JP6702488B2 - Conductive material for biosensor and biosensor - Google Patents

Description

The present invention relates to a biosensor conductive material and a biosensor using a metal nanowire.

Various methods have been developed as a method for qualitatively or quantitatively determining a specific component in a sample using a bio-related substance.
For example, immunochromatography is a test method utilizing an antigen-antibody reaction, and can detect a target substance by a simple procedure, and is therefore practically used for influenza virus tests, pregnancy tests, and the like. Immunochromatography has a great advantage in terms of portability and compatibility with various target substances, but has a problem such as poor sensitivity. Further, although the inspection time is relatively short, there are cases where detection in a shorter time is required. Specifically, in immunochromatography, when the target substance is low in concentration, it cannot be detected and the screening test accuracy is low. It takes about 5 to 30 minutes for the sample to move on the membrane. (Mobile phase) is required, and a highly viscous sample needs to be diluted, which may complicate the operation. There is still room for improvement to realize early detection and treatment of infectious diseases. ..

In order to solve the above problems, a biosensor using an electrochemical method has been developed and many studies have been made. For example, electrode materials and electrode structures have been studied, and recently, highly sensitive biosensors using nanomaterials such as carbon nanotubes have been studied (see, for example, Patent Documents 1 and 2).

JP, 2008-64724, A JP, 2010-230379, A

However, a biosensor using carbon nanotubes has a problem that the manufacturing process is complicated, and it is difficult to form a thin film or a pattern for carbon nanotubes. There is also a problem that carbon nanotubes have lower conductivity than metals.

The present invention has been made in view of the above problems, and a main object of the present invention is to provide a biosensor conductive material capable of increasing the sensitivity of the biosensor and a biosensor using the same.

The present invention, in order to achieve the above object, has a base material and a conductive layer formed on the base material and containing a resin and a metal nanowire, wherein the conductive layer is at least a part of the metal nanowire. Provides a conductive material for a biosensor, which has a metal nanowire exposed portion exposed on the surface of the conductive layer.

In the present invention, since the conductive layer can improve the conductivity by containing the metal nanowire, by using the biosensor conductive material of the present invention, it is possible to perform a highly sensitive and short-time inspection. It is also possible to detect trace components. Further, in the present invention, since the conductive layer contains the metal nanowire and the resin, pattern formation and thinning are easy.

In the above invention, the conductive layer is preferably formed in a pattern on the base material. It is possible to obtain a biosensor conductive material according to various forms.

Further, in the present invention, a specific binding substance that specifically binds to a target substance or the target substance may be fixed to the exposed portion of the metal nanowire. In this case, the specific binding substance is preferably an antibody or an aptamer. In the present invention, a target substance or a specific binding substance can be detected by utilizing a specific reaction.

Further, in the present invention, an insulating layer may be formed in a pattern on the base material on which the conductive layer is formed. It is possible to prevent the sample from coming into contact with the electrodes or wirings connected to the conductive layer.

The present invention also provides a biosensor including a sensor unit having the above-described biosensor conductive material.

In the present invention, by having the above-mentioned biosensor conductive material, it is possible to perform an inspection with high sensitivity and in a short time, and it is also possible to detect a trace component.

INDUSTRIAL APPLICABILITY The present invention has an effect that it is possible to provide a biosensor that can be tested with high sensitivity and in a short time, and that can detect even a trace amount of component.

It is a schematic sectional drawing which shows an example of the electrically conductive material for biosensors of this invention. It is a schematic sectional drawing which shows an example of the electrically conductive layer in the electrically conductive material for biosensors of this invention. It is a schematic sectional drawing which shows the other example of the electrically conductive material for biosensors of this invention. It is a schematic diagram which shows an example of the usage method of the biosensor of this invention. It is a schematic sectional drawing which shows the other example of the electrically conductive material for biosensors of this invention. It is the schematic plan view and sectional drawing which show the other example of the electrically conductive material for biosensors of this invention. It is a schematic plan view which shows the other example of the electrically conductive material for biosensors of this invention. It is a schematic diagram which shows an example of the biosensor of this invention. It is a schematic diagram which shows the other example of the biosensor of this invention.

Hereinafter, the conductive material for biosensor and the biosensor of the present invention will be described in detail.

A. Biosensor Conductive Material The biosensor conductive material of the present invention has a base material and a conductive layer formed on the base material and containing a resin and a metal nanowire, and the conductive layer is a metal nanowire. At least a part thereof has a metal nanowire exposed portion exposed on the surface of the conductive layer.

The conductive material for a biosensor of the present invention will be described with reference to the drawings.
FIG. 1A is a schematic cross-sectional view showing an example of a conductive material for a biosensor of the present invention, and FIG. 1B is an enlarged view of a broken line portion of FIG. 1A. As illustrated in FIG. 1A, the biosensor conductive material 1 includes a base material 2 on which a conductive layer 3 containing a resin and metal nanowires is formed. As illustrated in FIG. 1B, the conductive layer 3 has a metal nanowire exposed portion 5 in which a part of the metal nanowire 4 is exposed on the surface of the conductive layer 3.

Here, "at least a part of the metal nanowire is exposed on the surface of the conductive layer" means that the metal nanowire is in contact with the surface of the conductive layer. For example, it refers to the case as shown in FIG. 2(a) or FIG. 2(b). On the other hand, even if the metal nanowires 4 are present on the surface of the conductive layer 3 as shown in FIG. 2C, when the metal nanowires 4 are covered with the resin contained in the conductive layer 3, the metal nanowires are Is not exposed to the surface of the conductive layer.

FIG. 3A is a schematic cross-sectional view showing another example of the biosensor conductive material of the present invention, and FIG. 3B is an enlarged view of a broken line portion of FIG. 3A. As illustrated in FIGS. 3( a) and 3 (b ), in the biosensor conductive material 1, a target substance is provided in the metal nanowire exposed portion 5 where a part of the metal nanowire 4 is exposed on the surface of the conductive layer 3. The specific binding substance 7 that specifically binds is fixed.
In the example shown in FIG. 3, the specific binding substance is fixed to the exposed portion of the metal nanowire, but the present invention is not limited to this, and the target substance may be fixed to the exposed portion of the metal nanowire.
In the present invention, since the conductive layer has the exposed portion of the metal nanowire, the specific binding substance or the target substance can be fixed to the metal nanowire.

FIG. 4 is a schematic diagram showing an example of a method for detecting a target substance using the biosensor conductive material of the present invention. The biosensor conductive material shown in FIG. 4 is the same as the biosensor conductive material shown in FIG. 3. As shown in FIG. 4, in the biosensor conductive material 1, when a sample containing the target substance 10 is brought into contact with the conductive layer 3, the specific binding substance 7 fixed to the exposed portion of the metal nanowire of the conductive layer 3 becomes the target substance. It specifically binds to 10. Electrodes (not shown) are connected to the conductive layer 3, and the presence of the target substance 10 that specifically binds to the specific binding substance 7 can be measured as a change in current value.
In the example shown in FIG. 4, the target substance is detected using the conductive material for a biosensor of the present invention, but the present invention is not limited to this, and when the target substance is fixed to the exposed portion of the metal nanowire. Can detect specific binding substances.

In the present invention, since the conductive layer contains the metal nanowire, the conductivity is very excellent. Therefore, by using the biosensor conductive material of the present invention, it is possible to detect a target substance or a specific binding substance with high sensitivity in a short time. Moreover, since the detection sensitivity is high, even a trace amount of the target substance or the specific binding substance can be detected, and the accuracy of the screening test can be improved. Therefore, for example, early detection and early treatment of infectious diseases can be realized. Furthermore, in the present invention, since it is not necessary for the sample to move on the membrane as in the case of immunochromatography, there is no need to use a developing solution (mobile phase), and there is no need to dilute the sample even if it has a high viscosity. Since the sample can be directly supplied to the biosensor, the inspection can be performed by a simple operation.

FIG. 5 is a schematic cross-sectional view showing another example of the biosensor conductive material of the present invention. As illustrated in FIG. 5, in the biosensor conductive material 1, the conductive layer 3 is formed in a pattern on the base material 2.
In the present invention, since the conductive layer contains the metal nanowires and the resin, the conductive layer can be easily formed on the base material, and thinning is easy. Further, it is possible to easily form a fine conductive layer pattern by a known method such as a photolithography method. Therefore, by using the biosensor conductive material of the present invention, the biosensor can be applied to various fields. In addition, downsizing of the biosensor can be realized.

Hereinafter, each component of the biosensor conductive material of the present invention will be described.

1. Conductive Layer The conductive layer in the present invention is formed on a base material and contains a resin and a metal nanowire, and has a metal nanowire exposed portion in which at least a part of the metal nanowire is exposed on the surface of the conductive layer. Is. Hereinafter, each configuration of the conductive layer will be described.

(1) Metal Nanowire The metal constituting the metal nanowire used in the present invention is not particularly limited as long as it can immobilize a specific binding substance or a target substance, and examples thereof include silver, copper, and gold. Examples thereof include platinum, palladium, rhodium, iridium, ruthenium, osmium, iron, cobalt and tin. Of these, silver nanowires and copper nanowires are preferably used.

The average diameter of the metal nanowires is not particularly limited as long as the desired conductivity is obtained, and for example, can be in the range of 0.1 nm to 1000 nm. In addition, since the conductive layer does not need to be transparent in the present invention, the diameter of the metal nanowire may be large.

The average length of the metal nanowires is not particularly limited as long as it is sufficiently larger than the average diameter of the metal nanowires, and the desired conductivity can be obtained, and can be within a range of 50 nm to 2000 μm, for example. Above all, since the length distribution range during the production of the metal nanowire is wide, it is preferably within the range of 400 nm to 2000 μm. If the length of the metal nanowire is long, one metal nanowire can form a long conductive path.
Here, the diameter and length of the metal nanowire can be measured using, for example, a transmission electron microscope.

The method for producing the metal nanowire may be any known method and is not particularly limited.

The content of the metal nanowires in the conductive layer is not particularly limited as long as a conductive layer having a metal nanowire exposed portion can be obtained and desired conductivity is obtained, and for example, 0.01% by mass to 90% by mass. It may be in the range of mass%, and preferably in the range of 1 mass% to 80 mass%, particularly preferably in the range of 5 mass% to 40 mass%. In addition, since the conductive layer is not required to be transparent in the present invention, the content of the metal nanowire may be large.

(2) Metal Nanowire Exposed Portion In the present invention, in the metal nanowire exposed portion, at least a part of the metal nanowire is exposed on the surface of the conductive layer.
Here, the fact that at least a part of the metal nanowire is exposed on the surface of the conductive layer is directly confirmed using, for example, a commercially available atomic force microscope (AFM) having a function of observing the conductivity of the layer surface. be able to. For example, using a NanoNavi probe station equipped with a Nano-Pico CURRENT/CITS mode manufactured by Seiko Instruments Inc. and a high resolution small stage unit of S-image, a conductive cantilever (for example, SI-DF3-R) and a conductive layer are used. It is possible to confirm by scanning the surface of the conductive layer while applying a bias voltage (for example, 3 V to 5 V), detecting the current flowing between the conductive cantilever and the conductive layer, and observing the current distribution.

In the exposed portion of the metal nanowire, the metal nanowire may be exposed to the extent that at least a part of the metal nanowire is exposed to the extent that the specific binding substance or the target substance can be fixed. For example, as shown in FIG. 2A, the metal nanowire 4 may be partially exposed with respect to the diameter of the metal nanowire 4, or may be completely exposed with respect to the diameter of the metal nanowire 4 although not shown. Good. Specifically, the thickness of the portion where the metal nanowire projects from the surface of the conductive layer is preferably 20 nm or less. Here, the thickness of the portion where the metal nanowire protrudes from the surface of the conductive layer means the thickness d as shown in FIG.

In addition, the number of exposed metal nanowires in the conductive layer is preferably 5 or more, and more preferably 20 or more, per conductive layer arranged in the reaction region to which the sample is supplied. For example, in FIG. 7, one conductive layer 3 is arranged in one reaction region 11, and the number of exposed metal nanowires in the conductive layer 3 in this reaction region 11 is preferably within the above range. Further, for example, in FIGS. 6A and 6B, three conductive layers 3 a, 3 b, 3 c are arranged in one reaction region 11, and in each conductive layer 3 a, 3 b, 3 c in this reaction region 11. The number of exposed metal nanowires is preferably within the above range. Details of FIGS. 6 and 7 will be described later.

It suffices that the conductive layer has the exposed portion of the metal nanowire, and the ratio of the area occupied by the exposed portion of the metal nanowire on the surface of the conductive layer is not particularly limited and is appropriately adjusted according to the purpose.

(3) Resin The resin used for the conductive layer in the present invention is appropriately selected according to the method for forming the conductive layer.
For example, when forming a conductive layer by applying an ink containing a resin and a metal nanowire on a substrate, the resin is not particularly limited as long as it functions as a binder, and specifically, Examples thereof include curable resins such as thermosetting resins, ultraviolet curable resins, and electron beam curable resins, and thermoplastic resins. More specifically, polypropylene, polyethylene, polyethylene terephthalate, acrylic, polyester, polyurethane, polyvinyl chloride, acrylic urethane type resin, polyester acrylate type resin, epoxy acrylate type resin, polyol acrylate type resin and the like can be mentioned.
In addition, when an ink containing a metal nanowire and a solvent that swells the base material is applied on the base material to swell the base material and embed the metal nanowire on the surface of the base material, the resin is a predetermined solvent. As long as it swells, a curable resin such as a thermosetting resin, an ultraviolet curable resin, an electron beam curable resin, or a thermoplastic resin can be used. Specifically, resins such as those described in U.S. Patent Application Publication No. 2011/0281070 and Japanese Patent Publication No. 2012-500865 can be used. More specifically, examples thereof include acrylonitrile butadiene styrene copolymer (ABS resin), polycarbonate, acrylic resin such as polyacrylate and polymethylmethacrylate (PMMA), polystyrene, polyvinyl chloride and the like.

(4) Conductive Layer In the present invention, the conductive layer is preferably formed in a pattern on the base material.
For example, when a conductive layer is formed in a pattern on a substrate and a plurality of conductive layers are provided, at least one of the conductive layers is used for calibration or the number of samples is increased. Alternatively, different specific binding substances or target substances can be fixed to the exposed portions of the metal nanowires of the respective conductive layers. In addition, it is also possible to obtain a biosensor conductive material for multi-sided attachment.
Specifically, as shown in FIGS. 6A to 6D, the conductive layers 3a, 3b, 3c are formed in a pattern on the base material 2, and the plurality of conductive layers 3a, 3b, 3c are formed. When provided, the specific binding substance 7 is fixed to the metal nanowire exposed portions 5 of the conductive layers 3a and 3b and used for the inspection of the sample, and the metal nanowire exposed portions 5 of the other conductive layers 3c are unique. The binding substance 7 can be used for calibration without being fixed. The specific binding substances 7 fixed to the metal nanowire exposed portions 5 of the conductive layers 3a and 3b may be the same or different. If they are the same, the number of samples can be increased, and if they are different, it is possible to simultaneously inspect a plurality of items with one inspection. 6B is a sectional view taken along the line AA of FIG. 6A, FIG. 6C is a sectional view taken along the line BB of FIG. 6A, and FIG. It is an enlarged view of the broken line part of FIG.
Further, as shown in FIG. 7, the conductive layer 3 can be formed in a pattern on the base material 2 to provide a multi-sided conductive material for a biosensor. In addition, in FIG. 7, a part of the insulating layer 6 described later is shown by a broken line.

When the conductive layer is formed in a pattern, the number of conductive layers arranged in the reaction region to which the sample is supplied may be one or plural. Above all, from the above viewpoint, it is preferable that a plurality of conductive layers be arranged in the reaction region. For example, in FIGS. 6A and 6B, a plurality of conductive layers 3a, 3b, 3c are arranged in the reaction region 11, and in FIG. 7, one conductive layer 3 is arranged in the reaction region 11.

When the conductive layer used for calibration is not formed, the calibration data prepared in advance may be used.

In the case where the conductive layer is formed in a pattern, the width of the pattern of the conductive layer is not particularly limited as long as a desired conductivity can be obtained and the width can be formed. It can be set to about μm to several hundreds μm. Since the conductive layer is not required to be transparent in the present invention, the density of the metal nanowires in the conductive layer can be increased, so that the conductivity can be ensured even in a fine pattern.

The pattern shape of the conductive layer is not particularly limited and may be any shape.

The conductivity of the conductive layer is not particularly limited as long as it can be used as a biosensor, and for example, the surface resistivity of the conductive layer can be 500Ω/□ or less, and 100Ω/□ or less, It is particularly preferably 50Ω/□ or less. This is because if the surface resistivity of the conductive layer is high, it becomes impossible to measure with a minute voltage, and at high voltage, water decomposition and corrosion reaction in the sample are accelerated.
Here, the surface resistivity can be measured using, for example, a resistivity meter Loresta manufactured by Mitsubishi Chemical Corporation.

The thickness of the conductive layer is not particularly limited as long as desired conductivity is obtained, and is appropriately selected according to the method of forming the conductive layer.
For example, when the conductive layer is formed by applying the ink containing the resin and the metal nanowire on the base material, the thickness of the conductive layer can be, for example, in the range of 10 nm to 1 mm, and particularly 0.1 μm to 100 μm. It is preferable that it is within the range of, especially within the range of 0.3 μm to 50 μm. If the conductive layer is thin, it is difficult to obtain continuity and manufacturing becomes difficult. On the other hand, if the conductive layer is thick, the manufacturing cost increases. In the present invention, since the conductive layer does not need to be transparent, the conductive layer may have a large thickness.
When the ink containing the metal nanowires and the solvent for swelling the base material is applied on the base material to swell the base material and embed the metal nanowires on the surface of the base material, the metal nanowires are embedded on the surface of the base material. It is preferable that the thickness of the open portion, that is, the thickness of the conductive layer is equal to or larger than the diameter of the metal nanowire. Specifically, the thickness of the conductive layer can be in the range of 1 to 5 times the diameter of the metal nanowire. More specifically, the thickness of the conductive layer can be in the range of 0.1 nm to 5 μm. When the thickness of the portion where the metal nanowires are embedded on the surface of the base material is within the above range, a contact is easily formed between the metal nanowires, and good conductivity is obtained.

(5) Method of forming conductive layer The method of forming the conductive layer is not particularly limited as long as it is a method capable of forming a conductive layer having an exposed portion of the metal nanowire, and examples thereof include a resin and a metal nanowire on a base material. A method of forming a conductive layer by applying an ink containing a metal nanowire on a base material and an ink containing a solvent for swelling the base material, and swelling the base material to form a metal nanowire on the surface of the base material. There is a method of embedding. In the case of the former method, a commercially available ink can be used as the ink containing the resin and the metal nanowire. Moreover, you may use the commercially available electroconductive film by which the electroconductive layer was laminated|stacked on the base material. On the other hand, in the case of the latter method, specifically, the methods described in U.S. Patent Application Publication No. 2011/0281070 and JP 2012-500865 A can be applied.

The method of forming the conductive layer in a pattern is not particularly limited, and for example, a method of applying an ink containing a resin and a metal nanowire on a substrate in a pattern, forming a resist pattern on the conductive layer Then, a method of etching, a method of transferring the conductive layer onto the base material, a method of partially peeling off the conductive layer formed on the base material, and the like can be mentioned.

In addition, baking or pressurization may be performed in order to increase the conductivity of the conductive layer.

2. Substrate The substrate in the present invention supports the conductive layer.
The base material is not particularly limited as long as the conductive layer can be formed on the base material. The base material may or may not have transparency. For example, a glass base material, a resin base material, or the like can be used, and among them, a resin base material is preferably used from the viewpoint of lightness and flexibility.
Examples of the resin base material include polyester resins such as polyethylene terephthalate, polyethylene naphthalate, polyethylene, polypropylene and modified polyester, polyolefins such as polystyrene and cyclic olefin resin, and vinyl resins such as polyvinyl chloride and polyvinylidene chloride. , Polyetheretherketone, polysulfone, polyethersulfone, polycarbonate, polyamide, polyimide, acrylic, triacetylcellulose and the like.
In addition, the resin substrate may be surface-treated or provided with an easy-adhesion layer in order to secure the wettability and adhesiveness of the ink. As the surface treatment and the easy-adhesion layer, general ones can be applied.
The thickness of the base material may be any thickness as long as the conductive layer can be formed on the base material, and is appropriately selected depending on the application and the like.

3. Specific binding substance and target substance In the present invention, a specific binding substance or a target substance that specifically binds to the target substance may be fixed to the exposed portion of the metal nanowire. In the biosensor using the conductive material for a biosensor of the present invention, the specific binding substance or the target substance is fixed to the exposed portion of the metal nanowire.

The specific binding substance is not particularly limited as long as it specifically binds to the target substance, and examples thereof include an antibody and an aptamer.

Examples of target substances include substances that specifically bind to antigens and aptamers. Specifically, natural antigens such as viruses, bacteria, cells, proteins, peptides, saccharides, nucleic acids (DNA, RNA), lipids, coenzymes, complexes of these, and natural antigen derivatives, and artificially synthesized. Haptens, artificial antigens and the like.

As a method for immobilizing the specific binding substance or the target substance on the exposed portion of the metal nanowire, a general method as a method for immobilizing an antibody, an aptamer, an antigen or the like on the metal surface can be used. For example, a method of immobilizing a specific binding substance or a target substance on the surface of the exposed portion of the metal nanowire via a linker can be used.

4. Insulating Layer In the present invention, as illustrated in FIGS. 6A to 6C and FIG. 7, the insulating layer 6 is patterned on the base material 2 on which the conductive layers 3a, 3b, 3c or 3 are formed. It may be formed. The insulating layer is provided to define a reaction region to which the sample is supplied, to retain the sample on the conductive layer, and to prevent the sample from coming into contact with electrodes, wirings and the like.

The insulating material used for the insulating layer is not particularly limited as long as it can form a patterned insulating layer on the base material on which the conductive layer is formed, and either an organic material or an inorganic material can be used. Can also be used. Examples of the organic material include a photosensitive resin. Examples of the inorganic material include silicon oxide, silicon nitride, silicon oxynitride, and the like.

As the formation position of the insulating layer, as illustrated in FIGS. 6A to 6C and 7, so as to surround the reaction region 11 to which the sample is supplied, and the conductive layer 3a, 3b, 3c or 3 is formed. It suffices that the insulating layer 6 is formed so that the connection portions 12a and 12b connected to the electrodes, wirings, and the like are exposed.

The thickness of the insulating layer is not particularly limited as long as the sample does not overflow, and is appropriately adjusted.

The method for forming the insulating layer is not particularly limited as long as it is a method capable of forming an insulating layer in a pattern on the base material on which the conductive layer is formed, and examples thereof include a photolithography method and a printing method. Can be mentioned.

5. Biosensor conductive material The form of the biosensor conductive material of the present invention is not particularly limited, and is appropriately selected according to the inspection purpose, the inspection target, the inspection method, and the like, for example, a film shape, a plate shape, a rod shape. Etc. can be mentioned.

B. Biosensor The biosensor of the present invention is characterized by including a sensor unit having the above-mentioned biosensor conductive material.

Since the biosensor of the present invention has the above-mentioned conductive material for a biosensor, it is possible to perform inspection with high sensitivity and in a short time. In addition, it is possible to detect a trace amount of components and improve the accuracy of the screening test.
Hereinafter, each component of the biosensor of the present invention will be described.

1. Sensor part The sensor part in the present invention has the above-mentioned conductive material for biosensors.
In the biosensor of the present invention, the biosensor conductive material has a base material and a conductive layer formed on the base material and containing a resin and a metal nanowire, and the conductive layer is the metal nanowire. At least a part of which has a metal nanowire exposed portion exposed to the surface of the conductive layer, the metal nanowire exposed portion, a specific binding substance that specifically binds to a target substance or the target substance is fixed There is something.
The biosensor conductive material has been described in detail in the above section "A. Biosensor conductive material", and thus the description thereof is omitted here.

2. Electrodes and Wirings In the present invention, electrodes and wirings are usually connected to the conductive layer of the biosensor conductive material.
The electrodes and wirings are appropriately selected according to the application and structure of the biosensor of the present invention. Examples of the electrode include a working electrode, a counter electrode, a reference electrode and the like. Further, in the biosensor using the field effect transistor, the source electrode and the drain electrode are connected to the conductive layer. Specifically, in FIGS. 6A to 6C and FIG. 7, one of the connecting portions 12 a and 12 b at both ends of the conductive layers 3 a, 3 b, 3 c or 3 is connected to the source electrode and the other connecting portion 12 a. The drain electrode is connected to the portion 12b.

3. Biosensor The form of the biosensor of the present invention is not particularly limited, and is appropriately selected depending on the inspection purpose, the inspection object, the inspection method, etc., for example, a film shape, a plate shape, a rod shape, a cylindrical shape, a spherical shape, etc. Can be mentioned.

Specifically, a flat biosensor as shown in FIGS. 6(a) to 6(c) and FIG. 7 can be mentioned.

Further, a swab-type biosensor 20 as shown in FIG. 8 can be cited. The swab-type biosensor 20 has a support 21, a sensor portion 15 arranged at the tip of the support 21, and a covering portion 22 arranged so as to cover the sensor portion 15.
For example, when the inside of the nasal cavity or the oral cavity is wiped with the swab-type biosensor 20 and nasal discharge, mucous membrane, saliva or the like is attached as the sample to the coating portion 22, the sample passes through the coating portion 22 and is introduced into the sensor portion 15 for inspection. Be served. As described above, in the swab-type biosensor, a sample can be simply and quickly collected, and the target substance contained in the sample can be tested.

In the cotton swab-type biosensor, a material such as plastic used in conventional cotton swabs or a metal material can be used as the support. In the case of a metallic material, the support can function as an electrode. In this case, the surface of the support made of a metal material may be covered with an insulating material. The shape of the support is not particularly limited, but is generally rod-shaped.
The covering portion is not particularly limited as long as it allows the sample to pass therethrough, and it is preferable that the covering portion has, for example, hydrophilicity or permeability for allowing liquid to pass therethrough. Further, the material of the covering portion is preferably one that does not damage the skin and mucous membranes. Specific examples thereof include filter paper, a resin membrane used for chromatography, and a resin mesh.
In the cotton swab-type biosensor, it is preferable that the sensor unit is replaceable. In this case, for example, the tip portion provided with the sensor unit may be removable, and the swab-type biosensor may be disposable.

Further, a toothbrush type biosensor 30 as shown in FIG. 9 can be exemplified. The toothbrush-type biosensor 30 includes a support 31, a plurality of hair bundles 32 provided at the tip of the support 31, and a sample provided at the tip of the support 31 and arranged on the opposite side of the hair bundle 32. It has a sampling hole 33 and a sensor portion 15 connected to the sampling hole 33.
When the teeth in the oral cavity are brushed by the toothbrush type biosensor 30, saliva, plaque that has been brushed off, or the like is injected into the sample collection hole 33 as a sample. Then, the sample is introduced into the sensor unit 15 connected to the sample collection hole 33 and provided for inspection. As described above, in the toothbrush type biosensor, it is possible to easily and quickly collect a sample and inspect the target substance contained in the sample.
In this case, any antibody can be used as the specific binding substance in the sensor portion depending on the purpose of the test. For example, a monoclonal antibody against Streptococcus (S. mutans, S. sobrinus, S. cricetus, S. rattus, etc.) that is a causative bacterium of caries can be used.

In the toothbrush type biosensor, a material such as a resin used in a conventional toothbrush can be used as the support. The shape of the support may be the shape of a general toothbrush.
A plurality of hair bundles are arranged at the tip of the support. As the bristle bundle, a material usually used as a bristle bundle of a toothbrush such as an artificial material such as resin or a natural material such as pig hair can be used.
A sampling hole is provided in the vicinity of the hair bundle provided at the tip of the support. The position of the sample collection hole is at the tip of the support, in the vicinity of the hair bundle, and is particularly limited as long as it is a position where saliva etc. in the oral cavity can be collected when the toothbrush type biosensor is inserted in the oral cavity. Not something.
In the toothbrush type biosensor, the sensor unit is preferably replaceable. In this case, for example, the sensor unit may be detachable, the tip portion provided with the sensor unit may be detachable, and the toothbrush type biosensor may be disposable.

4. Inspection Method The biosensor of the present invention can be used by connecting to a measuring device. The measuring device connects a biosensor and measures an electric signal generated in the biosensor. A general measuring device can be used as the measuring device. For example, the measurement device includes a connection electrode for receiving an electric signal generated by the biosensor, a calculation unit, a power supply, a display unit, and an operation unit. When the biosensor is mounted on the mounting portion of the measuring device, the electrode of the biosensor or the end of the wiring is connected to the connecting electrode of the measuring device. By this connection, the electrical signal generated by the biosensor is transmitted to the measuring device.
As an inspection method, for example, a measurer attaches the biosensor to the measuring device, introduces a sample into the sensor section of the biosensor, and operates the operation section to start the measurement. When the sample contains the target substance, the target substance reacts with the specific binding substance of the sensor unit, and an electric signal is detected by the electrode of the biosensor and transmitted to the measuring device. The measuring device converts the electric signal received from the biosensor into a measured value by the arithmetic unit. The obtained measurement value is displayed on the display unit, and the measurer can visually recognize the measurement result.

The present invention is not limited to the above embodiment. The above-described embodiment is merely an example, and the invention having substantially the same configuration as the technical idea described in the scope of claims of the present invention and exhibiting the same action and effect is the present invention It is included in the technical scope of.

Hereinafter, the present invention will be specifically described with reference to examples.

[Example 1]
(Fabrication of biosensor)
First, a cover film of a transfer-type thin film transparent conductive film (Transparent Conductive Transfer Film; TCTF) manufactured by Hitachi Chemical Co., Ltd. was peeled off from a PET substrate having a thickness of 200 μm, and heat transfer was performed at 115° C. Next, the TCTF support is exposed on the TCTF support by a pattern formed of silver nanowires including an electrode pattern arranged in the reaction region, a wiring pattern drawn from the electrode pattern, and a connector pattern of a terminal, and the TCTF support is exposed. Was peeled off to expose the silver nanowire of TCTF. Then, sodium carbonate was washed to remove the unexposed portion. In this way, a conductive film in which a conductive layer containing silver nanowires was formed in a pattern was obtained.

Next, in the fine patterned conductive layer, an insulating resist is coated on the conductive film to insulate it so that the pattern arranged in the reaction region and the pattern connected to the source electrode and the drain electrode are exposed. The layers were patterned and provided with an insulating and water resistant coating.

Next, a solution prepared by adding 0.2% (W/W) dithiol to 0.1% (W/W) Tris buffer solution pH 7.2 of Roche, was prepared immediately before use. Under a microscope, this liquid was dropped on the conductive layer located in the reaction region, and naturally dried at room temperature to fix streptavidin to the silver nanowire by a thiol bond. From this, a biosensor was produced.

(Evaluation)
A conductor was fixed with a silver paste in a pattern connected to the source electrode and the drain electrode of the conductive layer and connected to a potentiostat. Thereafter, control saline and biotin 0.05% (W/W) saline produced by Roche were added to different reaction regions, and a cyclic voltammogram of 0.5 V to -0.2 V was applied. .. Biotin was detected in the reaction region to which streptavidin was immobilized.

[Example 2]
(Fabrication of biosensor)
As described below, a biosensor was produced in the same manner as in Example 1 except that the aptamer was fixed to the silver nanowire instead of streptavidin.
That is, a solution prepared by adding 0.2% (W/W) dithiol to a Tris buffer solution of Immuno-Aptamer ^™ , Mouse IgG 0.05% (W/W) manufactured by Nippon Gene was prepared immediately before use. Under a microscope, this liquid was dropped on the conductive layer located in the reaction region, and naturally dried at room temperature to fix the aptamer to the silver nanowire by a thiol bond.

(Evaluation)
A conductor was fixed with a silver paste in a pattern connected to the source electrode and the drain electrode of the conductive layer and connected to a potentiostat. Then, control saline and Mouse IgG 0.05% (W/W) saline produced by Roche were added to separate reaction areas, and a cyclic voltammogram of 0.5 V to -0.2 V was applied. did. IgG binding was detected in the reaction region where the aptamer was immobilized.

[Example 3]
(Fabrication of biosensor)
A biosensor was produced in the same manner as in Example 1 except that the conductive film was formed as described below.
That is, first, a PET film was coated with a coating material "Clear ohm" manufactured by Cambrios Co., Ltd., USA to form a conductive layer. Next, a photoresist was coated on the conductive layer, pattern exposure and washing were performed. After that, full etching was performed using "Silver nanowire etching solution Pure Etch GNW300" manufactured by Hayashi Junyaku Kogyo Co., Ltd., and the photoresist was peeled off to form a conductive film in which a conductive layer was formed in a pattern.

(Evaluation)
When evaluated in the same manner as in Example 1, similar results were obtained.

[Example 4]
(Fabrication of biosensor)
A biosensor was produced in the same manner as in Example 2 except that the conductive film was formed in the same manner as in Example 3.

(Evaluation)
When evaluated in the same manner as in Example 2, similar results were obtained.

1... Conductive material for biosensor 2... Substrate 3, 3a, 3b, 3c... Conductive layer 4... Metal nanowire 5... Metal nanowire exposed portion 6... Insulating layer 7... Specific binding substance 10... Target substance 11... Reaction region 15 ... Sensor part 20, 30 ... Biosensor

Claims (4)

Base material,
A conductive layer formed on the base material and containing a resin and a metal nanowire, wherein the conductive layer has the metal nanowire embedded in the resin, and at least a part of the embedded metal nanowire. Has a metal nanowire exposed portion exposed on the surface of the conductive layer,
A conductive material for a biosensor, wherein nucleic acid is immobilized on the exposed portion of the metal nanowire. The conductive material for a biosensor according to claim 1, wherein the conductive layer is formed in a pattern on the base material. The conductive material for biosensors according to claim 1 or 2, wherein an insulating layer is formed in a pattern on the base material on which the conductive layer is formed. A biosensor comprising a sensor unit having the biosensor conductive material according to any one of claims 1 to 3.

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