Receptors, sensors, synthetic systems, assay methods, and methods of making receptors

Abstract

This invention provides a receptor, a sensor, a synthesis system, a measurement method, and a method for manufacturing the receptor. The receptor comprises: a substrate; and a molecularly imprinted polymer membrane formed on the substrate, having spaces for capturing at least a portion of a compound having asymmetric carbon atoms. The receptor may include a metal layer formed between the substrate and the molecularly imprinted polymer membrane, having a nanostructure on the surface in contact with the membrane. In any of the above-described receptors, the molecularly imprinted polymer membrane may have non-covalently bound functional groups on the surface forming the spaces.

Description

Technical Field

[0001] This invention relates to receptors, sensors, synthesis systems, measurement methods, and receptor manufacturing methods. Background Technology

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

[0003] Non-patent literature 1 describes that, "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) Existing technical documents Patent documents Patent Document 1: Japanese Patent Application Publication No. 2023-61890 Patent Document 2: Japanese Patent Application Publication No. 2023-45665 Non-patent literature Non-patent literature 1: Zhang, Lijun, et al., Chirality detection of amino acid enantiomers by organic electrochemical transistor., Biosensors and Bioelectronics 105 (2018): 121-128. Non-patent literature 2: Tsuyoshi Minami et al., Supramolecular Sensor for Cancer-AssociatedNitrosamines, J. Am. Chem. Soc. 134, 49 (2012): 20021-20024. Summary of the Invention

[0004] (1) In a first aspect of the present invention, a receptor is provided comprising: a matrix; and a molecularly imprinted polymer film formed on the matrix, having a space for capturing at least a portion of a compound having asymmetric carbon atoms.

[0005] (2) The receptor in (1) above may have a metal layer formed between the substrate and the molecularly imprinted polymer film, and the metal layer has a nanostructure on the surface in contact with the molecularly imprinted polymer film.

[0006] (3) In the receptor of (1) or (2) above, the molecularly imprinted polymer film may have non-covalently bound functional groups on the surface forming the space.

[0007] (4) In the receptor of (3) above, the molecularly imprinted polymer membrane may have more than three of the non-covalently bound functional groups in one of the spaces.

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

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

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

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

[0012] (9) In the acceptor of (5) above, the monomer may not contain an alkyl group having more than 2 carbons in the substituent.

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

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

[0015] (12) In a second aspect of the present invention, a sensor is provided comprising: a receptor of any one of (1) to (11) above; a field-effect transistor having a gate connected to a metal, the metal being in contact with the molecularly imprinted polymer film in the receptor.

[0016] (13) In a third aspect of the present invention, 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) In a fourth aspect of the present invention, a method is provided in which the receptor of the sensor described in (12) is brought into contact with a sample containing a compound as the target of detection, and the compound in the sample is determined based on the change in the current-voltage characteristics of the field-effect transistor.

[0018] (15) The determination method described in (14) above can quantitatively determine the compound in the sample based on the changes in the current-voltage characteristics.

[0019] (16) In a fifth aspect of the present invention, a method is provided to measure the compound using two or more of the sensors described in (12) above that are different from the space-captured compound, and to determine the optical purity of the compound based on the measurement results.

[0020] (17) In a sixth aspect of the present invention, a method for manufacturing an acceptor is provided, wherein a compound having asymmetric carbon atoms is mixed with a monomer to prepare a monomer-containing solution, the monomer-containing solution is coated onto a substrate or the substrate is immersed in the monomer-containing solution, a polymer is formed by polymerizing the monomer, and a molecularly imprinted polymer film is formed by removing the compound.

[0021] (18) In the acceptor manufacturing method of (17) above, the polymerization may be electrolytic polymerization.

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

[0023] (20) The receptor manufacturing method of any one of (17) to (19) above may form a metal layer with a nanostructure on the surface of the substrate before the coating or the impregnation.

[0024] Furthermore, the above summary of the invention does not list all the features of the invention. Additionally, sub-combinations of these feature groups can also constitute inventions. Attached Figure Description

[0025] Figure 1 This is a cross-sectional view of the receptor 100 in this embodiment. Figure 2 This indicates the state in which a metal film 125 is formed on a substrate 110 in the method for manufacturing the receptor 100 of this embodiment. Figure 3 This indicates that the method for manufacturing the receptor 100 in this embodiment has resulted in the formation of a nanostructure 130. Figure 4 This indicates that the manufacturing method of the receptor 100 in this embodiment has resulted in the formation of polymer 400. Figure 5 Together with sample 540, the configuration of sensor 500 of this embodiment is shown. Figure 6 This describes the configuration of the measuring device 560 in this embodiment. Figure 7 This is the first example illustrating the operation flow of the sensor 500 in this embodiment. Figure 8 This is a second example illustrating the operation flow of the sensor 500 in this embodiment. Figure 9 Together with sample 540, the configuration of sensor 900 of the first modified example of this embodiment is shown. Figure 10 This describes the configuration of the synthesis system 1000 in the second variation of this embodiment. Figure 11 This describes the configuration of column 1100 in the third variation of this embodiment. Figure 12 This represents an example of the DPV measurement results using receptor 100 from the embodiment. Figure 13 The comparative example represents the DPV measurement results of receptor 100 using the comparative example. Figure 14 An example illustrating the response specificity of receptor 100 in the embodiment. Figure 15 V represents samples 540 with different optical purity. g -I d An example of a curve. Figure 16 This is an example of the threshold voltage of sample 540 with an optical purity of less than 80%ee. Figure 17 This is an example of the threshold voltage of sample 540, representing an optical purity of 80%ee or higher. Figure 18 This represents an example of the determination of optical purity using machine learning. Figure 19 Examples of computer 1200 that can be implemented in whole or in part in various ways of the present invention are shown. Detailed Implementation

[0026] The present invention will now be described through embodiments thereof; however, these embodiments do not limit the invention as defined in the claims. Furthermore, it is not necessary to include all combinations of features described in the embodiments in the complete solution of the invention.

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

[0028] The substrate 110 has surfaces on which the layers of the receptor 100 are formed (the upper surfaces in this figure). In this embodiment, the substrate 110 is plate-shaped. The substrate 110 can be formed of glass or resin. The substrate 110 can be formed of polyethylene naphthalate.

[0029] A molecularly imprinted polymer film 140 is formed on a substrate 110. Here, "on substrate 110" means that the molecularly imprinted polymer film 140 is formed in a region above the substrate 110, meaning that the substrate 110 and the molecularly imprinted polymer film 140 can 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 traps at least a portion of a compound having asymmetric carbon atoms.

[0030] The molecularly imprinted polymer film 140 may have non-covalently bonded functional groups on the surface forming space 150. Thus, space 150 can interact with at least a portion of the compound for trapping. The non-covalently bonded functional groups may be hydrogen bond donor substituents. These substituents may be at least one of hydroxyl (-OH), amino (-NH2, -NHR, -NR2), amide (-CONH2), carboxyl (-COOH), thio (-SH), urea (-NHCONH-), guanidinyl (-C(=NH)-NH2), sulfonamide (-SO2NH2), and imino (=NH). For example, the hydrogen bond donor substituent may be -OH, -NH2, or -C≡N. The molecularly imprinted polymer film 140 may have three or more non-covalently bonded functional groups in one space 150. This allows space 150 to trap 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 can be composed of aromatic monomers. Therefore, the molecularly imprinted polymer film 140 can have repeating units containing aromatic moieties. By forming the molecularly imprinted polymer film from aromatic monomers, the rigidity of the space 150 is enhanced, making it easier for the space 150 to selectively trap molecules. The molecularly imprinted polymer film 140 can be formed by oxidizing the monomers to generate free radicals and then polymerizing them. The monomers may also not contain alkyl groups with two or more carbon atoms in the substituents. By forming the molecularly imprinted polymer film 140 from such monomers, the rigidity of the space 150 is increased, making it easier for the space 150 to selectively trap molecules. For example, the monomers may contain hydrogen bond donor substituents in the substituents. The hydrogen bond donor substituent can be at least one of hydroxyl (-OH), amino (-NH2, -NHR, -NR2), amide (-CONH2), carboxyl (-COOH), thio (-SH), urea (-NHCONH-), guanidinyl (-C(=NH)-NH2), sulfonamide (-SO2NH2), and imino (=NH). The monomer can be at least one of 1,2-diaminobenzene, 1,3-diaminobenzene, 1,4-diaminobenzene, 2-aminobenzene, 1,3-dihydroxybenzene, and aniline.

[0032] The molecularly imprinted polymer membrane 140 can capture at least 60% of the first isomer among the total amount of the first and second isomers captured. Alternatively, the molecularly imprinted polymer membrane 140 can capture at least 70%, 80%, 90%, or 99% of the first isomer among the total amount of the first and second isomers captured. By having such a molecularly imprinted polymer membrane 140, the receptor 100 can selectively capture the first isomer among a plurality of molecules having the same chemical formula.

[0033] The compound captured by space 150 may have at least one of a heteroatom, an -OH group, and a -C=O group. Such a compound is readily captured by space 150. Here, the heteroatom may be at least one of a N atom, an O atom, a S atom, a P atom, a Cl atom, an I atom, and a Br atom. The captured compound may have at least one of a primary amino group and a secondary amino group. Therefore, the N atom in the compound may be either a primary amino group or a secondary amino group. The compound may be at least one of histidine (His), a His derivative, a His analog, a side-chain protecting form of His, and a peptide containing His.

[0034] A metal layer 120 is formed between the substrate 110 and the molecularly imprinted polymer film 140. The metal layer 120 can be formed of gold, aluminum, silver, copper, iron, titanium, or other metallic materials. Alternatively, a layer formed of indium tin oxide (ITO), poly(3,4-ethylenedioxythiophene), polystyrene sulfonic acid, conductive carbon nanotubes, graphene, or a conductive organic-inorganic composite material can be formed between the substrate 110 and the molecularly imprinted polymer film 140. In the example of this 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 film-shaped.

[0036] Nanostructure 130 is formed in the metal layer 120 on the surface that contacts the molecularly imprinted polymer film 140. The structure of nanostructure 130 is not limited as long as the surface area of ​​the surface of the metal film 125 that contacts the substrate 110 is greater than that of the surface of the surface of the metal film 125 that contacts the substrate 110. Nanostructure 130 can be a needle-like structure extending toward the molecularly imprinted polymer film 140. By having nanostructure 130, the metal layer 120 can increase the bonding force between the metal layer 120 and the molecularly imprinted polymer film 140 compared to the case without nanostructure 130. Nanostructure 130 can be formed from the same material as the metal film 125 or from a different material. Instead of the example in this figure, the substrate 110 and the metal film 125 can be formed from a single metal.

[0037] Figures 2 to 4 This describes 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 This indicates the state in which a metal film 125 has been formed on a substrate 110 in the manufacturing method of the receptor 100 of this embodiment. In this process, the metal film 125 can be formed on the substrate 110 by sputtering, vacuum evaporation, or plating.

[0038] Next, nanostructures 130 are formed on the metal film 125. Figure 3This indicates the state in which the nanostructure 130 is formed in the manufacturing method of the receptor 100 of this embodiment. In this process, the nanostructure 130 can be formed on the metal film 125 by increasing the surface area or roughening the surface of the metal film 125. The nanostructure 130 can 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 can be about 100 mM. Through this process, a metal layer 120 having the nanostructure 130 is formed on the surface of the substrate 110 before coating or impregnation with a monomer-containing solution. By forming a metal layer 120 having the nanostructure 130 on the surface of the substrate 110, the adhesion between the metal layer 120 and the polymer 400 or the molecularly imprinted polymer film 140 can be increased in subsequent processes.

[0039] Next, a molecularly imprinted polymer film 140 is formed on the nanostructure 130. In this step, a monomer-containing solution is prepared by mixing a compound 410 with asymmetric carbon atoms. The molar ratio of monomer to compound 410 in the monomer-containing solution can be 3:1 to 5:1. For example, the molar ratio of monomer to compound 410 in the monomer-containing solution can be 4:1. The concentration of monomer in the monomer-containing solution can be 8 mM, and the concentration of compound 410 can be 2 mM. Density functional theory (DFT) calculations are used to perform structural optimization calculations for mixtures of monomer and compound 410 with different molar ratios. Structural optimization calculations are performed using Gaussian 16 and a basis function system such as B3LYP(D3BJ) / 6-311G*, and an IEFCM model in aqueous solution. Here, "B3LYP" refers to mixed functional theory, "D3BJ" refers to dispersion correction, "6-311G*" is the basis function system, and "IEFPCM" refers to the continuous solvent model. Based on the molecular energy calculated through structural optimization calculations, the degree of energy stabilization of the compound by the monomer is calculated. Specifically, the stabilization energy of the mixture of the compound and the monomer is calculated by subtracting the individual energies of the compound and the monomer from the energy of the complex, after correcting for basis set superposition error (BSSE). Table 1 shows the DFT calculation results for the case where the monomer is 1,2-diaminobenzene and compound 410 is L-histidine.

[0040] [Table 1]

[0041] According to Table 1, the mixture with a monomer to compound 410 molar ratio of 4:1 is more stable than the 3:1 ratio. Also according to Table 1, the mixture with a 5:1 ratio is more stable than the 4:1 ratio, but the change in stabilization relative to the increase in the number of monomers is less pronounced than in the 3:1 ratio. Therefore, with a monomer to compound 410 molar ratio of 4:1, the hydrogen bonds at all binding sites of the four monomers to the template interact effectively, resulting in necessary and sufficient interaction between the monomers and compound 410. Based on the above, the preferred monomer to compound 410 molar ratio in the monomer-containing solution is approximately 4:1.

[0042] The monomer-containing solution is coated onto the substrate 110, or the substrate 110 is immersed in the monomer-containing solution. Polymer 400 is formed by polymerizing the monomer. Figure 4 This indicates the state in which polymer 400 has been formed in the manufacturing method of acceptor 100 according to this embodiment. Polymer 400 contains compound 410. In this process, polymerization can be electrolytic polymerization. Electrolytic polymerization can be carried out using cyclic voltammetry. Electrolytic polymerization is carried out by scanning the potential applied between the working electrode and the counter electrode using the potential of a reference electrode as a reference until the potential for chemical reaction is reached, and repeating this process. The potential scan can be repeated until no current flows in the working electrode. The reference electrode can be an Ag / AgCl electrode. The working electrode can be a substrate 110 with a metal layer 120 formed thereon. The counter electrode can be a platinum electrode. The potential applied between the working electrode and the counter electrode can be -0.5V to 1.5V, -0.5V to 1.0V, or 0.0V to 0.8V. By using electrolytic polymerization to polymerize the monomer, a uniform polymer 400 can be formed. Alternatively, instead of electrolytic polymerization, the monomer can be polymerized by adding a polymerization initiator.

[0043] Next, by removing compound 410 from polymer 400, a molecularly imprinted polymer film 140 is formed. By removing compound 410, a space 150 corresponding to the shape of compound 410 is formed. In this process, compound 410 can be removed by an electrochemical reaction. The electrochemical reaction can be carried out using cyclic voltammetry in an alkaline solution. Using the potential of a reference electrode as a reference, the potential applied between the working electrode and the counter electrode is scanned until it reaches the potential that breaks the chemical bond, and this process is repeated, thereby removing compound 410. The alkaline solution can be an aqueous solution of potassium hydroxide or sodium hydroxide. The alkaline solution can have a pH of 9 or higher, 10 to 15, or 11 to 13. The reference electrode can be an Ag / AgCl electrode. The working electrode can be a substrate 110 on which polymer 400 is formed. The counter electrode can be a platinum electrode. The potential applied between the working electrode and the counter electrode can be -1.0V to 1.0V. By removing compound 410 using an electrochemical reaction, compound 410 can be sufficiently removed. Alternatively, instead of an electrochemical reaction, compound 410 can be removed by washing polymer 400 or immersing polymer 400 in an alkaline solution.

[0044] According to the receptor 100 shown above, the molecularly imprinted polymer membrane 140 has a space 150 for capturing at least a portion of compounds having asymmetric carbon atoms, thereby enabling selective capture of enantiomers.

[0045] Figure 5 Together with sample 540, the configuration of sensor 500 of this embodiment is illustrated. Sample 540 contains a compound that is the target of detection. Sample 540 may also contain compounds other than the target of detection. Sample 540 may be a solution containing the compound that is the target of detection. For example, sample 540 may be an aqueous solution containing the compound that is the target of detection.

[0046] Sensor 500 is capable of detecting compounds contained in sample 540. In the example shown in this figure, sensor 500 includes acceptor 100, field-effect transistor 510, reference electrode 550, measuring device 560, first voltage source 570, second voltage source 575, and current measuring device 580.

[0047] Receptor 100 comes into contact with sample 540. Receptor 100 can interact with... Figure 1 The receptor 100 is the same.

[0048] The field-effect transistor 510 can be a conventionally constructed field-effect transistor or an organic field-effect transistor using organic semiconductors. 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 of the acceptor 100. The gate 525 may be connected to the metal layer 120.

[0049] The reference electrode 550 is connected to the source electrode 530. The reference electrode 550 is in contact with the sample 540. The reference electrode 550 provides a stable potential, enabling accurate measurements. The reference electrode 550 can 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 of the sensor 500. The measuring device 560 can be a PC (personal computer), tablet computer, smartphone, workstation, server computer, or general-purpose computer, or a computer system connecting multiple computers. Such a computer system is also a computer in a broad sense. Alternatively, the measuring device 560 can be implemented within a computer through one or more executable virtual computer environments. Alternatively, the measuring device 560 can be a dedicated computer designed for the sensor 500, or dedicated hardware implemented through dedicated circuitry.

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

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

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

[0054] Figure 6 The diagram illustrates 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 of the sensor 500. The storage unit 600 can 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 of this figure, the storage unit 600 is included in the measuring device 560, but the storage unit 600 can also be implemented by at least a portion of the storage area of ​​an external storage device such as a hard drive connected to the measuring device 560. For example, the storage unit 600 can be implemented by an external storage device of the measuring device 560 provided by a cloud storage service or the like.

[0056] When measuring a sample with a known concentration, the concentration acquisition unit 610 acquires the concentration of the sample. The concentration acquisition unit 610 can acquire the concentration of the 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 can exchange data with the user of the sensor 500 through an input / output device (keyboard, etc., and display device, etc.) 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 can simultaneously control V d Keep it constant, while making V g change.

[0058] The current measuring unit 630 is connected to the storage unit 600, the voltage control unit 620, and the current measuring device 580. The current measuring unit 630 measures the I of the field-effect transistor 510 via the current measuring device 580. d The current measuring unit 630 stores the measured 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 the 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 compound to be detected 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 processing to display the concentration calculated by the second calculation unit 650 on a screen or the like. Here, the processing of displaying the screen is not limited to actually displaying the screen on a display device, but also includes generating display data for displaying the screen on a remote display device.

[0062] Figure 7This figure shows a first example of the operation flow of the sensor 500 according to this embodiment. It illustrates the flow of the sensor 500 measuring a sample in which the concentration of the compound to be detected is known. In step 702 (S702), the receptor 100 and the reference electrode 550 are brought into contact with a sample 540 containing the compound to be detected. The receptor 100 and the reference electrode 550 can be separated and immersed in the sample 540 solution, thereby bringing the receptor 100 and the reference electrode 550 into contact with the sample 540. Through the contact between the receptor 100 and the sample 540, the compound in the sample 540 is captured by 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 can acquire the concentration of the compound to be detected based on user input. In the example shown in this figure, S704 is performed between S702 and S706, but S704 can also be performed at any time from S702 to S720.

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

[0065] In S710, the current measuring unit 630 measures I via the current measuring device 580. d In S712, the current measuring unit 630 obtains the concentration of the compound from the concentration obtaining unit 610, and obtains V from the voltage control unit 620. g The current measuring unit 630 measures the concentration of the compound and V. g and I d Stored in storage section 600. The higher the concentration of the compound, the more compound is captured by space 150, for the same V g The I below d The lower.

[0066] The current measuring unit 630 does not measure all V. g Measurement I d If the condition is "No" in S714, sensor 500 returns the processing to S708. In S708, which returns from S714, voltage control unit 620 sets V... g The voltage control unit 620 can adjust the voltage at constant intervals (0.1V, etc.). g Increase or decrease. In S710, the current measuring unit 630 measures I. dIn S712, the current measuring unit 630 obtains the changed V from the voltage control unit 620. g The concentration of the compound, V g and I d Stored in storage unit 600.

[0067] In the current measuring unit 630, for all V... g I was measured d In the case of "Yes" in S714, sensor 500 causes the processing to proceed to S716. In S716, the first calculation unit 640 obtains V, representing the concentration. g with I d V of the relationship g -I d Curve. The first calculation unit 640 can obtain the concentration and V at that concentration from the storage unit 600. g and I d The combination of these factors generates V at this concentration. g -I d curve.

[0068] In S718, the first calculation unit 640 calculates the threshold voltage at that concentration. The higher the concentration of the compound, the more compounds are captured by space 150, and the more negatively the threshold voltage shifts. The first calculation unit 640 can... d 1 / 2 power and V g The relationship becomes a linear region (saturation region), an approximate straight line is drawn, and its X-intercept value is calculated to calculate the threshold voltage. In S720, the first calculation unit 640 stores the concentration of the compound and the 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), sensor 500 returns the process to S702. In S702, the acceptor 100 and reference electrode 550 are brought into contact with the unmeasured samples 540. If all samples 540 with known compound concentrations have been measured ("Yes" in S722), sensor 500 terminates the process.

[0070] Figure 8 This is a second example illustrating the operation flow of the sensor 500 in this embodiment. Figure 8 This describes the procedure for sensor 500 to measure the concentration of a compound in sample 540, where the concentration is unknown. In step S802, the acceptor 100 and the reference electrode 550 are brought into contact with the sample 540 containing the compound to be detected. Step S802 can be... Figure 7 The same applies to the S702.

[0071] In S804, the voltage control unit 620 applies V through the first voltage source 570. d For example, V d It can be -1.0V. In S806, the voltage control unit 620 applies V through the second voltage source 575. g For example, V g It can be within the range of -0.5V to 3V.

[0072] In S808, the current measuring unit 630 measures I via the current measuring device 580. d In S810, the current measuring unit 630 obtains V from the voltage control unit 620. g The current measuring unit 630 measures V. g and I d Stored in storage unit 600.

[0073] The current measuring unit 630 does not measure all V. g Measurement I d If the condition is "No" in S812, sensor 500 returns the processing to S806. In S806, which returns from S812, voltage control unit 620 makes V g The voltage control unit 620 can adjust the voltage at constant intervals (0.1V, etc.). g Increase or decrease. In S808, the current measuring unit 630 measures I. d In S810, the current measuring unit 630 obtains the changed V from the voltage control unit 620. g V g and I d Stored in storage unit 600.

[0074] In the current measuring unit 630, for all V... g I was measured d In the case of "Yes" in S812, sensor 500 causes the processing to proceed to S814. In S814, the first calculation unit 640 obtains V, representing the concentration. g with I d V of the relationship g -I d Curve. The first calculation unit 640 can obtain the concentration and V at that concentration from the storage unit 600. g and I d The combination of these factors generates V at this concentration. g -I d curve.

[0075] In S816, the first calculation unit 640 calculates the threshold voltage. The first calculation unit 640 can be in I d 1 / 2 power and V g The relationship becomes a linear region (saturation region). Draw an approximate straight line, calculate its X-intercept value, and then calculate the threshold voltage.

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

[0077] According to the sensor 500 shown above, compounds having asymmetric carbon atoms can be detected easily and quickly. The sensor 500 allows for the detection of compounds having asymmetric carbon atoms without modification.

[0078] Alternatively, two or more sensors 500 capturing different compounds from space 150 can be used to determine the compound, and the optical purity of the compound can be determined based on the determination results. Two or more sensors 500 capturing different compounds from space 150 can be used separately... Figure 7 as well as Figure 8 The concentration of each compound is determined using a method described above. The optical purity of a compound can be determined based on the concentration of each compound calculated by each of the sensors 500. Each of two or more sensors 500 may capture different types of isomers among multiple isomers of the same chemical formula. For example, a sensor 500 with a space 150 that captures only the L-type isomer can be used to determine the concentration of the L-type isomer in sample 540, and a sensor 500 with a space 150 that captures only the D-type isomer can be used to determine the concentration of the D-type isomer in sample 540. The optical purity of the compound can then be determined based on the respective concentrations of the L-type and D-type isomers.

[0079] Alternatively, a single sensor 500 can be used to measure the compound, and the optical purity of the compound can be determined based on the measurement results. The first calculation unit 640 of the measuring device 560 can use multiple samples 540, each with a constant total amount of the target compound and its isomers, but varying optical purities, to... Figure 7 as well as Figure 8 The method described herein is used to calculate the threshold voltage of each sample 540. The second calculation unit 650 can... Figure 8 The method described herein obtains an optical purity-threshold voltage relationship curve. The second calculation unit 650 determines the optical purity of sample 540 from the threshold voltage of sample 540, where the optical purity is unknown but the total amount of the detection object and its isomers is known, based on the optical purity-threshold voltage relationship curve. The second calculation unit 650 can use support vector machine (SVM) regression to determine the optical purity based on the optical purity-threshold voltage relationship curve. As an example, the second calculation unit 650 can use the method described in Non-Patent Document 2 to perform SVM regression.

[0080] Figure 9 Together with sample 540, the configuration of sensor 900 in the first modified example of this embodiment is shown. Sample 540 can be used with... Figure 5 Similarly, sensor 900 can detect compounds contained in sample 540. In the example shown in this figure, sensor 900 includes acceptor 100, potentiostat 910, counter electrode 920, and reference electrode 930. Acceptor 100 functions as the working electrode. Acceptor 100 can interact with... Figure 1 same.

[0081] The counter electrode 920 is in contact with the sample 540. The counter electrode 920 is an electrode in which a reaction occurs corresponding to the redox reaction in the acceptor 100, which serves as the working electrode. The counter electrode 920 can be formed of a conductive material. The counter electrode 920 can be a metallic 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 measurements. The reference electrode 930 can be an Ag / AgCl electrode.

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

[0084] Figure 10 The diagram illustrates the configuration of a synthesis system 1000 according to a second variation of this embodiment. The synthesis system 1000 is a system for conducting chemical reactions involving compounds having asymmetric carbon atoms. In the example shown, the synthesis system 1000 includes one or more sensors 500, a reactor 1005, a control unit 1015, and a heater 1020.

[0085] Reactor 1005 is a vessel for carrying out a chemical reaction involving a compound having asymmetric carbon atoms. In the example shown in this figure, reactor 1005 is a tank reactor. Reactor 1005 contains solution 1010. Solution 1010 contains at least one of reactants and products. Solution 1010 contains a compound having asymmetric carbon atoms, either as a reactant or as a product. Solution 1010 may contain a compound having asymmetric carbon atoms as a product.

[0086] Sensor 500 is in contact with solution 1010. Sensor 500 quantitatively determines compounds with isomers contained in solution 1010. Sensor 500 can interact with... Figure 5 Similarly, sensor 500 can determine the optical purity of the compound contained in solution 1010. Synthesis system 1000 may have two or more sensors 500, and the optical purity of the compound contained in solution 1010 can be calculated based on the measurement results of the 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 from the sensor 500 from the measuring device 560. Based on the measurement results from the sensor 500, the control unit 1015 controls the reaction conditions of the reactor 1005. The control unit 1015 can control the temperature of the reactor 1005 based on the optical purity of the compound 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 a decrease in the optical purity of the compound contained in the solution 1010, it can lower the temperature of the reactor 1005. The control unit 1015 can also control factors other than the temperature of the reactor 1005 (flow rate, mixing ratio, stirring speed if the reactor 1005 is equipped with a stirrer, etc.).

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

[0089] According to the synthesis system 1000 shown above, the optical purity of a chemical reaction can be easily and quickly detected, 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 products in a chemical reaction.

[0090] Figure 11 This diagram illustrates the configuration of column 1100 in a third variation of this embodiment. Column 1100 separates enantiomers by selectively capturing one enantiomer of a compound having asymmetric carbon atoms. In the example shown, column 1100 is cylindrical. Column 1100 includes a plurality of fillers 1110.

[0091] Filler 1110 fills the column 1100. In the example shown in this figure, filler 1110 is spherical. Alternatively, filler 1110 may also have a cylindrical, cubic, cuboid, or other three-dimensional shape. Filler 1110 has a substrate 1115, a metal layer 1120, and a molecularly imprinted polymer film 1140.

[0092] The substrate 1115 has the outer surfaces of the layers forming the filler 1110. In this embodiment, the substrate 1115 is spherical. Alternatively, the substrate 1115 may also have a cylindrical, cubic, cuboid, or other three-dimensional shape. The substrate 1115 may be formed of silicone.

[0093] A molecularly imprinted polymer film 1140 is formed on a substrate 1115. The molecularly imprinted polymer film 1140 includes spaces 1150 for trapping at least a portion of a compound having asymmetric carbon atoms. The molecularly imprinted polymer film 1140 can be coupled with… Figure 1Similarly, in the molecularly imprinted polymer film 140, space 1150 can be with Figure 1 The space is 150 as well.

[0094] A metal layer 1120 is formed between the substrate 1115 and the molecularly imprinted polymer film 1140. The metal layer 1120 can be formed by... Figure 1 The same metallic material is formed for the metal layer 120. Instead of the metal layer 1120, a layer formed of indium tin oxide (ITO), poly(3,4-ethylenedioxythiophene), polystyrene sulfonic acid, conductive carbon nanotubes, graphene, or a conductive organic-inorganic composite material can be formed between the substrate 1115 and the molecularly imprinted polymer film 1140. In the example of 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 can be... Figure 1 Similarly, the metal film 125, and the nanostructure 1130 can be combined with... Figure 1 The same applies to the nanostructure 130.

[0095] According to column 1100 shown above, since space 1150 selectively captures compounds containing asymmetric carbon atoms, enantiomers can be separated by allowing a fluid containing compounds with asymmetric carbon atoms to flow through.

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

[0097] (Manufacturing of Receptor 100) (Example) The target substance is L-histidine, and the monomer is 1,2-diaminobenzene. According to... Figures 2-4 The method described herein uses a monomer-containing solution obtained by mixing 1,2-diaminobenzene and L-histidine in a molar ratio of 4:1 to manufacture receptor 100.

[0098] (Comparative example) The target substance was L-histidine, with monomers including 1,2-diaminobenzene and dopamine. According to... Figures 2-4 The method described herein involves using a monomer-containing solution obtained by mixing 1,2-diaminobenzene, dopamine, and L-histidine in a molar ratio of 1:4:1 to manufacture receptor 100.

[0099] (DPV measurement) Using the receptor 100 from the examples or comparative examples, a fabrication was made. Figure 9The sensor was 900. Sample 540 was prepared using 5 mM K3Fe(CN)6, 100 mM KCl, and multiple 100 mM phosphate-buffered saline solutions (pH 6.0) containing L-histidine. The measurement range was set to -0.05 V to 0.8 V (vs. Ag / AgCl).

[0100] Figure 12 as well as Figure 13 The results of the DPV measurement are shown. Figure 12 This figure shows an example of DPV measurement results for receptor 100 using the embodiment. DPV measurements were performed using samples 540 with L-histidine concentrations of 0, 0.9, 2, 4, 6, 8, or 10 mM. In this figure, the peak near 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 K3Fe(CN)6 redox reaction decreases as the L-histidine concentration increases. Therefore, the current-voltage characteristics in receptor 100 with a monomer of 1,2-diaminobenzene vary with the L-histidine content.

[0101] Figure 13 This figure shows an example of DPV measurement results using the comparative example receptor 100. DPV measurements were performed using samples 540 with L-histidine concentrations of 0, 1, 3, 5, 7, or 10 mM. Furthermore, data from sample 540 using an L-histidine concentration of 1 mM overlapped with data from sample 540 using an L-histidine concentration of 3 mM. In this figure, the peak current value of the K3Fe(CN)6 redox reaction remained essentially constant even with variations in the L-histidine concentration. Thus, no variation in current-voltage characteristics was observed with respect to the L-histidine content in the receptor 100 with monomers of 1,2-diaminobenzene and dopamine. Therefore, in this embodiment, by ensuring that the monomer does not contain alkyl groups with two or more carbon atoms in the substituents, the rigidity of the space 150 in the molecularly imprinted polymer membrane 140 is increased, making it easier for the space 150 to selectively trap molecules.

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

[0103] Figure 14 This illustrates an example of the response specificity of receptor 100 in the embodiment. According to this figure, in the determination of sample 540 containing L-histidine, V TH With V TH0 The difference was approximately -0.07V, but in the determination of sample 540 containing other compounds, V... TH With V TH0 The difference is less than -0.015V. Therefore, in the receptor 100 of the embodiment, no change in current-voltage characteristics was observed for compounds with different chemical formulas and isomers; the change in current-voltage characteristics was only observed for L-histidine, which is the target of detection. Based on the above, it is confirmed that the receptor 100 of the present invention can specifically capture specific molecules.

[0104] (Calculation of optical purity) Using the receptor 100 of the above embodiment, a Figure 5 Sensor 500. Sample 540 used multiple 100 mM phosphate-buffered saline solutions (pH 6.0) containing D-histidine and L-histidine. Here, L-histidine and D-histidine exist as isomers with the same chemical formula. The combined concentration of D-histidine and L-histidine in sample 540 was 300 μM, and the optical purity of histidine ranged from -5.1% ee to 87.9% ee. For each sample 540, using... Figure 7 The methods described in S702 to S716 have yielded various V values. g -I d Curve. Utilizing Figure 7 The method described in S718 calculates the threshold voltage (V). TH Here, in V d -2V, V g Measurements were performed within the range of -3V to 0.5V. Using a solution excluding D-histidine and L-histidine as sample 540, the baseline threshold voltage (V) was calculated using the same method. TH0 ).

[0105] Figures 15-18 This represents the measurement results of sample 540 with different optical purity. Figure 15 V represents samples 540 with different optical purity. g -I d An example of a curve. Figure 16 This figure represents an example of the threshold voltage (V) for a sample with an optical purity below 80%ee. In this figure, as the optical purity of L-histidine increases, (V... TH -V TH0 ) / V TH The current-voltage characteristics increase linearly. Therefore, in receptor 100, the current-voltage characteristics were observed to vary depending on the optical purity of the compound being detected.

[0106] Figure 17 This is an example of the threshold voltage of sample 540 with an optical purity of 80%ee or higher. Also shown in this figure... Figure 16 Similarly, as the optical purity of L-histidine increases, (V TH -V TH0 ) / V TH It increases linearly. On the other hand, in this figure (V) TH -V TH0 ) / V TH The slope and Figure 16 (V) TH -V TH0 ) / V TH The slopes differ. Therefore, it was observed that the linear response of the threshold voltage to optical purity varies depending on the region of optical purity.

[0107] according to Figure 16 as well as Figure 17 The optical purity was determined by SVM regression of the threshold voltage of each sample at 540. SVM regression was performed using the method described in Non-Patent Literature 2.

[0108] Figure 18 This figure illustrates an example of the results of determining optical purity using machine learning. In this graph, the vertical axis represents the optical purity value calculated via SVM regression, and the horizontal axis represents the actual optical purity value. According to this figure, even though the linear response of the threshold voltage to optical purity varies depending on the region of optical purity, it is still possible to determine the optical purity with high accuracy at, for example, four points simultaneously using SVM regression. Figure 18 In the above, the predicted %ee values ​​are 13.9%ee, 23.4%ee, 51.9%ee, and 84.1%ee. Therefore, as shown in this embodiment, by using only one optical isomer as the receptor 100 for the detection object, the sensor 500 is able to determine the optical purity of the detection object.

[0109] Various embodiments of the present invention can be described with reference to flowcharts and block diagrams, in which modules can represent (1) stages of a process for performing an operation or (2) portions of a device that performs the operation. Specific stages and portions can be implemented by dedicated circuits, programmable circuits supplied together with computer-readable instructions stored on a computer-readable medium, and / or processors supplied together with computer-readable instructions stored on a computer-readable medium. Dedicated circuits may include digital and / or analog hardware circuits, and may also include integrated circuits (ICs) and / or discrete circuits. Programmable circuits may include reconfigurable hardware circuits, including logic AND, logic OR, logic XOR, logic NAND, logic NOR and other logic operations, flip-flops, registers, field-programmable gate arrays (FPGAs), programmable logic arrays (PLAs), and other memory elements.

[0110] Computer-readable media can include any tangible device capable of storing instructions executable by a suitable device. Consequently, a computer-readable medium having instructions stored therein includes an article containing instructions executable by means of a flowchart or block diagram. Examples of computer-readable media include: electronic storage media, magnetic storage media, optical storage media, electromagnetic storage media, semiconductor storage media, etc. More specific examples of computer-readable media include: floppy disks, magnetic disks, 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), optical disc read-only memory (CD-ROM), digital multipurpose disc (DVD), Blu-ray disc, memory stick, integrated circuit card, etc.

[0111] Computer-readable instructions include any one of source code and object code described by any combination of one or more programming languages, including assembly instructions, instruction set architecture (ISA) instructions, machine instructions, machine-dependent instructions, microcode, firmware instructions, status setting data, or existing procedural programming languages ​​such as Smalltalk (registered trademark), JAVA (registered trademark), C++, and "C" or similar programming languages.

[0112] Computer-readable instructions can be provided to the processor or programmable circuitry of a programmable data processing device such as a computer via a local area network (LAN), wide area network (WAN), or the Internet, and are executed to create units for performing operations specified by flowcharts or block diagrams. Here, a computer can be a PC (personal computer), tablet computer, smartphone, workstation, server computer, general-purpose computer, or special-purpose computer, or a computer system connecting multiple computers. Such a computer system connecting multiple computers is also called a distributed computing system, which is a broad definition of a computer. In a distributed computing system, multiple computers execute different parts of a program, exchanging data between the computers as needed, thereby enabling multiple computers to centrally execute the program.

[0113] Examples of processors include computer processors, central processing units (CPUs), processing units, microprocessors, digital signal processors, controllers, and microcontrollers. A computer can have one or more processors. In a multiprocessor system with multiple processors, each processor executes a portion of the program, exchanging data between processors as needed, thus allowing multiple processors to execute the program collectively. For example, in multitasking, multiple processors can switch tasks by time slices, executing different parts of each task in a segmented manner. In this case, which part of the program each processor executes is dynamically changing. Alternatively, which part of the program each processor executes can be statically determined by the programming of the multiple processors.

[0114] Figure 19 Examples of computer 1200 that can implement the present invention in whole or in part are shown. Through programs installed on computer 1200, computer 1200 can perform operations associated with an apparatus or one or more parts of that apparatus as embodiments of the present invention, or execute that operation or those one or more parts, and / or computer 1200 can execute processes or stages of processes of embodiments of the present invention. To enable computer 1200 to perform specific operations associated with several or all of the modules in the flowcharts and block diagrams described in this specification, such programs can be executed by CPU 1212.

[0115] The computer 1200 of this embodiment includes a CPU 1212, RAM 1214, a graphics controller 1216, and a display device 1218, which are interconnected via a main controller 1210. The computer 1200 also includes a communication interface 1222, a storage device 1224 such as a hard disk drive, an input / output unit such as a DVD-ROM drive 1226, and an IC card drive, which are connected to the main controller 1210 via an input / output controller 1220. The computer also includes conventional 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 the program 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 the frame buffer or other storage provided in RAM 1214 or from its own storage, and displays the image data on the display device 1218.

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

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

[0119] The program is provided by 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 in a storage device 1224, RAM 1214, or ROM 1230, which is also an example of a computer-readable medium, and executed by the CPU 1212. The information processing described within these programs is read into the computer 1200, thereby enabling cooperation between the program and the aforementioned various types of hardware resources. The apparatus or method can be configured to perform information manipulation or processing in conjunction with the use of the computer 1200.

[0120] For example, when communication is performed between computer 1200 and an external device, CPU 1212 can execute a communication program loaded in RAM 1214, and instruct communication processing on communication interface 1222 based on the processing described in the communication program. Under the control of CPU 1212, 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, sends 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, etc.

[0121] Furthermore, the CPU 1212 can read all or necessary portions of files or databases stored on external recording media such as storage device 1224, DVD-ROM drive 1226 (DVD-ROM 1227), IC card, etc., into RAM 1214, and perform various types of processing on the data in RAM 1214. Then, the CPU 1212 writes the processed data back to the external recording medium.

[0122] Various types of information, such as programs, data, tables, and databases, can be stored in a recording medium and processed. The CPU 1212 executes various types of processing described throughout this invention on data read from RAM 1214 and writes the results back to RAM 1214. These various types of processing include operations specified by a sequence of program instructions, information processing, conditional judgments, conditional branches, unconditional branches, information retrieval / replacement, etc. Furthermore, the CPU 1212 can retrieve information from files, databases, etc., within the recording medium. For example, when multiple entries, each having an attribute value associated with a second attribute, are stored in the recording medium, the CPU 1212 can retrieve from these multiple entries an entry that matches a condition specifying the attribute value of the first attribute, and read the attribute value of the second attribute stored in that entry, thereby obtaining 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 can be stored on or near the computer 1200 on a computer-readable medium. Furthermore, recording media such as hard disks or RAM provided in a server system connected to a dedicated communication network or the Internet can be used as computer-readable media, thereby providing the program to the computer 1200 via the network.

[0124] The present invention has been described above using embodiments, but 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. As can be seen from the claims, such modifications or improvements may also be included within the technical scope of the present invention.

[0125] The execution order of actions, processes, steps, and stages in the apparatus, systems, programs, and methods shown in the claims, description, and drawings is not specifically stated as "earlier" or "before." Furthermore, it should be noted that any order is permissible as long as the output of the preceding process is not used in the subsequent process. Even if the flow of actions in the claims, description, and drawings is described using terms such as "firstly," "next," etc., for ease of explanation, it does not imply that the actions must be performed in that order. Explanation of reference numerals in the attached figures

[0126] 100 Acceptor, 110 Matrix, 120 Metal Layer, 125 Metal Film, 130 Nanostructure, 140 Molecularly 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 Measuring Device, 600 Storage Unit, 610 Concentration Acquisition Unit, 620 Voltage Control Unit, 630 Current Measuring 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 filler, 1115 substrate, 1120 metal layer, 1125 metal film, 1130 nanostructure, 1140 molecularly imprinted polymer film, 1150 space, 1200 computer, 1210 main 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. A receptor, wherein, have: Matrix; and A molecularly imprinted polymer film, formed on the substrate, has a space for capturing at least a portion of a compound having asymmetric carbon atoms.

2. The receptor according to claim 1, wherein, It has a metal layer formed between the substrate and the molecularly imprinted polymer film, and the surface in contact with the molecularly imprinted polymer film has a nanostructure.

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

4. The receptor according to claim 3, wherein, The molecularly imprinted polymer film has more than three of the non-covalently bound functional groups in one of the spaces.

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, and a -C=O group.

7. The receptor according to claim 1, wherein, The compound has at least one of a primary amino group and a secondary amino group.

8. The receptor according to claim 1, wherein, The compound is at least one of His, His derivatives, His analogs, His side-chain protected forms, and peptides containing His.

9. The receptor according to claim 5, wherein, The monomer does not contain alkyl groups with more than 2 carbon atoms in its substituents.

10. The receptor according to claim 9, wherein, The monomer contains hydrogen bond donor substituents in its substituents.

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-aminobenzene, 1,3-dihydroxybenzene, and aniline.

12. A sensor, wherein, have: The receptor as described in any one of claims 1 to 11; and A field-effect transistor having a gate connected to a metal that is in contact with the molecularly imprinted polymer film in the receptor.

13. A synthetic system, wherein, have: The sensor according to claim 12; Reactor; and The control unit controls the reaction conditions in the reactor based on the measurement results from the sensors.

14. A method for determination, wherein, The receptor of the sensor according to claim 12 is brought into contact with a sample containing a compound as the target of detection. The compounds in the sample were determined based on changes in the current-voltage characteristics of the field-effect transistor.

15. The determination method according to claim 14, wherein, The compounds in the sample are quantitatively determined based on the changes in the current-voltage characteristics.

16. A method in which, The compounds are determined using two or more sensors according to claim 12, which are different from the compounds captured in the space. The optical purity of the compound was determined based on the measurement results.

17. A method for manufacturing a receptor, wherein, A monomer-containing solution is prepared by mixing a compound with asymmetric carbon atoms. The monomer-containing solution is applied to the substrate or the substrate is immersed in the monomer-containing solution. Polymers are formed by polymerizing the monomers. A molecularly imprinted polymer film is formed by removing the compound.

18. The receptor manufacturing method according to claim 17, wherein, The polymerization is electrolytic polymerization.

19. The receptor manufacturing method according to claim 17, wherein, The compound is removed by an electrochemical reaction.

20. The method for manufacturing a receptor according to any one of claims 17 to 19, wherein, Prior to the coating or impregnation, a metal layer with a nanostructure is formed on the surface of the substrate.

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