Sensor for detecting organic compound including leaving group, and detecting method using the sensor

Abstract

To provide a sensor capable of detecting an organic compound including a leaving group such as an organic halide easily with high sensitivity, and a detecting method for an organic compound including a leaving group using the sensor.SOLUTION: A sensor is used to detect an organic group including a leaving group. The sensor includes a detection part and a transistor. The detection part is connected to the transistor. On a surface of the detection part, a nitrogen-containing heterocyclic compound including a thiol group is fixed through a sulfur atom of the thiol group. A detecting method for an organic compound including a leaving group using this sensor is also provided.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a sensor for detecting an organic compound containing a leaving group and a method for detecting an organic compound containing a leaving group using the same. [Background technology]

[0002] Organic halides such as alkyl halides are reagents that are widely used in the fields of organic synthesis chemistry, etc. However, due to their high reactivity, they can have adverse effects on the human body, such as toxicity and carcinogenicity, so it is significant to detect these organic halides.

[0003] Conventionally, the mainstream method for detecting organic halides contained in aqueous solvents has been the use of relatively large instrumental analytical equipment such as gas chromatography. However, there is a demand for a detection device and method that can detect organic halides in samples more easily, with higher sensitivity, and that can be used on-site.

[0004] For example, Non-Patent Document 1 describes a method for detecting an alkyl halide by measuring the fluorescence of a pyridinium salt obtained by reacting a compound having a pyridine ring and a benzene ring with the alkyl halide. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] J. S, Fossey et al, Chem. Commun., 2011, 47, 253 Summary of the Invention [Problem to be solved by the invention]

[0006] However, the detection method for alkyl halides described in Non-Patent Document 1 uses a fluorescent sensor, which results in extremely low detection sensitivity, making it difficult to distinguish even slight differences in the structure of the target species.

[0007] Therefore, an object of the present invention is to provide a sensor capable of detecting organic compounds containing a leaving group, such as organic halides, simply and with high sensitivity, and a method for detecting an organic compound containing a leaving group using the same. [Means for solving the problem]

[0008] As a result of intensive research aimed at achieving the above object, the present inventors have found that a sensor comprising a detection site and a transistor, in which a nitrogen-containing heterocyclic compound having a thiol group is immobilized on the surface of the detection site via a sulfur atom of the thiol group, can detect an organic compound having a leaving group simply and with high sensitivity. Based on this finding, the present inventors have further researched and completed the present invention.

[0009] That is, the present invention provides the following inventions. Section 1. A sensor used for detecting an organic compound containing a leaving group, the sensor comprising a detection site and a transistor, the detection site being connected to the transistor, and a nitrogen-containing heterocyclic compound having a thiol group being fixed to a surface of the detection site via a sulfur atom of the thiol group. Section 2. Item 2. The sensor according to item 1, wherein the nitrogen-containing heterocyclic compound having a thiol group is a compound represented by the following formula (1): [ka] (Wherein, ring A is a monocyclic nitrogen-containing heterocycle, R 1 is a single bond or an alkylene group, R 2 is an alkyl group which may have a hydroxyl group, n is an integer of 0, 1, 2 or 3, and when n is 2 or 3, R 2 may be the same or different.) Section 3. Item 3. The sensor according to item 2, wherein in formula (1), ring A is a monocyclic nitrogen-containing heterocycle containing 2, 3 or 4 nitrogen atoms. Section 4. Item 4. The sensor according to item 2 or 3, wherein in formula (1), ring A is a monocyclic nitrogen-containing aromatic heterocycle containing 3 or 4 nitrogen atoms. Section 5. 5. The sensor according to any one of items 2 to 4, wherein in the formula (1), ring A is a tetrazole ring. Section 6. In the formula (1), R 1 is a single bond, and R 2 Item 6. The sensor according to any one of items 2 to 5, wherein is an alkyl group having 1 to 6 carbon atoms and a hydroxyl group, and n is 1. Section 7. The organic compound containing the leaving group is sp 3 Item 7. The sensor according to any one of items 1 to 6, which is an organic compound having, in the molecule, a site where a leaving group is bonded to a hybridized carbon atom. Section 8. The leaving group is a halogen atom or a group of the formula: -OSO2-R 3 (In the formula, R 3 represents an alkyl group, a haloalkyl group, or an aryl group. Item 8. The sensor according to any one of items 1 to 7, wherein R is a group represented by the formula: Section 9. Item 9. The sensor according to any one of items 1 to 8, wherein the transistor is an organic thin film transistor. Section 10. Item 10. The sensor according to any one of items 1 to 9, wherein the organic compound having a leaving group is detected by measuring a change in threshold voltage of the transistor caused by a reaction between the nitrogen-containing heterocyclic compound having a thiol group and an organic compound having a leaving group at the detection site. Section 11. A method for detecting an organic compound having a leaving group, comprising a step of contacting a detection site of the sensor according to any one of items 1 to 10 with a sample containing an organic compound having a leaving group. Section 12. Item 12. The detection method according to item 11, further comprising a step of detecting an organic compound having a leaving group by measuring a change in threshold voltage of a transistor caused by a reaction between the nitrogen-containing heterocyclic compound having a thiol group and an organic compound having a leaving group at the detection site. Section 13. Item 13. A method for identifying an organic compound having a leaving group, comprising the steps of: creating a model by pattern learning using principal component analysis based on data on changes in transmission characteristics of a sensor obtained by using the method for detecting an organic compound having a leaving group according to item 12; and identifying the organic compound having a leaving group by pattern recognition. Section 14. A step of creating a model by pattern learning using principal component analysis based on data on the change in transfer characteristics of the sensor obtained using the method for detecting an organic compound containing a leaving group according to item 12, and identifying the organic compound containing a leaving group to be measured by pattern recognition; A method for measuring the concentration of an organic compound containing a leaving group, comprising: measuring the concentration of the organic compound containing a leaving group as the measurement target. Effect of the Invention

[0010] The sensor of the present invention makes it possible to simply and sensitively detect organic compounds (particularly organic halogen compounds) containing a leaving group in a sample. [Brief description of the drawings]

[0011] [Figure 1] FIG. 1 is a schematic cross-sectional view of the organic halide detection sensor used in Examples 1 to 6. [Diagram 2] FIG. 2 is a graph showing the results of X-ray photoelectron spectroscopy (XPS) measurement after immersion in 1-hydroxyethyl-5-mercapto-1H-tetrazole (EMT) [horizontal axis: binding energy (eV), vertical axis: photoelectron intensity (au)]. [Diagram 3]Figure 3 is a graph showing the results of photoelectron yield spectroscopy (PYS) measurements before and after EMT immersion [horizontal axis: binding energy (eV), vertical axis: square root of electron count rate]. In Figure 3, ○ indicates the results before EMT immersion, and △ indicates the results after EMT immersion. [Figure 4] FIG. 4 shows the results of contact angle measurements before and after immersion in EMT. [Diagram 5] FIG. 5 is a graph showing the results of linear sweep voltammetry measurements after immersion in EMT [horizontal axis: voltage (V), vertical axis: current value (μA)]. [Figure 6] FIG. 6 is a graph showing the relationship between the gate voltage and the absolute value of the drain current with the addition of methyl iodide in Example 1 (solid line: before addition, dashed line: after addition of methyl iodide (100 μM)). [Figure 7] FIG. 7 is a graph showing the relationship between the amount of change in threshold voltage of the transistor in Example 1 and the concentration of methyl iodide (μM). [Figure 8] FIG. 8 is a graph showing the results of X-ray photoelectron spectroscopy (XPS) measurement after immersion in methyl iodide [horizontal axis: binding energy (eV), vertical axis: photoelectron intensity (au)]. [Figure 9] FIG. 9 is a graph showing the relationship between the gate voltage and the absolute value of the drain current with the addition of ethyl iodide in Example 2 (solid line: before addition, dashed line: after addition of ethyl iodide (100 μM)). [Figure 10] FIG. 10 is a graph showing the relationship between the amount of change in threshold voltage of the transistor in Example 2 and the concentration of ethyl iodide (μM). [Figure 11] FIG. 11 is a graph showing the relationship between the gate voltage and the absolute value of the drain current with the addition of 2-iodo-2-methylpropane in Example 3 (solid line: before addition, dashed line: after addition of 2-iodo-2-methylpropane (100 μM)). [Figure 12] FIG. 12 is a graph showing the relationship between the amount of change in threshold voltage of the transistor in Example 3 and the concentration (μM) of 2-iodo-2-methylpropane. [Figure 13]FIG. 13 is a graph showing the relationship between the gate voltage and the absolute value of the drain current with the addition of bromoethane in Example 4 (solid line: before addition, dashed line: after addition of bromoethane (100 μM)). [Figure 14] FIG. 14 is a graph showing the relationship between the amount of change in threshold voltage of the transistor in Example 4 and the bromoethane concentration (μM). [Figure 15] FIG. 15 is a graph showing the relationship between the gate voltage and the absolute value of the drain current with the addition of benzyl bromide in Example 5 (solid line: before addition, dashed line: after addition of benzyl bromide (100 μM)). [Figure 16] FIG. 16 is a graph showing the relationship between the amount of change in threshold voltage of the transistor in Example 5 and the benzyl bromide concentration (μM). [Figure 17] FIG. 17 is a graph showing the relationship between the gate voltage and the absolute value of the drain current with the addition of methyl trifluoromethanesulfonate in Example 6 (solid line: before addition, dashed line: after addition of methyl trifluoromethanesulfonate (100 μM)). [Figure 18] FIG. 18 is a graph showing the relationship between the amount of change in threshold voltage of the transistor in Example 6 and the concentration (μM) of methyl trifluoromethanesulfonate. [Figure 19] FIG. 19 is a graph showing the relationship between the amount of change in threshold voltage of the transistor and the concentration (μM) of the electrophile in Examples 1 to 6. [Figure 20] FIG. 20 is a graph showing the relationship between the gate voltage and the absolute value of the drain current with the addition of 2-iodopropane in Example 7 (solid line: before addition, dashed line: after addition of 2-iodopropane (50 μM)). [Figure 21] FIG. 21 is a graph showing the relationship between the amount of change in threshold voltage of the transistor in Example 7 and the concentration (μM) of 2-iodopropane. [Figure 22]Fig. 22 is a graph (horizontal axis: first principal component, vertical axis: second principal component) obtained from the principal component analysis of six organic compounds containing a leaving group (methyl iodide, ethyl iodide, 2-iodopropane, 2-iodo-2-methylpropane, bromoethane, and methyl trifluoromethanesulfonate) in Example 8. In Fig. 22, ○ represents methyl iodide, □ represents ethyl iodide, △ represents 2-iodopropane, hexagonal symbols represent 2-iodo-2-methylpropane, ◇ represents bromoethane, and pentagonal symbols represent methyl trifluoromethanesulfonate. [Figure 23] Fig. 23 is a graph showing the results of the identification and concentration measurement test of six organic compounds containing leaving groups (methyl iodide, ethyl iodide, 2-iodopropane, 2-iodo-2-methylpropane, bromoethane, and methyl trifluoromethanesulfonate) by principal component analysis in Example 9 (horizontal axis: first principal component, vertical axis: second principal component). In Fig. 23, ○ represents methyl iodide, □ represents ethyl iodide, △ represents 2-iodopropane, hexagonal symbols represent 2-iodo-2-methylpropane, ◇ represents bromoethane, and pentagonal symbols represent methyl trifluoromethanesulfonate. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] Hereinafter, preferred embodiments of the present invention will be described in detail. The following description of the components may be based on representative embodiments and specific examples, but the present invention is not limited to such embodiments.

[0013] In the numerical ranges described in stages in this specification, the upper or lower limit of a certain numerical range can be arbitrarily combined with the upper or lower limit of another numerical range. In addition, in the numerical ranges described in this specification, the upper or lower limit of the numerical range may be replaced with a value shown in an example or a value that can be unambiguously derived from an example. Furthermore, in this specification, a numerical value connected with "~" means a numerical range that includes the numerical values ​​before and after "~" as the lower and upper limits.

[0014] In this specification, the expressions "contain" and "include" include the concepts of "contain", "include", "consist essentially of" and "consist only of".

[0015] In this specification, "A and / or B" means "one of A and B" or "both A and B", and specifically means "A", "B", or "A and B".

[0016] 1. Sensors The sensor of the present invention comprises a detection site and a transistor. A nitrogen-containing heterocyclic compound having a thiol group is fixed (or bonded) to the surface of the detection site via the sulfur atom of the thiol group. The detection site specifically comprises a substrate and a precious metal film provided thereon, and the nitrogen-containing heterocyclic compound is fixed to the surface of the precious metal film via the sulfur atom of the thiol group. In the sensor of the present invention, the transistor, which is the driving part, and the detection site, which is the detection part, are usually separated, and the transistor and the detection site are electrically connected. Typically, the gate electrode of the transistor and the precious metal film of the detection site are electrically connected.

[0017] The threshold voltage of the transistor changes as a result of the reaction between the nitrogen-containing heterocyclic compound and an organic compound (particularly an organic halide) containing a leaving group at the detection site. The organic compound containing a leaving group can be detected by measuring the resulting change in threshold voltage. With such a configuration, the sensor using the transistor of the present invention can easily detect an organic compound containing a leaving group in a sample with high sensitivity. The sensor of the present invention can also be easily fabricated as described below.

[0018] The sensor of the present invention may further include a device for detecting a change in the threshold voltage of the transistor, and such a device may be a known device. For example, a source meter (product name "KEITHLEY 2612B", manufactured by Tektronix & Fluke Corporation) may be mentioned. In this case, an embodiment including the sensor of the present invention and the device for detecting a change in the threshold voltage of the transistor may be understood as a system used to detect an organic compound containing a leaving group.

[0019] Hereinafter, in this specification, the sensor used for detecting an organic compound containing a leaving group of the present invention may be referred to as a "sensor for detecting an organic compound containing a leaving group" or simply as a "sensor of the present invention." In addition, a nitrogen-containing heterocyclic compound having a thiol group may be referred to simply as a "nitrogen-containing heterocyclic compound."

[0020] In the sensor of the present invention, the species to be detected is an organic compound containing a leaving group, typically sp 3 Examples of such organic compounds include organic compounds having a site in the molecule where a leaving group is bonded to a hybridized carbon atom. The molecule may have one or more such sites. Preferably, the compound has one site.

[0021] The leaving group in the organic compound containing a leaving group is preferably one that can react (nucleophilic substitution reaction) with the nitrogen atom of the nitrogen-containing heterocyclic compound present on the surface of the detection site based on the detection principle of the sensor of the present invention. Examples of the leaving group include a halogen atom, a compound represented by the formula (A): -OSO2-R 3 (In the formula, R 3 represents an alkyl group, a haloalkyl group, or an aryl group. ) a methylsulfonyl group, an ethylsulfonyl group, and the like. Among these, the leaving group is preferably a halogen atom or a group represented by the formula (A): -OSO2-R 3 (In the formula, R 3 represents an alkyl group, a haloalkyl group, or an aryl group.

[0022] Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, etc. A chlorine atom, a bromine atom, or an iodine atom is preferable, and a bromine atom or an iodine atom is more preferable.

[0023] In the group represented by formula (A), R 3 Examples of the alkyl group represented by the formula (I) include alkyl groups having 1 to 10 carbon atoms (1, 2, 3, 4, 5, 6, 7, 8, 9, or 10). Examples of the alkyl group having 1 to 10 carbon atoms include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an isopentyl group, a neopentyl group, a cyclopentyl group, an n-hexyl group, an n-heptyl group, an n-octyl group, an n-nonyl group, and an n-decyl group.

[0024] In the group represented by formula (A), R 3 The alkyl group represented by the formula (I) is preferably an alkyl group having 1 to 5 carbon atoms (1, 2, 3, 4 or 5), and more preferably a methyl group, an ethyl group, an n-propyl group or an isopropyl group.

[0025] In the group represented by formula (A), R 3 Examples of the haloalkyl group represented by the formula (I) include the above-mentioned alkyl groups in which some or all of the hydrogen atoms are substituted with halogen atoms (particularly, fluorine atoms). Specific examples include a trifluoromethyl group and a pentafluoroethyl group.

[0026] In the group represented by formula (A), R 3 Examples of the aryl group represented by the formula (I) include a phenyl group, a toluyl group, a xylyl group, and a naphthyl group.

[0027] The group represented by formula (A) is preferably a methanesulfonyloxy group (-OMs), a trifluoromethanesulfonyloxy group (-OTf) or a p-toluenesulfonyloxy group (-OTs), and particularly preferably a trifluoromethanesulfonyloxy group.

[0028] In the sensor of the present invention, the species to be detected is particularly preferably methyl iodide, ethyl iodide, 2-iodopropane, 2-iodo-2-methylpropane, bromoethane, benzyl bromide, or methyl trifluoromethanesulfonate.

[0029] The sensor of the present invention comprises a detection site and a transistor. A nitrogen-containing heterocyclic compound having a thiol group is fixed (or bonded) to the surface of the detection site via the sulfur atom of the thiol group. The detection site specifically comprises a substrate and a precious metal film provided thereon, and the nitrogen-containing heterocyclic compound is fixed to the surface of the precious metal film via the sulfur atom of the thiol group. The detection site is connected to the transistor, and typically, the gate electrode of the transistor is electrically connected to the precious metal film of the detection site.

[0030] The threshold voltage of the transistor changes as a result of the reaction between the nitrogen-containing heterocyclic compound and an organic compound (particularly an organic halide) containing a leaving group at the detection site. The organic compound containing a leaving group can be detected by measuring the resulting change in threshold voltage. With such a configuration, the sensor using the transistor of the present invention can easily detect an organic compound containing a leaving group in a sample with high sensitivity. The sensor of the present invention can also be easily fabricated as described below.

[0031] In the present invention, the transistor and the detection site are usually electrically connected. It is preferable that the sensor of the present invention comprises a transistor and a detection site, the transistor comprises a gate electrode, and the gate electrode is electrically connected to the detection site.

[0032] In this specification, being electrically connected means that the transistor and the detection site are connected via a conductive material (for example, a conductive cable, etc.).

[0033] In the present invention, the detection site means a site including a substrate and a precious metal film formed on the substrate. In the present invention, the surface of the detection site usually means the surface of the precious metal film formed on the substrate. Therefore, more specifically, being electrically connected means that the gate electrode of the transistor and the precious metal film of the detection site are electrically connected.

[0034] Examples of the noble metal constituting the noble metal film include gold, silver, copper, ruthenium, rhodium, palladium, osmium, iridium, platinum, etc. These noble metals can be used alone or in combination of two or more. Among these noble metals, gold, silver, palladium, and platinum are preferred, and gold is more preferred.

[0035] The noble metal film is preferably formed on the substrate by a vacuum deposition method. The thickness of the noble metal film is usually 10 nm to 100 nm, preferably 20 nm to 80 nm. The thickness of the film can usually be measured using a stylus-type thin film step gauge.

[0036] The material constituting the substrate at the detection site is not particularly limited, and may be any material commonly used in this technical field, such as polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polyethersulfone (PES), polyimide (PI), polyetheretherketone (PEEK), polycarbonate (PC), polyphenylene sulfide (PPS), polyetherimide (PEI), etc.

[0037] In the present invention, a nitrogen-containing heterocyclic compound having a thiol group is usually fixed to the surface of a detection site (preferably the surface of a precious metal film provided on a substrate, particularly preferably the surface of a gold thin film provided on a substrate) via a sulfur atom constituting the thiol group. The nitrogen-containing heterocyclic compound is chemically stable by being fixed to the surface of a detection site (preferably the surface of a precious metal film provided on a substrate, particularly preferably the surface of a gold thin film provided on a substrate) via the sulfur atom.

[0038] The amount of the nitrogen-containing heterocyclic compound having a thiol group fixed via a sulfur atom on the surface of the detection site (preferably the surface of a noble metal film provided on a substrate, particularly preferably the surface of a thin gold film provided on a substrate) can be expressed as the number of moles of the nitrogen-containing heterocyclic compound having a thiol group fixed (bonded) via a sulfur atom per unit area of ​​the detection site. This amount can be measured by linear sweep voltammetry described in the Examples. The amount of the nitrogen-containing heterocyclic compound having a thiol group fixed via a sulfur atom on the surface of the detection site (preferably the surface of a noble metal film provided on a substrate, particularly preferably the surface of a thin gold film provided on a substrate) is usually 0.1×10 -9 mol / cm 2 ~10.0×10 -9 mol / cm 2 and preferably 0.5×10 -9 mol / cm 2 ~7.0×10 -9 mol / cm 2 , more preferably 1×10 -9 mol / cm 2 ~5.0×10 -9 mol / cm 2 It is.

[0039] The sensor of the present invention has a configuration in which a nitrogen-containing heterocyclic compound having a thiol group is fixed (bonded) to the surface of a detection site via a sulfur atom constituting the thiol group. That is, the sensor has a configuration in which a nitrogen-containing heterocyclic compound having a thiol group is fixed to the surface of a detection site (preferably the surface of a noble metal film provided on a substrate, particularly preferably the surface of a thin gold film provided on a substrate) via a sulfide group (-S-) derived from the thiol group.

[0040] In other words, the sensor of the present invention has a structure in which a nitrogen-containing heterocyclic compound is bound to the surface of the detection site (preferably the surface of a precious metal film provided on a substrate, particularly preferably the surface of a gold thin film provided on a substrate) via -S-, and the nitrogen-containing heterocyclic compound is arranged as a monomolecule on the surface of the detection site (preferably the surface of a precious metal film provided on a substrate, particularly preferably the surface of a gold thin film provided on a substrate). Therefore, it can be said that a self-assembled monolayer (SAM) in which the nitrogen-containing heterocyclic compounds are arranged is formed on the surface of the detection site.

[0041] The method of forming this SAM on the surface of the detection site can be carried out, for example, as follows: By treating the surface of the detection site with a nitrogen-containing heterocyclic compound having a thiol group to form a self-assembled monolayer (SAM), it is possible to form a state in which the nitrogen-containing heterocyclic compound is immobilized on the surface of the detection site via the sulfur atom constituting the thiol group (i.e., a state in which the hydrogen atom of the thiol group at the end of the nitrogen-containing heterocyclic compound is eliminated, the sulfur atom is bonded to the surface of the detection site, and the structure of the surface of the detection site-S-nitrogen-containing heterocyclic compound is formed).

[0042] Typically, a SAM can be formed by reacting a nitrogen-containing heterocyclic compound having a thiol group with the surface of a detection site (preferably the surface of a precious metal film provided on a substrate, particularly preferably the surface of a gold thin film provided on a substrate). The reaction can be carried out in a solvent. From the viewpoint of the stability of the nitrogen-containing heterocyclic compound having a thiol group, it is preferable to use a reducing agent.

[0043] Examples of reducing agents include tris(2-carboxyethyl)phosphine hydrochloride (TCEP-HCl), dithiothreitol (DTT), 2-mercaptoethanol, sodium borohydride, and triphenylphosphine. These reducing agents can be used alone or in combination of two or more. Among these reducing agents, TCEP-HCl is preferred.

[0044] The amount of the reducing agent used is preferably 0.1 mol or more and 25 mol or less, more preferably 0.5 mol or more and 20 mol or less, more preferably 1 mol or more and 15 mol or less, and even more preferably 5 mol or more and 10 mol or less, relative to 1 mol of the nitrogen-containing heterocyclic compound having a thiol group.

[0045] The solvent is preferably a hydrophilic organic solvent, and examples thereof include alcohol solvents such as methanol, ethanol, isopropanol, propyl alcohol, butanol, and isobutanol.

[0046] In one example of the procedure for treating the surface of the detection site with a SAM using a nitrogen-containing heterocyclic compound having a thiol group, the nitrogen-containing heterocyclic compound and a reducing agent are first dissolved in a hydrophilic organic solvent to prepare a solution containing the nitrogen-containing heterocyclic compound and the reducing agent, and then the surface of the detection site is immersed in the prepared solution to form a SAM.

[0047] The temperature when the surface of the detection site is immersed in the prepared solution is usually 5°C or higher and 45°C or lower, preferably 10°C or higher and 40°C or lower, more preferably 15°C or higher and 35°C or lower, and even more preferably 20°C or higher and 30°C or lower.

[0048] The time for immersing the surface of the detection site in the prepared solution is usually from 10 minutes to 50 hours, preferably from 20 minutes to 65 hours, more preferably from 30 minutes to 20 hours, even more preferably from 45 minutes to 10 hours, and even more preferably from 1 hour to 5 hours.

[0049] The present invention also provides a member in which a noble metal (film) provided on a substrate is subjected to SAM treatment using a nitrogen-containing heterocyclic compound having a thiol group. The member includes a noble metal (film) provided on a substrate and a nitrogen-containing heterocyclic compound having a thiol group, and the nitrogen-containing heterocyclic compound is fixed to the surface of the noble metal (film) provided on the substrate via the sulfur atom of the thiol group. The member can be produced by reacting a nitrogen-containing heterocyclic compound having a thiol group with a noble metal (film) provided on a substrate in the presence of a reducing agent, as described above.

[0050] The thus obtained SAM is formed on the surface of the detection site (preferably the surface of a noble metal film provided on a substrate, particularly preferably the surface of a thin gold film provided on a substrate).

[0051] The detection principle of the organic compound (particularly, organic halide) containing a leaving group of the present invention is presumed to be as follows. That is, the sulfur atom constituting the thiol group of the nitrogen-containing heterocyclic compound reacts with the organic compound containing the leaving group to form a complex. The organic compound containing the leaving group can be detected by measuring the resulting change in threshold voltage of the transistor. In this reaction, the nitrogen atom of the nitrogen-containing heterocyclic compound having a thiol group reacts with the organic compound containing the leaving group to form an onium compound (onium salt) containing nitrogen, which is thought to cause a change in the threshold voltage. Therefore, the nitrogen-containing heterocyclic compound can be widely adopted as long as it has a nitrogen atom that can react with the organic compound containing the leaving group.

[0052] In the present invention, the nitrogen-containing heterocycle in the nitrogen-containing heterocyclic compound having a thiol group contains one or more nitrogen atoms, preferably 1 to 10 (1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) nitrogen atoms, more preferably 2 to 7 (2, 3, 4, 5, 6, or 7) nitrogen atoms, even more preferably 3 to 5 (3, 4, or 5) nitrogen atoms, and particularly preferably 4 nitrogen atoms. The nitrogen-containing heterocycle may contain, as heteroatoms, sulfur atoms, oxygen atoms, etc. in addition to the nitrogen atom.

[0053] The nitrogen-containing heterocycle may be either an aromatic heterocycle or an aliphatic heterocycle, and may be either a monocycle or a bicycle or more. A monocyclic nitrogen-containing aromatic heterocycle or a monocyclic nitrogen-containing aliphatic heterocycle is preferred, and a monocyclic nitrogen-containing aromatic heterocycle is more preferred.

[0054] Examples of the nitrogen-containing heterocycle include monocyclic nitrogen-containing aromatic heterocycles such as pyridine, pyridazine, pyrimidine, pyrazine, triazine, pyrrole, pyrazole, imidazole, triazole, tetrazole, oxazole, oxadiazole, and thiadiazole; bicyclic or more nitrogen-containing aromatic heterocycles such as indole, isoindole, 1H-indazole, purine, quinoline, isoquinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, pteridine, phenanthridine, and acridine; monocyclic nitrogen-containing aliphatic heterocycles such as pyrrolidine, pyrroline, imidazolidine, imidazoline, pyrazolidine, piperidine, piperazine, and morpholine; and bicyclic or more nitrogen-containing aliphatic heterocycles such as quinuclidine.

[0055] The nitrogen-containing heterocyclic compound having a thiol group means a compound in which a group having a thiol group as a substituent is bonded to a nitrogen-containing heterocycle, and includes a compound in which a thiol group is directly bonded to a nitrogen-containing heterocycle, a compound in which a group having a thiol group (e.g., a thioalkyl group, etc.) is bonded to a nitrogen-containing heterocycle, and the like.

[0056] A preferred example of the nitrogen-containing heterocyclic compound having a thiol group is a compound represented by the following formula (1). [ka] (Wherein, ring A is a monocyclic nitrogen-containing heterocycle, R 1 is a single bond or an alkylene group, R 2 is an alkyl group which may have a hydroxyl group, n is an integer of 0, 1, 2 or 3, and when n is 2 or 3, R 2 may be the same or different.)

[0057] Examples of the monocyclic nitrogen-containing heterocycle represented by ring A include monocyclic nitrogen-containing heterocycles containing 1 to 5 (1, 2, 3, 4 or 5) nitrogen atoms. Further examples include monocyclic nitrogen-containing heterocycles containing 2 to 4 (2, 3 or 4) nitrogen atoms, more preferably 3 or 4 nitrogen atoms, particularly 4 nitrogen atoms. The nitrogen-containing heterocycle may contain, as a heteroatom, a sulfur atom, an oxygen atom, etc., in addition to the nitrogen atom. The monocyclic nitrogen-containing heterocycle may be a monocyclic nitrogen-containing aromatic heterocycle or a nitrogen-containing aliphatic heterocycle, preferably a monocyclic nitrogen-containing aromatic heterocycle.

[0058] Specific examples of the monocyclic nitrogen-containing heterocycle include monocyclic nitrogen-containing aromatic heterocycles such as pyridine, pyridazine, pyrimidine, pyrazine, triazine, pyrrole, pyrazole, imidazole, triazole, tetrazole, oxazole, oxadiazole, thiadiazole, etc.; and monocyclic nitrogen-containing aliphatic heterocycles such as pyrrolidine, pyrroline, imidazolidine, imidazoline, pyrazolidine, piperidine, piperazine, morpholine, etc. Among these, monocyclic nitrogen-containing aromatic heterocycles such as pyridine, pyridazine, pyrimidine, pyrazine, triazine, pyrrole, pyrazole, imidazole, triazole, tetrazole, etc. are preferred.

[0059] R 1 Examples of the alkylene group represented by the formula (I) include an alkylene group having 1 to 10 carbon atoms (1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) (preferably an alkylene group having 1 to 5 carbon atoms (1, 2, 3, 4, or 5)). The alkylene group may be either linear or branched. 1 is preferably a single bond.

[0060] R 2 The alkyl group in the alkyl group which may have a hydroxyl group and is represented by the following formula (1): is an alkyl group having 1 to 10 carbon atoms (preferably an alkyl group having 1 to 5 (1, 2, 3, 4 or 5) carbon atoms, more preferably an alkyl group having 2 or 3 carbon atoms). The alkyl group may be either linear or branched. The alkyl group having a hydroxyl group is a group in which one or more (particularly one) hydrogen atoms on the above-mentioned alkyl group are substituted with a hydroxyl group, and specific examples thereof include a 1-hydroxymethyl group, a 1-hydroxyethyl group, a 2-hydroxyethyl group, a 2-hydroxypropyl group, and a 3-hydroxypropyl group, and preferably a 2-hydroxyethyl group.

[0061] n is preferably 1 or 2, and more preferably 1.

[0062] Preferred examples of the compounds represented by formula (1) include compounds in which ring A is an aromatic heterocycle containing 3 or 4 nitrogen atoms (particularly, a triazole ring or a tetrazole ring).

[0063] Other preferred compounds of the formula (1) include those represented by R 1 is a single bond, and R 2 is an alkyl group having 1 to 6 carbon atoms (1, 2, 3, 4, 5 or 6) and having a hydroxyl group, and n is 1. Further, examples of the compound include a compound in which ring A is a tetrazole ring.

[0064] Other preferred compounds among those represented by formula (1) include compounds represented by formula (2). [ka] (In the formula, ring A1 is a 5- or 6-membered nitrogen-containing aromatic heterocycle containing 1 to 5 (1, 2, 3, 4, or 5) nitrogen atoms, and R 21 is an alkyl group having 1 to 5 (1, 2, 3, 4 or 5) carbon atoms substituted with a hydroxyl group.

[0065] Examples of the 5- or 6-membered nitrogen-containing aromatic heterocycle containing 1 to 5 (1, 2, 3, 4 or 5) nitrogen atoms represented by Ring A1 include monocyclic nitrogen-containing aromatic heterocycles such as pyridine, pyridazine, pyrimidine, pyrazine, triazine, pyrrole, pyrazole, imidazole, triazole, tetrazole, oxazole, oxadiazole, and thiadiazole; among these, pyridine, triazole, tetrazole, and the like are preferred.

[0066] In addition, mercapto group (-SH) and R 21 are preferably bonded to two adjacent atoms constituting ring A1.

[0067] In the present invention, the nitrogen-containing heterocyclic compound having a thiol group is preferably 1-hydroxyethyl-5-mercapto-1H-tetrazole (EMT) or 1-(3-hydroxypropyl)-5-mercapto-1H-tetrazole, more preferably EMT.

[0068] The sensor of the present invention is a transistor-type sensor having a detection site and a transistor, and is capable of detecting an organic compound containing a leaving group. A nitrogen-containing heterocyclic compound having a thiol group is fixed to the surface of the detection site via a sulfur atom constituting the thiol group, and the nitrogen atom present in the nitrogen-containing heterocycle (particularly, ring A of the compound represented by formula (1)) reacts with an organic compound containing a leaving group to measure a change in the threshold voltage of the transistor, thereby enabling detection of the organic compound containing a leaving group.

[0069] The compound represented by the above formula (1) is R 1 It is immobilized on the surface of the detection site (preferably the surface of a precious metal film provided on a substrate, particularly preferably the surface of a thin gold film provided on a substrate) via a sulfur atom constituting a thiol group adjacent to the detection site.

[0070] In the present invention, the detection site preferably further comprises a reference electrode, which makes it possible to grasp the relative change (difference) in the detection target from a plurality of measured values, measured values ​​over time, etc.

[0071] When the detection site further comprises a reference electrode, it is preferable to use a silver / silver chloride electrode (Ag / AgCl electrode), a gold electrode treated with a self-assembled monolayer (SAM), or a metal covered with a polymer as the reference electrode, and an Ag / AgCl electrode is more preferable. By setting such a reference electrode, absolute evaluation of the detection target becomes easier.

[0072] The transistor in the transistor-type sensor of the present invention may have a wide variety of known transistor structures, but is preferably a thin-film transistor (TFT) because it is small and easy to use. In the case of using a TFT, a transistor-type sensor with a more flexible configuration can be constructed.

[0073] In the present invention, the transistor may be an inorganic transistor or an organic transistor, with an organic thin film transistor (organic TFT) being more preferred since it can be produced using a solution process and therefore can be mass-produced.

[0074] The transistor can be manufactured using, for example, a dry process such as a vapor deposition method or a sputtering method; coating such as spin coating, drop casting, dip coating, bar coating, die coating, or spray coating; or printing techniques using various printers such as screen printing, gravure offset printing, letterpress reverse printing, inkjet printing, etc. Among these, spin coating and drop casting can produce a transistor more efficiently and at a lower cost.

[0075] Examples of materials for the substrate constituting the transistor include inorganic materials such as glass, ceramics, aluminum oxide, silicon, silicon oxide, tantalum dioxide, tantalum pentoxide, and indium tin oxide; metal materials such as gold, copper, chromium, titanium, and aluminum; resin materials such as polyethylene naphthalate, polyethylene terephthalate, polyethylene, polypropylene, polystyrene, polyimide, and polyparaxylylene (Parylene (registered trademark)); paper materials such as coated paper and craft paper; and surface-coated nonwoven fabric. These materials can be used alone or in combination of two or more. Also, materials in which these materials are multilayered can be used.

[0076] When the transistor is an organic TFT, the substrate may be made of, for example, resin materials such as polyethylene naphthalate, polyethylene terephthalate, polyethylene, polyimide, polyparaxylylene (Parylene (registered trademark)), etc.; or paper materials such as coated paper and craft paper.

[0077] The semiconductor layer constituting the transistor is preferably a polymer semiconductor layer.

[0078] The materials constituting the polymer semiconductor layer are, in the case of P-type, pentacene, dinaphthothienothiophene, benzothienobenzothiophene (Cn-BTBT), 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS pentacene), 5,11-bis(triethylsilylethynyl)anthradithiophene (TES-ADT), rubrene, poly(3-hexylthiophene-2,5-diyl) (P3 HT), poly[2,5-bis(3-dodecylthiophene-2-yl)thieno[3,2-b]thiophene] (pBTTT-C12), poly[2,5-bis(3-tetradecylthiophene-2-yl)thieno[3,2-b]thiophene] (pBTTT-C14), poly(2,5-bis(3-hexadecylthiophene-2-yl)thieno[3,2-b]thiophene) (pBTTT-C16), etc. can be used.

[0079] As a constituent material of the polymer semiconductor layer, in the case of an N-type, for example, fullerene or the like can be used.

[0080] Examples of materials that can be used for the gate electrode of a transistor include aluminum, silver, gold, copper, titanium, indium tin oxide (ITO), poly(3,4-ethylenedioxythiophene):polystyrenesulfonic acid (PEDOT:PSS), etc. In the present invention, aluminum is preferred as the gate electrode material.

[0081] Examples of materials for the source electrode and drain electrode of a transistor include gold, silver, copper, platinum, aluminum, PEDOT:PSS, etc. Gold is preferred as the material for the source electrode and drain electrode.

[0082] Examples of materials for the gate insulating film that constitutes a transistor include silica, alumina, polystyrene, polyvinylphenol, polyvinyl alcohol, polymethyl methacrylate, polydimethylsiloxane, polysilsesquioxane, ionic liquid, polytetrafluoroethylene [Teflon (registered trademark) AF], and Cytop (registered trademark).

[0083] The transistor preferably includes a liquid repellent bank layer and a sealing film on the substrate.

[0084] Examples of materials for the sealing film (protective film) that constitutes the transistor include polytetrafluoroethylene (Teflon (registered trademark) AF), Cytop (registered trademark), and polyparaxylylene (Parylene (registered trademark)).

[0085] In the present invention, the transistor and the detection site are usually prepared separately, and when in use, they can be connected by a conductive cable. Since the detection site that directly contacts the sample (preferably a liquid sample) is easily consumed, only the detection site can be easily replaced and attached according to its lifespan. This allows measurement using the transistor in a stable state. In addition, there is no need to replace the entire transistor-type sensor, and the detection site can be used repeatedly by performing a cleaning operation, which is advantageous in terms of economy.

[0086] The transistor-type sensor of the present invention includes, in addition to the detection site and the transistor, for example, a reference electrode.

[0087] In the present invention, the amount of the nitrogen-containing heterocyclic compound having a thiol group immobilized via a sulfur atom on the surface of the detection site (preferably the surface of a precious metal film provided on a substrate, particularly preferably the surface of a gold thin film provided on a substrate) is usually 0.1 × 10 -9 mol / cm 2 ~10.0×10 -9 mol / cm 2 , preferably 0.5 x 10 ―9 mol / cm 2 Above 7.0×10 ―9 mol / cm 2 Less than or equal to 1.0×10 ―9 mol / cm 2 Above 5.0×10 ―9 mol / cm 2 The amount of the nitrogen-containing heterocyclic compound having a thiol group immobilized on the surface of the detection site via a sulfur atom can be measured by linear sweep voltammetry.

[0088] 2. Sensor Applications (1) Detection of organic compounds containing leaving groups The sensor of the present invention can easily and sensitively detect organic compounds containing a leaving group contained in a wide range of samples (preferably liquid samples). Therefore, it is useful as a sensor for detecting an organic compound containing a leaving group. The method for detecting an organic compound containing a leaving group includes a step (hereinafter referred to as "Step A") of contacting the sensor with a sample (preferably a liquid sample) containing an organic compound containing a leaving group. Details of the sensor are as described above in "1. Sensor" unless otherwise specified.

[0089] The organic compound containing a leaving group to be detected by the sensor of the present invention is as described above in "1. Sensor."

[0090] In the method for detecting an organic compound containing a leaving group of the present invention, data on the transmission characteristics of the sensor of the present invention accompanying the addition of an organic compound containing a leaving group (i.e., data on the transmission characteristics of the sensor of the present invention before and after the addition of an organic compound containing a leaving group) can be obtained. The transistor included in the sensor is preferably an organic thin film transistor.

[0091] In the above step A, the contacting means may be, for example, immersing all or a part of the detection site of the sensor of the present invention in a liquid sample containing an organic compound containing a leaving group. "Immersing the entire detection site" means that the detection site of the sensor of the present invention is completely immersed in a liquid sample containing an organic compound containing a leaving group. "Immersing a part of the detection site" means that the detection site of the sensor of the present invention is partially immersed in a liquid sample containing an organic compound containing a leaving group.

[0092] The sample is preferably a liquid sample. Examples of the sample include buffers such as HEPES buffer and MES buffer. When a HEPES buffer is used as the sample, the pH of the buffer is preferably 6.0 to 8.0, more preferably 6.5 to 7.5. When a MES buffer is used as the sample, the pH of the buffer is preferably 4.5 to 6.5, more preferably 5.0 to 6.0.

[0093] The method for detecting an organic compound containing a leaving group of the present invention preferably includes, after the step A, a step (step B) of detecting the organic compound containing a leaving group by measuring a change in the threshold voltage of a transistor caused by a reaction between the organic compound containing a leaving group contained in the sample (preferably a liquid sample) and a nitrogen atom constituting a nitrogen-containing heterocyclic compound. In this case, the sensor of the present invention preferably further includes a device for measuring the change in the threshold voltage of the transistor. The sensor of the present invention is capable of detecting an organic compound containing a leaving group even at a low concentration of the micromolar (μM) level in a liquid sample.

[0094] (2) Identification and concentration measurement of organic compounds containing leaving groups The method for identifying an organic compound containing a leaving group may include a step (hereinafter referred to as "step 1") of creating a model by performing pattern learning using principal component analysis (PCA) based on data on changes in transmission characteristics of a sensor obtained using the above-mentioned method for detecting an organic compound containing a leaving group, and identifying the organic compound containing a leaving group by pattern recognition.

[0095] In the method for identifying an organic compound containing a leaving group, the details of the sensor of the present invention are as described above in "1. Sensor" unless otherwise specified. The details of the method for detecting an organic compound containing a leaving group are as described above in "2.(1) Detection of an organic compound containing a leaving group" unless otherwise specified.

[0096] In step 1, the model is usually a canonical scores plot.

[0097] In step 1, it is preferable to identify organic compounds containing two or more types of leaving groups by pattern recognition.

[0098] The method for measuring the concentration of an organic compound containing a leaving group of this embodiment includes a step A of creating a model through pattern learning by principal component analysis based on data on changes in transmission characteristics of a sensor obtained using a method for detecting an organic compound containing a leaving group, and identifying the organic compound containing a leaving group to be measured by pattern recognition, and a step B of measuring the concentration of the organic compound containing a leaving group to be measured identified in step A.

[0099] In step B, it is preferable to measure the concentration of the target organic compound containing a leaving group identified in step A in the presence of contaminants other than the target organic compound containing a leaving group.

[0100] In the method for discriminating an organic compound containing a leaving group, it is preferable to further include, after step 1, a step (hereinafter referred to as "step 2") of measuring the concentration of the organic compound containing a leaving group discriminated in step 1 using a support vector machine (SVM), which is a type of machine learning model. In the method for discriminating an organic compound containing a leaving group, steps 1 and 2 are collectively referred to as a method for measuring the concentration of an organic compound containing a leaving group.

[0101] Step 2 is preferably a step of measuring the concentration of an organic compound containing a specific leaving group to be measured from among the organic compounds containing two or more types of leaving groups identified in step 1 using SVM.

[0102] In step 2, a calibration curve prepared from a calibration plot can usually be used for measuring the concentration.

[0103] The method for measuring the concentration of an organic compound containing a leaving group may include a step of measuring the concentration of the organic compound containing a leaving group to be measured in the presence of impurities other than the organic compound containing a leaving group to be measured, using a support vector machine, which is a type of machine learning model, based on data on the change in transmission characteristics of the sensor obtained using the method for detecting an organic compound containing a leaving group. In this step, a calibration curve created from a calibration plot can usually be used for the concentration measurement.

[0104] In the method for measuring the concentration of an organic compound containing a leaving group, the details of the sensor of the present invention are as described above in "1. Sensor" unless otherwise specified. The details of the method for detecting an organic compound containing a leaving group are as described above in "2.(1) Detection of an organic compound containing a leaving group" unless otherwise specified.

[0105] The above-mentioned impurities are preferably organic compounds other than the organic compound containing a leaving group to be measured, inorganic compounds, ions, etc. Since the sensor of the present invention can selectively detect an organic compound containing a leaving group, it is possible to effectively measure the concentration of an organic compound containing a specific leaving group even when impurities are present.

[0106] The organic compound containing a leaving group is as described above in "1. Sensor." The organic compound containing a leaving group to be measured is particularly preferably methyl iodide, ethyl iodide, 2-iodopropane, 2-iodo-2-methylpropane, bromoethane, benzyl bromide, or methyl trifluoromethanesulfonate. EXAMPLES

[0107] The present invention will be specifically described below based on Production Examples and Examples, but the present invention is not limited to the following Production Examples and Examples.

[0108] (Production Example 1) Fabrication of a sensor with a transistor and a sensing electrode with 1-hydroxyethyl-5-mercapto-1H-tetrazole (EMT) immobilized thereon A gate electrode 12 [aluminum (Al), 30 nm thick] was formed on a glass substrate 11 by vacuum deposition, and an aluminum oxide (AlOx) film was formed on the surface of the gate electrode 12 by reactive ion etching (RIE). Next, Cytop (registered trademark) CTL-809M was spin-coated on the surface of the formed aluminum oxide film, and then patterning was performed by RIE. The glass substrate 11 after patterning was immersed in a tetradecylphosphonic acid solution to form a gate insulating film 13. Next, a source electrode 14 [gold (Au), 30 nm thick] and a drain electrode 15 [gold (Au), 30 nm thick] were formed using a vacuum deposition device. Next, a 0.01 mass % solution of PBTTT-C14 (solvent is 1,2-dichlorobenzene) was prepared, and a polymer semiconductor layer 17 was formed by a drop cast method. Cytop (registered trademark) CTL-809M was spin-coated on the substrate to form a sealing film 18, and a transistor 1 was produced.

[0109] Next, a gold thin film 27 was formed on the surface of a PEN film substrate 21 (hereinafter referred to as "substrate 21") by vacuum evaporation. Further, a reference electrode (Ag / AgCl electrode) 22 was installed on the surface of the substrate 21. Next, 1 mM of 1-hydroxyethyl-5-mercapto-1H-tetrazole (EMT) and 5 mM of tris(2-carboxyethyl)phosphine hydrochloride (TCEP-HCl) as a reducing agent were dissolved in methanol to obtain a methanol solution containing EMT and TCEP-HCl. The substrate 21 (corresponding to the "detection site" of the present invention) having the gold thin film 27 formed on its surface was immersed in the methanol solution at 25°C for 1 hour (hereinafter also referred to as "EMT immersion"), whereby the gold thin film 27 on the surface of the substrate 21 (hereinafter referred to as "the gold thin film 27 on the substrate 21") was subjected to self-assembled monolayer (SAM) treatment using EMT to fabricate a detection electrode 2 (corresponding to the "nitrogen-containing heterocyclic compound having a thiol group + detection site" of the present invention). Then, the gold thin film 27 on the SAM-treated substrate 21 was connected to the gate electrode 12 of the transistor 1 with a conductive cable 4 to manufacture a sensor including the detection electrode 2 to which EMT was fixed and the transistor 1 (see FIG. 1).

[0110] [X-ray photoelectron spectroscopy (XPS) measurement, photoelectron yield spectroscopy (PYS) measurement, and contact angle measurement] By performing X-ray photoelectron spectroscopy (XPS) measurement, photoelectron yield spectroscopy (PYS) measurement, and contact angle measurement, it was confirmed whether EMT was fixed to the gold thin film 27 on the SAM-treated substrate 21 via a sulfide group (-S-).

[0111] The XPS measurement was performed using an X-ray photoelectron spectrometer (product name "ULVAC-PHI", manufactured by ULVAC-PHI, Inc.) under the following measurement conditions. Detection of the spectral signal attributed to the N1s orbital by narrow scan in the binding energy range of 411 eV to 391 eV, and detection of the spectral signal attributed to the S2p orbital by narrow scan in the binding energy range of 175 eV to 155 eV were performed. <XPS measurement conditions> ·Excitation source: Al Kα ·Photoelectron extraction angle: 45° ·Pass Energy: 1.5 keV

[0112] The PYS measurement was performed to measure the ionization potential (Ip) under the following measurement conditions using an atmospheric photoelectron yield spectrometer (product name: "AC-2", manufactured by Riken Keiki Co., Ltd.). <PYS Measurement Conditions> · Measurement wavelength range: 4.2 eV to 6.2 eV · Measurement interval: 0.05 eV · Measurement atmosphere: atmospheric pressure (0.10 MPa)

[0113] The contact angle measurement was performed to measure the contact angle of water under the following measurement conditions using a contact angle measuring device (manufactured by Kyowa Interface Science Co., Ltd., product name: "CA-X"). <Contact Angle Measurement Conditions> Solvent used: pure water Measurement temperature: 25 °C

[0114] Figure 2 shows the results of XPS measurement after EMT immersion. Since EMT was fixed to the gold thin film 27 on the SAM-treated substrate 21 via a sulfide group, a nitrogen peak (left figure in Figure 2) and a sulfur peak (right figure in Figure 2) were confirmed.

[0115] Figure 3 shows the results of PYS measurement before and after EMT immersion. The ionization potential of gold before EMT immersion was 4.9 eV, whereas the ionization potential of gold after EMT modification was 4.7 eV.

[0116] Figure 4 shows photographs of water droplets in contact with the gold thin film 27 on the substrate 21 before (upper figure in Figure 4) and after (lower figure in Figure 4) EMT immersion. The angle formed between the surface of the gold thin film 27 and the water droplet is called the contact angle. The contact angle before EMT immersion was 46.4°, whereas the contact angle after EMT immersion was 29.6°.

[0117] From the results of XPS measurement, PYS measurement, and contact angle measurement, it was confirmed that EMT was fixed to the gold thin film 27 on the SAM-treated substrate 21 via a sulfide group.

[0118] Furthermore, linear sweep voltammetry measurements were performed to confirm whether EMT was fixed via a sulfide group (-S-) to the gold thin film 27 on the SAM-treated substrate 21. The linear sweep voltammetry measurements were performed using an electrochemical analyzer (product name "SP-300 Potentiostat", manufactured by Biologic Co., Ltd.) under the following measurement conditions. <Linear sweep voltammetry measurement conditions> ·Sweep speed: 20mV / s Sweep range: 0 to -1.5V vs Ag / AgCl (silver / silver chloride electrode) Sweep direction: Negative

[0119] FIG. 5 shows the results of linear sweep voltammetry measurements after immersion in EMT. From the results in Figure 5, a peak was observed indicating that sulfur bound to gold was reduced to thiolate, and it was confirmed that EMT was immobilized on the gold thin film 27 via a sulfide group. The film density of the gold thin film 27 (the amount of EMT immobilized on the gold thin film 27) was (3.2±0.2)×10 -9 mol / cm 2 It was calculated that:

[0120] From the above, this manufacturing example made it possible to produce a transistor-type sensor (hereinafter also referred to as the "sensor produced in manufacturing example 1") having a detection electrode 2 in which EMT is fixed via a sulfide group to a thin gold film 27 on a SAM-treated substrate 21 and a transistor 1.

[0121] Example 1 Methyl iodide detection test using a sensor with an EMT-immobilized sensing electrode and a transistor A methyl iodide detection test was carried out using the sensor produced in Production Example 1 above. In this detection test, the detection electrode 2 of the sensor was immersed in a liquid sample, which was a measurement solution, and left to stand at 25°C for 10 minutes, after which the transfer characteristics of the transistor 1 electrically connected to the detection electrode 2 were measured using a source meter (product name "KEITHLEY 2612B", manufactured by Tektronix & Fluke Corporation). The measurement conditions were gate voltage (VGS ) = -3.0 to 0.5 V, drain voltage (V DS ) was set to -2.0 V. As the liquid sample (hereinafter also referred to as "liquid sample 1") which is the above measurement solution, a solution obtained by adding methyl iodide [0 to 100 micromoles (μM)] to a 100 mM HEPES buffer solution (containing 100 mM NaCl) with pH 7.4 was used.

[0122] Figure 6 shows a graph of the relationship between the gate voltage (V GS ) and the absolute value of the drain current (|I DS |) [solid line: before addition, dashed line: after addition of methyl iodide (100 μM)]. From the graph shown in Figure 6, it was confirmed that the transfer characteristics of transistor 1 changed with the addition of methyl iodide, indicating that methyl iodide can be detected. The shift of the gate voltage in the negative direction is considered to be a response caused by the reaction between the EMT fixed to the gold thin film 27 on the SAM-treated substrate 21 via a sulfide group and methyl iodide (specifically, a nucleophilic substitution reaction of the nitrogen atom contained in the EMT with methyl iodide) accompanying the addition of methyl iodide.

[0123] Figure 7 shows a graph showing the relationship between the change amount of the threshold voltage of the transistor and the methyl iodide molar concentration (μM). From the graph shown in Figure 7, it was confirmed that the threshold voltage of the transistor changes with the change in the methyl iodide molar concentration, indicating that the change in the methyl iodide molar concentration can be detected. Also, from the graph shown in Figure 7, it was confirmed that methyl iodide can be detected at a low concentration in units of micromoles (μM).

[0124] Furthermore, after immersing the detection electrode 2 of the sensor fabricated in Production Example 1 above in the above liquid sample 1 at 25°C for 10 minutes, XPS measurement was performed to detect the spectral signal attributed to the I3d orbital in a narrow scan in the range of binding energy from 633 eV to 613 eV. XPS was performed using an X-ray photoelectron spectrometer under the following measurement conditions. <XPS measurement conditions> · Excitation source: Al Kα · Photoelectron extraction angle: 45° Pass Energy: 1.5keV

[0125] The results of the XPS measurement are shown in Figure 8. As shown in Figure 8, two methyl iodide peaks were confirmed. These peaks are considered to be due to the formation of an onium salt by the reaction of EMT with methyl iodide.

[0126] (Examples 2 to 6) Detection test of organic compounds containing various leaving groups using a sensor equipped with a detection electrode and a transistor with an EMT fixed thereto Using the sensor prepared in the above Production Example 1, detection tests were carried out for ethyl iodide (Example 2), 2-iodo-2-methylpropane (Example 3), bromoethane (Example 4), benzyl bromide (Example 5), and methyl trifluoromethanesulfonate (Example 6). The detection tests were carried out in the same manner as in Example 1.

[0127] Example 2 Figure 9 shows the gate voltage (V GS ) and the absolute value of the drain current (|I DS 9 shows a graph of the relationship between the EMT immobilized on the thin gold film 27 on the SAM-treated substrate 21 via a sulfide group and the ethyl iodide (|) [solid line: before addition, dashed line: after addition of ethyl iodide (100 μM)]. From the graph shown in FIG. 9, a change in the transfer characteristics of the transistor 1 due to the addition of ethyl iodide can be confirmed, demonstrating that ethyl iodide can be detected. The shift in the gate voltage in the negative direction is considered to be a response resulting from the reaction between the EMT immobilized on the thin gold film 27 on the SAM-treated substrate 21 via a sulfide group and ethyl iodide due to the addition of ethyl iodide.

[0128] Figure 10 shows a graph showing the relationship between the amount of change in threshold voltage of a transistor and the molar concentration (μM) of ethyl iodide. From the graph shown in Figure 10, it was confirmed that the threshold voltage of the transistor changes with the change in the molar concentration of ethyl iodide, and it was confirmed that the change in the molar concentration of ethyl iodide can be detected. Furthermore, from the graph shown in Figure 10, it was confirmed that ethyl iodide can be detected at a low concentration of micromolar (μM).

[0129] Example 3 Figure 11 shows the gate voltage (V GS ) and the absolute value of the drain current (|I DS 11 shows a graph of the relationship between the voltage Vp and the EMT immobilized via a sulfide group on the gold thin film 27 on the SAM-treated substrate 21 and the voltage Vp (Vp) [solid line: before addition, dashed line: after addition of 2-iodo-2-methylpropane (100 μM)]. From the graph shown in FIG. 11, it is possible to confirm the change in the transfer characteristics of the transistor 1 with the addition of 2-iodo-2-methylpropane, and it is shown that 2-iodo-2-methylpropane can be detected. The shift in the gate voltage in the negative direction is considered to be a response resulting from the reaction between the EMT immobilized via a sulfide group on the gold thin film 27 on the SAM-treated substrate 21 and 2-iodo-2-methylpropane with the addition of 2-iodo-2-methylpropane.

[0130] Fig. 12 shows a graph showing the relationship between the amount of change in threshold voltage of a transistor and the molar concentration (μM) of 2-iodo-2-methylpropane. From the graph shown in Fig. 12, it was confirmed that the threshold voltage of the transistor changes with the change in the molar concentration of 2-iodo-2-methylpropane, and it was confirmed that the change in the molar concentration of 2-iodo-2-methylpropane can be detected. Furthermore, from the graph shown in Fig. 12, it was confirmed that 2-iodo-2-methylpropane can be detected at a low concentration in the micromolar (μM) range.

[0131] Example 4 Figure 13 shows the gate voltage (V GS ) and the absolute value of the drain current (|I DS 13 shows a graph of the relationship between the voltage Vp and the EMT immobilized via sulfide groups on the gold thin film 27 on the SAM-treated substrate 21 and the voltage Vp and the EMT immobilized via sulfide groups on the gold thin film 27 on the SAM-treated substrate 21. The graph in FIG. 13 shows ...

[0132] Figure 14 shows a graph showing the relationship between the amount of change in threshold voltage of the transistor and the molar concentration of bromoethane (μM). From the graph shown in Figure 14, it was confirmed that the threshold voltage of the transistor changes with the change in the molar concentration of bromoethane, and it was confirmed that the change in the molar concentration of bromoethane can be detected. In addition, from the graph shown in Figure 14, it was confirmed that bromoethane can be detected at a low concentration of micromolar (μM).

[0133] Example 5 Figure 15 shows the gate voltage (V GS ) and the absolute value of the drain current (|I DS 15 shows a graph of the relationship between the concentration of benzyl bromide and the amount of benzyl bromide added (|) [solid line: before addition, dashed line: after addition of benzyl bromide (100 μM)]. From the graph shown in FIG. 15, it was possible to confirm the change in the transfer characteristics of the transistor 1 with the addition of benzyl bromide, and it was shown that benzyl bromide detection can be performed. The shift in the gate voltage in the positive direction is considered to be a response resulting from the reaction between benzyl bromide and the EMT fixed via a sulfide group to the gold thin film 27 on the SAM-treated substrate 21 with the addition of benzyl bromide.

[0134] FIG. 16 shows a graph showing the relationship between the amount of change in threshold voltage of a transistor and the molar concentration of benzyl bromide (μM). From the graph shown in FIG. 16, it was confirmed that the threshold voltage of the transistor changes with the change in the molar concentration of benzyl bromide, and it was confirmed that the change in the molar concentration of benzyl bromide can be detected. In addition, from the graph shown in FIG. 16, it was confirmed that benzyl bromide can be detected at a low concentration of micromolar (μM).

[0135] Example 6 Figure 17 shows the gate voltage (V GS ) and the absolute value of the drain current (|I DS17 shows a graph of the relationship between the voltage Vp and the EMT immobilized via a sulfide group on the gold thin film 27 on the SAM-treated substrate 21 and the voltage Vt (Vp) [solid line: before addition, dashed line: after addition of methyl trifluoromethanesulfonate (100 μM)]. From the graph shown in FIG. 17, it was possible to confirm the change in the transfer characteristics of the transistor 1 with the addition of methyl trifluoromethanesulfonate, and it was shown that methyl trifluoromethanesulfonate can be detected. The shift in the negative direction of the gate voltage is considered to be a response resulting from the reaction between the EMT immobilized via a sulfide group on the gold thin film 27 on the SAM-treated substrate 21 and methyl trifluoromethanesulfonate with the addition of methyl trifluoromethanesulfonate.

[0136] Fig. 18 shows a graph illustrating the relationship between the amount of change in threshold voltage of a transistor and the molar concentration (μM) of methyl trifluoromethanesulfonate. From the graph shown in Fig. 18, it was confirmed that the threshold voltage of the transistor changes with the change in the molar concentration of methyl trifluoromethanesulfonate, and it was confirmed that the change in the molar concentration of methyl trifluoromethanesulfonate can be detected. Furthermore, from the graph shown in Fig. 18, it was confirmed that methyl trifluoromethanesulfonate can be detected at a low concentration in the micromolar (μM) range.

[0137] Figure 19 shows a graph showing the relationship between the amount of change in threshold voltage of the transistor and the molar concentration (μM) of the electrophile. From the graph shown in Figure 19, it was found that the sensor of the present invention shows different response patterns to six types of electrophiles. Furthermore, a response hierarchy based on the difference in reactivity was observed for alkyl iodides.

[0138] Example 7 2-Iodopropane detection test using a sensor equipped with an EMT-fixed sensing electrode and a transistor A 2-iodopropane detection test was carried out using the sensor produced in Production Example 1 above. In this detection test, the detection electrode 2 of the sensor was immersed in a liquid sample, which was a measurement solution, and left to stand at 25°C for 10 minutes, after which the transfer characteristics of the transistor 1 electrically connected to the detection electrode 2 were measured using a source meter (product name "KEITHLEY 2612B", manufactured by Tektronix & Fluke Corporation). The measurement conditions were gate voltage (V GS )=-3.0~0.5V, drain voltage (V DS )=-2.0 V. As the liquid sample (hereinafter also referred to as "liquid sample 1"), which is the measurement solution, a 100 mM HEPES buffer solution (containing 100 mM NaCl) having a pH of 7.4 to which 2-iodopropane [1 to 50 micromolar (μM)] was added was used.

[0139] Figure 20 shows the gate voltage (V GS ) and the absolute value of the drain current (|I DS 20 shows a graph of the relationship between the voltage Vp and the EMT immobilized on the gold thin film 27 on the SAM-treated substrate 21 via a sulfide group and 2-iodopropane (specifically, a nucleophilic substitution reaction of the nitrogen atom contained in the EMT with 2-iodopropane) [solid line: before addition, dashed line: after addition of 2-iodopropane (50 μM)]. From the graph shown in FIG. 20, a change in the transfer characteristic of the transistor 1 due to the addition of 2-iodopropane can be confirmed, and it was shown that 2-iodopropane can be detected. The shift in the negative direction of the gate voltage is considered to be a response due to the addition of 2-iodopropane, which is caused by the reaction between the EMT immobilized on the gold thin film 27 on the SAM-treated substrate 21 via a sulfide group and 2-iodopropane (specifically, a nucleophilic substitution reaction of the nitrogen atom contained in the EMT with 2-iodopropane).

[0140] FIG. 21 shows a graph illustrating the relationship between the amount of change in threshold voltage of a transistor and the molar concentration (μM) of 2-iodopropane. The threshold voltage of the transistor was measured at molar concentrations of 2-iodopropane of 1 μM, 2 μM, 3 μM, 5 μM, 7 μM, 10 μM, 20 μM, 30 μM, and 50 μM. From the graph shown in FIG. 21, it was confirmed that the threshold voltage of the transistor changes with the change in the molar concentration of 2-iodopropane, and it was confirmed that the change in the molar concentration of 2-iodopropane can be detected. In addition, from the graph shown in FIG. 21, it was confirmed that 2-iodopropane can be detected at a low concentration of micromolar (μM).

[0141] Example 8 Qualitative analysis of six organic compounds containing leaving groups by principal component analysis using a sensor equipped with a detection electrode and a transistor to which EMT is fixed In order to evaluate the multi-component detection ability of the sensor prepared in Production Example 1 above, a qualitative analysis was performed on six organic compounds containing leaving groups (methyl iodide, ethyl iodide, 2-iodopropane, 2-iodo-2-methylpropane, bromoethane, and methyl trifluoromethanesulfonate).

[0142] The data matrix for multi-component analysis contains the change in the transfer characteristic of the transistor 1 obtained by adding 5 μM of each of the six target organic compounds containing the above-mentioned leaving groups. To obtain the data, the change in the transfer characteristic of the transistor 1 was measured before and after the addition of the six target organic compounds containing the above-mentioned leaving groups.

[0143] Gate voltage (V GS ) was set to -3.0 to 0.5 V. The inset data was created by adding six organic compounds containing the above-mentioned target leaving groups and measuring the drain current (I DS ) and the drain current value before addition (I DS0 ) was used, and measurements were repeated three times for six organic compounds containing leaving groups.

[0144] To identify six types of organic compounds containing the above-mentioned target leaving groups, we used principal component analysis (PCA), a type of pattern learning.

[0145] The graph obtained from the principal component analysis of the six organic compounds containing the leaving group is shown in FIG. 22. Each cluster shown in FIG. 22 is composed of three plots representing three repeated measurements. The first principal component (PC1) and the second principal component (PC2) are the top two factors with the largest contribution rate in identifying the six organic compounds containing the leaving group, and the values ​​in parentheses for PC1 and PC2 indicate the cumulative contribution rate of the total variance of the PCA. The distribution of the classified clusters reflects the responsiveness of the transistor 1 based on the bulkiness of the six organic compounds containing the leaving group, and this result reveals that it is possible to identify the six organic compounds containing the leaving group with high accuracy by using a sensor equipped with a detection electrode and a transistor to which an EMT is fixed.

[0146] Example 9 Identification and concentration measurement of six organic compounds containing leaving groups by principal component analysis using a sensor equipped with a detection electrode and transistor to which EMT is fixed In order to evaluate the multi-component detection ability of the sensor prepared in Production Example 1 above, identification and concentration measurement tests were performed on six organic compounds containing leaving groups (methyl iodide, ethyl iodide, 2-iodopropane, 2-iodo-2-methylpropane, bromoethane, and methyl trifluoromethanesulfonate) by principal component analysis.

[0147] The data matrix for multi-component analysis contains the changes in the transfer characteristics of the transistor 1 obtained by adding six types of organic compounds containing the above-mentioned leaving groups as target species. In this test, the concentrations of the six types of organic compounds containing the above-mentioned leaving groups added were 0 μM, 2 μM, 5 μM, and 10 μM, respectively. To obtain the data, the changes in the transfer characteristics of the transistor 1 before and after the addition of the six types of organic compounds containing the above-mentioned leaving groups as targets were measured.

[0148] Gate voltage (V GS) was set to -3.0 to 0.5 V. The inset data was created by adding six organic compounds containing the above-mentioned target leaving groups and measuring the drain current (I DS ) and the drain current value before addition (I DS0 ) was used, and measurements were repeated three times for six organic compounds containing the above leaving groups.

[0149] FIG. 23 shows a graph showing the results of the discrimination and concentration measurement test of six organic compounds containing the above-mentioned leaving group by principal component analysis. Each cluster shown in FIG. 23 is composed of three plots representing three repeated measurements at each concentration (0 μM, 2 μM, 5 μM, and 10 μM). The concentration of each of the six organic compounds containing the above-mentioned leaving group at 0 μM was used as a control. The first principal component (PC1) and the second principal component (PC2) are the top two factors with the highest contribution rate in discriminating the six organic compounds containing the above-mentioned leaving group at different concentrations, and the values ​​in parentheses for PC1 and PC2 indicate the cumulative contribution rate of the total variance of PCA. FIG. 23 shows the concentration-dependent cluster distribution by PCA, and the results reveal that the use of a sensor equipped with a detection electrode and a transistor to which EMT is fixed allows qualitative and semi-quantitative discrimination of the six organic compounds containing the above-mentioned leaving group. It is presumed that by using the concentration-dependent cluster distribution by PCA in FIG. 23, it is possible to identify and measure the concentration of organic compounds containing leaving groups other than the six organic compounds containing leaving groups described above. [Explanation of symbols]

[0150] 1 Transistor 2,2A Detection electrode 3 Liquid samples 4 Conductive Cable 11 Glass substrate 12 Gate electrode 13 Gate insulating film 14 Source electrode 15 Drain electrode 16 Liquid-repellent bank layer 17 Polymer Semiconductor Layer 18 Sealing film 21 PEN film substrate 22 Reference electrode (Ag / AgCl electrode) 27 Gold Thin Film

Claims

1. A sensor used for detecting an organic compound containing a leaving group, the sensor comprising a detection site and a transistor, the detection site being connected to the transistor, and a nitrogen-containing heterocyclic compound having a thiol group being fixed to a surface of the detection site via a sulfur atom of the thiol group.

2. The sensor according to claim 1 , wherein the nitrogen-containing heterocyclic compound having a thiol group is a compound represented by the following formula (1): 【Chemistry 1】 (Wherein, ring A is a monocyclic nitrogen-containing heterocycle, R １ is a single bond or an alkylene group, R ２ is an alkyl group which may have a hydroxyl group, n is an integer of 0, 1, 2 or 3, and when n is 2 or 3, R ２ may be the same or different.)

3. The sensor according to claim 2 , wherein in the formula (1), ring A is a monocyclic nitrogen-containing heterocycle containing 2, 3 or 4 nitrogen atoms.

4. The sensor according to claim 3 , wherein in the formula (1), ring A is a monocyclic nitrogen-containing aromatic heterocycle containing 3 or 4 nitrogen atoms.

5. The sensor according to claim 4 , wherein in the formula (1), ring A is a tetrazole ring.

6. In the formula (1), R １ is a single bond, R ２ 6. The sensor according to claim 2, wherein: is an alkyl group having 1 to 6 carbon atoms and having a hydroxyl group; and n is 1.

7. The organic compound containing the leaving group is sp ３ 6. The sensor according to claim 1, which is an organic compound having in its molecule a site where a leaving group is bonded on a hybridized carbon atom.

8. The leaving group is a halogen atom or a group of the formula: ２ -R ３ (In the formula, R ３ The sensor according to claim 7 , wherein R 1 is a group represented by the formula:

9. The sensor according to any one of claims 1 to 5, wherein the transistor is an organic thin film transistor.

10. The sensor according to any one of claims 1 to 5, wherein the organic compound having a leaving group is detected by measuring a change in threshold voltage of the transistor caused by a reaction between the nitrogen-containing heterocyclic compound having a thiol group and an organic compound having a leaving group at the detection site.

11. A method for detecting an organic compound containing a leaving group, comprising a step of contacting a detection site of the sensor according to any one of claims 1 to 5 with a sample containing an organic compound containing a leaving group.

12. The detection method according to claim 11, further comprising a step of detecting an organic compound having a leaving group by measuring a change in a threshold voltage of a transistor caused by a reaction between the nitrogen-containing heterocyclic compound having a thiol group and an organic compound having a leaving group at the detection site.

13. A method for identifying an organic compound containing a leaving group, comprising a step of creating a model by performing pattern learning using principal component analysis based on data on changes in transmission characteristics of a sensor obtained using the method for detecting an organic compound containing a leaving group according to claim 12, and identifying the organic compound containing a leaving group by pattern recognition.

14. A step of creating a model by performing pattern learning using principal component analysis based on data on changes in transfer characteristics of a sensor obtained by using the method for detecting an organic compound containing a leaving group according to claim 12, and identifying the organic compound containing a leaving group to be measured by pattern recognition; and A method for measuring the concentration of an organic compound containing a leaving group, comprising the step of measuring the concentration of the organic compound containing a leaving group as the measurement target.

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