KR101592517B1 - Substrate for Laser Desorption Ionization Mass Spectrometry and method for manufacturing the same - Google Patents

Abstract

[0001] The present invention relates to a substrate for laser desorption ionization mass spectrometry (hereinafter referred to as " laser desorption ionization mass spectrometry ") using a matrix, and more particularly, to a substrate for laser desorption ionization mass spectrometry. A nanotube filler formed on the polymer substrate; And a metal thin film formed on the surface of the nanotube filler, wherein the substrate includes a matrix within the polymer substrate and the nanotube filler, and a method for manufacturing the substrate.

Description

 BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a substrate for laser desorption ionization mass spectrometry,

The present invention relates to a substrate for laser desorption ionization mass spectrometry in which a matrix is introduced and a nanotechnology is fused in a laser desorption ionization mass spectrometry (LDI-MS) method and a method for producing the same. More particularly, And the nanotube pillar has a surface coated with a metal thin film, interference is not generated by the matrix, and the sensitivity is improved, and a laser capable of easily desorption ionization To a substrate for desorption ionization mass spectrometry and a method for producing the same.

MALDI (Matrix-Assisted Laser Desorption / Ionization) is a mass spectrometry method widely used for analyzing organic materials, biomaterials, and polymers. It is made by mixing a sample with a relatively large molecular weight and a matrix, Method.

Specifically, a sample is mixed with a matrix to form a crystal. Immediately after irradiation of the crystal with a strong pulse-type UV laser, desorption ionization is induced from the crystal and released to gaseous ions, and the molecular weight is measured by a mass spectrometer Or analyze the structure.

In this method, not only the ionization of polymeric biochemical substances, which are difficult to make into gas ions, but also the generation of gaseous ions, is very sensitive to high molecular weight polymers such as proteins, peptides, DNAs and polymers, To the picomole level). However, since the irradiated laser energy is transferred to the sample through the crystallized matrix and ionized, a proper matrix selection and optimum crystallization depending on the kind of the sample have a very important influence on the experimental results.

In other words, crystals mixed with a sample and a matrix are not homogeneous, so ion signals of different intensities appear depending on analysis positions. Therefore, in order to obtain an ion signal of an appropriate intensity necessary for analysis, it is necessary to find a seet spot , Which makes it difficult to obtain reproducible and reliable measurement results.

In addition, in the case of analyzing a synthetic polymer sample in a low molecular weight region (1000 Da), there is a problem that the accuracy of mass measurement of the analytical sample is deteriorated due to the interference due to the peaks of the matrix used together.

Accordingly, a laser ionization mass spectrometry method which does not use a matrix has been devised.

U.S. Patent No. 6,288,390 B1 describes desorption / ionization of an analyte into a porous light absorbing semiconductor using DIOS MS (Desorption Ionization on Silicon Mass Spectroscopy). A method of analyzing the mass of the desorbed and ionized analyte by desorbing and ionizing the analyte by absorbing the laser light of the substrate by irradiating a UV laser in a reduced pressure state by infiltrating the analyte into the porous semiconductor substrate .

Here, since the porous semiconductor to be used is a porous silicon, it does not require a separate matrix in the DIOS MS and has the advantage of quantitatively analyzing not only a low molecular weight compound but also a high molecular weight substance. However, desorption / The precise energy transfer path is not known, and since the sample solution is permeated into the porous structure of the porous silicon substrate and dried, it is difficult to match the center of the sample crystal to the laser irradiation point, .

Korean Patent Laid-Open No. 10-2012-0042581 also discloses a matrixless laser light desorption ionization mass spectrometry method. More specifically, the present invention relates to a method for manufacturing a semiconductor device, which comprises applying an analytical solution containing an analyte containing an organic substance, an inorganic substance, a biochemical substance, or a complex thereof to an inorganic substrate, A method for mass spectrometry analysis of a desorption ionized analyte by desorption ionization of a substance to be analyzed, the method comprising the steps of: detecting a mass spectrometry of 0.01 m to less than 0.01 fmol, And also has the advantage of being able to detect a very large mass of substances. However, since the substrate uses the laser light absorbing and heating, there is a problem that it can be used only for a material having thermal properties under special conditions such as low thermal conductivity or very high specific heat.

In addition, Japanese Laid-Open Patent Publication No. 2012-47554 describes SALDI-MS using the surface of metal nanoparticles by plasmon excitation. Specifically, a metal nanoparticle having a self-assembled monolayer of organic molecules is dispersed or adhered on a surface of a substrate on which a two-dimensional ultrahigh-precision packed and fixed substrate is attached, and the surface of the metal nanoparticle To a method for measuring the mass using the ionisation of the measurement sample attached to the sample. In this method, the laser beam is prevented from being directly transferred to the sample due to the oil film deposited on the surface of the metal nanoparticles, thereby weakening the laser to be irradiated, preventing the sample from being broken, Mass can be analyzed by desorption ionization of the sample. However, it is necessary to irradiate the metal nanoparticles with a rare low light of a specific wavelength, and it is necessary to control the energy of the laser to be irradiated although there is a dielectric film.

Accordingly, the present invention has been made in order to solve the above-mentioned problems, and it is an object of the present invention to provide a method of improving the sensitivity and improving the desorption ionization by fusing nanotechnology while introducing a matrix into a laser desorption ionization mass spectrometry (LDI- It is an object of the present invention to provide a substrate for laser desorption ionization mass spectrometric analysis.

Another object of the present invention is to provide a method for manufacturing the substrate for laser desorption ionization mass spectrometry.

According to an aspect of the present invention for solving the problems of the present invention,

Polymer substrates;

A nanotube filler formed on the polymer substrate; And

And a metal thin film formed on the surface of the nanotube filler,

Wherein the substrate for laser desorption ionization mass spectrometry comprises a matrix within the polymer substrate and the nanotube filler.

Further, according to another aspect of the present invention,

A first step of forming a nanotube by a sol-gel method on a plurality of pores formed in an anodic aluminum oxide (AAO) template;

A second step of injecting and laminating a monomer solution containing a matrix in the nanotube and the aluminum anodized template to polymerize them to form a polymer substrate containing the matrix in the interior of the nanotubes and on the template;

A third step of removing the anodic aluminum template to form pillar-shaped nanotubes on the polymer substrate; And

And a fourth step of laminating a metal thin film on the surface of the nanotube filler. The present invention also provides a method of manufacturing a substrate for laser desorption ionization mass spectrometry.

The substrate for laser desorption ionization mass spectrometry according to the present invention is improved in sensitivity by using a nanotube filler and can be easily desorbed and ionized by a metal thin film formed on the surface of the nanotube filler have.

Further, since the matrix material of the present invention is located under the nanotube layer capable of forming a nanofiller and can only stay inside the nanotube layer, a commercialization matrix optimized for the MALDI-TOF device can be used as it is, The signal interference due to the matrix peak can be prevented. That is, according to the present invention, most of the laser energy irradiated is absorbed by the matrix material and is prevented from being damaged by the laser energy, and the matrix material absorbing the laser energy is stored in the nanotube filler The sample is vaporized and ionized so that laser desorption ionization is facilitated and signal generation is not induced in the detector, so that signal interference due to matrix peaks can be prevented in the mass spectrometry spectrum.

Therefore, in the mass spectrometric analysis according to the present invention, the desorption ionization is facilitated by the matrix, and the peak due to the matrix is not marked on the spectrum, thereby remarkably improving the sensitivity. Particularly, in the mass measurement of the low molecular weight (1000 Da) The interference due to the matrix peak is not generated, and the accuracy of the measurement can be improved.

In addition, the nanotube filler formed on the substrate for laser desorption ionization mass spectrometry of the present invention has a strong adhesive force on the surface, and it is possible to prevent the sample of the liquid phase from flowing down to the surface of the nanotube filler, The surface of the nanotube filler on the surface of the nanotube filler is narrow and the contact angle is 150 DEG or more, the liquid sample can be prevented from being deposited on the surface of the nanotube filler and wet.

FIG. 1 schematically shows a substrate for laser desorption ionization mass spectrometry according to the present invention.
FIG. 2 is a flowchart illustrating a manufacturing process of a substrate for laser desorption ionization mass spectrometry according to the present invention.
3A through 3D are schematic diagrams of substrates for laser desorption ionization mass spectrometry according to an embodiment of the present invention.
4A to 4E are schematic diagrams of a substrate for laser desorption ionization mass spectrometry manufactured according to one embodiment of the present invention.
5A to 5E are graphs showing a mass spectrometry spectrum according to an embodiment of the present invention.

The present invention relates to a substrate for laser desorption ionization mass spectrometry (LDI-MS), a laser desorption ionization mass spectrometry substrate incorporating a matrix and fusing nanotechnology.

Hereinafter, the present invention will be described in more detail.

In one aspect,

Polymer substrates; A nanotube filler formed on the polymer substrate; And a metal thin film formed on the surface of the nanotube filler, wherein the substrate includes a matrix inside the polymer substrate and the nanotube filler.

FIG. 1 is a schematic view of a substrate for laser desorption ionization mass spectrometry including a nanotube filler formed on a polymer substrate as a preferred embodiment of the present invention. Referring to FIG. 1, the laser desorption / The substrate includes a nanotube filler (A) formed on a polymer substrate (C), a metal thin film (B) formed on the surface of the nanotube filler, and a matrix (D) contained in the polymer substrate and the nanotube filler .

More specifically, the substrate for laser desorption ionization mass spectrometry according to the present invention comprises a nanotube filler (A) formed on the polymer substrate so that the matrix material inside the nanotube filler can emit laser energy The sample to be analyzed is efficiently adsorbed to generate desorption ionization which releases the sample to be analyzed and released into the vacuum, while preventing the signal interference due to the matrix peak, thereby significantly improving the sensitivity of mass spectrometry.

That is, since the substrate for laser desorption ionization mass spectrometry according to the present invention is located under the laser-transmissible nanotube layer forming the nanofiller (A) and remains only in the nanotube layer, Most of the energy is absorbed by the matrix material, and the sample to be analyzed is prevented from being damaged by the laser energy. In addition, the matrix material absorbing the laser energy vaporizes and ionizes the analytical sample, thereby facilitating laser desorption ionization.

In the present invention, the matrix material remains only inside the nanotube and is used only for laser desorption ionization to prevent signal interference due to matrix peaks in the mass spectrometry spectrum by not inducing signal generation in the detector, And the interference due to the matrix peak is not generated, thereby improving the accuracy. Particularly, this effect is conspicuous when the mass of the synthetic polymer in the low molecular weight (1000 Da) region is measured.

In addition, according to the present invention, since the nanotubes have a pillar shape, they have a strong adhesive force on the surface in terms of physical properties, and exhibit hydrophobic properties depending on the shape of the filler. That is, when the sample fine droplets in the liquid phase fall on the surface of the nanotube filler (A), the area of the nanotube filler (A) that is strongly adhered to the surface of the nanotube filler (A) becomes narrower, It is possible to prevent the phenomenon of deposition or wetting of the sample fine particles on the surface of the nanotube filler (A). As a result, sensitivity can be improved in mass spectrometry.

At this time, preferably, the nanotube filler may be formed of silicon or titanium oxide.

Also, in the present invention, a metal thin film (B) is deposited on the surface of the nanotube filler (A) so that the energy loss absorbed by the nanotube filler from the laser is minimized so that the desorption ionization by the nanotube filler The effect of facilitating the display is exhibited. At this time, preferably, the metal thin film (B) may be formed of at least one of gold, titanium, aluminum, silver, nickel, platinum, palladium, an alloy thereof or an oxide thereof.

Also preferably, the polymer substrate (C) is selected from the group consisting of polydimethylsiloxane (PDMS), polystyrene (PS), polymethylmethacrylate (PMMA), polytetrafluoroethylene (PTFE), polyethylene (PE), polyurethane ), Cellulose, and silicone rubber, and more preferably, it is formed of polydimethylsiloxane (PDMS).

Also, the matrix (D) introduced into the polymer substrate (C) and the nanotube filler (A) is a copolymer of? -Cyano-4-hydroxycinnamic acid (CHCA), 2,5-dihydroxybenzoic acid (DHB) (PA), 3-hydroxypicolinic acid (HPA), 3,5-dimethoxy-4-hydroxycinnamic acid (SA), 4-hydroxy-3-methoxonic acid Or more.

At this time, the matrix material (D) may be determined according to a sample to be analyzed among the commercialization matrices optimized for MALDI-TOF equipment. Namely, alpha -cyano-4-hydroxycinnamic acid (CHCA) is suitable as a matrix for mass spectrometry of peptides, lipids, DNA and RNA, 2,5-dihydroxybenzoic acid (DHB) (SA) is suitable for mass spectrometric analysis of RNA, oligonucleotide and oligosaccharide, and 3,5-dimethoxy-4-hydroxycinnamic acid (SA) Ferulic acid) is preferably used as a matrix when analyzing the mass of a protein, picolinic acid (PA) and 3-hydroxypicolinic acid (HPA) are used for analyzing the mass of oligonucleotides.

In another aspect,

A first step of forming a nanotube by a sol-gel method on a plurality of pores formed in an anodic aluminum oxide (AAO) template; A second step of injecting and laminating a monomer solution containing a matrix in the nanotube and the aluminum anodized template to polymerize them to form a polymer substrate containing the matrix in the interior of the nanotubes and on the template; A third step of forming a pillar-shaped nanotube on the polymer substrate by removing the anodized aluminum template; And a fourth step of laminating a metal thin film on the surface of the nanotube filler. The present invention also provides a method of manufacturing a substrate for laser desorption ionization mass spectrometry.

FIG. 2 shows a manufacturing process of a substrate for laser desorption ionization mass spectrometry according to the present invention, and FIGS. 3A to 3E show a substrate for laser desorption ionization mass spectrometry for each step.

The first step is a step of forming a nanotube by a sol-gel method on a plurality of pores formed in an AAO template. Specifically, as shown in FIG. 3A, the annealed aluminum film is subjected to first and second anodic oxidation, pore expansion is performed to form a uniform anodized aluminum template, and anodized portion is directed upward, By performing a sol-gel method with a material capable of forming a tube, a plurality of pores formed in the anodized aluminum template are coated to form nanotubes. At this time, it is preferable to use silicon or titanium oxide as a material capable of forming the nanotubes.

Next, the second step is a step of injecting and laminating a monomer solution containing a matrix into the nanotube and the aluminum anodic aluminum template, and polymerizing them to form a polymer substrate containing the matrix in the interior of the nanotube and on the template . As shown in FIG. 3B, the monomer solution containing the matrix is applied so that it can be sufficiently injected into and laminated on the inside of the coated nanotube and on the top of the anodized aluminum template, Thereby forming a polymer substrate containing the matrix. At this time, the polymer base layer including the matrix formed on the template may be formed to a thickness of 1 to 5 mm.

Next, the third step is a step of forming the pillar-shaped nanotube on the polymer substrate by removing the anodized aluminum template. More specifically, as shown in FIG. 3C, The anodic aluminum oxide template is completely removed by sequentially dissolving the remaining back-side aluminum layer and the anodic aluminum oxide (AAO) using an acidic solution. As the template is removed, pillar-shaped nanotubes are formed on the polymer substrate, which is formed on the template and inside the nanotube. As the nanotubes have a pillar shape on the polymer substrate, they have a strong adhesive force and exhibit hydrophobic properties, so that the nanotube filler surface is wetted by the sample while the mass analysis sample is strongly adhered, or the sample is deposited It is possible to improve the sensitivity in terms of mass spectrometry.

Next, a fourth step is a step of laminating a metal thin film on the surface of the nanotube filler. The lamination may be performed by a method commonly known in the art such as vacuum deposition, sputtering, CVD, The metal thin film can be laminated on the surface of the nanotube filler by a sputtering method.

At this time, it is preferable that the metal thin film is formed of at least one of gold, titanium, aluminum, silver, nickel, platinum, palladium, an alloy thereof or an oxide thereof, and a metal thin film is formed on the surface of the nanotube filler Thereby minimizing the energy loss absorbed by the nanotube filler from the laser, thereby facilitating laser desorption ionization.

Further, preferably, the substrate manufactured by the above-described manufacturing method is a substrate for laser desorption ionization mass spectrometry as described above.

Hereinafter, the present invention will be described in more detail by way of examples, but the scope of the present invention is not limited by the examples.

≪ Example 1 > Preparation of substrate for mass spectrometry 1

Anodic aluminum oxide (AAO) template formation

The aluminum film (0.25 nm thick) which had been annealed was degreased in acetone, electrolyzed at 15 V and 5 ° C in a solution containing perchloric acid and ethanol in a ratio of 1: 5, and subjected to primary anodization at 40 V and 10 ° C for 10 hours Respectively.

The non-uniform anodic aluminum oxide film obtained through the primary anodization was etched in a mixed solution of chromic acid and phosphoric acid, followed by secondary anodic oxidation for 20 minutes, followed by pore expansion for 40 minutes with a 5% phosphoric acid solution at 30 ° C To form a uniform anodized aluminum (AAO) template.

Formation of silica nanotubes (SNT) (sol-gel method)

The anodic aluminum oxide (AAO) template was immersed in the SiCl ₄ solution for 5 minutes, washed with hexane, washed again with a mixture of hexane and methanol, and washed with ethanol. Thereafter, after drying using nitrogen gas, the anodized aluminum template was immersed in water. This reaction was repeated four times.

A silica nanotube pillar is formed on a PDMS substrate

(10%, wt / wt) was added to the silica-coated anodized aluminum (AAO) template by placing the anodized aluminum oxide (AAO) template with the anodized face facing upward, In addition to the inside coated with silica, an upper part of anodized aluminum was also coated with a mixed solution of a matrix and a PDMS monomer.

After the silica was coated on both the inside and the top of the anodized aluminum coated with the silica by the mixed solution of the matrix and the monomer as described above, the PDMS layer containing 2 mm-thick matrix was formed by solidifying it at 70 ° C for 1 hour .

After the PDMS layer was formed, an aluminum layer and anodized aluminum (AAO) were sequentially dissolved and removed using HgCl ₂ and H ₃ PO ₄ solutions.

Au layer lamination on nanotube filler surface

The silica nanotube pillars on the PDMS were washed with deionized water and dried in the air, and then a 5 nm thick Au layer was laminated on the pillar using a sputterer to obtain the final structure.

A schematic view of the substrate manufactured in this embodiment is shown in FIG. 4A.

≪ Example 2 > Production of substrate for mass spectrometry 2

In this example, a mass spectrometric substrate was prepared by the method described in Example 1, except that the silica nanotubes were not formed on the anodized aluminum (AAO) template, and the mass of the PDMS substrate and the Au layer And a substrate for analysis was prepared.

A schematic view of the substrate manufactured in this embodiment is shown in FIG. 4B.

≪ Example 3 > Production of substrate for mass spectrometry 3

In this Example, a substrate for mass spectrometric analysis was prepared by the method described in Example 1, and a substrate for mass spectrometry was prepared without mixing the matrix in the process of forming the silica nanotube filler on the PDMS substrate.

A schematic view of the substrate manufactured in this embodiment is shown in Fig. 4C.

Example 4 Production of Substrate for Mass Spectrometry 4

In this example, a substrate for mass spectrometric analysis was prepared by the method described in Example 1, but a substrate for mass spectrometry was produced without laminating the Au layer.

A schematic view of the substrate manufactured in this embodiment is shown in Fig. 4D.

Example 5 Production of Substrate for Mass Spectrometry 5

In this example, a substrate for mass spectrometric analysis was prepared by the method described in Example 1, except that a PDMS layer and an Au layer containing a matrix were laminated on a flat glass substrate instead of AAO to prepare a mass spectrometry substrate.

A schematic view of the substrate manufactured in this embodiment is shown in Fig. 4E.

The conditions of the mass spectrometric substrates prepared in Examples 1 to 5 are summarized in Table 1 below.

< Test Example > Mass Spectrometry

The sensitivity of the mass spectrometry was confirmed by carrying out mass spectrometry using the substrates for mass spectrometry prepared in Examples 1 to 5 above. Here, the samples and devices used for the analysis are as follows.

- Analysis sample: acridine (MW: 179.22 g / mol, Conc: 0.64 mg / ml)

- Mass spectrometer: Voyager-DE-STR MALDI-TOF MS

(pulsed N ₂ laser (337 nm, 3 ns duration pulses)

5A to 5E show the results of the analysis.

FIG. 5A shows the mass spectrometry spectrum of Example 1. Compared with FIGS. 5B to 5E which are the mass spectrometry spectra of Examples 2 to 5, the peak mass-to-charge ratio (m / z) , And the intensity of the peaks was also found to be the strongest.

5B shows the mass spectrometry spectrum of Example 2, which does not include nanotubes but has a polymer base in the form of a filler. Compared with FIG. 5A which includes a pillar-shaped nanotube, the peak value is 40% , But the measurement sensitivity is improved by about 3 times as compared with Figs. 5C to 5E.

Although this does not include nanotubes, it includes a matrix material inside the filler-like polymer substrate, and a gold thin film on the surface of the filler-like polymer substrate, so that the matrix material absorbing the laser energy is absorbed by the Au layer It is believed that the sensitivity of the mass spectrometry improves because it remains only in the filler. That is, it is considered that the matrix material is kept in the filler by the filler shape in the substrate for laser desorption ionization mass spectrometry, thereby reducing the occurrence of signal interference due to the matrix during mass spectrometry, thereby improving the sensitivity in mass spectrometry.

On the other hand, FIGS. 5C to 5E show the mass spectrometry spectra of Examples 3 to 5 in which the matrix, Au layer, and filler-like nanotubes are not provided, respectively. In FIG. 5A, 5 level. In addition, it was confirmed that the number of peaks separated by mass on the X axis was also decreased. That is, it was confirmed that if the substrate for laser desorption ionization mass spectrometry does not contain any of the nanotubes, the matrix and the gold thin film, the sensitivity can not be improved.

The result of this embodiment is that the matrix material remains only in the nanotubes of the pillar shape and is used only for laser desorption ionization and does not induce the signal generation in the detector so that the signal interference due to the matrix peak does not occur in the mass spectrometry spectrum it means.

Therefore, the substrate for laser desorption ionization mass spectrometry according to the present invention can be manufactured by forming the nanotube into a pillar shape, introducing the matrix into the nanotube and the polymer substrate, and forming a metal thin film on the surface of the nanotube filler, The sensitivity and accuracy of mass spectrometry can be significantly improved as compared with the MS (Laser Desorption Ionization Mass Spectrometry) substrate. Further, since the interference due to the peak of the matrix does not occur, a sample of low molecular weight can be measured with excellent sensitivity do. Particularly, the nanotubes of the present invention have a filler shape, thereby increasing the hydrophobicity and surface adhesion of the nanotubes, and thus the mass spectrometry sensitivity can be further improved.

In addition, the substrate for laser desorption ionization mass spectrometry of the present invention facilitates laser desorption ionization by vaporizing and ionizing an analytical sample by a matrix material that absorbs laser energy, and minimizes energy loss absorbed by the Au layer by the Au layer , It is considered that the sensitivity can be improved during mass spectrometry.

A: Nanotube filler
B: metal thin film
C: polymer substrate
D: Matrix

Claims (7)

Polymer substrates;
A nanofiller pillar formed in a shape of an inverted 자 shape and having a closed upper end formed on the polymer substrate;
A matrix contained within the polymer substrate and the nanotube filler; And
A metal thin film formed on the surface of the nanotube pillars; / RTI &gt;
Wherein the nanotube filler is formed of silicon or titanium oxide. delete The method according to claim 1,
Wherein the metal thin film is formed of at least one of gold, titanium, aluminum, silver, nickel, platinum, palladium, alloys thereof, and oxides thereof. The method according to claim 1,
The matrix may be selected from the group consisting of? -Cyano-4-hydroxycinnamic acid (CHCA), 2,5-dihydroxybenzoic acid (DHB), 3,5-dimethoxy- Wherein the substrate is at least one selected from the group consisting of hydroxy-3-methoxylic acid (ferric acid), picolinic acid (PA) and 3-hydroxypicolinic acid (3-HPA). The method according to claim 1,
The polymer may be one of polydimethylsiloxane (PDMS), polystyrene (PS), polymethylmethacrylate (PMMA), polytetrafluoroethylene (PTFE), polyethylene (PE), polyurethane (PU), cellulose and silicone rubber Of the total mass of the laser desorption / ionization mass spectrometer. A first step of forming a nanotube by a sol-gel method on a plurality of pores formed in an anodic aluminum oxide (AAO) template;
A second step of injecting and laminating a monomer solution containing a matrix in the nanotube and the aluminum anodized template to polymerize them to form a polymer substrate containing the matrix in the interior of the nanotubes and on the template;
A third step of forming a pillar-shaped nanotube on the polymer substrate by removing the anodized aluminum template; And
And a fourth step of laminating a metal thin film on the surface of the nanotube filler. The method according to claim 6,
Wherein the substrate for laser desorption ionization mass spectrometry comprises:
Polymer substrates;
A nanofiller pillar formed in a shape of an inverted 자 shape and having a closed upper end formed on the polymer substrate;
A matrix contained within the polymer substrate and the nanotube filler; And
A metal thin film formed on the surface of the nanotube pillars; / RTI &gt;
Wherein the nanotube filler is formed of silicon or titanium oxide. &Lt; RTI ID = 0.0 &gt; 11. &lt; / RTI &gt;

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