Receptor, sensor, synthesis system, measurement method, and method for manufacturing a receptor

Abstract

The present invention provides a receptor comprising a molecular imprint film that can be applied to a field-effect transistor capable of detecting compounds having chiral carbon atoms. [Solution] A receptor comprising a substrate and a molecular imprinted polymer film formed on the substrate and having a space for capturing a portion of a compound having an asymmetric carbon atom. Receptor 100 comprises a metal layer 120 formed between the substrate 110 and the molecular imprinted polymer film 140, having a nanostructure 130 on the surface in contact with the molecular imprinted polymer film. The molecular imprinted polymer film may have non-covalent functional groups on the surface forming the space 150.

Description

[Technical Field]

[0001] This disclosure relates to receptors, sensors, synthesis systems, measurement methods, and methods for manufacturing receptors. [Background technology]

[0002] Patent Document 1 states that "a sensor equipped with a molecularly imprinted polymer on the surface of the detection electrode can quantitatively detect compounds" (paragraph 0005). Patent Document 2 states that "a sensor on which an oxytocin antibody is chemically bound to the surface of the detection electrode via a linker and a binding portion can detect oxytocin, which is an antigen" (paragraph 0005).

[0003] Non-patent document 1 states, "The MIP films, which can specifically recognize and have an electrocatalytic effect on the oxidation of Trp and Tyr, together with the amplification function of an OECT, provide a highly sensitive and selective OECT biosensor." (ABSTRACT) [Prior art document] [Patent] [Patent Document 1] Japanese Unexamined Patent Publication No. 2023-61890 [Patent Document 2] Japanese Unexamined Patent Publication No. 2023-45665 [Non-patent literature] [Non-patent Document 1] Zhang, Lijun, et al., Chirality detection of amino acid enantiomers by organic electrochemical transistor., Biosensors and Bioelectronics 105 (2018): 121-128. [Non-patent document 2] Tsuyoshi Minami et al., Supramolecular Sensor for Cancer-Associated Nitrosamines, J. Am. Chem. Soc.134, 49 (2012): 20021-20024. [Overview of the project]

[0004] (1) A first aspect of the present disclosure provides a receptor comprising a substrate and a molecular imprinted polymer film formed on the substrate and having a space for capturing at least a portion of a compound having asymmetric carbon atoms.

[0005] (2) The receptor described in (1) above may include a metal layer having a nanostructure on the surface in contact with the molecular imprinted polymer film, which is formed between the substrate and the molecular imprinted polymer film.

[0006] (3) In the receptor of (1) or (2) above, the molecular imprinted polymer film may have non-covalent functional groups on the surface that forms the space.

[0007] (4) In the receptor described in (3) above, the molecular imprinted polymer film may have three or more non-covalent functional groups in one space.

[0008] (5) In any of the receptors described in (1) to (4) above, the molecular imprinted polymer film may be composed of aromatic monomers.

[0009] (6) In any of the receptors described in (1) to (5) above, the compound may have at least one of a heteroatom, an -OH group, or an -C=O group.

[0010] (7) In any of the receptors described in (1) to (6) above, the compound may have at least one primary amine group or a secondary amine group.

[0011] (8) In any of the receptors described in (1) to (7) above, the compound may be at least one of histidine (His), a His derivative, a His analogue, a His side chain protector, or a peptide containing His.

[0012] (9) In the receptor of (5) above, the monomer does not need to contain an alkyl group having 2 or more carbon atoms as a substituent.

[0013] (10) In the receptor described in (9) above, the monomer may include a hydrogen bond donor substituent.

[0014] (11) In the receptor of (10) above, the monomer may be at least one of 1,2-diaminobenzene, 1,3-diaminobenzene, 1,4-diaminobenzene, 2-aminophenol, 1,3-dihydroxybenzene, or aniline.

[0015] (12) A second embodiment of the present disclosure provides a sensor comprising a receptor according to any of (1) to (12) above and a field-effect transistor having a gate connected to a metal in contact with the molecular imprinted polymer film in the receptor.

[0016] (13) In a third aspect of the present disclosure, a synthesis system is provided comprising the sensor described in (12) above, a reactor, and a control unit that controls the reaction conditions in the reactor based on the measurement results of the sensor.

[0017] (14) A fourth aspect of the present disclosure provides a measurement method in which a sample containing a compound to be detected is brought into contact with the receptor of the sensor described in (12) above, and the compound in the sample is measured based on the change in the current-voltage characteristics of the field-effect transistor.

[0018] (15) The measurement method described in (14) above may involve quantitatively measuring the compound in the sample based on the change in the current-voltage characteristics.

[0019] (16) A fifth aspect of the present disclosure provides a method for measuring a compound using two or more sensors described in (12) above, each capturing a different compound in the space, and determining the optical purity of the compound based on the measurement results.

[0020] (17) A sixth aspect of the present disclosure provides a method for producing a receptor, which involves mixing a compound having an asymmetric carbon atom with a monomer to prepare a monomer-containing solution, coating the monomer-containing solution onto a substrate or immersing the substrate in the monomer-containing solution, polymerizing the monomer to form a polymer, and removing the compound to form a molecular imprinted polymer film.

[0021] (18) In the receptor manufacturing method described in (17) above, the polymerization may be electrolytic polymerization.

[0022] (19) The receptor manufacturing method described in (17) or (18) above may remove the compound by an electrochemical reaction.

[0023] (20) Any of the receptor manufacturing methods described in (17) to (19) above may involve forming a metal layer having a nanostructure on the surface of the substrate prior to the coating or immersion.

[0024] It should be noted that the above summary of the invention does not enumerate all of its features. Furthermore, subcombinations of these features may also constitute an invention. [Brief explanation of the drawing]

[0025] [Figure 1] A cross-sectional view of the receptor 100 according to this embodiment is shown. [Figure 2] This diagram shows the state in which a metal film 125 is formed on a substrate 110 in the manufacturing method of the receptor 100 according to this embodiment. [Figure 3] This shows the state in which the nanostructure 130 is formed in the manufacturing method of the receptor 100 according to this embodiment. [Figure 4]This shows the state in which the polymer 400 has been formed in the manufacturing method of the receptor 100 according to this embodiment. [Figure 5] The configuration of the sensor 500 according to this embodiment is shown together with the sample 540. [Figure 6] The configuration of the measuring device 560 according to this embodiment is shown. [Figure 7] This shows a first example of the operation flow of the sensor 500 according to this embodiment. [Figure 8] A second example of the operation flow of the sensor 500 according to this embodiment is shown. [Figure 9] The configuration of the sensor 900 according to the first modified example of this embodiment is shown together with the sample 540. [Figure 10] The configuration of the synthesis system 1000 according to a second modified example of this embodiment is shown. [Figure 11] The configuration of column 1100 according to a third modified example of this embodiment is shown. [Figure 12] An example of DPV measurement results using receptor 100 of the example is shown. [Figure 13] A comparative example of DPV measurement results using Receptor 100 is shown. [Figure 14] An example of the response specificity in receptor 100 of the example is shown. [Figure 15] An example of a Vg-Id curve for sample 540 with different optical purities is shown. [Figure 16] An example of the threshold voltage for sample 540 with an optical purity of 80% ee or less is shown. [Figure 17] An example of the threshold voltage for sample 540 with an optical purity of 80% ee or higher is shown. [Figure 18] An example of the results of determining optical purity using machine learning is shown. [Figure 19] Examples of a computer 1200 in which multiple aspects of the present invention may be embodied in whole or in part are shown. [Modes for carrying out the invention]

[0026] The present invention will be described below through embodiments of the invention, but these embodiments are not intended to limit the invention as defined in the claims. Furthermore, not all combinations of features described in the embodiments are necessarily essential to the solution of the invention.

[0027] Figure 1 shows a cross-sectional view of the receptor 100 according to this embodiment. The receptor 100 is used as a detection electrode for detecting compounds having an asymmetric carbon atom. In the example shown in this figure, the receptor 100 comprises a substrate 110, a metal layer 120, and a molecular imprinted polymer film 140.

[0028] The substrate 110 has a surface (the upper surface in this figure) on which each layer of the receptor 100 is formed. In this embodiment, the substrate 110 is plate-shaped. The substrate 110 may be made of glass or resin. The substrate 110 may be made of polyethylene naphthalate.

[0029] The molecularly imprinted polymer film 140 is formed on the substrate 110. Here, "on the substrate 110" means that the molecularly imprinted polymer film 140 is formed in a region above the substrate 110, and the substrate 110 and the molecularly imprinted polymer film 140 may be in direct contact, or other layers may be included between the substrate 110 and the molecularly imprinted polymer film 140. The molecularly imprinted polymer film 140 has a space 150 that captures at least a portion of the compound having chiral carbon atoms.

[0030] The molecularly imprinted polymer film 140 may have non-covalent functional groups on the surface forming the space 150. This allows the space 150 to interact with and capture at least a portion of the compound. The non-covalent functional groups may be hydrogen bond donor substituents. The hydrogen bond donor substituents may be at least one of the following: hydroxyl group (-OH), amino group (-NH2, -NHR, -NR2), amide group (-CONH2), carboxyl group (-COOH), thiol group (-SH), urea group (-NHCONH-), guanidyl group (-C(=NH)-NH2), sulfonamide group (-SO2NH2), or imino group (=NH). For example, the hydrogen bond donor substituent may be an -OH group, an -NH2 group, or an -C≡N group. The molecularly imprinted polymer film 140 may have three or more non-covalent functional groups in one space 150. This allows space 150 to capture the compound more stably.

[0031] The molecularly imprinted polymer film 140 is formed by polymerizing one or more monomers. The molecularly imprinted polymer film 140 may be composed of aromatic monomers. Therefore, the molecularly imprinted polymer film 140 may have repeating units that include aromatic moieties. By forming a molecularly imprinted polymer film from aromatic monomers, the rigidity of the space 150 is increased, making it easier for the space 150 to more selectively capture molecules. The molecularly imprinted polymer film 140 can be formed by oxidation of monomers to generate radicals and then polymerization. The monomers do not need to contain alkyl groups with 2 or more carbon atoms as substituents. By forming a molecularly imprinted polymer film 140 from such monomers, the rigidity of the space 150 is increased, making it easier for the space 150 to more selectively capture molecules. For example, the monomers may contain hydrogen bond donor substituents as substituents. The hydrogen bond donor substituent may be at least one of the following: hydroxyl group (-OH), amino group (-NH2, -NHR, -NR2), amide group (-CONH2), carboxyl group (-COOH), thiol group (-SH), urea group (-NHCONH-), guanidyl group (-C(=NH)-NH2), sulfonamide group (-SO2NH2), or imino group (=NH). The monomer may be at least one of 1,2-diaminobenzene, 1,3-diaminobenzene, 1,4-diaminobenzene, 2-aminophenol, 1,3-dihydroxybenzene, or aniline.

[0032] The molecularly imprinted polymer film 140 may have a molecularly imprinted polymer film 140 such that, for first and second isomers having the same chemical formula, the proportion of the captured amount of the first isomer to the total captured amount of the first and second isomers is 60% or more. Alternatively, the molecularly imprinted polymer film 140 may have a molecularly imprinted polymer film 140 such that the proportion of the captured amount of the first isomer to the total captured amount of the first and second isomers is 70% or more, 80% or more, 90% or more, or 99% or more. By providing such a molecularly imprinted polymer film 140, the receptor 100 can selectively capture the first isomer from among multiple molecules having the same chemical formula.

[0033] The compound trapped in space 150 may have at least one of a heteroatom, an -OH group, or an -C=O group. Such a compound is easily trapped in space 150. Here, the heteroatom may be at least one of an N atom, an O atom, an S atom, a P atom, a Cl atom, an I atom, or a Br atom. The trapped compound may have at least one of a primary amine group or a secondary amine group. Therefore, the N atom in the compound may be an N atom in a primary amine group or an N atom in a secondary amine group. The compound may be at least one of histidine (His), a His derivative, a His analogue, a His side-chain protected form, or a His-containing peptide.

[0034] The metal layer 120 is formed between the substrate 110 and the molecularly imprinted polymer film 140. The metal layer 120 may be made of gold, aluminum, silver, copper, iron, titanium, or other metallic materials. Instead of the metal layer 120, a layer made of indium tin oxide (ITO), poly(3,4-ethylenedioxythiophene), polystyrene sulfonate, conductive carbon nanotubes, graphene, or conductive organic-inorganic composite material may be formed between the substrate 110 and the molecularly imprinted polymer film 140. In the example shown in the figure, the metal layer 120 has a metal film 125 and a nanostructure 130. Alternatively, the metal layer 120 may not have the nanostructure 130.

[0035] The metal film 125 is formed on the surface of the metal layer 120 that is in contact with the substrate 110. The metal film 125 is not particularly limited as long as it is in the form of a film.

[0036] The nanostructure 130 is formed on the surface of the metal layer 120 that is in contact with the molecularly imprinted polymer film 140. The structure of the nanostructure 130 is not limited as long as the surface area of ​​the surface of the nanostructure 130 in contact with the molecularly imprinted polymer film 140 is larger than the surface area of ​​the surface of the metal film 125 in contact with the substrate 110. The nanostructure 130 may be a needle-like structure extending toward the molecularly imprinted polymer film 140. By having the nanostructure 130 in the metal layer 120, the bonding force between the metal layer 120 and the molecularly imprinted polymer film 140 can be increased compared to the case where the nanostructure 130 is not present. The nanostructure 130 may be formed from the same material as the metal film 125, or from a different material. Instead of the example shown in this figure, the substrate 110 and the metal film 125 may be formed from a single metal.

[0037] Figures 2 to 4 show an example of a method for manufacturing the receptor 100 according to this embodiment. First, a substrate 110 is prepared, and a metal film 125 is formed on the substrate 110. Figure 2 shows the state in which the metal film 125 has been formed on the substrate 110 in the method for manufacturing the receptor 100 according to this embodiment. In this step, the metal film 125 may be formed on the substrate 110 by sputtering, vacuum deposition, or plating.

[0038] Next, a nanostructure 130 is formed on the metal film 125. Figure 3 shows the state in which the nanostructure 130 has been formed in the manufacturing method of the receptor 100 according to this embodiment. In this step, the nanostructure 130 may be formed on the metal film 125 by increasing the surface area or roughening the surface of the metal film 125. The nanostructure 130 may be formed on the metal film 125 by chronoamperometry using an aqueous solution of HAuCl4. In this case, the concentration of the aqueous solution of HAuCl4 may be about 100 mM. In this step, a metal layer 120 having the nanostructure 130 is formed on the surface of the substrate 110 before coating or immersion in the monomer-containing liquid. By forming a metal layer 120 having the nanostructure 130 on the surface of the substrate 110, the bonding strength between the metal layer 120 and the polymer 400 or molecular imprinted polymer film 140 can be increased in a later step.

[0039] Next, a molecular imprinted polymer film 140 is formed on the nanostructure 130. In this step, a monomer-containing solution is prepared by mixing a compound 410 having an asymmetric carbon atom with a monomer. The molar ratio of monomer to compound 410 in the monomer-containing solution may be 3:1 to 5:1. For example, the molar ratio of monomer to compound 410 in the monomer-containing solution may be 4:1. The concentration of monomer in the monomer-containing solution may be 8 mM, and the concentration of compound 410 may be 2 mM. Structural optimization calculations were performed for mixtures of monomer and compound 410 with different molar ratios using density functional theory (DFT). The structural optimization calculations were performed using Gaussian 16 with a basis set of B3LYP(D3BJ) / 6-311G* and an IEFPCM model in aqueous solution. Here, "B3LYP" means hybrid functional, and "D3BJ" means dispersion correction. "6-311G*" is the basis set, and "IEFPCM" means the continuum solvent model. Based on the molecular energy calculated by structural optimization calculations, the degree to which the compound's energy was stabilized by the monomer was calculated. Specifically, the stabilization energy of the compound and mixture of the compound and monomer was calculated by subtracting the energy of the compound alone and the energy of the monomer alone from the energy of the compound-monomer complex, and correcting for the basis set superposition error (BSSE). Table 1 shows the DFT calculation results when the monomer is 1,2-diaminobenzene and compound 410 is L-histidine.

[0040] [Table 1]

[0041] According to Table 1, the mixture was more stable when the molar ratio of monomer to compound 410 was 4:1 compared to when it was 3:1. Table 1 also shows that the mixture was more stable when the molar ratio of monomer to compound 410 was 5:1 than when it was 4:1, but the rate of change in the degree of stability with respect to the increase in the number of monomers was smaller than when the molar ratio was 3:1. Therefore, the monomer and compound 410 interact sufficiently when the molar ratio of monomer to compound 410 is 4:1. Based on the above, a molar ratio of approximately 4:1 between monomer and compound 410 in the monomer-containing solution is preferable.

[0042] The monomer-containing solution is applied to the substrate 110, or the substrate 110 is immersed in the monomer-containing solution. Polymer 400 is formed by polymerizing the monomer. Figure 4 shows the state in which polymer 400 has been formed in the method for manufacturing the receptor 100 according to this embodiment. Polymer 400 contains compound 410. In this step, polymerization may be electrolytic polymerization. Electrolytic polymerization may be carried out using cyclic voltammetry. Electrolytic polymerization may be carried out by repeatedly scanning the potential between the working electrode and the counter electrode with respect to the potential of the reference electrode, and bringing it to a potential at which a chemical reaction occurs. The potential scanning may be repeated until no current flows through the working electrode. The reference electrode may be an Ag / AgCl electrode. The working electrode may be a substrate 110 on which a metal layer 120 is formed. The counter electrode may be a platinum electrode. The potential applied between the working electrode and the counter electrode may be -0.5V to 1.5V, -0.5V to 1.0V, or 0.0V to 0.8V. A uniform polymer 400 can be formed by polymerizing the monomer by electrolytic polymerization. Instead of electrolytic polymerization, the monomer may be polymerized by adding a polymerization initiator.

[0043] Next, a molecularly imprinted polymer film 140 is formed by removing compound 410 from polymer 400. By removing compound 410, a space 150 corresponding to the shape of compound 410 is formed. In this step, compound 410 may be removed by an electrochemical reaction. The electrochemical reaction may be carried out using cyclic voltammetry in a basic solution. Compound 410 may be removed by repeatedly scanning the potential between the working electrode and the counter electrode with respect to the potential of the reference electrode, and reaching a potential at which the chemical bond is broken. The basic solution may be an aqueous solution of potassium hydroxide or sodium hydroxide. The basic solution may have a pH of 9 or higher, 10-15, or 11-13. The reference electrode may be an Ag / AgCl electrode. The working electrode may be a substrate 110 on which polymer 400 is formed. The counter electrode may be a platinum electrode. The potential applied between the working electrode and the counter electrode may be -1.0V to 1.0V. Compound 410 can be completely removed by an electrochemical reaction. Alternatively, compound 410 may be removed by washing the polymer 400 or by immersing the polymer 400 in a basic solution.

[0044] According to the receptor 100 described above, the molecular imprinted polymer film 140 has a space 150 that captures at least a portion of the compound having an asymmetric carbon atom, thereby enabling the selective capture of enantiomers.

[0045] Figure 5 shows the configuration of the sensor 500 according to this embodiment together with the sample 540. The sample 540 contains the compound to be detected. The sample 540 may further contain compounds other than the compound to be detected. The sample 540 may be a solution containing the compound to be detected. For example, the sample 540 may be an aqueous solution containing the compound to be detected.

[0046] The sensor 500 can detect compounds contained in the sample 540. In the example shown in this figure, the sensor 500 comprises a receptor 100, a field-effect transistor 510, a reference electrode 550, a measuring device 560, a first voltage source 570, a second voltage source 575, and a current measuring instrument 580.

[0047] Receptor 100 comes into contact with sample 540. Receptor 100 may be the same as the receptor 100 in Figure 1.

[0048] The field-effect transistor 510 may be a conventional field-effect transistor or an organic field-effect transistor using an organic semiconductor. The field-effect transistor 510 has a drain 520, a gate 525, and a source 530. The gate 525 is connected to a metal in contact with the molecularly imprinted polymer film 140 in the receptor 100. The gate 525 may be connected to a metal layer 120.

[0049] The reference electrode 550 is connected to the source 530. The reference electrode 550 is in contact with the sample 540. The reference electrode 550 provides a stable potential, enabling accurate measurement. The reference electrode 550 may be an Ag / AgCl electrode.

[0050] The measuring device 560 is connected to the field-effect transistor 510. The measuring device 560 controls the measurement performed by the sensor 500. The measuring device 560 may be a computer such as a PC (personal computer), tablet computer, smartphone, workstation, server computer, or general-purpose computer, or it may be a computer system in which multiple computers are connected. Such a computer system is also a computer in a broad sense. Alternatively, the measuring device 560 may be implemented by a virtual computer environment that can run one or more times within the computer. Instead, the measuring device 560 may be a dedicated computer designed for the sensor 500, or dedicated hardware realized by dedicated circuitry.

[0051] The first voltage source 570 is connected to the measuring device 560. The first voltage source 570 controls the voltage (V) between the source 530 and drain 520 of the field-effect transistor 510. d Apply ).

[0052] The second voltage source 575 is connected to the measuring device 560. The second voltage source 575 controls the gate voltage (V) of the field-effect transistor 510. g Apply ).

[0053] The current measuring instrument 580 is connected to the measuring device 560. The current measuring instrument 580 measures the current (I) flowing between the source 530 and the drain 520 in the field-effect transistor 510. d ) detects.

[0054] Figure 6 shows the configuration of the measuring device 560 according to this embodiment. In the example shown, the measuring device 560 includes a storage unit 600, a concentration acquisition unit 610, a voltage control unit 620, a current measuring unit 630, a first calculation unit 640, a second calculation unit 650, and an output unit 660.

[0055] The storage unit 600 stores the measurement data from the sensor 500. The storage unit 600 may be an electronic storage medium, a magnetic storage medium, an optical storage medium, an electromagnetic storage medium, or a semiconductor storage medium. In the example shown in the figure, the storage unit 600 is included in the measuring device 560, but it may be realized by at least a portion of the storage area of ​​an external storage device such as a hard disk drive connected to the measuring device 560, or by an external storage device provided by, for example, a cloud storage service.

[0056] The concentration acquisition unit 610 acquires the concentration of a sample when measuring a sample whose concentration is known. The concentration acquisition unit 610 may acquire the concentration of a sample based on input from the user of the sensor 500. The concentration acquisition unit 610 may have an input / output circuit or a transmit / receive circuit, and may exchange data with the user of the sensor 500 via an input / output device (such as a keyboard and display device) or a terminal device used by the user of the sensor 500.

[0057] The voltage control unit 620 is connected to the concentration acquisition unit 610, the first voltage source 570, and the second voltage source 575. The voltage control unit 620 controls the voltage of the field-effect transistor 510 via the first voltage source 570. g The voltage control unit 620 controls the voltage of the field-effect transistor 510 via the second voltage source 575. d The voltage control unit 620 controls V d While keeping V constant, g You may change it.

[0058] The current measuring unit 630 is connected to the memory unit 600, the voltage control unit 620, and the current measuring instrument 580. The current measuring unit 630 measures the current in the field-effect transistor 510 via the current measuring instrument 580. d The current measurement unit 630 stores the measurement data in the storage unit 600.

[0059] The first calculation unit 640 is connected to the storage unit 600. The first calculation unit 640 calculates a threshold voltage based on the measurement data stored in the storage unit 600. The first calculation unit 640 stores the calculated threshold voltage in the storage unit 600.

[0060] The second calculation unit 650 is connected to the storage unit 600 and the first calculation unit 640. The second calculation unit 650 calculates the concentration of the target compound contained in the sample based on the threshold voltage stored in the storage unit 600 and the threshold voltage of the sample obtained from the first calculation unit 640.

[0061] The output unit 660 is connected to the second calculation unit 650. The output unit 660 performs the process of displaying the concentration calculated by the second calculation unit 650 on a screen or the like. Here, the process of displaying a screen is not limited to actually displaying a screen on a display device, but also includes generating display data for displaying a screen on a remote display device.

[0062] FIG. 7 shows a first example of the operation flow of the sensor 500 according to the present embodiment. This figure shows a flow in which the sensor 500 measures a sample with a known concentration of a compound to be detected. In step 702 (S702), a sample 540 containing the compound to be detected is brought into contact with the receptor 100 and the reference electrode 550. The receptor 100 and the reference electrode 550 may be brought into contact with the sample 540 by immersing the receptor 100 and the reference electrode 550 in the sample 540 of the solution while separating them from each other. When the receptor 100 comes into contact with the sample 540, the compound in the sample 540 is captured in the space 150 of the receptor 100.

[0063] In S704, the concentration acquisition unit 610 acquires the concentration of the compound contained in the sample 540. The concentration acquisition unit 610 may acquire the concentration of the compound to be detected based on the input of the user. In the example of this figure, S704 is performed between S702 and S706, but may be performed at any timing from S702 to S720.

[0064] In S706, the voltage control unit 620 applies V via the first voltage source 570. For example, V may be -1.0V. In S708, the voltage control unit 620 applies V via the second voltage source 575. For example, V may be from -0.5V to 3V. d For example, V may be -1.0V. In S708, the voltage control unit 620 applies V via the second voltage source 575. For example, V may be from -0.5V to 3V. d In step S708, the voltage control unit 620 applies V via the second voltage source 575. For example, V may be from -0.5V to 3V. g In step S708, the voltage control unit 620 applies V via second voltage source 575. For example, V may be from -0.5V to 3V. g For example, V may be from -0.5V to 3V.

[0065] In S710, the current measurement unit 630 measures I via the current measuring device 580. In S d In S710, the current measurement unit 630 measures I via the current measuring device 580. g In S712, the current measurement unit 630 acquires the concentration of the compound from the concentration acquisition unit 610 and acquires V from the voltage control unit 620. The current measurement unit 630 stores the concentration of the compound, V, and I in the storage unit 600. As the concentration of the compound increases and more compounds are captured in the space 150, I at the same V decreases. g In S712, the current measurement unit 630 obtains the concentration of the compound from the concentration acquisition unit 610 and obtains V from the voltage control unit 620. d The current measurement unit 630 stores the concentration of the compound, V, and I in the storage unit 600. As the concentration of the compound increases and more compounds are captured in the space 150, I at the same V decreases. g As the concentration of the compound increases and more compounds are captured in the space 150, I at the same V decreases. d As the concentration of the compound increases and more compounds are captured in the space 150, I at the same V decreases.

[0066] The current measuring unit 630 measures all V g Regarding I d If the measurement is not taken (No. in S714), the sensor 500 returns to processing S708. In S708, which returns from S714, the voltage control unit 620 measures V g The voltage control unit 620 changes V g The current may be increased or decreased at regular intervals (e.g., 0.1V). In S710, the current measuring unit 630 is d The current measurement unit 630 measures the changed V from the voltage control unit 620. In S712, the current measurement unit 630 measures the changed V. g Obtain the compound concentration and V g , and I d The data is stored in the memory unit 600.

[0067] The current measuring unit 630 measures all V g Regarding I d If the measurement is taken (Yes in S714), the sensor 500 proceeds to S716. In S716, the first calculation unit 640 calculates the V at the concentration. g and I d V shows the relationship g ―I d The curve is obtained. The first calculation unit 640 receives the concentration and the V at that concentration from the storage unit 600. g and I d Obtain the combination and V at that concentration g ―I d You may generate a curve.

[0068] In S718, the first calculation unit 640 calculates the threshold voltage at the concentration. As the concentration of the compound increases and more compounds are trapped in space 150, the threshold voltage shifts in the negative direction. The first calculation unit 640 calculates I d 1 / 2 power and V gThe threshold voltage can be calculated by drawing an approximate straight line in the region where the relationship is linear (saturation region) and calculating the value of its X-intercept. In S720, the first calculation unit 640 stores the compound concentration and threshold voltage in the storage unit 600. The first calculation unit 640 may store the data in the same storage unit 600 as in S712, or it may store the data in a different storage unit 600 than in S712.

[0069] If all samples 540 with known compound concentrations have not been measured (No in S722), the sensor 500 returns the process to S702. In S702, which returns from S722, the unmeasured samples 540 are brought into contact with the receptor 100 and the reference electrode 550. If all samples 540 with known compound concentrations have been measured (Yes in S722), the sensor 500 terminates the process flow.

[0070] Figure 8 shows a second example of the operation flow of the sensor 500 according to this embodiment. Figure 8 shows the flow in which the sensor 500 measures a sample 540 in which the concentration of the compound to be detected is unknown. In S802, the sample 540 containing the compound to be detected is brought into contact with the receptor 100 and the reference electrode 550. S802 may be the same as S702 in Figure 7.

[0071] In S804, the voltage control unit 620 controls the voltage via the first voltage source 570. d Apply V. For example, V d This may be -1.0V. In S806, the voltage control unit 620 receives V via the second voltage source 575. g Apply V. For example, V g The voltage may be between -0.5V and 3V.

[0072] In S808, the current measuring unit 630 is connected to the current measuring instrument 580 via I d The current is measured. In S810, the current measuring unit 630 receives the voltage from the voltage control unit 620. g The current measuring unit 630 obtains V g and I d The data is stored in the memory unit 600.

[0073] The current measuring unit 630 measures all V g Regarding I d If the measurement is not taken (No. in S812), the sensor 500 returns to processing in S806. In S806, which returns from S812, the voltage control unit 620 measures V g The voltage control unit 620 changes V g The current may be increased or decreased at regular intervals (e.g., 0.1V). In S808, the current measuring unit 630 is I d The current measurement unit 630 measures the changed V from the voltage control unit 620. g Obtain V g and I d The data is stored in the memory unit 600.

[0074] The current measuring unit 630 measures all V g Regarding I d If the measurement is taken (Yes in S812), the sensor 500 proceeds to processing in S814. In S814, the first calculation unit 640 calculates the V at the concentration. g and I d V shows the relationship g ―I d The curve is obtained. The first calculation unit 640 receives the concentration and the V at that concentration from the storage unit 600. g and I d Obtain the combination and V at that concentration g ―I d You may generate a curve.

[0075] In S816, the first calculation unit 640 calculates the threshold voltage. The first calculation unit 640 calculates the threshold voltage. d 1 / 2 power and V g The threshold voltage can be calculated by drawing an approximate straight line in the region where the relationship is linear (saturation region) and calculating the value of its X-intercept.

[0076] In S818, the second calculation unit 650 acquires a concentration-threshold voltage relationship curve. The second calculation unit 650 may acquire a combination of concentration and threshold voltage at that concentration from the storage unit 600 and generate a concentration-threshold voltage relationship curve. In S820, the second calculation unit 650 calculates the concentration of the compound contained in the sample 540. The second calculation unit 650 may acquire the threshold voltage calculated in S816 from the first calculation unit 640. The second calculation unit 650 may calculate the concentration of the compound contained in the sample 540 from the threshold voltage calculated in S816 and the concentration-threshold voltage relationship curve. For example, the second calculation unit 650 may calculate the concentration of the compound contained in the sample 540 as the concentration corresponding to the threshold voltage calculated in S816 in the concentration-threshold voltage relationship curve. Therefore, the sensor 500 measures the compound in the sample 540 based on the change in the current-voltage characteristics of the field-effect transistor 510. The sensor 500 may quantitatively measure the compound in the sample based on the change in the current-voltage characteristics of the field-effect transistor 510. The output unit 660 may output the concentration of the compound calculated by the second calculation unit 650.

[0077] The sensor 500 described above allows for the simple and rapid detection of compounds containing chiral carbon atoms. Furthermore, the sensor 500 can detect compounds containing chiral carbon atoms without causing them to denature.

[0078] The optical purity of the compound may be determined based on the measurement results when measuring a compound using two or more sensors 500, each of which captures a different compound in space 150. The concentration of each compound may be measured using the methods shown in Figures 7 and 8, with each of the two or more sensors 500 capturing a different compound in space 150. The optical purity of the compound may be determined based on the concentration of each compound calculated by each sensor 500. Each of the two or more sensors 500 may capture a different type of isomer from among multiple isomers of the same chemical formula. For example, the concentration of the L-isomer in sample 540 may be measured using a sensor 500 equipped with space 150 that captures only the L-isomer, and the concentration of the D-isomer in sample 540 may be measured using a sensor 500 equipped with space 150 that captures only the D-isomer, and the optical purity of the compound may be determined based on the concentrations of the L-isomer and the D-isomer, respectively.

[0079] Alternatively, the compound may be measured using a single sensor 500, and the optical purity of the compound may be determined based on the measurement results. The first calculation unit 640 of the measuring device 560 may calculate the threshold voltage for each sample 540 using the method described in Figures 7 and 8, with a plurality of samples 540 having a constant total amount of the compound to be detected and its isomers, but with different optical purities of the compound to be detected. The second calculation unit 650 may obtain an optical purity-threshold voltage relationship curve using the method described in Figure 8. Based on the optical purity-threshold voltage relationship curve, the second calculation unit 650 may determine the optical purity of a sample 540 from the threshold voltage of a sample 540 whose optical purity is unknown and whose total amount of the compound to be detected and its isomers is known. The second calculation unit 650 may determine the optical purity from the optical purity-threshold voltage relationship curve using support vector machine (SVM) regression. As an example, the second calculation unit 650 may perform SVM regression using the method described in Non-Patent Literature 2.

[0080] Figure 9 shows the configuration of the sensor 900 according to the first modified example of this embodiment, together with a sample 540. The sample 540 may be the same as in Figure 5. The sensor 900 can detect compounds contained in the sample 540. In the example shown in this figure, the sensor 900 comprises a receptor 100, a potentiostat 910, a counter electrode 920, and a reference electrode 930. The receptor 100 functions as the working electrode. The receptor 100 may be the same as in Figure 1.

[0081] The counter electrode 920 is in contact with the sample 540. The counter electrode 920 is an electrode that undergoes a reaction corresponding to the redox reaction at the working electrode, receptor 100. The counter electrode 920 may be made of a conductive material. The counter electrode 920 may be a metal electrode or a carbon electrode.

[0082] The reference electrode 930 is in contact with the sample 540. The reference electrode 930 provides a stable potential, enabling accurate measurement. The reference electrode 930 may be an Ag / AgCl electrode.

[0083] The potentiostat 910 is connected to the metal in contact with the molecularly imprinted polymer film 140 in the receptor 100, the counter electrode 920, and the reference electrode 930. The potentiostat 910 may also be connected to the metal layer 120 in the receptor 100. The potentiostat 910 applies a voltage between the receptor 100 and the counter electrode 920 to control the potential between the receptor 100 and the reference electrode 930. The potentiostat 910 may evaluate the current-voltage characteristics of the receptor 100 by differential pulsed voltammetry (DPV). The sensor 900 may calculate the concentration of the compound contained in the sample 540 based on the change in the current value in DPV.

[0084] Figure 10 shows the configuration of a synthesis system 1000 according to a second modified example of this embodiment. The synthesis system 1000 is a system that performs chemical reactions involving compounds having asymmetric carbon atoms. In the example shown in this figure, the synthesis system 1000 comprises one or more sensors 500, a reactor 1005, a control unit 1015, and a heater 1020.

[0085] Reactor 1005 is a vessel in which a chemical reaction involving a compound having an asymmetric carbon atom takes place. In the example shown in this figure, reactor 1005 is a tank reactor. Reactor 1005 contains solution 1010. Solution 1010 contains at least one reactant or product. Solution 1010 contains a compound having an asymmetric carbon atom as either a reactant or a product. Solution 1010 may contain a compound having an asymmetric carbon atom as a product.

[0086] Sensor 500 comes into contact with solution 1010. Sensor 500 quantitatively measures the isomers of compounds contained in solution 1010. Sensor 500 may be the same as that shown in Figure 5. Sensor 500 may determine the optical purity of the compounds contained in solution 1010. The synthesis system 1000 may be equipped with two or more sensors 500, and the optical purity of the compounds contained in solution 1010 may be calculated based on the measurement results of two or more sensors 500.

[0087] The control unit 1015 is connected to the measuring device 560 of the sensor 500. The control unit 1015 obtains the measurement results of the sensor 500 from the measuring device 560. The control unit 1015 controls the reaction conditions in the reactor 1005 based on the measurement results of the sensor 500. The control unit 1015 may control the temperature of the reactor 1005 based on the optical purity of the compounds contained in the solution 1010 calculated from the measurement results of one or more sensors 500. For example, if the control unit 1015 obtains a measurement result from the measuring device 560 indicating that the optical purity of the compounds contained in the solution 1010 has decreased, it may lower the temperature of the reactor 1005. The control unit 1015 may also control factors other than the temperature of the reactor 1005 (flow rate, mixing ratio, stirring speed if the reactor 1005 has a stirrer, etc.).

[0088] The heater 1020 is connected to the control unit 1015. The control unit 1015 may control the temperature of the reactor 1005 via the heater 1020.

[0089] According to the synthesis system 1000 described above, the optical purity during a chemical reaction can be detected simply and quickly, and the chemical reaction can be controlled based on the detected optical purity. Therefore, the synthesis system 1000 can control the optical purity of the product in a chemical reaction.

[0090] Figure 11 shows the configuration of a column 1100 according to a third modified example of this embodiment. The column 1100 separates enantiomers by selectively capturing one enantiomer of a compound having an asymmetric carbon atom. In the example shown in this figure, the column 1100 is cylindrical. The column 1100 comprises a plurality of packing materials 1110.

[0091] The packing material 1110 is packed into the column 1100. In the example shown in this figure, the packing material 1110 is spherical. Alternatively, the packing material 1110 may have a cylindrical, cubic, rectangular prism, or other three-dimensional shape. The packing material 1110 comprises a substrate 1115, a metal layer 1120, and a molecularly imprinted polymer film 1140.

[0092] The substrate 1115 has an outer surface on which each layer of the filler 1110 is formed. In this embodiment, the substrate 1115 is spherical. Alternatively, the substrate 1115 may have a cylindrical, cubic, rectangular parallelepiped, or other three-dimensional shape. The substrate 1115 may be formed of silica gel.

[0093] The molecularly imprinted polymer film 1140 is formed on the substrate 1115. The molecularly imprinted polymer film 1140 includes a space 1150 that captures at least a portion of the compound having chiral carbon atoms. The molecularly imprinted polymer film 1140 may be the same as the molecularly imprinted polymer film 140 in Figure 1, and the space 1150 may be the same as the space 150 in Figure 1.

[0094] The metal layer 1120 is formed between the substrate 1115 and the molecularly imprinted polymer film 1140. The metal layer 1120 may be formed of a metallic material similar to the metal layer 120 in Figure 1. Instead of the metal layer 1120, a layer formed of indium tin oxide (ITO), poly(3,4-ethylenedioxythiophene), polystyrene sulfonate, conductive carbon nanotubes, graphene, or a conductive organic-inorganic composite material may be formed between the substrate 1115 and the molecularly imprinted polymer film 1140. In the example shown in this figure, the metal layer 1120 includes a metal film 1125 and a nanostructure 1130. Alternatively, the metal layer 1120 may not include the nanostructure 1130. The metal film 1125 may be similar to the metal film 125 in Figure 1, and the nanostructure 1130 may be similar to the nanostructure 130 in Figure 1.

[0095] According to the column 1100 described above, since the space 1150 selectively captures compounds containing chiral carbon atoms, enantiomers can be separated by passing a fluid containing compounds with chiral carbon atoms through it.

[0096] The present invention will be described in more detail below based on examples, but the present invention is not limited to these examples.

[0097] (Manufacturing of Receptor 100) (Examples) L-histidine was used as the target for detection, and 1,2-diaminobenzene as the monomer. Receptor 100 was prepared using a monomer-containing solution prepared by mixing 1,2-diaminobenzene and L-histidine in a molar ratio of 4:1, based on the methods described in Figures 2 to 4.

[0098] (Comparative example) The target for detection was L-histidine, and the monomers were 1,2-diaminobenzene and dopamine. Based on the methods described in Figures 2 to 4, receptor 100 was prepared using a monomer-containing solution in which 1,2-diaminobenzene, dopamine, and L-histidine were mixed in a molar ratio of 1:4:1.

[0099] (DPV measurement) Sensor 900, shown in Figure 9, was fabricated using receptor 100 from either the example or comparative example. Sample 540 consisted of multiple 100 mM phosphate-buffered salines (pH 6.0) containing 5 mM K3Fe(CN)6, 100 mM KCl, and L-histidine. The measurement range was -0.05 V to 0.8 V (vs. Ag / AgCl).

[0100] Figures 12 and 13 show the DPV measurement results. Figure 12 shows an example of DPV measurement results using Receptor 100 of the example. DPV measurements were performed using sample 540 with L-histidine concentrations of 0, 0.9, 2, 4, 6, 8, or 10 mM, respectively. In this figure, the peak around 0.22 V originates from the redox reaction of K3Fe(CN)6 contained in sample 540. In this figure, the peak current value of the redox reaction of K3Fe(CN)6 decreased as the L-histidine concentration increased. Therefore, in Receptor 100 with 1,2-diaminobenzene as the monomer, a change in the current-voltage characteristics according to the L-histidine content was observed.

[0101] Figure 13 shows an example of DPV measurement results using Receptor 100 of a comparative example. DPV measurements were performed using Sample 540 with L-histidine concentrations of 0, 1, 3, 5, 7, or 10 mM, respectively. Note that the data using Sample 540 with an L-histidine concentration of 1 mM overlaps with the data using Sample 540 with an L-histidine concentration of 3 mM. In this figure, the peak current value of the redox reaction of K3Fe(CN)6 remained almost constant even when the L-histidine concentration changed. Thus, in Receptor 100, in which the monomers were 1,2-diaminobenzene and dopamine, no change in the current-voltage characteristics depending on the L-histidine content was observed. Therefore, in this example, by not including alkyl groups with 2 or more carbon atoms in the substituents of the monomer, the rigidity of the space 150 in the molecular imprint polymer film 140 was increased, and the space 150 became more selective in capturing molecules.

[0102] (Confirmation of response specificity) Using the receptor 100 of the above embodiment, the sensor 500 shown in Figure 5 was manufactured. As sample 540, L-lysine (C6H 14 N2O2), L-tyrosine (C9H 11 NO3), L-histidine (C6H9N3O2), D-histidine (C6H9N3O2), L-tryptophan (C 11 H 12 N2O2), or L-phenylalanine (C9H 11 A solution containing 1 mM each of NO2 was used. Here, L-histidine and D-histidine are isomers with the same chemical formula. For each sample 540, the threshold voltage (V) was measured using the method described in S702 to S718 in Figure 7. TH The reference threshold voltage (V) was calculated using the same method by using a solution that does not contain these compounds as sample 540. TH0 ) was calculated.

[0103] Figure 14 shows an example of the response specificity in receptor 100 of the example. According to this figure, in the measurement of sample 540 containing L-histidine, V TH and V TH0 The difference was approximately -0.07V, but when measuring sample 540 containing other compounds, V TH and V TH0 The difference was -0.015V or less. Therefore, in the receptor 100 of the example, no change in current-voltage characteristics was observed for compounds and isomers with different chemical formulas, and a change in current-voltage characteristics was observed only for L-histidine, which was the target of detection. From the above, it was confirmed that the receptor 100 of the present invention specifically captures a particular molecule.

[0104] (Calculation of optical purity) Using the receptor 100 of the above embodiment, the sensor 500 of FIG. 5 was manufactured. As the sample 540, a plurality of 100 mM phosphate buffered saline (pH 6.0) containing D-histidine and L-histidine were used. Here, L-histidine and D-histidine are in an isomeric relationship having the same chemical formula. The total concentration of D-histidine and L-histidine in the sample 540 was 300 μM, and the optical purity of histidine was from -2.6% ee to 92.9% ee. For each sample 540, the respective V g -I d curves were obtained by the method described from S702 to S716 in FIG. 7. The threshold voltage (V TH ) was calculated by the method described in S718 of FIG. 7. Here, V d was set to -2 V, and V g was measured in the range from -3 V to 0.5 V. By using a solution containing neither D-histidine nor L-histidine as the sample 540, the reference threshold voltage (V TH0 ) was calculated by the same method.

[0105] FIGS. 15 to 18 show the measurement results of the samples 540 with different optical purities. FIG. 15 shows an example of the V g -I d curve in the samples 540 with different optical purities. FIG. 16 shows an example of the threshold voltage of the sample 540 with an optical purity of 80% ee or less. In this figure, as the optical purity of L-histidine increases, linearly (V TH -V TH0 ) / V TH increases. Therefore, in the receptor 100, a change in the current-voltage characteristics according to the optical purity of the compound to be detected was observed.

[0106] FIG. 17 shows an example of the threshold voltage of the sample 540 with an optical purity of 80% ee or more. Also in this figure, as in FIG. 16, as the optical purity of L-histidine increases, linearly (V TH -V TH0 ) / V TH increases. On the other hand, (V TH -V TH0 ) / V THThe slope in Fig. 16 is (V TH - V TH0 ) / V TH , which is different from the slope in Fig. 16. Therefore, it was observed that the linear responsiveness of the threshold voltage with respect to the optical purity varies depending on the region of the optical purity.

[0107] Based on the threshold voltages of each sample 540 in Figs. 16 and 17, the optical purity was determined by SVM regression. SVM regression was performed using the method described in Non-Patent Document 2.

[0108] Fig. 18 shows an example of the determination result of the optical purity using machine learning. In this figure, the vertical axis represents the value of the optical purity calculated by SVM regression, and the horizontal axis represents the value of the actual optical purity. According to this figure, even if the linear responsiveness of the threshold voltage with respect to the optical purity varies depending on the region of the optical purity, the optical purity can be accurately determined by using SVM regression. Therefore, as in this embodiment, by using the receptor 100 that detects only one of the optical isomers as the detection target, the sensor 500 can determine the optical purity of the detection target.

[0109] Various embodiments of the present invention may be described with reference to flowcharts and block diagrams, where the blocks may represent (1) a stage of a process in which an operation is performed or (2) a section of a device having a role of performing an operation. Specific stages and sections may be implemented by a dedicated circuit, a programmable circuit supplied with computer-readable instructions stored on a computer-readable medium, and / or a processor supplied with computer-readable instructions stored on a computer-readable medium. The dedicated circuit may include digital and / or analog hardware circuits, and may include integrated circuits (ICs) and / or discrete circuits. The programmable circuit may include a reconfigurable hardware circuit including memory elements such as logical AND, logical OR, logical XOR, logical NAND, logical NOR, and other logical operations, flip-flops, registers, field programmable gate arrays (FPGAs), programmable logic arrays (PLAs), etc.

[0110] Computer-readable media may include any tangible device capable of storing instructions to be executed by a suitable device, and as a result, computer-readable media having instructions stored therein will comprise a product containing instructions that can be executed to create means for performing operations specified in a flowchart or block diagram. Examples of computer-readable media may include electronic storage media, magnetic storage media, optical storage media, electromagnetic storage media, semiconductor storage media, etc. More specific examples of computer-readable media may include floppy disks, diskettes, hard disks, random access memory (RAM), read-only memory (ROM), erasable programmable read-only memory (EPROM or flash memory), electrically erasable programmable read-only memory (EEPROM), static random access memory (SRAM), compact disk read-only memory (CD-ROM), digital multipurpose disc (DVD), Blu-ray® disc, memory stick, integrated circuit card, etc.

[0111] Computer-readable instructions may include assembler instructions, instruction set architecture (ISA) instructions, machine instructions, machine-dependent instructions, microcode, firmware instructions, state setting data, or source code or object code written in any combination of one or more programming languages, including object-oriented programming languages ​​such as Smalltalk®, Java®, C++, and traditional procedural programming languages ​​such as the C programming language or similar programming languages.

[0112] Computer-readable instructions are provided locally or via a wide area network (WAN) such as a local area network (LAN) or the internet to the processor or programmable circuit of a programmable data processing device such as a computer, and may be executed to create means for performing operations specified in a flowchart or block diagram. Here, the computer may be a PC (personal computer), tablet computer, smartphone, workstation, server computer, general-purpose computer, or special-purpose computer, and may also be a computer system in which multiple computers are connected. Such a computer system in which multiple computers are connected is also called a distributed computing system and is a computer in a broad sense. In a distributed computing system, multiple computers execute a program collectively by each computer executing a part of the program and passing data during program execution between computers as needed.

[0113] Examples of processors include computer processors, central processing units (CPUs), processing units, microprocessors, digital signal processors, controllers, and microcontrollers. A computer may have one or more processors. In a multiprocessor system with multiple processors, each processor executes a portion of the program, and the processors collectively execute the program by passing program execution data between them as needed. For example, in the execution of multitasking, each of the multiple processors may execute a portion of each task in small chunks by switching tasks at each time slice. In this case, which part of a program each processor executes changes dynamically. Which part of a program each of the multiple processors executes may also be statically determined by multiprocessor-aware programming.

[0114] Figure 19 shows an example of a computer 1200 in which multiple aspects of the present invention may be embodied in whole or in part. A program installed on the computer 1200 can cause the computer 1200 to function as an operation or one or more sections of an apparatus according to an embodiment of the present invention, or to execute such operation or one or more sections, and / or to cause the computer 1200 to execute a process or a stage of such process according to an embodiment of the present invention. Such a program may be executed by the CPU 1212 to cause the computer 1200 to perform a particular operation associated with some or all of the blocks in the flowcharts and block diagrams described herein.

[0115] The computer 1200 according to this embodiment includes a CPU 1212, RAM 1214, a graphics controller 1216, and a display device 1218, which are interconnected by a host controller 1210. The computer 1200 also includes input / output units such as a communication interface 1222, a storage device 1224 such as a hard disk drive, a DVD-ROM drive 1226, and an IC card drive, which are connected to the host controller 1210 via an input / output controller 1220. The computer also includes legacy input / output units such as a ROM 1230 and a keyboard 1242, which are connected to the input / output controller 1220 via an input / output chip 1240.

[0116] The CPU 1212 operates according to programs stored in the ROM 1230 and RAM 1214, thereby controlling each unit. The graphics controller 1216 acquires image data generated by the CPU 1212 from a frame buffer provided in RAM 1214 or from itself, and displays the image data on the display device 1218.

[0117] The communication interface 1222 communicates with other electronic devices via a network. The storage device 1224 stores programs and data used by the CPU 1212 in the computer 1200. The DVD-ROM drive 1226 reads programs or data from the DVD-ROM 1227 and provides them to the storage device 1224 via the RAM 1214. The IC card drive reads programs and data from the IC card and / or writes programs and data to the IC card.

[0118] The ROM 1230 stores boot programs and / or programs that depend on the computer 1200's hardware, which are executed by the computer 1200 when activated. The input / output chip 1240 may also connect various input / output units to the input / output controller 1220 via a parallel port, serial port, keyboard port, mouse port, etc.

[0119] The program is provided on a computer-readable medium such as a DVD-ROM 1227 or an IC card. The program is read from the computer-readable medium and installed on a storage device 1224, RAM 1214, or ROM 1230, which are also examples of computer-readable medium, and executed by the CPU 1212. The information processing described within these programs is read by the computer 1200, resulting in coordination between the program and the various types of hardware resources described above. The apparatus or method may be configured to realize the manipulation or processing of information in accordance with the use of the computer 1200.

[0120] For example, when communication is performed between a computer 1200 and an external device, the CPU 1212 may execute a communication program loaded into RAM 1214 and, based on the processing described in the communication program, instruct the communication interface 1222 to perform communication processing. Under the control of the CPU 1212, the communication interface 1222 reads transmission data stored in a transmission buffer processing area provided in a recording medium such as RAM 1214, storage device 1224, DVD-ROM 1227, or IC card, transmits the read transmission data to the network, or writes received data received from the network to a receive buffer processing area provided on the recording medium.

[0121] Furthermore, the CPU 1212 may read all or necessary parts of a file or database stored on an external storage medium such as the memory device 1224, DVD-ROM drive 1226 (DVD-ROM 1227), or IC card into the RAM 1214, and perform various types of processing on the data in the RAM 1214. The CPU 1212 then writes the processed data back to the external storage medium.

[0122] Various types of information, such as various types of programs, data, tables, and databases, may be stored on the recording medium and subjected to information processing. The CPU 1212 may perform various types of processing on the data read from RAM 1214, including various types of operations, information processing, conditional judgments, conditional branching, unconditional branching, information retrieval / replacement, etc., as described throughout this disclosure and specified by the program instruction sequence, and write the results back to RAM 1214. The CPU 1212 may also retrieve information in files, databases, etc., within the recording medium. For example, if multiple entries are stored in the recording medium, each having an attribute value of a first attribute associated with an attribute value of a second attribute, the CPU 1212 may search among the multiple entries for an entry that matches the condition for which the attribute value of the first attribute is specified, read the attribute value of the second attribute stored in that entry, and thereby obtain the attribute value of the second attribute associated with the first attribute that satisfies a predetermined condition.

[0123] The programs or software modules described above may be stored on or near computer 1200 on a computer-readable medium. Alternatively, recording media such as hard disks or RAM provided within a server system connected to a dedicated communication network or the Internet can be used as computer-readable media, thereby providing programs to computer 1200 via the network.

[0124] Although the present invention has been described above using embodiments, the technical scope of the present invention is not limited to the scope described in the above embodiments. It will be apparent to those skilled in the art that various modifications or improvements can be made to the above embodiments. It will be clear from the claims that such modified or improved forms may also be included in the technical scope of the present invention.

[0125] It should be noted that the execution order of operations, procedures, steps, and stages in the apparatus, systems, programs, and methods shown in the claims, specifications, and drawings is not explicitly stated as "before," "prior to," etc., and that these can be implemented in any order unless the output of a previous process is used in a later process. Even if the operation flow in the claims, specifications, and drawings is described using phrases such as "first," "next," etc. for convenience, it does not mean that it is essential to perform the operations in that order. [Explanation of symbols]

[0126] 100 Receptor, 110 Substrate, 120 Metal layer, 125 Metal film, 130 Nanostructure, 140 Molecular imprinted polymer film, 150 Space, 400 Polymer, 410 Compound, 500 Sensor, 510 Field-effect transistor, 520 Drain, 525 Gate, 530 Source, 540 Sample, 550 Reference electrode, 560 Measuring device, 570 First voltage source, 575 Second voltage source, 580 Current meter, 600 Memory unit, 610 Concentration acquisition unit, 620 Voltage control unit, 630 Current measurement unit, 640 First calculation unit, 650 Second calculation unit, 660 Output unit, 900 Sensor, 910 Potentiostat, 920 Counter electrode, 930 Reference electrode, 1000 Synthesis system, 1005 Reactor, 1010 Solution, 1015 Control unit, 1020 Heater, 1100 Column, 1110 Packing material, 1115 Substrate, 1120 Metal layer, 1125 Metal film, 1130 Nanostructure, 1140 Molecular imprinted polymer film, 1150 Space, 1200 Computer, 1210 Host controller, 1212 CPU, 1214 RAM, 1216 Graphics controller, 1218 Display device, 1220 Input / Output controller, 1222 Communication interface, 1224 Storage device, 1226 DVD-ROM drive, 1227 DVD-ROM, 1230 ROM, 1240 Input / Output chip, 1242 Keyboard

Claims

1. Substrate and, A molecular imprinted polymer film formed on the substrate having a space for capturing at least a portion of a compound having asymmetric carbon atoms, A receptor equipped with [a specific feature / feature].

2. The receptor according to claim 1, further comprising a metal layer having a nanostructure on the surface in contact with the molecular imprinted polymer film, formed between the substrate and the molecular imprinted polymer film.

3. The receptor according to claim 1, wherein the molecularly imprinted polymer film has non-covalent functional groups on the surface forming the space.

4. The receptor according to claim 3, wherein the molecularly imprinted polymer film has three or more non-covalent functional groups in one space.

5. The receptor according to claim 1, wherein the molecularly imprinted polymer film is composed of aromatic monomers.

6. The receptor according to claim 1, wherein the compound has at least one of a heteroatom, an -OH group, or an -C=O group.

7. The compound is a receptor according to claim 1, having at least one primary amine group or a secondary amine group.

8. The receptor according to claim 1, wherein the compound is at least one of histidine (His), a His derivative, a His analog, a His side chain protector, or a peptide containing His.

9. The receptor according to claim 5, wherein the monomer does not contain an alkyl group having two or more carbon atoms as a substituent.

10. The receptor according to claim 9, wherein the monomer comprises a hydrogen bond donor substituent.

11. The receptor according to claim 10, wherein the monomer is at least one of 1,2-diaminobenzene, 1,3-diaminobenzene, 1,4-diaminobenzene, 2-aminophenol, 1,3-dihydroxybenzene, or aniline.

12. The receptor according to claim 1, A sensor comprising a field-effect transistor having a gate connected to a metal in contact with the molecular imprinted polymer film in the receptor.

13. The sensor according to claim 12, Reactor and A control unit that controls the reaction conditions in the reactor based on the measurement results of the sensor. A synthesis system equipped with the following features.

14. A sample containing the compound to be detected is brought into contact with the receptor of the sensor according to claim 12. A measurement method for measuring compounds in a sample based on changes in the current-voltage characteristics of the field-effect transistor.

15. The measurement method according to claim 14, wherein the compound in the sample is quantitatively measured based on the change in the current-voltage characteristics.

16. The compound is measured using two or more sensors according to claim 12, each capturing a different compound in the space. A method for determining the optical purity of the compound based on measurement results.

17. A monomer-containing solution is prepared by mixing a compound having an asymmetric carbon atom with a monomer. The monomer-containing liquid is applied to the substrate, or the substrate is immersed in the monomer-containing liquid. A polymer is formed by polymerizing the above monomer. A molecular imprinted polymer film is formed by removing the aforementioned compound. Receptor manufacturing method.

18. The method for producing a receptor according to claim 17, wherein the polymerization is electrolytic polymerization.

19. The method for producing a receptor according to claim 17, wherein the compound is removed by an electrochemical reaction.

20. The method for manufacturing a receptor according to claim 17, wherein a metal layer having a nanostructure is formed on the surface of the substrate prior to the coating or immersion.

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