WO2012115380A2

WO2012115380A2 - Sample plate for a maldi-tof mass spectrometer, and mass spectrometry method using the maldi-tof mass spectrometer implementing the sample plate

Info

Publication number: WO2012115380A2
Application number: PCT/KR2012/001048
Authority: WO
Inventors: 변재철
Original assignee: 연세대학교 산학협력단
Priority date: 2011-02-21
Filing date: 2012-02-13
Publication date: 2012-08-30
Also published as: KR101204342B1; KR20120095638A; WO2012115380A3

Abstract

The present invention relates to a mass spectrometer for a compound, and more particularly, to a sample plate for a matrix assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometer including a metal nanowire, and to a mass spectrometry method using the MALDI-TOF mass spectrometer including the metal nanowire. To accomplish the aim, the sample plate for a MALDI-TOF mass spectrometer according to the present invention comprises: a metal plate on which a metal oxide having a photocatalyst function is to be formed; and a metal-oxide nanowire spot formed by a plurality of metal oxide nanowires formed on at least a portion of the surface of the metal plate. The metal-oxide nanowire is grown in a top-down manner.

Description

[Specifications

[Name of invention]

Mass spectrometry using a sample plate for a malditop mass spectrometer and a malditop mass spectrometer using the sample plate

Technical Field

The present invention relates to a device for mass spectrometry of a compound, and more particularly to a sample plate for a MALDI 一 Tof (Matrix Assissted Laser Desorption Ionization Time of Flight) mass spectrometer and a malditop comprising the metal nanowires. It relates to a mass spectrometry method using a mass spectrometer.

Background Art

In general, a mass spectrometer is an analyzer that measures the mass of a compound to determine the molecular weight of the compound by measuring the mass-to-charge amount after charging and ionizing the compound. As a method of ionizing a compound, an electron ionization method using an electron beam, a method of colliding high-speed atoms, a method using a laser, and the like are known.

Among them, the method using a laser is characterized in that the matrix which helps the compound nitrate is mixed with the compound (sample) to be analyzed and placed on the target of the analytical device, and then irradiated to the sample to easily sample the sample with the aid of the matrix. It is a method of ionizing a sample using. The method is capable of measuring the molecular weight of the polymer material of 300 Da or more, high sensitivity can be analyzed even in the sample of the peptomol level, there is an advantage that can significantly reduce the phenomena of the compound to be analyzed during ionization. Therefore, the mass spectrometry using laser is effective for mass spectrometry of high molecular weight biochemicals such as proteins and nucleic acids, and the malditop mass spectrometer, a device for this, has recently been commercialized.

However, since the method ionizes the sample using the matrix, it is inconvenient to determine different matrix materials according to the type of the sample. In addition, a typical matrix material has a molecular weight of several hundred Da. If the molecular weight of the compound to be analyzed is similar to the molecular weight of the matrix material, matrix decomposition products appear in the mass spectrometry. To use The disadvantage is that it is difficult.

In addition, Malditop mass spectrometry is very effective for qualitative analysis of the composition of the sample. However, since the spatial distribution of the sample crystal obtained through the preparation of the sample is not uniform, the sample excited by the laser is irradiated according to the position where the laser is irradiated. Since the amount of is different, there is a disadvantage that the quantitative analysis of the sample is difficult.

In order to solve the above shortcomings, mal dtop mass spectrometry using metal nanowires instead of matrices has been proposed in Korean Patent Publication No. 10-2005—92809. Malditop mass spectrometry using the metal nanowires forms a nanowire spot by growing a plurality of nanowires in a specific region on a conductor or a semiconductor substrate, and then a compound (sample) to be subjected to mass spectrometry to the nanowire spot. After being placed in and dried, the laser beam is irradiated to the non-wiring spot to transfer energy to the sample through the nanowire, thereby desorbing and ionizing the sample.

However, in the case of using the above method, a material for growing nanowires on a metal catalyst on a substrate, commonly referred to as a vapor liquid solid (VLS) synthesis method, is used to form nanowires in the form of a vapor precursor. The logo is used to grow by flowing with high pressure carrier gas. However, in order to form a nanowire array by the VLS method, a metal catalyst must first be placed on a substrate in the form of an array. The application of the array technology is difficult due to the difficulty in mass production, and continuous formation of the same level of nanowires. It is difficult to do In addition, the VLS method has a disadvantage in that the production cost increases because the process is performed in a quartz tube of a high temperature and high pressure, and mass production is difficult.

[Detailed Description of the Invention]

[Technical problem]

The present invention aims to solve the shortcomings of the conventional Malditop mass spectrometer.

In particular, it is an object of the present invention to provide a sample plate for a maltope mass spectrometer, a mass plate capable of mass production and having a highly reproducible metal nanowire. In addition, an object of the present invention is to provide a Malditop mass spectrometer to which the sample plate is applied and a mass spectrometry method using the mass spectrometer.

Technical Solution

According to an embodiment of the present invention, a sample plate for a MALDI—Tof (Matrix Assissed Laser Desorption Ionization Time of Flight) mass spectrometer includes: a metal plate for forming a metal oxide having a photocatalytic function; And a metal oxide nanowire spot having a plurality of metal oxide nanowires formed on at least a portion of the metal plate surface, wherein the metal oxide nanowires are grown in a top-down manner on the metal substrate surface.

In addition, the metal oxide nanowires are formed by a wet corrosion method.

In addition, the metal plate is preferably at least one selected from Ti, Zn, Sn and Sr-Ti alloy.

In addition, the metal oxide nanowire having the photocatalytic function is preferably at least one selected from Ti0 ₂ , ZnO, Sn0 ₂ , SrTi0 ₃ , V2O5.

In addition, the metal oxide nanowire having the photocatalytic function is more preferably TiO ₂ .

In addition, the metal oxide nanowire is preferably in the anatase phase.

In addition, the sample plate for the mass spectrometer preferably further comprises a metal or semiconductor substrate formed on the opposite surface on which the TiO ₂ nanowire spot is formed.

In this case, the metal or semiconductor substrate may be stainless steel.

According to an aspect of the present invention, there is provided a method for preparing a sample plate for a mass spectrometer (MALDI-Tof; Matrix Assissted Laser Desorption Ionization Time of Flight) for preparing a metal plate for forming a metal oxide having a photocatalytic function. step; Forming a metal oxide nanowire spot by growing a plurality of metal oxide nanowires having a photocatalytic function on at least a portion of the metal plate in a top-down manner; Characterized in that it comprises a.

In addition, the forming of the metal oxide nanowire spot may include: the metal plate table Applying and patterning a photo mask on the surface; Wet etching the metal plate coated with the patterned photomas to form metal oxide nanowires; And removing the photo mask.

Alternatively, the forming of the metal oxide nanowire spot may include: applying a photomask patterned in a predetermined pattern on the surface of the metal plate; Wet etching the metal plate coated with the patterned photo mast to form metal oxide nanowires; And removing the photo mask.

In addition, the method of wet etching the metal plate comprises: immersing the metal plate coated with the patterned photo mask in an alkaline solution; And reacting the metal plate with pure H ₂ O.

In this case, the alkaline solution may be KOH.

In addition, the method may further include heat treating the metal plate on which the metal oxide nanowire spots are formed.

In this case, the heat treated metal oxide nanowires preferably have an anatase phase.

In addition, the metal oxide nanowires by a wet corrosion method ^; Characterized in that formed.

In addition, the metal plate is preferably at least one selected from Ti, Zn, Sn and V.

In addition, the metal oxide nanowires having a photocatalyst function is TiO _{_2,} ZnO, Sn0 _2, and V ₂ O ₅ ^is, preferably at least one selected from the.

In addition, in the preparing of the metal plate, the metal plate may be formed on another metal or semiconductor substrate.

In this case, the other metal or semiconductor substrate may be stainless steel. In addition, according to the present invention for achieving the above object (MALDI-Tof; Matrix Assissted Laser Desorption Ionization Time of Flight) mass spectrometer It characterized in that it comprises a sample plate formed by the configuration described above and / or the method described above.

A mass spectrometry method using a mass analyzer (MALDI-Tof; Matrix Assissted Laser Desorption Ionization Time of Flight) mass spectrometer according to the present invention for achieving the above object is: Positioning the metal oxide nanowire spot on the sample plate formed by the described method; Drying and crystallizing the sample; Desorption and ionization of the sample by irradiating a laser to the metal oxide nanowire spot on which the sample is mounted; And analyzing the mass of the silvered sample.

Advantageous Effects

According to the present invention, instead of a sample being ionized with the aid of a matrix by mixing a matrix to aid in ionization of a conventional compound, the compound is to be mass analyzed using a metal oxide having a photocatalytic function. The ionization may solve the disadvantage of having to determine different matrix materials according to the type of sample or difficult to use for mass spectrometry of hundreds of Da levels.

In addition, according to the present invention, since the metal oxide of the sample plate is formed by a top-down method rather than a conventional bottom-up method, mass production is easy, and a sample plate for a maltope mass spectrometer including a highly reproducible metal nanowire Can be provided.

In addition, according to the present invention, it is possible to manufacture a malditop mass spectrometer including a sample plate in which the mass production is easy and the metal nanowires having high reproducibility are formed.

In particular, since the metal oxide nanowires according to the present invention show effective decomposition properties such as 4-chlorophenol, benzene, and organic contaminants, methylene blue, oxylene, alkyl amrimatics, and the like, they may be particularly useful for mass analysis of such materials.

[Brief Description of Drawings]

1 is a view schematically showing a step of forming a sample plate for Maldilop mass spectrometer according to a preferred embodiment of the present invention.

FIG. 2 is a photograph of a TiO 2 nanowire structure formed according to a preferred embodiment of the present invention. FIG. 3 (a) is a view showing the structure of the rutile Ti0 ₂ according to a preferred embodiment of the present invention.

Figure 3 (b) is a view showing the structure of the anatase phase TiO ₂ according to a preferred embodiment of the present invention.

FIG. 3 (c) is a diagram showing the crystal structure peak of TiO ₂ shown in FIGS. 3 (a) and 3 (b).

4 is a diagram showing an example of a structure of a malditop mass spectrometer including a sample plate according to a preferred embodiment of the present invention.

5 is a view showing the results of analyzing the Enkephalin using a Malditop mass spectrometer according to a preferred embodiment of the present invention.

6 is a diagram showing the results of analyzing the Bradikynin fragment using a Malditop mass spectrometer according to a preferred embodiment of the present invention.

7 is a view showing the results of analyzing Angiotensin II (human) using a Malditop mass spectrometer according to a preferred embodiment of the present invention.

8 is a diagram showing the results of analyzing Pi4R (Synthetic peptide) using a Malditop mass spectrometer according to a preferred embodiment of the present invention.

9 (a) to 9 (c) are diagrams showing the results of quantitative analysis on the compounds shown in FIGS. 6 to 8, respectively.

[The best form for carrying out invention]

Reference to the accompanying drawings, the specific configuration and experimental results of the sample plate for the malditop mass spectrometer according to a preferred embodiment of the present invention and the malditop mass spectrometer equipped with the sample plate will be described below. On the other hand, in the following to clarify the features of the present invention as a configuration known in the art to which the configuration is not directly related to the features of the present invention will be omitted a detailed description.

1 is a view schematically showing a step of forming a sample plate for a malditop mass spectrometer according to a preferred embodiment of the present invention.

First, as shown in FIG. 1, a metal plate on which a metal oxide film is formed is prepared, and then a photo mask patterned in a predetermined pattern is applied. Or, applying a photo mask Afterwards, the photomask may be patterned into a desired shape at a position where the Ti0 ₂ nanowire spot is to be formed. At this time, the patterning method is not limited as long as it is a technique that can be commonly used for patterning a photo mask, such as plasma etching. On the other hand, in the present embodiment, a Ti plate was prepared as a metal plate, and thus a case of forming a TiO ₂ nanowire is described by way of example, but the metal oxide nanowires usable in the present invention are not limited to Ti0 ₂ .

Next, when the Ti plate coated with the photomask patterned to the desired position and shape is immersed in the KOH aqueous solution, the portion of the Ti plate from which the photomask is removed causes the following reaction with the KOH aqueous solution.

First, the TiO ₂ natural oxide film formed on the Ti flat surface is reacted as follows.

Ti0 + OH— = HTi0 ₃ —

The KOH solution then produces a reaction of Ti metal with the following reactions:

Ti + 30H ^" = Ti (OH) ₃ + + 4e ^to

_{^{Ti (OH) 3 + + 4e}} "= TiO 2 · H2O + 1 / 2H 2

Ti (OH) ₃ + + HO ^" = Ti (OH) ₄

TiO ₂ , nH ₂ O + OH— = ΗΤίθΓ · nH ₂ O

Subsequently, if the Ti flat plate on which ΗΉ0Γ · ηΗ ₂ 0 is formed is thoroughly reacted with pure ¾0, Ti0 ₂ nanowires having a desired structure from which impurities such as K + ions are removed may be obtained. 2 is a view of the structure of the TiO ₂ nanowires formed by the above method. As shown in FIG. 2, according to the present embodiment, it can be seen that TiO ₂ nanowires in the form of a thorn bush having a width of several tens of nm are formed while growing in a top-down manner from the surface of the Ti plate.

On the other hand, TiO ₂ formed by the above method may have a rutile (crystal) phase crystal structure, it is preferable to further perform the appropriate treatment during the heat treatment to have a crystal structure of the anatase (anatase) phase. 3 (a) and 3 (b) are diagrams comparing the case where the TiO 2 nanowires according to the present embodiment have a rudil structure and a case of anatase structure, respectively. As shown in FIG. 3 (b), the TiO 2 nanowires according to the present example have an anatase structure through proper heat treatment, thereby showing more excellent properties during mass analysis of the sample. In addition, Figure 3 (c) is a diagram showing the crystal structure peak of the Ti0 ₂ nanowires formed in accordance with the method presented in the above embodiment. Is shown in the FIG. 3 (c), performing the heat-treated Ti0 ₂ nm line may determine that the cause of methylene blue decomposition banung when photocatalyst banung, this one, Ti0 ₂ or route performing the heat treatment has a crystal structure on the anatase It is shown that it can be effectively used for mass spectrometry of compounds.

Next, FIG. 4 is a view showing an example of a structure of a malditop mass spectrometer including a sample plate according to a preferred embodiment of the present invention.

As shown in FIG. 4, the Malditop mass spectrometer according to a preferred embodiment of the present invention includes a main chamber in which a sample plate is disposed, a sample loading chamber in which a sample plate is positioned before inserting the sample plate into the main chamber. loading chamber, a laser irradiation device that irradiates a laser with a specific difference of a sample plate, a fly tube through which an ionized sample passes when at least a portion of the sample is ionized by laser irradiation, and an ionized sample collides A detector and a reflector that reflects the ionized sample.

Next, a method of performing mass spectrometry on a predetermined sample using a Malditop mass spectrometer equipped with a sample plate formed according to a preferred embodiment of the present invention will be described below.

First, a compound (sample) to be subjected to mass spectrometry is mixed with a predetermined solution to form a mixed solution, and then placed on a nanowire spot of a sample plate. The mixed solution on the nanowire spot is then dried to crystallize the sample. Subsequently, the sample plate is placed at a designated position in the main chamber, and the laser generator irradiates a laser. Then, the irradiated laser reaches the sample formed on the nanowire spot and then ionizes at least a portion of the sample, and the ionized sample passes through the flying stream to stratify the detector, and the mass spectrometer detects that the ionized sample is silvered and deductor. The component of the compound which comprises a sample can be grasped | ascertained by calculating the time to stratify into the sample.

Figure 5 shows the results of analyzing the sample "Enkephalin (molecular weight: 554)" using a Malditop mass spectrometer equipped with a sample plate formed according to a preferred embodiment of the present invention. As shown in Figure 5, when measured without the sample mass spectrometry peaks Although not occurring, it can be confirmed that the Enkephalin component is detected when the sample is included and the mass is measured.

6-8 is a figure which shows the result of having measured the mass of the compound (sample) which has a various molecular weight. That is, FIG. 6 shows Bradykinin fragment (molecular weight: 757), FIG. 7 shows Angiotensin II (human) (molecular weight 1047), and FIG. 8 shows P ₁₄ R (Synthetic peptide) (molecular weight 1534), respectively, using a conventional matrix. FIG. 2 is a diagram illustrating a case of using a Ti02 nanowire formed according to a preferred embodiment of the present invention and a case of not using a matrix and a Ti0 ₂ nanowire, respectively. 6 to 8, it can be seen that the mass spectrometry is not performed at all when the matrix and the Ti0 ₂ nanowire are not used, and the effect is superior to that of the conventional matrix when TiO ₂ or the route is used. You can check it.

9 (a) to 9 (c) show the results of quantitative analysis of the compounds according to FIGS. 6 to 8, respectively. FIG. 9 shows TiO ₂ nanowires according to the present embodiment. If used, it can be confirmed that quantitative analysis is possible.

On the other hand, the embodiment has been described for the case of forming a Ti0 ₂ nanowire spot using a Ti plate, for example, in addition to TiO ₂ other metal oxides having a photocatalytic function such as Zn, Sn0 ₂ , V ₂ O ₅ The nanowire spots formed by the PSA are also available as components of the sample plate for the Malditop mass spectrometer. In this case, those skilled in the art to which the present invention belongs ZnO, SnO ₂ , V ₂ O ₅ metal plate for forming a metal oxide nanowire spot is preferably a Zn plate, Sn plate and V plate, respectively It will be understood that the detailed description is omitted.

The method of manufacturing a sample plate according to a preferred embodiment of the present invention, a malditop mass spectrometer including the sample plate, and the mass spectrometry method of a compound using the mass spectrometer have been described in detail. However, one of ordinary skill in the art will appreciate that various modifications and variations to the configurations described in the preferred embodiments of the present invention are possible. Accordingly, the scope of the invention is limited only by the claims set forth below.

Claims

[Range of request]

[Claim 1]

A metal plate for forming a metal oxide having a photocatalyst function; And

A metal oxide nanowire spot having a photocatalytic function in which a plurality of metal plate nanowires for forming a metal oxide having a photocatalytic function are formed on at least a portion of the surface of the metal plate;

The metal oxide nanowire spot is grown in a top-down manner (MALDI-Tof; Matrix Assissted Laser Desorption Ionization Time of Flight) sample plate for mass spectrometer.

[Claim 2]

According to claim 1, The TiO ₂ nanowires sample plate for a malditop mass spectrometer, characterized in that formed by a wet corrosion method.

[Claim 3]

According to claim 1, wherein the TiO ₂ nanowires have a crystal structure of anatase phase sample plate for a malditop mass spectrometer.

[Claim 4]

The sample plate of claim 1, wherein the metal plate comprises at least one selected from Ti, Zn, Sn, and V. 3.

[Claim 5]

According to claim 1, wherein the metal oxide nanowire having a photocatalytic function is at least one selected from TiO ₂ , ZnO, SnO ₂ and V ₂ O ₅ Sample plate for a mass saw mass spectrometer.

[Claim 6]

The sample plate for a malditop mass spectrometer of claim 5, wherein the metal oxide nanowire having the photocatalytic function is Ti0 ₂ .

[Claim 7]

The method of claim 1, wherein the sample plate for the mass spectrometer further comprises a metal or semiconductor substrate formed on the opposite surface on which the metal oxide nanowire spot is formed A sample plate for a Malditop mass spectrometer.

[Claim 8]

8. The sample plate of Malditop mass spectrometer according to claim 7, wherein the metal or semiconductor substrate is stainless steel.

[Claim 9]

Preparing a metal plate for forming a metal oxide nanowire having a photocatalyst function; Growing a plurality of metal oxide nanowires on at least a portion of the metal plate in a top-down manner to form metal oxide nanowire spots;

Method of producing a sample plate for a malditop mass spectrometer comprising a.

[Claim 10]

10. The method of claim 9, wherein forming the metal oxide nanowire spots in a top-down manner is:

Applying and patterning a photo mask on the surface of the metal plate;

Wet etching the metal plate coated with the patterned photomast to form metal oxide nanowires; And

Method of manufacturing a sample plate for a mass saw mass spectrometer comprising the step of removing the photo mask.

[Claim 111]

The method of claim 10, wherein the wet plate is wet treated:

Immersing the metal plate coated with the patterned photo mask in an alkaline solution; And

Method for producing a sample plate for Maldilop mass spectrometer comprising the step of reacting the metal plate to p _Ure H ₂ O.

[Claim 12]

The method of claim 9, wherein the forming of the metal oxide nanowire spot is:

Applying a photo mask patterned in a predetermined pattern on the surface of the metal plate step;

Method of manufacturing a sample plate for a Malditop mass spectrometer comprising the step of removing the photo mask.

[Claim 13]

The method of claim 12, wherein the wet plate is wet treated:

The method of producing a sample plate for a malditop mass spectrometer comprising the step of reacting the metal plate in pure H ₂ O.

[Claim 14]

The method of claim 9, wherein the method further comprises the step of heat-treating the metal plate on which the metal oxide nanowire spots are formed.

[Claim 15]

15. The method of claim 14, wherein the heat treated metal oxide nanowires have a crystal structure of anatase phase.

[Claim 16]

10. The method of claim 9, wherein the metal plate comprises at least one selected from Ti, Zn, Sn and V.

[Claim 17]

The method of claim 9, wherein the metal oxide nanowire having the photocatalytic function is at least one selected from TiO ₂ , ZnO, SnO _2, and V ₂ 0 ₅ .

[Claim 18] 18. The method of claim 17, wherein the metal oxide nanowire having the photocatalytic function is Ti0 ₂ .

[Claim 19]

The method of claim 9, wherein in the preparing of the Ti plate, the Ti plate is formed on a metal or semiconductor substrate.

[Claim 20]

The method of claim 11 or 13, wherein the alkaline solution is KOH.

[Claim 21]

A maldilop mass spectrometer comprising a sample plate according to any one of claims 1 to 8 or a sample plate formed by the method according to any one of claims 9 to 19.

[Claim 22]

A sample subjected to mass spectrometry is placed on a metal oxide nanowire spot of a sample plate according to any one of claims 1 to 8 or a sample plate formed by the method according to any one of claims 9 to 19. Positioning;

Drying the crystallized sample to crystallize;

Irradiating a laser onto the metal oxide nanowire spot on which the sample is mounted to desorb and ionize the sample; And

Mass spectrometric analysis of the fresh-ion ionized sample

Mass spectrometry method using a Malditop mass spectrometer, characterized in that it comprises a.