / or Ag. If the material of the metal layer is Au or Ag, the metal layer material is chemically stable, and strong localized surface plasmon resonance can be generated.

  Further, an inorganic material layer may be further formed on the metal layer. This is because oxidative deterioration of the metal layer can be prevented and molecules such as proteins to be measured can be prevented from being deactivated. As the inorganic material, materials such as silicon dioxide, zinc oxide, tin oxide, and titanium oxide are suitable.

  In the localized surface plasmon resonance sensor chip according to the present embodiment, it is preferable that an organic molecular layer for immobilizing biomolecules is formed on the surface of the metal layer. Thereby, it becomes possible to use as a biosensor capable of detecting a specific biomolecule. That is, with the chip according to the present embodiment, the surface area for forming the organic molecular layer can be increased, and the sensor sensitivity can be improved.

  In the localized surface plasmon resonance sensor chip according to the present embodiment, the organic molecular layer has a length of 50 nm to 200 nm from the metal layer surface and a length of 1 nm from the metal layer surface. It is preferable that the molecular weight is less than 50 nm.

  When the organic molecular layer has molecules as described above, molecules having a length of 1 nm or more and less than 50 nm bind to biomolecules in the vicinity of the metal layer, and molecules having a length of 50 nm or more and 200 nm or less are separated from the metal layer. It binds to biomolecules at the moment. And when the molecule | numerator with a length of 50 to 200 nm which couple | bonded with the biomolecule bends, the biomolecule will also be drawn near the metal layer. Thereby, many biomolecules can be collected in the area | region of the vicinity of a metal layer, and sensor sensitivity can be improved further.

  Examples of the molecules constituting the organic molecular layer include biotin-modified polyethylene glycol, ORLA18 (trade name, manufactured by ORLA PROTEIN TECHNOLOGY), dextran, and the like.

  The molecular chain length of the molecule can be measured by a dynamic light scattering method.

As described above, in the localized surface plasmon resonance sensor chip according to the present invention, the dispersion density of the structure including the concave portions and the convex portions continuously protruding along the outer periphery thereof is 1 piece / 100 μm ² or more. It is preferable that it is in the range of 1,000 / 100 μm ² or less.

  According to the above configuration, stronger localized surface plasmon resonance can be generated, so that a more sensitive localized surface plasmon resonance sensor can be provided.

  Further, in the localized surface plasmon resonance sensor chip according to the present invention, the sum of the height of the convex portion and the depth of the concave portion in the structure including the concave portion and the convex portion continuously projecting along the outer periphery thereof. Is preferably in the range of 5 nm to 10 μm.

  According to the above configuration, stronger localized surface plasmon resonance can be generated, so that a more sensitive localized surface plasmon resonance sensor can be provided.

  Furthermore, in the localized surface plasmon resonance sensor chip according to the present invention, the height of the convex portion and the depth of the concave portion in the structure including the concave portion and the convex portion continuously projecting along the outer periphery thereof. The sum is preferably in the range of 10 nm to 500 nm.

  According to the above configuration, stronger localized surface plasmon resonance can be generated, so that a more sensitive localized surface plasmon resonance sensor can be provided.

  In the localized surface plasmon resonance sensor chip according to the present invention, the surface of the substrate in contact with the metal layer has a flat portion, a concave portion recessed with respect to the flat portion, and an outer periphery of the concave portion. Thus, it is preferable that a convex portion projecting continuously from the flat portion is formed, and the shape of the metal layer is formed in accordance with the shape of the substrate surface.

  According to the said structure, it can manufacture simply, stably and at low cost.

  Furthermore, in the localized surface plasmon resonance sensor chip according to the present invention, the metal layer preferably has a thickness of 10 nm or more.

  According to the above configuration, a highly sensitive localized surface plasmon resonance sensor can be provided.

  In the localized surface plasmon resonance sensor chip according to the present invention, an organic molecular layer for immobilizing biomolecules is preferably formed on the surface of the metal layer.

  According to the said structure, it becomes possible to use as a biosensor which can detect a specific biomolecule.

  Furthermore, in the localized surface plasmon resonance sensor chip according to the present invention, the organic molecular layer includes a molecule having a length of 50 nm or more and 200 nm or less from the metal layer surface and a length from the metal layer surface of 1 nm or more. It is preferable that it contains molecules less than 50 nm.

  According to the above configuration, molecules having a length of 1 nm or more and less than 50 nm bind to the biomolecule in the vicinity of the metal layer, and molecules having a length of 50 nm or more and 200 nm or less bind to the biomolecule at a distance from the metal layer. A molecule having a length of 50 nm or more and 200 nm or less bonded to a biomolecule attracts the biomolecule to the vicinity of the metal layer by bending the molecular chain. Thereby, many biomolecules can be collected in the area | region of the vicinity of a metal layer, and the biosensor with higher sensor sensitivity can be provided.

  In the localized surface plasmon resonance sensor chip according to the present invention, the metal layer preferably contains Au or Ag.

  According to the above configuration, Au or Ag is chemically stable and can generate strong localized surface plasmon resonance.

(III) Localized surface plasmon resonance sensor The localized surface plasmon resonance sensor according to the present embodiment includes the above-described localized surface plasmon resonance sensor chip according to the present embodiment and the localized surface plasmon. A light source for irradiating light to the resonance sensor chip; and a photodetector for receiving light reflected or transmitted by the localized surface plasmon resonance sensor chip.

  The localized surface plasmon resonance sensor according to the present embodiment generates a localized resonance electric field on the surface of the metal layer in the above-described localized surface plasmon resonance sensor chip, and emits it from the light source to be used for the sensor. Light incident on the surface of the chip and reflected or transmitted in a region where a resonance electric field is generated on the surface of the metal layer is received by the photodetector. Then, the reflectance, transmittance, or light intensity received by the photodetector in the sensor chip is measured.

  In the localized surface plasmon resonance sensor according to the present embodiment, light of two or more wavelengths is incident on the sensor chip perpendicularly to the sensor chip surface and reflected by the sensor chip. Alternatively, the reflectance or transmittance of the transmitted light of each wavelength, or the light intensity of the light of each wavelength may be measured by the photodetector.

  According to this embodiment, a change in resonance wavelength can be evaluated by comparing reflectance or transmittance and light intensity at two or more specific wavelengths. Therefore, it is desirable for the purpose of inspecting the presence or absence of known specific substances.

  When localized surface plasmon resonance occurs in the localized surface plasmon resonance sensor chip according to the present embodiment, the energy of the irradiated light is absorbed by the surface plasmon wave of the metal layer. ), The light reflectance or transmittance and the light intensity received by the photodetector are reduced.

  Since this resonance wavelength changes depending on the refractive index of the medium inside the region surrounded by the convex portion and the concave portion, according to the localized surface plasmon sensor, the fact that the dielectric substance has adhered to the region, Changes in the amount of adhesion can be detected. In particular, it can be preferably used as a biosensor for the detection of specific proteins.

  Moreover, in the localized surface plasmon resonance sensor according to the present embodiment, since a large electric field enhancement is observed in the region surrounded by the convex portion and the concave portion and in the convex portion, extremely strong surface plasmon resonance can be caused. Sensing with extremely high sensitivity can be performed as compared with conventional propagation type surface plasmon resonance sensors and localized type surface plasmon resonance sensors.

  In particular, since the localized surface plasmon resonance sensor according to the present embodiment includes the above-mentioned “barnacle body”, when light is incident perpendicularly to the surface in the region where the barnacle body is formed, the barnacle Coupling occurs between free electrons and incident light on the metal side surface of the inner wall of the body, and a strong electric field concentrates in the barnacle body, thereby generating stronger localized surface plasmon resonance.

  Furthermore, since the localized surface plasmon resonance sensor according to the present embodiment has sensitivity in a narrow region of about several tens of nanometers from the surface of the metal layer, noise due to a substance in a region away from the metal layer is small, and S / A localized surface plasmon resonance sensor having a good N ratio can be manufactured.

  Hereinafter, an example of a basic configuration of a reflection optical system of a localized surface plasmon resonance sensor (hereinafter referred to as a localized SPR sensor) according to the present embodiment will be described with reference to FIG.

  FIG. 1 is a plan view showing the outline of the basic configuration of the reflective optical system of the localized SPR sensor 24 according to the present embodiment.

  As shown in FIG. 1, the localized SPR sensor 24 includes a light source 25, a collimator lens 26, a collimator plate 27 having a pinhole, a beam splitter (may be a half mirror) 28, a spectroscope 29, a light A detector 33, a localized SPR sensor chip 30, and a data processing device 31 are provided.

  The light emitted from the light source 25 is guided to the collimator lens 26. The collimator lens 26 collimates the light emitted from the light source 25 and passes it as a parallel beam. The light collimated by the collimator lens 26 becomes a collimated beam that is narrowed down by passing through the pinhole of the collimator plate 27.

  The light that has passed through the pinhole of the collimator plate 27 enters the beam splitter 28, and only about ½ of the amount of incident light passes straight through the beam splitter 28. The parallel beam that has passed through the beam splitter 28 is applied to the measurement region (region where the barnacle body is formed) 32.

  The light irradiated to the measurement region 32 is reflected by the measurement region 32 and returns to the original direction. The measurement light that has returned to the original direction enters the beam splitter 28. As for the measurement light incident on the beam splitter 28, only about ½ of the amount of light is reflected by the bonding surface in the beam splitter 28 in the direction of 90 degrees.

  The light reflected by the beam splitter 28 passes through the spectroscope 29 and is split into light of each wavelength and received by the photodetector 33. Therefore, the light intensity of each wavelength can be detected by receiving the light separated by the spectroscope 29 by the photodetector 33.

  In the data processing device 31, the light intensity of each wavelength of light irradiated in a state where there is no specimen in the measurement region 32 is given in advance as data. Therefore, the data processor 31 compares the data given in advance with the light intensity of each wavelength detected by the light detector 33, so that the spectral characteristic (reflectance spectrum) of the reflectance of each wavelength in the measurement region 32 is obtained. ) And the like.

  Next, an example of the basic configuration of the transmission optical system of the localized SPR sensor according to the present embodiment will be described with reference to FIG.

  FIG. 2 is a plan view showing an outline of the basic configuration of the transmission optical system of the localized SPR sensor 34 according to the present embodiment.

  The localized SPR sensor 34 includes a light source 25, a collimator lens 26, a collimator plate 27 having a pinhole, a localized SPR sensor chip 30 including a measurement region 32, a spectrometer 29, a photodetector 33, and data. And a processing device 31.

  The light emitted from the light source 25 is guided to the collimator lens 26. The collimator lens 26 collimates the light emitted from the light source 25 and passes it as a parallel beam. The light collimated by the collimator lens 26 becomes a collimated beam that is narrowed down by passing through the pinhole of the collimator plate 27.

  The light that has passed through the pinhole of the collimator plate 27 is applied to the measurement region (region where the barnacle body is formed) 32. The light irradiated on the measurement region 32 passes through the measurement region 32. The transmitted measurement light passes through the spectroscope 29 and is split into light of each wavelength and received by the photodetector 33.

  In the data processing device 31, the light intensity of each wavelength of light irradiated in a state where there is no specimen in the measurement region 32 is given in advance as data. Therefore, the data processing device 31 compares the data given in advance with the light intensity of each wavelength detected by the photodetector 33, so that the spectral characteristic (transmittance spectrum) of the reflectance of each wavelength in the measurement region 32 is obtained. ) And the like.

  In the configuration of the reflection optical system and the transmission optical system, the light source 25 is preferably a light source that emits white light such as a halogen lamp, but may be any light source that includes light in the wavelength region used for measurement. Further, the parallel beam that has passed through the pinhole may be linearly polarized light, elliptically polarized light, circularly polarized light or the like having a certain polarization plane (for example, a polarization plane parallel to the paper surface of FIG. 4).

  Furthermore, the optical components (for example, a λ / 2 plate) for making the various polarization states may be arranged as necessary. In this embodiment, the vibration plane of the electric field of light (electromagnetic wave) is defined as the polarization plane, and the direction of the electric field is defined as the polarization direction.

  The photodetector 33 can be configured by a photodiode array having a plurality of light receiving surfaces, a light receiving device using a CCD or a plasmon phenomenon, or the like.

  Next, the measurement region 32 in the localized SPR sensors 24 and 34 will be described in detail with reference to FIG.

  3A is a plan view showing the measurement region 32 in an enlarged manner, and FIG. 3B is a cross-sectional view taken along line AA in FIG.

In the measurement region 32, a plurality of barnacle bodies 45 (barnacle bodies made of a metal thin film, within a broken line circle) are formed on the surface of the metal layer 52. The plurality of barnacle bodies 45 are arranged at a density of 60 / μm ² .

  Under such an arrangement, when light enters the measurement region 32 perpendicularly, the light enters the barnacle body 45, and an electric field is generated in and around the barnacle body 45. The light incident on the metal layer 52 having the barnacle body 45 generates an electric field in and around the barnacle body 45, and the electric field and the natural vibrations of free electrons in the metal layer 52 are coupled to each other. Occurs. Therefore, the energy of the light incident on the metal layer 52 is concentrated on the barnacle body 45 by the localized SPR, and a part of the light incident on the metal layer 52 is absorbed.

  As a result, the reflectance or transmittance obtained from the light received by the photodetector 33 becomes small at a specific wavelength (resonance wavelength). Since this specific wavelength changes depending on the refractive index of the test sample solution, the refractive index and type of the dielectric substance contained in the test sample solution should be inspected by examining the wavelength of the minimum reflectance point or its change. Can do.

  In addition, by using an antibody or the like that specifically binds a specific protein, the presence or content of the specific protein contained in the test sample solution can be inspected.

  In such a measurement region 32, the diameter and depth of the barnacle body 45 may be uniform or non-uniform.

  As described above, in the localized surface plasmon resonance sensor according to the present invention, two or more wavelengths of light are vertically incident on the surface of the localized surface plasmon resonance sensor chip, and the localized surface plasmon resonance sensor The reflectivity of each wavelength of light reflected by the surface plasmon resonance sensor chip, the transmittance of each wavelength transmitted through the localized surface plasmon resonance sensor chip, or the light intensity of each wavelength reflected or transmitted above It is preferable to measure with a photodetector.

  According to the above configuration, the change in resonance wavelength can be evaluated by comparing reflectance, transmittance, or light intensity at two or more specific wavelengths. For this reason, it can use suitably for the use which test | inspects the presence or absence of a known specific substance.

(IV) Manufacturing Method of Structure (IV-I) First Manufacturing Method The first manufacturing method of the structure according to the present embodiment includes (i) a suspension application step, and (ii) a light irradiation step. And (iii) a process for manufacturing the structure mold, and (iv) a process for replicating the structure using the mold.

[Suspension application process]
The suspension application step is a step of applying a suspension in which a solid is dispersed on a photoresponsive material.

  Here, as the photoresponsive material, the same materials as those exemplified in “(I) Structure” can be used.

  The solid has an average diameter in the range of 1 nm to 100 μm, more preferably in the range of 1 nm to 1 μm, and particularly preferably in the range of 1 nm to 500 nm.

  The average diameter of the solid means an average diameter of primary particles, and means a value measured by the BET method (specific surface area method).

  The solid is not particularly limited, and may be a rigid body such as a metal particle or a very flexible object such as an animal cell. More specifically, the solid is preferably made of at least one material selected from the group consisting of an inorganic material, a metal material, and a polymer material. Metal particles, metal oxide particles, semiconductor particles, ceramic particles, It may be a plastic particle or a particle composed of two or more of these materials (for example, a mixture of two materials or a multilayer structure).

  Examples of the metal particles include gold, silver, copper, aluminum, and platinum. Examples of the metal oxide particles include silica, titanium oxide, tin oxide, and zinc oxide. Examples of the plastic particles include polystyrene particles and acrylic particles.

  In the method according to the present embodiment, examples of the solvent for the suspension include organic solvents such as water, methanol, ethanol, and acetone, and mixtures of water and organic solvents. These solvents are used in combination with a surfactant. May be.

  Although the density | concentration of the said suspension liquid is not specifically limited, For example, it can be in the range of 1-90 mass%.

  As a coating method, it may be simply added with a dropper or the like, and a known method such as a spin coating method or a spray method can be used.

[Light irradiation process]
The light irradiation step is a step of irradiating the photoresponsive material coated with the suspension with light. In other words, it is a process in which a suspension containing a solid is applied to the surface of the photoresponsive material and light irradiation is performed until the suspension is dried.

  The light irradiation time may be appropriately adjusted according to the shape of the structure to be obtained. Also, the direction of light irradiation is not particularly limited, and light may be irradiated from the back surface (side where the suspension is not applied) of the photoresponsive material, or light may be applied from the side where the suspension is applied. It may be irradiated.

  As the irradiation light, any irradiation light such as propagating light, near-field light, or evanescent light can be used as long as there is no mismatch in combination with a material that causes optical deformation.

  Natural light, laser light, or the like can be used as the propagating light. The polarization characteristics can be used as propagating light, near-field light, or evanescent light.

  The wavelength of the irradiation light and the light source are not limited, but regarding the wavelength, a wavelength having a high absorption efficiency of a material that causes optical deformation is preferable. When the solid is likely to be inactivated or deteriorated by ultraviolet light (wavelength 300 to 400 nm), for example, visible light (wavelength 400 to 600 nm) is used as irradiation light, and visible light It is preferable to use a photoresponsive material capable of light immobilization of the solid by irradiation. In addition, pulsed light having a high peak output can be used. What is necessary is just to set the irradiation time of irradiation light arbitrarily as needed.

[Suspension removal step]
After the light irradiation step, the suspension is removed from the photoresponsive material. Through this process, the structure according to this embodiment is obtained.

  Specific methods for removing the suspension from the photoresponsive material include ultrasonic cleaning and a method of rinsing with a solvent constituting the suspension.

  Thereby, with the surface of the photoresponsive material before the light irradiation as a reference surface, a fine structure in which both a concave portion, a flat portion, and a protruding convex portion that are recessed from the reference surface are formed simultaneously after the light irradiation. Is obtained. In the present embodiment, since the concave portion, the flat portion, and the convex portion are formed at the same time in the structure, the structure that can stably provide a low-cost, high-sensitivity localized surface plasmon resonance sensor. Can be manufactured.

[Corona discharge treatment process]
The corona discharge treatment step is a step of performing the corona discharge treatment after removing the suspension on the photoresponsive material. As a corona discharge treatment method, a general corona discharge treatment method can be used (for example, Optics Letters, Vol. 26, No. 1, January 1, 2001, “Diffraction efficiency increase by corona discharge in photoinduced surface relief gratings on an azo polymer film ”). Moreover, what is necessary is just to adjust the intensity | strength of a corona discharge and processing time so that a desired structure may be obtained.

  The corona discharge treatment process itself may be performed if necessary to obtain a desired structure, and may not be performed if it is not necessary to perform the corona discharge treatment.

[Manufacturing process of structure mold]
The manufacturing process of the structure mold is to apply a thermosetting resin or a photocurable resin to the surface of the structure obtained by the suspension removing process (hereinafter referred to as the first structure), This is a step of peeling after curing. By this step, a second structure that is a mold of the first structure is obtained.

  As the thermosetting resin or photocurable resin, commonly used resins can be used, but for the thermosetting resin, those having a thermosetting temperature lower than the glass transition temperature of the photoresponsive material are used. It is preferable to do.

[Replication process of structure using mold]
In the process of replicating the structure using the mold (second structure), a thermosetting resin or a photocurable resin is applied to the surface of the structure mold (second structure), and after curing, the This is a step of peeling the resin.

  Specifically, the surface of the second structure is coated with an ultraviolet curable resin or a thermosetting resin, cured by irradiation with ultraviolet light or heat, and then the resin is peeled off to thereby respond to light. A structure (third structure) according to the present embodiment having substantially the same shape as that formed on the surface of the conductive material can be obtained.

  It should be noted that the shape of the resulting fine structure may differ depending on the transfer rate, not only when it is exactly the same as the fine structure formed on the surface of the photoresponsive material. The arrangement pattern in the plane is substantially the same.

  In the above description, the case of including “a structure mold manufacturing process” and “a structure replication process using a mold” is described, but the present invention is not limited to this. Instead of performing these steps, a structure may be produced from the suspension application step and the light irradiation step.

  However, when the mold is manufactured and the structure formed on the surface of the photoresponsive material is replicated by the mold as in this embodiment, the material constituting the structure is not limited to the photoresponsive material. Also, since it can be easily mass-produced, the effect is particularly great.

  As described above, in the method for producing a structure according to the present invention, the solid in the suspension may be made of at least one material selected from the group consisting of an inorganic material, a metal material, and a polymer material. preferable.

  According to the above method, a structure capable of providing a localized surface plasmon resonance sensor with higher sensitivity and more easily can be manufactured.

(IV-II) Second Manufacturing Method The second manufacturing method of the structure according to the present embodiment includes (i) a template placement step and (ii) a light irradiation step.

[Template placement process]
The template placement step may be any material as long as it is an intermediate material (a material having a refractive index greater than 1 at a light wavelength of 589 nm and satisfying the space between the template substrate and the photoresponsive material on the photoresponsive material. Water, alcohols, organic solvents, ionic liquids, etc.) and a template substrate is placed thereon.

  More specifically, in the template placement step, the step of applying an intermediate material having a refractive index greater than 1 on the photoresponsive material and the uneven surface of the template substrate having an uneven structure on at least one surface are applied. Placing the template substrate on the photoresponsive material so as to face the intermediate material formed.

  Here, as the photoresponsive material, the same materials as those exemplified in “(I) Structure” can be used.

  The template substrate is not particularly limited as long as it has a fine uneven shape on the surface.

[Light irradiation process]
The light irradiation step is a step of irradiating the photoresponsive material coated with the suspension with light. In other words, the intermediate material is applied to the surface of the photoresponsive material, and the template substrate is placed thereon to perform light irradiation.

  The light irradiation time may be appropriately adjusted according to the shape of the structure to be obtained. Also, the direction of light irradiation is not particularly limited, and light may be irradiated from the back surface (side where the suspension is not applied) of the photoresponsive material, or light may be irradiated from the template substrate side. .

  As the irradiation light, any irradiation light such as propagating light, near-field light, or evanescent light can be used as long as there is no mismatch in combination with a material that causes optical deformation.

  As described above, in the method for producing a structure according to the present invention, it is preferable that the concavo-convex structure on at least one surface of the template substrate is made of a solid having an average particle diameter in the range of 1 nm to 100 μm.

  Moreover, in the manufacturing method of the structure which concerns on this invention, it is preferable that the average particle diameter of the said solid is the range of 10 nm or more and 1 micrometer or less.

  Furthermore, in the method for manufacturing a structure according to the present invention, it is preferable that the concavo-convex structure on at least one surface of the template substrate is formed by alkali etching of a silicon substrate.

  In the structure manufacturing method according to the present invention, the concavo-convex structure on at least one surface of the template substrate is formed by applying or generating metal nanoparticles on the surface of the silicon substrate, followed by alkali and acid etching. It is preferable to become.

  Furthermore, in the structure manufacturing method according to the present invention, it is preferable that the template substrate has a metal layer formed so as to cover at least a part of the concavo-convex structure surface.

  Furthermore, in the method for producing a structure according to the present invention, the photoresponsive material preferably contains an azopolymer derivative.

  In the method for producing a structure according to the present invention, the photoresponsive material is preferably an azopolymer derivative having an azobenzene group in the main chain and / or side chain.

  Furthermore, the structure according to the present invention can be restated as a structure manufactured by any one of the manufacturing methods of the present invention. Here, the structure has a flat portion, a concave portion that is recessed with respect to the flat portion, and a convex portion that protrudes with respect to the flat portion, and the convex portion extends along an outer periphery of the concave portion. It is preferable that it protrudes continuously. Moreover, it is preferable to have a metal layer formed so as to cover at least part of the surface of the structure.

  Conventionally, there has been known an optical processing method for performing fine shape processing or optical information recording on a photoresponsive material by irradiating light from, for example, a laser light source. In addition, since an optical system using propagating light cannot be used in a region below the diffraction limit of light, a method using near-field light localized in a region smaller than the wavelength of light on the surface of a material has recently been proposed. Yes.

  As a technique for performing micro-shape processing on a photoresponsive material, Patent Document 2 (Japanese Patent Publication “JP 2002-301699 A”), Non-Patent Document 1 (Optics Communications, 161, pp. 6-12 (1999) )) And Non-Patent Document 2 (J. Micrography, vol. 202, Pt 1, April, pp. 162-171 (2000)) include acrylic polymer compounds and epoxy polymers having an azobenzene derivative in the side chain. A technique is disclosed in which a nanoparticle is arranged on the surface of a thin film using a compound and a urethane-based polymer compound, and then optical nanomachining is performed using near-field light induced in the vicinity of the nanoparticle by light irradiation. In the prior art, only the nano-particles are arranged on the photoresponsive material thin film, and no component such as a liquid exists at the time of light irradiation.

  In addition, in the prior art, only near the contact point between the arranged nanoparticles and the photoresponsive material (for example, a polymer material containing an azobenzene derivative or bonded with an azobenzene derivative) is deformed, and the optical response before light irradiation is changed. It is only deformed into a shape that is recessed (for example, like a dimple on a golf ball) with respect to the reference surface of the conductive material, and the depth of the recess is also about one-sixth or less of the diameter of the nanoparticle. It was small. Furthermore, when the surface of the photo-responsive material is depressed and deformed, a portion where the nanoparticles are captured is generated, and an extra process such as ultrasonic cleaning is required to use only the depressed portion. . In addition, since not all nanoparticles can be removed by post-treatment such as ultrasonic cleaning, there is a complaint that impurities are present when using the recessed shape. Furthermore, in the prior art, there is a complaint that the depth of the recessed portion cannot be made sufficiently deep.

  In addition, when particles are arranged on the surface of a photoresponsive material, the close-packed structure is relatively easy to form, but other periodic structures (periodic structures such as honeycombs, squares, and lines other than particles) and random arrangements are formed on the entire surface. There were complaints that it was difficult to form.

  Therefore, in the present invention, in the method of forming a fine shape on the surface of the photoresponsive material, the concave and convex portions are simultaneously formed on the surface of the photoresponsive material, the periodic structure, the honeycomb, the square or the wire other than the spherical shape. It is possible to provide a method of forming a structure such as a shape, a structure formed by this method, and a localized surface plasmon resonance sensor manufactured by laminating a metal on the structure.

(V) Method for Manufacturing Localized Surface Plasmon Resonance Sensor Chip A manufacturing method for a localized surface plasmon resonance sensor chip according to the present embodiment is structured by the above-described manufacturing method of the structure according to the present embodiment. And a step of forming a metal layer having a shape reflecting the shape of the substrate by depositing a metal on the surface of the structure.

[Process of manufacturing structure]
The process of manufacturing the structure is a process of manufacturing the structure by the method described in “(IV) Manufacturing method of structure”.

[Step of forming metal layer]
The step of forming a metal layer is a step of forming a metal layer having a shape reflecting the shape of the substrate by depositing metal on the surface of the structure.

  Formation of a metal layer can be performed by well-known methods, such as sputtering method and a vapor deposition method, for example.

  If the metal layer deposited by sputtering or vapor deposition is thin, the metal layer may not be deposited on the entire surface of the sensor chip. However, for the localized surface plasmon resonance sensor according to the present embodiment, Even in such a case, the localized surface plasmon resonance phenomenon is induced in the chip.

[Example of manufacturing method for localized surface plasmon resonance sensor chip]
Hereinafter, an example of a method for manufacturing a localized surface plasmon resonance sensor chip according to the present embodiment will be described in detail with reference to FIG.

  First, a photoresponsive material is applied onto the transparent substrate 46 by a spin coater or the like to form a layer (photoresponsive material layer) 48 made of a photoresponsive material (see FIG. 4A).

  Next, a suspension obtained by suspending the solid 47 in a solvent is dropped on the photoresponsive material layer 48 (see FIG. 4B). After irradiating predetermined light from the transparent substrate 46 side (see FIG. 4C), the suspension is removed and the photoresponsive material layer 48 is naturally dried to produce a substrate 49 having a barnacle body. (See (d) in FIG. 4).

  Next, a thermosetting resin is dropped onto the substrate 49, left in a hot-air oven, cured, and then peeled off to produce a thermosetting resin substrate 50 having a reverse transfer shape of a barnacle (FIG. 4 ( e)). Then, an ultraviolet curable resin is dropped on the thermosetting resin substrate 50 and is peeled off after photocuring to produce a transparent substrate 51 having a barnacle body.

  A metal layer 52 is formed on the surface of the transparent substrate 51 having the barnacle body thus obtained by depositing a metal such as Au or Ag by sputtering so as to reflect the barnacle-like shape. A substrate portion of the sensor chip 53 as shown in (f) can be obtained.

  When the adhesion between the surface of the transparent substrate 51 having the barnacle body and the metal layer 52 is insufficient, an adhesion layer such as Ti or Cr is formed between the transparent substrate 51 having the barnacle body and the metal layer 52. May be provided.

  In order to obtain a sufficient amount of reflected light, the thickness of the metal layer 52 is preferably 10 nm or more. However, if the metal layer 52 is too thick, the cost and the production throughput are not good, so a film thickness of about 10 to 100 nm is practically desirable.

  As described above, in the manufacturing method of the localized surface plasmon resonance sensor chip according to the present embodiment, the structure including the convex portions and the concave portions on the photoresponsive material once manufactured is subjected to heat or photo-curing resin. The structure which becomes the mold of the structure can be easily produced in large quantities by applying and peeling after curing.

  And the structure which has the same shape as the surface shape on a photoresponsive material can be obtained by further apply | coating a heat or photocurable resin to the structure used as the type | mold, and making it peel.

  Further, in the manufacturing method of the localized surface plasmon resonance sensor chip according to the present embodiment, since a large-scale device is not necessary, the capital investment is hardly required and the mass productivity is excellent. Sensor chips can be produced at low cost.

  In the above description, the case where the transparent substrate 46 is used as the substrate to which the photoresponsive material is applied has been described. However, the present invention is not limited to this. In the case of irradiating the light-responsive material side with a light, a non-light-transmitting substrate can be used.

  In the above description, the transparent substrate 51 is used as the substrate of the finally obtained localized surface plasmon resonance sensor chip. However, the present invention is not limited to this. In the case where the transmittance is not measured by the localized surface plasmon resonance sensor chip, a non-light-transmitting substrate can be used.

  Furthermore, in the above description, a mold of a structure is manufactured using a thermosetting resin, and then an ultraviolet curable resin is applied to the mold, and the final localized surface plasmon resonance sensor chip substrate is formed. However, the present invention is not limited to this.

  Fabricate the mold of the structure using a photo-curing resin such as UV curable resin, and then apply the thermosetting resin to the mold to produce the final localized surface plasmon resonance sensor chip substrate In either case, a photo-curing resin such as an ultraviolet curable resin may be used, or a thermosetting resin may be used for both.

  In the conventional localized surface plasmon resonance sensor chip, metal nanostructures (metal fine particles) are present intermittently (island-like), and thus it has been difficult to manufacture efficiently.

  On the other hand, in the manufacturing method of the localized surface plasmon resonance sensor chip according to the present embodiment, the metal layer can be formed continuously, so that it can be manufactured efficiently. That is, a flat portion, a convex portion, and a concave portion obtained by dropping a suspension in which a micro object is dispersed on a photoresponsive material and irradiating light with a wavelength that induces photoisomerization and mass transfer are formed. By forming a metal film on a substrate provided with a shape by a process such as vapor deposition or sputtering, a shape including a flat portion, a convex portion, and a concave portion can be efficiently formed.

  In recent years, the nanoimprint method is often used as a method for forming minute concave portions or convex portions having a size from submicron to several tens of nanometers. However, the nanoimprint method requires a stamper and an imprint apparatus, and although it is excellent in mass productivity, it cannot be said that it can be produced at low cost because the initial capital investment is high. In addition, only one of the concave portion or the convex portion is formed in the stamper, and it is difficult to produce a stamper in which both the convex portion and the concave portion coexist, and it is difficult to produce a complicated shape by the nanoimprint method. .

  The localized surface plasmon resonance sensor can be manufactured by a known method using the above localized surface plasmon resonance sensor chip.

  EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an Example, this invention is not limited to a following example.

[Example 1: Production of structure]
The structure shown below as a photoresponsive material

(N-phenylmaleimide (z), 4-isopropenylphenol (y), 4 ′-[N-ethyl-N- (4-isopropenylphenoxyethyl) amino] -4 ″ -nitroazobenzene Copolymer with (x) (x: y: z = 0.43: 0.07: 0.50), Mat. Res. Soc. Symp. Proc. Vol.488 (1998), pp.813-818, “ Synthesis of High-Tg Azo polymer and the optimization of its poling condition for stable EO system ”(see JP 2006-77239 A) (hereinafter sometimes abbreviated as“ PMPD43 ”). 50 nm) was formed on a glass substrate by spin coating. A suspension obtained by dispersing 0.1 g of silica nanoparticles (colloidal silica) having a primary particle diameter of 70 nm (trade name: “PL-7”, manufactured by Fuso Chemical Co., Ltd.) in 10 cc of water is placed on the azo polymer thin film by 1 cc. After the dropwise addition, light having a wavelength of 470 nm was irradiated with an intensity of 100 mW / cm ² for 20 minutes.

  After the irradiation, the suspension was removed, and the azo polymer thin film after the light irradiation was subjected to ultrasonic cleaning in water, and then the surface was observed with AFM. The result is shown in FIG. The barnacle body in the obtained structure has a diameter (the diameter of the shape formed by the apex of the convex part) of 55 nm, a depth (the sum of the height of the convex part of the barnacle body and the depth of the concave part) of 130 nm, the diameter and the depth. The ratio was 0.42.

[Example 2: Production of structure]
The same azopolymer derivative PMPD43 as that used in Example 1, which is a photoresponsive material, was applied to a transparent substrate with a thickness of 50 nm by a spin coater to form an azopolymer derivative thin film. Next, a suspension obtained by suspending 0.1% by mass of silica nanoparticles having a primary particle size of 220 nm (colloidal silica) (trade name: “PL-20”, manufactured by Fuso Chemical Co., Ltd.) in water is prepared on the azo polymer derivative thin film. It was dripped.

Thereafter, light having a wavelength of 470 nm (intensity: 80 mW / cm ² ) is irradiated from the transparent substrate side for 20 minutes, the suspension is removed, the azopolymer derivative thin film is naturally dried, and the substrate having the barnacle body on the azopolymer derivative Got.

  Next, using a silicone resin (trade name: “ELASTOSIL M8520”, manufactured by Wacker Asahi Kasei Silicone Co., Ltd., thermosetting temperature: 100 ° C., in an air atmosphere) as a thermosetting resin, a thermosetting silicone resin is dropped onto the substrate. Then, it was left in a hot air oven at 100 ° C. for 30 minutes, cured and peeled to obtain a silicone resin substrate having a reverse transfer shape including a barnacle body. Further, an ultraviolet curable resin was dropped on the silicone resin substrate, and was peeled after photocuring to obtain a transparent substrate having a barnacle body.

  The surface structure of the transparent substrate thus produced was confirmed by AFM. As a result, a barnacle body was formed in the same manner as in Example 1. The diameter of the barnacle body (the diameter of the shape formed by the apex of the convex portion) was 50 nm, and the depth (the height of the convex portion of the barnacle body and the depth of the concave portion). Sum) was 100 nm. The depth B of the barnacle body with respect to the flat portion and the height A of the convex portion with respect to the flat portion were both 50 nm.

[Reference Example 1: Simulation results]
FIG. 6 is a cross-sectional view showing a schematic configuration of the structure used for the simulation result of the intensity of electric field concentration in the localized surface plasmon resonance sensor chip. (A) shows a one-dimensional groove structure (grating structure), and (b) shows a structure according to the present invention.

  The simulation in this reference example was performed under the condition of irradiating 550 nm light by FDTD (Finite Difference Time Domain) method.

  As shown in FIG. 6A, the one-dimensional groove structure used as a reference has a structure in which a metal layer made of gold having a thickness of 40 nm is provided on a PMMA substrate having a width of 120 nm and a bottom width of 100 nm. This is a structure having a depth of 100 nm.

  On the other hand, in the structure according to the present invention, as shown in FIG. 6B, the PMMA substrate has a depth of the barnacle body of 80 nm and a diameter formed by the apex of the convex portion of the barnacle body is 120 nm. In this structure, a metal layer made of gold having a thickness of 40 nm is provided.

  FIG. 7 shows a simulation result when using the localized surface plasmon resonance sensor chip according to the present invention, (a) a simulation result of a one-dimensional groove structure, and (b) a structure according to the present invention. The simulation results are shown.

  As a result of the simulation, in the structure according to the present invention, the central strength is 2.5 and the edge strength is 6.04, and in the one-dimensional groove structure, the central strength is 1.7 and the edge strength is 4.25. .

  For this reason, in the structure according to the present invention, it was confirmed that the strength of the electric field concentration was larger than that in the simulation result of the one-dimensional groove structure, and stronger localized surface plasmon resonance was generated. Therefore, it was confirmed that the structure according to the present invention can provide a highly sensitive localized surface plasmon resonance sensor.

[Example 3: Production of structure]
The structure shown below as a photoresponsive material

The side-chain azo-polymer, poly (orange tom-1 isophoronedisocyanate) (reference, Direct Fabrication of Surface Relief Holographic Diffusers in Azobenzene Polymer Films, OPTICAL REVIEW Vol. 12, No. 5 (2005) 383- 386, which may be abbreviated as “POT1” in the examples), and a thin film (thickness 50 nm) of the azo polymer was formed on a glass substrate by spin coating. A suspension obtained by dispersing 0.1 g of silica nanoparticles (colloidal silica) having a primary particle diameter of 70 nm (trade name: “PL-7”, manufactured by Fuso Chemical Co., Ltd.) in 10 cc of water is placed on the azo polymer thin film by 1 cc. After the dropping, light with a wavelength of 470 nm was irradiated from the transparent substrate side for 20 minutes with an intensity of 100 mW / cm ² .

  After the irradiation, the suspension was removed, and the azo polymer thin film after the light irradiation was subjected to ultrasonic cleaning in water, and then the surface was observed with AFM. The result is shown in FIG.

The barnacle body in the obtained structure has a diameter (diameter of the shape formed by the apex of the convex part) of 550 nm, a depth (the sum of the height of the convex part of the barnacle body and the depth of the concave part) of 150 nm, the diameter and the depth. The ratio was 0.27. The density of the barnacle body was 25/100 μm ² .

  Gold was deposited to a thickness of 100 nm on the surface of the structure by a vacuum deposition method, and a localized surface plasmon resonance chip (hereinafter referred to as LSPR chip) was produced. A transmission spectrum measured by irradiating the LSPR chip with white light is shown in FIG. As shown in FIG. 12, an absorption peak due to localized surface plasmon resonance was observed, and it was confirmed that an LSPR chip having a peak wavelength near 760 nm was obtained.

  Next, the structure shown below

Functionalized thiol molecule having (N- (2- {2- [2- (1-mercaptoundec-11-yloxy) -ethoxy] -ethoxy} -ethyl) biotinamide, hereinafter HS-C11-EG ₃ -Biotin, and Was used to prepare an ethanol solution having a concentration of 2 mM. The LSPR chip was immersed in the solution for 12 hours at room temperature, then taken out and dried to prepare a surface-modified LSPR chip.

  When the surface of the surface modified LSPR chip was irradiated with white light and the transmission spectrum was measured, the absorption peak was 772 nm.

  Further, a phosphate buffer solution (pH 8.0) prepared by adjusting streptavidin to a concentration of 100 ng / mL is dropped on the surface of the surface-modified LSPR chip, dried, and then irradiated with white light to obtain a transmission spectrum. As a result, the absorption peak was 780 nm, and it was found that streptavidin could be detected and functioned as a highly sensitive biosensor.

[Example 4: Production of structure]
(Manufacture of template substrate)
After dispersing 0.1 g of silica nanoparticles (colloidal silica) having a primary particle diameter of 70 nm (trade name: “PL-7”, manufactured by Fuso Chemical Co., Ltd.) in 10 cc of toluene, polystyrene (G690N manufactured by Nippon Polystyrene Co., Ltd.) A solution in which 1 g was dissolved was dropped onto a glass substrate, and a template substrate was produced by forming a thin film by spin coating. A side view schematically showing the template substrate is shown in FIG.

(Manufacture of structure)
As the photoresponsive material, the above-mentioned PMPD43 was used, and a thin film (thickness 50 nm) of the azo polymer was formed on a glass substrate by spin coating. After dropping 1 cc of pure water on the azopolymer thin film and placing the particle-immobilized surface of the template substrate thereon, light having a wavelength of 470 nm was irradiated for 10 minutes at an intensity of 100 mW / cm ² .

After irradiation, the template substrate and pure water were removed, and the surface of the azopolymer thin film after light irradiation was observed with AFM. The result is shown in FIG. The obtained structure is a barnacle-like structure, the diameter (diameter of the shape formed by the apex of the convex portion) is 400 nm, and the depth (the sum of the height of the convex portion and the depth of the concave portion of the barnacle) is 140 nm. Met. The density of the barnacle body was 10/100 μm ² .

  When gold was deposited to a thickness of 100 nm on the surface of the structure by a vacuum deposition method, the appearance was reddish purple.

[Comparative Example 1]
As a comparative example, using a smooth glass slide with no irregularities on the surface as a template substrate and irradiating light in the same manner as in Example 4, there was no change in the surface of the photoresponsive material before and after the light irradiation. .

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

  The structure of this invention has a flat part, the said recessed part, and the said convex part. For this reason, it can use suitably for uses, such as a substrate for localized type surface plasmon resonance sensors.

1 Particles on the template substrate surface (silica nanoparticles)
2 Glass substrate 18 Localized surface plasmon resonance sensor 19 Substrate 20 Metal layer 21 Linearly polarized light 22 Electric field 24 Localized surface plasmon resonance sensor 25 Light source 26 Collimator lens 27 Collimator plate 28 Beam splitter 29 Spectroscope 30 Localized surface plasmon resonance Sensor chip 31 Data processing device 32 Measurement region 33 Photo detector 34 Localized surface plasmon resonance sensor 45 Barnacle body 46 Transparent substrate (substrate)
47 Solid 48 Photoresponsive material layer 49 Substrate having barnacle body (structure, first structure)
50 Thermosetting resin substrate (structure type, second structure)
51 Transparent substrate (third structure)
52 Metal layer 53 Sensor chip 54 Suspension

Claims (32)

A substrate and a metal layer formed so as to cover at least part of the surface of the substrate;
On the surface of the metal layer,
A flat part,
A recess recessed with respect to the flat portion;
A convex portion protruding relative to the flat portion;
Is formed,
The convex portion protrudes continuously along the outer periphery of the concave portion,
A localized surface plasmon resonance sensor chip characterized in that the diameter of the shape formed by the apexes of the convex portions continuously projecting along the outer periphery of the concave portion is in the range of 5 nm to 1,000 nm. Dispersion density of the structure consisting of the recess and the continuous protrusions and convex portions along its periphery, characterized in that it is a one / 100 [mu] m ² or more 1,000 / 100 [mu] m ² within the following ranges, wherein Item 2. The localized surface plasmon resonance sensor chip according to Item 1 . In the structure consisting of a continuous protrusion and the protrusion along the recess and the outer periphery thereof, and wherein the sum of the depths of the height and the recess of the convex portion is in the range of 5nm or more 10μm or less, wherein Item 3. A localized surface plasmon resonance sensor chip according to item 1 or 2 . In the structure consisting of a continuous protrusion and the protrusion along the recess and the outer periphery thereof, and wherein the sum of the depths of the height and the recess of the convex portion is in the range of 10nm or more 500nm or less, wherein Item 3. A localized surface plasmon resonance sensor chip according to item 1 or 2 . On the surface of the substrate in contact with the metal layer,
A flat part,
A recess recessed with respect to the flat portion;
A convex portion that continuously protrudes from the flat portion along the outer periphery of the concave portion;
Is formed,
5. The localized surface plasmon resonance sensor chip according to claim 1 , wherein a shape of the metal layer is formed in accordance with a shape of the surface of the substrate. 6. The localized surface plasmon resonance sensor chip according to claim 5 , wherein the metal layer has a thickness of 10 nm or more. The localized surface plasmon resonance sensor chip according to claim 5 , wherein an organic molecular layer for immobilizing biomolecules is formed on the surface of the metal layer. The organic molecular layer is characterized in that it comprises a molecular length of 50nm or more 200nm or less from the surface of the metal layer, and a molecule of less is 1nm or more in length 50nm from the metal layer surface, according to claim 7 Localized surface plasmon resonance sensor chip. The localized surface plasmon resonance sensor chip according to any one of claims 1 to 8 , wherein the metal layer contains Au or Ag. A localized surface plasmon resonance sensor chip according to any one of claims 1 to 9 ,
A light source for irradiating light to the localized surface plasmon resonance sensor chip;
A photodetector for receiving light reflected or transmitted by the localized surface plasmon resonance sensor chip;
A localized surface plasmon resonance sensor comprising: Reflectance of light of each wavelength reflected by the localized surface plasmon resonance sensor chip by causing light of two or more types of wavelengths to enter the surface of the localized surface plasmon resonance sensor chip perpendicularly, each wavelength transmittance transmitted through the local surface plasmon resonance sensor chip, or characterized by measuring these reflected or transmitted light intensity of each wavelength by the optical detector, according to claim 10 Localized surface plasmon resonance sensor. A suspension application step of applying a suspension in which a solid having an average diameter of 1 nm to 100 μm is dispersed on the photoresponsive material;
A light irradiation step of irradiating light to the photoresponsive material coated with the suspension;
It is a structure manufactured by the manufacturing method of a structure characterized by including ,
A structure having a metal layer formed so as to cover at least a part of the surface of the structure . The structure according to claim 12, wherein the solid in the suspension is made of at least one material selected from the group consisting of an inorganic material, a metal material, and a polymer material. Applying an intermediate material having a refractive index greater than 1 on the photoresponsive material;
Placing the template substrate on the intermediate material applied on the photoresponsive material so that the uneven surface of the template substrate having an uneven structure on at least one surface faces the applied intermediate material;
A light irradiation step of irradiating light to the photoresponsive material on which the template substrate is placed with an intermediate material interposed therebetween;
It is a structure manufactured by the manufacturing method of a structure characterized by including ,
A structure having a metal layer formed so as to cover at least a part of the surface of the structure . 15. The structure according to claim 14, wherein the uneven structure on at least one surface of the template substrate is made of a solid having an average particle diameter in the range of 1 nm to 100 μm. The structure according to claim 15, wherein the average particle size of the solid is in the range of 10 nm to 1 μm. The structure according to claim 14, wherein the uneven structure on at least one surface of the template substrate is formed by alkali etching of a silicon substrate. The concavo-convex structure on at least one surface of the template substrate is formed by alkali and acid etching after applying or generating metal nanoparticles on the surface of a silicon substrate . Structure . The structure according to any one of claims 14 to 18, wherein the template substrate has a metal layer formed so as to cover at least a part of the concavo-convex structure surface. The said photoresponsive material contains an azo polymer derivative, The structure of any one of Claims 14-19 characterized by the above-mentioned . The structure according to any one of claims 12 to 19, wherein the photoresponsive material is an azopolymer derivative having an azobenzene group in a main chain and / or a side chain. The structure includes a flat portion, a concave portion recessed with respect to the flat portion, and a convex portion protruding with respect to the flat portion, and the convex portion is continuously provided along an outer periphery of the concave portion. The structure according to any one of claims 12 to 21, wherein the structure is protruding. A suspension applying step of applying a suspension in which a solid having an average diameter of 1 nm to 100 μm is dispersed on the photoresponsive material, and the photoresponsive material to which the suspension is applied A step of manufacturing a structure by a method of manufacturing a structure including a light irradiation step of irradiating light ,
Forming a metal layer having a shape reflecting the shape of the structure by depositing metal on the surface of the structure;
A method for manufacturing a chip for a localized surface plasmon resonance sensor, comprising: The localized surface plasmon resonance according to claim 23, wherein the solid in the suspension is made of at least one material selected from the group consisting of an inorganic material, a metal material, and a polymer material. A method for manufacturing a sensor chip . A step of applying an intermediate material having a refractive index greater than 1 on the photoresponsive material, and the uneven surface of the template substrate having an uneven structure on at least one surface thereof, facing the applied intermediate material A step of placing the template substrate on the intermediate material applied on the photoresponsive material, and a light irradiation step of irradiating the photoresponsive material with the template substrate sandwiched between the intermediate materials. A step of manufacturing the structure by the method of manufacturing the structure,
Forming a metal layer having a shape reflecting the shape of the structure by depositing metal on the surface of the structure;
A method for manufacturing a chip for a localized surface plasmon resonance sensor, comprising: 26. The localized surface plasmon resonance sensor chip according to claim 25, wherein the concavo-convex structure on at least one surface of the template substrate is made of a solid having an average particle diameter in the range of 1 nm to 100 μm. Production method. 27. The method for manufacturing a localized surface plasmon resonance sensor chip according to claim 26, wherein an average particle diameter of the solid is in a range of 10 nm to 1 [mu] m. 26. The method for manufacturing a localized surface plasmon resonance sensor chip according to claim 25, wherein the concavo-convex structure on at least one surface of the template substrate is formed by alkali etching of a silicon substrate. The concavo-convex structure on at least one surface of the template substrate is formed by alkali or acid etching after applying or generating metal nanoparticles on the surface of a silicon substrate . A method for manufacturing a chip for a localized surface plasmon resonance sensor . 30. The localized surface plasmon resonance sensor according to claim 25, wherein the template substrate has a metal layer formed so as to cover at least a part of the concavo-convex structure surface . Chip manufacturing method. 31. The method for manufacturing a localized surface plasmon resonance sensor chip according to claim 23 , wherein the photoresponsive material includes an azo polymer derivative. 31. The localized surface plasmon resonance sensor according to claim 23, wherein the photoresponsive material is an azopolymer derivative having an azobenzene group in the main chain and / or side chain . Chip manufacturing method.