JP2012246163A - Nano-porous thin film and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a nano-porous thin film, wherein a material of a pore wall surrounding a periphery of a pore is optionally controlled in a film thickness direction, and to provide a method for producing the same.SOLUTION: The nano-porous thin film having nano-porous structure includes a plurality of layer regions along the film thickness direction. The plurality of layer regions include a first layer region having a first pore and a second layer region having a second pore, wherein the first pore and the second pore penetrate each other, and materials forming the first layer region and the second layer region are different.

Description

  The present invention relates to a nanoporous thin film and a method for producing the same. More specifically, it is used for supporting materials that support substances such as catalysts and functional molecules, adsorbing materials that adsorb substances, separation for separation and detection of substances, molecular recognition, sensor materials, transportation and exchange of substances. The present invention relates to a nanoporous thin film that can be used in a wide range such as a conductive material, an electronic device, an optical device, a nanostructure material used for a microdevice, and the like, and a manufacturing method thereof.

  In recent years, the development of nanotechnology has been remarkable, and various nanostructured materials having nanometer-sized structures have been proposed. In particular, nanoporous materials having a nanometer-sized space are used in many industrial fields such as adsorbent materials and carriers such as catalysts, material separation and recognition materials.

  As a method for producing this nanoporous material, there is a production method using a molecule as a template. For example, a mesoporous material prepared using a surfactant micelle as a template and a molecular imprinting method for forming a molecular recognition site using a recognition target molecule as a template are widely known.

  In order to further apply these nanoporous materials to the functional material field, a technique for controlling the morphology is important. For example, as a shape control technique suitable for device application, a technique for forming a nanoporous material in a thin film on a substrate is important. In particular, the ultra-thin film formation technology at a level where the nanospace is formed as a single layer is a very important technology that leads to the realization of a functional material carrier and a high-density recording material.

  For example, Non-Patent Document 1 discloses a method of forming a porous film using a surface sol-gel method using a dendrimer as a template. It is described that a thin film having a thickness of 8 to 10 nm having dendrimer-sized pores is formed on the substrate by this method.

  Non-Patent Document 2 discloses a method of forming a porous film using a surface sol-gel method using a peptide as a template. Here, the adsorption of the peptide on the substrate and the formation of the titania gel layer are repeated 10 cycles to form a film with a film thickness of 14 ± 3 nm, and its molecular recognition ability is evaluated.

J. et al. Huang, Chemical Communications, p. 2070 (2002) I. Ichinose, Chemistry Letters, p. 104 (2002)

However, in Non-Patent Document 1, there is only one kind of porous material, and the complicated shape and arrangement of the porous material and the porous material are not controlled.
Even in Non-Patent Document 2, although the film thickness is increased by repeated processing, the shape and arrangement of the porous tissue and the more complicated control of the porous material are not performed.

  Therefore, the present invention has been made in view of the above problems, and a porous thin film, particularly a nanoporous thin film in which the material of the pore wall surrounding the pores is arbitrarily controlled in the film thickness direction, and the production thereof It aims to provide a method. Furthermore, it aims at provision of a molecular recognition material and a sensor.

  The present invention is a nanoporous thin film having a nanoporous structure, having a plurality of layer regions along the film thickness direction, wherein the plurality of layer regions are first layers having first pores A second layer region having a region and a second pore, the first pore and the second pore penetrate, and the first layer region and the second layer region The constituent materials are different. Note that the material constituting at least one of the plurality of layer regions is preferably made of an inorganic oxide. Moreover, it is preferable that the isoelectric point of the material which comprises said 1st layer area | region and said 2nd layer area | region differs. In addition, it is preferable that the first pore and the second pore have different space sizes.

  The present invention also provides a molecular recognition material that selectively binds to a recognition target molecule, comprising a nanoporous thin film having a nanoporous structure held on a substrate, wherein the nanoporous thin film has a thickness direction. A plurality of layer regions, the plurality of layer regions including a first layer region having a first pore and a second layer region having a second pore, The layer region and the second layer region in this order along the film thickness direction from above the substrate, the first pore and the second pore penetrate, The material constituting the layer region and the second layer region are different. In addition, it is preferable that the size of the space of the second pore is larger than the size of the space of the first pore.

  The present invention also provides a sensor for detecting the presence and / or concentration of a recognition target molecule in a sample liquid, comprising a nanoporous thin film having a nanoporous structure held on a detection device, the nanoporous The thin film has a plurality of layer regions along the film thickness direction, and the plurality of layer regions are a first layer region having a first pore and a second layer region having a second pore. The first layer region and the second layer region in this order along the film thickness direction from above the substrate, the first pore and the second pore Are penetrated, and the materials constituting the first layer region and the second layer region are different. The detection device is preferably an FET device.

  Further, the present invention is a method for producing a nanoporous thin film having a nanoporous structure, the step of contacting a first reaction solution containing a first template molecule and a first polymerizable monomer to a substrate, Removing the solvent of the first reaction solution, polymerizing the first polymerizable monomer, and forming a first polymer film on the substrate; and a second different from the first polymerizable monomer A step of bringing a second reaction solution containing the polymerizable monomer and the second template molecule into contact with the first polymerized film; removing the solvent of the second reaction solution; and And a step of forming a second polymer film on the first polymer film and a step of removing the first and second template molecules. Furthermore, the first template molecule and the second template molecule are preferably different molecules.

  The present invention is also a method for producing a nanoporous thin film having a nanoporous structure, wherein a first solution containing a first template molecule is brought into contact with a substrate, and the first template molecule is placed on the substrate. After the immobilization, the step of bringing the third reaction solution containing the first polymerizable monomer into contact with the substrate, the solvent of the third reaction solution is removed, and the first polymerizable monomer is polymerized. Forming a first polymerized film on the substrate; and a second reaction solution containing a second polymerizable monomer different from the first polymerizable monomer and a second template molecule. A step of contacting the polymer film, a step of removing the solvent of the second reaction solution, polymerizing the second polymerizable monomer, and forming a second polymer film on the first polymer film; And removing the first and second template molecules.Furthermore, the first template molecule and the second template molecule are preferably different molecules.

  Further, the present invention is a method for producing a nanoporous thin film having a nanoporous structure, the step of contacting a first reaction solution containing a first template molecule and a first polymerizable monomer to a substrate, Removing the solvent of the first reaction solution, polymerizing the first polymerizable monomer, and forming a first polymer film on the substrate; and a second solution containing a second template molecule. A fourth polymer containing a second polymerizable monomer different from the first polymerizable monomer after contacting the first polymerized film and fixing the second template molecule on the first polymerized film; Contacting the first polymerized film with the first polymerized film; removing the solvent of the fourth reaction solution; polymerizing the second polymerizable monomer; Including a step of forming a polymerized film and a step of removing the first and second template molecules. And features. Furthermore, the first template molecule and the second template molecule are preferably different molecules.

  The present invention is also a method for producing a nanoporous thin film having a nanoporous structure, wherein a first solution containing a first template molecule is brought into contact with a substrate, and the first template molecule is placed on the substrate. After the immobilization, the step of bringing the third reaction solution containing the first polymerizable monomer into contact with the substrate, the solvent of the third reaction solution is removed, and the first polymerizable monomer is polymerized. A step of forming a first polymer film on the substrate; and a second solution containing a second template molecule is brought into contact with the first polymer film, and the second polymer film is formed on the first polymer film. After fixing the template molecule, a step of bringing a fourth reaction solution containing a second polymerizable monomer different from the first polymerizable monomer into contact with the first polymerized film, and the fourth reaction solution And the second polymerizable monomer is polymerized, and the second polymerized monomer is polymerized on the first polymer film. Characterized in that it comprises the forming a polymerized film, and removing the first and second template molecule. Furthermore, the first template molecule and the second template molecule are preferably different molecules.

  According to the present invention, a porous thin film, in particular, a nanoporous thin film in which the material of the pore wall surrounding the periphery of the pore is arbitrarily controlled in the film thickness direction together with the pore shape or pore arrangement, and a method for producing the same I will provide a. Furthermore, it is possible to provide a molecular recognition material and a sensor.

It is sectional drawing which shows typically the film | membrane structure of the thin film concerning this invention. It is a figure which shows typically the pore which concerns on this invention. It is a figure which shows typically the pore arrangement | sequence which concerns on this invention. It is a figure which shows typically the pore shape which concerns on this invention. It is a figure which shows typically the nanoporous thin film formed on the base | substrate which concerns on this invention. It is the figure which showed typically the sensor device carrying the molecular recognition material which concerns on this invention. It is the figure which showed typically the manufacturing method of the nanoporous thin film which concerns on this invention. It is the figure which showed the calibration curve typically. It is the figure which showed the structure of FET device typically.

  Next, a preferred embodiment of the present invention will be described in detail.

  First, the nanoporous thin film will be described in detail.

  The nanoporous thin film having a nanoporous structure according to the present invention has a plurality of layer regions along the film thickness direction, and the plurality of layer regions includes a first layer region having a first pore. A second layer region having a second pore, wherein the first pore and the second pore penetrate and constitute the first layer region and the second layer region It is characterized by different materials.

(Configuration of nanoporous thin film)
The nanoporous thin film having a nanoporous structure in the present invention is a thin film having a plurality of pores having a nanometer size in space.

  The pores in the present invention can be formed by using molecules as templates as will be described later. As a result, pores having a space size of nanometer size, that is, a maximum diameter of 0.1 nm to 1 μm, more preferably 0.2 nm to 100 nm, and still more preferably 0.2 nm to 10 nm are formed. Such a nanometer-sized space corresponds to a so-called ultrafine particle or molecular size, and by introducing these substances into the pores, application as a functional material is possible.

  The nanoporous thin film having a nanoporous structure in the present invention is composed of a plurality of layer regions laminated along the film thickness direction, and the plurality of layer regions include a first layer region having a first pore. And a second layer region having a second pore. Then, the first pore and the second pore penetrate, and the materials constituting the first layer region and the second layer region are different.

  The nanoporous thin film in the present invention is composed of a plurality of layer regions laminated along the film thickness direction. Each layer region consists of a single layer thin film. FIG. 1 is a cross-sectional view schematically showing a film configuration of a nanoporous thin film in the present invention. Single-layer thin films are continuously formed and laminated along the film thickness direction. A plurality of laminated layer regions means a state in which one layer region is continuously formed along the film thickness direction as shown in FIG. 1A and forms a layer region as a whole. In addition, a plurality of layer regions means that it is composed of a pair of layer regions, and even a pair of configurations as shown in FIG. 1A has a pair of layer regions as shown in FIG. It does not matter even if it is configured, as long as the first layer region 1 and the second layer region 2 are included therein. Further, as shown in FIG. 1C, the respective film thicknesses may be different. The first layer region 1 and the second layer region 2 are respectively composed of a first film 3 and a second film 4. The material constituting at least one of the plurality of layer regions is preferably made of an inorganic oxide.

  As shown in FIG. 2A, the first membrane 3 has first pores 5 and the second membrane 4 has second pores 6. The size of the space of these pores is the aforementioned nanometer size.

  In the present invention, the size of the pores existing in one membrane can be made substantially the same. In other words, the second membrane can be configured to have pores of the same size as the first membrane, or the second membrane can be configured to have no pores of the same size as the first membrane. You can also In addition, the 1st film | membrane and 2nd film | membrane in this invention should just be contained in the laminated | stacked several film | membrane, and multiple corresponding parts may be contained like FIG.2 (b).

Further, it is possible to adopt a configuration in which the arrangement of pores existing in one film is substantially monolayered as shown in FIG. A monolayer configuration is a configuration in which the arrangement of pores is arbitrarily controlled for each row in the film thickness direction of the thin film, and is mounted on a sensor in which the distance from the substrate surface and sensitivity are related. In this case, the most sensitive area can be used efficiently.
Such a monolayer arrangement of the pore arrangement is applied only to one film as shown in FIG. 3 even in the configuration (FIG. 2) applied to both the first film and the second film. The pore arrangement of this film may be multilayered.

Furthermore, the first pore and the second pore penetrate.
The penetration means that there is a site where the pores existing in one membrane and the pores existing in the other membrane are connected as shown in FIG. The first pore and the second pore may pass through in a one-to-one relationship, or may pass through a plurality of one-to-one or a plurality of pairs, and may be appropriately determined according to the intended use. For example, when a substance is introduced into a pore and used, it is preferable to penetrate through a plurality of locations from the viewpoint of increasing the access path.

Furthermore, in the present invention, the first film and the second film are made of different materials.
The different materials in the present invention refer to different component ratios, bonding states, distributions of functional groups, etc. constituting the membrane. By being different, that is, by using different materials, different characteristics can be imparted to the film, and the different characteristics can be used. For example, if the first film and the second film are formed of materials having different isoelectric points, the combination of the surface potentials (positive charge and positive charge, positive charge and negative charge, negative charge and negative charge) is adjusted to pH. It becomes possible to control freely. For example, each inorganic oxide has a specific isoelectric point, and is suitable for a material constituting the film. Further, the surface treatment of the film can be selectively performed by using different materials for each film. As described above, the function of changing the material characteristics for each film constituting the thin film can be suitably used when a substance is supported and released in the pores. In particular, when the present invention is used as a molecular recognition material and mounted on a sensor, when a non-specifically adsorbed substance is further removed after specifically recognizing a recognition target molecule in a sample liquid and capturing it in a pore. In addition, this difference in material properties can be preferably used. Furthermore, the use as a functional material is also possible by using materials having different physical properties such as conductivity and non-conductivity. Such films with different materials can be formed by using different polymerizable monomers in the method for producing a nanoporous thin film according to the present invention described later.

  Even if different template molecules are used, it is possible to change the bonding state of the components constituting the membrane and the distribution of the functional groups. For example, a polymerizable monomer including a monomer (functional monomer) having a functional group that can be bonded (covalently bonded or noncovalently bonded) to a template molecule is used by using a concept of molecular imprinting method described later. In that case, a recognition site (pore) is formed in which complementary functional groups are arranged at complementary positions corresponding to the shape and size of the template molecule. That is, when the functional group arrangement in the template molecule is different, the arrangement of the functional group on the pore surface, that is, the distribution of the functional group is also different. The nanoporous thin film in the present invention includes those having such a difference for each film. For example, if an optical isomer molecule is used as a template molecule and a first film and a second film are produced, the composition of the entire film is almost the same, but the distribution of functional groups on the pore surface is different. A nanoporous thin film having different materials constituting the first film and the second film is formed. This is suitable for capturing various types of recognition target molecules while controlling the position.

Further, the first pore and the second pore may have different space sizes.
The size of the space means either the maximum value, the minimum value, or the shape of the diameter in the pore. The pores having different space sizes are formed by using different template molecules in the production method described later. Further, the size relationship between the first pore and the second pore is not limited. For example, the nanoporous thin film according to the present invention includes either one of FIGS. 4 (a) and 4 (b). Is also included. By changing the size of the pore space, different functions depending on the size of the pore can be used simultaneously. For example, it can be used as a molecular recognition site and a path through which molecules pass, a substance loading site and a raw material introduction path. Moreover, since the extra space can be reduced by controlling the size of the pores for each membrane, it is excellent in function separation and density increase.

  The nanoporous thin film according to the present invention is preferably formed on a substrate. By being formed on the substrate, it is possible to improve strength and durability. Further, the substrate itself that holds the nanoporous thin film such as a sensor or an electrode may be a device, and the substrate is not limited to its shape. For example, not only a flat plate shape but also a substrate having an uneven surface or a particle shape may be used. Furthermore, a porous material having a large pore size such as a macroporous material may be used as the substrate in order to increase the amount of the nanoporous thin film mounted. When a nanoporous thin film is formed on a substrate, the order of arrangement of the first film and the second film, and the size relationship between the first pore and the second pore space are limited. Any arrangement is possible as shown in FIGS. 5A, 5B, and 5C. Further, as shown in FIG. 5D, a base film 8 may be formed on the substrate 7, and a nanoporous thin film may be held thereon. Further, the base film may be combined and regarded as a substrate. By using a protective film or an adhesion film as the base film, the strength and durability can be increased.

  Next, the molecular recognition material provided with the nanoporous thin film according to the present invention will be described.

(Molecular recognition material)
Molecular recognition materials that specifically identify and bind to specific molecules are widely used for separation, sensor materials, and the like. As this molecular recognition material, not only so-called biomaterials such as genes, antibodies and sugar chains but also many artificially synthesized materials have been proposed in recent years. One of these techniques is a technique called molecular imprinting (molecular template polymerization). The molecular imprinting method is a method in which a molecule to be specifically recognized (hereinafter, recognition target molecule) is used as a template molecule. The general procedure of this method is shown below. First, a template molecule and a monomer (functional monomer) having a functional group capable of binding (covalent bond or non-covalent bond) to the template molecule are self-assembled in the reaction solution, and the template molecule / functional monomer Make a complex. Thereafter, a polymerization reaction is performed on the functional monomer to fix the position of the functional group while maintaining complementarity with the template molecule. Finally, template molecules are extracted and removed from the obtained polymer. As a result, a recognition site (pore) corresponding to the shape and size of the template molecule and having complementary functional groups arranged at complementary positions is constructed in the polymer. And this molecular recognition ability is exhibited by this recognition site. This molecular imprinting method is characterized in that a recognition material can be easily constructed according to a desired recognition target molecule in principle, and is expected as a method for producing artificial antibodies and artificial receptors.

  On the other hand, many devices such as QCM, SPR, LSPR, and FET have been proposed for detecting a recognition target molecule in a sample liquid that is specifically bound and captured by these molecular recognition materials. These detection devices detect changes in physical quantities such as weight change, refractive index change, and potential change caused by the molecular recognition material selectively capturing molecules to be recognized in the sample liquid, and detect the capture.

A so-called chemical sensor is constructed by combining these detection devices and molecular recognition materials.
However, the above-described detection device has a problem that if a non-specifically adsorbing substance that adsorbs nonspecifically exists in the detection region, a change in physical quantity due to the non-specifically adsorbed substance is detected, resulting in increased noise. In addition, among these detection devices used in chemical sensors, the detection mechanism increases the detection sensitivity as the position where the recognition target molecule in the sample liquid is captured is closer to the detection device surface. . SPR, LSPR, FET, etc. are typical examples. In these detection devices, even if the recognition target molecule is captured at a position away from the detection device surface of the sensor, the sensitivity does not increase. In addition, there is a problem that a very large noise occurs when the non-specifically adsorbed substance is present on the detection device surface of the sensor. Therefore, a molecular recognition material that can reduce noise for such a detection device is desired.

  A molecular recognition material according to the present invention is a molecular recognition material that selectively binds to a molecule to be recognized, and includes a nanoporous thin film having a nanoporous structure held on a substrate. A plurality of layer regions along the film thickness direction, the plurality of layer regions include a first layer region having a first pore and a second layer region having a second pore, The first layer region and the second layer region have in this order along the film thickness direction from the base, the first pore and the second pore penetrate, The materials constituting the first layer region and the second layer region are different.

  FIG. 6 is a diagram schematically showing a sensor device equipped with a molecule recognition material that selectively binds to a recognition target molecule according to the present invention. The substrate in the present invention is a detection device. A first film having first pores is formed on the detection device using the concept of molecular imprinting. The recognition site formed using the recognition target molecule as a template molecule is the first pore in the present invention. In the present invention, the first and second pores formed in the nanoporous thin film held on the detection device penetrate, and the first membrane and the second membrane are made of different materials.

  For example, each inorganic oxide has a specific isoelectric point, and is suitable for a material constituting the film. Further, the surface treatment of the film can be selectively performed by using different materials for each film. As described above, the function of changing the material characteristics for each film constituting the thin film can be suitably used when a substance is supported and released in the pores. In particular, when the present invention is used as a molecular recognition material and mounted on a sensor, when a non-specifically adsorbed substance is further removed after specifically recognizing a recognition target molecule in a sample liquid and capturing it in a pore. In addition, this difference in material properties can be preferably used. Furthermore, the use as a functional material is also possible by using materials having different physical properties such as conductivity and non-conductivity.

  In this way, different characteristics can be used depending on the material constituting the film. For example, if the first film and the second film are formed of materials with different isoelectric points, the combination of the surface potentials of each film (positive charge and positive charge, positive charge and negative charge, negative charge and negative charge) Can be freely controlled by pH. When performing the molecular recognition reaction, the recognition target molecule and the molecular recognition material according to the present invention are electrostatically controlled by controlling the recognition target molecule so that the first and second films have different charges. It will be attracted and the reaction promotion effect of molecular recognition can be obtained. Then, after completion of the recognition reaction, only the second film has the same charge with respect to the recognition target molecule. In this way, the nonspecifically adsorbed substance having the same sign as the recognition target molecule adsorbed on the surface of the second film can be removed by charge repulsion. As a result, it is possible to reduce the noise of the detection device due to the nonspecific adsorption substance.

  The presence of the second pore also contributes to the noise reduction effect. The molecular recognition reaction is performed by bringing the molecular recognition material into contact with the sample liquid containing the recognition target molecule. At this time, the molecules to be recognized are selectively captured by the first pores, that is, the recognition sites, through the second pores formed on the side opposite to the substrate. Therefore, many non-specifically adsorbed substances due to the presence of the second pores, in particular, substances larger than the size of the second pore space cannot pass through the second pores. Therefore, the noise reduction effect by the nonspecific adsorption substance can be obtained. In this way, the presence and / or concentration of the recognition target molecule in the sample liquid can be detected. When a sensor device having a high sensitivity near the detection device surface of the sensor is used as a substrate, the pores of the second film held on the detection device are multilayered as shown in FIG. The film thickness may be appropriately controlled. By controlling the second film thickness and making the distance between the second film surface and the sensor device surface equal to or greater than the distance at which the sensor sensitivity decreases, the surface of the molecular recognition material, that is, the surface of the second film is non-specific. Even if the adsorbing substance is adsorbed, noise can be reduced. When using SPR, this distance is 300 nm or more, more preferably 1 μm or more. When using LSPR, this distance is 50 nm or more, more preferably 100 nm or more. When using FET, this distance is 50 nm or more. More preferably, it is 100 nm or more.

  Furthermore, in the molecular recognition material according to the present invention, it is desirable that the size of the space of the second pore 6 is larger than the size of the space of the first pore 5 (FIG. 6C). With this configuration, it is possible to ensure accessibility to the first pores of the recognition target molecule while obtaining the noise reduction effect described above.

  Next, the manufacturing method of a nanoporous thin film is demonstrated in detail.

(Method for producing nanoporous thin film)
The method for producing a nanoporous thin film having a nanoporous structure according to the present invention comprises a step of bringing a first reaction solution containing a first template molecule and a first polymerizable monomer into contact with a substrate; Removing the solvent from the reaction solution, polymerizing the first polymerizable monomer to form a first polymerized film on the substrate, and second polymerizability different from the first polymerizable monomer A step of bringing a second reaction solution containing a monomer and a second template molecule into contact with the first polymerized film; and removing a solvent of the second reaction solution to polymerize the second polymerizable monomer. And a step of forming a second polymer film on the first polymer film and a step of removing the first and second template molecules.

  In the method for producing a nanoporous thin film having a nanoporous structure according to the present invention, a first solution containing a first template molecule is brought into contact with a substrate, and the first template molecule is immobilized on the substrate. Then, the step of bringing the third reaction solution containing the first polymerizable monomer into contact with the substrate, the solvent of the third reaction solution is removed, the first polymerizable monomer is polymerized, and the substrate A step of forming a first polymerized film thereon, and a second reaction solution containing a second polymerizable monomer different from the first polymerizable monomer and a second template molecule is used as the first polymerized film. A step of contacting the second reaction solution, removing the solvent of the second reaction solution, polymerizing the second polymerizable monomer, and forming a second polymer film on the first polymer film, and the first And removing the first and second template molecules.

  The method for producing a nanoporous thin film having a nanoporous structure according to the present invention comprises a step of bringing a first reaction solution containing a first template molecule and a first polymerizable monomer into contact with a substrate; Removing the solvent from the reaction solution, polymerizing the first polymerizable monomer to form a first polymerized film on the substrate, and adding a second solution containing a second template molecule to the first A fourth reaction solution containing a second polymerizable monomer different from the first polymerizable monomer after contacting the polymerized film and fixing the second template molecule on the first polymerized film Contacting the first polymerized film, removing the solvent of the fourth reaction solution, polymerizing the second polymerizable monomer, and forming a second polymerized film on the first polymerized film. And forming, and removing the first and second template molecules That.

In the method for producing a nanoporous thin film having a nanoporous structure according to the present invention, a first solution containing a first template molecule is brought into contact with a substrate, and the first template molecule is immobilized on the substrate. Then, the step of bringing the third reaction solution containing the first polymerizable monomer into contact with the substrate, the solvent of the third reaction solution is removed, the first polymerizable monomer is polymerized, and the substrate Forming a first polymer film thereon, bringing a second solution containing a second template molecule into contact with the first polymer film, and placing the second template molecule on the first polymer film After fixing, a step of bringing a fourth reaction solution containing a second polymerizable monomer different from the first polymerizable monomer into contact with the first polymer film, and a solvent of the fourth reaction solution, Removing, polymerizing the second polymerizable monomer and second polymerizing on the first polymerized film Forming a, characterized in that it comprises a step of removing the first and second template molecule.
With such a manufacturing method, the nanoporous thin film according to the present invention can be manufactured.

  FIG. 7 is a view schematically showing a method for producing a nanoporous thin film according to the present invention. The nanoporous thin film has a plurality of layer regions along the film thickness direction, and the material constituting at least one of the plurality of layer regions is preferably made of an inorganic oxide.

(Step of bringing the first reaction solution containing the first template molecule and the first polymerizable monomer into contact with the substrate)
FIG. 7A is a schematic diagram corresponding to this step.
The template molecule in this production method is a molecule that occupies a space that later becomes a pore.
Therefore, the first template molecule is appropriately selected according to the desired size of the first pore. Dendrimers and dendrons are suitable as template molecules having a desired size. Dendrimers having a polyamidoamine (PAMAM) structure are commercially available in various sizes, and are preferably used when pores having a size of about 1 nm to 30 nm are formed. Protein molecules that are biomaterials also have various sizes, and are suitably used when forming pores with a size of several nanometers to several tens of nanometers.

  When the nanoporous thin film according to the present invention is used as a molecular recognition material that selectively binds to the recognition target molecule, the first pore serves as a molecular recognition site, and the first template molecule Is selected according to the recognition target molecule itself in the specimen, or the size, chemical structure, etc. of the recognition target molecule.

The first polymerizable monomer is a raw material for forming the first polymer film. A thin film-like first polymer film 16 is formed by polymerization. Therefore, this polymerization method is preferably a method capable of forming a thin film, and if it is an organic reaction, living radical polymerization capable of controlling the reaction, and if it is an inorganic reaction, a sol-gel method or a liquid phase precipitation method is preferably used. In particular, the sol-gel method is preferable because it can be thinned by a spin coating method, a dip coating method, or a surface sol-gel method. Examples of the polymerization monomer used in the sol-gel method include metal compounds such as metal alkoxides, metal organic acid salts, nitrates, and chlorides, which are also preferably used in the present invention.
The first polymerized film is the first film of the nanoporous thin film according to the present invention.

  When the nanostructured thin film according to the present invention is used as the molecular recognition material that selectively binds to the recognition target molecule, the first pore formed in the first film functions as a molecular recognition site. Is preferred. Therefore, the first polymerizable monomer preferably has a functional group complementary to the template molecule and also functions as a functional monomer. For example, as the silane agent, compounds having various functional groups are commercially available and are suitable as polymerizable monomers used in the sol-gel method. Illustrative examples include alkylalkoxysilanes, aminoalkoxysilanes, and vinylalkoxysilanes. In addition, you may mix these monomers and the above-mentioned polymerizable monomer, and may use the mixture as a 1st polymerizable monomer.

  In this step, the first reaction solution 12 containing the first polymerizable monomer may be brought into contact with the substrate 7 in the presence of the first template molecule 10. Therefore, the first reaction solution 12 in which the first template molecule 10 and the first polymerizable monomer are mixed may be applied to the substrate 7 (FIG. 7A). In this case, the thickness of the first film can be adjusted by appropriately adjusting the concentration of the first template molecule and the first polymerizable monomer with respect to the solvent, and the mixing ratio of the first template molecule and the first polymerizable monomer. , And the pore arrangement (single layer or multilayer) and pore density in the first membrane can be controlled.

  Further, after the first solution containing the first template molecule 10 is brought into contact with the substrate 7 and the first template molecule 10 is immobilized on the substrate 7, the third reaction containing the first polymerizable monomer is performed. The solution 14 may be applied to the substrate 7 (FIG. 7B). In this case, when the first template molecule is immobilized on the substrate, it may be carried out by simple adsorption reaction, or the substrate and the first template molecule may be chemically bonded via a spacer molecule.

  The first and third reaction solutions contain a solvent. In the former method, the first template molecule and the first polymerizable monomer can be dissolved, and in the latter method, the first polymerizable monomer can be dissolved. To be elected. Further, this solvent is removed in the step of FIG. Therefore, it is preferable to include an alcohol that can be easily removed by drying, and an organic solvent such as toluene and acetonitrile.

  Note that a base film may be formed on the surface of the substrate before such a process is performed. The formation of the base film increases the efficiency of immobilizing template molecules performed in a later step. In addition, when the same material is used for the molecular recognition material, it is possible to form a mutual functional group on the base film by using the same material for the base film and the thin film forming the pores. It is also possible to increase the affinity between the pore (molecular recognition site) and the molecule to be recognized. In these cases, it is preferable to use a substrate on which a base film is formed as the substrate.

(Step of removing the solvent of the first or third reaction solution and polymerizing the first polymerizable monomer to form the first polymer film on the substrate)
FIG. 7C is a schematic view corresponding to this step.
First, the solvent of the first reaction solution 12 or the third reaction solution 14 applied on the substrate 7 is removed. Solvent removal is preferably performed by drying. By drying, only the solvent can be selectively removed.
Further, the first polymerizable monomer is polymerized on the substrate 7 to form a first polymer film 16 on the substrate 7. When the sol-gel method is used, the first polymerizable monomer described above forms an inorganic polymer through a hydrolysis reaction and a condensation reaction. These reaction rates can be controlled by the composition of the reaction solution, such as the environment such as temperature and humidity, the pH, the amount of water, the type of polymerizable monomer used, and the mixing ratio.

  Among the sol-gel methods, there is a method called a surface sol-gel method in which a polymerizable monomer is provided on a substrate and washed with a predetermined solvent. This surface sol-gel method can form an ultrathin film layer having a thickness of angstroms or nanometers, and is suitably used in the present invention. In particular, the first solution containing the first template molecule is applied to the substrate, the first template molecule is immobilized on the substrate, and then the third reaction solution containing the first polymerizable monomer is applied to the substrate. It is suitable when using the method to do. The substrate on which the first template molecule is immobilized is immersed in a third reaction solution containing the first polymerizable monomer. After a predetermined time, the substrate is taken out and the surface of the substrate is washed with a predetermined solvent. By this washing, excess first polymerizable monomer is washed away. Thereafter, the solvent is removed by drying to form a first polymer film on the substrate. However, when this surface sol-gel method is used, the thickness of the polymer film formed at one time is very thin, and depending on the size of the template molecule, the surroundings cannot be sufficiently surrounded. In this case, the step of FIG. 7 (a) or (b) and the step of FIG. 7 (c), that is, immersion, washing and drying in the reaction solution containing the first polymerizable monomer may be repeated a plurality of times.

(Step of bringing a second reaction solution containing a second polymerizable monomer different from the first polymerizable monomer and a second template molecule into contact with the first polymerized film)
FIG. 7D is a schematic view corresponding to this step.
In this step, a second polymerizable monomer different from the first polymerizable monomer is used, and in the presence of the second template molecule, the second reaction solution 13 containing the second polymerizable monomer is added to the first reaction solution 13. If it contacts the surface of the polymerization layer 16, the operation in this step may be the same as the step in FIG. Therefore, a second reaction solution obtained by mixing the second template molecule and the second polymerizable monomer may be applied to the first polymer film.

  In addition, after the second solution containing the second template molecule 11 is brought into contact with the first polymer film 16 and the second template molecule 11 is immobilized on the first polymer film 16, the first polymerization is performed. A fourth reaction solution 15 containing a second polymerizable monomer different from the polymerizable monomer may be applied to the first polymer film 16 (FIG. 7E).

Further, the first template molecule and the second template molecule may be the same or different.
However, when the nanoporous thin film according to the present invention is used as a molecule recognition material, the second template molecule is preferably a larger molecule than the first template molecule.

(Step of removing the solvent of the second or fourth reaction solution, polymerizing the second polymerizable monomer, and forming a second polymer film on the first polymer film)
FIG. 7F is a schematic diagram corresponding to this step.
If the second polymer film 17 is formed on the first polymer film 16, the operation in this step may be the same as the step in FIG.

(Step of removing the first and second template molecules)
FIG. 7G is a schematic diagram corresponding to this step.
This step is a step of removing the first and second template molecules 10 and 11 from the first and second polymer films 16 and 17. By this step, first and second pores 5 and 6 are formed in these polymer films.

Therefore, the removal method in this step is not limited as long as the template molecule can be suitably removed. For example, light irradiation, ozone exposure, and decomposition of template molecules by heat treatment can be mentioned. These methods are preferred because of the high removal rate of template molecules.
It can also be removed by extraction with an organic solvent, acid, or alkali solution. In these solvent extraction methods, it is possible to remove template molecules without altering the polymerized film by appropriately selecting a solvent according to the material of the polymerized film.

When the nanoporous thin film according to the present invention is used as a molecular recognition material, the presence of complementary functional groups arranged on the pore (molecular recognition site) surface corresponding to the shape and size of the template molecule is important. . Therefore, a solvent extraction method with a low possibility of alteration of the polymer film is preferable.
A combination of these methods may be used.

  Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples, and nanostructures having similar functions and effects such as materials, composition conditions, reaction conditions, and the like. It can be freely changed as long as the porous thin film can be obtained.

  This example is an example of forming a porous thin film in which pores having substantially the same size are arranged in a single layer. The porous thin film shown in the present example is a film that is the basis of the configuration of the nanoporous thin film according to the present invention.

(Thin film production)
In this example, two types of substrates were used.
One type is a silicon substrate. First, the surface of the silicon substrate was washed with acetone, isopropyl alcohol, and pure water, and UV irradiation was performed for 10 minutes in an ozone generator to clean the substrate surface.
The other type is a gold substrate in which gold is sputtered on a silicon substrate to form a 100 nm thick gold layer on the surface. The gold substrate was subjected to a cleaning process similar to that for the silicon substrate. Further, this gold substrate was immersed in an ethanol solution of 10 mM mercaptoethanol overnight, thoroughly washed with ethanol, and further dried by nitrogen blowing. Through the above operation, a hydroxyl group was formed on the gold substrate surface.

Next, a reaction solution was prepared. The template molecule was a fourth generation of PAMAM dendrimer having an OH group at the end group, and titanium butoxide was used as the polymerizable monomer.
First, a 1: 1 mixed solvent of toluene and ethanol was prepared, and a dendrimer was mixed with this mixed solvent at a concentration of 0.05 mM and stirred. Next, titanium butoxide was mixed at a concentration of 10 mM. Thus, a reaction solution was prepared.

  Next, this reaction solution was applied onto a silicon substrate and a gold substrate by a spin coating method, and the substrate surface and the reaction solution were brought into contact with each other. The spin coating conditions were 500 rpm for 5 seconds, followed by 3000 rpm for 60 seconds. During the spin coating operation, the solvent of the reaction solution was evaporated and removed. Moreover, hydrolysis and dehydration condensation of titanium butoxide proceeded by moisture contained in the reaction solution and moisture in the air, and a polymer film was formed on the silicon substrate and the gold substrate.

  Next, as a template molecule removal process, each of the silicon substrate and the gold substrate on which the polymer film was formed was irradiated with UV for 10 minutes in an ozone generator.

(Thin film analysis)
High sensitivity reflection infrared spectroscopy (IRRAS) was performed on the thin film formed on the gold substrate by the above method. As for the thin film before the removal treatment of the template molecule, an absorption peak derived from dendrimer and an absorption peak derived from titanium oxide were confirmed. Furthermore, the absorption peak intensity derived from a dendrimer decreased by performing a removal process. From this, it is confirmed that the template molecule is removed by the template molecule removal process in this example.

(Pore observation)
The surface and cross section of the thin film formed on the silicon substrate by the above method were observed with an electron microscope. It was confirmed that a thin film having a plurality of pores having a diameter of about 5 nm was formed on the Si substrate. Furthermore, the state where each pore exists independently was also confirmed. In addition, a state in which the pores were monolayered with respect to the thin film was observed.

  From the above results, in this example, a porous thin film in which pores of substantially the same size, which are the basis of the configuration of the nanoporous thin film according to the present invention, are arranged in a single layer can be formed. confirmed.

  This example is another example of forming a porous thin film in which pores having substantially the same size are arranged in a single layer. The porous thin film shown in this example is a film that is the basis of the structure of the nanoporous thin film according to the present invention.

(Thin film production)
In this example, two types of substrates were used as in Example 1. The cleaning method is the same as that in the first embodiment.
Next, a reaction solution for forming a base film was prepared. First, a 1: 1 mixed solvent of toluene and ethanol was prepared, and titanium butoxide was mixed at a concentration of 100 mM to obtain a reaction solution.
Next, a base film was formed on the surfaces of the silicon substrate and the gold substrate. The cleaned silicon substrate and gold substrate were immersed in the reaction solution for 3 minutes. Then, the excess reaction solution was removed by immersing in toluene and washing with ethanol. Furthermore, it was dried by nitrogen blowing. Hydrolysis of titanium butoxide proceeds by water contained in the reaction solution or water supplied from moisture in the air, and further polymerization proceeds by dehydration condensation. In addition, after immersion in toluene or after nitrogen blowing, it may be immersed in water or water-saturated toluene for about 1 minute to promote the hydrolysis and condensation reaction more actively. The process from immersion to drying was repeated several times to form a base film made of titanium oxide on the silicon substrate and the gold substrate.
In this embodiment, a silicon substrate and a gold substrate having such a base film formed on the surface are used as a base.

  Next, a fourth generation of PAMAM dendrimer having an OH group at the end group was used as a template molecule to prepare a 1 wt% solution of this dendrimer (solvent: ethanol / methanol mixed solvent). The substrate was immersed in this dendrimer solution for 20 minutes to adsorb the dendrimer to the substrate surface. Further, washing with methanol and drying with nitrogen blowing were performed.

  Next, a reaction solution similar to the reaction solution used for forming the base film was prepared. The substrate was immersed in the reaction solution and washed with toluene and ethanol in the same manner as in the base film formation step. Furthermore, it was dried by nitrogen blowing. This process from immersion to drying was repeated several times to form a polymerized film on the substrate.

  Next, as a template molecule removal process, each of the silicon substrate and the gold substrate on which the polymer film was formed was irradiated with UV for 10 minutes in an ozone generator.

(Thin film analysis)
High sensitivity reflection infrared spectroscopy (IRRAS) was performed on the thin film formed on the gold substrate by the above method. As for the thin film after template molecule adsorption, an absorption peak derived from dendrimer and an absorption peak derived from titanium oxide were confirmed. After the polymerization, the thin film before the removal treatment of the template molecule was confirmed to have an absorption peak derived from dendrimer and an absorption peak derived from titanium oxide. In addition, it was also confirmed that the absorption peak intensity derived from titanium oxide is increased as compared with that after adsorption of the template molecule. Furthermore, it was also confirmed that the absorption peak intensity derived from the dendrimer decreases by removing the template molecule. From this, in this example, it was confirmed that the polymer film was formed in the presence of the template molecule, and the template molecule was removed by the template molecule removal treatment.

(Pore observation)
The surface and cross section of the thin film formed on the silicon substrate by the above method were observed with an electron microscope. It is confirmed that a thin film having a plurality of pores having a diameter of about 5 nm is formed on the Si substrate. Furthermore, the state where each pore exists independently was also confirmed. In addition, a state in which the pores were monolayered with respect to the thin film was observed.

  From the above results, in this example, a porous thin film in which pores of substantially the same size, which are the basis of the configuration of the nanoporous thin film according to the present invention, are arranged in a single layer can be formed. confirmed.

  In this example, a nanoporous thin film is formed on a substrate to produce a molecular recognition material and a sensor.

(Crystal oscillator substrate)
In this embodiment, a crystal oscillator (hereinafter referred to as a QCM chip) is used for the substrate.
QCM is a method of measuring a minute weight change using a crystal resonator as a sensor. When a substance adheres to the electrode surface of the crystal oscillator, the resonance frequency varies (lowers) according to the mass of the substance. In this example, a quartz crystal coated with gold was used as a substrate.

(Production of molecular recognition materials)
First, pretreatment of the QCM chip as the substrate was performed. Concentrated sulfuric acid: hydrogen peroxide solution was mixed at a ratio of 3: 1 to prepare a piranha cleaning solution. Next, this piranha cleaning solution was dropped on the gold surface of the QCM chip, and then allowed to stand for 5 minutes, and then thoroughly washed with pure water. This operation was repeated three times and dried by nitrogen blowing. Next, this QCM chip was immersed in an ethanol solution of 10 mM mercaptoethanol overnight, thoroughly washed with ethanol, and further dried by nitrogen blowing. Through the above operation, a hydroxyl group was formed on the gold surface.

Next, a reaction solution for forming a base film was prepared. The polymerizable monomer was titanium butoxide, and it was prepared in the same manner as the reaction solution for forming the base film in Example 2. Further, the reaction solution for forming the base film was applied on the gold surface of the QCM chip in the same manner as in Example 2, and the solvent of the reaction solution was removed. Titanium butoxide was polymerized to form a base film on the gold surface of the QCM chip.
In this example, a QCM chip having such a base film formed on the surface was used as a substrate.

  Next, a first polymer film was formed. Arginine, which later becomes a recognition target molecule, was used as the first template molecule. Arginine is a basic amino acid with an isoelectric point of 10.8. An aqueous solution of this arginine was prepared. The substrate was immersed in this arginine solution for 10 minutes to adsorb arginine on the surface of the base film of the substrate. At this time, it is preferable to make the arginine aqueous solution weakly alkaline and charge the surface of the base film formed earlier to the negative charge side. Further, it was washed with pure water and dried.

  Next, a first reaction solution was prepared in the same manner as the reaction solution used for forming the base film, and the substrate was immersed in the first reaction solution for 3 minutes. After washing with toluene and ethanol, it was immersed in water for 1 minute to promote hydrolysis condensation of the alkoxide. Further, the first reaction solution was dried by nitrogen blowing. This process from immersion to drying was repeated several times to form a first polymer film on the base film of the substrate.

  Next, a second reaction solution was prepared. In the second reaction solution, the same arginine as the first template molecule was used as the second template molecule, and aluminum butoxide was used as the second polymerizable monomer. The arginine was mixed with a 1: 1 mixed solvent of toluene and ethanol, and aluminum butoxide was further mixed to prepare a second reaction solution.

  Next, this second reaction solution was applied onto the substrate on which the first polymer film was formed by spin coating, and the solvent of the second reaction solution was removed. Aluminum butoxide was polymerized to form a second polymer film on the surface of the first polymer film.

  Next, as described above, UV irradiation was performed for 10 minutes in an ozone generator as a removal process of the first and second template molecules.

  Through the above operation, a nanoporous thin film was formed on the substrate. In this embodiment, titanium butoxide is used as the first polymerizable monomer and aluminum butoxide is used as the second polymerizable monomer. Titanium oxide and aluminum oxide formed by the respective polymerizations have different isoelectric points. The isoelectric point of titanium oxide is around 6 and the isoelectric point of aluminum oxide is around 9.

(Chemical sensor noise verification)
As a comparative example, a porous film 1 in which only the first polymer film was formed without forming the second polymer film and the template molecule was removed was produced on a similar substrate, and used as a comparative material 1.

  About the noise at the time of using a chemical sensor, using the molecular recognition material and the comparative material 1 according to the present embodiment, the recognition target molecule is detected from the sample liquid in which both the recognition target molecule and the nonspecifically adsorbed substance are mixed. It is verified by performing detection. In this example, an aqueous solution in which arginine, which is a recognition target molecule, and egg white lysozyme, which is a basic protein with an isoelectric point of around 11, was used as a nonspecific adsorption substance in the sample solution.

First, the resonance frequency in the dry state of the QCM chip on which the comparative material 1 was formed was measured, and the value was set as the initial value. Next, arginine and egg white lysozyme were mixed and the comparative material 1 was added to the liquid adjusted to pH10. After dipping for 10 minutes, the comparative material 1 was washed several times with the washing solution 1 (adjusted to pH 10) and dried. Then, the resonance frequency of the comparative material 1 was measured again, and when the frequency was stabilized, the value was taken as the coupling value 1, and the difference from the initial value was calculated. This difference is defined as a frequency change ΔF1, and ΔF1 corresponds to the adsorption amount of arginine and egg white lysozyme. Thereafter, the comparative material 1 was washed several times with the washing solution 2 (adjusted to pH 7.5) and dried. Then, the resonance frequency of the comparative material 1 was measured again, and when the frequency was stabilized, the value was set as the coupling value 2, and the difference from the initial value was calculated. This difference is defined as a frequency change ΔF2, and ΔF2 corresponds to the adsorption amount after washing arginine and egg white lysozyme. Thereafter, the comparative material 1 was washed with alkali (1 wt% NH ₃ aqueous solution) and acid (pH 5 hydrochloric acid) to remove the adsorbed substances. Completion of the removal is confirmed by returning the resonance frequency at the time of drying after the removal to the initial value.

  By performing the above operation, the concentration of egg white lysozyme was kept constant, and only the concentration of arginine was changed to perform multipoint measurement, and a calibration curve in which the binding value 2 was plotted against the concentration of arginine was created. (Fig. 8)

Next, a calibration curve was similarly prepared for the QCM chip on which the molecular recognition material according to this example was formed.
In the calibration curve, the region where the concentration and the binding value are linearly related is the concentration detectable range, the region where the relationship is broken on the low concentration side is the concentration undetectable range, and the concentration detection not possible on the low concentration side of the concentration detectable range. The density at the boundary with the possible range is the lower limit of detection.

Since the comparative material 1 is made of titanium oxide, the surface potential is negatively charged during cleaning with the cleaning liquid 1 (pH 10) and the cleaning liquid 2 (pH 7.5). On the other hand, since the isoelectric point of arginine is around 10.8 and the isoelectric point of egg white lysozyme is around 11.2, the washing solution is positively charged. Therefore, it was difficult to remove these molecules, both those bound to the recognition site and those non-specifically bound to the surface other than the recognition site.
On the other hand, in the molecular recognition material according to the present example, the second polymerization layer is made of aluminum oxide and is positively charged during cleaning with the cleaning liquid 2 (pH 7.5). Therefore, those non-specifically bound to the surface other than the recognition site are easily removed. As a result, the amount of nonspecific adsorption decreased.
These were confirmed from the fact that the lower limit of detection when the molecular recognition material according to this example was used was lower than the lower limit of detection when the comparative material 1 was used.

  By the above operation, the effect of noise reduction by the molecular recognition material according to the present invention was confirmed.

  In this embodiment, a nanoporous thin film is formed on a substrate to produce a molecular recognition material and a sensor.

(FET device substrate)
In this example, an FET device substrate was used as the substrate.
The FET device substrate is a device having a structure as shown in FIG. 9 in which a source region 19, a drain region 20, a channel region 21, and a gate insulating film 22 are formed on a semiconductor substrate 18. A known method can be applied to the method of manufacturing the FET device substrate. For example, a p-type silicon substrate having a (100) orientation is used, and an impurity (for example, phosphorus) for forming an n-type semiconductor is diffused or implanted by a thermal diffusion method or an ion implantation method to form a source region and a drain region. In addition, it is possible to use a general FET manufacturing method in which a gate insulating film is formed by heat treatment in a dry oxygen atmosphere or formation of a silicon nitride film by a CVD method.
In this example, an FET device substrate was used as a substrate, and the molecular recognition material according to the present invention was formed on the gate insulating film.

  The source region and the drain region are connected to an electrode and an electric circuit (not shown), and when the recognition target molecule in the sample liquid is captured by the molecular recognition material on the gate insulating film, the current value between the source and the drain changes. . Therefore, by measuring this change, the FET device equipped with the molecular recognition material according to the present embodiment can be used as a chemical sensor for detecting the presence and / or concentration of the recognition target molecule in the sample liquid.

(Production of molecular recognition materials)
First, the surface of the FET device substrate was cleaned by UV irradiation for 10 minutes in an ozone generator.
Next, a reaction solution for forming a base film was prepared. The polymerizable monomer was titanium butoxide, and it was prepared in the same manner as the reaction solution for forming the base film in Example 2.
Further, a reaction solution for forming a base film was applied on the gate insulating film by the same method as in Example 2, and the solvent was removed. Titanium butoxide was polymerized to form a base film on the gate insulating film.
In this example, an FET device substrate having such a base film formed on the surface was used as a substrate.

  Next, arginine, which later becomes a recognition target molecule, was used as the first template molecule. Arginine is a basic amino acid with an isoelectric point of 10.8. An aqueous solution of this arginine was prepared. The substrate was immersed in this arginine solution for 10 minutes to adsorb arginine on the substrate surface. At this time, it is preferable to make the arginine aqueous solution weakly alkaline and charge the surface of the base film formed earlier to the negative charge side. Further, it is washed with pure water and dried.

  Next, a first reaction solution was prepared in the same manner as the reaction solution used for forming the base film, and the substrate was immersed in the first reaction solution for 3 minutes. After washing with toluene and ethanol, it was immersed in water for 1 minute to promote hydrolysis and condensation of titanium butoxide. Furthermore, it was dried by nitrogen blowing. Thus, the solvent of the first reaction solution was removed. This process from immersion to drying was repeated several times to form a first polymer film on the substrate.

  Next, a second reaction solution was prepared. In the second reaction solution, the second generation of the PAMAM dendrimer having an OH group at the end group was used as the second template molecule, and aluminum butoxide was used as the polymerizable monomer. This dendrimer was mixed with a mixed solvent of toluene and ethanol 1: 1, and aluminum butoxide was further mixed to prepare a second reaction solution.

  Next, this second reaction solution was applied onto the substrate on which the first polymer film was formed by spin coating, and the solvent of the second reaction solution was removed. Aluminum butoxide was polymerized to form a second polymer film on the surface of the first polymer film.

Through the above operation, a nanoporous thin film is formed on the substrate. In this example, arginine is used as the first template molecule, and the second generation of PAMAM dendrimer is used as the second template molecule. Arginine is a smaller molecule than the second-generation dendrimer, and pores having different space sizes are formed by laminating polymer films along the film thickness direction using these different template molecules. In this example, the first pore formed on the substrate side uses arginine as a template, and the second pore formed on the side opposite to the substrate uses a second generation dendrimer as a template. The size of the pore space is larger than the size of the first pore space. This was confirmed by electron microscope observation.
The first pore is produced using the recognition target molecule as a template, and this first pore becomes a recognition site for the molecule. In particular, in this embodiment, molecular recognition sites are formed in a region close to the surface of the substrate, that is, the FET device substrate. This is suitable for FET devices with high sensitivity in the region close to the surface.

(Chemical sensor noise verification)
As a comparative example, a porous film 2 in which only the first polymer film was formed without forming the second polymer film and the template molecule was removed was prepared on a similar substrate, and used as a comparative material 2.

  Regarding noise when using the chemical sensor, the molecular recognition material according to this example and the comparative material 2 are used to detect the recognition target molecule from the sample liquid in which both the recognition target molecule and the nonspecifically adsorbed substance are mixed. It is verified by performing detection. In this example, an aqueous solution in which arginine as a recognition target molecule and egg white lysozyme as a non-specific adsorbent were mixed in the sample liquid.

  First, the FET device on which the comparative material 2 was formed was immersed in a phosphate buffer solution. Thereafter, the arginine solution was injected into the buffer solution. Furthermore, the egg white lysozyme solution was injected into the buffer solution. During this time, the current change between the source and the drain was measured. A similar operation was performed on an FET device having a molecular recognition material formed on the surface. The effect of noise is verified by comparing the ratio of the current change amount when the arginine solution is injected and the current change amount when the egg white lysozyme solution is injected between the comparative material 2 and the molecular recognition material according to this example. Is done. In Comparative Material 2, the current change (corresponding to noise) when the egg white lysozyme solution was added was large, but was small in the molecular recognition material according to this example.

  By the above operation, the effect of noise reduction by the molecular recognition material according to the present invention was confirmed.

  Support materials that carry substances such as catalysts and functional molecules, adsorbent materials that adsorb substances, separation used for separation and detection of substances, molecular recognition, sensor materials, conductive materials used for transport and exchange of substances, It can be used in a wide range of nanostructure materials used for electronic devices, optical devices, micro devices, and the like.

1. First layer region 2. Second layer region 3. First membrane 4. Second membrane 5. First pore 6. Second pore 7. Base 8 8. Underlayer film Support material 10. First template molecule 11. Second template molecule 12. First reaction solution 13. Second reaction solution 14. Third reaction solution 15. Fourth reaction solution 16. First polymerized film 17. Second polymerized film 18. Semiconductor substrate 19. Source region 20. Drain region 21. Channel region 22. Gate insulation film

Claims (13)

A nanoporous thin film having a nanoporous structure,
It has a plurality of layer regions along the film thickness direction,
The plurality of layer regions include a first layer region having a first pore and a second layer region having a second pore,
The first pore and the second pore penetrate,
A nanoporous thin film characterized in that materials constituting the first layer region and the second layer region are different.   2. The nanoporous thin film according to claim 1, wherein the material constituting at least one of the plurality of layer regions is made of an inorganic oxide.   The nanoporous thin film according to claim 1, wherein isoelectric points of materials constituting the first layer region and the second layer region are different.   The nanoporous thin film according to claim 1, wherein the first pore and the second pore have different space sizes. A molecular recognition material that selectively binds to a recognition target molecule,
Comprising a nanoporous thin film having a nanoporous structure held on a substrate;
The nanoporous thin film has a plurality of layer regions along the film thickness direction,
The plurality of layer regions include a first layer region having a first pore and a second layer region having a second pore,
The first layer region and the second layer region have in this order along the film thickness direction from above the substrate,
The first pore and the second pore penetrate,
A molecular recognition material characterized in that materials constituting the first layer region and the second layer region are different.   The molecular recognition material according to claim 5, wherein the size of the space of the second pore is larger than the size of the space of the first pore. A sensor for detecting the presence and / or concentration of a molecule to be recognized in a sample liquid,
Comprising a nanoporous thin film having a nanoporous structure held on a detection device;
The nanoporous thin film has a plurality of layer regions along the film thickness direction,
The plurality of layer regions include a first layer region having a first pore and a second layer region having a second pore,
The first layer region and the second layer region have in this order along the film thickness direction from above the substrate,
The first pore and the second pore penetrate,
The material which comprises said 1st layer area | region and said 2nd layer area | region differs.   8. A sensor according to claim 7, wherein the detection device is a FET device. A method for producing a nanoporous thin film having a nanoporous structure,
Contacting a substrate with a first reaction solution containing a first template molecule and a first polymerizable monomer;
Removing the solvent of the first reaction solution, polymerizing the first polymerizable monomer, and forming a first polymer film on the substrate;
Contacting a second reaction solution containing a second polymerizable monomer different from the first polymerizable monomer and a second template molecule with the first polymerized film;
Removing the solvent of the second reaction solution, polymerizing the second polymerizable monomer, and forming a second polymer film on the first polymer film;
Removing the first and second template molecules, and a method for producing a nanoporous thin film. A method for producing a nanoporous thin film having a nanoporous structure,
A first solution containing a first template molecule is brought into contact with the substrate, the first template molecule is immobilized on the substrate, and then a third reaction solution containing a first polymerizable monomer is added to the substrate. Contacting with
Removing the solvent of the third reaction solution, polymerizing the first polymerizable monomer, and forming a first polymer film on the substrate;
Contacting a second reaction solution containing a second polymerizable monomer different from the first polymerizable monomer and a second template molecule with the first polymerized film;
Removing the solvent of the second reaction solution, polymerizing the second polymerizable monomer, and forming a second polymer film on the first polymer film;
Removing the first and second template molecules, and a method for producing a nanoporous thin film. A method for producing a nanoporous thin film having a nanoporous structure,
Contacting a substrate with a first reaction solution containing a first template molecule and a first polymerizable monomer;
Removing the solvent of the first reaction solution, polymerizing the first polymerizable monomer, and forming a first polymer film on the substrate;
A second solution containing a second template molecule is brought into contact with the first polymer film, and after fixing the second template molecule on the first polymer film, the first polymerizable monomer and Contacting the first polymerized film with a fourth reaction solution containing a different second polymerizable monomer;
Removing the solvent of the fourth reaction solution, polymerizing the second polymerizable monomer, and forming a second polymer film on the first polymer film;
Removing the first and second template molecules, and a method for producing a nanoporous thin film. A method for producing a nanoporous thin film having a nanoporous structure,
A first solution containing a first template molecule is brought into contact with the substrate, the first template molecule is immobilized on the substrate, and then a third reaction solution containing a first polymerizable monomer is added to the substrate. Contacting with
Removing the solvent of the third reaction solution, polymerizing the first polymerizable monomer, and forming a first polymer film on the substrate;
A second solution containing a second template molecule is brought into contact with the first polymer film, and after fixing the second template molecule on the first polymer film, the first polymerizable monomer and Contacting the first polymerized film with a fourth reaction solution containing a different second polymerizable monomer;
Removing the solvent of the fourth reaction solution, polymerizing the second polymerizable monomer, and forming a second polymer film on the first polymer film;
Removing the first and second template molecules, and a method for producing a nanoporous thin film.   The method for producing a nanoporous thin film according to any one of claims 9 to 12, wherein the first template molecule and the second template molecule are different molecules.

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