JP2020165707A - Organic silica substrate for laser desorption/ionization mass spectrometry and laser desorption/ionization mass spectrometry using the same - Google Patents

Abstract

To provide an organic silica substrate for laser desorption/ionization mass spectrometry which, when used for mass spectrometry, can make signal intensity of a molecule to be measured higher in mass spectrum to be obtained and enables higher sensitivity analysis.SOLUTION: An organic silica substrate for laser desorption/ionization mass spectrometry includes: an organic silica thin film 2 consisting of organic silica having an organic group capable of absorbing laser light in a skeleton; and a hydrophobic layer 3 laminated on the surface of the organic silica thin film. The hydrophobic layer is a layer consisting of a hydrophobic material having a functional group capable of covalently bonding with a hydrophobic group having an aliphatic carbon skeleton as the main skeleton and the silica skeleton of the organic silica. Further, the thickness of the hydrophobic layer is 0.2 to 5.5 nm.SELECTED DRAWING: Figure 3

Description

The present invention relates to an organic silica substrate for laser desorption / ionization mass spectrometry, and a laser desorption / ionization mass spectrometry method using the same.

In mass spectrometry (MS), a sample containing a molecule to be measured is ionized, and ions derived from the molecule to be measured are separated and detected by a mass-to-charge ratio (mass / charge (m / z)). This is an analytical method for obtaining information on the chemical structure of the molecule to be measured. In such mass spectrometry (MS), ionization of a sample is an important process that affects the propriety of analysis and the quality of the obtained spectrum, and the method (ionization method) includes, for example, a laser desorption / ionization method. (Laser resolution / ionization: LDI) is known. In recent years, in mass spectrometry methods that employ such a laser desorption / ionization method (LDI), various types of analytical substrates have been studied in order to further improve the accuracy of the analysis. ..

For example, in Japanese Patent Application Laid-Open No. 2018-185200 (Patent Document 1), the skeleton has an organic group capable of absorbing laser light, the pores have an average pore diameter of 5 to 50 nm, and the surface aperture ratio. Disclosed is an organic silica substrate for laser desorption / ionized mass spectrometry that comprises an organic silica porous membrane of 33-70%. Such an organic silica substrate for laser desorption / ionization mass spectrometry as described in Patent Document 1 can perform analysis with sufficient sensitivity when used in the laser desorption / ionization mass spectrometry method. Met. However, in the field of mass spectrometry that employs such a laser desorption / ionization method (LDI), a new method that enables more sensitive analysis so that more accurate analysis can be performed. The emergence of various analytical substrates is desired.

JP-A-2018-185200

The present invention has been made in view of the above-mentioned problems of the prior art, and when used for mass spectrometry, the signal intensity of the molecule to be measured can be made higher in the obtained mass spectrum, which is higher. It is an object of the present invention to provide an organic silica substrate for laser desorption / ionization mass spectrometry capable of performing sensitive analysis, and a laser desorption / ionization mass spectrometry method using the same.

As a result of diligent research to achieve the above object, the present inventors have obtained an organic silica substrate for laser desorption / ionization mass analysis, which is composed of an organic silica having an organic group capable of absorbing laser light as a skeleton. It is provided with a silica thin film and a hydrophobic layer laminated on the surface of the organic silica thin film, and the hydrophobic layer is shared with a hydrophobic group having an aliphatic carbon skeleton as a main skeleton and the silica skeleton of the organic silica. By forming a layer made of a hydrophobic material having a bondable functional group and setting the thickness of the hydrophobic layer to 0.2 to 5.5 nm, the mass spectrum obtained when this is used for mass analysis We have found that the signal intensity of the molecule to be measured can be made higher, which makes it possible to perform more sensitive analysis, and have completed the present invention.

That is, the organic silica substrate for laser desorption / ionization mass analysis of the present invention is laminated on the surface of an organic silica thin film made of organic silica having an organic group capable of absorbing laser light as a skeleton. The hydrophobic layer is a layer made of a hydrophobic material having an aliphatic carbon skeleton as a main skeleton and a functional group covalently bonded to the silica skeleton of the organic silica. Moreover, the thickness of the hydrophobic layer is 0.2 to 5.5 nm.

Further, in the organic silica substrate for laser desorption / ionization mass analysis of the present invention, the hydrophobic group contains an alkyl group, an alkynyl group, an alkenyl group, a fluorine atom-containing group, and a halogen atom other than the fluorine atom. It is preferably at least one group selected from the group consisting of a group, an alkynyl halide group containing a halogen atom other than a fluorine atom, and an alkenyl halide group containing a halogen atom other than a fluorine atom.

Further, in the organic silica substrate for laser desorption / ionization mass spectrometry of the present invention, it is preferable that the organic group capable of absorbing the laser light has a maximum absorption wavelength in the wavelength range of 200 to 600 nm.

Further, in the organic silica substrate for laser desorption / ionization mass spectrometry of the present invention, it is preferable that the organic silica thin film has a concavo-convex structure.

Further, in the laser desorption / ionization mass spectrometry method of the present invention, the analysis substrate used in the laser desorption / ionization mass spectrometry is the organic silica substrate for the laser desorption / ionization mass spectrometry of the present invention. This is a characteristic method.

The reason why the above object is achieved by the organic silica substrate for laser desorption / ionization mass spectrometry of the present invention is not always clear, but the present inventors speculate as follows.

That is, in laser desorption / ionization mass spectrometry, in order to perform more sensitive analysis, it is necessary to more efficiently ionize and desorb the molecule to be measured (substance to be analyzed) coated on the surface of the analysis substrate. It is clear that there is. Considering here, first, when the molecule to be measured (substance to be analyzed) and the surface of the substrate (solid surface) strongly interact with each other, the desorption of the molecule to be measured from the substrate surface is hindered, and mass spectrometry is performed. It is considered that the accuracy of In addition, when the molecule to be measured (substance to be analyzed) and the surface of the substrate (solid surface) strongly interact with each other, the target substance specifically aggregates in the process of drying the dropped solution of the molecule to be measured, and the agglomerates form. Can be easily generated. When a large number of such agglomerates of the target substance are generated, the carrying concentration of the measurement target molecule varies greatly within the application position of the solution of the measurement target molecule, so that the analysis accuracy is lowered or the analysis result is obtained. It is considered that it can be a factor that causes variation. In addition, in order to obtain sufficient spectral intensity (signal intensity) for identifying the measurement target molecule, the intensity of the laser beam used during analysis may be increased to ionize and desorb the measurement target molecule (substance to be analyzed). It is conceivable that when the laser intensity is increased, impurities and the like are likely to be ionized at the same time, so that the resolution and S / N (signal / noise) ratio are rather lowered, and highly accurate analysis cannot be performed. Problems can arise. In consideration of these points, the present inventors have conducted extensive research in order to obtain an analytical substrate capable of obtaining a higher signal intensity without such enhancement of the laser intensity. It is provided with an organic silica thin film made of organic silica having an organic group capable of absorbing the above, and a hydrophobic layer laminated on the surface of the organic silica thin film, and the hydrophobic layer is mainly composed of an aliphatic carbon skeleton. Laser desorption in which the layer is made of a hydrophobic material having a hydrophobic group as a skeleton and a functional group covalently bonded to the silica skeleton of the organic silica, and the thickness of the hydrophobic layer is 0.2 to 5.5 nm. An organic silica substrate for separation / ionization mass analysis has been found.

Here, when a conventional organic silica substrate for laser desorption / ionization mass spectrometry as described in Patent Document 1 is examined, the surface of the organic silica thin film has a hydroxyl group and is sometimes contained in the skeleton of the organic silica. Since there may be polar groups and the like derived from the organic groups, if the molecule to be measured (substance to be analyzed) has a group that easily interacts with the hydroxyl groups and polar groups on the surface of the organic silica thin film, Since the molecule to be measured can strongly interact and be adsorbed on the surface of the organic silica thin film, it is not always sufficient to efficiently perform desorption and ionization at a higher level depending on the type of the molecule to be measured. It is speculated that cases may occur. Considering this point, in recent years, laser desorption / ionized mass spectrometry has been applied to metabolomics, proteomics, pharmaceuticals, biopharmaceuticals, etc., and laser desorption / ionized mass spectrometry is used for drug discovery and disease diagnosis clinical practice. It is being applied to various fields such as research. In these fields, water-soluble molecules such as proteins, peptides and biomarkers are often measured. Then, when the case where such a water-soluble molecule (hydrophilic molecule) is used as the measurement target molecule is examined, the conventional organic silica substrate for laser desorption / ionization mass spectrometry as described in Patent Document 1 is organic. Since it is considered that the molecule to be measured can be more strongly adsorbed from the hydroxyl group on the surface of the silica thin film, desorption and ionization can be efficiently performed at a higher level as described above depending on the type of molecule to be measured. There may be cases where it is not always sufficient to do so. Therefore, the conventional organic silica substrate for laser desorption / ionization mass spectrometry as described in Patent Document 1 can be obtained when analyzing a molecule to be measured that can be strongly adsorbed on the surface of the organic silica thin film. It was not always sufficient in terms of making the signal intensity (peak intensity) of the molecule to be measured in the spectrum higher.

On the other hand, the organic silica substrate for laser desorption / ionization mass spectrometry of the present invention has an organic silica thin film composed of organic silica having an organic group capable of absorbing laser light as a skeleton and the surface of the organic silica thin film. It has a hydrophobic layer laminated on silica. Such a hydrophobic layer includes a polar group such as a hydroxyl group on the surface of the organic silica thin film and a functional group capable of covalently bonding with the silica skeleton of the organic silica in the hydrophobic material (for example, the hydrophobic material is the hydrophobic material. In the case of a metal alkoxide having a group, it is laminated on the surface of an organic silica thin film by reacting with a structural portion (alkoxide group) other than the hydrophobic group). Here, since such a hydrophobic material has a hydrophobic group as described above, the hydrophobic layer has a hydrophobicity derived from the hydrophobic group. Therefore, when mass spectrometry is performed using the organic silica substrate of the present invention, even if the molecule to be measured is a water-soluble molecule (hydrophilic molecule), the surface of the substrate is formed by the hydrophobic layer formed on the surface. The interaction between the above polar groups such as hydroxyl groups and water-soluble molecules can be sufficiently weakened. Therefore, when the molecule to be measured is supported on the organic silica substrate of the present invention, the molecule to be measured is weakly adsorbed on the surface of the substrate, and the molecule is more efficiently desorbed during mass spectrometry. It becomes possible. Further, as described above, even if the molecule to be measured (substance to be analyzed) is a water-soluble molecule (hydrophilic molecule), the adsorptive power of the water-soluble molecule on the surface of the substrate is reduced by the hydrophobic layer, so that the molecule to be measured is supported. At that time, the specific adsorption of the molecule to be measured on the surface of the substrate can be suppressed, and the concentration distribution of the molecule to be measured is generated due to the specific adsorption in the carrying region of the molecule to be measured (adsorption). The occurrence of unevenness) is suppressed more sufficiently. As described above, according to the hydrophobic layer, the specific adsorption of the measurement target molecule can be suppressed and the measurement target molecule can be supported more uniformly. Therefore, according to the present invention, a plurality of different measurement target molecules are supported in the support region. Even when mass analysis is performed on the measurement points of, it is possible to make the average value of the signal intensity of the measurement target molecule measured at each measurement point higher, and further, it is measured at each measurement point. The present inventors presume that the variation in the signal intensity of the measurement target molecule can be made smaller. Further, in the present invention, the organic silica thin film included in the organic silica substrate is made of organic silica having an organic group capable of absorbing laser light in its skeleton, and the energy of the laser light absorbed by the thin film is placed on the substrate. It is possible to ionize the (supported) molecule to be measured by efficiently moving it (such performance is hereinafter referred to as "LDI support performance" in some cases). In the present invention, the thickness of the hydrophobic layer is set to 0.2 from the viewpoint of sufficiently exerting such LDI support performance on the organic silica thin film and suppressing coating unevenness of the molecule (sample) to be measured. It is set to ~ 5.5 nm. When the thickness of the hydrophobic layer is made thicker than 5.5 nm, the energy transfer from the organic silica to the molecule to be measured may be hindered, which may lead to a decrease in analytical ability. Further, when the thickness of the hydrophobic layer is made thicker than 5.5 nm, the hydrophobicity of the hydrophobic layer becomes too high, and for example, the molecule to be measured (substance to be analyzed) is a water-soluble molecule (hydrophilic molecule). In this case, the application of the solution of the molecule to be measured may be uneven, and the concentration distribution of the molecule to be measured may occur in the carrying region. From this point of view, in order to suppress the inhibition of the LDI support performance of the organic silica thin film by the hydrophobic layer while exhibiting appropriate hydrophobicity in the hydrophobic layer so that the application of the solution of the molecule to be measured is not uneven. In addition, in the present invention, the thickness of the hydrophobic layer is set to 0.2 to 5.5 nm (in order to sufficiently prevent the transfer of energy from the organic silica to the molecule to be measured by the hydrophobic layer). It should be noted that the hydrophobic layer having such a thickness facilitates the desorption and ionization of the molecule to be measured from the surface of the substrate more efficiently while maintaining the light absorption ability of the organic silica and the energy transfer ability to the target substance. Even if the concentration of the molecule to be measured (substance to be analyzed) is low, more sensitive analysis is possible. As described above, in the present invention, the organic silica thin film made of organic silica having an organic group capable of absorbing laser light as described above in the skeleton and the hydrophobic layer laminated on the surface of the organic silica thin film are provided. Because it is provided, the interaction between the molecule to be measured (substance to be analyzed) and the surface of the organic silica thin film can be weakened, and smooth desorption / ionization of the substance to be analyzed can be promoted, so that it is more sensitive and more uniform. The present inventors presume that it is possible to carry out various analyzes.

According to the present invention, when used for mass spectrometry, the signal intensity of the molecule to be measured can be made higher in the obtained mass spectrum, and laser desorption that enables more sensitive analysis can be performed. It becomes possible to provide an organic silica substrate for / ionization mass spectrometry and a laser desorption / ionization mass spectrometry method using the same.

It is a schematic vertical sectional view schematically showing one preferable embodiment of the laminated body provided with an organic silica thin film (porous film). It is an enlarged view of the region R of the organic silica thin film shown in FIG. It is a schematic diagram schematically showing a preferred embodiment of a substrate provided with a hydrophobic layer and an organic silica thin film when the hydrophobic material is an alkoxysilane compound. 6 is a scanning electron microscope (SEM) photograph of the surface of the organic silica thin film formed in Example 5. It is a graph which shows the ultraviolet / visible absorption spectrum of the organic silica thin film obtained by using the compound represented by the following formula (A). It is a graph of the calibration curve obtained from the relationship between the sample (organic silica substrate) for measuring the calibration curve and the XPS data and the EDX data of the organic silica substrate obtained in Example 3 and Comparative Example 2. It is a graph of the mass spectrum (LDI-MS spectrum) obtained as a result of the mass spectrometry performed in Example 6 (mass spectrometry using the organic silica substrate obtained in Example 1). It is a graph of the mass spectrum (LDI-MS spectrum) obtained as a result of the mass spectrometry performed in Example 6 (mass spectrometry using the organic silica substrate obtained in Example 1). It is a graph of the mass spectrum (LDI-MS spectrum) obtained as a result of the mass spectrometry performed in Example 7 (mass spectrometry using the organic silica substrate obtained in Example 1). It is a graph of the mass spectrum (LDI-MS spectrum) obtained as a result of the mass spectrometry performed in Example 7 (mass spectrometry using the organic silica substrate obtained in Example 1). Mass spectrometry performed in Example 8 (mass spectrometry using the organic silica substrate obtained in Example 1) and mass spectrometry performed in Comparative Example 4 (mass spectrometry using the organic silica substrate obtained in Comparative Example 2) It is a graph of the mass spectrum (LDI-MS spectrum) obtained as a result of). It is a graph of the mass spectrum (LDI-MS spectrum) obtained as a result of the mass spectrometry performed in Example 9 (mass spectrometry using the organic silica substrate obtained in Example 2). Spectral intensity (signal intensity) of 25 measurement sites in a 1 mm square region obtained by mass spectrometry performed in Example 14 (first mass spectrometry using the organic silica substrate obtained in Example 5). ) Is a drawing showing a two-dimensional distribution (intensity distribution) (a drawing showing the relationship between 25 measurement sites and the signal intensity of each measurement site). 6 is a graph of a mass spectrum (LDI-MS spectrum) obtained as a result of the second mass spectrometry performed in Example 14 with a laser intensity of 8%. 6 is a graph of a mass spectrum (LDI-MS spectrum) obtained as a result of the second mass spectrometry performed in Example 14 with a laser intensity of 8%.

Hereinafter, the present invention will be described in detail according to the preferred embodiment thereof.

[Organic silica substrate for laser desorption / ionization mass spectrometry]
The organic silica substrate for laser desorption / ionization mass analysis of the present invention comprises an organic silica thin film composed of organic silica having an organic group capable of absorbing laser light as a skeleton, and a hydrophobic layer laminated on the surface of the organic silica thin film. A layer is provided, and the hydrophobic layer is a layer made of a hydrophobic material having an aliphatic carbon skeleton as a main skeleton and a functional group covalently bonded to the silica skeleton of the organic silica. The hydrophobic layer is characterized in that the thickness is 0.2 to 5.5 nm.

(Organic silica thin film)
The organic silica thin film according to the present invention is a thin film made of organic silica having an organic group capable of absorbing laser light in its skeleton. As described above, the organic silica constituting the thin film has an organic group capable of absorbing laser light in its skeleton. Here, "capable of absorbing laser light" is not particularly limited to the absorption wavelength or the like, and may be any as long as it can absorb light of any wavelength. Further, in the present invention, the "organic group capable of absorbing laser light" is an organic group having an absorption maximum wavelength in the wavelength range of 200 to 600 nm (more preferably 250 to 450 nm, particularly preferably 300 to 400 nm). preferable. When the absorption maximum wavelength of such an organic group is less than the above lower limit, when it is used for the laser desorption / ionization method (LDI), when the laser light of such a wavelength is absorbed, the object to be measured (the molecule to be measured). At the same time, the organic groups in the organic silica thin film are decomposed by the light, and as a result, it tends to be difficult to perform mass spectrometry efficiently. On the other hand, when the upper limit is exceeded, light having such a wavelength is emitted. Even if it is irradiated to absorb light, it tends to be difficult to obtain the light energy required for ionizing the measurement target molecule. As described above, when the organic group has an absorption maximum wavelength in the above wavelength range, it is possible to more efficiently absorb the laser light in the wavelength range used for mass spectrometry.

Further, examples of the "organic group capable of absorbing laser light" contained in the skeleton of the organic silica thin film include an organic group having a structural portion capable of absorbing laser light used in mass spectrometry. Be done. Such an organic group includes an organic group having an aromatic ring as a structural part capable of absorbing the laser light (for example, triphenylamine, naphthalimide, fluorene, acrydone), although it depends on the wavelength of the laser light used. , Methylacridone, quaterphenyl, anthracene, etc.). As described above, the organic groups capable of absorbing the laser beam (organic groups having an absorption maximum wavelength in the wavelength range of 200 to 600 nm) may have, for example, substituents, triphenylamine and na. Examples thereof include phthalimide, styrylbenzene, fluorene, divinylbenzene, divinylpyridine, acridone, methylacridone, quaterphenyl, anthracene and the like.

Further, the organic group capable of absorbing such laser light (preferably an organic group having an absorption maximum wavelength in the wavelength range of 200 to 600 nm) is more preferably an aromatic organic group containing 10 or more carbons. preferable. According to such an aromatic organic group, it becomes possible to absorb the laser light more efficiently. Examples of such aromatic organic groups include triphenylamine, naphthalimide, styrylbenzene, fluorene, acridone, methylacridone, quaterphenyl, anthracene, pyrene, and acrydin, which may have substituents, respectively. , Phenylpyridine, perylene, perylenebisimide, diphenylpyrene, tetraphenylpyrene, porphyrin, phthalocyanine, diketopyrrolopyrrole, dithienylbenzothiazol and the like. Further, the organic silica thin film may have one type of organic group alone as an organic group, or may have a combination of a plurality of types of organic groups. Among such organic groups, from the viewpoint of chemical stability against light irradiation, at least one of triphenylamine, naphthalimide, pyrene, perylene, and aclidene is contained (at least one of the organic groups). Is at least one of triphenylamine, naphthalimide, pyrene, perylene, and acrydone).

Further, in the organic silica thin film, "having an organic group in the skeleton" means that the organic is directly or indirectly (via other elements) bonded to silicon (Si) forming the silica skeleton of the silica thin film. It means that the group exists. In addition, such an organic silica thin film has a skeleton due to having a structure (crosslinked structure) in which silicon atoms forming a siloxane structure (formula: − (Si—O) _y− structure) are crosslinked by an organic group. It is more preferable that an organic group is introduced into the silicon.

Further, in the organic silica thin film, the content ratio of silicon constituting the organic silica and the organic group capable of absorbing the laser light is the ratio of the mass of silicon to the mass of the organic group ([mass of silicon] / [organic]. Group mass]) of 0.05 to 0.50 (more preferably 0.10 to 0.40, still more preferably 0.10 to 0.35, particularly preferably 0.15 to 0.35). It is preferably in the range. If such a mass ratio ([mass of silicon] / [mass of organic group]) is less than the lower limit, the crosslink density of the organic silica thin film tends to be low, and the film tends not to be sufficiently cured, while exceeding the upper limit. In addition, the absorption intensity of laser light tends to decrease due to the relative decrease in the density of organic groups, and further, when a film having an uneven structure (for example, a porous structure) is to be produced, the film is formed. The degree of cross-linking tends to increase excessively at the stage, and it tends to be difficult to form an uneven structure by nanoimprinting. The organic silica thin film having such a mass ratio has an organic group having a maximum absorption wavelength in the range of 200 to 600 nm as an organic group capable of absorbing laser light, and the content ratio of silicon and the organic group is as described above. 0.05 to 0.50 (more preferably 0.10 to 0.40, still more preferably 0) based on the ratio of the mass of silicon to the mass of organic groups ([mass of silicon] / [mass of organic groups]). A thin film made of a polymer (condensation) of an organic silicon compound in the range of 10.10 to 0.35, particularly preferably 0.15 to 0.35) can be preferably used.

Examples of such an organosilicon compound include the following general formulas (1-i) to (1-iv):

[In the formulas (1-i) to (1-iv), X represents an m-valent organic group, and R ¹ is an alkoxy group (preferably an alkoxy group having 1 to 5 carbon atoms) and a hydroxyl group (-OH). , Allyl group (CH ₂ = CH-CH _2- ), ester group (preferably ester group having 1 to 5 carbon atoms) and halogen atom (chlorine atom, fluorine atom, bromine atom, iodine atom) selected from the group. R ² indicates at least one selected from the group consisting of an alkyl group and a hydrogen atom, and n and (3-n) are R ¹ bonded to a silicon atom (Si), respectively. And R ² , where n represents an integer of 1-3, m represents an integer of 1-4, and L in formula (1-iv) is a single bond or ether group, ester group, amino group, It represents any one divalent organic group selected from the group consisting of an amide group and a urethane group, and Y in the formula (1-iv) represents an alkylene group having 1 to 4 carbon atoms. ]
The content ratio of silicon and the organic group capable of absorbing light is the ratio of the mass of silicon to the mass of the organic group capable of absorbing laser light ([mass of silicon] / [mass of organic group]). An organosilicon compound in the range of 0.05 to 0.50 is preferable. Regarding the "organic group capable of absorbing laser light" in the compounds represented by the general formulas (1-i) to (1-iv), the compound represented by the general formula (1-i). In the above formula, the group represented by X (m-valent organic group (bonding hand is omitted)) becomes the “organic group capable of absorbing laser light” and is represented by the general formula (1-ii). In the compound, the formula:

[In the formula (I), X represents an organic group having an m valence, and m represents an integer of 1 to 4 (thus, X and m are in the general formulas (1-i) to (1-iv). Is synonymous with X and m). ]
The organic group represented by is an "organic group capable of absorbing laser light", and in the compound represented by the general formula (1-iii), the formula:

[In formula (II), X represents an organic group having an m valence, and m represents an integer of 1 to 4 (thus, X and m are in the general formulas (1-i) to (1-iv). Is synonymous with X and m). ]
The organic group represented by the above becomes an "organic group capable of absorbing laser light", and in the compound represented by the general formula (1-iv), the formula:
X- (LY) _m- (III)
[In formula (III), X represents an m-valent organic group, and L is a divalent of any one selected from the group consisting of a single bond or an ether group, an ester group, an amino group, an amide group and a urethane group. Indicates an organic group of, Y represents an alkylene group having 1 to 4 carbon atoms, and m represents an integer of 1 to 4 (thus, X, L, Y and m are in the general formula (1-iv). X, L, Y and m). ]
The organic group represented by is an "organic group capable of absorbing laser light". As described above, the organic group of the structural portion containing the group represented by X in the formula, which is a group bonded to silicon in the compound, becomes an "organic group capable of absorbing laser light".

The organic silica thin film is represented by the above general formulas (1-i) to (1-iv), and the content ratio of silicon and an organic group capable of absorbing light is the organic group capable of absorbing the light. A group consisting of organosilicon compounds in the range of 0.05 to 0.50 based on the ratio of the mass of silicon to the mass ([mass of silicon] / [mass of organic group]) (hereinafter, composed of the organosilicon compound). For convenience, the group is preferably an organic silica thin film composed of a polymer of at least one organosilicon compound selected from (sometimes simply referred to as “compound group (A)”). As described above, as the organic silica thin film, an organic silica thin film made of a polymer of one kind of organosilicon compound selected from the compound group (A) is preferable.

According to the organic silica thin film composed of a polymer of at least one organosilicon compound selected from the compound group (A), the so-called light collecting antenna function tends to be exhibited more efficiently. This tends to make it possible to ionize the molecule to be measured more efficiently. The "light collection antenna function" referred to here is a function of absorbing light energy when irradiated with light and concentrating the excited energy inside the pores, and if such a function is used, it is absorbed. There is a tendency that the light energy of the generated laser light can be efficiently transferred by the measurement target molecule carried inside the pores. The definition of such a "light collecting antenna function" is the same as the definition described in Japanese Patent Application Laid-Open No. 2008-084836.

Further, the polymer of at least one organosilicon compound selected from the compound group (A) forms a siloxane structure (formula: structure represented by − (Si—O) _y− ). The silicon atoms have a structure (crosslinked structure) in which the silicon atoms are crosslinked by an organic group, whereby the structure has the organic group in the skeleton (a so-called “crosslinked organic silica thin film”). Here, the crosslinked structure will be described by taking as an example a polymerization reaction of an organosilicon compound represented by the above general formula (1-i) and in which R ¹ is an ethoxy group, n is 3 and m is 2. The following general formula (2):

[In the formula, X represents an m-valent organic group and p represents an integer corresponding to the number of repeating units. ]
The organic silica thin film obtained after polymerization by the reaction represented by is crosslinked with silicon atoms forming a siloxane structure (formula: structure represented by − (Si—O) _y− ) by the organic group (X). It has a repeating unit of the above-mentioned structure (the number of ps is not particularly limited, but is generally preferably in the range of about 10 to 1000). When such a crosslinked structure is formed (when the organic silica thin film becomes the crosslinked organic silica thin film), when this is used for mass spectrometry, the irradiation laser light is absorbed more efficiently and organic. The excitation energy tends to be transferred more efficiently to the molecule to be measured carried in the pores of the silica thin film. The organic silica composed of the polymer having the repeating unit represented by the general formula (2) is the ratio of the total amount (mass) of the organic groups (X) to the total amount (mass) of Si in the organic silica. [Silicon mass] / [Organic group mass]) is preferably a value in the range of 0.05 to 0.50.

As the R ¹ in the general formula (1-i) ~ (1 -iv), an alkoxy group and / or hydroxyl group is preferred from the viewpoint of easy control of the condensation reaction (polymerization reaction). In the case where there are a plurality of R ¹ in the same molecule, R ¹ may be the same or different. As the alkyl group that can be selected as R ² in such general formulas (1-i) to (1-iv), an alkyl group having 1 to 5 carbon atoms is preferable. In the case where there are a plurality of R ² in the same molecule, R ² may be the same or different.

In the above general formulas (1-i) to (1-iv), n and (3-n) in the formula indicate the number of R ¹ and R ² bonded to the silicon atom (Si), respectively. Here, n represents an integer of 1 to 3, but it is particularly preferable that n is 3 from the viewpoint that the structure after condensation can be made more stable.

Further, m in the general formulas (1-i) to (1-iv) indicates the number of silicon atoms (Si) directly or indirectly bonded to the organic group (X). Such m represents an integer of 1 to 4. Such m is more preferably 2 to 4 (particularly preferably 2 to 3) from the viewpoint of easily forming a stable siloxane network.

Further, as L in the formula (1-iv), a single bond or an ether group is more preferable from the viewpoint of ensuring high chemical stability. When a plurality of Ls are present in the same molecule, the Ls may be the same or different. Further, the Y in the formula (1-iv) is more preferably an ethylene group or a propylene group from the viewpoint of achieving both high density of silicon after polymerization and flexibility of the film. When a plurality of Ys are present in the same molecule, the Ys may be the same or different.

Further, X in the above general formulas (1-i) to (1-iv) represents an m-valent organic group. Further, among such m-valent organic groups, the following general formulas (101) to (112):

[In the general formulas (101) to (112), the symbol * indicates that the connecting hand with the symbol is a joining hand that binds to X in the above formulas (1-i) to (1-iv). Shown. ]
The organic group represented by is particularly preferable. In the organic groups represented by the general formulas (101) to (112), the bond represented by the symbol * is directly bonded to silicon from the viewpoint of increasing the density and stable immobilization of the organic group. Is more preferable.

Among such organic groups (X in the formulas (1-i) to (1-iv)), the organic groups represented by the general formulas (101) to (110) (the above formulas (101), (102). ), (103), (104), (105), (106), (107), (108), (109) and (110) are more preferable. Any of the organic groups represented by the general formulas (101) to (106) and (109) is more preferable, and the organic group (triphenylamine) represented by the general formula (101) and the above general formula ( Any of the organic groups represented by 102) to (103) (organic groups containing a naphthalimide ring in the structure) is particularly preferable.

The "organic group capable of absorbing laser light" contained in the organic silica thin film is an organic group containing a naphthalimide ring in its structure from the viewpoint of the ability to absorb laser light having a wavelength of 300 to 400 nm and high chemical stability. It is particularly preferable that it is a group.

Further, the organic silica thin film made of organic silica having an organic group capable of absorbing such laser light in its skeleton may contain one kind of organic group alone, or two or more kinds of organic groups. It may contain a combination of organic groups. As the organic silica thin film containing two or more kinds of organic groups in combination, a plurality of kinds represented by any of the above general formulas (1-i) to (1-iv) and different in the kind of X. Examples thereof include polymers of organosilicon compounds.

The polymer of at least one organosilicon compound selected from the above-mentioned compound group (A) has a range in which the effect of the present invention is not impaired (for example, the thin film itself has a mass of silicon relative to the mass of an organic group). The organosilicon compound for which the polymer is prepared may contain other organosilicon compounds other than those selected from the above-mentioned compound group (A) within the range that satisfies the conditions such as the ratio). Examples of such other organosilicon compounds include tetraalkoxysilanes such as tetramethoxysilane, tetraethoxysilane, and tetrabutoxysilane.

Further, as such an organic silica thin film, it is more preferable that the thin film has an uneven structure because the adsorption amount of the molecule to be analyzed increases as the surface area increases. Such an uneven structure is preferably a porous structure in which pores composed of columnar voids are formed, or a pillar array structure in which columnar bodies are arranged. The "columnar" referred to here has a size (diameter, length, etc.) at both ends, such as a substantially conical shape or a substantially polygonal pyramid, in addition to a so-called columnar shape such as a substantially cylindrical cylinder or a substantially polygonal prism. It is a concept that includes those with different shapes. Such an uneven structure can be efficiently manufactured by nanoimprint. For example, when the mold used for nanoimprint has a pillar array structure, the porous structure to which the characteristics of the structure are transferred can be the uneven structure of the thin film, and conversely, the mold used for nanoimprint is columnar. When it has a porous structure in which pores composed of voids are formed, the pillar array structure to which the characteristics of the structure are transferred can be used as the uneven structure of the thin film. Further, when forming a concavo-convex structure by nanoimprint (when forming a concavo-convex structure which is a nanoimprint transfer structure), even if a mold having the concavo-convex structure is used and the characteristics are repeatedly transferred and inverted to form the concavo-convex structure. Good.

Further, as such a concavo-convex structure, the axial direction of the concavo-convex structure is substantially perpendicular to the surface of the surface opposite to the surface on which the concavo-convex structure of the organic silica thin film is formed. Is preferable. This point will be briefly described with reference to the drawings. FIG. 1 is a schematic vertical sectional view schematically showing a preferred embodiment of a structure (multilayer structure: laminated body) including the organic silica thin film. The laminate (multilayer structure) shown in FIG. 1 includes a base material 1 and an organic silica thin film 2 (note that such a base material 1 will be described later).

Here, "the axial direction of the concavo-convex structure is substantially perpendicular to the surface of the surface opposite to the surface on which the concavo-convex structure of the organic silica thin film is formed" means, for example, the organic silica thin film 2. When the void portion (recess space) of the uneven portion of the above is a columnar pore (when the organic silica thin film 2 has a porous structure), the direction of the major axis of the space shape (void portion shape) of the pore is refers that it is substantially perpendicular to the opposite surface S ₂ of the surface to the surface S ₁ on the side where the uneven structure of the organic silica film 2 is formed, also, the unevenness of the organic silica film 2 When the convex portion is a columnar body (pillar shape) (when the organic silica thin film 2 has a pillar array structure), the concave-convex structure of the organic silica thin film 2 is formed in the direction of the long axis of the columnar body (pillar shape). the surface S ₁ on the side are means that are substantially perpendicular to the opposite surface S ₂ of the surface. As described above, the "axial direction of the concavo-convex structure" refers to the direction of the long axis of the pores when the concavo-convex structure is a porous structure, and when the concavo-convex structure is a pillar array structure, the columnar body (pillar). The direction of the long axis. Further, the "long axis" referred to here refers to the shape of the voids of the pores or the axis in the longitudinal direction passing through the center of gravity of the columnar body, and can be obtained based on the vertical cross-sectional view of the columnar body.

Here, the concept of "substantially vertical" will be described with reference to FIG. FIG. 2 is an enlarged view of the region R shown in FIG. Here, an example is taken when the voids (spaces of the recesses) of the uneven portions shown in FIGS. 1 and 2 are columnar pores (when a porous structure in which the recesses are columnar pores is formed). to illustrate, the axial direction of the relief structure is to be in a direction substantially perpendicular to the surface of the surface S _2, the surface S ₁ of the uneven structure of the organic silica film 2 is formed opposite to the surface S ₂ of The angle α formed by the major axis C (major axis C of the pores) of the spatial shape of the pores (columnar shape of the voids) with respect to the surface is 90 ° ± 30 ° (more preferably 90 ° ± 20 °). It means that it is in the range of. Incidentally, the columnar body protrusion even if a (pillared) (when the organic silica film 2 has a pillar array structure), the axial direction of the uneven structure is in a direction substantially perpendicular to the surface of the surface S ₂ , to the opposite surface S ₂ of the surface to the surface S ₁ of the uneven structure of the organic silica film 2 is formed, the angle of the major axis forms such columnar body (pillar-shaped) is 90 ° ± 30 ° It means that it is in the range (more preferably 90 ° ± 20 °).

Thus, uneven structure is formed on the organic silica film 2, the axial direction of the relief structure substantially perpendicular to the surface of the surface S ₂ of the organic silica film 2 (90 ° ± 30 °, more preferably is 90 ° ± 20 °) is preferably in the (angle formed substantially perpendicular (90 ° ± 30 ° between the axial and the organic silica film 2 surface S ₂ of the surface of the uneven structure, and more preferably 90 ° ± It is preferable that the direction is 20 °)). When the axial direction of the concavo-convex structure formed on the organic silica thin film 2 is not in the above direction, even if laser light is irradiated when used for mass spectrometry, the concavo-convex void portion (in the case of pores) The molecules adsorbed in the pore space tend to be difficult to desorb and vaporize out of the film. In the case of the laminate shown in FIG. 1 (multilayer structure), the surface of the surface S ₂ of the organic silica film 2 is a plane, an organic silica film 2 is laminated on the base material 1, and group It is a surface facing the surface of the material 1. Moreover, in this way whether the axial direction of the uneven structure is in a direction substantially perpendicular to the surface of the surface S ₂ of the organic silica film 2 determination is performed as follows. That is, the cross section of the organic silica thin film is obtained by atomic force microscope (AFM) measurement, and the axial directions of arbitrary 100 or more concavo-convex structures are measured, respectively, and the concavo-convex structure is formed in the axial direction of each concavo-convex structure. When the surface is substantially perpendicular to the surface of the surface opposite to the surface (90 ° ± 30 °, more preferably 90 ° ± 20 °), the axial direction of the concave-convex structure is the concave-convex structure of the organic silica thin film. It can be judged that the direction is substantially perpendicular to the surface of the surface opposite to the surface on which the is formed.

Further, such an organic silica thin film is composed of a porous film having a concavo-convex structure in which concave portions are formed by columnar pores, or a pillar array in which convex portions are formed by columnar bodies and the columnar bodies are arranged. It is preferably a thin film having an uneven structure. That is, such an uneven structure is an uneven structure in which the concave portions are formed by columnar pores, or an uneven structure composed of a pillar array in which the convex portions are formed by columnar bodies and the columnar bodies are arranged. It is preferably a structure.

In the uneven structure of such an organic silica thin film, the average value of the distances between the wall surfaces of the convex portions is preferably 5 to 500 nm, more preferably 5 to 200 nm, and further preferably 5 to 100 nm. preferable. If the average value of the distances between the wall surfaces of such convex portions is less than the lower limit, it tends to be difficult to introduce and adsorb molecules having a large molecular weight into the irregular gaps (pore spaces in the case of pores). On the other hand, if the upper limit is exceeded, the effect of increasing the surface area due to the formation of the uneven structure tends not to be sufficiently obtained. The average value of the distances between the wall surfaces of such convex portions is obtained by measuring the uneven structure using an interatomic force microscope (AFM) and obtaining a cross-sectional view (longitudinal cross-sectional view) of the uneven structure. Based on the above, for any 100 or more convex portions, the height of the convex portion is half the average height of the convex portion described later (note that the convex portion used for measuring the distance between the wall surfaces). The height position is determined for each convex portion in the lowest point of the concave portion between the convex portion and the closest convex portion as a reference for height (height is 0 nm). It can be obtained by obtaining the distance between the wall surfaces (distance in the horizontal direction) between the convex portion and the closest convex portion and calculating the average thereof. The distance between the wall surfaces (horizontal distance) between the closest convex portions at the position where the height of the convex portion is half the average height of the convex portion described later is regarded as the distance between the convex portions. As a result, even if the convex portion has the shape of a columnar body having different sizes (diameter, length, etc.) at both ends, the distance between the columnar bodies can be measured, whereby, for example, in a concave portion. It is also possible to appropriately study the design according to the type of the molecule to be measured to be introduced. That is, the distance between the wall surfaces between the convex portions can be used as an index of the size of the gap portion of the concave portion. The distance between the wall surfaces of such a convex portion can be regarded as the diameter of the pores when the concave portion has a concavo-convex structure formed by columnar pores. From this point of view, when the concave portion has a concavo-convex structure formed by columnar pores, the average pore diameter of the pores is 5 to 500 nm (more preferably 5 to 200 nm, still more preferably 5 to 5). It can be said that it is preferably 100 nm), and similarly, in the case of a concavo-convex structure composed of pillar arrays in which the convex portions are formed of columnar bodies and the columnar bodies are arranged, the distance between the wall surfaces of the convex portions (between pillars). It can be said that the average value of (distance) is preferably 5 to 500 nm (more preferably 5 to 200 nm, still more preferably 5 to 100 nm).

Further, in the uneven structure of such an organic silica thin film, the average height of the convex portion (average depth of the concave portion) is preferably equal to or more than the average value of the distance between the wall surfaces of the convex portion, and is 20 to 1500 nm. It is more preferable that the thickness is 50 to 500 nm. It is more preferable that the average height of the convex portion (average depth of the concave portion) is in the same range as the thickness T of the film described later. If the average height of such convex portions (average depth of concave portions) is less than the lower limit, the effect of increasing the surface area due to the formation of the concave-convex structure tends not to be sufficiently obtained, while if it exceeds the upper limit, the organic silica thin film tends to be thin. Even if laser light is applied when using the above for mass spectrometry, it is difficult to desorb and vaporize the molecules adsorbed in the deep part of the void (in the case of pores, in the pore space) to the outside of the film. It tends to be. The average height of the convex portion (average depth of the concave portion) referred to here is obtained by measuring the uneven structure using an atomic force microscope (AFM) and obtaining a cross-sectional view (vertical cross-sectional view) of the concave-convex structure. Based on the cross-sectional view, the difference in height between the lowest point (the lowest point of the concave portion) and the apex of the convex portion (the lowest point of the concave portion) among the adjacent concave portions with respect to any 100 or more convex portions. It can be calculated by calculating the distance in the vertical direction) and calculating the average.

Further, as such an uneven structure, the average pitch of the unevenness is preferably 20 to 1000 nm, more preferably 20 to 500 nm, and further preferably 20 to 200 nm. If the average pitch of such irregularities is less than the lower limit, it tends to be difficult to manufacture an uneven structure having a high aspect ratio, while if it exceeds the upper limit, the effect of increasing the surface area by forming the uneven structure cannot be sufficiently obtained. There is a tendency. As such an average pitch, the concavo-convex structure is measured using an atomic force microscope (AFM), a cross-sectional view (longitudinal cross-sectional view) of the concavo-convex structure is obtained, and any 100 points or more are obtained based on the cross-sectional view. Between the convex part and the closest convex part, the apex of the convex part (the cross-sectional shape of the convex part is approximately rectangular, etc., and the upper part of the convex part is a straight line including the apex of the convex part). (For example, when the convex part is columnar and the upper part is flat), the horizontal distance between the two (the center point of the upper part) is measured, and the value obtained as the average of each measured value is calculated. adopt.

When the concavo-convex structure of such an organic silica thin film is a concavo-convex structure composed of a pillar array in which the convex portions are formed of columnar bodies and the columnar bodies are arranged, the average length of the minor axis of the columnar bodies is It is preferably 10 to 500 nm, more preferably 10 to 200 nm, and even more preferably 10 to 150 nm. If the average length of such a minor axis is less than the lower limit, it tends to be difficult to manufacture a concavo-convex structure having a high aspect ratio, while if it exceeds the upper limit, the effect of increasing the surface area by forming the concavo-convex structure is sufficiently obtained. It tends not to be. The length of the minor axis of such a columnar body is determined by measuring the uneven structure using an atomic force microscope (AFM), obtaining a cross-sectional view (longitudinal cross-sectional view) of the uneven structure, and based on the cross-sectional view. It can be obtained by obtaining the length of the minor axis of an arbitrary 100 or more columnar bodies and calculating the average thereof. The minor axis of the columnar body referred to here means an axis that passes through the center of gravity of the columnar body and is perpendicular to the major axis, and can be obtained based on a vertical cross-sectional view of the columnar body.

The thickness T of such an organic silica thin film is preferably 20 to 2000 nm, more preferably 50 to 1000 nm, and even more preferably 100 to 500 nm. If such a thickness is less than the lower limit, the laser beam cannot be sufficiently absorbed when used as a substrate for mass spectrometry, and the efficiency of desorption and ionization of the molecule to be measured tends to decrease. When the upper limit is exceeded, the proportion of the membrane that is not involved in the analysis increases (the region that is not involved in the analysis increases in the membrane), and the cost tends to increase, and the adhesion to the substrate tends to decrease.

Further, such an organic silica thin film may be used as a form such as a laminated body laminated on another base material, as shown in FIGS. 1 and 2, for example. Such a base material 1 may be any one capable of supporting an organic silica thin film, and is not particularly limited as long as it is a known base material (for example, a known base material that can be used in producing a silica film). Silicon base material (Si base material), ITO base material, FTO base material, quartz base material, glass base material, various metal base materials, various thin films, etc.) can be appropriately used. Among them, laser desorption / ionization mass spectrometry A conductive substrate is preferable because it can be used more favorably. Such a conductive substrate is not particularly limited, but for example, a stainless steel, a silicon base material, a base material made of an ITO film, a base material made of a ZnO film, a base material made of a SnO ₂ film, and an FTO. A base material made of a film or the like can be used. The form of such a base material 1 is not particularly limited, but a flat plate shape is preferable.

The method for producing such an organic silica thin film is not particularly limited, and a known method can be appropriately used. For example, the organosilicon compound having an organic group capable of absorbing laser light (more preferably, the above-mentioned). A sol solution obtained by partially polymerizing (one type of organosilicon compound selected from the compound group (A)) is used to form a coating film of the sol solution on the substrate, and then The method (I) for obtaining an organic silica thin film by curing this may be preferably used. In the case where the method (I) is adopted, for example, after forming a coating film using the sol solution, a concave-convex structure is formed on the coating film by nanoimprint before curing, and then the coating film is cured. It is also possible to obtain a porous film (organic silica thin film) having an uneven structure. Hereinafter, such a method (I) will be briefly described.

The sol solution (colloidal solution) used in such method (I) is obtained by partially polymerizing the organosilicon compound having an organic group capable of absorbing the laser beam. Such a sol solution is a so-called sol in the field of producing a silica structure, except that the organosilicon compound (more preferably one organosilicon compound selected from the compound group (A)) is used. -It can be appropriately formed by adopting a known method known as a gel method. It is preferable that such a sol solution is a solution containing a partial polymer obtained by partially hydrolyzing and condensing the organosilicon compound. The solvent used for such a solution is not particularly limited, and a known solvent used in the so-called sol-gel method can be appropriately used. For example, methanol, ethanol, methoxyethanol, 1-propanol, isopropanol, acetone, and tetrahydrofuran can be used. , N, N-Dimethylformamide, 1,4-dioxane, acetonitrile and other organic solvents. Among such solvents, methoxyethanol, 1-propanol, isopropanol, 1,4-dioxane and tetrahydrofuran are preferable from the viewpoint of volatility near room temperature and high solubility of organic compounds.

Further, when preparing such a sol solution, the conditions (temperature and reaction time) for partially polymerizing the organosilicon compound are not particularly limited, and for example, depending on the type of the organosilicon compound used. The reaction temperature may be about 0 to 100 ° C., and the reaction time may be about 5 minutes to 24 hours. Further, from the viewpoint of efficiently advancing such partial polymerization, it is preferable to use an acid catalyst. Examples of such an acid catalyst include mineral acids such as hydrochloric acid, nitric acid, and sulfuric acid.

As a method for preparing such a sol solution, for example, a solution containing the organic silicon compound, the solvent, and the acid catalyst is prepared, and the solution is prepared at room temperature (20 to 28 ° C, preferably 25 ° C). A method may be adopted in which the organic silicon compound is partially polymerized (partially hydrolyzed and partially polycondensed) to prepare a sol solution by stirring the mixture for about 0.5 to 12 hours. In the case of stirring and reacting in this way, if the stirring time is less than the lower limit, the hydrolysis reaction of the silyl group becomes insufficient, and the curing reaction of the film after film formation tends to be difficult to proceed.

In the sol solution, if it is possible to satisfy the above-mentioned conditions for the finally obtained organosilica thin film, an organosilicon compound other than the organosilicon compound (for example, tetramethoxysilane, etc.) (Tetraalkoxysilane such as tetraethoxysilane and tetrabutoxysilane) may be further contained.

Further, as the sol solution, the content of the organosilicon compound in the solvent is preferably 0.2 to 20% by mass, more preferably 0.5 to 7% by mass. If the content of such an organosilicon compound is less than the lower limit, it tends to be difficult to produce a uniform film while controlling the thickness, while if it exceeds the upper limit, the reaction can be controlled in the sol solution. It becomes difficult, and it tends to be difficult to prepare a stable sol solution.

Further, as such a sol solution, the content of the organosilicon compound in the solvent is preferably 2 to 200 g / L, and more preferably 5 to 150 g / L. If the content of such an organosilicon compound is less than the lower limit, it tends to be difficult to produce a uniform film while controlling the thickness, while if it exceeds the upper limit, the reaction can be controlled in the sol solution. It becomes difficult, and it tends to be difficult to prepare a stable sol solution.

Further, such a sol solution is formed by partially polymerizing the organosilicon compound, and then filtered through a membrane filter or the like from the viewpoint of preventing contamination during production and ensuring higher smoothness, and then forming a film. It is preferable to use it for.

The method for forming the coating film obtained from the above sol solution is not particularly limited, and a method of casting the sol solution into a mold or a method of applying the sol solution to the substrate by various coating methods is preferably adopted. Further, as such a coating method, a known method (for example, a method of applying using a bar coater, a roll coater, a gravure coater, etc., a method of dip coating, spin coating, spray coating, etc.) may be appropriately adopted. it can.

The thickness of the film (uncured or semi-cured) obtained from such a sol solution is preferably 0.1 to 100 μm, more preferably 0.1 to 25 μm. If the thickness of the film is less than the lower limit, it tends to be difficult to keep the thickness of the film uniform on the entire surface of the substrate. It is in.

Further, as a method for curing such a coating film, conditions may be appropriately adopted such that the hydrolysis and condensation reactions proceed according to the type of the organosilicon compound used, and the temperature, heating time and the like may be appropriately adopted. Is not particularly limited, but it is preferable to heat the compound at a temperature of about 25 to 150 ° C. for about 1 to 48 hours. By heating in this way, the hydrolysis and condensation reaction of the organosilicon compound and / or the partial polymer of the organosilicon compound can be further promoted, whereby the coating film obtained from the sol solution can be further promoted. It can be cured to form the organosilica thin film. In such a curing step, in order to promote the hydrolysis of the residual alkoxy group and the curing of the thin film more efficiently, the coating film is heated in the above temperature range (25 to 150 ° C.) for 1 to 1 It is preferable to expose to the vapor of hydrochloric acid for about 48 hours. Such exposure to hydrochloric acid vapor makes it possible to promote the reaction not only on the surface of the coating film but also inside the coating film, and it is possible to promote the hydrolysis of residual alkoxy groups and the curing of the thin film more efficiently. It is also possible to expose the hydroxyl groups on the surface of the obtained thin film.

In such a method (I), as described above, after forming a coating film using the sol solution, a concave-convex structure is formed on the coating film by nanoimprint before curing, and then curing is performed. It is also possible to obtain a porous film (organic silica thin film) having an uneven structure by squeezing.

When the nanoimprint step (step of forming a concavo-convex structure by nanoimprint and curing) in such a method (I) is adopted, the influence of structural shrinkage due to solvent evaporation is minimized in the nanoimprint step. , The film obtained from the sol solution is a film from which the solvent has been removed (even if the film has been subjected to a treatment for removing the solvent, the solvent is volatilized (removed) in the coating step using a volatile solvent. It may be a film obtained by the above method). In the coating film obtained from such a sol solution, depending on the type of solvent in the sol solution, the solvent may almost evaporate (volatilize) in the step of forming the film (coating step, etc.). In such a case, it is possible to minimize the influence of structural shrinkage due to evaporation (volatilization) of the solvent without performing a treatment for removing the solvent. Further, for the "nanoimprint" referred to here, a known technique known as a so-called nanoimprint method can be appropriately adopted, and a mold (nanostructure) in which a fine uneven pattern is formed is used, and the pattern of the mold is used. It is possible to appropriately adopt a method of transferring (nanoimprint method).

As the mold used for such nanoimprint, a mold that can be used for a known nanoimprint method can be appropriately used, and a commercially available product may be used. Further, as such a mold (nanostructure), any one having a desired concavo-convex structure such as a nanostructure in which a fine concavo-convex pattern is formed can be appropriately used.

In the mold used for such nanoimprint, the axial direction of the uneven structure of the formed organic silica thin film is substantially perpendicular to the surface of the surface opposite to the surface on which the uneven structure of the organic silica thin film is formed. It is preferable that the structure has an uneven structure so as to be oriented. By using such a mold, the characteristics of the unevenness of the mold are transferred, and the axial direction of the uneven structure is a direction substantially perpendicular to the surface of the surface opposite to the surface on which the uneven structure of the thin film is formed. Therefore, it is possible to efficiently manufacture an organic silica thin film having an uneven structure. For example, when a flat plate having a concavo-convex structure is used as a mold, the concavo-convex structure of the mold is applied to the surface of a surface whose axial direction of the concavo-convex structure is opposite to the surface on which the concavo-convex structure is formed. By assuming that the directions are substantially vertical, when the uneven pattern of the mold is transferred, the axial direction of the uneven structure formed on the organic silica thin film is more efficiently set on the organic silica thin film. The direction can be substantially perpendicular to the surface of the surface opposite to the surface on which the uneven structure is formed.

Further, the concave-convex structure of the mold used for such nanoimprint is an uneven structure composed of a pillar array in which the convex portions are formed of columnar bodies and the columnar bodies are arranged, or the concave-convex structure is formed by columnar pores. It is preferable that the structure is uneven. It should be noted that such a concave-convex structure of the mold is suitable for forming the uneven structure on the organic silica thin film by transferring (reversing) the characteristics of the concave-convex structure by nanoimprint. The conditions are the same as the various conditions (for example, average pore diameter, average pitch, etc.) described in the above-mentioned uneven structure of the organic silica thin film.

Further, as a method of forming an uneven structure by nanoimprint and curing it, a treatment of removing a solvent from a film obtained from the sol solution (a coating film of the sol solution (uncured or semi-cured), or a coating film of the sol solution). After placing the mold on the surface of the film (which may be uncured or semi-cured), the mold is placed so that the characteristics of the unevenness formed on the mold are transferred (reversed). It is preferable to adopt a method of heating and curing the film obtained from the sol solution with the sol solution on the surface. After removing the mold from the thin film cured by heating in this way, the thin film is converted into hydrochloric acid vapor from the viewpoint of hydrolyzing the alkoxy groups remaining in the thin film and further curing the thin film. May be exposed. In this way, the porous film can be efficiently formed by nanoimprint, and this can be used as the organic silica thin film.

(Hydrophobic layer)
The hydrophobic layer according to the present invention is a layer laminated on the surface of an organic silica thin film, and the hydrophobic layer can be covalently bonded to a hydrophobic group having an aliphatic carbon skeleton as a main skeleton and the silica skeleton of the organic silica. It is a layer made of a hydrophobic material having various functional groups.

The hydrophobic group in such a hydrophobic material has an aliphatic carbon skeleton as a main skeleton. Here, the "aliphatic carbon skeleton" includes a portion having a carbon skeleton structure similar to that of an aliphatic hydrocarbon, and has a structure (skeleton) having a plurality of carbon atoms (C) in the skeleton. It may be a skeleton formed only by carbon atoms of an aliphatic hydrocarbon, or a skeleton (fat) formed by a bond between a carbon atom of an aliphatic hydrocarbon and another atom (hetero atom). It may be a skeleton having a structure in which at least a part of carbon of the group hydrocarbon is substituted with a hetero atom (for example, an oxygen atom, a nitrogen atom, etc.). As such an "aliphatic carbon skeleton", the content ratio of carbon atoms to all the atoms forming the skeleton is preferably 20 at% (more preferably 25 at%) or more. Further, in the present invention, the "hydrophobic group having an aliphatic carbon skeleton as the main skeleton" means a hydrophobic group in which the main skeleton is formed by the above-mentioned aliphatic carbon skeleton. It should be noted that such a hydrophobic group having an aliphatic carbon skeleton as the main skeleton can have a low affinity for hydrophilic groups such as hydroxyl groups, mainly derived from the structure of the carbon skeleton of the main skeleton.

The hydrophobic group having such an aliphatic carbon skeleton as the main skeleton is not particularly limited, but is an alkyl group, an alkynyl group, an alkenyl group, a fluorine atom-containing group, and a halogen containing a halogen atom other than the fluorine atom. At least one selected from the group consisting of an atom-containing group (preferably an alkyl halide group containing a halogen atom other than a fluorine atom, an alkynyl halide group containing a halogen atom other than a fluorine atom, a halogen atom other than a fluorine atom). Is preferred.

The alkyl group, alkynyl group, and alkenyl group suitable as such a hydrophobic group each have 1 to 40 carbon atoms (more preferably 1 to 30, particularly preferably 1 to 20). With respect to such an alkyl group, an alkynyl group and an alkenyl group as a hydrophobic group, if the number of carbon atoms exceeds the above upper limit, it becomes difficult to obtain a commercially available hydrophobic material having such a group as a hydrophobic group, and it is also hydrophobic. The reactivity of the sex material tends to decrease. The alkyl group, alkynyl group, and alkenyl group may be linear or branched, respectively, from the viewpoint of low steric hindrance and easy reaction. , Linear ones are more preferable.

Further, examples of the fluorine atom-containing group suitable as such a hydrophobic group include a fluoroalkyl group and a fluoroether group. Here, the fluoroalkyl group means an alkyl group in which at least a part of a hydrogen atom is substituted with a fluorine atom (an alkyl group or a perfluoroalkyl group in which a hydrogen atom is partially substituted with a fluorine atom). Such a fluoroalkyl group may be an alkyl group in which a hydrogen atom bonded to a carbon atom is substituted with one or more fluorine atoms, and may be a linear one or a branched chain one. May be good.

Further, the carbon number (carbon number of the alkyl chain) of the main skeleton (carbon skeleton) of such a fluoroalkyl group (alkyl group in which at least a part of a hydrogen atom is replaced with a fluorine atom) is 1 to 16 (more preferably). It is preferably 1 to 10, particularly preferably 1 to 8). The lower limit of the numerical range of the number of carbon atoms in the main skeleton of such a fluoroalkyl group is more preferably 3. When the number of carbon atoms exceeds the upper limit, the molecules of the hydrophobic material having such a group become bulky, and the reaction at the time of introducing the hydrophobic group tends to be difficult to proceed due to the steric effect. By setting the number of carbon atoms within the above range, a higher degree of hydrophobicity tends to be obtained when the hydrophobic layer is formed.

When the hydrophobic material having such a fluoroalkyl group as a hydrophobic group has a plurality of fluoroalkyl groups, the plurality of fluoroalkyl groups may be the same or may be the same. It may be different. Here, each of the plurality of fluoroalkyl groups is a linear chain having 1 to 16 (more preferably 1 to 8) carbon atoms in which the hydrogen atom bonded to the carbon atom is replaced by one or more fluorine atoms. Alternatively, it is preferably a branched alkyl group.

Further, such a fluoroalkyl group is more preferably a perfluoroalkyl group which is linear and in which all the hydrogen atoms in the alkyl group are substituted with fluorine atoms. Further, as such a linear perfluoroalkyl group, one having 3 to 8 carbon atoms is particularly preferable. If the number of carbon atoms is less than the lower limit, the hydrophobic effect tends not to be sufficiently obtained. On the other hand, if the number of carbon atoms exceeds the upper limit, the hydrophobic group becomes bulky and the reaction when introducing the hydrophobic group is steric. It becomes difficult to proceed due to the obstacle, and the reaction with the organic silica thin film tends not to proceed sufficiently.

Examples of such fluoroalkyl groups include the formulas: CF _3- , CF _3- CH _2- , CF _3- CF _2- , CF _3- CH _2- CH _2- , CF _3- CF _2- CH _{2- , CF 3 -CF 2 -CF 2 -} , CF 3 -CF 2 -CH 2 -CH 2 -, F-CH 2 -CF 2 -CH 2 -CH 2 -, CF 2 (CF 3) -CH 2 -CH Examples include groups represented by _2- .

Among such fluoroalkyl groups, 3,3, from the viewpoints of versatility of the hydrophobic material (reagent) having such a group and easier control of the reaction of the hydrophobic material. More preferably, 3-trifluoropropyl group, 1H, 1H, 2H, 2H-nonafluorohexyl group, 1H, 1H, 2H, 2H-perfluorooctyl group. Among these, the fluoroalkyl group is a 3,3,3-trifluoropropyl group, 1H, 1H, 2H, 2H from the viewpoint that the reactivity is more easily controlled and it is not easily affected by steric hindrance during the reaction. -Nonafluorohexyl groups are particularly preferred.

Further, a fluoroether group suitable as the fluorine atom-containing group is described in the following general formula (i):

[In formula (i), R ¹⁰ represents a divalent alkylene group (fluorinated alkylene group) in which at least a part of a hydrogen atom is replaced with a fluorine atom. ]
A group having a structure represented by. As R ¹⁰ (alkylene group in which at least a part of hydrogen atom is substituted with fluorine atom (fluorinated alkylene group)) in the formula (i), the following general formula (ii):
−C _n F _2n − (ii)
[In formula (ii), n represents an integer of 1 to 10 (preferably 1 to 5, more preferably 1 to 4). ]
The divalent perfluoroalkylene group represented by is more preferable. Such a divalent perfluoroalkylene group may be linear or branched chain, and is not particularly limited, but a linear group is more preferable. Further, in such a divalent perfluoroalkylene group, when the value of n exceeds the upper limit, steric hindrance is large and the reaction with organic silica tends to be difficult to proceed. As described above, when R ¹⁰ in the above formula (i) is a group represented by the above formula (ii) (in this case, the structure represented by the above formula (i) is represented by the formula: −C _n F _2n. a structure represented by -O-), as being suitable as a structure represented by the formula (i), for example, the _{formula: -CF 2 -CF 2 -O -,} - CF 2 -CF 2 - _{CF 2 -O -, - CF 2} -CF 2 -CF 2 -CF 2 -O- , a group represented by and the like.

Examples of the fluoroether group having a structure represented by the formula (i) include the following general formula (iii):
^{_{R 20 - (O-C n}} F 2n) α - (iii)
[In formula (iii), R ²⁰ represents an alkyl group having 1 to 16 carbon atoms in which a hydrogen atom may be substituted with one or more fluorine atoms, and n is 1 to 10 (preferably 1 to 5, More preferably, it indicates an integer of 1 to 4), and α indicates an integer of 1 or more. ]
In may be exemplified a group having the structure represented as being preferred (Note that if such a fluoroether group is contained more in the hydrophobic material, R ^2, n and α respectively in the fluoroether group They can be selected independently and may be the same or different).

Such may be selected as R ²⁰ in the formula (iii), an alkyl group which may be substituted hydrogen atoms by one or more fluorine atoms, be in a straight chain, branched It may be a linear one, and is not particularly limited, but a linear one is preferable. The number of carbon atoms of such R ²⁰ as selected may one or more fluorine atoms by an optionally substituted alkyl group, from the viewpoint of preventing the reaction inhibition due to steric hindrance, more preferably from 1 to 16 , 1 to 8, more preferably. Such R ²⁰ is preferably any one of the groups represented by the formulas: CF _3- , CF _3- CF _2- O-, and CF _3- CF _2- CF _2- O-.

Further, the structural portion represented by the formula: −C _n F _2n − in the above formula (iii) is a perfluoroalkylene group represented by the above formula (iii). For example, the _{formula: -CF 2 -, - CF (} CF 3) -, - CH 2 -CF 2 -, - CF 2 -CF 2 -, - CF 2 -CF 2 -CH 2 -CH 2 -, - CH 2 Examples thereof include groups represented by −CF ₂ −CH ₂ −CH ₂ − and −CF (CF ₃ ) −CH ₂ −CH ₂ −.

Further, in such an equation (iii), α represents a number in which a structure represented by the equation: ( _{OC n} F _2n ) in the equation (iii) is introduced. The value of such α may be 1 or more, but more preferably 1 to 100, and further preferably 1 to 40. If the value of α exceeds the upper limit, it tends to be difficult to control the reactivity.

Further, when α is an integer of 2 or more in the above formula (iii), it contains a structure represented by a plurality of formulas: ( _{OC n} F _2n ). In this case, a plurality of structures are included. The structures represented by the formula: − (OC _n F _2n ) − may be the same or different. Further, in the above formula (iii), the structural portion represented by the formula: − (OC _n F _2n ) _α − is subject to the following conditions (A) to (F) :.
Condition (A) Formula: Having a groups represented by-(OC ₄ F ₈ )-.
Condition (B) Formula: Having b groups represented by-(OC ₃ F ₆ )-.
Condition (C) Formula: Having c groups represented by-(OC ₂ F ₄ )-.
Condition (D) Formula: Having d groups represented by-(OCF ₂ )-.
Condition (E) The above a, b, c and d independently indicate 0 to 200.
Condition (F) The sum of the above a, b, c and d is 1 or more.
Is more preferable (here, the sum of a, b, c and d is particularly preferably 1 to 100). In addition, a, b, c and d are each preferably 1 to 60, and more preferably 1 to 40, respectively. Further, the structural portion represented by the formula: − (OC _n F _2n ) _α − in the structure represented by the formula: O—C _n F _2n is preferably linear, and among them, the formula: O. -CF ₂ CF ₂ , O-CF ₂ CF ₂ CF ₂ , O-CF ₂ CF ₂ CF ₂ It is more preferable to have a structure represented by CF ₂ . Further, the structural portion represented by the formula: − (OC _n F _2n ) _α − satisfying the above conditions (A) to (F) is, for example, the formula: − (O−CF ₂ CF ₂ CF ₂ ). _The structure may be represented by _b − (OCF ₂ CF ₂ ) _c −.

Further, as a group having a structural portion represented by the above formula (iii) (a group suitable as a fluoroether group), the following formula (iii-1):
^{_{R 20 - (O-C n}} F 2n) α -X- (iii-1)
^Wherein has the same meaning as ^{R 20, R 20} in the n and alpha, respectively formula (iii), n and alpha, X represents a single bond or a divalent organic group. ]
It may be a group represented by. The divalent organic group that can be selected as X in the formula (iii-1) is any of the groups represented by the formulas: -CH _2- , -CF _2- , -CHF-. It is preferable to have.

Further, the halogen atom-containing group containing a halogen atom other than the fluorine atom, which is suitable as the hydrophobic group, has the same structure as the above-mentioned fluorine atom-containing group except that a halogen atom is used instead of the fluorine atom. Can be used as appropriate. As such a halogen atom-containing group other than the fluorine atom, an alkyl halide group containing a halogen atom other than the fluorine atom, an alkynyl halide group containing a halogen atom other than the fluorine atom, and a halogen atom other than the fluorine atom are preferable.

Such an alkyl halide group containing a halogen atom other than a fluorine atom is a group composed of an alkyl group (alkyl halide group) in which at least a part of the hydrogen atom is replaced with a halogen atom other than the fluorine atom. As the halogen atom other than the fluorine atom, a chlorine atom, a bromine atom and an iodine atom are preferable, and a chlorine atom and a bromine atom are more preferable, from the viewpoint of high versatility, stability and ease of reproduction. Chlorine atoms are particularly preferred. The number of carbon atoms of such an alkyl halide group is preferably 1 to 5 (more preferably 1 to 4, particularly preferably 1 to 3). When the number of carbon atoms exceeds the upper limit, the reactivity becomes low and the formation of the hydrophobic layer tends not to proceed sufficiently.

Such halogenated alkyl group, for example, the _{formula: CCl 3 -, CBr 3 -} , CCl 2 (CCl 3) -, CBr 2 (CBr 3) -, CH 3 -CCl 2 -, CH 3 -CBr 2 _{-, CCl 3 -CCl 2 -,} CBr 3 -CBr 2 -, CCl 3 -CCl 2 -CH 2 -CH 2 -, CBr 3 -CBr 2 -CH 2 -CH 2 -, - CH 2 -CH 2 -Cl _{, -CH 2 -CH 2 -Br, -CH} 2 -CH 2 -O-CH 2 -Cl, -CH 2 Cl, -CH 2 Br, a group represented by _-CH 2 _-CH 2 _-CH 2 -Cl Among them, the groups represented by the formulas: -CH ₂ Cl and -CH _2- CH _2- Cl are preferable from the viewpoint of high versatility of the reagent and easiness of reaction.

The halogenated alkenyl group containing a halogen atom other than the fluorine atom is a group composed of an alkenyl group (halogenated alkenyl group) in which at least a part of the hydrogen atom is replaced with a halogen atom other than the fluorine atom. As the halogen atom other than the fluorine atom, a chlorine atom, a bromine atom and an iodine atom are preferable, and a chlorine atom and a bromine atom are more preferable, from the viewpoint of high versatility, stability and ease of reproduction. Chlorine atoms are particularly preferred. The number of carbon atoms of such a halogenated alkenyl group is preferably 2 to 5 (more preferably 2 to 4, particularly preferably 2 to 3). When the number of carbon atoms exceeds the upper limit, the reactivity becomes low and the formation of the hydrophobic layer tends not to proceed sufficiently.

Further, the halogenated alkynyl group containing a halogen atom other than the fluorine atom is a group composed of an alkynyl group (halogenated alkynyl group) in which at least a part of the hydrogen atom is replaced with a halogen atom other than the fluorine atom. As the halogen atom other than the fluorine atom, a chlorine atom, a bromine atom and an iodine atom are preferable, and a chlorine atom and a bromine atom are more preferable, from the viewpoint of high versatility, stability and ease of reproduction. Chlorine atoms are particularly preferred. The number of carbon atoms of such a halogenated alkynyl group is preferably 2 to 5 (more preferably 2 to 4, particularly preferably 2 to 3). When the number of carbon atoms exceeds the upper limit, the reactivity becomes low and the formation of the hydrophobic layer tends not to proceed sufficiently.

Further, the functional group of the hydrophobic material that can be covalently bonded to the silica skeleton of organic silica is not particularly limited, but for example, the following general formula (iv):
Me-Z (iv)
[In formula (iv), Me represents a metal atom and Z represents a hydrolyzable substituent. ]
Examples thereof include groups having a structural portion represented by.

Examples of Me (metal atom) in such a formula (iv) include silicon atom, aluminum atom, titanium atom, zirconium atom, etc. Among them, from the viewpoint of reagent safety and ease of reaction control. Therefore, a silicon atom is particularly preferable.

Further, such a hydrolyzable substituent (Z) is not particularly limited, and is represented by a halogen atom, a linear or branched alkoxy group (more preferably, the formula: −OR ³⁰ described later). Alkoxy group), hydroxyl group, linear or branched alkyl group, O atom which is a partial structure of Si—O—Si crosslinked when Me is a silicon atom, Si when Me is a silicon atom N atom is part structure of -N-Si crosslinking ^{formula: -OCOR 31, -O-N =} , - C (R 31) 2 - R 31 group (wherein, represented by a substituted or unsubstituted (Shows an alkyl group having 1 to 4 carbon atoms) and the like.

Formulas relating to such hydrolyzable substituents: As the group represented by −Z, from the viewpoint of versatility and reagent stability, a group in which Z is a halogen atom (more preferably a chlorine atom), Alternatively, the following general formula (v):
−OR ³⁰ (v)
[R ³⁰ represents an alkyl group having 1 to 8 carbon atoms (more preferably 1 to 5, particularly preferably 1 to 3). ]
The alkoxy group represented by is more preferable. Alkyl groups such may be selected as R ³⁰ can be of a straight chain, it may be one branched, from the viewpoint of easiness and industrial use easiness of availability Is more preferably linear. If the number of carbon atoms of R ³⁰ exceeds the above upper limit, the reactivity of the alkoxy group is lowered, and hydrolysis tends not to proceed sufficiently.

In addition, since the alkoxy group represented by the formula: −OR ³⁰ has a structural portion bonded to a metal atom (Me), it easily hydrolyzes with the hydroxyl group (−OH) on the organic silicon thin film. This makes it possible to more efficiently introduce the metal atom (Me) into the silicon atom (Si) forming the silica skeleton via oxygen (formula: Me-O). -Si (Si in such a formula can form a structural portion represented by a silicon atom forming a silica skeleton) more efficiently), the silica skeleton of the organic silica forming the organic silica thin film and the hydrophobicity. It becomes possible to react (covalently bond) the sex material more efficiently.

Further, as the hydrophobic material having such a hydrophobic group and a functional group covalently bonded to the silica skeleton of organic silica, the following formula (vi):

[In the formula, D is the hydrophobic group (the alkyl group, the alkynyl group, the alkenyl group, the fluorine atom-containing group, the alkyl halide group containing a halogen atom other than the fluorine atom, the halogen atom other than the fluorine atom. It shows (preferably at least one group selected from the group consisting of a halogenated alkynyl group containing a halogen atom and a halogenated alkenyl group containing a halogen atom other than the fluorine atom) (when a plurality of D's are present, D is preferable). Each may be the same or different), where Z indicates the hydrolyzable substituent (Z is synonymous with Z in formula (iv). If present, Z may be the same or different, respectively), Me represents a metal atom (Me is synonymous with Me in formula (iv)), and e and f are: When each is an integer of 1 or more independently and the sum of e and f is the same value as the valence (valence) of the metal atom Me (for example, when Me is Si), the value is selected. Since the valence is 4, the integers selected so that the sum of e and f is 4, respectively (e and f are e + f = 4, e ≧ 1, f ≧ 1 when Me is Si, etc.) It is an integer that satisfies the condition).]
The compound represented by is preferably used.

The hydrophobic group represented by D in such a formula (vi) may be any hydrophobic group having the above-mentioned aliphatic carbon skeleton as the main skeleton, and is not particularly limited. Among them, the alkyl group, More preferably, it is an alkyl halide group containing the alkynyl group, the alkenyl group, the fluorine atom-containing group, and a halogen atom other than the fluorine atom. Further, as the hydrolyzable substituent represented by Z in such a formula (vi), a halogen atom, an alkoxy group (more preferably, the above formula: an alkoxy group represented by −OR ³⁰ ), a hydroxyl group , A linear or branched alkyl group, an O atom which is a part of the Si—O—Si crosslink when Me is a silicon atom, and a part of the Si—N—Si bridge when Me is a silicon atom. The N atom having a structure is preferable, and a chloro atom or an alkoxy group is particularly preferable. As the metal atom represented by Me in such a formula (vi), a silicon atom is particularly preferable.

When Me is a silicon atom and Z indicates an O atom which is a partial structure of Si—O—Si crosslink, the compound represented by the above formula (vi) is of the formula:
_{(D) e -Si (Z)} f -O-Si (Z) f - (D) e
[In the equation, e and f each indicate an integer of 0 to 3 selected so that the sum of them is 3 (note that e and f are 1 or more, respectively). preferable). ]
It is preferable that the compound is represented by, and as the compound in this case, for example, hexamethyldisiloxane or 1,1,3,3-tetramethyldisiloxane may be used. When Me is a silicon atom and Z indicates an N atom which is a partial structure of Si—N—Si crosslink, the compound represented by the above formula (vi) is of the formula:
(D) _e -Si-NH-Si- (D) _e
[In the formula, e indicates an integer of 3]
It is preferable that the compound is represented by, and as the compound in this case, for example, tetramethyl-1,3-bis (chloromethyl) disilazane and hexamethyldisilazane may be used.

Examples of the compound represented by the formula (vi) (a compound suitable as a hydrophobic material) include, for example, when the metal atom (Me) in the formula (iv) is a silicon atom, the formula:

[D in the formula represents the hydrophobic ^{group, R 30} has the same meaning as ^{R 30} in formula (v). ]
Alkoxysilane compound represented by, formula:

[D in the formula represents an alkyl group. ]
A chlorotrialkylsilane compound represented by is preferably used.

Further, as a compound represented by such a formula (vi) (a compound suitable as a hydrophobic material), when the metal atom (Me) in the formula (iv) is a silicon atom, the formula (iv) is used. Depending on the type of hydrolyzable substituent (Z) in, for example, trimethoxy (3,3,3-trifluoropropyl) silane, triethoxy (1H, 1H, 2H, 2H-perfluorooctyl) silane, Fluoroalkyltrialkoxysilanes such as trimethoxy (1H, 1H, 2H, 2H-nonafluorohexyl) silanes, triethoxy (1H, 1H, 2H, 2H-tridecafluorooctyl) silanes; trifluoropropyldimethylchlorosilanes and the like Fluoroalkyldialkylchlorosilanes; trialkylchlorosilanes such as chlorotrimethylsilane, chlorotriethylsilane, tripropylchlorosilane; alkyltrialkoxysilanes chloride such as (2-chloroethyl) trimethoxysilane, 3-chloropropyltrimethoxysilane; (heptadecafluoro) -1,1,2,2-tetrahydrodecyl) dimethylchlorosilane, octadecyltrichlorosilane, tetramethyl-1,3-bis (chloromethyl) disilazane, hexamethyldisilazane, 3- (methacryloyloxy) propyltrimethoxysilane, etc. A silane compound containing a hydrophobic group and the like can be mentioned as suitable ones.

Further, as the hydrophobic material having a functional group covalently bonded to the hydrophobic group and the silica skeleton of the organic silica, the following formula (vii):

[In the formula, D is the hydrophobic group (the alkyl group, the alkynyl group, the alkenyl group, the fluorine atom-containing group, the alkyl halide group containing a halogen atom other than the fluorine atom, the halogen atom other than the fluorine atom. (Preferably at least one group selected from the group consisting of a halogenated alkynyl group containing the above and a halogenated alkenyl group containing a halogen atom other than the fluorine atom), where Z is the hydrolyzable substituent. (Z is synonymous with Z in the formula (iv). When there are a plurality of Z, Z may be the same or different), Me indicates a metal atom. (Me is synonymous with Me in formula (iv)), R ⁴⁰ is a divalent group in which one hydrogen atom is replaced with a group represented by the formula: -Me- (Z) g (among others, Preferably, an alkylene group, an alkenylene group and an alkynylene group in which one hydrogen atom is substituted with a group represented by the formula: -Me- (Z) g; and at least one hydrogen atom of these groups. Further, a group selected from the group consisting of groups substituted with halogen atoms) is shown, and g is an integer of 1 or more and the same value as the valence (atomic value) of the metal atom Me minus 1. (For example, when Me is Si, since the valence is 4, g is an integer selected so as to be 3), and h is An integer of 1 to 16 (more preferably an integer of 1 to 10) is shown. ]
The compound represented by is also preferably used.

The hydrophobic group represented by D in such a formula (vii) may be any hydrophobic group having the above-mentioned aliphatic carbon skeleton as the main skeleton, and is not particularly limited. Among them, the alkyl group, The alkynyl group, the alkenyl group, the fluorine atom-containing group, and the alkyl halide group containing a halogen atom other than the fluorine atom are more preferable, and the fluorine atom-containing group is further preferable. Further, as the hydrophobic group represented by D in the formula (vii), the group represented by the above formula (iii-1) is more preferable.

Further, the hydrolyzable substituent represented by Z in such a formula (vii) is a halogen atom, and an alkoxy group represented by the above formula: −OR ³⁰ (R ³⁰ in the formula is the formula (v). .) the same meaning as ^{R 30} in), wherein: -OCOR ^{R 31} group (wherein, represented by ³¹ represents a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms), - O-. group represented by N =, and, ^{-C (R} _{31) 2} - group represented by (. ^{R 31} in the formula which represents a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms) in the Any of them is preferable, and the above alkoxy group is more preferable from the viewpoint of controlling the reaction.

Alkoxy groups are particularly preferred. In addition, g in the above formula (vii) indicates the number of introduced groups represented by the formula: −Z. When such g is 2 or more, that is, when there are a plurality of groups represented by the formula: −Z, Z may be the same or different. Further, as the metal atom represented by Me in such a formula (vi), a silicon atom is particularly preferable.

In such a compound represented by the formula (vii), the value of h is an integer of 1 to 16 (more preferably an integer of 1 to 10). When such a value of h exceeds the upper limit, the steric hindrance of the molecule is large, the number of molecules that cannot react with the surface of organic silica increases, and a sufficient hydrophobic effect tends to be not obtained.

Further, the group represented by R ⁴⁰ in such a formula (vii) is a divalent group in which one hydrogen atom is replaced with a group represented by the formula: -Me- (Z) g. Any structure may be used as long as it has a structure capable of forming various polymers having a group represented by the formula: -Me- (Z) g in the side chain, and is not particularly limited, but among them, one hydrogen atom is used. Formula: An alkylene group, an alkenylene group and an alkynylene group substituted with a group represented by -Me- (Z) g; and a group in which at least one hydrogen atom of these groups is further substituted with a halogen atom. It is preferably a group selected from the group consisting of. The carbon number of such an alkylene group, an alkenylene group and an alkynylene group is preferably 2 to 8 (more preferably 2 to 4).

Further, as a compound represented by such a formula (vii), for example, the following general formula (viii):

[H in the formula indicates an integer of 1 to 10. ]
The compound (polymer component) represented by is preferably used. As the compound represented by such a formula (vii), a commercially available product (for example, a trade name "Optur (registered trademark) DSX" manufactured by Daikin Industries, Ltd.) can be appropriately used.

Further, examples of the hydrophobic material having a functional group covalently bonded to the hydrophobic group and the silica skeleton of the organic silica include the following general formula (ix):

Wherein, D, Z, ^{Me, R} 40, g, h is the D respectively in the above formula ^{(vii), Z, Me,} R 40, g, and h ^{synonymous, R 50} is a divalent radical However, i indicates an integer of 1 to 16 (more preferably, an integer of 1 to 10). ]
It may be a compound represented by. In such compounds, the ^formula:> a repeating unit represented by R 40 -Me- _{(Z) g,} wherein: ^{-R 50} - introducing the form of a repeating unit represented by is not particularly limited, for example, It may be introduced at random, or it may be introduced in a block, alternate manner, or the like.

Incidentally, R ⁵⁰ in the formula (ix) may be any divalent group, it can be appropriately used those having a structure such as to form a variety of polymers, among others, alkylene group, alkenylene group and alkynylene group; and , It is preferable that at least one of these groups is a group selected from the group consisting of groups further substituted with halogen atoms. The carbon number of such an alkylene group, an alkenylene group and an alkynylene group is not particularly limited.

The hydrophobic material may be any material having a functional group that can be covalently bonded to the hydrophobic group and the silica skeleton of the organic silica, and is a known material (for example, a hydrolyzable silane having the hydrophobic group). A compound, a metal alkoxide having the hydrophobic group, a silicone resin having the hydrophobic group in the side chain and a functional group covalently bonded to the silica skeleton, etc.) may be appropriately used, or a commercially available product may be used. ..

Further, the hydrophobic layer according to the present invention is a layer made of the hydrophobic material. The layer made of such a hydrophobic material can also be formed, for example, by contacting a treatment liquid containing the hydrophobic material on the surface of the organic silica thin film. The state of the hydrophobic layer when the treatment liquids are brought into contact with each other in this way is described below, taking as an example the case where the hydrophobic material is an alkoxysilane compound represented by the above formula (vi-1). , Refer to FIG. That is, first, the treatment liquid containing the alkoxysilane compound is brought into contact with the surface of the organic silica thin film 2, and the alkoxy group (group represented by the formula: −OR ³⁰ ) in the alkoxysilane compound and the organic. When the hydroxyl group on the surface of the silica thin film 2 is reacted, the silicon atom (Si) forming the silica skeleton and the structural portion represented by the formula: D—Si are bonded via oxygen to form the hydrophobic layer 3. It is presumed that it can be formed. When the hydrophobic layer 3 is produced by bringing the treatment liquid containing the alkoxysilane compound represented by the formula (vi-1) into contact with each other, as shown in FIG. 3, some of the hydrophobic materials are used together. Is introduced onto the surface of the organic silica thin film as a condensed (polymerized) polymer, or the surface of the organic silica thin film is in a state where only some alkoxy groups contribute to the reaction and the remaining alkoxy groups remain. It is expected that it will be introduced above. Therefore, it is difficult to specifically specify the structure of the hydrophobic layer 3 after supporting the hydrophobic material, but the obtained layer made of the hydrophobic material is caused by the hydrophobic group (D) possessed by the hydrophobic material. It is clear that the layer becomes hydrophobic. As described above, the layer made of the hydrophobic material (hydrophobic layer 3) is, for example, when the hydrophobic material is the metal alkoxide (preferably the alkoxysilane compound), the hydrophobic material and the organic silica thin film. A layer that can be formed by reacting (hydrolyzing) with hydroxyl groups on the surface, and can form a layer to which the metal alkoxide and / or a condensate thereof are bonded on the surface of the organic silica thin film. You might also say that. A method that can be suitably used as a method for producing a layer made of such a hydrophobic material (hydrophobic layer) will be described separately.

The thickness of the hydrophobic layer according to the present invention is 0.2 to 5.5 nm. If such a thickness is less than the above lower limit, the hydrophobicity is not always sufficient, and the interaction between the surface of the organic silica thin film and the molecule to be measured (material to be analyzed) cannot be sufficiently weakened. , Molecules to be measured are strongly adsorbed on the surface of the organic silica thin film, and it becomes difficult to efficiently (smoothly) laser desorb / ionize when irradiated with laser light. On the other hand, if the thickness of the hydrophobic layer exceeds the above upper limit, it becomes difficult to transfer energy from the organic silica thin film to the molecule to be measured (material to be analyzed) even if laser light is irradiated (the thickness of the hydrophobic layer causes energy). The movement of the molecule is likely to be hindered), and the efficiency of laser desorption / ionization of the molecule to be measured is reduced. Further, the thickness of such a hydrophobic layer is more preferably 0.3 to 5 nm from the same viewpoint, from the viewpoint of further improving the efficiency of laser desorption / ionization of the molecule to be measured, 0.5. It is more preferably ~ 4 nm.

In the present invention, the thickness of the hydrophobic layer can be a value measured as follows according to the type of hydrophobic group and the like. That is, first, when the material forming the hydrophobic layer is a hydrophobic material having a hydrophobic group composed of a fluoroalkyl group or a fluoroether group, and the material is not introduced into a single layer (it is a monomolecular layer). If not) will be explained. When measuring the thickness of such a hydrophobic layer, an analytical sample provided with a hydrophobic layer made of a hydrophobic material is prepared, and a position 10 nm from the surface toward the depth direction (thickness 10 nm from the surface) with respect to the analytical sample. X-ray photoelectron spectroscopy (XPS) analysis (XPS analysis) is performed up to (range up to) to determine the composition of the elements of the film up to a depth of 10 nm, and all elements up to a depth of 10 nm (hydrogen). The amount ratio of fluorine (F) to (excluding) ([amount of fluorine (F) determined by XPS analysis] / [amount of all elements (excluding hydrogen) determined by XPS analysis]) is determined. When the hydrophobic material has a hydrophobic group composed of a fluoroalkyl group, it is considered that all the repeating units in the hydrophobic material are groups represented by the formula:-(CF ₂ )-. The following formula (IA):

[For symbols in formula (IA), Y indicates the amount ratio of fluorine elements from the surface to the region of 10 nm depth determined by XPS analysis, and M indicates the molecular weight of the repeating unit of the hydrophobic material (hydrophobic material). When has a hydrophobic group consisting of a fluoroalkyl group, the repeating unit is considered to be a group represented by the formula:-(CF ₂ )-, so the molecular weight of CF ₂ is 50), and ρ is hydrophobic. The density of the layer is shown, L is the thickness of the hydrophobic layer, m _f is the number of fluorine atoms (the number of atoms) in the repeating unit in the hydrophobic material, and m is the total number of atoms of the repeating unit in the hydrophobic material. (However, the number of hydrogen atoms is excluded: for example, 3 when the repeating unit is a group represented by the formula:-(CF ₂ )-, and the repeating unit is the formula:-(CF ₂ O). 4 when the group is represented by −), ρ'indicates the density of the organic silica thin film, N indicates the molecular weight of the repeating unit of the organic silica thin film, and n constitutes the repeating unit of the organic silica thin film. Indicates the number of all atoms (number of atoms) to be used (however, the number of hydrogen atoms is excluded). ]
The thickness (L) of the hydrophobic layer can be obtained by calculating. In the present invention, the value of L obtained by such a calculation formula (IA) is regarded as the "thickness of the hydrophobic layer". In the XPS analysis as described above, the average ratio of F (sparse analysis state) existing from the surface to the position of 10 nm in the depth direction (range from the surface to the thickness of 10 nm) is obtained. , Such a formula (IA) is a calculation formula for obtaining the thickness of the hydrophobic layer on the assumption that F (the target element for obtaining the quantitative ratio in XPS analysis) is present in a unit area in the hydrophobic layer. (That is, it is a calculation formula for calculating the thickness by regarding the thickness of F in the unit area as the thickness of the hydrophobic layer). In addition, in such a calculation formula (IA), regarding the density ρ of the hydrophobic layer, basically, when a film made of a polymer of a hydrophobic material is formed, the density of the polymer does not change significantly. In the specification, it is assumed that the value of ρ is 1.5 (note that the value of such density is manufactured by Daikin Industries, which is typical as a hydrophobic material having a hydrophobic group composed of a fluoroether group. The value of the density of the hydrophobic layer formed by using the product name "Optur (registered trademark) DSX" is adopted, and in this specification, the value of ρ is fixed to 1.5 for calculation. Obtain the thickness of the hydrophobic layer when various hydrophobic materials are used). For ρ', which is the density value of the organic silica thin film, a measured value (1.18) obtained by producing a bulk body of organic silica and applying Archimedes' principle is adopted. Since hydrogen atoms cannot generally be detected in XPS analysis, the number of hydrogen atoms is excluded from the number of atoms represented by m and n in the calculation formula (IA). Further, the repeating unit of the organic silica thin film may be obtained based on the material used when producing the organic silica thin film (for example, the repeating unit as described in the above formula (2). You may consider it as a calculation). In addition, Y in the formula (IA) is essentially the amount ratio of the target element for which the amount ratio is to be obtained in XPS analysis, and is relative to the hydrophobic material having a hydrophobic group composed of a fluoroalkyl group as described above. Fluorine is targeted in all measurements. Such a target element depends on the type of the hydrophobic group, but when the hetero atom is bonded to the carbon atom of the repeating unit of the hydrophobic group, the element related to the hetero atom (for example, the formula:- F element can be selected for the repeating unit represented by CF _2- , and Cl element, etc. can be selected for the repeating unit represented by the formula: −CCl _2- . The method of determining the thickness of the hydrophobic layer in the case where the material forming the hydrophobic layer has a hydrophobic group composed of a fluoroalkyl group has been described above. For example, the material forming the hydrophobic layer is composed of a fluoroether group. When it has a hydrophobic group, it is considered that the repeating unit in the hydrophobic material is a group represented by the formula:-(CF ₂ O)-, and the molecular weight of M in the above formula is changed from 50. , Formula: The value obtained by the above formula (IA) can be adopted in the same manner as the above method except that the molecular weight of the repeating unit represented by −CF ₂ O− is changed to “66”. ..

As the value of Y (quantity ratio of fluorine elements obtained by XPS analysis) in the above formula (IA), any three or more analytical samples having different thicknesses of the hydrophobic layer are prepared, and the analytical samples thereof. A scanning electron microscope equipped with an energy dispersive X-ray spectroscopy (EDX) analyzer while performing XPS analysis from the surface to a position of 10 nm (range from the surface to the thickness of 10 nm) in the depth direction. EDX analysis was performed from the surface to a position of 100 nm in the depth direction under the condition of an acceleration voltage of 3 kV using SEM), and the content ratio of fluorine elements was obtained for each analysis (XPS analysis, EDX analysis). The vertical axis is the content ratio of fluorine element by XPS analysis, and the horizontal axis is the content ratio of fluorine element by EDX analysis. After that, EDX analysis is performed on the organic silica substrate whose thickness of the hydrophobic layer is to be measured. Then, from the data of the EDX analysis, the content ratio of the fluorine element that would be contained in the range from the surface to the thickness of 10 nm when the XPS analysis is performed is estimated from the relationship with the above calibration line, and such a value is calculated. It may be used by imitating the amount of F element obtained by XPS analysis. When the types of elements to be analyzed are the same, the film thickness can be measured by using the calibration curve as described above.

Further, as a method for measuring the thickness of the hydrophobic layer, even if the material forming the hydrophobic layer is a hydrophobic material having another hydrophobic group, unless the hydrophobic material is introduced into a single layer (single molecule). (If it is not a layer), basically, the components (elements) that form the hydrophobic layer are analyzed by XPS analysis, and there is a target element in the unit area for which the quantitative ratio is calculated in XPS analysis. Assuming that such a target element exists in the honey (thickness (L)) is calculated (for example, when the hydrophobic group is an alkyl chloride group, the value of Y is the value of the fluorine element. Using the amount ratio of chlorine element instead of the amount ratio, it is considered that all the repeating units in the hydrophobic material consist of the groups represented by the formula: -CCl _2- , and the density ρ of the hydrophobic layer is 1. By calculating the above formula (IA) assuming that it is 5.5, the range (thickness (L)) in which Cl, which is the target element for which the quantitative ratio is to be obtained in the XPS analysis, exists in the unit area. The thickness of the hydrophobic layer can be obtained by calculating). The molecular weight of the repeating unit used for such a calculation is obtained by simulating that the hydrophobic group is composed of a repeating unit containing only one carbon atom, depending on the type of the hydrophobic group (for example,). When the hydrophobic group is a fluoroalkyl group as described above, the repeating unit is represented by the formula: −CF ₂ −, and when the hydrophobic group is an alkyl group, the repeating unit is represented by the formula: −CH ₂ −. When the unit or hydrophobic group is a fluoroether group, it is determined by assuming that it is composed of a repeating unit represented by the formula: −CF ₂ O−).

Further, in the present invention, when the hydrophobic layer is a layer in which a hydrophobic material is introduced into a single layer by a coupling reaction or the like (from the manufacturing process, the hydrophobic layer has a single layer structure of the hydrophobic material). (When it is clear that it will be a monomolecular layer), from the structure of the hydrophobic material after introduction, from the silicon (Si) on the surface of the organic silica, the end of the hydrophobic group in the bonded hydrophobic material. The length to the part is obtained, and this is simulated as the thickness of the hydrophobic layer. For example, when the hydrophobic material is chlorotrimethylsilane [formula: a compound represented by (CH ₃ ) ₃ -Si-Cl], silicon on the surface of the organic silica (formula: a compound represented by ₃ -Si-Cl) is reacted with a hydroxyl group on the surface of the organic silica thin film. Since the group represented by the formula: -O-Si- (CH ₃ ) ₃ is introduced into a single layer with respect to Si), the length of the group represented by the formula: -O-Si- (CH ₃ ) ₃ is introduced. From (0.4 nm: the size of the molecule of chlorotrimethylsilane is 0.41 nm), it can be determined that the distance from the surface to the end of the hydrophobic group is 0.4 nm.

The hydrophobic layer preferably has hydrophobicity (water repellency) such that the contact angle of water is 90 ° or more (more preferably 92 to 150 °). If the contact angle of water is less than the lower limit, the affinity with the hydrophobic layer becomes high when the molecule to be measured is a water-soluble molecule, and the molecule to be measured is relatively strongly adsorbed to the hydrophobic layer. When irradiated with laser light, it tends to be difficult to smoothly desorb / ionize the laser. On the other hand, when the contact angle of the water exceeds the upper limit, it becomes super water repellent, and it tends to be difficult to drop the water-soluble sample onto the membrane and support it.

The method that can be preferably used as a method for producing a layer made of such a hydrophobic material (hydrophobic layer) is not particularly limited, but for example, the hydrophobic material and a solvent are placed on the surface of the organic silica thin film. A method (X) of forming a thin film made of the hydrophobic material on the surface of the organic silica thin film by contacting and reacting the hydrophobic treatment liquid containing the above can be adopted. Hereinafter, such a method (X) will be briefly described.

The solvent of the hydrophobic treatment liquid used in such method (X) is not particularly limited, and a known solvent can be appropriately used. For example, the hydrophobic group in the hydrophobic material contains a fluorine atom. When it is a group, a fluorine-based solvent, hexane, chloroform, diethyl ether, tetrahydrofuran, acetone, N, N-dimethylformamide and the like can be appropriately used. As such a solvent, when the hydrophobic group in the hydrophobic material is a fluorine atom-containing group, it is a highly soluble solvent that can completely remove unreacted molecules, and thus is fluorine-based. Solvents are more preferred. Examples of such a fluorine-based solvent include hydrofluorocarbons, perfluorocarbons, hydrofluoroethers, perfluoropolyethers and the like. When the hydrophobic group in the hydrophobic material is a group that does not contain sparse atoms, ethanol, methanol, toluene, tetrahydrofuran and the like can be preferably used as the solvent, and the hydrophobic material is diluted with such a solvent. It can be suitably used as a hydrophobizing treatment liquid.

The content of the hydrophobic material in such a hydrophobizing treatment liquid is not particularly limited, but is preferably 0.01 to 10% by mass, more preferably 0.05 to 1% by mass. .. If the content of such a hydrophobic material is less than the lower limit, it tends to be difficult to uniformly coat the surface of the organic silica thin film with molecules of the hydrophobic material, while if it exceeds the upper limit, the hydrophobic layer is formed. It becomes thicker and the LDI support performance tends to decrease.

Further, the method of bringing such a hydrophobizing treatment liquid into contact with the surface of the organic silica thin film is not particularly limited, and a method of immersing the organic silica thin film in the hydrophobizing treatment liquid and hydrophobizing the surface of the organic silica thin film. A known method such as a method of applying a treatment liquid can be appropriately adopted.

Further, after the hydrophobizing solution is brought into contact with the surface of the organic silica thin film, the reaction between the functional group of the hydrophobic material and the hydroxyl group on the surface of the organic silica thin film is allowed to proceed. Here, when the hydrophobic material has a hydrolyzable substituent as a functional group covalently bonded to the silica skeleton of the organic silica, it is sufficient to take time without humidification at room temperature. The method (step) for advancing the reaction is not particularly limited because the reaction can be allowed to proceed, but the functional group of the hydrophobic material and the surface of the organic silica thin film are not particularly limited. It is preferable to employ a step of exposing to saturated steam under heating conditions so that the reaction with the above hydroxyl group proceeds efficiently. In this way, exposure to saturated water vapor makes it possible to efficiently hydrolyze the hydrophobic material and covalently bond it with the silica skeleton of organic silica. The heating conditions in the step of exposing to such saturated steam are preferably 30 to 150 ° C, more preferably 40 to 80 ° C. Further, the heating time in the step of exposing to such saturated steam is more preferably 0.5 to 24 hours. If the heating temperature or heating time is less than the lower limit, it becomes difficult to sufficiently laminate the hydrophobic layers, and the effect of hydrophobization tends to decrease. On the other hand, if the heating time exceeds the upper limit, the hydrophobic layer becomes thicker and LDI. Support performance tends to decrease.

Further, after the hydrophobizing solution is brought into contact with the surface of the organic silica thin film, the reaction between the functional group of the hydrophobic material and the hydroxyl group on the surface of the organic silica thin film is sufficiently promoted in the atmosphere. In an atmosphere, the heat treatment may be performed at a temperature of about 50 to 150 ° C. for 0.5 to 24 hours.

In this way, after the hydrophobizing solution is brought into contact with the surface of the organic silica thin film and reacted, a cleaning treatment is performed using the solvent in order to remove excess hydrophobizing material. Is preferable. When such a cleaning treatment is not performed, the film thickness of the hydrophobic layer exceeds 5.5 nm due to the excess hydrophobic material, although it depends on the type of the hydrophobic material and the concentration of the hydrophobic treatment liquid. It tends to end up. That is, from the viewpoint of reducing the film thickness of the hydrophobic layer to 5.5 nm or less, it is preferable to perform the cleaning treatment. The method of such a cleaning treatment is not particularly limited, but for example, the organic silica thin film having a layer made of a hydrophobic material formed by the above-mentioned reaction is placed in the above-mentioned solvent (preferably a fluorine-based solvent). It is preferable to adopt a method of immersing and ultrasonic cleaning.

In this way, the organic silica thin film and the organic silica thin film are formed by laminating a layer made of the hydrophobic material (a layer formed by using the hydrophobic material) on the surface of the organic silica thin film. It is possible to obtain an organic silica substrate for laser desorption / ionized mass spectrometry of the present invention, which comprises a hydrophobic layer laminated on the surface of the above. When the organic silica thin film used in the method (X) has a structure laminated on the base material, the organic silica substrate for laser desorption / ionization mass spectrometry of the present invention The form of a laminate comprising the substrate, the organic silica thin film formed (laminated) on the surface of the substrate, and the hydrophobic layer formed (laminated) on the surface of the organic silica thin film. It is also possible to.

The organic silica substrate for laser desorption / ionization mass spectrometry of the present invention has been described above, but the laser desorption / ionization mass spectrometry method of the present invention will be described below.

[Laser desorption / ionization mass spectrometry]
The laser desorption / ionized mass spectrometry method of the present invention is characterized in that the analytical substrate used for the laser desorption / ionized mass spectrometry is the organic silica substrate for the laser desorption / ionized mass spectrometry of the present invention. How to do it.

As such a method of laser desorption / ionization mass spectrometry, the organic silica substrate for laser desorption / ionization mass spectrometry of the present invention as an analysis substrate (hereinafter, in some cases, simply "the organic silica substrate of the present invention" is used. ”) Is not particularly limited, and for example, laser desorption / ionization mass spectrometry is performed by adopting the same conditions as those adopted by a known method using the organic silica substrate. The method of doing so can be adopted as appropriate. Further, as a method of such laser desorption / ionization mass spectrometry, for example, the organic silica substrate of the present invention is used as the analysis substrate, and the surface (surface) of the organic silica substrate on which the hydrophobic layer is formed is formed. A method of ionizing the molecule to be measured and performing mass spectrometry by irradiating the sample-carrying site on the substrate with a laser beam after supporting the sample containing the molecule to be measured on the substrate is adopted as a suitable method. can do. Hereinafter, a mass spectrometry method suitable as such a laser desorption / ionization mass spectrometry method of the present invention will be briefly described.

The sample used in such a method contains the molecule to be measured. Such a molecule to be measured is not particularly limited, but according to the present invention, it is possible to measure with a higher detection sensitivity, so that it is preferably a molecule derived from a living body or a molecule in a biological sample. As such molecules derived from living organisms or molecules in biological samples, sugars, proteins, peptides, glycoproteins, glycopeptides, nucleic acids, glycolipids and the like are more preferable, and the effects of the present invention can be applied to these molecules. It tends to be possible to make it more sophisticated. In addition, such molecules to be measured include those prepared from natural products, those prepared by partially modifying natural products chemically or enzymatically, and those prepared chemically or enzymatically. It may be a thing. Further, it may have a partial structure of a molecule contained in a living body or may be produced by imitating a molecule contained in a living body.

Further, such a sample (a sample containing a measurement target molecule) may be the measurement target molecule itself, or a sample containing the measurement target molecule (for example, a living tissue, cell, body fluid or secretion (for example). , Blood, serum, urine, semen, saliva, tears, sweat, feces, etc.)). As described above, as the sample (sample containing the molecule to be measured), a biological sample may be directly used. Further, after the precursor of the sample (precursor of the molecule to be measured, etc.) is supported on the surface (surface) of the organic silica substrate of the present invention on which the hydrophobic layer is formed, an enzyme treatment or the like is performed to carry out organic treatment. The molecule to be measured may be prepared on the surface of the silica substrate. In this case, the sample precursor is supported on the organic silica substrate of the present invention and then treated, and as a result, the hydrophobic layer of the organic silica substrate of the present invention is formed on the sample. It will be supported on the surface (surface).

Further, the above-mentioned "molecule to be measured" may be a molecule contained in the sample and may be the molecule itself whose chemical structure is desired to be determined, or a molecule contained in the sample. It may be a molecule obtained by derivatizing a molecule whose chemical structure is desired to be determined (for example, a molecule used for mass analysis obtained by binding a so-called labeled molecule to a molecule whose chemical structure is desired to be determined). As described above, the "measurement target molecule" may be a molecule that has not been derivatized, or a molecule that has been derivatized by a labeled molecule. The presence or absence of derivatization is not particularly limited, and may be appropriately determined according to the type of organic group of the organic silica thin film to be used, the type of molecule whose chemical structure is desired to be determined, and the like. As described above, it is not always necessary to perform derivation depending on the molecule whose chemical structure is to be determined. The molecular weight of the molecule to be measured is not particularly limited, but it is preferably 160 or more because it is difficult to perform accurate measurement by other measurement methods and the features of the present invention are more easily exhibited. , 500 or more is more preferable, and 1000 or more is particularly preferable.

Further, when a molecule obtained by derivatizing a molecule whose chemical structure is desired to be determined is used as the molecule to be measured, the derivation receives the light energy absorbed by the organic group (light energy absorbed by the organic silica thin film). It is preferably carried out by covalently bonding with a labeling molecule that enables the labeling molecule, preferably a labeling molecule having an absorption band having an overlap between the emission spectrum and the spectrum of the organic silica thin film.

Such a labeled molecule is not particularly limited as long as it has an effect as a receptor for energy donated from the organic silica thin film, but a molecule commercially available as a fluorescent labeling reagent may be used. Examples of such a labeling molecule include pyrene derivatives, fluorescein derivatives, rhodamine derivatives, cyanine dyes, Alexa Fluor (registered trademark), 2-aminoacridone, 6-aminoquinoline and the like.

In addition, the combination of the organic silica thin film, which is an energy donor, and the labeled molecule, which is an energy receptor, determines the efficiency of energy transfer, the overlap between the emission spectrum of the organic silica thin film and the absorption spectrum of the molecule to be measured, the intensity of interaction, and the like. It can be decided appropriately from the point. For example, when a crosslinked organic silica thin film having a triphenylamine group is used as the organic silica thin film, 2-aminoacridone or the like can be preferably used as the labeling molecule, and a methylacridone group can be used as the organic silica thin film. When the crosslinked organic silica thin film having the same is used, 4-Fluoro-7-nitrovenzofurazan, 4-Fluoro-7-sulfobenzofurazan, 3-Chlorocarbonyl-6,7-dimethoxy-1-methyl-2 (1H) are used as labeling molecules. -Quinoxaline and the like can be preferably used. Such a labeled molecule preferably has a functional group that easily chemically bonds with the target molecule, and may be used after derivatization in another container, or the hydrophobic layer of the organic silica substrate of the present invention. It may be done on the surface (surface) on which is formed.

The reason why the molecule to be measured can be ionized more efficiently by using the organic silica substrate of the present invention as a substrate for analysis is not always clear, but the present inventors speculate as follows. .. That is, first, when the organic silica thin film included in the organic silica substrate of the present invention is irradiated with laser light, the organic groups in the film absorb the laser light. By absorbing the laser beam in this way, the light energy absorbed by the organic silica thin film can be transferred to the measurement target molecule (energy receptor). As described above, the organic silica thin film according to the present invention acts as an energy donor that transfers light energy to the measurement target molecule (energy receptor) when irradiated with laser light. The energy transfer from such an organic silica thin film (energy donor) to the molecule to be measured (energy acceptor) includes energy transfer that does not pass through light emission (for example, excitation energy transfer or electron transfer between molecules, or heat. Transfer as energy) and energy transfer via light emission (for example, energy transfer in which the molecule to be measured absorbs light emitted from an organic group of an organic silica thin film that has absorbed laser light (energy transfer by light emission reabsorption)) Can be considered. Then, the present inventors presume that such energy transfer makes it possible to more efficiently ionize the molecule to be measured by using the laser beam.

Further, in the present invention, it is considered that such energy transfer makes it possible to more efficiently ionize the molecule to be measured by using the laser beam. Therefore, the molecule to be measured and the organic group are selected. It is preferable to select so as to satisfy the following relationship. That is, no matter what the energy transfer (energy transfer from the organic silica thin film (energy donor) to the measurement target molecule (energy acceptor)), it is possible to transfer energy more efficiently. From the viewpoint, the spectrum of light emitted from the organic group of the organic silica thin film after the irradiation laser light is absorbed by the organic group in the organic silica thin film (emission spectrum from the organic group) and the measurement target molecule. It is more preferable to select the organic group and the molecule to be measured so that the absorption spectra of the above are overlapped at at least one wavelength. As described above, when the emission spectrum from the organic group and the absorption spectrum of the molecule to be measured overlap at a certain wavelength, the light energy absorbed by the organic silica thin film or the excitation energy of the organic silica thin film is obtained. Tends to move more efficiently depending on the molecule to be measured. In particular, when energy is transferred via light emission, the organic silica thin film absorbs the irradiation laser light and emits light, and the emission spectrum of the organic silica thin film (emission spectrum from an organic group) and the above. It is more preferable that the absorption spectra of the molecules to be measured overlap at least at one wavelength. This is because the light energy emitted from the organic silica thin film tends to be efficiently transferred to the molecule to be measured by such light emission.

In addition, regardless of the form of energy transfer (whether via light emission or not), the short wavelength end of the emission spectrum of the organic silica thin film However, because the absorption spectrum of the measurement target molecule is on the short wavelength side from the long wavelength end, the emission spectrum of the organic silica thin film and the absorption spectrum of the measurement target molecule overlap at least at one wavelength. Is more preferable. In such a case, the light energy absorbed by the organic silica thin film tends to move more efficiently with respect to the molecule to be measured as light energy or excitation energy.

In such a laser desorption / ionized mass spectrometry method, in mass spectrometry, first, a sample containing a molecule to be measured is supported on the surface on which the hydrophobic layer of the organic silica substrate of the present invention is formed. The method for supporting such a sample is not particularly limited, but for example, by applying a solution containing the sample to the surface (surface) of the organic silica substrate on which the hydrophobic layer is formed and removing the solvent. It is preferable to adopt the method of supporting the sample on the organic silica substrate of the present invention by placing the sample. The solvent used for the solution containing such a sample is not particularly limited, but when a peptide molecule is used as the measurement target molecule, water, acetonitrile, and methanol are used from the viewpoint of solubility and versatility. , And it is preferable to use a mixed solvent of two or more of these. Further, the method of applying the solution containing the sample is not particularly limited, but since the amount of the adjusted solution may be small and the specified amount of sample can be introduced (supported) more efficiently, the method of applying the solution by dropping the solution. It is preferable to adopt. As described above, the sample precursor (molecule before enzyme treatment) is supported on the organic silica substrate of the present invention and then subjected to enzyme treatment to prepare the molecule to be measured (enzyme-treated product) on the substrate. As a result, the sample containing the molecule to be measured (enzyme-treated product) may be supported on the surface (surface) on which the hydrophobic layer of the organic silica substrate of the present invention is formed. In this way, the sample finally containing the measurement target molecule (the measurement target molecule itself, the derivative of the measurement target molecule, the mixture of the measurement target molecule and the standard substance, etc.) is supported on the organic silica substrate of the present invention. If possible, the method of supporting the sample is not particularly limited.

In the present invention, as described above, after the sample containing the molecule to be measured is supported on the surface on which the hydrophobic layer of the organic silica substrate of the present invention is formed, laser light is applied to the sample-supporting portion of the film. By irradiating with, the molecule to be measured is ionized and mass spectrometry is performed.

The laser light source used for such mass analysis is not particularly limited, and examples thereof include a nitrogen laser (337 nm), a YAG laser triple wave (355 nm), an NdYAG laser (256 nm), and a carbon dioxide gas laser (9400 nm, 10600 nm). A laser light source can be mentioned, but a nitrogen laser or a YAG laser triple wave laser light source is preferable from the viewpoint that the organic silica thin film is a laser light source having a wavelength capable of efficiently absorbing light.

Further, the laser light source (for example, a light source of a nitrogen laser) is used to irradiate the sample-carrying portion on the organic silica substrate with laser light. By irradiating the sample-carrying site with the laser beam in this way, the molecule to be measured can be ionized. As described above, the ionization mechanism is caused by the irradiation laser being absorbed by the organic group existing at the irradiation site of the laser and the absorbed light energy being efficiently transferred to the measurement target molecule. The present inventors infer. The irradiation conditions of the laser beam (irradiation intensity, irradiation time, etc.) are not particularly limited, and the optimum conditions may be appropriately selected and set from the known mass spectrometry conditions according to the molecule to be measured. ..

The ion separation and detection method for mass spectrometry is not particularly limited, and is a double convergence method, a quadrupole focusing method (quadrupole (Q) filter method), a tandem quadrupole (QQ) method, and ions. A trap method, a flight time (TOF) method, or the like can be appropriately adopted, whereby ionized molecules can be separated and detected according to a mass / charge ratio (m / z). A commercially available device can be appropriately used for such ion separation detection. For example, a mass spectrometer manufactured by Bruker Daltonics (trade name “autflex” or the like), an ion trap time-of-flight mass manufactured by Shimadzu, etc. An analyzer (trade name “AXIMA-QIT, etc.”) or the like may be used as appropriate. In this way, mass spectrometry of the ionized molecule to be measured can be performed.

Since the laser desorption / ionization mass spectrometry method of the present invention uses the organic silica substrate of the present invention as the analysis substrate, the hydrophobic layer specifically adsorbs the sample containing the molecule to be measured. Etc. are suppressed, and a sample containing the molecule to be measured can be more uniformly supported on the substrate, and the interaction between the surface of the substrate and the molecule to be measured is sufficiently suppressed, so that it is easy to irradiate the laser beam. It is possible to desorb / ionize the molecule to be measured, to make the signal intensity of the molecule to be measured higher in the mass spectrum, and to perform more sensitive analysis. The inventors speculate. Further, in the present invention, since it is not necessary to use a sample (sample) in which a matrix compound (low molecular weight organic substance) is mixed with the measurement target molecule (analysis target compound), the measurement is performed without detecting the peak derived from the matrix. It is also possible to measure the peak derived from the target molecule with high sensitivity.

Hereinafter, the present invention will be described in more detail based on Examples and Comparative Examples, but the present invention is not limited to the following Examples.

(Example 1)
<Preparation process of organic silica thin film>
The following formula (A):

[Group wherein ^(A), represented by i Pr denotes an isopropyl group. ]
Ratio of the mass of silicon ([mass of silicon] / [mass of organic group]) to the mass of organic group in the compound represented by (180 mg; mass ratio of silicon is 17.4 mass%). compound, as used herein, the term "organic group", the above formula (a) from the two equations: ^-Si a (O i _Pr) means a residue obtained by removing a group represented by _3), of 2mL It was dissolved in 1-propanol to obtain a mixed solution. Next, 24 μL of 2 M (mol / L) hydrochloric acid was added to the mixed solution, and the mixture was stirred at room temperature for 60 minutes, and then 400 μL of 2-methoxyethanol was further added and stirred for 5 minutes to prepare a sol solution. .. Next, after filtering the obtained sol solution with a membrane filter, the filtered sol solution is spin-coated (4 s at 1400 rpm) on a silicon substrate to form an uncured organic silica thin film on the silicon substrate. did. In the film (uncured organic silica thin film) thus obtained from the sol solution, most (almost) of the solvent was evaporated (volatile) during spin coating. It was confirmed by observing the film immediately after the film formation with an atomic force microscope (AFM) that the film thickness was in the range of 250 to 350 nm. The purpose of the silicon substrate coated with the organic silica thin film in this manner is to promote the hydrolysis of the residual alkoxy group and the curing of the thin film, and to expose the hydroxyl groups (groups capable of reacting with the hydrophobic material) to the surface of the organic silica thin film. , 6N (specified) hydrochloric acid vapor was exposed at 80 ° C. for 3 hours to prepare an organic silica thin film on a silicon substrate (base material). In this way, a laminated body in which an organic silica thin film was laminated on a silicon substrate (base material) was obtained.

<Preparation process of hydrophobic layer>
Apart from the preparation of the organic silica thin film, a hydrophobic material made of silicon alkoxide having a fluoroether group as a hydrophobic group (trade name "Optur (registered trademark) DSX" manufactured by Daikin Industries Co., Ltd.) is hydrofluoroether by 0.1 mass. A hydrophobized solution was prepared by diluting to%. Then, the laminate obtained after being exposed to the vapor of hydrochloric acid as described above was immersed in the hydrophobized solution for 1 minute. Next, the laminate is slowly pulled up from the hydrophobized solution and then exposed to saturated steam at 60 ° C. for 2 hours to form a layer made of a hydrophobic material on the surface of the organic silica thin film of the laminate. A hydrophobic treatment was performed, and a hydrophobic layer (a layer made of a hydrophobic material) was laminated on the surface of the organic silica thin film. Next, the laminate immediately after the hydrophobizing treatment was immersed in hydrofluoroether and ultrasonically cleaned for 5 minutes to remove excess hydrophobic material. In this way, a layer made of a hydrophobic material (hydrophobic layer) is formed on the surface of the organic silica thin film on the base material, and the organic silica substrate (base material / organic silica thin film) for laser desorption / ionization mass analysis is formed. (Laminated body laminated in the order of / hydrophobic layer) was obtained.

(Example 2)
First, in the same manner as in the preparation step of the organic silica thin film adopted in Example 1, except that 200 μL of 2-methoxyethanol was added instead of 400 μL of 2-methoxyethanol when preparing the sol solution. An organic silica thin film was prepared on a silicon substrate (base material). Then, during the hydrophobizing treatment, the process was the same as in the preparation step of the hydrophobic layer adopted in Example 1 except that the product was exposed to saturated water vapor at 60 ° C. for 3 hours instead of being exposed to saturated water vapor at 60 ° C. for 3 hours. (Adopting the conditions of), a layer made of a hydrophobic material (hydrophobic layer) is formed on the surface of the organic silica thin film on the base material, and the organic silica substrate for laser desorption / ionization mass analysis (base material / A laminate in which the organic silica thin film / hydrophobic layer was laminated in this order) was obtained.

(Example 3)
<Preparation process of organic silica thin film>
A sol solution was prepared by dissolving the compound (90 mg) represented by the above formula (A) in 1 mL of 1-propanol, adding 10 μL of 2 M (mol / L) hydrochloric acid, and stirring at room temperature for 60 minutes. .. Next, after filtering the obtained sol solution with a membrane filter, the filtered sol solution is spin-coated (4 s at 1400 rpm) on the silicon substrate to form an organic silica thin film (thickness: 250 to 250). The range of 350 nm) was formed. The purpose of the silicon substrate coated with the organic silica thin film in this way is to promote the hydrolysis of residual alkoxy groups and the curing of the thin film, and to expose the hydroxyl groups (groups capable of reacting with the hydrophobic material) to the surface of the organic silica thin film. Then, the organic silica thin film was prepared on a silicon substrate (base material) by exposing it to 6N (specified) hydrochloric acid vapor at 80 ° C. for 3 hours. In this way, a laminated body in which an organic silica thin film was laminated on a silicon substrate (base material) was obtained.

<Preparation process of hydrophobic layer>
Instead of using the above hydrophobized solution, hydrophobic material composed of trimethoxy (3,3,3-trifluoropropyl) silane (silicon alkoxide having 3,3,3-trifluoropropyl group as hydrophobic group) is hydrophobized. The same as the step of preparing the hydrophobic layer adopted in Example 1 (adopting the same conditions) except that the hydrophobized solution prepared by diluting to 0.1% by mass with fluoroether was used. , A layer made of a hydrophobic material (hydrophobic layer) is formed on the surface of the organic silica thin film on the base material, and the organic silica substrate for laser desorption / ionization mass analysis (base material / organic silica thin film / hydrophobic layer) (Laminated body laminated in order) was obtained.

(Example 4)
<Preparation process of organic silica thin film>
An organic silica thin film was prepared on a silicon substrate (base material) in the same manner as in the step of preparing the organic silica thin film adopted in Example 1. In this way, a laminated body in which an organic silica thin film was laminated on a silicon substrate (base material) was obtained.

<Preparation process of hydrophobic layer>
Apart from the preparation of the organic silica thin film, a hydrophobized solution containing dehydrated toluene (10 mL) and a hydrophobic material (2 mL) composed of chlorotrimethylsilane (a silane compound having a methyl group as a hydrophobic group) was prepared. Then, the laminate obtained as described above is immersed in the hydrophobized solution and then heated at 110 ° C. for 12 hours in an Ar atmosphere on the surface of the organic silica thin film of the laminate. It was hydrophobized to form a layer of hydrophobic material. In this way, after forming a layer made of a hydrophobic material on the surface of the organic silica thin film (after reacting a hydroxyl group or the like on the surface with the hydrophobic material to make the hydrophobic material hydrophobic). The laminated body after the hydrophobizing treatment was immersed in dehydrated toluene and ultrasonically cleaned for 5 minutes to remove excess hydrophobic material. In this way, a layer made of a hydrophobic material (hydrophobic layer) is formed on the surface of the organic silica thin film on the base material, and the organic silica substrate (base material / organic silica thin film) for laser desorption / ionization mass analysis is formed. (Laminated body laminated in the order of / hydrophobic layer) was obtained.

The hydrophobic material used for producing such an organic silica substrate is chlorotrimethylsilane, and since such chlorotrimethylsilane reacts only with the hydroxyl group on the surface of the organic silica thin film, the organic silica It is clear that a hydrophobic material is introduced into a single layer on the surface of the thin film, and a monomolecular film of chlorotrimethylsilane is formed as a hydrophobic layer. Therefore, the thickness of the hydrophobic layer is 0.4 nm because of the size of the introduced component (it is clear that it is introduced in the structure of the group represented by the formula: -O-Si- (CH ₃ ) ₃ ). (Note that the molecular size of chlorotrimethylsilane is about 0.4 nm).

(Example 5)
<Preparation process of organic silica thin film>
The compound (180 mg) represented by the above formula (A) was dissolved in 2 mL of 1-propanol to obtain a mixed solution. Next, 24 μL of 2 M (mol / L) hydrochloric acid was added to the mixed solution, and the mixture was stirred at room temperature for 60 minutes, and then 200 μL of 2-methoxyethanol was further added and stirred for 5 minutes to prepare a sol solution. .. Next, after filtering the obtained sol solution with a membrane filter, the filtered sol solution is spin-coated (4 s at 1400 rpm) on a 2 cm square size silicon substrate to uncured organic matter on the silicon substrate. A silica thin film (thickness: in the range of 250 to 350 nm) was formed. Next, a thin film (trade name "FleFimo" manufactured by Soken Kagaku Co., Ltd., nanopillar array, pitch 250 nm, pillar diameter 150 nm, pillar height 250 nm) made of polyethylene terephthalate was spin-coated on a silicon substrate as described above. Immediately after forming the uncured organic silica thin film), the nanomold was quickly placed on the surface of the thin film (uncured organic silica thin film) and pressed at 1.4 ton for 2 hours using a flat plate press. Then, the nanomold was removed to obtain an organic silica thin film having an uneven structure. In this way, after obtaining a silicon substrate on which organic silica thin films having an uneven structure are laminated, hydrolysis of residual alkoxy groups and curing of the thin films are promoted, and hydroxyl groups (groups capable of reacting with hydrophobic materials) are made of organic silica. For the purpose of exposing to the surface of the thin film, an organic silica thin film having an uneven structure was prepared on a silicon substrate (base material) by exposing it to 6N (specified) hydrochloric acid vapor at 80 ° C. for 3 hours. In this way, a laminated body in which an organic silica thin film having an uneven structure was laminated on a silicon substrate (base material) was obtained.

<Preparation process of hydrophobic layer>
The step of preparing the hydrophobic layer adopted in Example 2 except that the laminate thus obtained (an organic silica thin film having an uneven structure laminated on a silicon substrate (base material)) was used. In the same manner (adopting the same conditions), a layer made of a hydrophobic material (hydrophobic layer) is formed on the surface of an organic silica thin film having an uneven structure on a base material, and laser desorption / ionization mass is formed. An organic silica substrate for analysis (a laminate in which a base material / an organic silica thin film having an uneven structure / a hydrophobic layer was laminated in this order) was obtained.

[Regarding the uneven structure on the surface of the organic silica thin film prepared in Example 5]
<Measurement of organic silica thin film with uneven structure with a microscope>
During the production of the organic silica thin film having the uneven structure as described above (porous organic silica thin film), the organic silica thin film having the uneven structure after removing the nanomold (before exposure to the vapor of 6 mol / L hydrochloric acid). The surface shape of the thin film) was measured by a scanning electron microscope (SEM) and an atomic force microscope (AFM). As a scanning electron microscope (SEM), a scanning electron microscope (trade name "Hitachi S-4800") manufactured by Hitachi High-Technologies Co., Ltd. is used, and as an atomic force microscope, a scanning probe is used as a measuring device. A microscope (SPM / AFM: trade name "NanoNavi E-sweep" manufactured by Hitachi High-Tech Science) was used.

As a result of such measurement, a scanning electron microscope (SEM) photograph of the surface of the organic silica thin film prepared in Example 5 is shown in FIG. As is clear from the SEM image shown in FIG. 4, the organic silica thin film prepared in Example 5 has a regular nanoporous structure (pore structure) to which the nanomold structure is transferred. I understood.

Further, in the measurement by the atomic force microscope (AFM), the measurement points were changed and the measurement was performed at a plurality of points, and the cross-sectional view (vertical cross-sectional view) was obtained at each measurement point. Then, when the axial direction (the direction of the long axis of the pores) of an arbitrary 100 points of the concave-convex structure was measured from a plurality of cross-sectional views obtained by such AFM measurement, the axial direction of the measured uneven structure was eventually determined. However, the angle is within the range of 90 ° ± 15 ° with respect to the surface of the surface opposite to the surface on which the uneven structure of the organic silica thin film is formed, and the axial direction of the uneven structure is that of the organic silica thin film. It was confirmed that the surface was oriented substantially perpendicular to the surface of the surface opposite to the surface on which the uneven structure was formed. Further, from the cross-sectional view obtained by such AFM measurement, for each of the convex portions at any 100 points, between the convex portions and the closest convex portion at a height of half the average height described later. The distance between the wall surfaces (horizontal distance) was measured, the average was calculated, and the average value of the distance between the wall surfaces of the convex portion (average pore diameter of the pores) was measured. It was confirmed that the average value of the distances between the wall surfaces of the convex portions (the average pore diameter of the pores) was 140 nm. Further, when the average height of the convex portion (average depth of the pores (concave)) was obtained for an arbitrary 100-point uneven structure from the cross-sectional view obtained by AFM measurement of the organic silica thin film, the height of the convex portion was obtained. It was found that the average value of (depth of recess) was 220 nm.

(Comparative Example 1)
By preparing the organic silica thin film on the silicon substrate (base material) in the same manner as in the step of preparing the organic silica thin film adopted in Example 1, the organic silica thin film is laminated on the silicon substrate (base material). After obtaining the body, the laminate was immersed in ethanol and subjected to ultrasonic treatment for 5 minutes, and the organic silica substrate for laser desorption / ionization mass analysis for comparison (base material / organic silica thin film was laminated in this order). A laminate) was obtained. As described above, in Comparative Example 1, the laminate obtained in the same manner as the preparation step of the organic silica thin film adopted in Example 1 was washed with ethanol without forming a hydrophobic layer on the surface of the organic silica thin film. Then, it was used as it was as an organic silica substrate for comparison.

(Comparative Example 2)
First, in the same manner as in the step of preparing the organic silica thin film adopted in Example 3, an organic silica thin film is prepared on a silicon substrate (base material), and the organic silica thin film is laminated on the silicon substrate (base material). I got a body. Then, instead of exposing to saturated water vapor at 60 ° C. for 2 hours, it is exposed to saturated water vapor at 80 ° C. for 3 hours, and the time for ultrasonic cleaning of the laminate after hydrophobization treatment (immersion in hydrofluoroether and ultrasonic waves). A layer made of a hydrophobic material on the surface of the organic silica thin film on the base material in the same manner as the step of preparing the hydrophobic layer adopted in Example 3 except that the washing time) was changed from 5 minutes to 30 minutes. A (hydrophobic layer) was formed, and an organic silica substrate for laser desorption / ionized mass analysis (a laminate in which a substrate / an organic silica thin film / a hydrophobic layer was laminated in this order) was obtained for comparison.

(Comparative Example 3)
First, in the same manner as in the process of preparing the organic silica thin film adopted in Example 1, an organic silica thin film is prepared on a silicon substrate (base material), and the organic silica thin film is laminated on the silicon substrate (base material). I got a body. Next, the laminate was immersed in the hydrophobic treatment solution for 1 minute using the same hydrophobic treatment solution as the hydrophobic treatment solution used in the preparation step of the hydrophobic layer adopted in Example 1. Next, the laminate was slowly pulled up from the hydrophobized solution and allowed to stand for 12 hours under a nitrogen atmosphere at room temperature (25 ° C.), and then heated at 60 ° C. for 3 hours under an air atmosphere. The surface of the organic silica thin film is hydrophobized to form a layer made of a hydrophobic material (hydrophobic layer) on the surface of the organic silica thin film on the substrate, for laser desorption / ionization mass analysis for comparison. (A laminate in which a base material / an organic silica thin film / a hydrophobic layer was laminated in this order) was obtained. In this way, after the hydrophobic layer was formed, the organic silica substrate was formed without ultrasonic cleaning.

[Evaluation of the characteristics of the organic silica substrate obtained in Examples 1 to 5 and Comparative Examples 2 to 3]
<Characteristics of organic silica thin film included in organic silica substrate>
In order to measure the absorption wavelength of the organic group in the organic silica thin film provided on the organic silica substrate, a measurement sample was formed as follows and the ultraviolet / visible absorption spectrum was measured. That is, first, a sol solution is prepared in the same manner as in Example 1, filtered through a membrane filter, and then the filtered sol solution is spin-coated (4 s at 1400 rpm) on a silica substrate to uncured organic. After forming the silica thin film, the organic silica thin film was cured by heating at 80 ° C., and this was used as a sample for measurement. The ultraviolet / visible absorption spectrum of the sample for such measurement is shown in FIG. As is clear from the result of the ultraviolet / visible absorption spectrum of the sample for such measurement (FIG. 5), the organic silica thin film (represented by the above formula (A)) included in the organic silica substrate obtained in Example 1 It was confirmed from the ultraviolet / visible absorption spectrum that the organic group in the compound (polymer of the organic silicon compound) has an absorption maximum wavelength at 243 nm, 344 nm, and 354 nm, and the organic silica thin film obtained in Example 1 was obtained. It was confirmed that the organic group inside was capable of absorbing laser light. Considering that all of the organic silica thin films formed in Examples 2 to 5 were formed by using the compound represented by the above formula (A), they were formed in Examples 2 to 5. It is clear that the organic groups in the organic silica thin film can also absorb the laser beam.

<Measurement of hydrophobic layer thickness>
In order to measure the thickness of the hydrophobic layer, first, a sample (organic silica substrate) for calibration curve measurement was separately manufactured as follows. That is, instead of immersing the laminate immediately after the hydrophobization treatment in hydrofluoroether and performing ultrasonic cleaning for 5 minutes, the laminate after the hydrophobization treatment is allowed to stand (leave) for 12 hours under room temperature conditions. ), Then the sample for calibration line measurement (base material / organic silica thin film / hydrophobic layer) was laminated in the same order as in Example 1 except that it was immersed in hydrofluoroether and ultrasonically cleaned for 5 minutes. An organic silica substrate made of a laminated body) was obtained.

Next, the energy dispersive type is applied to the organic silica substrates obtained in Examples 1 to 5 and Comparative Examples 2 to 3 and the sample for calibration curve measurement (organic silica substrate) prepared as described above. Using a scanning electron microscope (SEM: trade name "SU3500" manufactured by Hitachi High-Technologies Co., Ltd.) equipped with an X-ray spectroscopy (EDX) analyzer, EDX analysis was performed under the condition of an acceleration voltage of 3 kV, and the surface of each organic silica substrate was used. The contents of the elements (C, Si, F, O, N) constituting the vicinity (range of 100 nm from the surface to the thickness direction) were determined, and among all the elements (C, Si, F, O, N). The mass ratio (wt%) of F was calculated.

In addition to the EDX analysis, the surface layer of the sample for calibration curve measurement (organic silica substrate) and the organic silica substrates obtained in Example 3 and Comparative Example 2 by X-ray photoelectron spectroscopy (XPS). The composition analysis (analysis of the composition of C, Si, F, O, N) of the part (range of 10 nm from the surface to the thickness direction) was performed. In such XPS analysis, the XPS device (trade name "PHI 5000 Versaprobe II" manufactured by ULVAC-PHI) was used as the measuring device, and the following measurement conditions were adopted.
[Measurement conditions for X-ray photoelectron spectroscopy]
X-ray source: AlKα
Photoelectron extraction angle: 18 °
Analysis area: Area with a diameter of 100 μm Path energy: 93.8 eV
Energy step: 0.2 eV.

Then, from the relationship between the XPS data and the EDX data of the sample for the calibration curve measurement (organic silica substrate) and the organic silica substrate obtained in Example 3 and Comparative Example 2, a calibration curve relating to the amount ratio of F element is obtained. Obtained (Fig. 6). Although the types of hydrophobic materials used for forming the hydrophobic layer are different between Example 3 and Comparative Example 2 and the sample for calibration curve measurement, both are measured by targeting the fluorine element. In the calculation described later, it is considered that the distribution state of fluorine in the formed hydrophobic layer is the same, and when XPS analysis is performed regardless of the type of hydrophobic material used in these examples and the like. A calibration curve for estimating the value of the elemental ratio of fluorine that would have been measured can be obtained.

Next, using the calibration curve, from the results of the EDX data (values obtained by EDX analysis) of the organic silica substrate obtained in Examples 1 and 2 and 5 and Comparative Example 3, Examples 1 and 2 and With respect to the organic silica substrate obtained in 5 and Comparative Example 3, the element amount ratio of F that would be obtained when XPS was performed in the range of 10 nm from the surface in the thickness direction was estimated. Since the sample (organic silica substrate) for measuring the calibration curve and the XPS data of the organic silica substrate obtained in Example 3 and Comparative Example 2 can be used as they are, the calculation from the calibration curve is not particularly performed. ..

Then, using the values and the like thus obtained, the following formula (IA):

[In the formula, Y is the amount ratio of fluorine elements determined by XPS analysis (formula: [amount of fluorine (F) determined by XPS analysis] / [amount of all elements (excluding hydrogen) determined by XPS analysis]]. It is a value obtained by calculation. In some cases, it may be a quantitative ratio of fluorine elements calculated from a calibration line), and M is a repeating unit of a hydrophobic material (hydrophobic molecule). Indicates the molecular weight of, ρ indicates 1.5 (value of the density of the hydrophobic layer), L indicates the thickness of the hydrophobic layer, and m _f indicates the number of fluorine atoms (number of atoms) in the repeating unit in the hydrophobic material. Shown, m indicates the total number of atoms of the repeating unit of the hydrophobic material (however, the number of hydrogen atoms is excluded), ρ'is 1.18 which is the density value of the organic silica thin film, and N is the organic silica thin film. Indicates the molecular weight of the repeating unit of (it can be seen from the type of compound represented by the above formula (A) that it is "426"), and n is the number of all atoms constituting the repeating unit of the organic silica thin film (however, hydrogen). The number of atoms is excluded: It can be seen from the type of compound represented by the above formula (A) that it is "28"). ]
The thickness of the hydrophobic layer in the organic silica substrates obtained in Examples 1 to 3 and Comparative Examples 2 to 3 and the sample for calibration curve measurement (organic silica substrate) prepared as described above. Asked. The results obtained are shown in Table 1.

The hydrophobic material used in Examples 1 to 2 and 5 and Comparative Example 3 is Optool DSX (the number m of all atoms excluding the number of hydrogen atoms in the repeating unit of the hydrophobic material is 4), which is hydrophobic. Since the group is composed of a fluoroether group, in the calculation of the above formula (IA), the repeating unit of the hydrophobic group is a repeating unit represented by the formula: −OCF _2- (molecular weight M: 66, m _f : The calculation was performed by imitating what is 2). The hydrophobic material used in Example 3 and Comparative Example 3 is trimethoxy (3,3,3-trifluoropropyl) silane (the number m of all atoms excluding the number of hydrogen atoms in the repeating unit of the hydrophobic material is 3). The hydrophobic group is composed of a fluoroalkyl group (the hydrophobic group is a 3,3,3-trifluoropropyl group). Therefore, in the calculation of the above formula (IA), a repeating unit of the hydrophobic group is used. There formula: -CF ₂ - repeating units (molecular weight _{M: 50, m f: 2} ) represented by a calculation was performed by fiction as a. For the density ρ'of the organic silica thin film, a bulk body of organic silica was prepared, and the value obtained by applying Archimedes' principle was used. Further, the value of Y (quantity ratio of fluorine element obtained by XPS analysis) in the formula (IA) is obtained in the sample for calibration curve measurement (organic silica substrate) and in Example 3 and Comparative Example 2. For the obtained organic silica substrate, the measured values obtained by XPS analysis were used as they were, and for the organic silica substrates obtained in Examples 1 to 2, 5 and Comparative Example 3, the F estimated from the above calibration curve. The element amount ratio of was used. The results obtained are shown in Table 1. In addition, Table 1 also shows the elemental ratio of F used in the calculation in percentage (value with the unit as "at%").

In Comparative Example 1, since the hydrophobic layer was not formed, the thickness of the hydrophobic layer was 0 nm, but the thickness is also shown in Table 1 for reference. Further, regarding the thickness of the hydrophobic layer of the organic silica substrate obtained in Example 4, it is clear from the method for producing the hydrophobic layer that a monomolecular layer (monomolecular film) of chlorotrimethylsilane was formed as the hydrophobic layer. Since it is considered that the group represented by the formula: -O-Si- (CH ₃ ) ₃ was introduced on the surface of the organic silica thin film, the formula: -O-Si- (CH ₃ ) ₃ It can be seen that it is 0.4 nm based on the size of the group represented by (0.4 nm). These results are also shown in Table 1.

As is clear from the results shown in Table 1, the film thickness of the hydrophobic layer varies depending on the time of ultrasonic cleaning and the reaction conditions from the steps of preparing the hydrophobic layer adopted in Examples 1 and 3 and Comparative Examples 2 and 3. It turned out to be different.

(Example 6)
Using the organic silica substrate obtained in Example 1 as a substrate for analysis used in the laser desorption / ionization mass spectrometry method, laser desorption / ionization mass spectrometry (LDI-MS) is performed as follows. It was.

That is, first, angiotensin I is selected as the molecule to be measured, and angiotensin I is dissolved in a mixed solvent of water and acetonitrile (volume ratio of water to acetonitrile ([water] / [acetonitrile]) is 9/1). , A solution (A) of angiotensin I having a concentration of 1 pmol / μL was obtained. Next, the solution (A) was applied by dropping 1.0 μL onto the organic silica substrate obtained in Example 1. Next, the organic silica substrate after applying the solution (A) was naturally dried, and angiotensin I (sample) was supported on the surface of the substrate. Next, a mass spectrometer (MALDI-TOF-MS device, trade name "Autoflex") manufactured by Bruker Daltonics Co., Ltd. was used as an analyzer in the same place in the region carrying angiotensin I (the place where the solution was applied). Then, N ₂ laser (wavelength: 337 nm) was irradiated, and mass spectrometry (LDI-MS) was performed in the reflector mode. At the time of analysis, the N ₂ laser was irradiated 10 times under the condition of a laser intensity of 30% (10 shots in total), and the mass spectrum was obtained by integrating the spectra.

[Results of mass spectrometry in Example 6]
The graphs of the mass spectrum obtained as a result of the mass spectrometry of Example 6 are shown in FIGS. 7 and 8. As is clear from the results shown in FIGS. 7 and 8, in the obtained mass spectrum, the signal of the proton adduct of angiotensin I containing an isotope is m / z = 1296.6, 1297.6, It was clearly confirmed at the position of 1298.6. From these results, it was found that when the organic silica substrate obtained in Example 1 was used for mass spectrometry, it was possible to perform analysis with sufficiently high sensitivity.

(Example 7)
The concentration obtained by dissolving angiotensin I in a mixed solvent of water and acetonitrile (volume ratio of water and acetonitrile ([water] / [acetonitrile]) is 6/4) instead of the solution (A) is Laser desorption / ionization mass spectrometry (LDI-MS) was performed in the same manner as in Example 6 except that a solution (B) of 50 fmol / μL of angiotensin I was used.

[Results of mass spectrometry in Example 7]
Graphs of the mass spectrum obtained as a result of the mass spectrometry of Example 7 are shown in FIGS. 9 and 10. As is clear from the results shown in FIGS. 9 and 10, three signals (m / z = 1296.6, 1297) of the proton adduct of angiotensin I containing an isotope in the obtained mass spectrum. The peaks at positions of .6 and 1298.6) were clearly observed.

From the result of the mass spectrometry of Example 7 and the result of the mass spectrometry of Example 6 described above, when the organic silica substrate obtained in Example 1 was used for mass spectrometry, the concentration was low. Even when a solution of the target molecule (concentration: 50 fmol / μL) is used, the signal intensity of the target molecule (angiotensin I) to be measured can be clearly confirmed under the same laser irradiation conditions, and sufficiently sensitive analysis can be performed. It turned out to be.

(Example 8)
Instead of the solution (A), a solution (C) of insulin having a concentration of 1.0 pmol / μL obtained by dissolving insulin (molecular weight: 5303.64) in water was used, and linear instead of the reflector mode. Laser desorption / ionized mass spectrometry (LDI-MS) was performed in the same manner as in Example 6 except that the mode was adopted and measurement (mass spectrometry) was performed.

(Comparative Example 4)
Laser desorption / ionization mass spectrometry (LDI-MS) in the same manner as in Example 8 except that the organic silica substrate obtained in Comparative Example 2 was used instead of the organic silica substrate obtained in Example 1. Was done.

[Results of mass spectrometry in Example 8 and Comparative Example 4]
The graph of the mass spectrum obtained as a result of the mass spectrometry of Example 8 and Comparative Example 4 is shown superimposed on FIG. As is clear from the results shown in FIG. 11, in the mass spectrometry (Example 8) using the organic silica substrate obtained in Example 1, the signal intensity derived from insulin was strongly detected as 46. On the other hand, in the mass spectrometry using the organic silica substrate obtained in Comparative Example 2 (Comparative Example 4), the signal intensity derived from insulin was 11, and it was difficult to distinguish it from the noise peak. From these results, when the organic silica substrate obtained in Example 1 is used for mass spectrometry, the signal intensity of the molecule to be measured (insulin) can be made higher in the obtained mass spectrum. It was confirmed that it is possible to perform more sensitive analysis.

(Example 9)
Instead of using the organic silica substrate obtained in Example 1, the organic silica substrate obtained in Example 2 was used, and instead of the solution (A), polyethylene glycol dimethyl ether having an average molecular weight of 2000 was dissolved in water. Laser desorption / ionized mass spectrometry (LDI-MS) was carried out in the same manner as in Example 6 except that the solution (D) of polyethylene glycol dimethyl ether having a concentration of 5.0 pmol / μL was used.

[Results of mass spectrometry in Example 9]
A graph of the mass spectrum obtained as a result of the mass spectrometry of Example 9 is shown in FIG. As is clear from the results shown in FIG. 12, in the obtained mass spectrum, equidistant signal patterns peculiar to polymers such as ethylene oxide were clearly observed. From these results, it was found that even when the organic silica substrate obtained in Example 2 is used for mass spectrometry, it is possible to perform analysis with sufficiently high sensitivity.

(Examples 10 to 13)
In each example, as the organic silica substrate, the organic silica substrate obtained in Example 1 (Example 10), the organic silica substrate obtained in Example 2 (Example 11), and the organic obtained in Example 3 The silica substrate (Example 12) and the organic silica substrate (Example 13) obtained in Example 4 are used, respectively, and in the region carrying angiotensin I (the place where the solution is applied), 5 different points are arbitrarily selected. In the same manner as in Example 6 except that the measurement sites of the above were irradiated with laser light to perform mass spectrometry, a total of 5 measurement sites were subjected to laser desorption / Ionized mass spectrometry (LDI-MS) was performed. Then, in each example, the average value, standard deviation, and variation value of the signal intensity were obtained from the measurement results of the five different measurement sites.

(Comparative Examples 5 to 7)
Instead of using the organic silica substrate obtained in Example 1, the organic silica substrate obtained in Comparative Example 1 (Comparative Example 5), the organic silica substrate obtained in Comparative Example 2 (Comparative Example 6), and comparison, respectively. Laser desorption / ionization mass for a total of 5 measurement sites for each comparative example in the same manner as in Example 10 except that the organic silica substrate (Comparative Example 7) obtained in Example 3 was used. Analysis (LDI-MS) was performed. Then, in each comparative example, the average value, standard deviation, and variation value of the signal intensity were obtained from the measurement results of the five different measurement sites.

[Results of mass spectrometry of Examples 10 to 13 and Comparative Examples 5 to 7]
Mean value and standard deviation of spectral intensity (signal intensity) obtained from the results of mass spectrometry of Examples 10 to 13 and Comparative Examples 5 to 7 (results of spectral intensities at 5 measurement sites in total). And the variation values are shown in Table 2, respectively.

As is clear from the results shown in Table 2, when the organic silica substrates obtained in Examples 1 to 4 are used (Examples 10 to 13), the organic silica substrates obtained in Comparative Examples 1 to 3 are used. Since the average value of the spectral intensities of the measurement target molecule (angiotensin I) is higher than that in the case of using (Comparative Examples 5 to 7), it was confirmed that more sensitive analysis can be performed. It was. From these results, it is possible to perform more sensitive analysis when an organic silica substrate (Examples 1 to 4) having a hydrophobic layer thickness of 0.2 to 5.5 nm is used. Do you get it. Further, when the organic silica substrates obtained in Examples 1 to 4 were used (Examples 10 to 13), the confirmed signal intensity was 352 or more, and the variation value (ratio) of the signal intensity was high. In contrast to less than 30%, when the organic silica substrates obtained in Comparative Examples 1 to 3 were used (Comparative Examples 5 to 7), the intensity was 187 or less and the variation value of the signal intensity (variable value of signal intensity (Comparative Examples 5 to 7)) The ratio) was larger than 47%. Considering such a result and the thickness of the hydrophobic layer of the organic silica substrate obtained in Examples 1 to 4 and the organic silica substrate obtained in Comparative Examples 1 to 3, the thickness of the hydrophobic layer is 0.2 to 0.2. When an organic silica substrate having a diameter of 5.5 nm (Examples 1 to 4) is used, the signal intensity of the molecule to be measured (angiotensin I) becomes a higher value, and more sensitive analysis can be performed. At the same time, it can be seen that it is possible to perform more accurate analysis with less variation in signal intensity.

(Example 14)
<First mass spectrometry>
Using the organic silica substrate obtained in Example 5, laser desorption / ionization mass spectrometry (LDI-MS) was performed on a total of 25 measurement sites as follows. That is, first, an angiotensin I solution similar to the solution (A) prepared in Example 6 was prepared, and 1.0 μL of the angiotensin I solution was added dropwise to the organic silica substrate obtained in Example 5. Next, the organic silica substrate after applying the solution of angiotensin I was air-dried, and angiotensin I (sample) was supported on the surface of the substrate. Next, by irradiating a 1 mm square region in the region carrying angiotensin I (where the solution was applied) with laser light at intervals of 200 μm, a total of 25 measurement sites were irradiated with laser light, respectively. The spectral intensities at the measurement sites were determined respectively. The measurement of the spectral intensity by such mass spectrometry (LDI-MS) is performed by using a mass spectrometer (MALDI-TOF-MS device, trade name "Autoflex") manufactured by Bruker Daltonix Co., Ltd. as an analyzer. _{N 2} laser (wavelength: 337 nm) as the laser beam irradiated was performed by measuring in reflectron mode. At the time of analysis, the N ₂ laser for each measurement site, respectively irradiated 10 times under the conditions of 30% laser intensity (total 10 shots), by integrating the spectrum to determine the intensity.

<Second mass spectrometry>
Apart from the first mass spectrometry, the organic silica substrate obtained in Example 5 was used instead of the organic silica substrate obtained in Example 1, and the laser intensity was changed from 30% to 8%. Laser desorption / ionization mass spectrometry (LDI-MS) was performed in the same manner as in Example 6 except for the above.

[Results of mass spectrometry in Example 14]
From the result of the first mass spectrometry of Example 14 (value of the spectral intensity at 25 measurement sites), the two-dimensional spectrum intensity (signal intensity) in the 1 mm square region where the first mass spectrometry was performed. The distribution was calculated. The obtained results are shown in FIG. As is clear from the results of the two-dimensional distribution of the spectral intensity (signal intensity) shown in FIG. 13, when the organic silica substrate obtained in Example 5 was used, the entire measured region (25 measurement sites) was used. ), The signal of the proton adduct of the measurement target molecule (angiotensin I) containing the isotope peak was clearly observed at a signal intensity of 100 to 500. The average value of the signal intensities of these 25 measurement sites was 428. Considering these results together with the results of Comparative Examples 5 to 7 (laser desorption / ionized mass spectrometry of 5 measurement sites using the organic silica substrates obtained in Comparative Examples 1 to 3), When the organic silica substrate obtained in Example 5 was used, the average signal intensity of the molecule to be measured (angiotensin I) was compared with the case where the organic silica substrate obtained in Comparative Examples 1 to 3 was used. It was confirmed that the value became higher, and it was found that more sensitive analysis could be performed when the organic silica substrate obtained in Example 5 was used.

Further, the mass spectra obtained by laser desorption / ionized mass spectrometry (LDI-MS: the second mass spectrometry) in which the laser intensity adopted in Example 14 was changed from 30% to 8% are shown in FIGS. 14 and 15. Shown in. As is clear from the results shown in FIGS. 14 and 15, in the obtained mass spectrum, the signal of the proton adduct of angiotensin I containing an isotope was m / z = 1296.6, 1297.6, 1298.6. It was clearly observed at the position of. From these results, even when the laser intensity is low, when the organic silica substrate obtained in Example 5 is used for mass spectrometry, a spectrum of sufficient intensity required for substance identification can be clearly obtained. It was found that it is possible to perform a sufficiently sensitive analysis.

As described above, according to the present invention, when it is used for mass spectrometry, the signal intensity of the molecule to be measured can be made higher in the obtained mass spectrum, and more sensitive analysis can be performed. It is possible to provide an organic silica substrate for laser desorption / ionization mass spectrometry, and a laser desorption / ionization mass spectrometry method using the same. As described above, the organic silica substrate for laser desorption / ionization mass spectrometry of the present invention is particularly useful as an analysis substrate for use in the laser desorption / ionization method (LDI).

1 ... Base material, 2 ... Organic silica thin film, 3 ... Hydrophobic layer, S ₁ ... Surface on the side where the uneven structure of the organic silica thin film having an uneven structure is formed, S ₂ ... Surface on the side opposite to S ₁ ( The surface on the side where the uneven structure is not formed), C ... The major axis of the pore space shape (columnar shape of the void) of the organic silica thin film having the uneven structure, α ... The space shape of the surface S ₂ and the pores. Angle formed by the long axis C of T ... The thickness of the organic silica thin film having an uneven structure.

Claims (5)

It is provided with an organic silica thin film made of organic silica having an organic group capable of absorbing laser light as a skeleton and a hydrophobic layer laminated on the surface of the organic silica thin film, and the hydrophobic layer is an aliphatic carbon skeleton. The layer is made of a hydrophobic material having a hydrophobic group having a main skeleton and a functional group covalently bonded to the silica skeleton of the organic silica, and the thickness of the hydrophobic layer is 0.2 to 5.5 nm. An organic silica substrate for laser desorption / ionized mass analysis. The hydrophobic group is an alkyl group, an alkynyl group, an alkenyl group, a fluorine atom-containing group, an alkyl halide group containing a halogen atom other than a fluorine atom, an alkynyl halide group containing a halogen atom other than a fluorine atom, and a non-fluorine atom. The organic silica substrate for laser desorption / ionization mass analysis according to claim 1, wherein the group is at least one selected from the group consisting of halogenated alkenyl groups containing a halogen atom. The organic silica substrate for laser desorption / ionization mass spectrometry according to claim 1 or 2, wherein the organic group capable of absorbing laser light has a maximum absorption wavelength in the wavelength range of 200 to 600 nm. The organic silica substrate for laser desorption / ionization mass spectrometry according to any one of claims 1 to 3, wherein the organic silica thin film is a thin film having an uneven structure. A laser characterized in that the analytical substrate used in the laser desorption / ionization mass spectrometry is the organic silica substrate for laser desorption / ionization mass spectrometry according to any one of claims 1 to 4. Desorption / ionization mass spectrometry.