KR102207765B1 - Sample plate and method of fabricating the same - Google Patents

Abstract

The present invention relates to a sample plate using a composite matrix in which metal nanoparticles and metal nanoislets are coated on a photoreaction catalyst layer. A sample plate according to an embodiment of the present invention includes a metal substrate, a photoreaction catalyst layer formed on the metal substrate, and a composite matrix including metal nanostructures spaced apart from each other coated on the photoreaction catalyst layer. The photoreaction catalyst layer may include metal oxide nanowires, and the metal nanostructures spaced apart from each other may include metal nanoparticles coated on the metal oxide nanowires or metal nanoislands coated on the metal oxide nanowires. have.

Description

Sample plate and method of fabricating the same}

The present invention relates to a technique for mass spectrometry of a sample to be analyzed, and more particularly, to a sample plate for mass spectrometry and a method of manufacturing the same.

In general, a mass spectrometer is an analysis device that measures the mass of a compound to be analyzed. After charging and ionizing the compound to be analyzed, the molecular weight of the compound is determined by measuring mass-to-charge (m/z). . As a method of ionizing the compound to be analyzed, an electron ionization method using an electron beam, a method of colliding atoms at a high speed, a method using a laser, and a method of spraying a sample in an electric field are known.

As a representative mass spectrometer, the Malditop mass spectrometer (Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectroscopy; MALDI-TOF MS Apparatus) is a target of the analyte by mixing an organic matrix that helps ionization of a sample to be analyzed with the sample. After being placed in, when a laser is irradiated onto the sample to be analyzed, mass spectrometry is performed using the property that the sample to be analyzed is easily ionized with the help of the organic matrix. The malditop mass spectrometry method has an advantage in that it is possible to analyze a sample to be analyzed at a level of peptomol due to its high sensitivity, and it is possible to greatly reduce the phenomenon that the compound to be analyzed is fragmented during ionization. Mass spectrometry using a laser is effective for mass spectrometry of biochemical substances having a high molecular weight such as proteins and nucleic acids, and thus the malditop mass spectrometry has been actively applied in recent years. In general, in the case of ionizing the sample to be analyzed in the malditop mass spectrometry method, since the valent number of the ion of the sample to be analyzed is +1 or +2, it is an easy method to measure the molecular weight of the sample molecule before ionization. .

However, since the malditop mass spectrometry method ionizes the sample to be analyzed using an organic matrix, there is a disadvantage in that different organic matrix materials must be determined according to the type of the sample to be analyzed. In addition, a commonly used organic matrix material has a molecular weight of several hundred Da, and when the molecular weight of the sample to be analyzed is similar to or less than the molecular weight of the organic matrix material, the organic matrix decomposition product is reflected in the mass peak of the mass spectrometry spectrum. Therefore, it has a limitation that is difficult to use for mass spectrometry targeting samples to be analyzed at a level of several hundred Da. In addition, the conventional mass spectrometry method using an organic matrix material has a problem in that ionization efficiency is low.

The technical problem to be solved by the present invention is a sample plate applicable to mass spectrometry, and noise in the mass spectrometry spectrum due to decomposition substances in the matrix for ionization of the sample can be removed or reduced, the ionization efficiency of the sample is high, and the desorption of the sample It is to provide a sample plate that efficiently performs.

In addition, another technical problem to be solved by the present invention is to provide a method of manufacturing a sample plate capable of easily manufacturing a sample plate having the above advantages.

In order to solve the above problems, the sample plate using the composite matrix according to the present invention may include a metal substrate, a photoreaction catalyst layer formed on the metal substrate, and a metal nanostructures spaced apart from each other coated on the photoreaction catalyst layer. have. Optionally, the metal nano-islands may have a diameter of 34.6 nm to 123.5 nm.

In another embodiment, the metal nanostructures spaced apart from each other may include metal nanoparticles and metal nanoislets. In addition, the metal substrate is titanium (Ti), tantalum (Ta), tin (Sn), tungsten (W), zinc (Zn), vanadium (V), ruthenium (Ru), iridium (Ir), iron (Fe , Stainless steel) may include at least one or more.

In one embodiment, the photoreaction catalyst layer is titanium (Ti), tantalum (Ta), tin (Sn), tungsten (W), zinc (Zn), vanadium (V), ruthenium (Ru), iridium (Ir) And at least one of oxides of iron (Fe). In another embodiment, the photoreaction catalyst layer may include TiO ₂ nanowires.

In order to solve the above problems, the method of manufacturing a sample plate according to the present invention comprises the steps of forming a metal substrate, corroding the surface of the metal substrate, cleaning it by exposing it in a cleaning solution, and heat treatment to form the photoreaction catalyst layer. And forming the metal nanostructures spaced apart from each other on the photoreaction catalyst layer, and optionally, the metal nanostructures spaced apart from each other may include metal nanoparticles and metal nanoislets, In another embodiment, the metal nanostructures spaced apart from each other may include a non-oxidizing metal.

In one embodiment, the non-oxidizing metal may include gold (Au), platinum (Pt), silver (Ag), palladium (Pd), aluminum (Al), titanium (Ti), and optionally, the Forming the metal nanoparticles may include dropping a colloidal solution of the metal nanoparticles onto the photoreaction catalyst layer, and in another embodiment, forming the metal nanoislets includes the photoreaction It may include depositing a metal thin film on the catalyst layer and heat treating the metal thin film.

In an embodiment, the thickness of the metal thin film may include that of 1 to 15 nm, and optionally, the heat treatment step is heat-treated at 200° C. to 1200° C. for 2 hours to effectively generate nano islands. In another embodiment, the metal nano-islands include gold (Au) nano-islands, the metal thin film includes a gold (Au) thin film, and the thickness of the gold thin film is 1 nm to 15 nm, and may further include a step of dripping and drying a sample including at least one of taclolimus, cyclosporine A, sirolimus, and everolimus.

According to an embodiment of the present invention, a sample plate using a composite matrix is formed by forming a photoreaction catalyst layer including nanowires of metal oxide and an inorganic-based three-dimensional composite structure coated with the metal nanostructure on the photoreaction catalyst layer. , Unlike the conventional organic matrix by promoting and enhancing the ionization action of the sample by the photoreaction catalyst layer according to laser irradiation, there is no noise, and by amplifying the intensity of the mass peak compared to the sample plate having a simple photoreaction catalyst layer, A sample plate can be provided that greatly improves the measurement sensitivity and measurement limits.

In addition, according to an embodiment of the present invention, a method of manufacturing a sample plate coated with the metal nanoparticles differentiated from the inorganic matrix having a single structure by a simple process of dropping a colloidal solution of metal nanoparticles on the photoreaction catalyst layer Can be provided.

In addition, according to an embodiment of the present invention, by depositing a metal thin film on the photoreaction catalyst layer and heat-treating the intermediate product, metal nanoislets are formed, and a mass peak than that of the sample plate coated with the metal nanoparticles It is possible to provide a sample plate whose size is greatly improved, and measurement sensitivity and measurement limit are improved. Through this, noise, which has been a problem of the conventional organic matrix, can be removed and mass analysis with high reliability is possible.

1A is a diagram schematically illustrating a method of manufacturing a sample plate 100 including a photoreaction catalyst layer CL according to an embodiment of the present invention, and FIG. 1B is A diagram illustrating a method of manufacturing the sample plate 200, and FIG. 1C is a diagram illustrating a method of manufacturing the sample plate 300 coated with metal nanoislets according to another exemplary embodiment.
FIG. 2A is a scanning electron microscope (SEM) image of a surface of a sample plate 200 coated with metal nanoparticles according to an embodiment of the present invention, and FIG. 2B is a metal nano-island coating according to another embodiment. It is a scanning electron microscope image of the surface of the sample plate 300, and FIG. 2C is a scanning electron microscope image showing the size of the metal nanoislets according to the thickness of the metal thin film.
FIG. 3 is a graph showing the intensity of a gyrirang peak according to the thickness of the gold thin film when the photoreaction catalyst layer CL composed of TiO ₂ nanowires according to an embodiment of the present invention is coated with the gold nano islands.
4 is a graph showing the results of mass analysis of the sample plate 100 including the photoreaction catalyst layer CL and the sample plate 200 coated with the metal nanoparticles according to an exemplary embodiment of the present invention.
Figure 4a is a mass spectrometry diagram of the four immunosuppressants analyzed using a sample plate 200 coated with gold nanoparticles according to an embodiment of the present invention, and Figure 4b is a mass spectrometry diagram according to an embodiment of the present invention. It is a mass spectrometry diagram analyzing the four types of immunosuppressants using the sample plate 300 coated with the metal nanoislets.
5 is a sensitivity and analysis limit of the analysis results of the four immunosuppressants using a sample plate 200 coated with metal nanoparticles and a sample plate 300 coated with metal nanoislets according to an embodiment of the present invention. This is a graph comparing (limit of detection).

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.

The embodiments of the present invention are provided to more completely describe the present invention to those of ordinary skill in the art, and the following examples may be modified in various other forms, and the scope of the present invention is It is not limited to the following examples. Rather, these embodiments are provided to make the present disclosure more faithful and complete, and to completely convey the spirit of the present invention to those skilled in the art.

In addition, in the following drawings, the thickness or size of each layer is exaggerated for convenience and clarity of description, and the same reference numerals refer to the same elements in the drawings. As used herein, the term “and/or” includes any and all combinations of one or more of the corresponding listed items.

The terms used in this specification are used to describe specific embodiments, and are not intended to limit the present invention. As used herein, the singular form may include the plural form unless the context clearly indicates another case. Further, as used herein, "comprise" and/or "comprising" specifies the presence of the mentioned shapes, numbers, steps, actions, members, elements and/or groups thereof. And does not exclude the presence or addition of one or more other shapes, numbers, actions, members, elements, and/or groups.

In the present specification, terms such as first and second are used to describe various members, parts, regions, layers and/or parts, but these members, parts, regions, layers and/or parts are limited by these terms. It is self-evident. These terms are only used to distinguish one member, component, region, layer or portion from another region, layer or portion. Accordingly, a first member, part, region, layer or part to be described below may refer to a second member, part, region, layer or part without departing from the teachings of the present invention.

In the present specification, a sample to be analyzed refers to any material that is disposed, coated, or bonded on a photoreaction catalyst layer to be effectively ionized and desorbed by the composite matrix layer when UV is applied to fly with a detector. The sample to be analyzed may be an organic molecular compound, protein or peptide as a representative example.

1A is a diagram schematically illustrating a method of manufacturing a sample plate 100 including a photoreaction catalyst layer CL according to an embodiment of the present invention, and FIG. 1B is A diagram illustrating a method of manufacturing the sample plate 200, and FIG. 1C is a diagram illustrating a method of manufacturing the sample plate 300 coated with metal nanoislets according to another exemplary embodiment.

Referring to FIG. 1A, in order to manufacture the sample plate 100 on which the photoreaction catalyst layer CL is formed, first, a substrate SS on which the photoreaction catalyst layer is formed is prepared. In one embodiment, the substrate SS may include a part or all of metal atoms constituting the photoreaction catalyst layer. In FIG. 1A, a substrate SS including metal atoms constituting the photoreaction catalyst layer is illustrated. In this case, a photoreaction catalyst layer may be formed by directly forming a reaction layer from the surface of the substrate SS. For example, when the photoreaction catalyst layer CL includes a metal oxide, the surface or the whole of the substrate SS may include the metal of the metal oxide, and a part of the surface thereof is oxidized to form the photoreaction catalyst layer CL. ) Can be formed.

The substrate SS is, for example, a titanium substrate provided by polishing a titanium plate. In another embodiment, the substrate SS is tantalum (Ta), tin (Sn), tungsten (W), zinc (Zn), vanadium (V), ruthenium (Ru), iridium (Ir), iron (Fe, stainless steel). Steel) or an alloy thereof.

In one embodiment, the surface of the substrate SS is corroded by exposing the surface of the substrate SS to the oxidizing solvent OS. For example, the substrate SS is immersed in the oxidizing solvent OS and maintained at room temperature for about 24 hours to corrode the surface. In an embodiment, before immersing the substrate SS in the oxidizing solvent OS, a step of polishing the surface of the substrate SS may be further performed. The oxidizing solvent (OS) is an alkaline solution that causes corrosion to metals such as KOH and NaOH. The concentration of the oxidizing solvent (OS) may be 10 M in the concentration range of 2 M to 20 M (see step 1 of FIG. 1A ). The present invention is not limited by the concentration of the oxidizing solvent (OS), and may be variously selected according to the type and characteristics of the sample to be analyzed for mass spectrometry. While corrosion of the surface of the substrate SS occurs by the oxidizing solvent OS, an oxidation reaction proceeds on the surface of the substrate SS to form the oxide layer OL.

Thereafter, the substrate SS is cleaned using a cleaning solution (CW) such as alcohol or distilled water (DW). For example, the substrate SS may be immersed in the cleaning solution CW, for example, for about 48 hours to absorb the cleaning solution CS into the surface layer of the corroded substrate SS, and this process is at least It may be repeated more than once, for example 3 times (see step 2 in FIG. 1A). In this process, the oxidizing solvent OS remaining on the surface of the titanium substrate SS is replaced with a cleaning solution.

Since the surface of the substrate (SS) corroded by the oxidizing solvent has nano-scale pores, the corroded substrate (SS) needs to be exposed in the cleaning solution (CW) for a sufficient time in order to complete this replacement process. There is. In one embodiment, the substrate SS is immersed in the cleaning solution CW for 48 hours at room temperature RT, and the cleaning process may be performed about 3 times (see step 2 of FIG. 1A ).

Thereafter, the cleaned substrate may be heat treated (see step 3 of FIG. 1A ). The heat treatment may be performed within a range of about 200° C. to 1,200° C., and the present invention is not limited thereto, and the temperature of the heat treatment is a photocatalyst for light irradiation of a predetermined frequency of the corroded surface layer of the substrate SS. It can be adjusted to have a crystal structure or microstructure suitable for inducing a reaction. In one embodiment, the substrate SS may be heat-treated at about 600° C. for a predetermined time (eg, 2 hours) in an inert gas atmosphere, for example, an Ar gas atmosphere.

Accordingly, the sample plate 100 in which the photoreaction catalyst layer CL is formed on the surface of the substrate SS may be provided. When the substrate SS is a titanium substrate, a TiO ₂ nanoarray layer may be formed as the photoreaction catalyst layer CL.

In the above-described embodiment, the photoreaction catalyst layer CL is obtained by modifying the surface of the substrate SS. In another embodiment, when the substrate SS does not contain or is not related to the element of the photoreaction catalyst layer CL, a metal layer containing the metal element of the photoreaction catalyst layer CL on the surface of the substrate SS And performing steps 1 to 3 shown in FIG. 1A to form a photoreaction catalyst layer CL from the metal layer.

In another example, the photoreaction catalyst layer CL is a dry vapor deposition method such as chemical vapor deposition, physical vapor deposition, or atomic layer deposition on the substrate SS on which the metal catalyst layer in the form of a dot array is formed to form a nano-scale structure. It may also be synthesized through a wet film formation method such as a sol-gel method. With respect to the precursor material for synthesis, known techniques may be taken into account, and the present invention is not limited thereto. However, preferably, in the case of forming the photoreaction catalyst layer CL by the wet corrosion method described with reference to FIG. 1A, the photoreaction catalyst layer in the shape of a nanoscale structure is obtained by obtaining a porous surface layer by corrosion without the formation of the metal catalyst layer. (CL) can be formed easily.

The above-described photoreaction catalyst layer CL is not consumed by directly participating in the photolysis reaction of the organic molecular compound as an analyte, but may be formed of a material that accelerates the photolysis of the organic molecular compound. In one embodiment, the photoreaction catalyst layer CL is titanium (Ti), tantalum (Ta), tin (Sn), tungsten (W), zinc (Zn), vanadium (V), ruthenium (Ru), iridium ( Ir) and iron (Fe) may contain an oxide of at least one metal. The photoreaction catalyst layer CL is at least one of gold (Au), silver (Ag), platinum (Pt), silicon (Si), germanium (Ge), and gallium (Ga) on or inside the metal oxide. It may further include. Doping of such impurities may be effective in controlling the frequency of a light source for photoreaction of the organic molecular compound.

Preferably, the photoreaction catalyst layer CL may include titanium oxide (TiO ₂ ) having an anatase crystal structure. The titanium oxide (TiO ₂ ) is relatively inexpensive compared to other metal oxides, has a smooth supply, has no photocorrosion, and has a band gap of 3.2 eV and is photodecomposed by photoactivation through short-wavelength light irradiation including ultraviolet rays of about 380 nm or less. There is an advantage of increasing the efficiency of the reaction.

The surface of the photoreaction catalyst layer CL may have a nanoscale structure according to the above corrosion method. The nano-scale structure may have a porosity, and may have a shape in which a fibrous, wire, needle, rod, column, or combination thereof is combined, and may be patterned by photolithography or a shadow masking method.

1A illustrates that the photoreaction catalyst layer CL is formed in an array on the substrate SS. Nanoscale structures of titanium oxide (TiO ₂ ) constituting the photoreaction catalyst layer CL shown in FIG. 1A may be patterned in the form of spots having a diameter of 1 mm. For example, the size of the substrate SS may be about 3 cm x 3 cm, and there may be a plurality of spots of nanoscale structures of titanium oxide (TiO ₂ ) formed on the substrate SS.

The nanoscale structure of the photoreaction catalyst layer CL formed on the substrate SS has the aforementioned porous structure. By expanding the surface area by the porous structure, the contact area with the sample is increased, and the ionization of the sample may be effective.

Referring to FIG. 1B, a metal nanoparticle solution may be provided in the photoreaction catalyst layer (CL of FIG. 1A ). In one embodiment, the photoreaction catalyst layer CL may include TiO ₂ nanowires, and the metal nanoparticles may include gold (Au) nanoparticles. For example, a dispersion solution of gold (Au) nanoparticles may be deposited on the nanoscale structure spot of the TiO ₂ photoreaction catalyst layer CL. In another embodiment, the metal nanoparticle solution may be a suspension solution, and the concentration of the metal nanoparticle solution may be 0.5 mg/ml to 3 mg/ml. However, the concentration range of the exemplified metal nanoparticle solution may be determined by factors such as the type of the metal, the size of the nanoparticle, and the type of analyte to maximize the ionization amplification effect of the photoreaction catalyst layer. It is not. When the concentration of the metal nanoparticle solution is less than the lower limit critical concentration value, the density of the coated metal nanoparticles decreases, so that the ionization amplification effect of the photoreaction catalyst layer cannot be sufficiently obtained. Conversely, when the concentration is higher than the upper limit critical concentration value, the coated The ionization amplification effect may be reduced by aggregation between metal nanoparticles.

In addition, the metal nanoparticles may contain a non-oxidizing metal. It may contain a material having a low specific heat such as gold (Au), platinum (Pt), silver (Ag), palladium (Pd), aluminum (Al), and titanium (Ti). However, it is not limited to these materials, and for example, it is applicable to all metals having low specific heat and considerably high thermal conductivity. In one embodiment, the specific heat of the metal nanoparticles may be 0.1 J/gK to 0.3 J/gK, for example, the specific heat of the gold nanoparticles may be 0.129 J/gK. Further, the thermal conductivity of the metal nanoparticles may be 280 W/mK to 350 W/mK, and for example, the gold nanoparticles may be 318 W/mK. In this example, specific heat and thermal conductivity can be measured by Perkin Elmer's DSC 8500. This is because, in the case of a material having low specific heat and high thermal conductivity, heat transfer to the sample to be analyzed increases, thereby promoting ionization and desorption of the sample to be analyzed, and the case of metal nanoislets, which will be described later, is the same.

Referring to FIG. 1C, in an embodiment, a metal thin film is formed on the photoreaction catalyst layer (CL in FIG. 1A ). The photoreaction catalyst layer CL may include TiO ₂ nanowires, and the metal thin film may include a gold (Au) thin film. Here, the metal nano-islets coated on the photoreaction catalyst layer (CL) have a small specific heat such as gold (Au), platinum (Pt), silver (Ag), palladium (Pd), aluminum (Al), and titanium (Ti). It may contain substances. In order to form the metal thin film, in one embodiment, deposition is performed using sputtering, and the operating conditions of the sputtering may be set to deposit the metal thin film to a thickness of 30 nm or less for 5 to 70 seconds with 100W power, and , Preferably, the deposition thickness may be 1 nm to 15 nm, and the size and distribution of the metal nanoislets may be controlled by adjusting the thickness of the metal thin film according to the sample.

Thereafter, the deposited metal thin film is heat treated. In the case of a gold (Au) thin film, the heat treatment may be performed within a range of about 200° C. to 1200° C. for about 2 hours in order to effectively generate nano islands, and, for example, may be processed at 600° C. The present invention is not limited thereto, and the temperature of the heat treatment may be adjusted so that the metal nanoislets are evenly distributed.

2A is a scanning electron microscope image of a surface of a sample plate 200 coated with metal nanoparticles according to an embodiment of the present invention, and FIG. 2B is a surface of a sample plate 300 coated with metal nanoislets according to another embodiment. Is a scanning electron microscope image of, and FIG. 2C is a scanning electron microscope image showing the size of a metal nanoislet according to the thickness of a metal thin film. 2A and 2B, the photoreaction catalyst layer CL may include TiO ₂ nanowires, the metal nanoparticles may include gold nanoparticles, and the metal nanoislands may include gold nanoislands. . During the scanning electron microscope analysis, the area of the four analyzed locations may be set to 0.484 μm ² , and it can be confirmed whether the metal nanoparticles and the metal nanoislets are evenly distributed through the scanning electron microscope image.

Referring to FIG. 2A, it was observed that the metal nanoparticles were unevenly bonded to the photoreaction catalyst layer CL in a clustered state. At this time, a portion of the photoreaction catalyst layer CL that was exposed without being bonded to the metal nanoparticles was observed, and the metal nanoparticles were observed in an aggregated form. In addition, in one embodiment, the metal nanoparticles may be gold (Au) nanoparticles, the concentration of the gold nanoparticle solution may be 1.23 mg/ml, and the average diameter of the gold nanoparticles is 13 nm to 15 nm Can be

Referring to FIG. 2B, the size and distribution of the metal nanoislets are determined according to the thickness of the metal thin film deposited on the photoreaction catalyst layer CL by sputtering. In one embodiment, the thickness of the metal thin film was adjusted to 1 nm, 5 nm, 10 nm and 15 nm. As the thickness of the gold thin film increases, the size of the coated gold nanoislets increases, and the coated gold nanoislets particles are evenly distributed.

Referring to Figure 2c, in one embodiment, the metal nano-islands may include gold nano-islets, and when the gold thin film has a thickness of 1 nm, 5 nm, 10 nm, and 15 nm, Average diameters may be 34.6 nm, 40.7 nm, 91.5 nm, and 123.4 nm, respectively. The thickness of the metal thin film may be 1 nm to 15 nm, preferably 4 nm to 6 nm. This is because ionization of the sample to be analyzed is promoted as the surface area of the sample plate increases, and the surface area tends to increase as the size of the nanoislets decreases, but decreases again when it is smaller than the lower critical size. The numerical values in this example are illustrative and are not limited to the above examples.

FIG. 3 is a graph showing the intensity of a mass peak according to the thickness of a metal thin film when the photoreaction catalyst layer CL composed of TiO ₂ nanowires according to an embodiment of the present invention is coated with a metal nano island. In FIG. 3, the photoreaction catalyst layer CL may include TiO ₂ nanowires, the metal nanoparticles may include gold nanoparticles, and the metal nanoislands may include gold nanoislets.

3, the thickness of the gold thin film was set to 1 nm, 5 nm, 15 nm, and 20 nm, and in this example, samples included taclolimus, cyclosporine A, sirolimus, and everolimus. It can be four types of immunosuppressants. In the mass spectrometry of the present invention, the concentration of the immunosuppressant sample was 100 μg/ml, and 1 μl was dropped on the sample plate 200 coated with gold nanoparticles and dried to prepare a sample plate.

After the photolysis reaction of the dried sample plate is completed, laser desorption/ionization mass analysis may be performed using, for example, a mass analyzer of Bruker's Microflex type. The mass spectrometer may be a mass spectrometer for malditop analysis. In one embodiment, the reflector of the mass spectrometer is set to a positive mode, the power intensity of the laser is adjusted to a level of several to tens of% based on the maximum output, and the gain value of the detector can be appropriately adjusted.

Referring to FIG. 3 again, as a result of analysis with the sample plate, the mass peak was obtained as a potassium adduct, and no matrix noise generated when using an existing organic matrix was found. In addition, the mass peak showed the greatest intensity when the gold thin film thickness was 5 nm. Accordingly, in mass spectrometry of the four immunosuppressants, it can be seen that the optimum gold thin film thickness is 5 nm when the sample plate is prepared.

4A is a graph showing the results of mass analysis of the sample plate 100 including the photoreaction catalyst layer CL and the sample plate 200 coated with metal nanoparticles according to an exemplary embodiment of the present invention. In FIG. 4A, the photoreaction catalyst layer CL may include TiO ₂ nanowires, the metal nano particles may include gold nano particles, and the metal nano islands may include gold nano islands. In one embodiment, the photoreaction catalyst layer CL may be formed of the TiO ₂ nanowires. It can be seen that the intensity of the mass peak can be maximized compared to the case of using the conventional organic matrix or the sample plate 100 including the photoreaction catalyst layer CL. Mass spectrometry samples were prepared using the four immunosuppressants, but the results of the experiment may not be limited to the samples. The concentration of the four immunosuppressants may be prepared at 1 μg/ml, and the sample plate 100 including CHCA, DHB, the gold nanoparticles, and a photoreaction catalyst layer (CL) corresponding to the existing organic matrix, and The measurement was made using a sample plate 200 coated with gold nanoparticles. The sample may be the above four immunosuppressants, and the mass peak of potassium adduct may be measured.

In the analysis results of the conventional organic matrix, only the noise peak, which is a problem of the conventional mass spectrometer, was observed and the mass peak of the sample was not observed. In addition, in the case of the gold nanoparticles, the mass peak of the sample was not observed. In contrast, in the case of the sample plate 100 including the photoreaction catalyst layer CL and the sample plate 200 coated with metal nanoparticles, a mass peak was observed, and no noise peak was found.

In addition, the intensity of the mass peak in the case of using a composite matrix including a photoreaction catalyst layer (CL) coated with metal nanoparticles or a photoreaction catalyst layer (CL) coated with metal nanoislets is an organic material used in the existing organic matrix, It can be seen that the increase is increased compared to the case of using a single matrix including only the gold nanoparticles or the photoreaction catalyst layer CL. These results were observed for each of the four immunosuppressants. The reason why the difference in mass peak intensity as described above occurs is, first, that in the case of the composite matrix, the contact area is increased by the metal nanoparticles and the metal nanoislets. Second, it is because the photocatalytic reactivity of the metal is improved by interfering with the recombination of electrons and holes due to the formation of a Schottky barrier by the interaction of the metal and the TiO ₂ nanowire. Third, because of the low specific heat and high thermal conductivity of the gold (Au), a large amount of thermal energy is transferred to the sample.

FIG. 4B is a mass spectrometry diagram analyzing the four types of immunosuppressants using the sample plate 300 coated with metal nanoislets according to an embodiment of the present invention. The immunosuppressant, the existing organic matrix, the element to be analyzed (potassium adduct), and the metal nanoparticles are as described above.

In the case of using the sample plate 300 coated with metal nanoislets, noise generated in the existing organic matrix was not found, and the intensity of the mass peak increased compared to the case in which the single matrix was used. In addition, it can be seen that the increase in the mass peak intensity is significantly increased compared to the case of the sample plate 200 coated with metal nanoparticles. For example, it can be seen that the S/N ratio increased by 17.94 times to 391.20 times in the case of the sample plate 300 coated with metal nanoislets compared to the case of using the single matrix.

5 is a sensitivity and analysis limit of the analysis results of the four immunosuppressants using a sample plate 200 coated with metal nanoparticles and a sample plate 300 coated with metal nanoislets according to an embodiment of the present invention. This is a graph comparing (limit of detection). The photoreaction catalyst layer CL may include TiO ₂ nanowires, the metal nanoparticles may include gold nanoparticles, and the metal nanoislands may include gold nanoislands. The comparison of the analysis results may be made in the range of 10 ng/ml to 10000 ng/ml of the concentration of the four immunosuppressants.

In each of the four immunosuppressants, the sample plate 200 coated with the metal nanoparticles exhibits an improved mass peak intensity compared to the sample plate 100 including the photoreaction catalyst layer CL, and the metal nanoislets are The coated sample plate 300 exhibits a significantly improved mass peak intensity. In addition, the analysis limit is found to decrease in the order of the sample plate 100 including the photoreaction catalyst layer (CL), the sample plate 200 coated with metal nanoparticles, and the sample plate 300 coated with metal nanoislets. I can. From the difference in the mass peak intensity, in the case of the composite matrix sample coated with the metal nanostructure, the size of the mass peak was greatly improved compared to the sample plate using the conventional organic matrix and the single matrix, and the measurement sensitivity and measurement limit were significantly You can see that it has improved.

As described above, a sample plate according to various embodiments of the present invention, a manufacturing method thereof, and a mass spectrometry method using the same have been described in detail. However, those of ordinary skill in the technical field to which the present invention pertains will understand that various modifications and variations to the configuration are possible within the scope of the present invention. Accordingly, the scope of the present invention is limited only by the following claims.

SS: Substrate
OS: oxidizing solvent
OL: oxide layer
CW: cleaning liquid
100: a sample plate on which a photoreaction catalyst layer was formed
200: sample plate coated with metal nanoparticles
300: sample plate coated with metal nanoislets

Claims (15)

Metal substrate;
A photoreaction catalyst layer formed on the metal substrate; And
Including metal nanostructures spaced apart from each other coated on the photoreaction catalyst layer,
The photoreaction catalyst layer includes metal oxide nanowires,
The metal nanostructures spaced apart from each other include metal nanoparticles coated on the metal oxide nanowires or metal nanoislands coated on the metal oxide nanowires,
Sample plate using a composite matrix. delete The method of claim 1,
The metal substrate is titanium (Ti), tantalum (Ta), tin (Sn), tungsten (W), zinc (Zn), vanadium (V), ruthenium (Ru), iridium (Ir), iron (Fe, stainless steel). Steel) sample plate comprising at least one or more. The method of claim 1,
The photoreaction catalyst layer is titanium (Ti), tantalum (Ta), tin (Sn), tungsten (W), zinc (Zn), vanadium (V), ruthenium (Ru), iridium (Ir) and iron (Fe) A sample plate comprising at least one or more of oxides of. The method of claim 1,
The photoreaction catalyst layer is a sample plate comprising TiO ₂ nanowires. The method of claim 1,
The metal nano-islands are sample plates having a diameter of 34.6 nm to 123.5 nm. Forming a metal substrate;
Forming a photoreaction catalyst layer by corroding the surface of the metal substrate, cleaning by exposure to a cleaning solution, and heat treatment; And
Including the step of forming metal nanostructures spaced apart from each other on the photoreaction catalyst layer,
The photoreaction catalyst layer includes metal oxide nanowires,
The metal nanostructures spaced apart from each other include metal nanoparticles coated on the metal oxide nanowires or metal nanoislands coated on the metal oxide nanowires,
Method of making a sample plate. delete The method of claim 7,
The metal nanostructures spaced apart from each other are a method of manufacturing a sample plate containing a non-oxidizing metal. The method of claim 9,
The non-oxidizing metal is a method of manufacturing a sample plate containing gold (Au), platinum (Pt), silver (Ag), palladium (Pd), aluminum (Al), and titanium (Ti). The method of claim 7,
The forming of the metal nanoparticles comprises dropping a colloidal solution of the metal nanoparticles on the photoreaction catalyst layer. The method of claim 7,
The forming of the metal nano-island may include depositing a metal thin film on the photoreaction catalyst layer; And
Method of manufacturing a sample plate comprising the step of heat-treating the metal thin film. The method of claim 12,
The thickness of the metal thin film, a method of manufacturing a sample plate comprising that 1 ~ 15nm. The method of claim 12,
The step of heat-treating includes heat-treating at 200°C to 1200°C for 2 hours to effectively generate nano islands. The method of claim 12,
The metal nano-islets include gold (Au) nano-islets,
The metal thin film includes a gold (Au) thin film,
The thickness of the gold thin film is 1 nm to 15 nm,
Taclolimus, cyclosporine A, sirolimus, and a method of manufacturing a sample plate further comprising the step of drying after dripping a sample containing at least one or more of everolimus.

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