Robust molecular recognition elements, sensors, and methods for manufacturing the same

Abstract

To provide a robust molecule recognition element capable of functioning in a severe environment of high temperature,.SOLUTION: A molecule recognition element includes: a base material composed of ceramic; and an atomic layer deposition film composed of ceramic on the base material. The atomic layer deposition film has a recognition part capable of recognizing a molecular shape of one or a plurality of target molecules and composed of a pore formed from a template of the molecular shape of the target molecule.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a molecular recognition element, a sensor, and a method for manufacturing the same that function even in harsh environments. [Background technology]

[0002] Molecular imprinting (MI) is a method for synthesizing artificial receptors that can specifically recognize target molecules. MI uses the target molecule as a template to artificially construct binding sites that are selective for the target molecule within a material. Polymers synthesized using MI are called molecularly imprinted polymers (MIPs).

[0003] MIPs are molecular recognition materials that have a binding space for target molecules, which are obtained by forming a complex between a target molecule or its derivative and a functional monomer through covalent or non-covalent bonds, polymerizing it with a crosslinker, and then removing the target molecule.Because they can be mass-produced cheaply and stably, they are attracting attention as an alternative to expensive and unstable biomaterials.

[0004] Furthermore, a molecular recognition material has been proposed that has high sensitivity and high selectivity for volatile aldehydes, particularly for volatile aldehydes contained in biological samples as biomarkers (Patent Document 1). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2018-75518 Summary of the Invention [Problem to be solved by the invention]

[0006] These conventional molecular recognition materials can function in relatively mild environments at low temperatures, but because they are composed of polymers, it is difficult to make them function in harsh environments at high temperatures. Therefore, there is a need for robust molecular recognition elements that can function in harsh environments at high temperatures. [Means for solving the problem]

[0007] The gist of the present invention is as follows. (1) a substrate made of ceramics, and An atomic layer deposition film made of ceramics on the substrate Including, The atomic layer deposition film has a recognition portion configured with a hole capable of recognizing the molecular shape of one or more types of target molecules and using the molecular shape of the target molecule as a template. Molecular recognition element. (2) The molecular recognition element according to (1) above, wherein the atomic layer deposition film has an average thickness of 0.5 to 30 nm. (3) The molecular recognition element according to (1) or (2) above, wherein the atomic layer deposition film contains a cationic ionic oxide in which six oxygen atoms are coordinated to a metal atom. (4) A sensor comprising the molecular recognition element according to any one of (1) to (3) above. (5) Placing one or more target molecules having polar functional groups on a substrate made of ceramics having OH groups on the surface; forming an atomic layer deposition film made of ceramics on the substrate on which the target molecules are arranged by using an atomic layer deposition method; and heat-treating the substrate on which the atomic layer deposition film is formed to remove the target molecules, thereby forming a recognition portion configured with holes using the molecular shape of the target molecule as a template, which is capable of recognizing the molecular shape of the target molecule; A method for producing a molecular recognition element, comprising: (6) The method for producing a molecular recognition element according to (5) above, wherein the atomic layer deposition film has an average thickness of 0.5 to 30 nm. (7) The method for producing a molecular recognition element according to (5) or (6) above, wherein the atomic layer deposition film contains a cationic ionic oxide in which oxygen atoms are six-coordinated to a metal atom. (8) The method for producing a molecular recognition element according to any one of (5) to (7) above, wherein the temperature of the heat treatment is 300° C. or higher. [Effects of the Invention]

[0008] The present invention makes it possible to provide a robust molecular recognition element that can function in a harsh environment at high temperatures. [Brief explanation of the drawings]

[0009] [Figure 1] FIG. 1 is a cross-sectional view illustrating an example of the configuration of a molecular recognition element of the present disclosure. [Figure 2] FIG. 2 is a schematic diagram of an example of the manufacturing method of the present disclosure. [Figure 3] FIG. 3 is a schematic diagram showing an example of the state when an atomic layer deposition film is formed by the ALD method, when the target molecules are desorbed, and when molecular recognition is performed, when the substrate is needle-like crystals of ZnO having a hexagonal wurtzite structure. [Figure 4] FIG. 4 is a schematic diagram showing an example of the state when the target molecule, nonanal, is pinned to the m-plane of the ZnO substrate via a carbonyl group, when the target molecule is placed, when an atomic layer deposition film is formed, and when the target molecule is removed. [Figure 5] FIG. 5 is a graph evaluating molecular selectivity, with the horizontal axis representing the number of ALD step cycles (hereinafter also referred to as the ALD cycle number) and the vertical axis representing the amount of desorption (nmol) measured by gas chromatography-mass spectrometry (TPD-GC / MS). [Figure 6] FIG. 6 is a graph evaluating molecular selectivity, with the horizontal axis representing the number of ALD cycles and the vertical axis representing the amount of desorption (nmol) measured by TPD-GC / MS. [Figure 7] FIG. 7 is a graph evaluating molecular selectivity, with the horizontal axis representing the number of ALD cycles and the vertical axis representing the amount of desorption (nmol) measured by TPD-GC / MS. [Figure 8] FIG. 8 is a graph in which the horizontal axis represents decanal (C8), nonanal (C9), and octanal (C10), and the vertical axis represents the amount of desorption (nmol) measured by TPD-GC / MS. [Figure 9] FIG. 9 is a graph evaluating molecular selectivity, with the horizontal axis representing the number of ALD cycles and the vertical axis representing the amount of desorption (nmol) measured by TPD-GC / MS. [Figure 10] FIG. 10 is a graph showing molecular selectivity evaluation, with the horizontal axis representing the number of ALD cycles and the vertical axis representing the amount of desorption (nmol) measured by TPD-GC / MS. [Figure 11] FIG. 11 is a graph evaluating molecular selectivity, with the horizontal axis representing the number of ALD cycles and the vertical axis representing the amount of desorption (nmol) measured by TPD-GC / MS. [Figure 12] FIG. 12 is a graph evaluating molecular selectivity, with the horizontal axis representing the number of ALD cycles and the vertical axis representing the amount of desorption (nmol) measured by TPD-GC / MS. [Figure 13] FIG. 13 shows infrared absorption spectroscopy (IR) spectra of CH2 and CH3 when the number of ALD cycles was set to 0 to 600 on a ZnO substrate having nonanal adsorbed thereon as a target molecule. [Figure 14] FIG. 14 is a graph in which the horizontal axis represents the number of ALD cycles and the vertical axis represents the amount (nmol) of nonanal desorbed from the substrate as a target molecule. [Figure 15] FIG. 15 is a scanning electron microscope (SEM) photograph of the molecular recognition element fabricated by 60 cycles of ALD in Example 1. [Figure 16] FIG. 16 shows a transmission electron microscope (TEM) image of the cross section of the molecular recognition element of FIG. 15, and elemental mapping images of Zn and Ti measured from the surface of the molecular recognition element by energy dispersive X-ray spectroscopy (EDX). [Figure 17] FIG. 17 shows a cross-sectional TEM image of a comparative sample prepared by 60 cycles of ALD in Comparative Example 1, and elemental mapping images of Zn and Ti measured from the surface of the comparative sample by energy dispersive X-ray spectroscopy (EDX). [Figure 18]FIG. 18 is a graph showing the average thickness of TiOx atomic layer deposition films versus the number of ALD cycles. [Figure 19] FIG. 19 shows infrared absorption spectroscopy (IR) spectra of CH2 and CH3 when a ZnO substrate having nonanal adsorbed thereon as a target molecule is heat-treated at temperatures of 100 to 250°C. [Figure 20] FIG. 20 is a graph showing the amount of desorbed molecules versus the number of ALD cycles. [Figure 21] FIG. 21 is a graph comparing the peak positions of the amount of molecules desorbed depending on the number of ALD cycles for a molecular recognition element fabricated with preheating at 175° C. and a molecular recognition element fabricated without preheating. [Figure 22] Figure 22 shows a chromatograph of the molecular recognition element prepared in Example 1, which was heat-treated at 300 to 600°C for 30 minutes, then exposed to a saturated vapor pressure mixed gas containing equal amounts of hexanal, nonanal, and undecanal, and the amount of hexanal, nonanal, and undecanal desorbed was measured using TPD-GC / MS. [Figure 23] FIG. 23 is a graph in which the chromatographic measurement values ​​obtained in FIG. 22 are converted into molar units. [Figure 24] Figure 24 is a graph showing the amounts of hexanal, nonanal, and undecanal desorbed from the molecular recognition element prepared in Example 1, which was heat-treated at 400°C for 1 hour, 1 day, 1 week, and 1 month, and then exposed to a saturated vapor pressure mixed gas containing equal amounts of hexanal, nonanal, and undecanal, measured using TPD-GC / MS. [Figure 25] Figure 25 is a graph showing the ratio of the amount of nonanal desorbed to that of hexanal, measured by TPD-GC / MS after the molecular recognition element prepared in Example 1 was heat-treated at 300 to 600°C for 30 minutes to 3 months and then exposed to a mixed gas at saturated vapor pressure containing equal amounts of hexanal, nonanal, and undecanal. [Figure 26] FIG. 26 shows (A) a schematic view of the appearance of a QCM device, and (B) a schematic view of the appearance of a molecular recognition element placed on the quartz crystal of the QCM device. [Figure 27] Figure 27 shows a graph of the frequency change ΔF of the quartz crystal oscillator versus time (seconds) for (A) a comparative sample that was subjected to atomic layer deposition without the use of a target molecule, and (B) a molecular recognition element with nonanal as the target molecule placed on the quartz crystal of a QCM device, when gases containing hexanal, nonanal, and undecanal were separately flowed into the chamber of the QCM device and the samples were exposed to each other. DETAILED DESCRIPTION OF THE INVENTION

[0010] The present disclosure relates to a molecular recognition element that includes a substrate made of ceramic and an atomic layer deposition film made of ceramic on the substrate, wherein the atomic layer deposition film has a recognition portion made of a hole templated by the molecular shape of one or more target molecules, and is capable of recognizing the molecular shape of the target molecule.

[0011] The inventors have conducted extensive research and have succeeded in realizing a molecular recognition element made of ceramics that is robust and has excellent molecular recognition capabilities by making full use of spatially selective crystal growth technology in which target molecules are intentionally interposed at the crystal growth interface using atomic layer deposition (ALD).

[0012] This molecular recognition element can be fabricated by placing target molecules on a substrate and growing crystals of an atomic layer deposition film using atomic layer control using the ALD method. Normally, ALD removes as many impurities as possible before deposition, but this technology deliberately adsorbs the target molecules onto the substrate, performs atomic deposition of ceramics starting from the substrate surface to cover the target molecules, and then removes the target molecules by heat treatment, thereby enabling the atomic layer deposition film to exhibit target molecule recognition functionality.

[0013] In this molecular recognition element, the material and average thickness of the atomic layer deposition film, which is controlled at the atomic layer level, can be easily selected according to the properties of the desired target molecule, making this molecular recognition element applicable to a wide variety of molecular groups.

[0014] This molecular recognition element is composed of a ceramic substrate and a ceramic atomic layer deposition film, and therefore has excellent heat resistance. This molecular recognition element is heat resistant to temperatures of preferably 300°C or higher, more preferably 400°C or higher, even more preferably 500°C or higher, and even more preferably 600°C or higher. Heat resistance can be determined by evaluating whether selective molecular recognition is possible after heat treatment at that temperature.

[0015] The present molecular recognition element has excellent heat resistance and can function in harsh high-temperature environments. For example, the present molecular recognition element can function even when exposed to high temperatures of 300 to 400°C. The present molecular recognition element can also be used repeatedly for long periods, such as one month or more, for example, 20 or more times in three months. Therefore, the present molecular recognition element can withstand long-term repeated use at high temperatures of 300 to 400°C, for example, 20 or more times in three months.

[0016] The molecular recognition element has excellent heat resistance, so it can be initialized by high-temperature heat treatment. To substantially eliminate the organic compound, heat treatment is preferably performed at 300 to 400°C, preferably 400°C. However, the molecular recognition element can withstand heat treatment at 300°C or higher, for example, 400°C, so it can be almost completely initialized and can be repeatedly used as a molecular recognition element while maintaining the accuracy of molecular recognition.

[0017] Conventional gas-phase odor sensors, for example, those that use a sensitive film, have had issues with the time required to initialize the film surface and the difficulty of achieving complete initialization. This is because heat treatment at approximately 300-400°C is required to completely remove gas-phase molecules from a solid surface, but conventional sensitive films cannot withstand such high-temperature heat treatment. The same is true for MIPs. In contrast, the molecular recognition element can be initialized by heat treatment at 300-400°C as described above, and can be used repeatedly as a molecular recognition element while maintaining the accuracy of molecular recognition.

[0018] Furthermore, this molecular recognition element is capable of recognizing small molecules and distinguishing subtle differences in molecular structure. Conventional MIPs and Patent Document 1 can recognize molecules with large molecular weights and many characteristics, but have difficulty recognizing small molecules with few characteristics. This molecular recognition element can recognize small molecules with few characteristics and even slight differences in their structure.

[0019] 1 shows a cross-sectional schematic diagram illustrating an example of the configuration of a molecular recognition element 10 of the present disclosure. The molecular recognition element 10 includes a substrate 1 and an atomic layer deposition film 2 on the substrate 1. The atomic layer deposition film 2 has a recognition portion 3 that can recognize the molecular shape of a target molecule. The recognition portion 3 is composed of a hole that uses the molecular shape of the target molecule as a template.

[0020] The substrate 1 is not particularly limited as long as it is a ceramic that can pin target molecules to its surface and that can deposit an atomic layer deposition film on its surface by ALD in the manufacturing process of the molecular recognition element 10. The substrate 1 can be an oxide, nitride, carbide, or the like, such as zinc oxide, tin oxide, zirconium oxide, aluminum oxide, iron oxide, copper oxide, tungsten oxide, hafnium oxide, titanium oxide, cobalt oxide, gallium oxide, gallium nitride, aluminum nitride, silicon nitride, or silicon carbide.

[0021] The substrate 1 can have any shape, such as a plate, rod, needle, or sphere. From the viewpoint of increasing the surface area, the substrate 1 is preferably a rod- or needle-shaped nanowire or a spherical nanoparticle. The nanowire has, for example, a diameter of 10 to 200 nm and a length of 100 to 10,000 nm. The nanoparticle has, for example, a diameter of 10 to 200 nm.

[0022] When the substrate 1 is rod-shaped or needle-shaped, such as a nanowire, zinc oxide having a (1010) plane can be used. For example, when the target molecule is nonanal and the substrate is zinc oxide, the carbonyl group of nonanal and the Zn of the substrate can be bonded to each other. 2+For example, if the target molecule is nonanal and the substrate is tin lead oxide, the carbonyl group of nonanal and the Sn 4+ The target molecule can be pinned onto the substrate by interaction with the substrate.

[0023] The atomic layer deposition film 2 may be composed of a ceramic material with a polar surface, which may interact with the nonpolar main chain portion of the target molecule. The atomic layer deposition film 2 may also be composed of a ceramic material with a hydrophilic surface, which may interact with the hydrophobic main chain portion of the target molecule. This interaction can be confirmed by first-principles calculations. Because this interaction occurs at multiple locations within a single recognition portion 3 in the atomic layer deposition film 2, it is believed that the recognition portion can precisely recognize the shapes of the three molecules.

[0024] The atomic layer deposition film 2 can be amorphous or crystalline, but is preferably amorphous. The atomic layer deposition film 2 can be a ceramic having covalent bonds, ionic bonds, or a combination thereof, but is preferably a ceramic having mainly ionic bonds. Covalent crystals have directional bonds, whereas ionic crystals bond cations and anions through Coulomb forces, which widens the range of possible coordination angles between cations and anions, making them favorable for molecular recognition.

[0025] The atomic layer deposition film 2 is preferably an oxide, more preferably a metal oxide, further preferably a cationic ion oxide in which oxygen atoms are six-coordinated to a metal atom, and even more preferably a metal oxide having a rutile structure. Examples of the atomic layer deposition film 2 include titanium oxide, tin oxide, zirconium oxide, aluminum oxide, iron oxide, copper oxide, tungsten oxide, and hafnium oxide.

[0026] The atomic layer deposition film 2 is formed by the ALD method. By forming the atomic layer deposition film 2 by the ALD method, it becomes possible to form a thin film at the atomic layer level, and the atomic layer deposition film 2 can exhibit its functions.

[0027] Since the ALD method is a film formation method capable of depositing atomic layers one at a time, the resulting atomic layer deposition film usually has a uniform thickness. However, in the manufacturing process of the molecular recognition element 10, the atomic layer deposition film is formed with target molecules interposed therebetween, and then the target molecules are removed by heat treatment, so the thickness may become non-uniform.

[0028] The atomic layer deposition film preferably has an average thickness of 0.5 to 30 nm, more preferably 0.7 to 20 nm, even more preferably 1 to 12 nm, and even more preferably 1.5 to 10 nm. As described above, the atomic layer deposition film 2 has a non-uniform thickness because it has recognition portions 3 composed of holes that use the molecular shape of the target molecule as a template. However, by keeping the average thickness within the above preferred range, more accurate molecular recognition is possible. The thickness of the atomic layer deposition film can be observed using a transmission electron microscope (TEM). The average thickness can be calculated by measuring the thickness of the atomic layer deposition film at 20 random points.

[0029] CVD and PVD have a high growth rate, making it difficult to stably form thin films of the desired thickness, and because they lack selectivity, they can also deposit on target molecules. However, the ALD method uses OH groups on the substrate surface as base points and can deposit one atomic layer at a time on the substrate so as to cover the periphery of the target molecules.

[0030] The recognition portion 3 is a hole templated by the molecular shape of the target molecule. The hole templated by the molecular shape of the target molecule can be formed by removing the target molecule by heat treating a ceramic atomic layer deposition film formed by the ALD method so as to cover the target molecule.

[0031] The recognition unit 3 can recognize any target molecule, whether it is a hydrophilic or hydrophobic molecule. When the target molecule is a hydrophobic molecule, it is preferable that at least a portion of the target molecule has a polar functional group in order to pin it to the substrate.

[0032] The recognition unit 3 may be capable of recognizing one type of target molecule, or multiple types of target molecules. By forming the atomic layer deposition film 2 with one type of target molecule interposed therebetween, a recognition unit 3 capable of recognizing one type of target molecule can be formed. By forming the atomic layer deposition film 2 with multiple types of target molecules interposed therebetween, a recognition unit 3 capable of recognizing multiple types of target molecules can be formed. That is, when there is one type of target molecule, the atomic layer deposition film 2 has one type of hole molded after the molecular shape of the one type of target molecule, and when there are multiple types of target molecules, the atomic layer deposition film 2 has multiple types of hole molded after the molecular shapes of the multiple types of target molecules.

[0033] Preferably, the recognition unit 3 is capable of recognizing multiple types of target molecules having a predetermined ratio (molar ratio). By forming the atomic layer deposition film 2 with multiple types of target molecules having a predetermined ratio (molar ratio) interposed therebetween, it is possible to form the recognition unit 3 capable of recognizing multiple types of target molecules having a predetermined ratio (molar ratio).

[0034] The atomic layer deposition film 2 with the recognition unit 3 is made of ceramics and is not flexible like conventional MIPs, but is rather hard. The fact that the atomic layer deposition film 2 with the recognition unit 3 is made of a hard material is also thought to contribute to the ability to recognize the shape of molecules more precisely than conventional methods and for a long period of time without deterioration.

[0035] The recognition unit 3 can recognize the shape of a molecule, not the size of the molecule. Therefore, the recognition unit 3 of the atomic layer deposition film 2 has the concept of the shape of the hole, not the size of the hole. Therefore, it can recognize only the target molecule without misrecognizing not only large molecules but also small molecules. For example, 18 When we want to recognize nonanal represented by O, atomic layer deposition film 2 is a relatively large molecule with the chemical formula C 11 H 22 Undecanal, represented by O, as well as relatively small molecules with the formula CH 12It is possible to recognize only nonanal without misrecognizing hexanal represented by O. When nonanal is the target molecule, the distance between the carbonyl group, where the target molecule is adsorbed to the substrate, and the methyl group at the other end farther from the substrate is shorter in hexanal, and the bulky methyl group cannot enter the recognition unit 3.

[0036] The molecular recognition element 10 is capable of recognizing structural isomers that have the same molecular weight, chemical properties, and reactivity. For example,

[0037] [ka] 2-nonanone having the structure

[0038] [ka] 3-nonanone having the structure

[0039] [ka] 5-nonanone having the structure shown above is a structural isomer that differs only in the position of the carbonyl group and has approximately the same vapor pressure, but the molecular recognition element 10 can selectively recognize it.

[0040] Because the recognition unit 3 can precisely recognize the shape of a molecule, as described above, the recognition unit 3, which targets long molecules, can correctly and selectively recognize only the target molecule without erroneously recognizing not only longer molecules but also shorter molecules. This is because the recognition unit 3 recognizes the shape of the molecule, not its size. Without being bound by theory, it is believed that this is because the formation process of the recognition unit 3, which is formed by heat-treating a ceramic atomic layer deposition film formed by the ALD method so as to cover the target molecule and then removing the target molecule, produces a mold that can recognize the molecular shape resulting from the molecular motion of the target molecule.

[0041] Molecules that can be recognized by the molecular recognition element 10 are preferably molecules having 4 to 15 carbon atoms. This molecular recognition element can also recognize structural isomers of low molecules such as acetaldehyde. When low molecules are used as target molecules, it is preferable to keep the conditions of the ALD method as mild as possible so that the target molecules do not volatilize during the ALD process.

[0042] The molecular recognition element 10 can be used in sensors such as odor sensors, molecularly selective solid catalysts, diagnostic equipment requiring high accuracy, personal authentication, etc. When the molecular recognition element 10 is needle-shaped and used as a QCM sensor, for example, the surface area is extremely large, about 100 times that of conventional sensors, making it possible to clearly detect even a small number of molecules.

[0043] The present disclosure also provides a method for producing a nano-sized nanoparticle by disposing one or more target molecules having polar functional groups on a substrate made of a ceramic having OH groups on the surface thereof; forming an atomic layer deposition film made of ceramics on the substrate on which the target molecules are arranged by using an atomic layer deposition method; and heat-treating the substrate on which the atomic layer deposition film is formed to remove the target molecules, thereby forming a recognition portion configured with holes using the molecular shape of the target molecule as a template, which is capable of recognizing the molecular shape of the target molecule; The present invention relates to a method for manufacturing a molecular recognition element, comprising:

[0044] A schematic diagram of an example of the manufacturing method of the present disclosure is shown in Figure 2. Target molecules 4 are placed on a substrate 1, an atomic layer deposition (ALD) film 2 is formed, and the target molecules 4 are removed by heat treatment to form a recognition portion 3 in the atomic layer deposition film 2 that has the function of recognizing the molecular shape.

[0045] The ALD method is preferably carried out at a temperature at which the adsorbed target molecules do not volatilize in large amounts. In the ALD method, atomic layer deposition is preferably carried out at a temperature of about 100 to 200°C.

[0046] The temperature of the heat treatment is preferably 300°C or higher, more preferably 350°C or higher, and even more preferably 400°C or higher. By performing the heat treatment at the preferred temperature, the target molecules can be substantially removed. The upper limit of the heat treatment temperature can be a temperature that the atomic layer deposition film 2 and the recognition unit 3 made of ceramic can withstand, for example, 600°C, 500°C, or 400°C.

[0047] Figure 3 shows a schematic diagram illustrating an example of the state when an atomic layer deposition film 2 is formed by the ALD method on a substrate 1 made of needle-shaped ZnO crystals with a hexagonal wurtzite structure, when a target molecule 4 is desorbed (heat-treated), and when a molecular recognition element 10 recognizes a molecule. The atomic layer deposition film 2 is formed on the surface of the substrate 1, which is made of needle-shaped ZnO crystals, with the target molecule 4 interposed therebetween, and the target molecule 4 is desorbed (volatilized) by heat treatment to form a recognition unit 3. The recognition unit 3 can recognize only molecules that are compatible not only in size but also in shape.

[0048] Atomic layer deposition (ALD) allows atomic layers to be deposited one by one on a substrate 1. The ALD process involves (1) introducing a first material in vapor (gas) form as a precursor, (2) purging, (3) introducing a second material as another precursor, and (4) purging. These four steps constitute one cycle, and by repeating the cycle and adjusting the number of cycles, a film of the desired thickness can be formed. For example, a TiOx film can be formed at a thickness of approximately 0.5 Å per cycle, so a film thickness of approximately 100 Å (approximately 5 nm) can be obtained by performing 100 cycles. The temperature during ALD is preferably approximately 150 to 170°C.

[0049] In this method, a precursor of the first material is introduced together with a carrier gas and is allowed to adhere (physical adsorption) to the surface of the substrate 1. The precursor of the first material can bond with an OH group on the surface of the substrate 1. A single atom bonds to form a nucleus on the substrate 1, and a film grows laterally from the nucleus to form a film.

[0050] The first material can be tetrakisdimethylaminotitanium (TDMAT) as a titanium precursor, trimethylaluminum (TMA) as an aluminum precursor, bis(dimethylamino-2-methyl-2-butoxy)tin(II) [Sn(dmamb)2], etc. The second material can be water.

[0051] The ALD method can be carried out for, for example, 10 to 600 cycles, 15 to 400 cycles, 20 to 200 cycles, 25 to 100 cycles, 30 to 80 cycles, or 40 to 60 cycles.

[0052] The target molecule 4 can be any molecule to be recognized as long as it has a polar functional group. The target molecule 4 is disposed on the substrate 1 before the atomic layer deposition film 2 is formed. The target molecule 4 may be one type or two or more types depending on the type of molecule to be recognized.

[0053] By disposing multiple types of target molecules 4 at a predetermined ratio on the substrate 1, it is possible to recognize multiple types of molecules at a predetermined ratio. Because the molecular recognition element 10 can recognize multiple types of molecules at a predetermined ratio, it can be suitably used in an olfactory sensor. For example, by exposing the substrate 1 to a gas that exhibits the smell of bananas and forming an atomic layer deposition film 2, it is possible to obtain a molecular recognition element 10 equipped with a recognition unit 3 that can recognize a predetermined ratio of molecules that exhibit the smell of bananas.

[0054] The method for placing the target molecules 4 on the substrate 1 is not particularly limited, and can be performed by exposing the substrate 1 to a gas containing the target molecules 4, immersing the substrate 1 in a solution containing the target molecules 4, physical transport (PVT) method, chemical transport (CVT) method, etc.

[0055] The substrate 1 is not particularly limited as long as it is a ceramic material that can pin target molecules to its surface during the manufacturing process of the molecular recognition element 10 and on which an atomic layer deposition film can be deposited by the ALD method, i.e., a ceramic material that has OH groups on its surface.

[0056] The target molecule 4 to be adsorbed on the surface of the substrate 1 has a polar functional group for pinning to the substrate 1. The polar functional group is not particularly limited, but examples thereof include a carbonyl group, an amino group, an amide group, and combinations thereof.

[0057] For example, when nonanal is placed on the (1010) surface of ZnO, which is the substrate 1, the carbonyl group of nonanal can be adsorbed to the Lewis acid site on the (1010) surface through an acid-base interaction. In this case, the carbonyl group is pinned to the surface of the substrate 1, so that the target molecule 4 does not detach from the surface of the substrate 1 due to damage during deposition by the ALD method, and an atomic layer deposition film 2 can be deposited.

[0058] FIG. 4 shows a schematic diagram illustrating an example of the state when the target molecule 4, nonanal, is pinned to the m-plane of the ZnO substrate 1 via a carbonyl group, when the target molecule 4 is placed, when the atomic layer deposition film 2 is formed, and when the target molecule 4 is removed.

[0059] The target molecules 4 are preferably arranged at intervals on the substrate 1 rather than densely arranged on the substrate 1. By the ALD method, nuclei for crystal growth are formed on the substrate 1 in areas where no target molecules 4 are present, and an atomic layer deposition film can be formed so as to cover the periphery of the target molecules 4, starting from the nuclei.

[0060] The arrangement density of the target molecules 4 on the substrate 1 can be adjusted by the arrangement method and arrangement conditions of the target molecules 4 on the substrate 1.

[0061] After the target molecules 4 are disposed on the substrate 1, preheating may be performed to adjust the density of the target molecules 4 before forming the atomic layer deposition film 2 by the ALD method. Preheating allows the arrangement density of the target molecules 4 on the substrate 1 to be adjusted so as to decrease. The preheating temperature is preferably 160 to 200°C. During the cycle of forming the atomic layer deposition film by the ALD method, the target molecules 4 may gradually desorb, and therefore the density of the target molecules 4 on the substrate 1 may be adjusted by adjusting the temperature conditions, number of cycles, etc. of the ALD method.

[0062] Qualitative and quantitative analysis of molecules recognized by the molecular recognition element 10 can be performed by thermal generation gas chromatography mass spectrometry (TPD-GC / MS). The molecular recognition element used for molecular recognition is heated to approximately 300 to 500°C to desorb the molecules from the recognition unit 3, and the type and amount of the molecules can be measured by TPD-GC / MS. In TPD-GC / MS, peak area calibration is obtained in advance, and the measured values ​​can be converted to molar units. [Example]

[0063] (Example 1) Preparation of a molecular recognition element targeting nonanal

[0064] A molecular recognition element targeting nonanal was fabricated using the process shown in Figure 4. First, a needle-shaped ZnO substrate with a diameter of 20 nm and a length of 6000 nm and an m-plane was fabricated. The ZnO substrate was fabricated by hydrothermal synthesis. The ZnO substrate had OH groups on the m-plane.

[0065] The prepared ZnO substrate was immersed in a nonanal solution, taken out and dried, allowing nonanal molecules to be adsorbed onto the surface of the m-plane of the ZnO substrate.

[0066] Atomic layer deposition (ALD) (Veeco, Savannah G2 S100) was used to form an atomic layer deposition (ALD) film with an average thickness of 0.75 nm on the m-face of a ZnO substrate with nonanal adsorption. The ZnO substrate with nonanal adsorption was placed in a chamber, which was heated to 160°C. The ALD process consisted of 20 cycles: (1) adding tetrakisdimethylaminotitanium (TDMAT) as the first titanium precursor, (2) purging, (3) adding water as another precursor, and (4) purging.

[0067] Next, a heat treatment at 400°C was performed to remove the target molecules and form the recognition part, thereby producing a molecular recognition element having a ZnO substrate, a TiOx atomic layer deposition film, and a recognition part for nonanal molecules.

[0068] Similarly, the ALD step was repeated 40 cycles, 60 cycles, 100 cycles, and 600 cycles to fabricate molecular recognition elements, respectively.

[0069] (Evaluation of molecular selectivity) Molecular recognition elements fabricated by repeating the ALD step for 20, 40, 60, 100, and 600 cycles were exposed to a saturated vapor pressure mixture containing equal amounts of hexanal (C6), nonanal (C9), and undecanal (C11) to evaluate their selective recognition of the nonanal molecule. A control sample was also evaluated, in which no ALD film was formed. The average thicknesses of the atomic layer deposition films fabricated by repeating the ALD step for 20, 40, 60, 100, and 600 cycles were less than 0.2 nm, 0.5 nm, 1 nm, 2 nm, and 12 nm, respectively. The average thicknesses were calculated by measuring the thickness of the atomic layer deposition film at 20 random points.

[0070] Figure 5 shows a graph of molecular selectivity evaluation, with the horizontal axis representing the number of ALD cycles (hereafter also referred to as the ALD cycle number) and the vertical axis representing the amount of desorption (nmol) measured by TPD-GC / MS (Shimadzu Corporation, GCMS-QP2010). The amount of desorption was measured by TPD-GC / MS after heating at 300 °C (similar below). The molecular recognition elements fabricated after 20 to 100 cycles were able to selectively recognize nonanal. The comparison sample fabricated after 0 cycles lacked molecular selectivity because it did not have a recognition moiety. The molecular recognition element fabricated after 600 cycles likely had a poorly formed recognition moiety due to the target molecule being desorbed from the substrate surface, or the atomic layer deposition film was too thick to cover the recognition moiety, preventing it from functioning.

[0071] (Example 2) Preparation of a molecular recognition element targeting undecanal and evaluation of molecular selectivity A molecular recognition element having a ZnO substrate, a TiOx atomic layer deposition film, and a recognition portion for undecanal molecules was fabricated and its selective recognition of undecanal molecules was evaluated in the same manner as in Example 1. The average thicknesses of the atomic layer deposition films of the molecular recognition elements fabricated after 20, 40, 60, 100, and 600 cycles were 0 nm, 0.5 nm, 1 nm, 2 nm, and 12 nm, respectively.

[0072] Figure 6 shows a graph of molecular selectivity evaluation, with the horizontal axis representing the number of ALD step cycles and the vertical axis representing the amount of desorption (nmol) measured by TPD-GC / MS. The molecular recognition element fabricated after 20 to 40 cycles was able to selectively recognize undecanal. The comparison sample fabricated after 0 cycles had no molecular selectivity because it had no recognition moiety. For the molecular recognition element fabricated after 60 to 100 cycles, it is thought that either the target molecule desorbed from the substrate surface, resulting in insufficient formation of the recognition moiety, or the atomic layer deposition film was too thick, covering the recognition moiety and preventing it from functioning.

[0073] (Comparative Example 1) A comparative sample was prepared by forming a TiOx atomic layer deposition film on a ZnO substrate in the same manner as in Example 1, except that no target molecule was interposed. The sample was exposed to a saturated vapor pressure mixed gas containing equal amounts of hexanal (C6), nonanal (C9), and undecanal (C11), and the selective molecular recognition was evaluated.

[0074] Figure 7 shows a graph of molecular selectivity evaluation, with the horizontal axis representing the number of ALD cycles and the vertical axis representing the amount of desorption (nmol) measured by TPD-GC / MS. At any cycle number, the amount of desorption was small, and the molecule could not be recognized in significant amounts.

[0075] (Example 3) Evaluation of molecular selectivity of molecular recognition element targeting nonanal The molecular recognition element prepared in Example 1 was subjected to 100 ALD cycles and exposed to saturated vapor pressure gases containing decanal (C8), nonanal (C9), and octanal (C10), respectively, to evaluate selective recognition.

[0076] Figure 8 shows a graph in which the horizontal axis represents decanal (C8), nonanal (C9), and octanal (C10), and the vertical axis represents the amount of desorption (nmol) measured by TPD-GC / MS. Although decanal (C8), nonanal (C9), and octanal (C10) are molecules with similar numbers of carbon atoms, the molecular recognition element prepared in this example was able to selectively recognize nonanal.

[0077] (Example 4) Preparation of a molecular recognition element targeting 2-nonanone and evaluation of molecular selectivity Molecular recognition elements having a ZnO substrate, a TiOx atomic layer deposition film, and a recognition moiety for the 2-nonanone molecule were fabricated in the same manner as in Example 1, except that the target molecule was 2-nonanone and the ALD cycles were 20, 40, 60, 80, and 100. The fabricated molecular recognition elements were exposed to a saturated vapor pressure mixed gas containing equal amounts of 2-nonanone, 3-nonanone, and 5-nonanone, and the selective recognition of the 2-nonanone molecule was evaluated. The average thicknesses of the atomic layer deposition films of the molecular recognition elements fabricated after 20, 40, 60, 80, and 100 cycles were less than 0.2 nm, 0.4 nm, 0.6 nm, 0.8 nm, and 1 nm, respectively.

[0078] Figure 9 shows a graph of molecular selectivity evaluation, with the horizontal axis representing the number of ALD cycles and the vertical axis representing the amount of desorption (nmol) measured by TPD-GC / MS. Molecular recognition elements fabricated after 20 to 100 cycles, especially 40 to 60 cycles, were able to selectively recognize 2-nonanone. The comparison sample fabricated after 0 cycles lacked molecular selectivity because it lacked a recognition moiety. The molecular recognition element fabricated after 20 cycles showed little recognition moiety formation. The molecular recognition element fabricated after 80 to 100 cycles likely showed that the target molecule desorbed from the substrate surface, resulting in insufficient formation of a recognition moiety, or that the atomic layer deposition film was too thick and covered the recognition moiety, reducing its recognition function.

[0079] (Example 5) Preparation of a molecular recognition element targeting 3-nonanone and evaluation of molecular selectivity A molecular recognition element having a ZnO substrate, a TiOx atomic layer deposition film, and a recognition portion for the 3-nonanone molecule was fabricated and its selective recognition of the 3-nonanone molecule was evaluated in the same manner as in Example 4. The average thicknesses of the atomic layer deposition films of the molecular recognition elements fabricated after 20, 40, 60, 80, and 100 cycles were less than 0.2 nm, 0.4 nm, 0.6 nm, 0.8 nm, and 1 nm, respectively.

[0080] Figure 10 shows a graph of molecular selectivity evaluation, with the horizontal axis representing the number of ALD cycles and the vertical axis representing the amount of desorption (nmol) measured by TPD-GC / MS. The molecular recognition elements fabricated after 20 to 100 cycles, particularly 40 to 80 cycles, and even 40 to 60 cycles, were able to selectively recognize 3-nonanone.

[0081] (Example 6) Preparation of a molecular recognition element targeting 5-nonanone and evaluation of molecular selectivity A molecular recognition element having a ZnO substrate, a TiOx atomic layer deposition film, and a recognition portion for the 5-nonanone molecule was fabricated and its selective recognition of the 5-nonanone molecule was evaluated in the same manner as in Example 4. The average thicknesses of the atomic layer deposition films of the molecular recognition elements fabricated after 20, 40, 60, 80, and 100 cycles were less than 0.2 nm, 0.4 nm, 0.6 nm, 0.8 nm, and 1 nm, respectively.

[0082] Figure 11 shows a graph of molecular selectivity evaluation, with the horizontal axis representing the number of ALD cycles and the vertical axis representing the amount of desorption (nmol) measured by TPD-GC / MS. The molecular recognition element fabricated after 40 to 80 cycles, especially 40 to 60 cycles, was able to selectively recognize 5-nonanone.

[0083] (Comparative Example 2) A TiOx atomic layer deposition film was formed on a ZnO substrate in the same manner as in Example 4, except that no target molecule was interposed. The film was then exposed to a saturated vapor pressure mixed gas containing equal amounts of 2-nonanone, 3-nonanone, and 5-nonanone, and the selective molecular recognition was evaluated.

[0084] Figure 12 shows a graph of molecular selectivity evaluation, with the horizontal axis representing the number of ALD cycles and the vertical axis representing the amount of desorption (nmol) measured by TPD-GC / MS. At any cycle number, the amount of desorption was small, and the molecule could not be recognized in significant amounts.

[0085] (Evaluation of desorption of target molecules by ALD cycle) Figure 13 shows the infrared absorption spectroscopy (IR) spectra of CH2 and CH3 when atomic layer deposition was performed on a ZnO substrate with nonanal adsorbed as the target molecule, with the ALD step cycle numbers set to 0 to 600, using the same method as in Example 1. The peak intensities of CH2 and CH3 tended to decrease as the ALD cycle number increased.

[0086] Figure 14 shows a graph with the horizontal axis representing the number of ALD cycles and the vertical axis representing the amount (nmol) of nonanal desorbed from the substrate as a target molecule. The amount of nonanal desorbed tended to decrease as the number of ALD cycles increased. The results in Figures 13 and 14 suggest that the target molecules adsorbed on the substrate surface tended to desorb more as the number of ALD cycles increased.

[0087] (Atomic layer deposition film thickness evaluation) 15 shows a scanning electron microscope (SEM) photograph of the molecular recognition element fabricated by 60 cycles of ALD in Example 1. The molecular recognition element has a TiOx film (atomic layer deposition film) with a recognition moiety on a ZnO substrate with a needle-shaped m-plane.

[0088] Figure 16 shows a cross-sectional TEM image of the molecular recognition element in Figure 15 and elemental mapping images of Zn and Ti measured from the surface of the molecular recognition element by energy dispersive X-ray spectroscopy (EDX). Amorphous TiOx is deposited on a crystalline ZnO substrate, but because TiOx was deposited on the ZnO substrate with nonanal molecules interposed between them, there are irregularities at the interface between the ZnO substrate and TiOx (shown by the dashed line) and on the surface of the TiOx (shown by the solid line), and the TiOx film has an uneven thickness.

[0089] 17 shows a cross-sectional TEM image of the comparative sample prepared by 60 cycles of ALD in Comparative Example 1, and elemental mapping images of Zn and Ti measured from the surface of the comparative sample by energy dispersive X-ray spectroscopy (EDX). Amorphous TiOx was deposited on a crystalline ZnO substrate, and both the interface between the ZnO substrate and TiOx and the surface of the TiOx were flat, with the TiOx film having a uniform thickness of 2.1 nm.

[0090] (Evaluation of the relationship between the number of ALD cycles and the thickness of atomic layer deposition films) As in Example 1, a molecular recognition element was fabricated using 20 to 400 ALD cycles with nonanal target molecules interposed between them, and cross-sectional TEM observation was performed to measure the average thickness of the TiOx atomic layer deposition film, as in Figure 16. A comparative sample was fabricated in the same manner except that 0 to 400 ALD cycles were performed without interposing the target molecules between them, and cross-sectional TEM observation was performed to measure the average thickness of the TiOx atomic layer deposition film, as in Figure 17.

[0091] Figure 18 shows a graph showing the average thickness of the TiOx atomic layer deposition film versus the number of ALD cycles. The average thickness of the TiOx increased in proportion to the number of ALD cycles. The average thickness of the atomic layer deposition film was slightly smaller for the molecular recognition element with the target molecule interposed than for the comparison sample without the target molecule interposed, but the trend was roughly the same regardless of the presence or absence of the target molecule.

[0092] (Evaluation of desorption of target molecules depending on heat treatment temperature) 19 shows the infrared absorption spectroscopy (IR) spectra of CH2 and CH3 when a ZnO substrate, onto which nonanal was adsorbed as a target molecule by the same method as in Example 1, was heat-treated at temperatures of 100 to 250°C. When the heat treatment temperature was 250°C, the peaks of CH2 and CH3 became small, suggesting that nonanal had volatilized, but when the heat treatment temperature was in the range of 100 to 200°C, the peaks of CH2 and CH3 were observed, suggesting that nonanal was present on the substrate.

[0093] Molecular recognition elements were fabricated using 20 to 600 ALD cycles in the same manner as in Example 1, except that preheating at 175°C was performed before forming the atomic layer deposition film. The fabricated molecular recognition elements were exposed to a saturated vapor pressure mixed gas containing equal amounts of hexanal (C6), nonanal (C9), and undecanal (C11), and the selective recognition of nonanal molecules was evaluated. Figure 20 shows a graph showing the amount of desorbed molecules versus the number of ALD cycles. The molecular recognition element fabricated by preheating at 175°C was also able to selectively recognize nonanal. As suggested by the results in Figure 19, the target molecule nonanal remained on the substrate even after heating at 175°C, and the recognition moiety for nonanal molecules was successfully formed in the atomic layer deposition film.

[0094] FIG. 21 shows a graph comparing the peak positions of the amount of molecules desorbed depending on the number of ALD cycles for a molecular recognition element prepared in Example 1 without preheating and a molecular recognition element prepared with preheating at 175°C.

[0095] The peak position of the desorption amount due to the number of ALD cycles differs between molecular recognition elements fabricated without preheating and those fabricated with preheating at 175°C. The molecular recognition element fabricated with preheating shows a peak in the desorption amount when the number of ALD cycles is smaller (when the atomic layer deposition film thickness is smaller). This is because the target molecule arrangement density is low, so the atomic layer deposition film is more likely to be formed with fewer ALD cycles, and the recognition moiety is more likely to be formed with fewer ALD cycles.

[0096] (Evaluation of heat resistance of molecular recognition elements) Figure 22 shows a chromatogram of a molecular recognition element for nonanal as a target molecule, which was prepared in Example 1 by 60 ALD cycles, which was heat-treated at 300 to 600°C for 30 minutes, and then exposed to a saturated vapor pressure mixed gas containing equal amounts of hexanal, nonanal, and undecanal, and the amounts of hexanal, nonanal, and undecanal desorbed were measured using TPD-GC / MS.

[0097] Figure 23 is a graph in which the chromatographic measurement values ​​obtained in Figure 22 were converted into nmol units. The results in Figures 22 and 23 show that the molecular recognition element prepared in Example 1 was able to selectively recognize the target molecule nonanal even after heat treatment at 300 to 600°C.

[0098] 24 shows a graph of the amounts of hexanal, nonanal, and undecanal desorbed from a molecular recognition element fabricated in Example 1 using 60 ALD cycles, which was heat-treated at 400°C for 1 hour, 1 day, 1 week, and 1 month, and then exposed to a saturated vapor pressure mixed gas containing equal amounts of hexanal, nonanal, and undecanal, measured by TPD-GC / MS. The molecular recognition element was able to selectively recognize the target molecule nonanal, even after heat treatment at 400°C for 1 month.

[0099] Figure 25 is a graph showing the ratio of the amount of nonanal desorbed to that of hexanal, measured by TPD-GC / MS, after a molecular recognition element with nonanal as the target molecule, produced in Example 1 by 60 ALD cycles, was heat-treated at 300 to 600°C for 30 minutes to 3 months and then exposed to a mixed gas at saturated vapor pressure containing equal amounts of hexanal, nonanal, and undecanal.

[0100] The molecular recognition element produced was able to selectively recognize the target molecule nonanal even after a long heat treatment at 300-400°C for three months. At a heat treatment temperature of 500°C, the ratio of nonanal to hexanal desorbed from the molecular recognition element decreased slightly. At a heat treatment temperature of 600°C, the ratio of nonanal to hexanal desorbed further decreased, but nonanal selectivity was still observed. The molecular recognition element was able to selectively recognize the target molecule nonanal even after heat treatment at 300-600°C, and even after heat treatment at 300-400°C with particular success.

[0101] (Evaluation of the characteristics of molecular recognition element-applied devices) The molecular recognition element, which targets nonanal and was fabricated using 60 ALD cycles in Example 1, was placed on the quartz crystal of a quartz crystal microbalance (QCM) device, and the QCM sensor performance was evaluated. Figure 26 shows (A) a schematic diagram of the appearance of the QCM device, and (B) a schematic diagram of the appearance of the molecular recognition element placed on the quartz crystal of the QCM device.

[0102] Figure 27 shows a graph of the frequency change ΔF of the quartz crystal oscillator versus time (seconds) when exposed to gases containing hexanal at saturated vapor pressure, nonanal at saturated vapor pressure, and undecanal at saturated vapor pressure, respectively, for (A) a comparative sample that was subjected to atomic layer deposition without the use of a target molecule, and (B) a molecular recognition element with nonanal as the target molecule placed on the quartz crystal of a QCM device. Each gas was flowed for 300 to 600 seconds and 900 to 1200 seconds.

[0103] The comparison sample prepared without the intervening target molecule did not exhibit molecular selectivity. The comparative sample prepared without the intervening target molecule showed a relatively large increase in ΔF when a gas containing hexanal was flowed. This is because hexanal has a small molecular weight and a high vapor pressure, resulting in a large number of molecules. The molecular recognition element with nonanal as the target molecule was able to selectively recognize nonanal, and its ΔF rose immediately when exposed to a gas containing the molecule, and decreased immediately when the flow of the gas containing the molecule was stopped. Thus, it was confirmed that this molecular recognition element can operate as a high-performance QCM sensor. [Explanation of symbols]

[0104] 10 Molecular Recognition Element 1 Base material 2 Atomic layer deposition film 3 Recognition part 4. Target molecule

Claims

1. a substrate made of ceramics, and An atomic layer deposition film made of ceramics on the substrate Including, The atomic layer deposition film has a recognition portion configured with a hole capable of recognizing the molecular shape of one or more types of target molecules and using the molecular shape of the target molecule as a template. Molecular recognition element.

2. 2. The molecular recognition element according to claim 1, wherein the atomic layer deposition film has an average thickness of 0.5 to 30 nm.

3. 3. The molecular recognition element according to claim 1, wherein the atomic layer deposition film contains a cationic ion oxide in which oxygen atoms are six-coordinated to a metal atom.

4. A sensor comprising the molecular recognition element according to claim 1 or 2.

5. disposing one or more types of target molecules having polar functional groups on a substrate made of ceramic having OH groups on its surface; forming an atomic layer deposition film made of ceramics on the substrate on which the target molecules are arranged by using an atomic layer deposition method; and heat-treating the substrate on which the atomic layer deposition film is formed to remove the target molecules, thereby forming a recognition portion configured with holes using the molecular shape of the target molecule as a template, which is capable of recognizing the molecular shape of the target molecule; A method for producing a molecular recognition element, comprising:

6. The method for producing a molecular recognition element according to claim 5, wherein the atomic layer deposition film has an average thickness of 0.5 to 30 nm.

7. 7. The method for producing a molecular recognition element according to claim 5, wherein the atomic layer deposition film contains a cationic ionic oxide in which oxygen atoms are six-coordinated to a metal atom.

8. 7. The method for producing a molecular recognition element according to claim 5, wherein the temperature of the heat treatment is 300[deg.] C. or higher.

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