Device, concentration measurement apparatus provided with same, and concentration measurement method using same

Abstract

[Problem] To provide a device that can be used in a concentration measurement apparatus and a concentration measurement method with which it is possible to selectively detect a detection object in a specimen and accurately detect the presence / absence or concentration of said detection object using a small amount of energy. [Solution] This device has an insulating substrate, at least one insulating composite layer, and a retention part that can retain a specimen. The insulating composite layer has a pair of electrodes, and a semiconductor layer that is in contact with the pair of electrodes. A catalyst layer that includes a catalyst is provided between the insulating composite layer and the retention part. The catalyst promotes ionization of a detection object, said ionization causing a transfer of electrons with regard to the detection object in the specimen, or promotes ionization of a coenzyme.

Description

Device, concentration measuring apparatus equipped therewith, and concentration measuring method using the same.

[0001] This invention relates to the magnitude of the current flowing between a pair of electrodes according to the concentration of the substance to be detected in the sample, and the threshold voltage V, which is the voltage value of the third electrode when it switches between whether or not current flows between the pair of electrodes. th Regarding devices where the current magnitude and threshold voltage V change, more specifically, the magnitude of the current and threshold voltage V th This invention relates to a concentration measuring device and a concentration measuring method for measuring the concentration of a target substance in a test fluid based on changes in that concentration.

[0002] In the coming super-smart society, Society 5.0, the goal is to achieve both economic development and the resolution of social issues, and the IoT that supports this will require sensors for data acquisition.

[0003] Conventionally, electrochemical sensors using semiconductors have been known as a method for detecting the presence or concentration of specific components in a gas. A conventional gas sensor 200, for example, as shown in Figure 9, has a configuration comprising a pair of electrodes 241 and 242 on an insulating substrate 212, and a semiconductor layer 244 that is in contact with the pair of electrodes 241 and 242. In such a gas sensor 200, when it comes into contact with the gas being tested, the target substance to be detected in the test sample is adsorbed onto the semiconductor layer 244, and the resistance value of the semiconductor layer 244 changes. By measuring this change in the resistance value of the semiconductor layer 244, the presence or concentration of the target substance to be detected in the test sample can be detected.

[0004] In general, tin oxide (SnO2) is used as the semiconductor layer 244 of such a gas sensor 200. However, because the tin oxide semiconductor layer 244 adsorbs any gas molecule, it has low selectivity for the target to be detected, and in some cases, it is not possible to accurately detect the presence or concentration of a specific target.

[0005] Furthermore, some gas sensors have an insulating film formed on the semiconductor layer 244 for the purpose of protecting the semiconductor layer 244. However, the insulating film also has the problem of adsorbing any gas molecule, resulting in low selectivity for the object to be detected.

[0006] Furthermore, in such a gas sensor, accurate detection may be difficult in some cases because the change in the resistance value of the semiconductor layer 244 is small. In this case, it has also been practiced to increase the change in the resistance value of the semiconductor layer 244 by heating the semiconductor layer 244 to raise its temperature. However, this requires a mechanism for heating the semiconductor layer 244, leading to an increase in the energy required for measurement.

[0007] In view of such current circumstances, an object of the present invention is to provide a device that can be used in a concentration measurement apparatus and a concentration measurement method, which is capable of selectively detecting a detection target in an analyte and accurately detecting the presence / absence and concentration of the detection target with low energy.

[0008] The present invention has been made to solve the above-described problems in the prior art, and the device of the present invention, a concentration measurement apparatus including the same, and a concentration measurement method using the same include those configured as follows.

[0009] [1] A device comprising: an insulating substrate, at least one insulating composite layer, and a reservoir capable of storing an analyte, wherein the insulating composite layer comprises a pair of electrodes and a semiconductor layer in contact with the pair of electrodes, a catalyst layer containing a catalyst is provided between the insulating composite layer and the reservoir, and the catalyst promotes ionization of the detection target that causes transfer of electrons with respect to the detection target in the analyte, or promotes ionization of a coenzyme.

[0010] [2] The device according to [1], wherein the catalyst is an enzyme.

[0011] [3] The device according to [2], wherein the enzyme is an oxidoreductase or a hydrolase.

[0012] [4] The device according to [3], wherein the enzyme is any one of primary alcohol dehydrogenase, secondary alcohol dehydrogenase, aldehyde dehydrogenase, glucose dehydrogenase, urease, methane monooxygenase, ethylene oxidase, and creatinine deiminase.

[0013] [5] The device according to any one of [1] to [4], wherein the catalyst layer contains a coenzyme.

[0014] [6] The device according to any one of [1] to [5], wherein the object to be detected is a substance that is difficult to ionize.

[0015] [7] The device according to any one of [1] to [6], wherein the semiconductor layer is composed of an oxide containing indium (In), zinc (Zn), and an additive element (X), and the additive element (X) includes at least one element selected from tantalum (Ta), strontium (Sr), and niobium (Nb).

[0016] [8] The device according to any one of [1] to [7], wherein the storage section has a gas separation membrane.

[0017] [9] The device according to any one of [1] to [8], wherein the catalyst layer is in the form of a sheet.

[0018]

[10] The device according to [9], wherein the sheet-like catalyst layer is gel-like or sponge-like.

[0019]

[11] The device according to any one of [1] to

[10] , further comprising a third electrode formed on the insulating substrate in an insulated state from the insulating composite layer.

[0020]

[12] The field effect mobility of the semiconductor layer is 20 cm 2 A device according to any of [1] to

[11] , wherein the value is greater than or equal to / Vs.

[0021]

[13] The OFF current between the pair of electrodes of the semiconductor layer is 1 × 10 -12 A device that is A or less, as described in any of [1] to

[12] .

[0022]

[14] A concentration measuring device comprising a device described in any of [1] to

[13] and a control device, wherein the control device includes a voltage applying means for applying a voltage between the pair of electrodes, a current measuring means for measuring the current flowing between the pair of electrodes when a voltage is applied by the voltage applying means, and a concentration calculating means for calculating the concentration of a target to be detected in the subject based on the inter-electrode current measured by the current measuring means.

[0023]

[15] The device comprises the device described in

[11] and a control device, the control device comprising: a voltage applying means for varying the voltage applied between the electrode into which current flows and the third electrode of the pair of electrodes; a current measuring means for measuring the current flowing between the pair of electrodes; and a threshold voltage V, which is the voltage value of the third electrode when it switches whether or not current flows between the pair of electrodes, based on the voltage value applied by the voltage applying means and the current value measured by the current measuring means. th A threshold voltage detection means for detecting the threshold voltage V detected by the threshold voltage detection means th A concentration measuring device comprising a concentration calculation means for calculating the concentration of a target to be detected in the subject based on the above.

[0024]

[16] A concentration measurement method for detecting the concentration of a target to be detected in a subject using a device described in any of [1] to

[13] , comprising measuring the inter-electrode current, which is the value of the current flowing between the pair of electrodes when a voltage is applied between the pair of electrodes, and measuring the concentration of the target to be detected in the subject based on the inter-electrode current.

[0025]

[17] A concentration measurement method for detecting the concentration of a target to be detected in a subject using the device described in

[11] , wherein the threshold voltage V is the voltage value of the third electrode when it switches whether or not current flows between the pair of electrodes. th Detect the threshold voltage V th A method for measuring concentration, which measures the concentration of a target substance in a sample based on the above.

[0026] According to the present invention, in the catalyst layer, by causing transfer of electrons with respect to a detection target in an analyte, promoting ionization of the detection target, or promoting ionization of a coenzyme, changing the amount of charge present in the catalyst layer changes the magnitude of a current flowing between a pair of electrodes, and changes a threshold voltage V which is the voltage value of a third electrode when switching whether a current flows between the pair of electrodes th , and thus the concentration of the detection target in the analyte can be measured using such a current value or threshold voltage value.

[0027] FIG. 1 is a schematic diagram for explaining the configuration of a concentration measuring apparatus according to the present embodiment. FIG. 2 is a schematic diagram for explaining the configuration of a device used in the concentration measuring apparatus of FIG. 1. FIG. 3 is a schematic diagram showing a modified example of a device 10 used in the concentration measuring apparatus 50 shown in FIG. 1. FIG. 4 is a schematic diagram for explaining the configuration of another embodiment of the concentration measuring apparatus of the present invention. FIG. 5 is a schematic front view showing a device 10 used in the concentration measuring apparatus 50 shown in FIG. 4. FIG. 6 is a schematic side view of the device 10 shown in FIG. 5. FIG. 7 is a graph showing the amount of change in threshold voltage V with respect to ethanol concentration th . FIG. 8 is a graph showing the amount of change in threshold voltage V with respect to acetone concentration th . FIG. 9 is a schematic diagram for explaining the configuration of a conventional gas sensor.

[0028] Hereinafter, embodiments (working examples) of the present invention will be described in more detail with reference to the drawings. FIG. 1 is a schematic diagram for explaining the configuration of a concentration measuring apparatus according to the present embodiment, and FIG. 2 is a schematic diagram for explaining the configuration of a device used in the concentration measuring apparatus of FIG. 1.

[0029] In the present embodiment, unless otherwise stated, the state of the "analyte" is not particularly limited as long as the detection target in the analyte can transfer electrons or ions, and the analyte may be gaseous, liquid, or solid.

[0030] In addition, in the present specification, the "third electrode" is an expression equivalent to a gate electrode.

[0031] As shown in Figure 1, the concentration measuring device 50 of this embodiment comprises a device 10 having an insulating substrate 12, at least one insulating composite layer 14, and a storage section 16 capable of storing a sample, and a control device 60.

[0032] Furthermore, the device 10 configured as shown in Figure 2 can also be a semiconductor element such as a field-effect transistor (FET) or a metal-oxide-semiconductor field-effect transistor (MOSFET).

[0033] The insulating substrate 12 is a substrate made of an insulating material such as glass or ceramics.

[0034] The insulating composite layer 14 has a pair of electrodes (a first electrode 141 and a second electrode 142) and a semiconductor layer 144 that is in contact with the pair of electrodes 141 and 142.

[0035] The storage section 16 is not particularly limited as long as it is capable of storing the sample, but in this embodiment, as will be described later, it is composed of a partition section 16a that surrounds the catalyst layer 18 placed inside the storage section 16.

[0036] Furthermore, a catalyst layer 18 is provided between the insulating composite layer 14 and the storage section 16. The catalyst layer 18 may include a catalyst that causes the transfer of electrons to the target to be detected in the sample, promotes the ionization of the target to be detected, or promotes the ionization of coenzymes. In another embodiment, the catalyst layer 18 may include a catalyst that causes the transfer of electrons to the target to be detected in the sample, or promotes the ionization of coenzymes. In yet another embodiment, the catalyst layer 18 may include a catalyst that causes the transfer of electrons to the target to be detected in the sample. In yet another embodiment, the catalyst layer 18 may include a catalyst that promotes the ionization of coenzymes.

[0037] Enzymes can be used as catalysts, specifically dehydrogenases and hydrolases. While not limited to these, examples of such enzymes include primary alcohol dehydrogenases, secondary alcohol dehydrogenases, aldehyde dehydrogenases, glucose dehydrogenases, ureases, methane monooxygenases, ethylene oxidases, and creatinine deiminases. Generally, the dehydrogenases mentioned above refer to enzymes that remove one or more hydrogen atoms from a substrate; however, depending on the pH of the sample, dehydrogenases may also donate one or more hydrogen atoms to the substrate.

[0038] Furthermore, such a catalyst layer 18 may contain coenzymes. Examples of coenzymes include pyrroloquinoline quinone (PQQ), nicotinamide adenine dinucleotide (NADH), and flavin adenine dinucleotide (FAD).

[0039] The method for producing such a catalyst layer 18 is not particularly limited. For example, a sheet-like catalyst layer containing the enzyme can be created by impregnating a porous material such as a nonwoven fabric or carbon sheet with the enzyme overnight at room temperature, or by mixing the enzyme with a porous polymer such as polyvinyl alcohol (PVA), polyethylene glycol (PEG), or polyvinyl chloride (PVC), or by impregnating the porous polymer overnight at room temperature. By impregnating the enzyme with a porous material, a sponge-like catalyst layer can be produced, while by mixing the enzyme with a polymer, a gel-like catalyst layer can be produced.

[0040] The sheet-like catalyst layer 18 created in this way can be cut to an appropriate size and attached to the insulating composite layer 14 so that no air is trapped inside. The storage section 16 can then be attached to the attached catalyst layer 18 using, for example, epoxy resin, to create the device 10.

[0041] By creating the catalyst layer 18 in this manner, it becomes possible to easily replace the catalyst layer 18 even when it reaches the end of its lifespan due to use or other reasons.

[0042] The insulating composite layer 14 is provided with an insulating film 146 at least in the area that comes into contact with the catalyst layer 18. The insulating film 146 also serves as a protective layer to protect the semiconductor layer 144 from the object being examined. By providing the insulating film 146, corrosion of the semiconductor layer 144 can be prevented, and the durability and reliability of the semiconductor layer 144 can be improved. As for the material of the insulating film 146, any known insulating material can be used, and corrosion-resistant material is preferred. Examples of insulating materials include Ta2O5, Si3N4, and SiO2, and its thickness is preferably 0.01 μm to 0.5 μm, and more preferably 0.03 μm to 0.2 μm.

[0043] Furthermore, the semiconductor layer 144 has a field-effect mobility of 20 cm². 2 It is preferable that the value be 60 cm or higher, and especially 60 cm. 2 It is even more preferable that it be greater than or equal to / Vs.

[0044] Such a semiconductor layer 144 is composed of an oxide containing indium (In), zinc (Zn), and an additive element (X), the additive element (X) being at least one element selected from tantalum (Ta), strontium (Sr), and niobium (Nb).

[0045] Specifically, it is preferable that the atomic ratios of In and X satisfy the following formula (1) (wherein X is the sum of the content ratios of the added elements. The same applies to formulas (2) and (3) below): 0.4 ≤ (In + X) / (In + Zn + X) ≤ 0.8 (1) It is preferable that the atomic ratio of Zn satisfy the following formula (2): 0.2 ≤ Zn / (In + Zn + X) ≤ 0.6 (2) It is preferable that the atomic ratio of X satisfy the following formula (3): 0.001 ≤ X / (In + Zn + X) ≤ 0.015 (3)

[0046] When the atomic ratios of In, Zn, and X satisfy equations (1) to (3), the semiconductor layer 144 exhibits the field-effect mobility and OFF current described above.

[0047] In order for the semiconductor layer 144 to exhibit a higher field-effect mobility and a lower OFF current, it is more preferable that the atomic ratios of In, Zn, and X satisfy equations (1-2), (2-2), and (3-2). 0.43 ≤ (In + X) / (In + Zn + X) ≤ 0.79 (1-2) 0.21 ≤ Zn / (In + Zn + X) ≤ 0.57 (2-2) 0.0015 ≤ X / (In + Zn + X) ≤ 0.013 (3-2)

[0048] Furthermore, it is more preferable that the atomic ratios of In, Zn, and X satisfy equations (1-3), (2-3), and (3-3). 0.48 ≤ (In + X) / (In + Zn + X) ≤ 0.78 (1-3) 0.22 ≤ Zn / (In + Zn + X) ≤ 0.52 (2-3) 0.002 < X / (In + Zn + X) ≤ 0.012 (3-3)

[0049] Furthermore, it is more preferable that the atomic ratios of In, Zn, and X satisfy equations (1-4), (2-4), and (3-4). 0.53 ≤ (In + X) / (In + Zn + X) ≤ 0.75 (1-4) 0.25 ≤ Zn / (In + Zn + X) ≤ 0.47 (2-4) 0.0025 ≤ X / (In + Zn + X) ≤ 0.010 (3-4)

[0050] Furthermore, it is more preferable that the atomic ratios of In, Zn, and X satisfy equations (1-5), (2-5), and (3-5). 0.58 ≤ (In + X) / (In + Zn + X) ≤ 0.70 (1-5) 0.30 ≤ Zn / (In + Zn + X) ≤ 0.42 (2-5) 0.003 ≤ X / (In + Zn + X) ≤ 0.009 (3-5)

[0051] As described above, one or more additive elements (X) are selected from Ta, Sr, and Nb. These elements can be used individually or in combination of two or more. Additive elements (X) may include elements other than Ta, Sr, and Nb, but preferably they consist only of these elements.

[0052] Furthermore, the thinner the semiconductor layer 144, the greater the change in conductivity of the surface layer, which in turn leads to a larger change in the moving charge, as will be described later, and thus improves measurement accuracy. The thickness of such a semiconductor layer 144 is preferably 0.5 μm or less, more preferably 0.1 μm or less, and particularly preferably 0.05 μm or less. There is no specific lower limit specified for the thickness of the semiconductor layer 144, but it is generally 0.005 μm or more.

[0053] Furthermore, it is preferable that the surface 144a of the semiconductor layer 144 on the catalyst layer 18 side be as smooth as possible. If the surface 144a of the semiconductor layer 144 is not smooth, for example, a gap may form between it and the insulating film 146, or the insulating film 146 may be formed discontinuously, reducing the adhesion between the insulating film 146 and the catalyst layer 18, making it impossible to accurately capture changes in the charge amount in the catalyst layer 18. As a result, the measurement accuracy may decrease or the operation may become unstable.

[0054] Specifically, the maximum height Sz of the surface 144a of the semiconductor layer 144 is preferably 0.05 μm or less, more preferably 0.01 μm or less, and most preferably 0.003 μm or less. There is no particular requirement for the lower limit of this maximum height Sz, but it is generally 0.0005 μm or more. Furthermore, the arithmetic mean height Sa of the surface 144a of the semiconductor layer 144 on the catalyst layer 18 side is preferably 0.03 μm or less, more preferably 0.005 μm or less, and most preferably 0.002 μm or less. There is no particular requirement for the lower limit of this arithmetic mean height Sa, but it is generally 0.0002 μm or more.

[0055] Here, the maximum height Sz and the arithmetic mean height Sa are surface roughness parameters defined in ISO 25178, and such parameters can be measured, for example, by a 3D surface roughness shape measuring machine (Zygo, NexView). In this case, the measurement conditions are preferably carried out according to the following.

[0056] Measurements are performed in accordance with ISO 25178, using a 50x objective lens, a 20x zoom lens, and a measurement range of 89 μm × 87 μm. A roughness curve of 3 μm × 3 μm is extracted from the obtained three-dimensional surface shape, and the roughness curve is corrected using the analysis program "Mx" attached to the 3D surface roughness shape measuring machine under the following correction conditions to calculate the maximum height Sz and arithmetic mean height Sa.

[0057] <Correction Conditions> -Remove: Form Remove -Filter Type: Spline -Filter: Low Pass -Type: Gaussian Spline Auto

[0058] When forming the device 10 described above as an FET structure, it can be formed using the same methods as conventionally known FETs and MOSFETs. For example, it can be formed by depositing conductive metal thin films as the first electrode 141 and the second electrode 142 on an insulating substrate 12 using a sputtering apparatus, and then depositing an oxide thin film with the above-described configuration as the semiconductor layer 144 using a sputtering apparatus. A shadow mask can be used for patterning during the deposition of the first electrode 141 and the second electrode 142 and the semiconductor layer 144.

[0059] The conductive metals used as the first electrode 141 and the second electrode 142 are not particularly limited, but for example, molybdenum (Mo) or tungsten (W) can be used, and alloys of these metals with cerium oxide (CeO2), copper (Cu), silver (Ag), etc. can also be used.

[0060] Next, an insulating film 146 can be formed by depositing a ceramic thin film on top of this. Specifically, for example, the insulating film 146 can be formed by depositing a SiOx thin film using a plasma CVD apparatus such as the PD-2202L manufactured by Samco Corporation, under the conditions of a deposition gas: SiH4 / N2O / N2 mixed gas, deposition pressure: 110 Pa, and substrate temperature: 250°C to 400°C.

[0061] In the device 10 described above, when the sample stored in the storage section 16 comes into contact with the catalyst layer 18, the catalyst contained in the catalyst layer 18 causes electron transfer to and from the target to be detected in the sample, promotes the ionization of the target to be detected, or promotes the ionization of coenzymes. As a result, the amount of charge present in the catalyst layer 18 changes, and the magnitude of the current flowing between the pair of electrodes also changes.

[0062] In this invention, since, for example, primary alcohol dehydrogenases and secondary alcohol dehydrogenases can be used as catalysts in the catalyst layer 18, even compounds that are difficult to ionize (substances that are poorly ionizable), such as alcohols and acetone, can be included as targets for detection.

[0063] Furthermore, the control device 60 of the concentration measuring device 50 in this embodiment includes a variable voltage source 32 (voltage application means) for applying a voltage between the first electrode 141 and the second electrode 142, and an ammeter 36 (current measuring means) for measuring the current value between the first electrode 141 and the second electrode 142.

[0064] The control device 60 has a computer equipped with calculation means, storage means, input / output means, etc., and is configured to control the applied voltage of the variable voltage source 32 and measure the current value of the ammeter 36 based on a program stored in the storage means.

[0065] Furthermore, the control device 60 further includes an electrode-to-electrode current detection means 61. The electrode-to-electrode current detection means 61 is configured to control the voltage applied by the variable voltage source 32 and to receive the current value measured by the ammeter 36 as an electrical signal. Such an electrode-to-electrode current detection means 61 can be implemented by a computer or the like incorporated into the control device 60.

[0066] The electrode current detection means 61 uses a variable voltage source 32 to detect a predetermined voltage V between the first electrode 141 and the second electrode 142. ds With the current applied, the inter-electrode current I flowing between the first electrode 141 and the second electrode 142 is measured by the ammeter 36. ds Detects.

[0067] Here, a predetermined voltage Vds The voltage is not particularly limited as long as it is large enough to allow current to flow through the semiconductor layer 144. In this embodiment, a predetermined voltage V ds Since it is sufficient to apply a constant voltage, the system can also be configured to use a constant voltage source instead of the variable voltage source 32.

[0068] The inter-electrode current I detected in this manner ds The magnitude of the current I correlates with the amount of charge in the catalyst layer 18, that is, with the concentration of the substance to be detected in the sample. For example, the concentration of the substance to be detected and the electrode current I ds By creating a calibration curve in advance that shows the relationship between the electrode current I measured using the concentration measuring device 50, ds Based on this, the concentration of the substance being detected can be determined.

[0069] Alternatively, the concentration of the substance being detected and the electrode current I ds By associating these with each other and using them as training data, machine learning is performed, and artificial intelligence (AI) is used to determine the inter-electrode current I measured using the concentration measuring device 50. ds It is also possible to determine the concentration of the substance being detected based on this.

[0070] The control device 60 of this embodiment further comprises a concentration calculation means 64, which calculates the inter-electrode current I detected by the inter-electrode current detection means 61. ds Based on this, the device is configured to calculate the concentration of the substance to be detected, as described above. Such a concentration calculation means 64 can be implemented by a computer incorporated into the control device 60.

[0071] Figure 3 is a schematic diagram showing a modified version of the device 10 used in the concentration measuring device 50 shown in Figure 1. Since this concentration measuring device 50 has basically the same configuration as the concentration measuring device 50 shown in Figures 1 and 2, the same reference numerals are used for similar components, and their detailed explanations are omitted.

[0072] In the concentration measuring device 50 of this embodiment, a gas permeable membrane 17 is provided on the surface of the catalyst layer 18. The gas permeable membrane 17 has the property of selectively allowing only the desired gas to pass through. Examples of such a gas permeable membrane 17 include porous materials such as polydimethylsiloxane (PDMS) and polytetrafluoroethylene (PTFE).

[0073] By configuring the sample in this way, even when the sample is a gas containing multiple components, the gas-permeable membrane 17 can selectively allow the gas to be detected to pass through, enabling more accurate detection of the presence and concentration of the target substance in the sample.

[0074] Figure 4 is a schematic diagram illustrating the configuration of another embodiment of the concentration measuring device of the present invention, Figure 5 is a schematic front view showing the device 10 used in the concentration measuring device 50 shown in Figure 4, and Figure 6 is a schematic side view of the device 10 shown in Figure 5. Since this concentration measuring device 50 has basically the same configuration as the concentration measuring devices 50 shown in Figures 1 to 3, the same reference numerals are used for similar components, and their detailed explanations are omitted.

[0075] In the concentration measuring device 50 of this embodiment, as shown in Figures 4 and 5, a gate electrode layer 13 is provided between the insulating substrate 12 and the insulating composite layer 14. The gate electrode layer 13 has a gate electrode 131, which is a third electrode formed on the insulating substrate 12, and an insulating film 132 for insulating the space between the gate electrode 131 and the insulating composite layer 14.

[0076] Furthermore, the control device 60 includes a variable voltage source 34 (voltage application means) for applying a voltage between the first electrode 141 and the gate electrode 131, and a voltmeter 38 (voltage measurement means) for measuring the voltage value between the first electrode 141 and the gate electrode 131.

[0077] In this embodiment, the control device 60 has a computer equipped with calculation means, storage means, input / output means, etc., and is configured to control the applied voltage of the variable voltage source 32 and variable voltage source 34, measure the current value using the ammeter 36, and measure the voltage value using the voltmeter 38, based on a program stored in the storage means.

[0078] Furthermore, the control device 60 further includes a threshold voltage detection means 62. The threshold voltage detection means 62 controls the voltage applied by the variable voltage source 32 and the variable voltage source 34, and is configured to receive current and voltage values ​​measured by the ammeter 36 and the voltmeter 38 as electrical signals. Such a threshold voltage detection means 62 can be implemented by a computer or the like incorporated into the control device 60.

[0079] The threshold voltage detection means 62 uses a variable voltage source 32 to determine a predetermined voltage V between the first electrode 141 and the second electrode 142. ds With the voltage V applied, the variable voltage source 34 applies a voltage V between the first electrode 141 and the gate electrode 131. g The current is gradually increased. The threshold voltage detection means 62 then uses the ammeter 36 to determine the current I flowing between the first electrode 141 and the second electrode 142. d The change is detected, and the voltage between the first electrode 141 and the gate electrode 131 is measured by the voltmeter 38. g By detecting changes in the threshold voltage V th Measure.

[0080] In this case, the semiconductor layer 144 is a threshold voltage V in the device 10 having the above-described configuration, where the voltage applied to the gate electrode 131 is a threshold voltage V th When the following conditions are met, the OFF current, which is the current flowing from the first electrode 141 to the second electrode 142 or from the second electrode 142 to the first electrode 141, is 1 × 10⁻¹⁰ -12 It is preferable that it be A or less, and especially 1 × 10 -14 It is even more preferable that it be less than or equal to A. Because the OFF current is small in this way, the threshold voltage V will be reduced, as will be described later. th When detecting the threshold voltage V, even if the voltage applied between the first electrode 141 and the second electrode 142 is small, the threshold voltage V can be detected with higher accuracy. th It can be detected.

[0081] In the device 10 having the configuration described above, the threshold voltage V th This changes depending on the amount of charge in the catalyst layer 18. Therefore, this threshold voltage V thBy measuring this, the concentration of the target substance contained in the sample can be detected.

[0082] Note that the threshold voltage V th The measurement method is not particularly limited, and for example, a current I between the first electrode 141 and the second electrode 142 d Voltage V when the current starts to flow g It may also detect current I d When the current is flowing, the voltage V g Gradually decrease the current I d Voltage V at which the current stops flowing g It may also detect voltage V. g By changing the current I d is a predetermined value (for example, 1 × 10) -9 V when A) is reached ds The value of the threshold voltage V th While conventional methods can be used, such as the above, from the perspective of more accurate measurement, voltage V ds Assuming that is constant, the voltage V g A certain range is applied, and the current I that flows at that time is applied. d Measure and V within a predetermined range. g √I d The approximate line is calculated using the least squares method, and the √I of that approximate line is calculated. d V when = 0 g threshold voltage V th It is preferable to do so.

[0083] The threshold voltage V measured in this manner th Since there is a correlation between the concentration of the substance being detected and the threshold voltage V, for example, the concentration of the substance being detected and the threshold voltage V th By creating a calibration curve in advance that shows the relationship with the threshold voltage V measured using the concentration measuring device 50, th Based on this, the concentration of the substance being detected can be determined.

[0084] Alternatively, the concentration of the substance being detected and the threshold voltage V th By associating these with each other and using them as training data, machine learning is performed, and artificial intelligence (AI) is used to determine the threshold voltage V measured using the concentration measuring device 50. thIt is also possible to determine the concentration of the substance being detected based on this.

[0085] The concentration calculation means 64 of this embodiment uses the threshold voltage V detected by the threshold voltage detection means 62. th Based on this, the device is configured to calculate the concentration of the substance to be detected, as described above. Such a concentration calculation means 64 can be implemented by a computer incorporated into the control device 60.

[0086] (Example 1) The results of measuring the ethanol concentration using a device 10 having the structure shown in Figure 2 are shown. The catalyst layer 18 of the device 10 was formed by immersing a polyvinyl chloride (PVC) film manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. in an enzyme solution overnight at room temperature. The degree of polymerization of the PVC is 1050 or less.

[0087] In this example, the enzyme solution was prepared using 0.03 mg / mL of alcohol dehydrogenase (ADH) manufactured by Sigma-Aldrich as the enzyme, 0.05 mmol / L of pyrroloquinoline quinone disodium (PQQ) manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. as the coenzyme, and Tris-HCl buffer manufactured by Nippon Gene Co., Ltd. at pH 7 as the solvent.

[0088] The electrical characteristics of device 10 were measured under the following conditions: Gate voltage V g The voltage is swept within the range of -1.5V to +1.5V, and the drain voltage V d The voltage was fixed at 1V. A semiconductor analyzer (KEYSIGHT B1500A) was used to measure the electrical characteristics.

[0089] In the storage section 16, ethanol solutions manufactured by Kanto Chemical Co., Ltd. were stored so that the ethanol concentrations were 0.001 M, 0.01 M, and 0.1 M, respectively, and the I obtained under each concentration condition ds -V g Based on the characteristics, threshold voltage V th The change in [the value] was calculated.

[0090] Figure 7 shows the threshold voltage V with respect to ethanol concentration. thThis is a graph showing the amount of change. As shown in Figure 7, in the ADH / PQQ system, electrons are generated in conjunction with the oxidation reaction of ethanol, and these electrons are stimulated by the oxide semiconductor layer, causing the threshold voltage V of device 10 to change. th It was confirmed that a shift occurred.

[0091] Also, the threshold voltage V th The amount of shift tended to increase with increasing ethanol concentration. From these results, it was confirmed that the device 10 according to this embodiment functions as a biotransistor for ethanol detection.

[0092] (Example 2) The results of measuring the acetone concentration using a device 10 with the structure shown in Figure 2 are shown. The catalyst layer 18 of the device 10 was formed by immersing a polyvinyl chloride (PVC) film manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. in an enzyme solution overnight at room temperature. The degree of polymerization of the PVC is 1050 or less.

[0093] In this example, the enzyme solution was prepared using 0.41 mg / mL of secondary alcohol dehydrogenase (S-ADH) manufactured by Daicel Corporation as the enzyme, 20 mmol / L of β-nicotinamide adenine dinucleotide (reduced form) (NADH) manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. as the coenzyme, and Tris-HCl buffer manufactured by Nippon Gene Co., Ltd. at pH 7 as the solvent.

[0094] The electrical characteristics of device 10 were measured under the following conditions: Gate voltage V g The voltage is swept within the range of -1.5V to +1.5V, and the drain voltage V d The voltage was fixed at 1V. A semiconductor analyzer (KEYSIGHT B1500A) was used to measure the electrical characteristics.

[0095] In the storage section 16, acetone solutions manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. were stored so that the acetone concentrations were 0 mM (Tris-HCl buffer), 2 mM, and 20 mM, respectively, and I obtained under each concentration condition. ds -V g Based on the characteristics, threshold voltage V th The change in [the value] was calculated.

[0096] Figure 8 shows the threshold voltage V with respect to acetone concentration. th This is a graph showing the amount of change. As shown in Figure 8, in the S-ADH / NADH system, NAD+ is generated in conjunction with the reduction reaction of acetone, and the charge change resulting from this reaction is sensed by the oxide semiconductor layer, causing the threshold voltage V of device 10 to change. th It was confirmed that a shift occurred.

[0097] Also, the threshold voltage V th The amount of shift tended to increase with increasing acetone concentration. From these results, it was confirmed that the device 10 according to this embodiment functions as a biotransistor for acetone detection.

[0098] Although preferred embodiments of the present invention have been described above, the present invention is not limited thereto, and various modifications are possible without departing from the object of the present invention.

[0099] 10 Device 12 Insulating substrate 13 Gate electrode layer 131 Gate electrode 132 Insulating film 14 Insulating composite layer 141 First electrode 142 Second electrode 144 Semiconductor layer 144a Surface 146 Insulating film 16 Storage section 16a Partition section 17 Gas permeable film 18 Catalyst layer 32 Variable voltage source 34 Variable voltage source 36 Ammeter 38 Voltmeter 50 Concentration measuring device 60 Control device 61 Inter-electrode current detection means 62 Threshold voltage detection means 64 Concentration calculation means

Claims

1. A device comprising an insulating substrate, at least one insulating composite layer, and a storage section capable of storing a sample, wherein the insulating composite layer comprises a pair of electrodes and a semiconductor layer in contact with the pair of electrodes, and a catalyst layer containing a catalyst is provided between the insulating composite layer and the storage section, wherein the catalyst promotes the ionization of the object to be detected in the sample, or promotes the ionization of a coenzyme, by causing the transfer of electrons to or from the object to be detected in the sample.

2. The device according to claim 1, wherein the catalyst is an enzyme.

3. The device according to claim 2, wherein the enzyme is an oxidoreductase or a hydrolase.

4. The device according to claim 3, wherein the enzyme is any one of a primary alcohol dehydrogenase, a secondary alcohol dehydrogenase, an aldehyde dehydrogenase, a glucose dehydrogenase, a urease, a methane monooxygenase, an ethylene oxidase, and a creatinine deiminase.

5. The device according to claim 1, wherein the catalyst layer contains the coenzyme.

6. The device according to claim 1, wherein the object to be detected is a substance that is difficult to ionize.

7. The device according to claim 1, wherein the semiconductor layer is composed of an oxide containing indium (In), zinc (Zn), and an additive element (X), and the additive element (X) includes at least one element selected from tantalum (Ta), strontium (Sr), and niobium (Nb).

8. The device according to claim 1, wherein the storage section has a gas separation membrane.

9. The device according to claim 1, wherein the catalyst layer is in the form of a sheet.

10. The device according to claim 9, wherein the sheet-like catalyst layer is gel-like or sponge-like.

11. The device according to claim 1, further comprising a third electrode formed on the insulating substrate in an insulated state from the insulating composite layer.

12. The field-effect mobility of the semiconductor layer is 20 cm². 2 The device according to claim 1, wherein / Vs is greater than or equal to Vs.

13. The OFF current between the pair of electrodes in the semiconductor layer is 1 × 10 -12 The device according to claim 1, wherein A is less than or equal to A.

14. A concentration measuring device comprising: a device according to any one of claims 1 to 13; a control device, the control device comprising: a voltage applying means for applying a voltage between the pair of electrodes; a current measuring means for measuring the current flowing between the pair of electrodes when a voltage is applied by the voltage applying means; and a concentration calculating means for calculating the concentration of a target to be detected in the subject based on the inter-electrode current measured by the current measuring means.

15. The device comprises the device according to claim 11 and a control device, wherein the control device includes: a voltage applying means for varying the voltage applied between the electrode into which current flows and the third electrode; a current measuring means for measuring the current flowing between the pair of electrodes; and a threshold voltage V, which is the voltage value of the third electrode when it switches whether or not current flows between the pair of electrodes, based on the voltage value applied by the voltage applying means and the current value measured by the current measuring means. th A threshold voltage detection means for detecting the threshold voltage V detected by the threshold voltage detection means th A concentration measuring device comprising a concentration calculation means for calculating the concentration of a target to be detected in the subject based on the above.

16. A concentration measurement method for detecting the concentration of a target to be detected in a sample using the device described in any one of claims 1 to 13, comprising: measuring the inter-electrode current, which is the value of the current flowing between the pair of electrodes when a voltage is applied between the pair of electrodes; and measuring the concentration of the target to be detected in the sample based on the inter-electrode current.

17. A concentration measurement method for detecting the concentration of a target to be detected in a sample using the device described in claim 11, wherein the threshold voltage V is the voltage value of the third electrode when it switches whether or not current flows between the pair of electrodes. th Detect the threshold voltage V th A method for measuring concentration, which measures the concentration of a target substance in a sample based on the above.

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