Transistor type sensor

Abstract

To provide a transistor type sensor capable of quantitatively detecting chemical substances, in which a field effect transistor including an operation electrode connected to a gate electrode is used, and a capacitor is connected in series between a power source and a counter electrode.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. A capacitor is connected in series between the counter electrode and the power source. 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 provided with a working electrode having a molecularly imprinted polymer, a method for manufacturing the field-effect transistor-type sensor, and a measurement method for quantitatively measuring a compound 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 studying a detection method using a small transistor-type sensor as a method for detecting chemical substances such as compounds, the inventors of the present invention have found that a transistor-type sensor having the following configuration can obtain highly reproducible measurement results and can detect chemical substances more stably than the prior art, and have reached 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, 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, The working electrode is connected to the gate electrode, A capacitor is connected in series between the counter electrode and a power source, 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] A measurement method for quantitatively measuring a chemical substance by using a transistor-type sensor, A step of disposing the capture electrode of the transistor-type sensor according to [1] 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 gate voltage to a capacitor connected in series with the counter electrode; A measurement method including a step of measuring a current Id flowing between the drain electrode and the source electrode of the field-effect transistor. [3] 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 a current Id of the chemical substance; The measuring method according to [2], further comprising a step of 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. [4] The measuring method according to [3], wherein the step of obtaining the concentration-current Id relationship curve includes the following steps A to D; 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 the average of two Id2 values before and after one Id1 value, for a plurality of Id1 values and Id2 values alternately obtained in the step C. [5] 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. In the step D, an Ida3 value, which is the average of two Ida2 values before and after one Ida1 value, is calculated. The measuring method according to [4]. [Advantages of the Invention]

[0008] In the transistor-type sensor of the present invention, in a system closed by a capacitor and an insulating film of a field effect transistor, except for a special case where charges are generated by an electrochemical reaction, the charges existing in the system are usually in a conserved state. Thereby, the bond to the electrode surface generated in the electrochemical cell becomes the movement of charges in the closed system. In such a state, when an electrode is connected to a capacitor connected in series to a power supply and used as a counter electrode and placed in an aqueous solution containing a chemical substance to be measured, it can be detected more precisely as an output from the field effect transistor. In addition, by measuring the current value of an aqueous solution with an unknown concentration and determining the concentration from the value, the chemical substance can be quantitatively measured. Furthermore, when obtaining the concentration-current Id relationship curve, by alternately measuring the current Id for a solution containing a chemical substance with a known concentration and a solution not containing the chemical substance, the influence of the change over time of the baseline composed of the Id values of the solution not containing the chemical substance can be suppressed, and it becomes possible to obtain highly reproducible results. Note that the transistor-type sensor of the present invention does not require a reference electrode.

Brief Description of the Drawings

[0009]

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BEST 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 Transistor-Type Sensor] FIG. 1 is a circuit diagram of a transistor-type sensor 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 capacitor 10 is connected in series between the counter electrode 12 and a power supply Vg. Note that the working electrode 11 is an extended gate electrode of the field-effect transistor T. Hereinafter, each component will be described. Note that, for easy understanding of applying charges (applying voltages) to each component, FIG. 2 shows, for convenience, that terminals C1, C2, and C3 of charge application means are connected to the counter electrode 12, the drain electrode 5, and the source electrode 4, respectively.

[0012] (Transistor) FIG. 1 shows a transistor-type sensor S which is one of the embodiments of the present invention. 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 particularly preferable. In addition, 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 having a typical configuration as shown in FIG. 2. The field-effect transistor T in FIG. 1 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. 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 also be applied. As the gate electrode 2, aluminum, silver, gold, copper, 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 material 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 is used, and when the semiconductor layer is n-type, a substrate doped with p-type is 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 polyethylenedioxythiophene 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 subjected to surface treatment. 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. However, when it is an organic semiconductor and of the p-type, 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. When it is an organic semiconductor and of the n-type, fullerenes, etc. can be used. Among them, the following compounds, etc. are preferably used, and in some examples described in this specification, they are used as the semiconductor material of an organic semiconductor transistor (OFET). [Chemical formula]

[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, for detecting a liquid, the working electrode 11 and the counter electrode 12 are disposed in the aqueous solution 12. In this specification, 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 the 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 may contain an organic solvent, but the organic solvent in the aqueous solution is preferably 50% by mass or less based on 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 disposed 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. Similar to the gate electrode 2, the material of the working electrode body 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. 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 may form an insulating film such as SiO2 having a surface thickness of 1 nm to 1000 nm, preferably 1 nm to 50 nm. 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. The self-supporting electrode may be enclosed in a glass container if a liquid junction part exists.

[0016] The counter electrode 12 can use a metal electrode or a carbon electrode in the same manner as the working electrode 11. The counter electrode 12 may form a conductive film on a substrate equivalent to the material of the working electrode substrate 10, 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 an intermediate treatment. However, the counter electrode 12 and the working electrode 11 must not be in contact. The shape of the electrode used to capture the measurement object is not particularly limited, and the electrode surface may be planar or curved. Which of the working electrode 11 and the counter electrode 12 captures the measurement object can be arbitrarily set. Hereafter, the electrode on the substrate for capturing the measurement object is called a capture electrode. This applies to either one of the working electrode 11 and the counter electrode 12, and also to both cases.

[0017] The capacitor 10 is connected in series between the counter electrode 12 and the power supply Vg. By providing the capacitor 10, the direct continuity between Vg and the counter electrode 12 is interrupted, and the system between the capacitor 10 and the insulating film 3 of the field effect transistor T is in a state where it is not electrically connected to the outside (floating state), and the charges existing there will be conserved (however, this is not the case when new charges are generated by an electrochemical reaction). The action on the surface of the working electrode 11 occurring in the aqueous solution 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 is used in the sense that no new charges enter from the outside into the system including the capacitor 10, the counter electrode 12, the aqueous solution 13, the working electrode 11, and the gate electrode 2, except for the charges introduced from the capacitor 10. The capacitance of the capacitor 15 is not particularly limited. For example, a capacitance of 0.1 μF to 1000 μF can be used.

[0018] 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. According to the compound to be detected, the surface treatment method of the capture electrode can be changed. Specific examples of the surface treatment of the capture electrode will be described below.

[0019] (1) Method of using the capture electrode untreated or forming a heterogeneous metal film For example, the capture electrode can be left untreated or a heterogeneous 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 with a capture electrode equipped with a metal film are not particularly limited as long as they can interact with the surface metal. Among these, 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 used to link 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 can also be first bonded 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 for 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 with 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 charged substances (electrostatic interaction type), (C) a method of disposing complex molecules on the capture electrode to capture ions to be detected (complex formation type), (D) a method of disposing a compound capable of incorporating a compound on the capture electrode and capturing the compound to be detected therein (inclusion compound type), etc. can be mentioned. Thus, the method for 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 capable of becoming 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 capable of becoming 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 for forming a molecular template on the capture electrode A method of forming a molecular template on the capture electrode can be mentioned. For example, a molecular template can be formed on the capture electrode 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. 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, a compound containing a -SH group, -S-S- bond, or -C≡C-H group, etc. is also preferable. Regardless of which of the above (1) to (5) capture electrodes is used, the target compound can be detected using the transistor-type sensor of the present invention.

[0020] 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 C3 is set to 0 V and a voltage Vd is applied between the terminals C2 - C3, if carriers are generated in the field-effect transistor T due to the application of the gate voltage, a current will flow between the source electrode 4 and the drain electrode 5. When the terminal C3 is set to 0 V and a voltage Vg is applied between the terminals C1 - C3, charges are accumulated in the capacitor 10, 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 on the working electrode 11. 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 on the working electrode 11 are accumulated on the gate electrode 2. As a result, carriers are generated in the field-effect transistor T, and a current Id flows between the terminals C2 - C3.

[0021] When measuring an aqueous solution with an unknown concentration using the transistor-type sensor S, after creating a relationship curve between the current value Id and the concentration, the current value Id of the aqueous solution with an unknown concentration can be measured, and the concentration can be determined from that value. That is, the method of measuring the measurement object is performed as follows. That is; A step of disposing 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; A step of applying a drain voltage between the drain electrode and the source electrode of the transistor; A step of applying a gate voltage to the capacitor connected in series with the counter electrode; Including a step of measuring the current Id flowing between the drain electrode and the source electrode of the transistor, preferably further including 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 capture electrode into contact with the solution containing the chemical substance with an unknown concentration to obtain the current Id of the chemical substance with an unknown concentration; It is performed by a method including a step of comparing the current Id of the chemical substance with unknown concentration with the concentration-current Id relationship curve to determine the concentration of the current Id of the chemical substance with unknown concentration.

[0022] (Detected concentration) The concentration in the aqueous solution of the substance to be measured 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).

[0023] As an example of the measurement method of the detection target, a predetermined voltage (for example, -3.0 V or -1.0 V, etc.) is applied to Vd, a voltage is applied to Vg step by step from +0.5 V to -3.0 V in steps of 0.1 V, and the Id at that time is measured. A graph of the concentration versus Id at a specific voltage is created by plotting the corresponding Id on the Y-axis using the value of the concentration or the common logarithm of the concentration on the X-axis. By drawing a graph of the concentration versus 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 taken as Id target and a reference concentration is set, and the current value Id value at that time is taken 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.

[0024] (Examination of a highly reproducible measurement method) An example of the measurement results by the transistor type sensor is shown in Fig. 3. In Fig. 3(a), the X-axis represents the measurement number and the Y-axis represents Id (at Vg). As such, 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 when the chemical substance which is the object to be measured is not included changes over time. Regarding the phenomenon that the baseline changes over time, it is considered that one of the reasons is that charges accumulate in the liquid of the object or on the electrodes etc. each time, 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, A step (step A) of obtaining the current Id1 value of the solution containing the chemical substance with a known concentration at a predetermined voltage value, A step (step B) of obtaining the current Id2 value of the 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 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 by the step C.

[0025] Also, preferably, by adopting the following method, more highly 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, the 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).

[0026] 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 the solution containing the chemical substance with a known concentration is defined as the Id1 value, and the Id value obtained when using the solution not containing the chemical substance is defined as the Id2 value. Next, for a group of measurement values (Id1 and Id2) measured a plurality of times, the average value of the group is obtained (Fig. 3(b)). Let the group of measurement values measured a plurality of times be Ida1 and Ida2. Note that the Ida1 value and Ida2 value may be calculated after all the 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 alternately plotted with the Ida1 value of the solution containing the chemical substance with a 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 (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 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 is measured "alternately a plurality of 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 Id1.

[0027] 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 be at the above concentration, it is preferable to immerse the detection electrode in the solution containing the substance to be detected for detection.

Example

[0028] Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited by these examples.

[0029] Fabrication of Organic Semiconductor Transistor First, a substrate 1 (the material is a Si substrate treated with SiO2, SiO2 100 nm) was prepared, and further, source and drain electrodes 4 and 5 (both materials are gold) were formed by patterning. Then, a bank 6 (the material is polytetrafluoroethylene) was formed, and a layer of an organic semiconductor thin film 7 was formed. Finally, a sealing film 8 (the material is polytetrafluoroethylene) was formed by a slit coating method or the like to fabricate a field effect transistor T1. The structure is the same as that of the field effect transistor T shown in FIG. 2.

[0030] Operation Confirmation of Field Effect Transistor (Organic Semiconductor Transistor) The gate electrode 2, source electrode 4, and drain electrode 5 of the field effect transistor using the obtained organic semiconductor were connected to the terminals of a semiconductor parameter analyzer (not shown), respectively. Electrical measurements were performed with the source-drain voltage (Vd) set to -3.0 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 order of magnitude smaller than the source-drain current (Id), and that the threshold voltage shift is sufficiently small.

[0031] Operation Confirmation of Field Effect Transistor (MOSFET) Using the purchased field-effect transistor T2 (manufactured by Toshiba Corporation: SSM3J15FS), operation confirmation was carried out under the same conditions as the above organic semiconductor transistor. However, the source-drain voltage (Vd) was set to -0.1V.

[0032] Fabrication of Transistor-Type Sensor A transistor-type sensor S1 with the same configuration as in Fig. 1 was fabricated. The capacitor 15 (manufactured by Murata Manufacturing Co., Ltd.: multilayer ceramic capacitor) provided between the counter electrode 12 and the power supply Vg was 10 μF and was connected in series. The working electrode was connected to the gate electrode 2 of the field-effect transistor. Then, the counter electrode 12 and the working electrode 11 were placed in an aqueous solution of a predetermined compound and a predetermined concentration.

[0033] [Example 1] As the electrodes, those with the working electrode and the counter electrode formed on a substrate (material: polyethylene naphthalate) were used. The surfaces of the working electrode and the counter electrode were Au, and fabrication was carried out using a metal mask to deposit an Au thin film with a thickness of 100 nm by vapor deposition. The electrode area was 10 mm 2 for both, and a comb-shaped structure was used.

[0034] Glutathione solutions (solvent: ultrapure water) adjusted to concentrations of 0.01, 0.1, 1, 10, and 100 ppm were respectively placed in glass containers, and the above-prepared electrodes were immersed and left standing for 5 minutes. This operation was set so that the scientific interaction with the electrodes proceeded sufficiently.

[0035] Measurement of the measurement object was performed using the glutathione solution, the working electrode and the counter electrode, and the transistor-type sensor S1 using an organic semiconductor transistor as the transistor. The measurement was carried out with the source-drain voltage (Vd) set to -3.0V and the gate voltage (Vg) set to 0.5 to -3.0V. Vg was applied in steps of 0.1V and measured in a reciprocating manner. The measurement was carried out sequentially from the low-concentration side and repeated 5 times.

[0036] The measurement results are shown in Fig. 4. This is the current-voltage characteristic obtained by taking the average of the current values measured five times for each concentration. In Fig. 4, it was found that by increasing the concentration, the absolute value of the current increases.

[0037] Furthermore, the drain current Id at Vg = -1.5V was plotted for each glutathione concentration. The results are shown in Fig. 5. A graph of the concentration versus Id at Vg = -1.5V was created by using the value of the concentration as the common logarithm on the X-axis and plotting the corresponding Id on the Y-axis. When the transistor-type sensor S1 was used, a correlation was observed between Id and the concentration (Fig. 5).

[0038] Furthermore, based on the average value of the current values at 0.01 ppm, how much the current values at other concentrations change was calculated as the current shift (Fig. 6). As a method for calculating the shift, it can be obtained by subtracting the average value of the reference current value from the average value of the current values at each concentration and dividing by the average value of the reference current value, as shown in Equation 1 below. By drawing a graph of the concentration versus the Id shift, it was possible to measure how much Id changed relatively. By using this as a calibration curve and obtaining the Id shift in the detection target with an unknown concentration, it becomes possible to measure the concentration. [Equation 1] JPEG2025104610000003.jpg23140

[0039] [Comparative Example 1] Fabrication of a comparative transistor-type sensor S2 A comparative field-effect transistor-type sensor S2 was fabricated in the same manner as in Example 1, except that a 10 μF capacitor 10 was not used between the counter electrode 12 and the power supply. 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.

[0040] The measurement results are shown in Fig. 7. This is the current-voltage characteristic obtained by taking the average of the current values measured five times for each concentration.

[0041] Regarding the detection experiment of Comparative Example 1, the results of plotting the drain current Id at Vg = -1.5 V against the glutathione concentration are shown in FIG. 8. From this graph, it can be seen that the relationship between the concentration and the current value is not monotonically increasing or decreasing.

[0042] Furthermore, regarding the detection experiment of Comparative Example 1, the drain current shift was calculated and the results plotted against the glutathione concentration are shown in FIG. 9. From these results, it was found that there is no correlation between the concentration and the drain current shift, and thus it cannot be used for concentration estimation.

[0043] (Example 2) Measurement of the object to be measured As the electrode, one with a working electrode formed on a substrate (material: PEN) 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 was used. In glass containers, cysteine solutions adjusted to concentrations of 0, 0.01, 0.1, 1, and 10 ppm (solvent: DPBS, Dulbecco's phosphate buffered saline) were prepared, 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 the cysteine solution and working electrode in the glass container, an Ag / AgCl electrode as the counter electrode, and a MOSFET (T2) as the transistor, the transistor-type sensor S3 was used to measure the object to be measured.

[0044] (Measurement of the baseline and the object to be measured) Using DPBS in a glass container, a Pt electrode as the working electrode, and an Ag / AgCl electrode as the counter electrode, the transistor-type sensor S3' was used to measure the baseline. As the measurement procedure, the baseline was measured, the object to be measured was measured, these were repeated, and finally the baseline was measured again. The measurement of the object to be measured was carried out sequentially from the low concentration side. The measurement was carried out with the source-drain voltage (Vd) set to -0.1 V and the gate voltage (Vg) set to 0.5 to -3.0 V. The baseline measurement and the object measurement were each carried out 5 times.

[0045] The measurement results are shown in Fig. 10. This is the result of taking the average of the current values measured five times for each concentration and plotting the current Id at Vg = -1.0V, with the last measurement of five out of the total number of measurements on the X-axis. Since there was a significant difference in the current values between the baseline measurement and the measurement of the object, the Y-axis was divided into two axes. From this graph, it can be seen that the baseline has slight fluctuations and the measurement of the object to be measured has a large change. It is considered that the adsorption of cysteine on the electrode contributes to the increase in the output current.

[0046] Furthermore, regarding the detection experiment of Example 2, Fig. 11 shows the result of plotting the current shift calculated 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 object to be measured 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 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 unknown concentration, it becomes possible to measure the concentration.

[0047] (Example 3) Measurement of the object to be measured As the electrode, one with a working electrode formed on a substrate (material: PPS, polyphenylene sulfide) was used. The conductive material of the working electrode was Au. It was fabricated by using a metal mask and depositing Au with a thickness of 100 nm by vapor deposition to obtain electrode X. The electrode area was 20 mm 2 as such. 0.5 mM of cortisol and 2.5 mM of diaminobenzene were added to Dulbecco's phosphate buffered saline to prepare Treatment Solution 1. Treatment Solution 1 was placed in a container, and electrode X, a platinum counter electrode, and an Ag / AgCl reference electrode were immersed, and a voltage was applied using cyclic voltammetry. The voltage range was -0.5 to 0.8 V and the scan rate was 100 mV / s. This was performed for 20 cycles, and then it was washed with ultrapure water and dried to obtain electrode X'.

[0048] Furthermore, potassium hydroxide was added to ultrapure water to a concentration of 0.1 M to prepare Treatment Solution 2. Treatment Solution 2 was placed in a container, and Electrode X’, a platinum counter electrode, and an Ag / AgCl reference electrode were immersed therein, and a voltage was applied using cyclic voltammetry. With the voltage range set to 0 to 1.0 V and the scan rate set to 100 mV / s, this was performed for 5 cycles, and then it was washed with ultrapure water and dried, thereby obtaining a polymer-immobilized capture electrode (the capture electrode (detection electrode) of Example 3) having a space inside that mimics the molecule of cortisol.

[0049] In glass containers, cortisol solutions (solvent: DPBS, Dulbecco's phosphate buffered saline) adjusted to concentrations of 0, 0.1, 10, 1,000, and 100,000 ppb were prepared respectively, the working electrode prepared before measurement was immersed therein, and it was left standing for 10 minutes. This operation was set so that the scientific interaction with the electrode would proceed sufficiently. Measurement of the measurement object was performed using Transistor-Type Sensor S4 that used the cysteine solution and the working electrode in the glass container, an Ag / AgCl electrode as the counter electrode, and a MOSFET (T2) as the transistor.

[0050] (Measurement of Baseline and Measurement of Object) Baseline measurement was performed using Transistor-Type Sensor S4’ that used DPBS in the glass container, a Pt electrode as the working electrode, and an Ag / AgCl electrode as the counter electrode. As the measurement procedure, baseline measurement was performed, measurement of the measurement object was performed, these were repeated, and finally baseline measurement was performed. Measurement of the measurement object was carried out sequentially from the low concentration side. For the measurement, the source-drain voltage (Vd) was set to -0.1 V, and the gate voltage (Vg) was set to 0.5 to -3.0 V. Baseline measurement and measurement of the object were each performed 5 times.

[0051] The measurement results are shown in Fig. 12. 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 Vg = -1.0V using the last measurement number out of the total number of measurements for 5 times on the X-axis. Since there was a large difference in the current values between the baseline measurement and the measurement of the object, the Y-axis is divided into two axes. From this graph, it can be seen that the baseline has minute fluctuations and the measurement of the object to be measured has a large amount of change. It is considered that the inclusion of cortisol in the electrode inhibits the permeation of ions and contributes to the decrease in the output current.

[0052] Furthermore, regarding the detection experiment of Example 3, Fig. 13 shows the result of calculating the current shift and plotting it for each cortisol concentration. The calculation method of the shift was the same as that of Example 2. From this result, it is possible to obtain a calibration curve of the object concentration and the shift 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.

[0053] The conditions of the examples and comparative examples are as shown in Table 1.

Table 1

Industrial Applicability

[0054] The field effect transistor type sensor of the present invention can quantitatively measure chemical substances very simply and has industrial applicability.

[0055] Explanation 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 10 Capacitor 11 Working electrode (extended gate electrode) 12 Counter electrode 13 Aqueous solution containing the detection target S transistor type sensor (S1, S2, S3)

Claims

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, wherein the working electrode is connected to the gate electrode, a capacitor is connected in series between the counter electrode and a power supply, and 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. A measurement method for quantitatively measuring a chemical substance by using a transistor-type sensor, comprising: disposing the capture electrode of the transistor-type sensor according to Claim 1 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 field-effect transistor; applying a gate voltage to the capacitor connected in series with the counter electrode; and measuring a current Id flowing between the drain electrode and the source electrode of the field-effect transistor.

3. measuring the current Id for each concentration of the chemical substance to obtain a concentration-current Id relationship curve; bringing the solution containing the chemical substance into contact with the capture electrode to obtain the current Id of the chemical substance; and further comprising comparing the current Id of the chemical substance with the concentration-current Id relationship curve to determine the concentration of the current Id of the chemical substance.

4. The measurement method according to Claim 3, wherein the step of obtaining the concentration-current Id relationship curve includes the following steps A to D; obtaining a current Id1 value of a solution containing the chemical substance with a known concentration at a predetermined voltage value (step A); obtaining a current Id2 value of a solution not containing the chemical substance at a predetermined voltage value (step B); alternately performing steps A and B while changing the concentration of the chemical substance in step A (step C); and calculating an 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 step C (step D).

5. In the A process and the B process, the current value is measured a plurality of times, 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 D process, an Ida3 value which is the average of two Ida2 values before and after one Ida1 value is calculated. The measurement method according to claim 4.

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