JP2011080798A - Method of manufacturing chemical substance sensing element - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method of manufacturing a chemical substance sensing element including marker selectivity and high performance for a marker included in bioinformation. <P>SOLUTION: In the method of manufacturing a chemical substance sensing element for detecting a specific chemical substance, the surface of a conductive substrate is surface-modified with a material capable of specifically adsorbing to the specific chemical substance. The method of manufacturing a chemical substance sensing element includes a process for calculating adsorption energy with each specific chemical substance for a candidate material including a possibility of adsorbing to an electron track of the specific chemical substance relating to bonding to the specific chemical substance, and for selecting a material predicted to be suitable for a surface modification material of the conductive substrate from among the candidate materials, based on the results. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a method of manufacturing a chemical substance sensing element for detecting a specific chemical substance, wherein the surface of a conductive substrate is surface-modified with a material capable of specifically adsorbing to the specific chemical substance.

  In 2055, Japan is facing a super-aging society where only 1.5 people are supported by one elderly person. Currently, Japan has problems such as insurance premiums and local doctor shortages. In these societies, public awareness about health is high, and the health market such as many health foods and supplements is on the rise, with a focus on prevention before suffering from illness (here, “medical prevention” We call on the realization of society.

  When managing health at home or individually, a device that can easily measure the degree of health is required. For example, a sphygmomanometer is one of the health equipments that are widely used, from those that can be measured with the wrist to full-fledged ones. There are other ways to analyze easily sampled blood, urine, saliva, exhaled breath, etc., to determine which disease may be caused by the specific chemicals contained. Chemical substances corresponding to such diseases are called “markers”.

  For example, in Wenqing Cao et al., “Breath Analysis: Potential for Clinical Diagnosis and Exposure Assessment”, Clinical Chemistry, Vo. 52: 5, p.800-811 (2006) (Non-Patent Document 1) The relationship is shown. Quotations related to exhalation are quoted in Table 1.

  It can be seen from Table 1 that there are many markers especially in exhalation. This is considered because the taken-in air exists in the alveoli in close proximity to the blood in the capillaries and the thin film.

  Gas chromatography and chemiluminescence methods are known as methods for measuring markers in exhaled breath. However, these measuring methods are not practical because they require large-scale and expensive measuring instruments and require familiarity with operation methods. Absent. Although measurement using an oxide semiconductor gas sensor is also known, the detection limit is as low as 103 ppm level and the sensitivity is low, and it is not suitable for measurement of a marker in exhaled breath having a concentration on the order of ppm from ppb. Furthermore, since it is necessary to heat to 300 ° C. in order to operate as a gas sensor, it is not practical.

  For example, Riichiro Saito, “Outline and Issues of Carbon Nanotubes”, Functional Materials, Vol.21, No.5, p.6-14, May 2001 (Non-Patent Document) Patent Document 2) proposes a gas sensor using carbon nanotubes (CNT). CNT is a tubular carbon material having a diameter of nano order, and has a structure in which a graphene sheet is rolled into a cylindrical shape. The graphene sheet is a two-dimensional continuous graphite structure in which six carbon atoms form a regular hexagonal plate-like structure and are bonded. Since CNT has high conductivity and is a nano-order material, the gas sensor disclosed in Non-Patent Document 2 can realize ultra-small size, low power consumption and portability, and is simple and practical. Ideal as a health check device. However, since the selectivity with respect to the gas to be measured is low, the resistance change occurs in the same manner regardless of what gas molecules approach, and there is a problem that the qualitative analysis of the substance present in the atmosphere cannot be performed.

  As shown in Table 1, nitric oxide (NO), which is one of the markers during expiration, is detected at a high concentration in the expiration of asthma patients. NO is one of the neurotransmitters in the living body, and is known to play an important role in immune reactions and blood pressure regulation. Therefore, it is possible to know the prediction and degree of disease by detecting the NO concentration in exhaled breath, and it is desired to realize a high-performance nitric oxide sensor (NO sensor).

Also, Alexander Star et al., “Carbon Nanotube Sensors For Exhaled Breath Components”, Nanotechnology, Vol.18, p.375502 (7pp), (2007) (Non-Patent Document 3) proposes a NO sensor using CNT. Has been. The NO sensor disclosed in Non-Patent Document 3 improves the selectivity for the measurement target gas by modifying the CNT surface with a substance that reacts with a specific substance. That is, by using a CNT whose surface is modified with polyethyleneimine that reacts with nitrogen dioxide (NO ₂ ), and further providing a catalyst for converting nitrogen monoxide to nitrogen dioxide, it is a specific marker in the exhaled breath. Nitric oxide (NO) is detected.

Wenqing Cao et al., "Breath Analysis: Potential for Clinical Diagnosis and Exposure Assessment", Clinical Chemistry, Vo. 52: 5, p.800-811 (2006) Riichiro Saito, “Outline and Issues of Carbon Nanotubes”, Functional Materials, Vol.21, No.5, p.6-14, May 2001 Alexander Star et al., "Carbon Nanotube Sensors For Exhaled Breath Components", Nanotechnology, Vol.18, p.375502 (7pp), (2007)

  In general, the NO concentration in the exhalation of a healthy person is about 10 ppb, and the NO concentration in the exhalation of an asthmatic patient is about 50 ppb. Therefore, the NO sensor for detecting NO in exhalation has a lower detection limit. A ppb level and high sensitivity are required. In the NO sensor disclosed in Non-Patent Document 3, such a high level of sensitivity that can detect NO in exhalation has not been achieved.

In addition, the NO sensor disclosed in Non-Patent Document 3 does not operate normally unless the catalyst used is in an environment with a humidity of about 15 to 30%, so the humidity of the gas to be measured must be adjusted. Further, in order to detect an accurate NO concentration, nitrogen dioxide (NO ₂ ) contained in the measurement target gas must be removed in advance. Therefore, when NO in exhalation is measured by the NO sensor disclosed in Non-Patent Document 3, not only the catalyst but also removal of nitrogen dioxide (NO ₂ ) contained in about 4% in exhalation and adjustment of humidity Therefore, there is a problem in that the size of the apparatus is increased. Further, there is a problem that the measurement time becomes long because a multi-step process is required for the measurement.

  The present invention has been made in order to solve the above-described problems, and an object thereof is to manufacture a chemical substance sensing element having marker selectivity and high performance with respect to a marker included in biological information. It is to provide a way that can be done.

  The present invention is a method for producing a chemical substance sensing element for detecting a specific chemical substance, wherein the surface of a conductive substrate is modified with a material capable of specifically adsorbing to the specific chemical substance. For candidate materials that have the possibility of being adsorbed on the electron orbit of the specific chemical substance related to the bond with the substance, the adsorption energy with each specific chemical substance is calculated. The method includes a step of selecting a material that is predicted to be suitable for the surface modification material of the conductive substrate.

  In the method for producing a chemical substance sensing element of the present invention, it is preferable to use density functional theory for prediction of the surface modifying material.

  In the method for producing a chemical substance sensing element of the present invention, the specific chemical substance is preferably nitric oxide.

  The surface modifying material selected in the present invention is preferably a metal complex, and the metal complex is particularly preferably a metal phthalocyanine.

  According to the present invention, a surface modification material for specifically adsorbing and detecting a specific chemical substance used for surface modification of a conductive substrate can be efficiently selected according to the specific chemical substance, and thereby included in biological information. Therefore, it is possible to manufacture a chemical substance sensing element having marker selectivity and high performance with respect to the marker. Further, according to the present invention, not only the adsorption energy between the specific chemical substance and the candidate material for the surface modification material, but also which electron orbit of the specific chemical substance is involved in the adsorption can be grasped from such a viewpoint. A surface modifying material can be selected. Further, by examining various candidate materials, it is possible to select a plurality of surface modifying materials, and it is possible to easily cope with an array of chemical substance sensing elements.

It is a figure which shows typically the chemical substance sensing element 1 of a preferable example manufactured by this invention. It is a figure which expands and shows the sensing part of FIG. It is a figure which shows the most stable structure of a cobalt phthalocyanine (CoPc) modification graphite sheet and NO. 4A is a graph showing the local state density of CoPc, and FIG. 4B is a graph showing the local state density of CoPc + NO. FIG. 5A is a graph showing the local state density of MnPc, and FIG. 5B is a graph showing the local state density of MnPc + NO. 6A is a graph showing the local state density of FePc, and FIG. 6B is a graph showing the local density of FePc + NO.

  Prior to the description of the method for producing the chemical substance sensing element of the present invention, first, the chemical substance sensing element produced by the present invention will be described. FIG. 1 is a diagram schematically showing a preferred example of the chemical substance sensing element 1 manufactured according to the present invention, and FIG. 2 is an enlarged view of the sensing part of FIG. As shown in FIG. 1, a chemical substance sensing element 1 manufactured according to the present invention basically includes a conductive substrate 2 and a sensing unit 3, and the conductive substrate 2 has positive and negative electrodes 4 and 4, respectively. The negative electrode 5 is electrically connected to the power source 6. The sensing unit 3 is a part that specifically adsorbs and detects a specific chemical substance. By detecting a change in electrical conductivity of the sensing unit 3 caused by bringing a specimen, for example, exhaled breath, into contact with the sensing unit 3 The presence and content of specific chemicals in exhaled breath can be clarified. As shown in an enlarged view in FIG. 2, the sensing unit 3 is formed by surface-modifying the surface of the conductive substrate 2 with a material (surface modifying material) 7 that can specifically adsorb to a specific chemical substance. .

  The method for producing a chemical substance sensing element of the present invention is a method capable of efficiently selecting the surface modifying material according to the specific chemical substance to be detected using the chemical substance sensing element. That is, the present invention is a method for producing a chemical substance sensing element for detecting a specific chemical substance, wherein the surface of a conductive substrate is surface-modified with a material capable of specifically adsorbing to the specific chemical substance, For candidate materials that have the possibility of being adsorbed on the electron orbit of the specific chemical substance related to the binding with the specific chemical substance, the adsorption energy with each specific chemical substance is calculated. And selecting a material that is predicted to be suitable for the surface modification material of the conductive substrate.

  The specific chemical substance in the present invention is not particularly limited, and examples thereof include breath marker substances shown in Table 1, such as nitric oxide (NO), carbon monoxide (CO), hydrogen, ammonia, and the like. . Among them, NO, which is an exhalation marker for asthma, has a problem in current NO measurement that the measurement time becomes long because a multi-step process is required by using the method for manufacturing a chemical substance sensing element of the present invention. The specific chemical substance is preferably NO because it can be solved.

  In the present invention, first, a candidate material having a possibility of being adsorbed on the electron orbit of a specific chemical substance related to the binding with the specific chemical substance is selected. This candidate material is selected in view of the characteristics of the candidate material. Whether or not there is a possibility of being adsorbed on the electron orbit of the specific chemical substance related to the bond with the specific chemical substance is determined by actually setting the initial structure and calculating the adsorption energy after the calculation. Can do.

In the case where the specific chemical substance is NO, candidate materials having a possibility of being adsorbed on the electron orbit of the specific chemical substance related to the binding with the specific chemical substance may be materials having metals, such as metal phthalocyanine, porphyrin And so on. Among these, metal phthalocyanine as noted by the present inventors is preferred because of its stability and availability. The metal phthalocyanine is a complex of a cyclic compound phthalocyanine having a structure in which four phthalimides are bridged by a nitrogen atom (Phthalocyanine or Tetrabenzoazoline, C ₃₂ N ₈ H ₁₆ ) and a metal (Metal) disposed in the central portion thereof It is.

  In the present invention, it is preferable to use a simulation using Density Functional Theory (DFT) to select a material that is predicted to be suitable for the surface modification material of the conductive substrate from the candidate materials. DFT is a theory that it is possible to calculate physical properties such as energy of an electron system from the electron density. The simulation using this theory uses a plane wave / suspected potential basis based on the density functional method. A simulator VASP (Vienna Ab-initio Simulation Package), which is a one-principles electronic state calculation program package, can be suitably used.

  As will be described later in the experimental examples, the present inventors have predicted using a simulator VASP a material that is predicted to be suitable for the surface modification material of the conductive substrate when the specific chemical substance is NO. Specifically, for metal phthalocyanine (hereinafter referred to as “MePc”) as a candidate material, the central metal is manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), When substituting with zinc (Zn), the adsorption energy and local density of states when NO was adsorbed on each metal were calculated using a simulator (VASP) based on DFT. As a result, it was found that a difference appears in the adsorption ability for nitric oxide (NO), which is a marker of asthma, depending on the difference in the central metal of metal phthalocyanine.

  Further, the present inventors searched for an adsorption site of NO on the surface of the graphite sheet surface-modified with cobalt (Co) phthalocyanine, investigated the electronic state when NO was adsorbed on the stable adsorption site, and performed first-principles calculations. When the most stable structure was obtained by the above, it was found that in the most stable structure, the π * orbit of NO and the dzz orbit of Co that existed in the vicinity of Fermi energy were mixed to form a bonding orbit and an antibonding orbit. . From this result, it is predicted that the electrical conductivity of the conductor surface-modified with cobalt phthalocyanine changes due to NO adsorption.

  In addition, regarding manganese phthalocyanine and iron phthalocyanine other than cobalt phthalocyanine, the calculation of the local state density of the system in which the metal and NO were adsorbed revealed that the energy gap expanded before and after the adsorption of NO. Although the electrical conductivity was predicted to change even when modified, nickel phthalocyanine, copper phthalocyanine, and zinc phthalocyanine also had low adsorption energy, and there was no widening of the energy gap even as a result of local density of states. The electrical conductivity was not expected to change.

  As described above, in the present invention, it is preferable that a simulation based on DFT is performed, and it is possible to adsorb to the electron orbit of the specific chemical substance related to the binding with the specific chemical substance without performing an experiment. It is possible to obtain knowledge that can be predicted that any of the candidate materials is suitable for the surface modification material of the conductive substrate. In addition, by being able to study multiple materials without experimenting, it is possible to identify multiple materials that are expected to be suitable as surface modification materials for conductive substrates from candidate materials, and array chemical substance sensing elements. It is very useful for review.

  Thus, the chemical substance sensing element for NO detection formed by, for example, modifying the surface of a conductive substrate with cobalt phthalocyanine is suitably produced by the method for producing a chemical substance sensing element of the present invention. Such a chemical substance sensing element for detecting NO has the advantage that it can specifically detect NO and the user can objectively know the degree of symptoms for lung diseases such as asthma.

In the chemical substance sensing element manufactured according to the present invention, the conductive substrate is preferably composed of a nanostructure. In the present invention, the nanostructure refers to a structure such as a nanotube, nanowire, or fullerene, and the surface area thereof is preferably in the range of 100 to 3000 cm ² / cm ³ . Since the conductive substrate is a nanostructure, when a sensing device is constructed, there is an advantage that ultrasensitive sensing that cannot be obtained with an oxide semiconductor sensor is possible at room temperature.

  In the chemical substance sensing element manufactured according to the present invention, the conductive substrate is particularly preferably a nanostructure (carbon nanostructure) made of carbon nanotubes (CNT). This is because the carbon nanotube not only exhibits electrical conductivity at a nanometer size but also becomes a semiconductor depending on its chirality, and has a property of obtaining an amplification effect of sensitivity by a control voltage (gate voltage).

  The impurities in the carbon nanotube are preferably in the range of 0.001 to 0.05 in strength ratio to carbon (carbon (C)), and preferably in the range of 0.001 to 0.01. Particularly preferred. Here, the impurity means a generic name of elements other than C, such as K, Mg, Ca, Na, Al, Si, S, Fe, Co, and Ni. The intensity ratio is, for example, energy dispersive X-rays The count value detected by the analyzer shall be indicated. When the intensity ratio of each impurity (Ca, Mg, S, Si, etc.) to carbon, which is the main constituent element of CNT, is calculated, if it is less than 0.001, there may be a problem in data reliability. If it exceeds 0.05, the conductivity due to impurities may affect the sensing characteristics.

  When sensing with a chemical substance sensing element, an electric field is applied to measure the change in electrical resistance. Thereby, movement of electrons occurs inside the carbon nanostructure. When reacting with the specified chemical substance, the change in electrical properties is transferred to the carbon nanostructure at a high speed by the π-electron bond common to cobalt phthalocyanine and carbon nanostructure in the entire molecular structure, and the electrical resistance changes. To generate quickly.

  In addition, in order to reuse this chemical substance sensing element, it is necessary to remove the specific chemical substance previously measured. In this case, the adsorbed specific chemical substance can be desorbed by raising the temperature of the chemical substance sensing element. Various means can be provided to raise the temperature of the chemical substance sensing element. For example, the specific chemical substance can be removed by raising the temperature of the chemical substance sensing element to about 200 ° C. by adjusting the voltage of the DC power supply to a high level during the gas separation process. Moreover, you may provide a means for heating a chemical substance sensing element periodically at 150 degreeC. Further, heating by laser light irradiation with a semiconductor laser may be performed. The method of desorbing the specific chemical substance is not limited to this, and can be performed by evacuation.

  Hereinafter, although an example of an experiment is given and the present invention is explained in detail, the present invention is not limited to these.

<Experimental example 1>
For the metal phthalocyanine (MePc) in which the central metal was replaced with manganese (Mn), the adsorption energy and local state density when NO was adsorbed on the metal were calculated using a simulator VASP based on DFT. As a result, it was found that the adsorption energy of manganese (Mn) phthalocyanine and NO was 1.738 eV, and MnPc and NO formed a strong bond.

<Experimental example 2>
For the metal phthalocyanine (MePc) with the central metal substituted with iron (Fe), the adsorption energy and local state density when NO was adsorbed on the metal were calculated in the same manner as in Experimental Example 1. As a result, the adsorption energy between iron (Fe) phthalocyanine and NO was 1.899 eV, and it was found that FePc and NO form a strong bond.

<Experimental example 3>
For the metal phthalocyanine (MePc) in which the central metal was replaced with cobalt (Co), the adsorption energy and local state density when NO was adsorbed on the metal were calculated in the same manner as in Experimental Example 1. As a result, it was found that the adsorption energy of cobalt (Co) phthalocyanine and NO was 1.552 eV, and a strong NO bond was formed with FePc.

<Experimental example 4>
In the case where the central metal of metal phthalocyanine (MePc) was replaced with nickel (Ni), the adsorption energy and local state density when NO was adsorbed on the metal were calculated in the same manner as in Experimental Example 1. As a result, it was found that the adsorption energy of nickel (Ni) phthalocyanine and NO was 0.104 eV, and NiPc and NO formed a weak bond.

<Experimental example 5>
For the metal phthalocyanine (MePc) in which the central metal was replaced with copper (Cu), the adsorption energy and local state density when NO was adsorbed on the metal were calculated in the same manner as in Experimental Example 1. As a result, it was found that the adsorption energy of copper (Cu) phthalocyanine and NO was 0.033 eV, and CuPc and NO formed a weak bond.

<Experimental example 6>
In the case where the central metal of metal phthalocyanine (MePc) was substituted with zinc (Zn), the adsorption energy and local state density when NO was adsorbed on the metal were calculated in the same manner as in Experimental Example 1. As a result, it was found that the adsorption energy between zinc (Zn) phthalocyanine and NO was 0.006 eV, and ZnPc and NO formed a weak bond.

  Table 2 summarizes the results of Experimental Examples 1 to 6.

<Experimental example 7>
The NO adsorption site on the surface of the CoPc-modified graphite sheet was searched, the electronic state when NO was adsorbed on the stable adsorption site was examined, and the local state density was calculated. The most stable structure obtained by the first principle calculation is shown in FIG. 4A is a graph showing the local density of states of CoPc and FIG. 4B is a graph showing the local density of states of CoPc + NO (without graphene sheet), both of which the vertical axis is DOS (arbit.units) and the horizontal axis is energy (eV). Is shown. In the most stable structure shown in FIG. 3, the π * orbit of NO11 existing in the vicinity of Fermi energy and the dzz orbit of Co in CoPc13 on the graphene sheet 12 are mixed to form a bonding orbit and an antibonding orbit. . From this result, it is considered that the electrical conductivity of the CoPc-modified CNT changes due to NO adsorption.

<Experimental Example 8>
As for MnPc, the local state density was calculated in the same manner as in Experimental Example 7 for the system in which NO was adsorbed (without the graphene sheet). FIG. 5A is a graph showing the local density of states of MnPc and FIG. 5B is a graph showing the density of local states of MnPc + NO. Both the vertical axis shows DOS (arbit.units) and the horizontal axis shows energy (eV). Even in the case of MnPc, the energy gap expanded before and after NO adsorption. From this, it is considered that the electrical conductivity changes even with MnPc.

<Experimental Example 9>
For FePc, the local state density was calculated in the same manner as in Experimental Example 7 for the system in which NO was adsorbed (without the graphene sheet). 6A is a graph showing the local density of FePc, and FIG. 6B is a graph showing the density of local states of FePc + NO. In both cases, the vertical axis represents DOS (arbit.units), and the horizontal axis represents energy (eV). Even in the case of FePc, the energy gap expanded before and after NO adsorption. From this, it was considered that the electrical conductivity changes even with FePc.

<Experimental example 10>
In the case of NiPc, CuPc, and ZnPc, the local state density was calculated in the same manner as in Experimental Example 7 for the system in which NO was adsorbed (without the graphene sheet). In these cases, it was considered that the electrical conductivity did not change from the time when the adsorption energy was small and the energy gap was not widened as a result of the local density of states.

  The embodiments and experimental examples disclosed this time should be considered as illustrative in all points and not restrictive. The scope of the present invention is defined by the terms of the claims, rather than the description above, and is intended to include any modifications within the scope and meaning equivalent to the terms of the claims.

  DESCRIPTION OF SYMBOLS 1 Chemical substance sensing element, 2 Conductive substrate, 3 Sensing part, 4 Positive electrode, 5 Negative electrode, 6 Power supply, 7 Surface modification material, 11 Nitric oxide (NO), 12 Graphene sheet, 13 Cobalt phthalocyanine (CoPc).

Claims (5)

A method for producing a chemical substance sensing element for detecting a specific chemical substance, wherein the surface of a conductive substrate is modified with a material capable of specifically adsorbing to the specific chemical substance,
For candidate materials that have the possibility of being adsorbed on the electron orbit of the specific chemical substance related to the binding with the specific chemical substance, the adsorption energy with each specific chemical substance is calculated. A method for producing a chemical substance sensing element, comprising a step of selecting a material that is predicted to be suitable as a surface modification material for a conductive substrate.   The method of claim 1, wherein density functional theory is used to predict the surface modifying material.   The method according to claim 1 or 2, wherein the specific chemical substance is nitric oxide.   The method of claim 3, wherein the candidate material is a metal complex.   The method according to claim 4, wherein the metal complex is metal phthalocyanine.

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