Sample liquid concentration device, sample liquid analysis auxiliary device, method for producing same, and sample liquid concentration method

Abstract

In order to increase the efficiency with which an analysis using an enhanced electric field based on a microstructure is made, an embodiment of the present disclosure provides a plate-shaped sample liquid concentration device (10) that is to be used being placed over a microstructure substrate which has disposed on the surface thereof a microstructure capable of generating an enhanced electric field with respect to incident light. The sample liquid concentration device includes a first surface and a second surface that defines a thickness together with the first surface, and has formed therein a plurality of passage parts connecting the first surface and the second surface. The passage parts each have a first opening and a second opening formed respectively in the first surface and the second surface and are each defined by an inner surface connecting the first opening and the second opening. With the first surface disposed in proximity to the surface of the microstructure substrate, the first opening can be positioned corresponding to the position of the microstructure. The second opening can receive a sample liquid that contains a detection target object.

Description

Sample liquid concentrating device, sample liquid analysis auxiliary device, manufacturing method thereof, and sample liquid concentrating method

[0001] The present disclosure relates to a sample liquid concentrating device, a sample liquid analysis auxiliary device, a manufacturing method thereof, and a sample liquid concentrating method. More specifically, the present disclosure relates to a sample liquid concentrating device, a sample liquid analysis auxiliary device, a manufacturing method thereof, and a sample liquid concentrating method that improve the practicality of analysis using microstructures.

[0002] It is known that when light is irradiated onto tiny components ("microstructures") made of metals or other materials, a strong optical electric field can be generated due to the resonant interaction between the microstructure and the light waves. For example, when light of a specific wavelength is irradiated onto metal nanoparticles such as gold or silver, the free electrons within the nanoparticles can undergo collective oscillations, known as localized surface plasmons. When localized surface plasmons are excited within the microstructure, an extremely strong electric field (called an enhanced electric field) is generated near the surface of the microstructure. In microstructures, strong enhanced electric fields can also be generated by the Mie resonance phenomenon that occurs in nanoparticles with high refractive indexes, such as silicon. These enhanced electric fields are generally generated in the vicinity of the microstructure or in a localized area of ​​the microstructure, and the location where the enhanced electric field is formed is sometimes called a hotspot.

[0003] The enhanced electric field generated at the hotspot can be considered a bright light source, and methods have been proposed to utilize the enhanced electric field to improve the sensitivity of various optical measurement methods. For example, when a material is irradiated with light, the scattered light generates a light component in which the molecular vibration frequency is added (or subtracted) from the original light frequency as a result of the interaction between the light and the molecules that make up the material. This is Raman scattered light, and precise measurement of the frequency of Raman scattered light can provide information about the material's composition (Raman scattering spectroscopy). However, the intensity of this Raman scattered light is generally extremely low, with a scattering efficiency approximately one millionth that of direct scattered light (Rayleigh scattering) without frequency change. This low intensity has limited the application range of Raman scattering spectroscopy. Therefore, a technique has been devised to overcome the low scattering efficiency of Raman scattered light by using the enhanced electric field described above and enhance the Raman scattered light itself. This technique is called surface-enhanced Raman scattering spectroscopy.

[0004] In addition to Raman scattering spectroscopy, many other methods have been proposed that utilize an enhanced electric field generated by illumination light using a microstructure, such as infrared spectroscopy and fluorescence observation.

[0005] Non-Patent Document 1 discloses a device having metal microstructures that respond differently to the chirality of circularly polarized light, which was previously developed by a group including the present inventor. Non-Patent Document 2 also relates to devices having microstructures, and discloses a device having metal microstructures patterned in the shapes of "L" and "I."

[0006] Takumi Iida, Atsushi Ishikawa, Takuo Tanaka, Atsuya Muranaka, Masanobu Uchiyama, Yasuhiko Hayashi, and Kenji Tsuruta, "Super-chiral vibrational spectroscopy with metasurfaces for highly sensitive identification of alanine enantiomers," Applied Physics Letters 117, 101103 (DOI: 10.1063 / 5.0012331) (2020)Atsushi Ishikawa, Shuhei Hara, Takuo Tanaka, Yasuhiko Hayashi, and Kenji Tsuruta, "Cross-Polarized Surface-Enhanced Infrared Spectroscopy by Fano-Resonant Asymmetric Metamaterials," Scientific Reports 7, 3205 (DOI: 10.1038 / s41598-017-03545-8) (2017)

[0007] To utilize an enhanced electric field, the substance to be measured (referred to as the "detection target"), such as a sample molecule, must be present within a hot spot near the microstructure. However, if the detection target is dispersed in a sample liquid (referred to as the "sample liquid" in this application) or if the concentration of the detection target is low, even if the sample liquid is brought into contact with the surface of the microstructure, the detection target in the liquid may not necessarily be appropriately positioned near the microstructure or within the hot spot. The present disclosure provides a novel method that can solve this problem, thereby contributing to significantly improving the practicality of analytical methods that utilize the enhanced electric field created by microstructures.

[0008] The inventor conceived the idea that if the concentration of the substance to be detected in the sample liquid could be locally increased in the hot spot area, the practicality of analytical methods that utilize microstructures could be improved, and completed the invention of the present disclosure.

[0009] That is, in one aspect of the present disclosure, there is provided a plate-shaped sample liquid concentrating device for use by being placed on a microstructure substrate having microstructures arranged on its surface that can generate an enhanced electric field in response to incident light, the sample liquid concentrating device having a first surface and a second surface that forms a thickness together with the first surface, and a plurality of passage sections connecting the first surface and the second surface, the passage sections having first and second openings formed on the first and second surfaces, respectively, and defined by inner surfaces connecting the first openings and the second openings, the first surface being arranged close to the surface of the microstructure substrate, so that the first opening can be positioned corresponding to the position of the microstructure, and the second opening is adapted to receive a sample liquid containing a detection target.

[0010] In addition, in one aspect of the present disclosure, there is also provided a method for manufacturing a sample liquid concentration device, comprising the steps of: forming a passage portion in a plate-shaped member that connects a first surface and a second surface that form the thickness of the plate-shaped member; wherein the passage portion has a first opening formed in the first surface and a second opening formed in the second surface, and is defined by an inner surface that connects the first surface and the second surface, and wherein the first opening is positioned corresponding to the position of a microstructure that can generate an enhanced electric field in response to incident light.

[0011] In addition, one aspect of the present disclosure also provides a sample liquid analysis auxiliary device that utilizes the above-described sample liquid concentrating device.

[0012] In addition, in one aspect of the present disclosure, there is also provided a method for concentrating a sample liquid, which includes the steps of: positioning a first opening formed on a first surface of a passage portion connecting a first surface and a second surface that form the thickness of a plate-like member, in correspondence with the position of a microstructure that can generate an enhanced electric field in response to incident light; receiving a sample liquid containing a substance to be detected into a second opening formed on the second surface of the passage portion; and volatilizing the solvent of the sample liquid.

[0013] In this application, the term "microstructure" generally refers to a nanostructure that utilizes a material that responds to incident electromagnetic waves. A sample liquid refers to a liquid or liquid-like substance that contains, in some form, the substance to be analyzed (referred to as the "detection target"). In this application, the term "electromagnetic wave" may include electromagnetic waves of any wavelength or frequency. In this application, terms for light, including visible light, may be used to describe interactions and phenomena with electromagnetic waves.

[0014] According to any aspect of the present disclosure, it is possible to improve the practicality of analytical techniques that utilize minute structures.

[0015] FIGS. 1A-1E are explanatory diagrams illustrating an example of a microstructure used in an embodiment of the present disclosure, including a perspective view (FIG. 1A), scanning electron microscope images (FIGS. 1B and 1C), and calculated values ​​of optical chiral components (FIGS. 1D and 1E). FIGS. 2A-2E are explanatory diagrams illustrating another example of a microstructure used in an embodiment of the present disclosure, including a perspective view (FIG. 2A), a scanning electron microscope image (FIG. 2B), and calculated values ​​of light intensity distribution (FIGS. 2C-2E). FIG. 3 is a perspective view illustrating an outline of the inventor's idea in this embodiment. FIG. 4 is a scanning microscope image showing components of an example that may be candidates for a sample liquid concentrating device in an embodiment of the present disclosure. FIGS. 5A-5C are cross-sectional views of each stage illustrating a method for concentrating a sample liquid in an embodiment of the present disclosure. FIG. 6 is a flowchart of a concentration method in an embodiment of the present disclosure. FIGS. 7A-7D are cross-sectional views showing modified examples of a sample liquid concentrating device and a method of using the same in an embodiment of the present disclosure. FIG. 8 is a flowchart showing an outline of a method for manufacturing a sample liquid analysis auxiliary device in an embodiment of the present disclosure. 9 is a flowchart showing another method for manufacturing the sample liquid analysis auxiliary device of this embodiment, and FIGS. 10A to 10C are cross-sectional views showing the configuration at each stage of the manufacturing process.

[0016] Hereinafter, embodiments of the diffuser according to the present disclosure will be described with reference to the drawings. In the description, common parts or elements are designated by common reference numerals unless otherwise specified. Furthermore, in the drawings, elements of each embodiment are not necessarily shown to scale.

[0017] 1. Overview 1-1. Relationship between Enhanced Electric Field and Detectable Object Figures 1A-1E are explanatory diagrams illustrating an example of a microstructure used in this embodiment, including a perspective view (Figure 1A), scanning electron microscope images (Figures 1B and 1C), and calculated values ​​of optical chiral components (Figures 1D and 1E). Figures 1B and 1C also show enlarged partial images. The microstructure 52A is formed on a substrate 50 by repeatedly arranging patterns of a material, such as gold, that responds to incident electromagnetic waves. The material that responds to incident electromagnetic waves is typically a noble metal, but may also include inorganic materials such as Si, Ge, and Ga, or compounds such as TiN and HfN. Figure 1A shows the scope of the unit cell of this repeating arrangement. The substrate is made of any material, such as silicon, that can form a fine pattern. Localized surface plasmons, for example, are induced in the layer of the microstructure 52A when electrons respond to the incident electromagnetic waves. This localized surface plasmon responds resonantly to the vibration of electromagnetic waves. If we define the substrate surface as the xy plane and the normal direction to it as the z-axis, as shown in the figure, then of the various types of polarized electromagnetic waves incident generally perpendicularly with their wave vectors pointing toward the -z axis, the electric field E and magnetic field H components oriented toward the y-axis and z-axis, respectively, are involved in this resonance. The unit cell in Figure 1A is 2000 nm (2 μm) square, and the representative dimensions of each component are clearly shown in Figure 1A. In this example, a metal pattern, e.g., a gold thin film, is formed within the unit cell. Two rectangular patterns, each 300 nm wide in the x-axis and 800 nm long in the y-axis, are offset in the y-axis direction with a 300 nm gap between them. The two metal patterns are offset by 400 nm, and depending on the offset, two types of arrangements are possible, as shown in Figures 1B and 1C. These are referred to as left-handed and right-handed configurations, respectively. Figures 1D and 1E show the chiral component, or handedness, calculated using the FDTD method and plotted as a concentration. Electromagnetic waves are classified into circularly polarized, elliptically polarized, and linearly polarized waves, in descending order of chiral component abundance. Dark areas indicate areas where chiral components close to circular polarization are dominant, while bright areas indicate areas where linear polarization is dominant. The electric field is strong where the chiral components, indicated by + and - handedness, are biased, forming an enhanced electric field. The enhanced electric field reaches its maximum value in the area between adjacent patterns.

[0018] Figures 2A to 2E are explanatory diagrams illustrating another example of a microstructure used in this embodiment, including a perspective view (Figure 2A), a scanning electron microscope image (Figure 2B), and calculated values ​​of light intensity distribution (Figures 2C to 2E). Figure 2B also shows an enlarged image of a portion. The microstructure 52B is also formed by repeatedly arranging a metal pattern, such as gold, on a substrate 50. Figure 2A shows the range of the unit cell of this repeated arrangement. The substrate is made of any material, such as silicon, that can support a flat, fine pattern. The size of each component indicated by a symbol in Figure 2A is adjusted; typically, Px = Py = 1 μm, and h / S = 0.75. Dipole and quadrupole enhanced electric fields are induced in the metal layer of the microstructure 52B. These are shown as intensities in Figures 2C and 2D. At the position, the electric field is strengthened by localized surface plasmons, resulting in the formation of an enhanced electric field. The enhanced electric field is mainly formed in the positions adjacent to the metal patterns and in the region between adjacent metal patterns. When a molecule characteristic of the target substance having a chemical bond C=O (carbonyl group) is present near the gap, electrical vibrations are excited by Fano resonance. This is illustrated in Figure 2E. The enhanced electric field is mainly maximized in the region between adjacent metal patterns.

[0019] In this way, localized surface plasmons are induced in the microstructure, and an enhanced electric field is formed around it due to its action. The position affected by this enhanced electric field (hot spot) is strongly related to the position of the microstructure. In order to detect a target substance with high sensitivity using the microstructure, it is important that the target substance is present in the hot spot.

[0020] 1-2. Concept / Structure The inventors of the present disclosure focused on the idea that if sample liquid is placed near microstructures or in hotspot areas and the solvent (e.g., water) can be evaporated from the sample liquid, the concentration of the target substance near the microstructure or in the hotspot area can be increased, thereby improving the sensitivity of subsequent analysis. Specifically, they came up with the idea of ​​stacking a sample liquid concentrator 10 having a passage 20 on a microstructure substrate 50 on which a microstructure 52 is formed. Figure 3 is a perspective view illustrating an outline of the inventors' idea in this embodiment. The microstructure 52 is disposed on the surface of the microstructure substrate 50. The microstructure 52 can generate an enhanced electric field in response to incident light (incident electromagnetic field). The arrangement of the passages 20 in the sample liquid concentrator 10 can be adapted to the arrangement of the microstructures 52. The passages 20 are formed on a concentrator substrate 16. The first surface 11 and the second surface 12, which form the thickness of the concentrator substrate 16, are connected by the passage 20. The passage portion 20 has a first opening 21 and a second opening 22 in the first surface 11 and the second surface 12, and is defined by an inner surface 23 that penetrates the concentrator substrate 16. The first surface 11 is disposed in close contact with or close to the surface of the microstructure substrate 50, i.e., in close proximity. For the sake of explanation, the sample liquid concentrator 10 is depicted in Figure 3 separated from the microstructure substrate 50. This allows the first opening 11 to be positioned corresponding to each position on the microstructure 50. The second surface 12 is configured to receive a sample liquid containing a detection target substance.

[0021] FIG. 4 is a scanning microscope photograph showing an example of a component that could be a candidate for the sample liquid concentrating device 10. The silicon substrate 80 is a substrate with a <100> orientation. When a crystal such as silicon is chemically etched using an etching solution, the etching rate varies depending on the crystal orientation, and the etching occurs anisotropically, resulting in the self-organizing formation of a concave-convex structure on the material surface. This passage 90 is also formed by etching silicon with a potassium hydroxide solution using crystal anisotropic etching, and is etched into an inverted pyramid (square pyramid) shape. For example, a square pyramid-shaped concave structure can be fabricated in any location using microfabrication technology. Details will be described later.

[0022] 1-3. Concentration Operation FIGS. 5A-5C are cross-sectional views illustrating each step of the method for concentrating a sample liquid in this embodiment. FIGS. 5A-5C show the steps of concentrating a sample liquid using a sample liquid concentrating device 10 with a structure similar to that of FIG. 3 in chronological order. FIG. 6 is a flowchart of the concentration method in this embodiment. In the concentration operation, first, the sample liquid concentrating device 10 is positioned so that the first opening 21 of the passage 20 corresponds to the position of the hot spot of the microstructure (FIG. 6, S02). Next, the sample liquid 70 containing the target substance 72 is placed so that it can be received by the second opening 22 of the passage 20 (S04). This placement can be performed by any method, such as dropping the sample liquid or dipping the entire device including the sample liquid concentrating device 10 into a container containing the sample liquid 70. The sample liquid 70 is typically a solution of a suitable solvent containing the target substance 72. As a result, as shown in FIG. 5A, the sample liquid 70 is placed in the passage 20 defined by the inner surface 23. The solvent in the sample liquid 70 is then evaporated (S06). This reduces the volume of the sample liquid 70, as shown in FIG. 5B, and increases the concentration of the target substance 72. As the evaporation proceeds, the concentration of the target substance 72 in the sample liquid 70 increases sufficiently, resulting in a high probability of the target substance 72 being located in a hot spot near the microstructure 52. Because the inner surface 23 of the passage 20 typically functions as a funnel, the concentrated sample liquid 70 collects near the microstructure 52. Whether to completely evaporate the solvent and dry the sample liquid 70 or to stop evaporation midway and concentrate the sample liquid 70 can be determined depending on the properties of the sample liquid 70 and the analytical conditions. An analysis is then performed that utilizes the interaction between the target substance 72 and the microstructure 52 (S08). A typical example of this analysis is spectroscopic analysis, including Raman spectroscopy, but the analytical technique is not particularly limited. If it is acceptable for the sample liquid concentrating device 10 to be present during the analysis stage, the analysis may be carried out as is, or if there is some reason, the sample liquid concentrating device 10 may be removed and the analysis may be carried out.

[0023] 1-4. Improvements Suitable for Concentration Various improvements may be made to the sample liquid concentrator 10 to achieve the concentration described above. This is because the surface properties of the passages fabricated using such techniques are relevant to the concentration of the sample liquid 70. For example, if the concentrator substrate 16 for the sample liquid concentrator 10 is a single-crystal silicon substrate, after forming the passages 20 using crystal anisotropic etching, it is useful to modify the outermost surface of the single-crystal silicon substrate, including the inner surface 23, to a superhydrophobic state using reactive ion etching at the final stage of forming the inner surface 23. More specifically, the native oxide film that naturally forms on the surface of the single-crystal silicon substrate, including the inner surface 23, is removed, and the surface is then treated with CF plasma. This treatment can modify the surface to a superhydrophobic state.

[0024] Among the surfaces of the concentrator substrate 16, the surfaces whose properties are preferably controlled are typically the second surface 12 and the inner surface 23, but may also be either one of these. The properties suitable for this surface may be hydrophobic treatment, including superhydrophobic treatment, or hydrophilic treatment (including superhydrophilic treatment). The properties suitable for this surface depend on the substance of the sample liquid 70 and the concentration process. The solvent in the sample liquid 70 is typically water, but can also be an organic solvent. Note that the operation shown in Figures 5A-C is a process in which the concentration of the target substance 72 in the sample liquid 70 increases as the solvent evaporates. In this process, surfaces that can appropriately concentrate the sample liquid 70 include not only superhydrophobic surfaces, but also hydrophobic and hydrophilic surfaces. To create a hydrophobic surface, for example, a silane coupling agent treatment using hexamethyldisilazane (HMDS) or the aforementioned fluorine plasma treatment can be used. To create a hydrophilic surface, for example, if the concentrator substrate 16 is a silicon substrate, the native oxide film can be removed or oxygen plasma treatment can be used. In reality, a native oxide film forms on the surface of a Si substrate, but since this film is not necessarily clean, simply removing it can sometimes result in hydrophilicity. Oxygen plasma treatment can also achieve hydrophilicity by removing organic matter adhering to the substrate surface. Note that when a Si substrate is subjected to oxygen plasma treatment, a new oxide film is formed, so the oxide film remains. Other hydrophobic and hydrophilic treatment methods can also be employed. The water repellency, hydrophobicity, and hydrophilicity of a surface can be quantitatively evaluated by measuring the contact angle.

[0025] In this embodiment, the surface properties of the second surface 12 and the inner surface 23 can be correlated with each other or controlled independently, thereby enabling the concentrator substrate 16 to exhibit its functions. Typical combinations include four patterns: one in which both the second surface 12 and the inner surface 23 are hydrophobic or superhydrophobic, one in which the inner surface 23 is hydrophobic and the surface 12 is hydrophilic, one in which the inner surface 23 is hydrophilic and the surface 12 is hydrophobic, and one in which both the inner surface 23 and the surface 12 are hydrophilic.

[0026] 1-5. Modifications Figures 7A to 7D are cross-sectional views showing modifications of the sample liquid concentrating device 10 and its method of use according to this embodiment. The sample liquid concentrating device 10 in Figure 7A is similar to that shown in Figure 4 and illustrates the sample liquid 70 in Figure 5C after concentration. Unlike the previous explanations, the passages 20 in the sample liquid concentrating device 10 do not necessarily have to be arranged in one-to-one correspondence with the microstructures 52. For example, as shown in Figure 7B, when the microstructures 52 are formed at a high density, this embodiment also includes a configuration in which the first openings 21 of the passages 20 are positioned to correspond to only a portion of the multiple microstructures 52. Although not shown, this embodiment also includes a configuration in which multiple microstructures 52 are positioned corresponding to the first openings 21 of the passages 20.

[0027] 7C, a sample liquid concentrating device 10A having columnar passages 20A instead of conical passages 20A can also be used to concentrate the sample liquid 70. The columnar passages 20A can be arranged with a high surface density.

[0028] The sample liquid concentrating devices 10 and 10A described above operate in combination with a microstructure 52 formed on a microstructure substrate 50. This embodiment also includes an arrangement in which a support film 30 is formed on the first surface 11 of the concentrating device substrate 16, and the microstructure 52 is formed at a position through the thickness of the support film 30, as shown in FIG. 7D . If the support film 30 has appropriate dielectric properties and thickness, an enhanced electric field due to the microstructure 52 is also formed at a position through the thickness of the support film 30, allowing the concentrated sample liquid 70 to be placed within the range of the enhanced electric field. Even with this configuration, analytical sensitivity can be improved. Furthermore, this configuration has the advantage that the sample liquid 70 does not directly contact the microstructure 52 but is placed through the support film 30, thereby increasing the options for materials for the sample liquid 70 and the microstructure 52. Note that if the support film 30 is thin and mechanically weak, it is preferable to add a protective layer 32 as needed to easily maintain the shape of the sample liquid concentrating device 10 for analysis, for example.

[0029] Furthermore, this embodiment also includes a configuration in which, instead of the passage 20 connecting both sides of the sample liquid concentrating device 10, a structure (recessed structure) deeply carved from one side but not extending to the other side is used (not shown). Substrates such as silicon wafers can be used as substrates for forming the microstructure 52, as well as for forming the passage 20 or similar structures. Therefore, by forming a recessed structure corresponding to the passage 20 on one side of the substrate and placing the microstructure 52 on the other side, the concentrated sample liquid 70 can be placed within the range where the enhanced electric field is generated by the microstructure 52. To achieve this, the bottom of the recessed structure must be sufficiently thin, and both sides of the substrate must be processed in alignment. This configuration can also provide the same advantages as the sample liquid concentrating device 10A. Furthermore, when using both sides of such a single substrate, it is advantageous to penetrate the bottom of the recessed structure to form the passage 20 and place the microstructure 52 so that it is partially floating above the first opening 21.

[0030] 1-6. Manufacturing of the Sample Liquid Analysis Auxiliary Device Figure 8 is a flowchart showing an outline of a manufacturing method for the sample liquid analysis auxiliary device of this embodiment. Here, the sample liquid analysis auxiliary device is a device that simplifies the analysis of sample liquids by combining the sample liquid concentrating device 10 configured as shown in Figure 4 with a microstructure substrate 50 on which microstructures 52 are formed. The process for manufacturing the sample liquid analysis auxiliary device generally includes a nanostructure array manufacturing process (S22 to S28) for forming microstructures 52 on the microstructure substrate 50, a funnel array manufacturing process (S42 to S48) for forming passage portions 20 on the substrate, and an assembly process (S62 to S64) for combining these processes.

[0031] 1-6-1. Fabrication of Nanostructure Arrays The microstructures 52 are formed by forming a film of a material that responds to incident electromagnetic waves on one side of a silicon wafer (S22), and then performing resist patterning (S24) and etching (S26) using techniques such as photolithography. The resist is then removed (S28). Various specific microfabrication techniques can be employed, and a technique can be selected appropriately based on the size and material of the microstructures 52.

[0032] 1-6-2. Fabrication of Funnel Arrays The sample liquid concentrating device 10 begins with a <100> silicon wafer serving as the concentrating device substrate 16, with SiO or SiN mask layers formed on both surfaces. A photoresist layer is then formed on the mask layer on the second surface 12, which is one of the surfaces, followed by exposure and dry etching (S42), to form window-like openings in the mask layer (S44). The second surface 12 of the silicon substrate is then wet-etched through these window-like openings using an etching solution such as KOH (S46). By appropriately setting the wet etching conditions, a quadrangular pyramidal recess corresponding to the crystal orientation is formed on the second surface 12 of the silicon substrate, forming a channel 20 defined by the inner surface 23. The mask layer is then removed as needed (S48). While the channel 20 connects both surfaces of the silicon substrate, a recessed structure with a sufficiently thin bottom but not a continuous structure can also be fabricated by adjusting the conditions.

[0033] 1-6-3. Assembling The concentrator substrate 16 on which the passage 20 is formed and the microstructure substrate 50 on which the microstructure 52 is formed are aligned so that the microstructure 52 is positioned in the first opening 21 of the passage 20 (S62). At this time, the first surface 11 of the concentrator substrate 16 faces the surface of the microstructure substrate 50 on which the microstructure 52 is formed. In this state, the concentrator substrate 16 and the microstructure substrate 50 are fixed to each other (S64). Thereafter, any necessary protective treatment (not shown) is carried out as appropriate. By assembling the concentrator substrate 16 and the microstructure substrate 50 in this manner, the sample liquid concentrating device 10 shown in FIG. 3 is produced.

[0034] 1-6-4. Modifications of Manufacturing the Sample Liquid Analysis Auxiliary Device The sample liquid analysis auxiliary device of this embodiment can be manufactured by any manufacturing method that can ultimately produce the configuration of sample liquid concentrating device 10 shown in Figures 7A to 7D. Figure 9 is a flowchart showing another manufacturing method of the sample liquid analysis auxiliary device of this embodiment, and Figures 10A to 10C are cross-sectional views showing the configuration at each stage of manufacturing.

[0035] The sample liquid concentrating device 10 can also be manufactured by using a different method for fabricating the funnel array. First, as shown in FIG. 9 , the nanostructure array fabrication process (S22 to S28) is performed to form the microstructures 52 on the microstructure substrate 50. This process is similar to that described above. At this stage, the microstructures 52 are formed on the microstructure substrate 50 ( FIG. 10A ). Then, the funnel array layer 162 is formed on the surface of the microstructure substrate 50 on which the microstructures 52 are formed ( S72 , FIG. 10B ). The material to be deposited is a layer of polysilicon or the like, which will later form the passage 20. A suitable method for forming the layer is adopted depending on the material. Next, a mask layer (not shown) is formed on the surface of the funnel array layer 162 to coincide with the positions of the microstructures 52 ( S74 ). Furthermore, the mask layer is etched ( S76 ), forming openings in the mask layer ( S78 ). Crystal anisotropic etching is then performed on the funnel array layer 162 ( S80 ). This forms the passages 20 in the funnel array layer 162. Thereafter, the mask layer is removed as necessary (S82, FIG. 10C).

[0036] 1-6-5. Modified Materials The sample liquid concentrating device 10 (FIG. 3) of this embodiment can also use a material that generates a self-organized shape by utilizing crystalline anisotropy, such as a silicon substrate with a <100> orientation, to form the passage 20. Examples of such materials other than silicon include CaF2, which exhibits crystalline anisotropy when etched. CaF2 is also highly useful because it is transparent from the visible to infrared range. For example, the position of the formed funnel hole can be aligned while checking it with an optical microscope. The sample liquid concentrating device 10 can also be formed into any pattern using existing microfabrication techniques in other fields, such as MEMS (Micro Electro Mechanical Systems).

[0037] The embodiments of the present disclosure have been specifically described above. The above-mentioned embodiments and examples have been described in order to explain the invention, and the scope of the invention of this application should be determined based on the description of the claims. In addition, modifications within the scope of the present disclosure, including other combinations of the embodiments, are also included in the claims.

[0038] REFERENCE SIGNS LIST 10, 10A Sample liquid concentrator 11 First surface 12 Second surface 16 Concentrator substrate 162 Funnel array layer 20, 20A Passage section 21 First opening 22 Second opening 23 Inner surface 30 Support film 32 Protective layer 50 Microstructure substrate 52, 52A, 52B Microstructure 70 Sample liquid 72 Object to be detected 80 Silicon substrate 90 Passage section

Claims

1. A plate-shaped sample liquid concentrating device to be used by being placed on a microstructure substrate having microstructures arranged on its surface that can generate an enhanced electric field in response to incident light, the sample liquid concentrating device having a first surface and a second surface that forms a thickness together with the first surface, and having a plurality of passages connecting the first surface and the second surface, the passages having first and second openings formed on the first and second surfaces, respectively, and defined by inner surfaces connecting the first openings and the second openings, the first surface being arranged close to the surface of the microstructure substrate so that the first openings can be positioned corresponding to the positions of the microstructures, and the second openings are capable of receiving sample liquid containing a detection target.

2. The sample liquid concentrating device according to claim 1, wherein either or both of the second surface and the inner surface are super-water-repellent surfaces.

3. The sample liquid concentrating device according to claim 1, wherein either or both of the second surface and the inner surface are hydrophobic surfaces.

4. The sample liquid concentrating device according to claim 1, wherein either or both of the second surface and the inner surface are hydrophilic surfaces.

5. The sample liquid concentrating device according to claim 1, wherein either the second surface or the inner surface is a hydrophilic surface, and the other is a hydrophobic surface.

6. The sample liquid concentrating device according to claim 1, wherein the passage is formed in a silicon crystal substrate, the second opening is larger than the first opening, and the passage is funnel-shaped.

7. The sample liquid concentrating device according to claim 6, wherein the inner surface is in the shape of a polygonal pyramid.

8. A sample liquid analysis auxiliary device comprising: the sample liquid concentrating device according to claim 1; and a microstructure substrate having microstructures arranged on its surface that can generate an enhanced electric field in response to incident light, wherein the sample liquid concentrating device and the microstructure substrate are arranged so that the first surface is close to the surface of the microstructure substrate, thereby positioning the first opening in accordance with the position of the microstructure.

9. A plate-shaped sample liquid analysis auxiliary device, the sample liquid analysis auxiliary device having a first surface and a second surface forming a thickness together with the first surface, and having a plurality of passages connecting the first surface and the second surface, the passages being defined by inner surfaces connecting the first opening and the second opening, with a first opening and a second opening formed in the first surface and the second surface, respectively, a film being formed on the first surface so as to cover at least a part of the first opening, and a microstructure capable of generating an enhanced electric field in response to incident light being disposed on a portion of the surface of the film which corresponds to the first opening, and the second opening being adapted to receive a sample liquid containing a detection target.

10. A sample liquid analysis auxiliary device comprising: a microstructure substrate on the surface of which microstructures capable of generating an enhanced electric field in response to incident light are arranged; and a funnel array layer arranged in contact with the surface of the microstructure substrate, wherein the funnel array layer has a first surface in contact with the surface of the microstructure substrate and a second surface forming a thickness together with the first surface, and wherein a plurality of passages are formed connecting the first surface and the second surface, wherein the passages have first and second openings formed in the first and second surfaces, respectively, and are defined by inner surfaces connecting the first openings and the second openings, wherein the first openings are positioned corresponding to the positions of the microstructures, and the second openings are adapted to receive a sample liquid containing a detection target.

11. A method for manufacturing a sample liquid concentration device, comprising the steps of: forming a passageway in a plate-like member that connects a first surface and a second surface that form the thickness of the plate-like member; wherein the passageway is defined by an inner surface that connects the first surface and the second surface, with a first opening formed in the first surface and a second opening formed in the second surface; and positioning the first opening in correspondence with the position of a microstructure that can generate an enhanced electric field in response to incident light.

12. A method for manufacturing a sample liquid concentrating device, comprising the steps of: arranging microstructures capable of generating an enhanced electric field in response to incident light on a surface of a microstructure substrate; forming a funnel array layer in contact with the surface of the microstructure substrate, covering the microstructures, and having a thickness formed between a first surface and a second surface in contact with the surface; and forming a passage portion in the funnel array layer, connecting the first surface and the second surface, wherein the passage portion has a first opening formed in the first surface and a second opening formed in the second surface, and is defined by an inner surface connecting the first surface and the second surface, and the first opening is positioned corresponding to the position of the microstructure.

13. The method for manufacturing a sample liquid concentrating device according to claim 11 or 12, wherein the step of forming the passage portion is a step of forming the inner surface on a silicon crystal substrate by crystal anisotropic etching.

14. A method for concentrating a sample liquid, comprising the steps of: positioning a first opening formed on a first surface of a passageway connecting a first surface and a second surface that form the thickness of a plate-like member, in correspondence with the position of a microstructure capable of generating an enhanced electric field in response to incident light; receiving a sample liquid containing a detection target into a second opening formed on the second surface of the passageway; and volatilizing the solvent in the sample liquid.

Images