Sensor

Abstract

To provide a technique for releasing a target substance captured by a molecularly imprinted polymer.SOLUTION: A sensor for detecting a target substance is provided, the sensor comprising a detection unit including a membrane having a space for the target substance to enter and containing a molecularly imprinted polymer for capturing the target substance entering the space, and a release mechanism for releasing the target substance captured by the molecularly imprinted polymer from the molecularly imprinted polymer, where the release mechanism vibrates the membrane.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present disclosure relates to sensors. [Background technology]

[0002] Several proposals have been made to detect target substances using molecularly imprinted polymers. For example, Patent Document 1 discloses a field-effect transistor having a detection electrode on the surface of which a film of molecularly imprinted polymer is formed. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Publication No. 2023-061890 Summary of the Invention [Problem to be solved by the invention]

[0004] In order to repeatedly use a sensor that uses a molecularly imprinted polymer, it is necessary to desorb the target substance captured by the molecularly imprinted polymer. In Patent Document 1, in the process of preparing a template for the target substance during the production of the molecularly imprinted polymer, a cyclic voltammetry technique is used to scan the potential applied between the working electrode and the counter electrode relative to the potential of the reference electrode, and the target substance is removed by reaching a potential at which the chemical bond is broken. However, if such a method is used as a desorption method for repeated use of the sensor, there is a risk that the molecularly imprinted polymer will deteriorate due to electron exchange. Therefore, there is a need for another technique that can desorb the target substance captured by the molecularly imprinted polymer. [Means for solving the problem]

[0005] The present disclosure can be realized in the following forms.

[0006] (1) According to one aspect of the present disclosure, there is provided a sensor for detecting a target substance, the sensor comprising: a detection unit having a space for the target substance to enter and a membrane containing a molecular imprinted polymer that captures the target substance that has entered the space; and a desorption mechanism for desorbing the target substance captured by the molecular imprinted polymer from the molecular imprinted polymer, the desorption mechanism vibrating the membrane. The sensor of this aspect is characterized in that the desorption mechanism vibrates the membrane, and therefore, the vibration can provide energy that exceeds the interaction between the captured target substance and the molecular imprinted polymer, thereby desorbing the target substance captured by the molecular imprinted polymer.

[0007] (2) In the sensor described in (1) above, the detachment mechanism may include a piezoelectric element. In this form of sensor, the membrane is vibrated by the piezoelectric element, so that the sensor can be prevented from becoming large in size compared to a vibration generator including a magnetostrictive element.

[0008] (3) In the sensor described in (1) or (2), the detachment mechanism may be a piezoelectric MEMS element including a diaphragm, the membrane may be formed on the diaphragm, and the area of ​​the diaphragm may be larger than that of the membrane. In this sensor, the membrane is formed on the diaphragm, and the area of ​​the diaphragm is larger than that of the membrane. Therefore, vibrations by the detachment mechanism can be efficiently transmitted to the membrane, and as a result, the target substance captured by the molecularly imprinted polymer can be efficiently detached.

[0009] (4) In the sensor according to any one of (1) to (3), the membrane and the detachment mechanism may be connected via an arbitrary substance. In this sensor, the membrane and the detachment mechanism are connected via an arbitrary substance, so that vibrations caused by the detachment mechanism can be efficiently transmitted to the membrane.

[0010] (5) The sensor according to any one of (1) to (4) above may be a field-effect transistor type sensor. According to this type of sensor, since it is a field-effect transistor type sensor, it is possible to suppress a decrease in detection sensitivity.

[0011] The present disclosure can be realized in various forms, for example, a method for manufacturing a sensor, a method for monitoring a target substance using a sensor, and the like. [Brief explanation of the drawings]

[0012] [Figure 1] FIG. 2 is a cross-sectional view schematically illustrating the general configuration of a sensor. [Figure 2] FIG. 10 is an explanatory diagram illustrating a schematic configuration of a sensor according to a second embodiment. [Figure 3] FIG. 10 is an explanatory diagram schematically illustrating the general configuration of a sensor according to a third embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0013] A. First embodiment FIG. 1 is a cross-sectional view showing a schematic configuration of a sensor 100 according to an embodiment of the present disclosure. For convenience of illustration, FIG. 1 shows only the configuration of the main parts of the sensor 100. The sensor 100 detects a target substance contained in a sample. The sample is not particularly limited, but examples thereof include gases such as air and exhaled breath, and liquids such as water. The sensor 100 of this embodiment is a resistance-type sensor. The sensor 100 includes a detection unit 10 and a detachment mechanism 20.

[0014] The detection unit 10 has a membrane 12 containing a molecularly imprinted polymer (MIP). A space 14 into which a target substance enters is formed in this molecularly imprinted polymer. This space 14 is formed according to the size and surface structure of the target substance by a method described below. The molecularly imprinted polymer chemically interacts with the target substance in this space 14, thereby capturing the target substance that has entered the space 14. The chemical interaction is not particularly limited, but examples thereof include hydrogen bonding.

[0015] The molecularly imprinted polymer is not particularly limited, but preferably has a non-covalent functional group in the main chain or branched chain. Examples of the non-covalent functional group include, but are not particularly limited to, an OH group. Examples of the molecularly imprinted polymer include, but are not particularly limited to, polypyrrole, polyaniline, acrylic polymers, photocurable polymers, and photosolubilizable polymers. The monomer for forming the molecularly imprinted polymer is not particularly limited, but preferably has a double bond for polymerization. The double bond may be present in the molecular chain or may be a double bond of an aromatic ring. Furthermore, from the viewpoint of the polymerization reaction, a monomer having an amino group is preferred. Therefore, the monomer for forming the molecularly imprinted polymer is preferably a compound having a double bond, an OH group, and an amino group.

[0016] Although one type of monomer may be used as the monomer for forming the molecularly imprinted polymer, it is preferable to use two or more types of monomers. When two or more types of monomers are used, a monomer without a non-covalent functional group may be included. The monomer for forming the molecularly imprinted polymer may be either water-soluble or water-insoluble, but a water-soluble monomer is preferable from the viewpoint of ease of handling. Specific examples of the monomer for forming the molecularly imprinted polymer include pyrrole, aniline, ortho-phenylenediamine, acrylamide, N,N'-methylenebisacrylamide, aminophenylboronic acid, aminophenol, aminobenzoic acid, and dopamine.

[0017] The target substance is not particularly limited, and examples thereof include substances with three-dimensional structures, chemical substances, fine particles, etc. The substances with three-dimensional structures are not particularly limited, and examples thereof include viruses, fungi, microorganisms, proteins, etc. The fungi are not particularly limited, and examples thereof include bacteria, fungi, archaea, etc. The viruses and fungi may be pathogenic to animals such as humans. The microorganisms are not particularly limited, and examples thereof include yeasts and algae. The proteins are not particularly limited, and examples thereof include disease-related proteins, antibodies, antigens, etc. The antigens may contain polysaccharides, peptides, nucleic acids, etc., or may be protein-free substances such as lipopolysaccharides. The chemical substances are not particularly limited, and examples thereof include drugs and hormones. The fine particles are not particularly limited, and examples thereof include pollen, PM2.5, yellow sand, aerosols, etc.

[0018] The target substance may be one or more types, but is preferably one type from the viewpoint of preventing a decrease in detection accuracy. In an embodiment in which two or more types of target substances are detected, two or more types of spaces 14 are formed in the molecular imprinted polymer according to the target substances.

[0019] The detection unit 10 of this embodiment further includes a pair of detection electrodes 18 and a substrate 19. When a target substance is captured in the space 14 formed in the molecularly imprinted polymer, the current flowing between the pair of detection electrodes 18 fluctuates, and the target substance can be detected based on this current value. The detection electrodes 18 are not particularly limited as long as they are conductive, and may be formed from, for example, metal, conductive carbon, conductive polymer, etc. Examples of metals include, but are not limited to, gold, silver, copper, aluminum, indium tin oxide (ITO), etc. The substrate 19 is not particularly limited, and may be formed from, for example, glass, ceramics, resin, etc. Examples of resins include, but are not limited to, polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polyether ether ketone, polycarbonate (PC), etc.

[0020] The detachment mechanism 20 vibrates the membrane 12 to detach the target substance captured by the molecularly imprinted polymer from the molecularly imprinted polymer. In this embodiment, the detachment mechanism 20 is a vibration generator 80 including a piezoelectric element. In this embodiment, the detection unit 10 is provided on the vibration generator 80. More specifically, an intervening layer 81 is provided on the vibration generator 80, and a substrate 19 and the membrane 12 are provided thereon. The intervening layer 81 is not particularly limited as long as it can transmit the vibration of the vibration generator 80 to the membrane 12. It may be formed of, for example, a metal or a resin. The metal may be formed of, for example, aluminum or stainless steel. The resin may be formed of, for example, PET, PEN, polyether ether ketone, or PC. By connecting the vibration generator 80 and the membrane 12 via any material such as the intervening layer 81, the vibration generated by the vibration generator 80 can be efficiently transmitted to the membrane 12.

[0021] The timing of activating the desorption mechanism 20, i.e., the timing of vibrating the membrane 12 by the vibration generator 80, is not particularly limited. For example, the membrane 12 may be vibrated at regular intervals. However, it is preferable to vibrate the membrane 12 after the target substance is captured by the detection unit 10. Examples of methods for vibrating the membrane 12 after the target substance is captured include applying a voltage to a piezoelectric element to vibrate the piezoelectric element after detecting a signal resulting from the capture of the target substance in the detection unit 10. When the vibration of the vibration generator 80 serving as the desorption mechanism 20 is transmitted to the membrane 12 containing the molecularly imprinted polymer, energy exceeding the chemical interaction between the captured target substance and the molecularly imprinted polymer is applied, thereby releasing the target substance captured by the molecularly imprinted polymer. The vibration frequency is not particularly limited, but is preferably 10 kHz to 60 kHz, and more preferably 30 kHz to 40 kHz. The duration for vibrating the membrane 12 is not particularly limited, but is preferably 10 seconds to 60 seconds, and more preferably 20 seconds to 40 seconds.

[0022] The desorption mechanism 20 vibrates the membrane 12, thereby reducing the chemical interaction between the target substance and the molecularly imprinted polymer, thereby suppressing deterioration of the molecularly imprinted polymer. Therefore, compared to an embodiment in which the target substance is removed by, for example, using cyclic voltammetry, scanning the potential between the working electrode and the counter electrode relative to the potential of the reference electrode until the potential reaches a potential at which the chemical bond is broken, the degradation of the molecularly imprinted polymer due to electron exchange can be suppressed. As a result, a decrease in the detection accuracy of the sensor 100 can be suppressed. This allows the sensor 100 to be used repeatedly, and a shortened lifespan of the sensor 100 can be suppressed. Furthermore, compared to an embodiment in which the target substance is removed using an organic solvent such as acetonitrile or a base such as sodium hydroxide, the use of an organic solvent or base can be omitted, thereby suppressing deterioration of the molecularly imprinted polymer. Furthermore, compared to an embodiment in which the target substance is removed using an organic solvent, the environmental impact can be reduced. Furthermore, compared to an embodiment in which the target substance is removed using an organic solvent, the sensor 100 is not limited to locations where organic solvents can be used, thereby expanding the range of use of the sensor 100. Furthermore, since the detachment mechanism 20 of this embodiment is formed by a vibration generator 80 including a piezoelectric element, coils and yokes for the field magnet can be omitted compared to a vibration generator including a magnetostrictive element, thereby preventing the vibration generator 80 from becoming larger.

[0023] The uses of the sensor 100 of this embodiment are not particularly limited, but may be applied to, for example, virus and bacteria monitoring, air quality monitoring, water quality management, food hygiene management, health management of humans, animals and plants, high sensitivity sensors, etc.

[0024] The method for manufacturing the detection unit 10 having the membrane 12 containing the molecularly imprinted polymer of this embodiment and the sensor 100 are not particularly limited, but they can be manufactured by the following method, for example. Hereinafter, an example of a method for manufacturing a molecularly imprinted polymer when the target substance is Escherichia coli will be described. First, a substrate 19 including a pair of detection electrodes 18 with a gap of about 10 μm is washed with ethanol and ultrapure water, and then the potential is scanned from −0.7 V to +0.7 V five times in a solution containing 0.1 M LiClO4 and 50 mM pyrrole, thereby electropolymerizing pyrrole. Then, 1×10 4 After adding CFU / mL of E. coli to the electropolymerization cell, molecularly imprinted polymers were synthesized by scanning the potential at a scan rate of 100 mV / s for five more cycles. This was followed by ultrasonic cleaning in water for 5 minutes or by 1 × 10 -3 The detection unit 10 having the membrane 12 containing the molecularly imprinted polymer can be manufactured by incubating the detection unit 10 in a surfactant solution containing M, thereby removing the E. coli used for template formation from the molecularly imprinted polymer. The completed detection unit 10 is attached onto the vibration generator 80 so as to overlap with the vibration generator 80 via the intervening layer 81, thereby manufacturing the sensor 100.

[0025] B. Second embodiment FIG. 2 is an explanatory diagram showing a schematic configuration of a sensor 100a according to a second embodiment. The sensor 100a according to the second embodiment differs from the sensor 100 according to the first embodiment in that it is a FET-type sensor including a field-effect transistor (FET sensor). The other components, including the detachment mechanism 20 (vibration generator 80), are the same as those in the first embodiment, and therefore the same components are denoted by the same reference numerals and detailed description thereof will be omitted. Note that the sensor 100a according to the second embodiment is a so-called extended-gate FET sensor, but is not limited to this and may be any FET sensor, such as a bottom-contact type or a top-contact type.

[0026] The sensor 100 a includes a substrate 61 , a gate electrode 62 , a gate insulating film 63 , a source electrode 64 , a drain electrode 65 , a bank 66 , a semiconductor thin film 67 , a sealing film 68 , a detection unit 10 a , and a desorption mechanism 20 .

[0027] The substrate 61 is not particularly limited and may be formed from an inorganic or organic material. Examples of inorganic materials include, but are not limited to, glass, ceramics, and metals. Examples of organic materials include, but are not limited to, resins and paper. The gate electrode 62 is not particularly limited and may be formed from, but is not limited to, aluminum, silver, gold, copper, titanium, ITO, poly(3,4-ethylenedioxythiophene), polystyrene sulfonate, conductive carbon nanotubes, graphene, conductive organic-inorganic composite materials, and the like. The gate insulating film 63 is not particularly limited and may be formed from, but is not particularly limited to, silica (silicon oxide), alumina (aluminum oxide), self-assembled monolayers, polystyrene, polyvinylphenol, polyvinyl alcohol, polymethyl methacrylate, polydimethylsiloxane, polysilsesquioxane, ionic liquids, polytetrafluoroethylene, and the like. The substrate 61 and the gate electrode 62 may be integrally formed, and for example, a metal substrate or a Si substrate may be used. The Si substrate is preferably doped to improve conductivity, and when the semiconductor thin film is p-type, it is preferable to use an n-type doped substrate, and when the semiconductor thin film is n-type, it is preferable to use a p-type doped substrate. SiO2 formed by oxidizing the surface of the Si substrate may also be used as the gate insulating film 63.

[0028] The source electrode 64 and the drain electrode 65 may be formed of, but are not limited to, a metal, a conductive polymer, conductive carbon, a conductive organic-inorganic composite material, or the like. Examples of metals include, but are not limited to, gold, silver, copper, platinum, and aluminum. Examples of conductive polymers include, but are not limited to, PEDOT and PSS. Examples of conductive carbon include, but are not limited to, conductive carbon nanotubes and graphene. The substrate 61, the gate electrode 62, the gate insulating film 63, the source electrode 64, and the drain electrode 65 may be subjected to a surface treatment, and for example, a self-assembled monolayer may be formed on the surface to adjust the liquid repellency.

[0029] The bank 66 may be formed of, for example, polytetrafluoroethylene, and the sealing film 68 may be formed of, for example, polytetrafluoroethylene, polyparaxylylene, etc. The semiconductor thin film 67 is not particularly limited, but if it is an organic semiconductor of P type, it may be formed of pentacene, dinaphthothienothiophene, benzothienobenzothiophene (Cn-BTBT), TIPS pentacene, TES-ADT, rubrene, P3HT, PBTTT, etc., and if it is an organic semiconductor of N type, it may be formed of fullerene, etc.

[0030] The detection unit 10a has a substrate 70, an extended gate electrode 71, and a counter electrode 72. The detection unit 10a is placed in an aqueous solution 73 containing a target substance.

[0031] The extended gate electrode 71 is electrically connected to the gate electrode 62 via a conductive wire 69. A film 12 containing a molecularly imprinted polymer is provided on the surface of the extended gate electrode 71. The extended gate electrode 71 may be formed, for example, from the same material as the gate electrode 62 described above. A metal thin film, a conductive inorganic material thin film, or a conductive organic material thin film having a thickness of, for example, 10 nm to 1000 μm may be formed on the surface of the extended gate electrode 71. Examples of metals include, but are not limited to, gold. Examples of conductive inorganic materials include, but are not limited to, carbon nanotubes and graphene. Furthermore, a metal oxide film having a thickness of 1 nm to 1000 nm, preferably 1 nm to 50 nm, may be formed on the surface of the extended gate electrode 71. Examples of metal oxides include, but are not limited to, SiO2. In the present disclosure, the term "surface of the extended gate electrode 71" includes both an embodiment in which the material of the extended gate electrode 71 itself is the surface and an embodiment in which a metal thin film or a metal oxide film is formed on the surface.

[0032] The substrate 70 is provided on the surface of the extended gate electrode 71 opposite to the surface on which the film 12 is provided. A vibration generator 80 serving as the detachment mechanism 20 is laminated on the substrate 70. Therefore, the detachment mechanism 20 and the film 12 are connected via the substrate 70. The substrate 70 is not particularly limited, and may be formed from, for example, glass, ceramics, metal, resin, etc. The resin is not particularly limited, and examples thereof include PET, PEN, polyether ether ketone, and PC.

[0033] The counter electrode 72 is not particularly limited as long as it is conductive, and may be formed of, for example, a metal electrode or a carbon electrode. The counter electrode 72 may be formed by forming a conductive film on a substrate made of the same material as the substrate 70. The counter electrode 72 may also be formed by forming a film made of the same material as the molecularly imprinted polymer-containing film 12 or a different material. The counter electrode 72 may also be a reference electrode made of Ag / AgCl or the like.

[0034] Measurement using the sensor 100a is performed, for example, with the detection unit 10a immersed in an aqueous solution containing a target substance. When a target substance is captured in the space 14 formed in the molecularly imprinted polymer, the value of the threshold voltage changes depending on the concentration of the target substance. Therefore, for example, a relationship curve between the concentration of the target substance and the threshold voltage is created in advance, and then the threshold voltage of the aqueous solution containing the target substance to be measured is measured, thereby allowing the concentration of the target substance to be calculated based on the relationship curve. Alternatively, measurement may be performed using a current value instead of the threshold voltage.

[0035] C. Third embodiment 3 is an explanatory diagram showing a schematic configuration of a sensor 100b according to a third embodiment. The sensor 100b according to the third embodiment differs from the sensor 100 according to the first embodiment in the specific configuration of the detachment mechanism 20b. The other configurations, including the configuration of the detection unit 10, are the same as those in the first embodiment, and therefore the same components are denoted by the same reference numerals and detailed description thereof will be omitted.

[0036] The detachment mechanism 20b (vibration generator 80b) in the third embodiment is formed by a piezoelectric MEMS element 40 including a diaphragm 48. The piezoelectric MEMS element 40 of this embodiment has a substrate 42 and a piezoelectric element 44.

[0037] In this embodiment, the substrate 42 is formed of a semiconductor on which an insulating film is formed. Examples of the semiconductor include, but are not limited to, silicon, silicon carbide, and gallium nitride. Examples of the insulating film include, but are not limited to, silicon oxide and silicon nitride. A cavity 49 is formed in the substrate 42 by removing a portion of the substrate 42. The thin-film portion of the substrate 42 that forms the cavity 49 corresponds to the diaphragm 48. The piezoelectric element 44 is embedded in the diaphragm 48. The piezoelectric element 44 has a structure in which, for example, a piezoelectric layer (not shown) is sandwiched between a pair of electrodes. The piezoelectric layer may be formed of, for example, a piezoelectric ceramic, but is not limited to, a material. The pair of electrodes may be formed of, for example, platinum, but is not limited to, a material. The piezoelectric element 44 vibrates when a voltage is applied to the electrodes.

[0038] In the sensor 100b of the third embodiment, the detection unit 10 is provided on the diaphragm 48 of the piezoelectric MEMS element 40. Therefore, the film 12 containing the molecularly imprinted polymer is formed on the diaphragm 48. In this embodiment, the area of ​​the diaphragm 48 is larger than the area of ​​the film 12. With this configuration, the vibration of the piezoelectric element 44 can be amplified and transmitted to the film 12, and as a result, the target substance captured by the molecularly imprinted polymer can be efficiently desorbed. In this disclosure, the areas of the diaphragm 48 and the film 12 refer to the areas in a plane perpendicular to the stacking direction of the diaphragm 48 and the film 12.

[0039] D. Variations The configurations of the sensors 100, 100a, and 100b in the above-described embodiments are merely examples and may be modified in various ways. For example, the sensors 100, 100a, and 100b are not limited to resistive sensors or FET sensors, but may be any type of sensor, such as an impedance sensor or a QCM (Quartz Crystal Microbalance) sensor. Furthermore, for example, the vibration generators 80 and 80b serving as the detachment mechanisms 20 and 20b may include a magnetostrictive element instead of a piezoelectric element. Furthermore, for example, in the above-described embodiments, the area of ​​the diaphragm 48 is larger than the area of ​​the film 12. However, the area of ​​the diaphragm 48 may be the same as or smaller than the area of ​​the film 12. Furthermore, for example, the piezoelectric MEMS element 40 includes the diaphragm 48. However, the diaphragm 48 may be omitted. Furthermore, the location of the detachment mechanism 20 is not limited as long as it can vibrate the film 12. Furthermore, for example, the desorption mechanism 20 may be used in combination with a desorption mechanism having another mechanism for desorbing a target substance captured by the molecularly imprinted polymer. The desorption mechanism having another mechanism is not particularly limited, but examples thereof include a mechanism for desorption by releasing a stimulant, a mechanism for desorption by light irradiation, a mechanism for desorption by heating or cooling, and a mechanism for desorption by electrostatic repulsion of the surface potential. A preferred desorption mechanism having another mechanism is a mechanism for desorption by electrostatic repulsion of the surface potential. The stimulant may be, for example, at least one selected from the group consisting of ozone, hydroxyl radicals, and superoxide.

[0040] The present invention is not limited to the above-described embodiments and can be realized in various configurations without departing from the spirit of the present invention. For example, the technical features in the embodiments and examples corresponding to the technical features in each aspect described in the Summary of the Invention section can be appropriately replaced or combined to solve some or all of the above-described problems or achieve some or all of the above-described effects. Furthermore, if a technical feature is not described as essential in this specification, it can be deleted as appropriate. [Explanation of symbols]

[0041] 10, 10a...detection portion, 12...membrane, 14...space, 18...detection electrode, 19...substrate, 20, 20b...detachment mechanism, 40...piezoelectric MEMS element, 42...substrate, 44...piezoelectric element, 48...diaphragm, 49...cavity, 61...substrate, 62...gate electrode, 63...gate insulating film, 64...source electrode, 65...drain electrode, 66...bank, 67...semiconductor thin film, 68...sealing film, 69...conductor, 70...substrate, 71...extension gate electrode, 72...counter electrode, 73...aqueous solution, 80, 80b...vibration generator, 81...intervening layer, 100, 100a, 100b...sensor

Claims

1. A sensor for detecting a target substance, a detection unit having a space into which the target substance enters and a membrane containing a molecular imprinted polymer that captures the target substance that has entered the space; a desorption mechanism for desorbing the target substance captured by the molecular imprinted polymer from the molecular imprinted polymer; Equipped with The release mechanism vibrates the membrane. A sensor characterized by:

2. 2. The sensor of claim 1, the detachment mechanism includes a piezoelectric element. A sensor characterized by:

3. 3. The sensor according to claim 1, the detachment mechanism is a piezoelectric MEMS element including a diaphragm, the membrane is formed on the diaphragm; The area of ​​the diaphragm is greater than the area of ​​the membrane. A sensor characterized by:

4. 3. The sensor according to claim 1, The membrane and the detachment mechanism are connected via an arbitrary substance. A sensor characterized by:

5. 3. The sensor according to claim 1, It is a field effect transistor type sensor, A sensor characterized by:

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