Transistor type sensor

Abstract

To provide a transistor type sensor capable of estimating the concentration of a target chemical substance from multiple perspectives, in which the influence of an error, if the error exists, can be reduced and a measurement result with high reproducibility can be obtained.SOLUTION: A transistor type sensor detects chemical substances in a solution, and includes a field effect transistor including a gate electrode, an operation electrode disposed in the solution and connected to the gate electrode, and a counter electrode disposed in the solution and disposed apart from the operation electrode. The operation electrode is connected to the gate electrode. To the counter electrode, a first application circuit is connected in series in order to apply a voltage to the aqueous solution. Between the gate electrode and the operation electrode, a second application circuit to apply a voltage to the aqueous solution is connected. A surface of at least one of the operation electrode and the counter electrode is a capture electrode configured to capture the chemical substance in the solution.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a transistor-type sensor for detecting chemical substances and a measurement method for quantitatively measuring chemical substances by using the transistor-type sensor.

Background Art

[0002] In recent years, with the trend towards a healthier lifestyle, the demand for easily monitoring chemical substances has been increasing. To analyze biomarkers in biological samples, nutrients in food, environmental pollutants, etc., large and expensive analytical instruments such as mass spectrometers and expensive analytical reagents have been required until now. However, in the future, rapid and simple analytical methods will be demanded, and it is expected that this will make human life more comfortable.

[0003] Under such circumstances, research and development have been progressing on treating the surface of metal electrodes and interacting with the target substance to be detected to extract an electrical signal. Examples of the interaction include chemical reactions such as covalent bonds, antibody-antigen reactions, supramolecular recognition by host-guest, and methods using molecular templates. As a measurement device using such an interaction, a transistor-type sensor is known.

[0004] As an example of a transistor-type sensor, Patent Document 1 can be cited. Patent Document 1 discloses a field-effect transistor-type sensor having a working electrode with a molecularly imprinted polymer, a method for manufacturing the field-effect transistor-type sensor, and a measurement method for quantitatively measuring chemical substances by using the field-effect transistor-type sensor.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] As a result of further examining a detection method using a transistor-type sensor as a method for detecting chemical substances such as compounds, the inventors of the present invention found that a transistor-type sensor having the following configuration can reduce the influence even if there is an error, obtain highly reproducible measurement results, and estimate the concentration of the target chemical substance from multiple aspects, and can detect chemical substances more stably than the prior art, thus arriving at the present invention.

Means for Solving the Problems

[0007] That is, the present invention includes the following. [1] A transistor-type sensor for detecting a chemical substance in a solution, comprising: A field-effect transistor having a gate electrode; A working electrode disposed in the solution and connected to the gate electrode; A counter electrode disposed in the solution and spaced apart from the working electrode, and The working electrode is connected to the gate electrode, A first application circuit for applying a voltage to the aqueous solution is connected in series to the counter electrode, A second application circuit for applying a voltage to the aqueous solution is connected between the gate electrode and the working electrode, and A transistor-type sensor, wherein at least one of the working electrode and the counter electrode is a capture electrode configured such that the surface captures a chemical substance in the solution. [2] The transistor-type sensor according to [1], wherein the first application circuit includes a capacitor, and the capacitor is disposed in series between a power source connected to the first application circuit and the counter electrode. [3] The transistor-type sensor according to [1], wherein the second application circuit includes a capacitor, and when a location where the second application circuit is connected to a conducting wire connecting the gate electrode and the working electrode is defined as a connection portion, the capacitor is disposed in series between a power source connected to the second application circuit and the connection portion. [4] A measurement method for quantitatively measuring a chemical substance by using a transistor-type sensor, comprising: The capture electrode of the transistor type sensor according to any one of [1] to [3] is placed in a solution containing a chemical substance to be detected, and the step of bringing the chemical substance into contact with the capture electrode; A step of placing in a solution containing a chemical substance to be detected and bringing the chemical substance into contact with the capture electrode; A step of applying a drain voltage between the drain electrode and the source electrode of the field effect transistor; A step of applying a first voltage to the counter electrode by the first application circuit; A step of applying a second voltage to the gate electrode and the working electrode by the second application circuit; A measuring method including a step of measuring a current Id flowing between the drain electrode and the source electrode of the field effect transistor. [5] A step of measuring the current Id for each concentration of the chemical substance to obtain a concentration-current Id relationship curve; A step of bringing the solution containing the chemical substance into contact with the capture electrode to obtain the current Id of the chemical substance; Comparing the current Id of the chemical substance with the concentration-current Id relationship curve; The measuring method according to [4], further including a step of determining the concentration of the current Id of the chemical substance. [6] The step of obtaining the concentration-current Id relationship curve includes the following steps A to D; the measuring method according to [5]; A step (step A) of obtaining a current Id1 value of a solution containing the chemical substance with a known concentration at a predetermined voltage value; A step (step B) of obtaining a current Id2 value of a solution not containing the chemical substance at a predetermined voltage value; A step (step C) of alternately performing the step A and the step B while changing the concentration of the chemical substance in the step A; A step (step D) of calculating an Id3 value, which is an average of two Id2 values before and after one Id1 value, for a plurality of Id1 values and Id2 values alternately obtained by the step C. [7] In the step A and the step B, the current value is measured a plurality of times, and an average value (Ida1 value) of the plurality of current Id1 values and an average value (Ida2 value) of the plurality of current Id2 values are calculated; The measuring method according to [6], wherein in the step D, the average value Ida3 of two Ida2 values before and after one Ida1 value is calculated.

Advantages of the Invention

[0008] In the transistor-type sensor disclosed in the present specification, since the first application circuit is connected to the counter electrode disposed in the solution containing the target chemical substance, and the second application circuit is connected to the working electrode disposed in the solution, the voltage of the field-effect transistor provided in the transistor-type sensor is affected by the application of the first application circuit and the application of the second application circuit. Therefore, by setting the voltages of the two application circuits respectively, the situation of the target chemical substance can be measured according to the set values of the two voltages, and a lot of data can be obtained. Therefore, even if there is an error, the influence of the error can be reduced, and it can be found that the concentration of the target chemical substance can be estimated from various angles. The second application circuit is connected between the gate electrode and the working electrode. By adjusting the potential applied from the second application circuit and the potential applied from the first application circuit, the current value for each potential can be measured. Further, when there is a change in concentration, the second application circuit can make it easier to find where the fluctuation of the current value is large, and it becomes possible to measure more easily. In some cases, the potential applied from the second application circuit may be referred to as the control potential. Also, when each of the first application circuit and the second application circuit is provided with a capacitor, since the capacitor of the first application circuit and the space closed by the insulating film of the field-effect transistor are in a floating state not connected to the outside, the charge is conserved except when charge is generated by an electrochemical reaction. In this case, since the action on the electrode surface generated in the electrochemical cell is the movement of charge in the closed space, the reference electrode may not be necessary, and when taking out the charge with the field-effect transistor, it can be detected as a more precise output. Also, the current value of an aqueous solution with an unknown concentration can be measured, and the chemical substance can be quantitatively measured by determining the concentration from that value.

Brief Description of the Drawings

[0009]

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Mode for Carrying Out the Invention

[0010] Hereinafter, embodiments for carrying out the invention will be described, but the present invention is not limited to the embodiments for carrying out the invention.

[0011] [Regarding the transistor-type sensor] FIG. 1 is a circuit diagram of a transistor-type sensor S which is one of the embodiments of the present invention, and FIG. 2 is a schematic diagram of a transistor-type sensor S which is a specific example of the embodiment of the present invention. The transistor-type sensor S includes a working electrode 11 for detecting a target chemical substance, and a field-effect transistor T having a gate electrode connected to the working electrode 11. Further, a counter electrode 12 is disposed in an aqueous solution 13 containing the target chemical substance, and a first capacitor 10A is connected in series between the counter electrode 12 and a power source V1. Furthermore, a power source V2 is connected between the working electrode 11 and the gate electrode 2, and a second capacitor 10B is provided between the power source V2 and a connection portion 17. The working electrode 11 is an extended gate electrode of the field-effect transistor T. Hereinafter, each component will be described. Note that, in FIG. 2, for the sake of easy understanding of applying charges (applying voltages) to each component, for convenience, terminals C1, C2, C3, and C4 of charge application means to be connected are shown as being connected to the counter electrode 12, the working electrode 11, the gate electrode 2, the drain electrode 5, and the source electrode 4, respectively.

[0012] (Transistor) The transistor-type sensor S in FIG. 1 includes a field-effect transistor T. Specific examples of the field-effect transistor T include a junction field-effect transistor and a metal oxide semiconductor field-effect transistor. Among them, a thin-film transistor made of an inorganic semiconductor or an organic semiconductor is preferable in that it can be formed on the same substrate as the electrodes, and a thin-film transistor made of an organic semiconductor is more preferable. Note that, in terms of the configuration of the transistor-type sensor, if the field-effect transistor T has an insulating film 3, it is preferable that the insulating film 3 does not contact other power sources. The field effect transistor T can be a field effect transistor with a typical configuration as shown in FIG. 2. The field effect transistor T in FIG. 2 is composed of a substrate 1, a gate electrode 2, a gate insulating film 3, a source electrode 4, a drain electrode 5, a bank 6, a semiconductor thin film 7, and a sealing film 8. The materials constituting the field effect transistor T are not particularly limited either. For example, as the substrate 1, in addition to inorganic materials such as glass, ceramics, semiconductor materials, and metals, organic materials such as resins and papers can be applied. As the gate electrode 2, aluminum, silver, gold, copper, platinum, titanium, indium tin oxide (ITO), poly(3,4-ethylenedioxythiophene), polystyrene sulfonate, conductive carbon nanotubes, graphene, conductive organic-inorganic composite materials, etc. can be used. As the constituent materials of the gate insulating film 3, for example, silica (silicon oxide), alumina (aluminum oxide), self-assembled monolayers, polyimide, polystyrene, polyvinylphenol, polyvinyl alcohol, polymethyl methacrylate, polydimethylsiloxane, polysilsesquioxane, ionic liquids, polytetrafluoroethylene, etc. can be mentioned. The substrate 1 and the gate electrode 2 may be integrated, and a metal substrate or an Si substrate can be used. The Si substrate is preferably doped to improve conductivity. When the semiconductor layer is p-type, a substrate doped with n-type can be used, and when the semiconductor layer is n-type, a substrate doped with p-type can be used. Further, the gate insulating film 3 may use SiO2 formed by surface oxidation of the Si substrate. As the materials of the source electrode 4 and the drain electrode 5, metals such as gold, silver, copper, platinum, and aluminum, metal mixtures or alloys thereof, conductive polymers such as polyethylene dioxythiophene doped with polystyrene sulfonic acid (PEDOT:PSS), conductive carbon nanotubes, graphene, conductive organic-inorganic composite materials, etc. can be mentioned. As the constituent material of the bank 6, polytetrafluoroethylene can be mentioned, and as the constituent material of the sealing film 8, polytetrafluoroethylene, polyparaxylylene, etc. can be mentioned. The substrate 1, the gate electrode 2, the gate insulating film 3, the source electrode 4, and the drain electrode 5 may be surface-treated. For example, a self-assembled monolayer may be formed to adjust the liquid repellency of the surface.

[0013] The semiconductor thin film 7 is not particularly limited in terms of material as long as its function can be exerted. In the case of an organic semiconductor and a p-type semiconductor, pentacene, dinaphthothienothiophene, benzothieno[3,2-b]benzothiophene (Cn-BTBT), 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS pentacene), 5,11-bis(triethylsilylethynyl)anthradithiophene (TES-ADT), rubrene, poly(3-hexylthiophene-2,5-diyl) (P3HT), poly[2,5-bis(3-dodecylthiophen-2-yl)thieno[3,2-b]thiophene] (PBTTT), etc. can be used. In the case of an organic semiconductor and an n-type semiconductor, fullerenes, etc. can be used.

[0014] In FIGS. 1 and 2, the detection unit E includes a conducting wire 9, a working electrode 11, a counter electrode 12, and an aqueous solution 13 containing a chemical substance to be detected. Since the working electrode 11 is electrically connected to the gate electrode 2 of the field effect transistor T by the conducting wire 9, the working electrode 11 serves as an extension electrode of the gate electrode 2. Note that the working electrode 11 can include a working electrode substrate and a working electrode body. Experimentally, in order to detect a liquid, the working electrode 11 and the counter electrode 12 are disposed in the aqueous solution 13. In this specification, a solution or an aqueous solution can contain an electrolyte so that the electrolyte can move electrically. For example, if the target substance is in the state of ions (anions or cations) in an aqueous solution, it is not necessary to add an electrolyte other than the substance to be detected, but an electrolyte can be added to achieve a preferable potential state. Note that the aqueous solution can contain an organic solvent, but the organic solvent in the aqueous solution is preferably 50% by mass or less with respect to the total mass of the aqueous solution.

[0015] Examples of the material of the working electrode substrate of the working electrode 11 include polyethylene naphthalate and polyethylene terephthalate. The working electrode body (extended gate electrode body) is arranged on the surface of the working electrode substrate. However, when the working electrode body is self-supporting, it may also serve as the working electrode substrate. The material of the working electrode body, similar to that of the gate electrode 2, can be aluminum, silver, gold, platinum, copper, titanium, indium tin oxide (ITO), poly(3,4-ethylenedioxythiophene), polystyrene sulfonate, conductive carbon nanotubes, graphene, conductive organic-inorganic composite materials, etc. When polymerizing by electrolytic polymerization, it is preferably highly chemically stable, and it is preferable to use gold, platinum, conductive carbon nanotubes, or graphene. The working electrode substrate may be surface-treated to improve the adhesion with the working electrode body, or a thin film may be formed between the working electrode substrate and the working electrode body. For example, a resin may be applied to the surface of the working electrode substrate, or a metal may be vapor-deposited before forming the working electrode body, and its material and structure are not particularly limited. Note that the working electrode body preferably forms a metal thin film such as gold having a thickness of 10 nm to 1000 μm, or a carbon nanotube, graphene, conductive inorganic material thin film, or conductive organic material thin film, and an insulating film such as SiO2 having a surface thickness of 1 nm to 1000 nm, preferably 1 nm to 50 nm, may be formed. In this specification, the surface of the working electrode body includes both the case where the material of the working electrode body itself is the surface and the surface on which a metal thin film or metal oxide film is formed. Examples of self-supporting working electrode bodies include wires or coils of gold or platinum, or silver / silver chloride. Note that a self-supporting electrode may be enclosed in a glass container if a liquid junction portion exists.

[0016] The counter electrode 12 can use a metal electrode or a carbon electrode in the same way as the working electrode 11. The counter electrode 12 may form a conductive film on a substrate equivalent to the material of the substrate of the working electrode, or may form a conductive film on the working electrode substrate common to the working electrode. Also, a film of the same or different material may be formed on the counter electrode 12. The film on the counter electrode 12 may be subjected to the same treatment as the film of the working electrode 11, or may be subjected to intermediate treatments. However, the counter electrode 12 and the working electrode 11 must not be in contact with each other.

[0017] The counter electrode 12 is provided with a first application circuit capable of applying a predetermined voltage to the aqueous solution 13. The first application circuit is not particularly limited as long as the object of the present invention can be achieved. For example, it can include a first capacitor 10A, and a power source V1 can be connected to the first application circuit. At this time, as shown in FIGS. 1 and 2, the first capacitor 10A is preferably connected in series with the counter electrode 12 and the power source V1. When connected in series, the direct continuity of the conductive wire 9 is interrupted, and the space closed by the gate insulating film 3 of the first capacitor 10A and the field effect transistor T is in a floating state not connected to the outside, and the charges existing therein are stored (however, this is not the case when charges are generated by an electrochemical reaction). The action on the surface of the working electrode 11 occurring in the aqueous solution 13 is the movement of charges in a closed system, and the transistor-type sensor S does not need to be provided with a reference electrode. By closing electrically, when detecting a voltage change with the field effect transistor T, the power output can be detected more precisely. Here, the closed system means that in the system including the capacitor 10A, the capacitor 10B, the counter electrode 12, the aqueous solution 13, the working electrode 11, and the gate electrode 2, no new charges enter from the outside other than the charges introduced from the capacitor. The capacitance of the first capacitor 10A is not particularly limited. For example, 0.1 μF to 1000 μF can be used.

[0018] A second application circuit for applying a predetermined voltage to the aqueous solution 13 is connected between the gate electrode 2 and the working electrode 11. The second application circuit is not particularly limited as long as the object of the present invention can be achieved. For example, it can include a second capacitor 10B, and a power source V2 can be connected to the second application circuit. The second application circuit is connected to a connection portion 17 provided in the conducting wire between the gate electrode 2 and the working electrode 11. When the second application circuit includes the power source V2 and the second capacitor 10B, the second capacitor 10B is connected in series between the connection portion 17 and the power source. When there is no second application circuit, since the connected portion of the gate electrode 2 and the working electrode 11 is not connected to the outside, charges are stored, and the voltage Vg applied to the gate electrode 2 of the transistor changes only due to the influence of the voltage applied to the counter electrode 12 (applied by the first application circuit) via the aqueous solution 13. In this case, if the voltage applied between the counter electrode 12 and the working electrode 11 is Ve, although there is an influence of the interaction of the measurement target substance with the electrode, Ve is almost synonymous with Vg. Therefore, when the voltage to be applied between the counter electrode 12 and the working electrode 11 for measurement is different from the voltage required to drive the transistor, it is necessary to change the transistor itself. On the other hand, since the transistor-type sensor S of the present invention includes a second application circuit, new charges can be externally added to the gate electrode 2 and the working electrode 11. Thereby, Ve and Vg can be set to different values, and the voltage to be applied between the counter electrode 12 and the working electrode 11 for measurement and the voltage required to drive the transistor can be set separately.

[0019] The chemical substance to be detected is not particularly limited as long as it can chemically bond to the surface of the capture electrode. In this specification, the chemical substance is intended to include all compounds, metals, ions, etc. The surface treatment method of the capture electrode can be changed according to the compound to be detected. Specific examples of the surface treatment of the capture electrode will be described below. Here, the capture electrode means an electrode for capturing a chemical substance, and in the configuration of the present invention, either the working electrode 11 or the counter electrode 12 can be used as the capture electrode.

[0020] (1) Method of using the capture electrode untreated or forming a different metal film For example, the capture electrode can be left untreated or a different metal film different from the main body of the capture electrode can be formed on the surface. Specifically, gold can be formed on the surface of the capture electrode. The metal can be appropriately selected according to the chemical substance to be detected, and examples thereof include noble metals such as gold, silver, and copper. The chemical substances that can be detected by the capture electrode provided with a metal film are not particularly limited as long as they can interact with the surface metal. Among them, compounds containing a -SH group, -S-S- bond, or -C≡C-H group are preferable in that a chemical bond can be formed on the capture electrode. Examples of compounds containing a -SH group, -S-S- bond, or -C≡C-H group include glutathione, oxytocin, and cysteine. Even when the compound to be detected does not contain a -SH group, -S-S- bond, or -C≡C-H group, there is a method in which a linking compound containing a -SH group, -S-S- bond, or -C≡C-H group and for linking the compound to be detected and the capture electrode is first chemically bonded onto the capture electrode, and then the compound to be detected is bonded to the linking compound on the surface of the capture electrode. However, the linking compound and the chemical substance to be detected may be first bonded together and then bonded to the capture electrode. (2) Method of forming an organic polymer thin film or an inorganic oxide film on the surface of the working electrode For the main purpose of physically adsorbing the compound to be detected, an organic polymer thin film or an inorganic oxide film can be formed on the metal surface of the working electrode. Although it cannot be bonded to the surface of the electrode by chemisorption, it can change the charge on the electrode surface by receiving an electrical interaction. (3) Method of forming a predetermined compound on the surface of the capture electrode A predetermined compound can be formed on the surface of the capture electrode. For example, (A) a method of disposing a functional group capable of chemically bonding to the compound to be detected on the capture electrode to capture the compound to be detected (chemical reaction type), (B) a method of disposing polarized molecules on the capture electrode to capture a charged substance (electrostatic interaction type), (C) a method of disposing complex molecules on the capture electrode to capture the ions to be detected (complex formation type), (D) a method of disposing a compound capable of incorporating the compound to be detected on the capture electrode and capturing the compound to be detected therein (inclusion compound type), and the like can be mentioned. Thus, the method of forming a predetermined compound on the surface of the capture electrode mainly targets low-molecular compounds. (4) Method using antigen-antibody reaction A method of disposing a compound that can become an antigen on the capture electrode and capturing the compound to be detected that becomes an antibody, or conversely, a method of disposing a compound that can become an antibody on the working electrode and capturing the compound to be detected that becomes an antigen can be performed. As a specific example, the capture electrode can be fabricated by the method described in JP-A-2023-045665 and used in the sensor of the present invention. The target compound is not particularly limited as long as it can undergo an antigen-antibody reaction. For example, using the oxytocin-oxytocin antibody reaction, the target compound can be oxytocin or an oxytocin antibody. (5) Method of forming a molecular template on the capture electrode A method of forming a molecular template on the capture electrode can be mentioned. For example, by coexisting the compound to be detected and a resin on the capture electrode, curing the resin, and then removing the compound to be detected from the capture electrode, a molecular template can be formed on the capture electrode. Techniques related to the formation of molecular templates are disclosed, for example, in JP-A-2023-061890. When using a capture electrode with a molecular template, compounds containing -SH groups, -S-S- bonds, or -C≡C-H groups are also preferable. Regardless of which of the above (1) to (5) capture electrodes are used, the target compound can be detected using the transistor-type sensor of the present invention.

[0021] In the transistor-type sensor S, the current value Id changes according to the concentration of the chemical substance to be detected in the aqueous solution. Therefore, after creating a relationship curve between the current value Id and the concentration in advance, the current value Id of the aqueous solution with an unknown concentration is measured, and the concentration is determined from that value. The specific method is described below. Refer to FIG. 2. When the terminal C4 is set to 0 V and a voltage Vd is applied between the terminals C3 - C4, if carriers are generated in the field-effect transistor T when a gate voltage is applied, a current will flow between the source electrode 4 and the drain electrode 5.

[0022] When the terminal C3 is set to 0 V and a voltage V1 is applied between the terminals C1 - C3, a voltage will be applied to the counter electrode 12. When the capacitor 10B is present, charges are accumulated in the capacitor 10B, and a voltage is applied to the counter electrode 12. The voltage of the counter electrode 12 acts on the working electrode 11, and charges are accumulated in the working electrode 11. At this time, the substance in the aqueous solution 13 acts on the working electrode 11 or the counter electrode 12, which is a capture electrode for capturing the chemical substance, and information about the chemical substance is imparted to the charges accumulated in the working electrode 11 and the counter electrode 12. Since the working electrode 11 is connected to the gate electrode 2 as an extended gate electrode, charges with the opposite sign to those accumulated in the working electrode 11 are accumulated in the gate electrode 2. As a result, carriers are generated in the field-effect transistor T, and a current Id flows between the terminals C3 - C4. When the capture electrode captures the chemical substance to be detected, the influence of the interaction between the chemical substance and the capture electrode appears in the current Id. When terminal C3 is set to 0V and a voltage V2 is applied between terminals C2 and C3, voltages will be applied to the working electrode 11 and the gate electrode 2. When the capacitor 10A exists, charges will be accumulated in the capacitor 10A, and voltages will be applied to the working electrode 11 and the gate electrode 2. The voltage of the working electrode 11 acts on the counter electrode 12, and charges are accumulated in the counter electrode 12. At this time, the substance of the aqueous solution 13 acts on the working electrode 11 or the counter electrode 12 which is a capture electrode for capturing chemical substances, and information on the chemical substances is imparted to the charges accumulated in the working electrode 11 and the counter electrode 12. The charges with the information on the chemical substances accumulated in the working electrode 11 also affect the gate electrode 2. As a result, carriers are generated in the field-effect transistor T, and a current Id flows between terminals C3 and C4. When the capture electrode captures the chemical substance to be detected, the influence of the interaction between the chemical substance and the capture electrode appears in the current Id. When both the voltage V1 and the voltage V2 are applied, the above actions are totaled, and the influence of the interaction between the chemical substance and the capture electrode appears in the current Id flowing between terminals C3 and C4. Also, when each of the first application circuit and the second application circuit is provided with a capacitor, in a system including the capacitor 10A of the first application circuit, the aqueous solution 13, the capacitor 10B of the second application circuit, and the gate electrode 2, since the closed space is in a floating state not connected to the outside, the total amount of carriers can be kept constant except when charges are generated by an electrochemical reaction. In addition, in a system including the working electrode 11, the capacitor 10B of the second application circuit, and the gate electrode 2, similarly, the amount of carriers can be kept constant. Due to these effects, the difference in the values of minute currents can be measured more accurately. When measuring an aqueous solution of unknown concentration using the transistor-type sensor S, after creating a relationship curve between the current value Id and the concentration, measure the current value Id of the aqueous solution of unknown concentration, and the concentration can be determined from that value.

[0023] Summarizing the measurement method, it is as follows. When measuring an aqueous solution of unknown concentration using the transistor-type sensor S, after creating a relationship curve between the current value Id and the concentration, measure the current value Id of the aqueous solution of unknown concentration, and from that value, the concentration can be determined. That is, the method for measuring the measurement target is performed as follows. That is; Placing the capture electrode of the transistor-type sensor in a solution containing the chemical substance to be detected and bringing the chemical substance into contact with the capture electrode; Applying a drain voltage between the drain electrode and the source electrode of the transistor; Applying a gate voltage to a capacitor connected in series with the counter electrode; Including the step of measuring the current Id flowing between the drain electrode and the source electrode of the transistor, and preferably further Measuring the current Id for each concentration of the chemical substance to obtain a concentration-current Id relationship curve; Bringing the capture electrode into contact with a solution containing the chemical substance of unknown concentration to obtain the current Id of the chemical substance of unknown concentration; Comparing the current Id of the chemical substance of unknown concentration with the concentration-current Id relationship curve and determining the concentration of the current Id of the chemical substance of unknown concentration. The method is performed by a method including this step.

[0024] The concentration in the aqueous solution of the measurement target substance (chemical substance) is not particularly limited, but it is considered to be in the range of 0.01 ppb to 1000 ppm. However, in view of the results obtained from actual examples, it is in the range of 0.001 ppm to 10 ppm. In this specification, ppb and ppm are units based on weight (w / w).

[0025] As an example of the measurement method for the detection target, a predetermined voltage such as -3.0 V or -0.1 V is applied to Vd, V1 and V2 are applied in a matrix form, and Id at that time is measured. For example, V1 is set to -0.6 V to -1.6 V and applied step by step at 0.1 V intervals, and V2 is set to -0.6 V to -1.6 V and applied step by step at 0.2 V intervals. Basically, since one potential is fixed, a method is adopted in which V2 is set to -0.6 V and V1 is swept and measured, and then V2 is set to -0.8 V and measured. When sweeping, it can be measured back and forth. A graph of the concentration against Id is created by using the value of the concentration or the common logarithm of the concentration on the X-axis and plotting the corresponding Id on the Y-axis. By drawing a graph of the concentration against Id and obtaining the Id in the detection target with unknown concentration, the concentration can be measured. At a predetermined voltage value, the measured Id value is defined as Id target and a reference concentration is set, and the current value Id value at that time is defined as Id base and ((Id target - Id base ) / Id base ) is calculated. When setting the reference, it is advisable to use the current value at a concentration of 0 or the current value at the lowest concentration. Then, a concentration-Id relationship curve at a predetermined voltage can be obtained, and this concentration-Id relationship curve can confirm how much the current value has fluctuated from the reference concentration.

[0026] (Examination of a highly reproducible measurement method) An example of the measurement result by a transistor-type sensor is shown in FIG. 3. In FIG. 3(a), the X-axis is plotted as the measurement number and the Y-axis is plotted as Id (at predetermined V1 and V2). Thus, at the time of FIG. 3(a), it can be understood that not only the decrease in Id due to the measurement of the object but also the baseline, which is the case when the chemical substance that is the measurement object is not included, changes with time. The phenomenon that the baseline changes with time is considered to be one of the causes that charges accumulate in the liquid of the object or on the electrode, etc. each time the number of times is followed, but it is not certain. In this measurement, by performing the following steps A to D, the influence of the change over time of the baseline can be suppressed, and highly reproducible measurement results can be obtained; The step of obtaining the concentration-current Id relationship curve includes the following steps A to D, At a predetermined voltage value, a step of obtaining the current Id1 value of a solution containing the chemical substance with a known concentration (step A), At a predetermined voltage value, a step of obtaining the current Id2 value of a solution not containing the chemical substance (step B), A step of alternately performing the step A and the step B while changing the concentration of the chemical substance in the step A (step C), For a plurality of Id1 values and Id2 values alternately obtained by the step C, a step of calculating an Id3 value which is the average of two Id2 values before and after one Id1 value (step D).

[0027] Also, preferably, by adopting the following method, more reproducible results can be obtained. In the step A and the step B, the voltage value is measured a plurality of times respectively, the average value (Ida1 value) of the plurality of current Id1 values and the average value (Ida2 value) of the plurality of current Id2 values are calculated, and in the step D, an Ida3 value which is the average of two Ida2 values before and after one Ida1 value is calculated. And after the step D, standardization is performed using the above Id1 value (or Ida1 value) and Id3 value (or Ida3 value).

[0028] A specific example of the above method will be described with reference to the drawings. First, as shown in Fig. 3(a), the current Id is measured alternately a plurality of times for a solution containing a chemical substance with a known concentration and a solution not containing the chemical substance. Here, the Id value obtained when using a solution containing a chemical substance with a known concentration is defined as the Id1 value, and the Id value obtained when using a solution not containing the chemical substance is defined as the Id2 value. Next, for a group of measured values (Id1 and Id2) measured multiple times, the average value of the group is obtained (Fig. 3(b)). Let the measured values of the group measured multiple times be Ida1 and Ida2. Note that the Ida1 value and Ida2 value may be calculated after all measurements are completed, or may be measured each time a group of measurements is completed. As shown in Fig. 3(b), the obtained average values are plotted alternately with the Ida1 value of the solution containing the chemical substance with known concentration and the Ida2 value of the solution not containing the chemical substance. Next, as shown in Fig. 3(c), the average value (Ida3) of the Ida2 values (the two points before and after) of the solution not containing the chemical substance before and after the Ida1 value of the solution containing the known chemical substance is calculated. Let the current value (Id1 value or Ida1 value) of the solution containing the chemical substance be Id target and let the current value calculated from the current value of the solution not containing the chemical substance (Id3 value or Ida3 value) be Id base and calculate ((Id target -Id base ) / Id base ). Then, a concentration-Id relationship curve at a predetermined voltage can be obtained (Fig. 3(d)). This concentration-Id relationship curve makes it clearer that the measurement results deviate from the baseline. By obtaining the concentration-Id relationship curve while changing the voltage, data of the concentration-Id relationship curve corresponding to the characteristics of the chemical substance can be obtained. As a specific example, the current Id value was measured "alternately multiple times", but theoretically, the Id values (Id1 value, Id2 value) can be measured alternately one by one, and the Ida3 value can be obtained from the Ida2 values before and after one point of the Id1 value.

[0029] In this example, the temperature at the time of detection is not particularly limited, but it can be carried out at room temperature. Also, the pressure at the time of detection is not particularly limited either, but it can be carried out under atmospheric pressure. However, since it is preferable that the substance to be detected is at the above concentration, it is preferable to immerse the detection electrode in the solution containing the substance to be detected for detection.

Example

[0030] Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

[0031] [Example 1] Manufacture of the transistor-type sensor S1 of the present invention First, using a purchased field-effect transistor (MOSFET, manufactured by Toshiba Corporation: SSM3J15FS), operation confirmation was performed under the same conditions as the above organic semiconductor transistor. The gate electrode 2, source electrode 4, and drain electrode 5 of this field-effect transistor were respectively connected to the terminals of a semiconductor parameter analyzer (not shown). Electrical measurements were performed with the source-drain voltage (Vd) set to -0.1 V and the gate voltage (Vg) set to 0.5 to -3.0 V. It was confirmed that it can be driven within Vg of -3.0 V, that the source-gate current (Ig) is at least one digit smaller than the source-drain current (Id), and that the threshold voltage shift is sufficiently small. Next, using this field-effect transistor, the transistor-type sensor S1 shown in FIG. 2 was fabricated. A 10 μF first capacitor 10A (manufactured by Murata Manufacturing Co., Ltd.: multilayer ceramic capacitor) was connected in series between the counter electrode 12 and the power supply, and a 10 μF second capacitor 10B (manufactured by Murata Manufacturing Co., Ltd.: multilayer ceramic capacitor) was connected in series between the connection part 17 and the power supply.

[0032] [Measurement of the object to be measured] As the electrode, one with a working electrode formed on a substrate (material: polyethylene naphthalate) was used. The surface of the working electrode was Au, and it was fabricated by using a metal mask and depositing Au with a thickness of 100 nm by vapor deposition. The electrode area was 20 mm 2 and. Cysteine solutions (solvent: DPBS, Dulbecco's phosphate-buffered saline) adjusted to concentrations of 0, 0.01, 0.1, 1, 10, and 100 ppm were prepared in glass containers, and the working electrodes fabricated before measurement were immersed and left standing for 5 minutes. This operation was set so that the scientific interaction with the electrode would proceed sufficiently. Using a cysteine solution contained in a glass container, a working electrode, and a platinum electrode as a counter electrode, and using a MOSFET as a transistor, the measurement object was measured.

[0033] The measurement results are shown in Figure 4. This is the result of taking the average of the current values measured 5 times for each concentration, and plotting the drain current Id at V1 = -0.6 to -0.8 V and V2 = -0.8 V to -1.2 V, with the average of the current values for 5 measurements for each concentration on the X-axis, and using the last measurement number out of 5 measurement numbers.

[0034] Furthermore, for the detection experiment of Example 1, Figure 5 shows the result of calculating the current shift and plotting it for each cysteine concentration. As the calculation method of the shift, the average of the current values of the baseline measurement sandwiching the measurement of the measurement object is used as the average value of the reference current value, and it can be obtained by subtracting the average value of the reference current value from the average value of the current values of each concentration and dividing by the average value of the reference current value. From this result, a calibration curve of the measurement object concentration and the shift can be obtained more accurately. By using this calibration curve and obtaining the Id shift in the detection object with an unknown concentration, it becomes possible to measure the concentration. [Equation 1] JPEG2025104611000002.jpg23140

[0035] [Example 2] The same experiment as in Example 1 was conducted except that the measurement object compound was changed from cysteine to glutathione. The results are shown in Figures 6 and 7. It was found that glutathione can be measured in the same manner as in Example 1.

[0036] [Comparison between Cysteine and Glutathione] Figure 8 is a diagram comparing the shifts at respective concentrations for cysteine and glutathione. It can be seen that the shift for cysteine is larger than that for glutathione. Since the shift patterns of cysteine and glutathione are different, it is considered possible to perform both identification and quantification of substances by comprehensively analyzing data at various voltages.

[0037] [Comparative Example 1] Fabrication of a transistor-type sensor for comparison A field-effect transistor-type sensor S2 for comparison was fabricated in the same manner as in Example 1, except that it differed from Example 1 in the following points. · Not using two capacitors. · Not using V2 in FIG. 2. · Using an organic semiconductor transistor instead of a MOSEFT. · Using ultrapure water instead of DPBS as the solvent. · Setting Vg to 0.5 to -3.0 V · Setting Vd to -3.0 V · Using the same counter electrode as the working electrode (Au electrode). · Not performing baseline measurement.

[0038] In the same manner as in Example 1, a glutathione detection experiment was conducted using the field-effect transistor-type sensor S2 obtained in Comparative Example 1. Based on the current-voltage characteristic results obtained by taking the average of the current values for five measurements for each concentration, the current Id at Vg = -1.5 V was plotted for each glutathione concentration, and the results are shown in FIG. 9. From this graph, it can be seen that the relationship between the concentration and the current value is not monotonically increasing or decreasing.

[0039] Furthermore, for the detection experiment of Comparative Example 1, the current shift was calculated based on the average value of the current values at 0.01 ppm, and the results plotted for each glutathione concentration are shown in FIG. 10. From these results, it was found that there is no correlation between the concentration and the current shift, and it cannot be used for concentration estimation.

[0040] In addition, in the measurement of the comparative example, although the various conditions were changed except for not using two capacitors and not using V2, it was confirmed that the change in the various conditions did not affect the correlation. Therefore, it was concluded that the correlation between the concentration and the current shift could not be obtained by not using two capacitors and not using V2.

Industrial Applicability

[0041] The field-effect transistor type sensor of the present invention can quantitatively measure a compound very simply and has industrial applicability.

[0042] Description of Signs T Field-effect transistor E Detection unit 1 Substrate 2 Gate electrode 3 Gate insulating film 4 Source electrode 5 Drain electrode 6 Bank 7 Semiconductor thin film 8 Sealing film 9 Conductive wire 10A First capacitor 10B Second capacitor 11 Working electrode (extended gate electrode) 12 Counter electrode 13 Aqueous solution containing the detection target 17 Connection part

Claims

1. A transistor-type sensor for detecting a chemical substance in a solution, an insulated gate field-effect transistor having a gate electrode, a working electrode disposed in the solution and connected to the gate electrode, a counter electrode disposed in the solution and spaced apart from the working electrode, the working electrode being connected to the gate electrode, a first application circuit for applying a voltage to the aqueous solution is connected in series to the counter electrode, a second application circuit for applying a voltage to the aqueous solution is connected between the gate electrode and the working electrode, A transistor-type sensor, wherein at least one of the working electrode and the counter electrode is a capture electrode configured such that the surface captures a chemical substance in the solution.

2. The transistor-type sensor according to claim 1, wherein the first application circuit includes a capacitor, and the capacitor is connected in series between a power supply connected to the first application circuit and the counter electrode.

3. The transistor-type sensor according to claim 1, wherein the second application circuit includes a capacitor, and when a connection location where the second application circuit is connected to a conducting wire connecting the gate electrode and the working electrode is defined as a connection portion, the capacitor is connected in series between a power supply connected to the second application circuit and the connection portion.

4. A measurement method for quantitatively measuring a chemical substance by using a transistor-type sensor, placing the capture electrode of the transistor-type sensor according to any one of claims 1 to 3 in a solution containing a chemical substance to be detected, and bringing the chemical substance into contact with the capture electrode; applying a drain voltage between the drain electrode and the source electrode of the insulated gate field-effect transistor; applying a first voltage to the counter electrode by the first application circuit; applying a second voltage to the gate electrode and the working electrode by the second application circuit; and measuring a current Id flowing between the drain electrode and the source electrode of the insulated gate field-effect transistor.

5. measuring the current Id for each concentration of the chemical substance to obtain a concentration-current Id relationship curve; bringing the capture electrode into contact with the solution containing the chemical substance to obtain the current Id of the chemical substance; comparing the current Id of the chemical substance with the concentration-current Id relationship curve; and determining the concentration of the current Id of the chemical substance. The measurement method according to claim 4, further comprising the step of

6. The method according to claim 5, wherein the step of obtaining the concentration-current Id relationship curve includes the following steps A to D; The step of obtaining the current Id1 value of the solution containing the chemical substance with a known concentration at a predetermined voltage value (step A), The step of obtaining the current Id2 value of the solution not containing the chemical substance at a predetermined voltage value (step B), The step of alternately performing the step A and the step B while changing the concentration of the chemical substance in the step A (step C), The step of calculating the Id3 value, which is the average of two Id2 values before and after one Id1 value, for the plurality of Id1 values and Id2 values alternately obtained in the step C (step D).

7. In the step A and the step B, the current value is measured a plurality of times, and the average value (Ida1 value) of the plurality of current Id1 values and the average value (Ida2 value) of the plurality of current Id2 values are calculated. The measurement method according to claim 6, wherein in the step D, the Ida3 value, which is the average of two Ida2 values before and after one Ida1 value, is calculated.

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