JP2010071664A - Device for mass spectrometric analysis, method of preparing the same, laser desorption ionization mass spectrometer using the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a laser desorption ionization mass spectrometer analysis having high quantitative performance, by reducing a disturbance peak originating in an ionization accelerator, by preventing scattering of unwanted ionization accelerator. <P>SOLUTION: This device for mass spectrometer analysis is used for a laser desorption ionization mass spectrometry of measuring the mass spectra of ionized material to be analyzed. This device has a micro-structure layer, having a plurality of recessed micro-structures, and the opening width of an opening in the recessed micro-structures is set to be smaller than the structure width of the recessed micro-structures. The ionization accelerator is stored in the recessed micro-structures whose outlet is made narrow by making the opening small. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to laser desorption ionization mass spectrometry in which a mass spectrum of an analyte is measured by laser light irradiation.

  In a mass spectrometry method used for identifying a substance or the like, an analyte is ionized by some method, and an electric field or a magnetic field is applied to the analyte to separate and analyze, and an ionized analyte m / z value (here, , M is a dimensionless quantity obtained by dividing the mass of the ion by the unit of atomic mass, and z is the charge valence of the ionized analyte. A method for analyzing an analyte is known. In this case, the ionization method includes an electrospray ionization (ESI) method, a field desorption (FD) method, a fast atom bombardment (FAB) method, and a laser desorption ionization. (Laser Desorption Ionization: LDI) method and the like. Examples of the separation analysis type include a magnetic field deflection type, a quadrupole type, an ion trap type, and a time-of-flight (TOF) type.

  Usually, mass spectrometry is performed by selecting one from the ionization method and separation analysis type as described above in consideration of the compatibility and combining them. For example, the LDI-TOF method, which combines the above LDI method and the TOF type, irradiates the analyte to be supplied onto the mass spectrometric device with laser light to ionize and desorb the analyte. The analyte is caused to fly a predetermined distance while being accelerated by an electromagnetic field generator, and the m / z value of the analyte ionized by this flight time is analyzed (Patent Document 1). The LDI-TOF method has both the features of the LDI method (measuring a minute region, etc.) and the TOF type features (high sensitivity detection, etc.) and is widely used.

  However, the conventional LDI-TOF method has a problem that it is difficult to apply when a high-molecular-weight polymerized substance (polymer) such as a biological substance (protein or the like) or a synthetic resin (nylon or the like) is an analyte. . This is because, by laser light irradiation, in addition to polymer desorption / ionization, polymer decomposition also occurs at the same time, and the polymer peak cannot be obtained with sufficient intensity. Furthermore, since the peak of the decomposition product itself is also detected, the mass spectrum is complicated and the analysis is difficult. If desorption and ionization can be performed without decomposing the polymer, it is possible to obtain a lot of chemical structural information not only on the molecular weight but also on the repeating unit and end group structure from the m / z value of each peak in the mass spectrum. It becomes. Therefore, development of a soft ionization method for ionizing a polymer without decomposing has been widely promoted.

  Typical soft ionization methods include matrix-assisted laser desorption ionization (Matrix-Assisted LDI: MALDI) method and surface-assisted laser desorption ionization (Surface-Assisted LDI: SALDI) method. The MALDI method and the SALDI method are known as analytical methods that can measure a polymer having a molecular weight exceeding 10,000 and have little chemical influence on an analyte.

  The MALDI method uses a sample mixed with an analyte in a matrix agent (such as sinapinic acid or glycerin), vaporizes the analyte together with the matrix using the light energy absorbed by the matrix agent, and then the analyte This is a method of ionizing the. In this MALDI method, since the matrix agent absorbs the energy of the irradiation laser beam and is desorbed / ionized, the influence of the irradiation laser beam on the analyte contained in the matrix agent is reduced (FIG. 14B). . Therefore, decomposition of the analyte can be suppressed, and detection can be performed with high sensitivity. MALDI-TOF MS, in which this MALDI method is applied to TOF-MS, has become widespread in the field of biological materials and synthetic polymers, and MALDI-TOF MS that enables more accurate analysis has been studied (patents). Reference 2). However, since the MALDI method greatly depends on the mixed crystal state of the analyte and the matrix agent, there is a problem that know-how and a certain amount of trial and error are required for the selection of the matrix agent and sample preparation.

  On the other hand, the SALDI method uses a device surface having a function of supporting desorption / ionization of an analyte. For example, the forerunner of this is the DIOS (Desorption / Ionization On porous Silicon) method. The DIOS method uses a porous silicon substrate having a nanometer-level microstructure as a device having the above functions. This porous silicon substrate can be produced by a method such as electric field etching of a silicon wafer in a hydrofluoric acid solution under light irradiation. In the DIOS method, the analyte can be ionized without being decomposed by simply applying a sample solution containing the analyte on the surface of the device and irradiating it with a laser beam. The SALDI method is a simple and highly quantitative analysis method because it does not depend on the mixed crystal state of the analyte and the matrix agent unlike the MALDI method. However, the SALDI method is inferior to the MALDI method in terms of ionization efficiency (or detection sensitivity). For this reason, when it is necessary to increase the ionization efficiency in the SALDI method, an initiator agent that promotes ionization of the analyte is used. Unlike the matrix agent, the initiator agent can promote ionization without forming a mixed crystal with the analyte, so that the ionization efficiency can be easily improved by simply applying the initiator agent to the device surface. Is possible.

As described above, matrix agents and initiator agents that play a role in promoting ionization of analytes (hereinafter collectively referred to as ionization accelerators) play a very important role in the LDI method.
JP 2004-184137 A JP 9-320515 A

  However, when an ionization accelerator is added in the LDI method, there is a problem that an interference peak derived from the ionization accelerator occurs. For example, as shown in FIG. 14B, in the conventional MALDI method, scattered ions (I ′ in FIG. 14B) of only the matrix agent that does not contain the analyte are a serious problem. Usually, since the molecular weight of the ionization accelerator is approximately 500 Da or less, many interference peaks derived from the ionization accelerator are generated in a mass region of 500 Da or less. This makes it very difficult to analyze an analyte having a molecular weight of 500 Da or less.

  The present invention has been made in view of the above problems, and in the LDI method, the scattering of unnecessary ionization accelerators is prevented to reduce interference peaks derived from ionization accelerators, thereby enabling more quantitative analysis. An object of the present invention is to provide a device for mass spectrometry, a method for producing the device, a laser desorption / ionization mass spectrometer using the device, and an analysis method.

In order to solve the above problems, a device for mass spectrometry according to the present invention comprises:
In a laser desorption ionization mass spectrometry method in which an analyte supplied on a supply surface of a mass spectrometry device is desorbed from the mass spectrometry device by laser light irradiation and a mass spectrum of the ionized analyte is measured. In the device for mass spectrometry used,
Comprising a microstructure layer having a plurality of concave microstructures;
A plurality of concave microstructures have openings in the supply surface;
The opening width of this opening is smaller than the structure width of the concave microstructure.

  Furthermore, in the device for mass spectrometry according to the present invention, the concave microstructure is preferably a micropore.

  Here, the “concave microstructure” means that a plane parallel to the supply surface is taken as an xy plane, and a direction perpendicular to the supply surface is taken as a z-axis and a cross section is taken along the yz plane or the zz plane. Furthermore, it shall mean the fine structure which can confirm the shape (concave shape) hollow with respect to the supply surface. Here, even if the concave microstructure is a channel-type microstructure (a shape in which the concavo-convex structure extending in a line shape on the supply surface is repeated in a stripe shape), the hole-shaped microstructure (with respect to the area of the supply surface) In a relatively small and limited region, it may be a shape that is mainly recessed in the depth direction (so-called micropores). Furthermore, the concave microstructure may be an intermediate structure between a channel-type microstructure and a micropore.

  The “structural width of the concave microstructure” means a width of a concave shape in a direction parallel to the xy plane. For example, when the concave microstructure is a channel-type microstructure, the structure width means the width of the recess (channel width) in the direction perpendicular to the line of the concavo-convex structure, and when the concave microstructure is a micropore, The structure width means the length of the fine hole diameter (hole diameter).

  The “opening width” means the length of the opening in a direction parallel to the structure width of the concave microstructure. For example, when the concave microstructure is a channel-type microstructure, the opening width means the length of the opening in a direction parallel to the channel width, and when the concave microstructure is a fine hole, the opening width is the hole diameter. Means the length (diameter) of the diameter of the opening in the direction parallel to.

  Furthermore, the micropores preferably store an ionization accelerator that promotes ionization of the analyte.

  Here, the “ionization promoter” means a material added to promote ionization of an analyte in the LDI method. Here, the so-called matrix agent and initiator agent are included in the ionization accelerator.

  And it is preferable to provide the heat insulation layer adjacent to the surface of the porous layer on the opposite side to the side with a supply surface.

  Here, the “heat insulating layer” means a layer having a thermal conductivity lower than that of the microstructure layer.

  Moreover, it is preferable to provide a metal layer on the surface of the device for mass spectrometry opposite to the side where the supply surface is present.

Furthermore, a method for producing a device for mass spectrometry according to the present invention includes:
Mass used in a laser desorption ionization mass spectrometry method in which an analyte supplied on a device for mass spectrometry is desorbed from the device for mass analysis by laser light irradiation and a mass spectrum of the ionized analyte is measured. In the method for producing an analytical device,
Forming a plurality of concave microstructures so as to have openings in one surface of the microstructure layer precursor;
The coating material is obliquely deposited from one or more directions with respect to the surface having the opening.

  Here, the “fine structure layer precursor” means an object that is a basis of the fine structure layer.

And, in a method for producing a device for mass spectrometry according to the present invention,
The microstructure layer precursor is an anodized material,
As a plurality of concave microstructures, it is preferable to form a plurality of micropores having openings on the anodized surface subjected to the anodization treatment by subjecting the material to be anodized to anodization.

  Moreover, it is preferable to perform an etching process on the plurality of concave microstructures after performing oblique vapor deposition.

Furthermore, the laser desorption ionization mass spectrometer according to the present invention is:
A device for mass spectrometry as described above;
A laser light source for irradiating the analyte supplied on the device for mass spectrometry with laser light;
A device support for supporting the device for mass spectrometry;
An analysis unit that separates an ionized analyte that has been desorbed and ionized from the device for mass spectrometry by laser light irradiation according to the m / z value of the ionized analyte;
A detection unit for detecting the ionized analyte;
And a data processing unit that forms a mass spectrum of the ionized analyte based on the detection data obtained by the detection unit.

Furthermore, the laser desorption ionization mass spectrometry method according to the present invention includes:
Using the device for mass spectrometry described above,
Analyte the substance supplied on the device for mass spectrometry is desorbed and ionized from the device for mass spectrometry by laser light irradiation,
According to the m / z value of the ionized analyte, the ionized analyte is separated and detected,
Based on the detection data obtained by the detection, a mass spectrum of the ionized analyte is formed.

  Here, m is a dimensionless quantity obtained by dividing the mass of the ion by the unit of unified atomic mass, and z is the valence of the charge of the ionized analyte.

  The device for mass spectrometry according to the present invention has a concave microstructure and is configured such that the opening width of the concave microstructure is smaller than the structural width of the concave microstructure. Therefore, by storing the ionization accelerator in the concave microstructure in the LDI method, it is possible to prevent unnecessary scattering of the ionization accelerator due to laser irradiation. Thereby, the interference peak derived from an ionization promoter can be reduced, and mass spectrometry with high quantitative property is attained.

  Hereinafter, although an embodiment of the present invention is described using a drawing, the present invention is not limited to this.

"Device for mass spectrometry and its fabrication method"
<First Embodiment of Device for Mass Spectrometry>
First, the configuration of the mass spectrometry device 10 according to the present embodiment will be described. FIG. 1A and FIG. 1B are a schematic perspective view and a schematic front view showing the overall configuration of the mass spectrometry device 10 according to the present embodiment, respectively. FIG. 1C is a schematic front view showing a state in which the ionization accelerator is filled in the concave microstructure of the device 10 for mass spectrometry.

  As shown in FIGS. 1A and 1B, a mass spectrometry device 10 is formed on a metal layer 11, a microstructure layer 12 having a concave microstructure formed on the metal layer, and a microstructure layer 12. And a coating layer 14 having a protruding portion 14a for narrowing the opening 15b of the fine hole 15a.

  The metal layer 11 and the microstructure layer 12 are porous oxidized materials obtained by anodizing the anodized material. As shown in FIGS. 2A and 2B, when the anodized material 90 (fine structure layer precursor) is anodized, an oxidation reaction proceeds from the surface in a direction substantially perpendicular to the surface, and an anodized film 12 is formed. Is done. Further, as shown in FIG. 2B, the anodic oxide film 12 produced by anodic oxidation has a structure in which a number of fine columnar bodies having a substantially regular hexagonal shape are arranged without gaps, for example, in plan view. A non-penetrating fine hole 15a extending substantially straight from the surface in the depth direction is opened at a substantially central portion of each fine columnar body. Further, the bottom surface of each fine columnar body has a rounded shape. That is, the porous oxide material 13 is composed of a non-porous lower layer 11 and a porous upper layer 12 that have not been oxidized. In the present embodiment, the fine holes 15a are concave microstructures in the present invention, the anodized film 12 is a microstructure layer in the present invention, and the non-anodized portion 11 of the anodized material 90 is a metal layer. is there. The shape of the anodized material 90 is not particularly limited, and a plate shape or the like is preferable. Further, it may be used in a form with a support, such as a layer in which the anodized material 90 is formed on the support.

  As the porous oxide substance 13, porous alumina (Al2O3) obtained by anodizing a part of a metal body (anodized substance) mainly composed of Al is well known. However, the material of the anodized substance 90 is not particularly limited, and any material can be used as long as it can be anodized. For example, other than Al, Si, Ti, Ta, Hf, Zr, In, Zn, etc. can be used. Further, the anodized substance 90 may include two or more materials that can be anodized. Although the planar pattern of the fine holes 15a to be formed varies depending on the type of the anodized material 90 to be used, a structure in which the fine holes 15a having substantially the same shape in plan view are arranged adjacent to each other is not changed.

  The micropores 15a serve as a reservoir for ionization promoters in the present invention. In this embodiment, as shown in FIG. 1B, the structure width of the concave microstructure is the hole diameter W1 of the microhole 15a. The micropore 15a has an opening 15b on the upper surface 14s of the coating layer 14 by forming the coating layer 14 on the upper surface 13s (FIG. 2B) of the porous oxide material 13. The aperture W2 of the opening 15b is the opening width in the present invention. Further, as shown in FIG. 1B, since the coating layer 14 is formed so that a part 14a of the coating layer 14 enters in the upper part of the fine hole 15a, the diameter W2 is formed to be smaller than the hole diameter W1. ing. That is, the diameter W2 of the opening 15b of the minute hole 15a is narrowed by the protruding portion 14a that is a part of the coating layer 14 that has entered the upper part of the minute hole 15a. Here, in the present embodiment, the value of the aperture W2 is basically determined by the length of the opening (15c in FIG. 2B) and the thickness of the protruding portion 14a at the time of being formed by anodic oxidation. Therefore, the value of the diameter W2 can be adjusted by the conditions of anodization or oblique vapor deposition. And the cross-sectional shape of the microhole 15a, the hole diameter, and the arrangement pitch of adjacent micropores can be controlled by anodizing conditions, and are not particularly limited. Usually, the pitch between adjacent fine holes 15a can be controlled in the range of 10 to 500 nm, and the hole diameter W1 of the fine holes 15a can be controlled in the range of 5 to 400 nm. Japanese Patent Application Laid-Open Nos. 2001-9800 and 2001-138300 disclose methods for finely controlling the formation position and the hole diameter of fine holes. By using these methods, the micropores having an arbitrary pore diameter and depth within the above range can be arranged almost regularly.

  The coating layer 14 is formed on the upper surface 13s of the porous oxide material 13 so that a part 14a thereof enters the upper part of the fine hole 15a, and functions to narrow the opening of the fine hole 15a. In the present embodiment, the upper surface 14 s of the coating layer 14 becomes the sample supply surface 10 s of the device for mass spectrometry 10. The material of the coating layer 14 is not particularly limited, and a metal material, a semiconductor material, a polymer material, or the like can be used. For example, when the material of the coating layer 14 is a metal material, an electric field enhancement effect by plasmons can be obtained at the edge of the coating layer 14 in the opening 15b. In this case, examples of the metal material include Au, Ag, Cu, Pt, Ni, Ti and the like from the viewpoint of efficiently inducing plasmon, and Au, Ag, and the like having a high electric field enhancing effect are particularly preferable.

  The ionization accelerator I is not particularly limited as long as it has such a function by accelerating ionization of the analyte by supplying protons and energy to the analyte by irradiation with laser light. Documented in the literature Nature Vol. 449 1033-1037 (2007) when a high molecular weight polymer (polymer) such as biological material (protein, etc.) or synthetic resin (nylon, etc.) is the analyte (Supplementary Information, 16 Bis (tridecafluoro-1,1,2,2-tetrahydrooctyl) tetramethyl-disiloxane, 1,3-dioctyltetramethyldisiloxane, 1,3-bis (hydroxybutyl) tetramethyl Organosilicon compounds such as disiloxane and 1,3-bis (3-carboxypropyl) tetramethyldisiloxane are preferred. Other ionization accelerators include carbon nanotubes, substrates, fullerenes and the like. Nicotinic acid, picolinic acid, 3-hydroxypicolinic acid, 3-aminopicolinic acid, 2,5-dihydroxybenzoic acid, α-cyano-4-hydroxycinnamic acid, sinapinic acid, 2- (4-hydroxyphenylazo) Benzoic acid, 2-mercaptobenzothiazole, 5-chloro-2-mercaptobenzothiazole, 2,6-dihydroxyacetophenone, 2,4,6-trihydroxyacetophenone, disranol, benzo [a] pyrene, 9-nitroanthracene, 2 A so-called matrix agent used in the MALDI method such as-[(2E) -3- (4-tret-butylphenyl) -2-methylprop-2-enylidene] malononitryl may also be used as the ionization accelerator I. As the ionization accelerator I, one type of compound may be used, or a mixture or laminate of two or more types of compounds may be used.

  Next, a method for manufacturing the mass spectrometry device 10 will be described with reference to FIGS.

  The device 10 for mass spectrometry includes an anodized film 12 having a fine hole 15a based on the anodized material 90 by causing anodization to proceed from one surface 90s of the anodized material 90 (FIG. 2A). A porous oxide material 13 composed of the non-anodized portion 11 is formed (FIG. 2B), and a coating material is obliquely deposited from one or more directions on the opening surface 13s of the porous oxide material 13 (FIG. 3A). 3B), the coating layer 14 is formed so that a part 14a enters the fine hole 15a.

  In the anodizing treatment, for example, the material to be anodized 90 is used as an anode, carbon or aluminum is used as a cathode (counter electrode), these are immersed in an anodizing electrolyte, and a voltage is applied between the anode and the cathode. Can be implemented. Since the film structure of the anodic oxide film 12 varies depending on conditions such as the type of electrolytic solution, current density, and liquid temperature, the electrolytic solution is usually treated with a porous type (porous type) or non-porous type (barrier type). ) Is selected as appropriate. Generally, when a treatment is performed with an electrolytic solution having a high film solubility, a porous film is formed. The porous electrolyte is not particularly limited, and sulfuric acid, oxalic acid, phosphoric acid, chromic acid, sulfamic acid, benzenesulfonic acid, and the like can be used. Moreover, the acidic electrolyte solution containing 2 or more of these acids is preferable.

  For example, when Al is anodized as the anodized material 90, as shown in FIG. 2B, the oxidation reaction proceeds in a substantially vertical direction from the surface 90s (upper surface in the figure), and the alumina layer 12 (anodized film) having the fine holes 15a is obtained. ) Is generated. In this case, the alumina layer 12 becomes the microstructure layer in the present invention. The alumina layer 12 produced by anodization has a structure in which fine columnar bodies having a substantially regular hexagonal shape in plan view are arranged adjacent to each other. A minute hole 15 a is opened in the depth direction from the upper surface 13 s of the porous oxide material 13 at a substantially central portion of each fine columnar body. Further, the bottoms of the micro holes 15a and the micro columnar bodies have rounded shapes as shown in the drawing. The structure of the alumina layer 12 produced by anodization is as follows: Hideki Masuda, “Preparation of mesoporous alumina by anodization and application as a functional material”, Material Technology Vol.15, No.10, 1997, p.34, etc. It is described in. The conditions of the anodizing treatment may be appropriately designed in consideration of the material of the anodized substance 90, the depth of anodizing, the shape of the micro holes 15a, and the like. When oxalic acid is used as the electrolytic solution, preferable conditions include an electrolytic solution concentration of 0.5 M, a liquid temperature of 15 ° C., and an applied voltage of 40 V. By changing the electrolysis time, the alumina layer 12 having an arbitrary layer thickness can be generated. When the thickness of the anodized material 90 before anodization is set thicker than the alumina layer 12 to be generated, the non-anodized portion 11 remains, and this non-anodized portion 11 becomes a metal layer. In this way, the porous oxide material 13 composed of the anodized film 12 having the fine holes 15a and the non-anodized portion 11 can be formed.

  The oblique deposition is performed by depositing a coating material from one or more directions on the opening surface 13 s of the porous oxide material 13. That is, as shown in FIG. 4, in the direction D in which the vapor deposition material flies, the three-dimensional coordinate is taken with the tip of the direction D as the origin, and the angle formed between the half line a passing through the origin and parallel to the direction D and the z axis is θ (0 <θ <90), where φ (0 ≦ φ <360) is an angle formed by the projection line b on the xy plane in the direction D and the x axis, (θ, φ) is a value of 1 or more. It means that the vapor deposition is performed from such a direction. For example, in FIG. 3A, the oblique deposition is performed from the direction D1 (θ = θo, φ = 90 °), and in FIG. 3B, the oblique deposition is performed from the direction D2 (θ = θo, φ = 270 °). Of course, the value of (θ, φ) is not particularly limited. When the coating layer 14 ′ is formed by only one-direction oblique deposition shown in FIG. 3A, the protruding portion 14a ′ exists only in a part of the opening 15b ′, but the opening 15b ′ can be narrowed. It is. That is, also in this case, it can be formed such that the diameter W2 of the opening 15b is smaller than the diameter W1 of the microhole 15a. Further, the porous oxide material 13 may be continuously rotated during the oblique deposition. The method for forming the coating layer 14 is not particularly limited, and vapor deposition methods such as a vacuum deposition method, a sputtering method, a CVD method, a laser deposition method, and a cluster ion beam method can be used. By the oblique vapor deposition as described above, the coating layer 14 can be formed such that a part 14a of the coating layer 14 enters the upper portion of the fine hole 15a.

  As described above, the mass spectrometric device 10 according to the present embodiment has the concave microstructure 15a and is configured such that the opening width W2 of the concave microstructure 15a is smaller than the structural width W1 of the concave microstructure 15a. Has been. Therefore, by storing the ionization accelerator in the concave microstructure 15a in the LDI method, it is possible to prevent unnecessary ionization accelerators from being scattered by the laser irradiation. FIG. 14A is a diagram conceptually illustrating the prevention of scattering of the ionization accelerator. It can be seen that by storing the ionization accelerator in the concave microstructure 15a having the opening width W2 narrowed, unnecessary scattering of the ionization accelerator is prevented as compared with the conventional method (FIG. 14B). Thereby, the interference peak derived from an ionization promoter can be reduced, and mass spectrometry with high quantitative property is attained.

  Furthermore, in this embodiment, if the material of the coating layer 14 is a metal material as described above, an electric field enhancement effect by plasmons can also be obtained. Usually, the ionization degree of the analyte depends on the intensity of the irradiation laser beam. This is because the ionization accelerator is excited by irradiation with laser light, and the analyte is ionized by supplying protons, ions, energy, or the like from the ionization accelerator in the excited state. Therefore, when there is an electric field enhancement effect due to plasmons, the intensity of the irradiation laser light can be enhanced by this electric field enhancement effect and the ionization efficiency of the analyte can be improved. As a result, the absolute intensity of the detection signal can be enhanced, mass analysis with higher quantitativeness can be performed, and further, the laser light intensity can be reduced.

<Design changes>
Moreover, although the case where the micropores 15a are regularly arranged using anodization has been described, the method for forming the micropores 15a is not limited to anodic oxidation. In addition to using anodization, a method of forming a plurality of concave microstructures regularly arranged on the surface of a substrate such as resin by nanoimprint technology, a focused ion beam (FIB), an electron beam (EB) on the surface of a substrate such as metal And a method of drawing a plurality of concave microstructures regularly arranged by an electronic drawing technique such as. However, it can be said that the above-described embodiment using anodization is more preferable because the entire surface can be collectively processed, the area can be increased, and an expensive apparatus is not required. The fine holes 15a may or may not be regularly arranged.

<Second Embodiment of Device for Mass Spectrometry>
First, the configuration of the mass spectrometry device 20 according to the present embodiment will be described. FIG. 5 is a schematic front view showing the device 20 for mass spectrometry. The mass spectrometric device 20 has the same configuration as the mass spectrometric device 10 according to the first embodiment. Different. Therefore, the description of the same components as those of the mass spectrometry device 10 is omitted unless particularly necessary.

  As shown in FIG. 5, the mass spectrometry device 20 includes a metal layer 21, a microstructure layer 22 having a concave microstructure 25 a and a protrusion 22 a formed on the metal layer, and a microstructure layer 22. And a coating layer 24 having a protruding portion 24a for narrowing the opening 25b of the fine hole 25a. The fine structure layer 22 has a fine hole 25a in which the hole diameter W1 is enlarged so as to leave the upper protrusion 22a. That is, the micro hole 25a in the present embodiment has a structure in which the opening 25b is narrowed by the protruding portion 22a and the protruding portion 24a. Here, the surface 24 s of the coating layer 24 becomes the sample supply surface 20 s of the device 20 for mass spectrometry. Further, in the present embodiment, the value of the diameter W2 is basically determined by the length of the opening (15c in FIG. 2B) and the thickness of the protruding portion 24a when formed by anodization. Therefore, the value of the diameter W2 can be adjusted by the conditions of anodization or oblique vapor deposition.

  Next, a method for manufacturing the mass spectrometry device 20 will be described. The mass spectrometric device 20 is manufactured by proceeding anodization from one surface 90s of the anodized material 90 (FIG. 2A), thereby making the anodized film 22 (having the fine holes 25a based on the anodized material 90). A porous oxide material 23 composed of a fine structure layer) and a non-anodized portion 21 is formed, and a coating material is obliquely deposited from one or more directions on the opening surface of the porous oxide material 23, thereby partially The coating layer 24 is formed so that 24a enters the fine holes 25a, and then the inner walls of the fine holes 25a are etched. That is, by forming the mass spectrometric device 10 and etching the inner wall of the micropore 15a in the mass spectrometric device 10, the micropore 25a having an enlarged pore diameter W1 is formed. At this time, the upper portion 22 a of the anodic oxide film 22 is left without being etched due to the presence of the protruding portion 24 a of the coating layer 24.

  The etching method of the fine holes 25a is not particularly limited, and wet etching or the like can be used. For example, when the fine structure layer 22 is alumina (Al 2 O 3), the inner wall of the fine hole 25 a can be dissolved and etched with a 5 wt% phosphoric acid solution having a liquid temperature of 30 ° C.

  As described above, the mass spectrometric device 20 according to the present embodiment also has a concave microstructure as in the first embodiment, and the opening width W2 of the concave microstructure is larger than the structure width W1 of the concave microstructure. Is also configured to be small. Therefore, the same effect as the first embodiment can be obtained.

  Furthermore, in the present embodiment, the micropores 25a are further enlarged by etching the inner walls of the micropores 25a. Therefore, more ionization accelerator can be stored in the micropores 25a, and the efficiency of mass spectrometry can be improved.

<Third embodiment of device for mass spectrometry>
First, the configuration of the mass spectrometry device 30 according to the present embodiment will be described. FIG. 6 is a schematic front view showing the device 30 for mass spectrometry. The mass spectrometric device 30 has substantially the same configuration as the mass spectrometric device 20 according to the second embodiment, but differs from the mass spectrometric device 20 in that there is no coating layer. Therefore, the description of the same components as those of the mass spectrometry device 20 is omitted unless particularly necessary.

  As shown in FIG. 6, the mass spectrometric device 30 includes a metal layer 31 and a microstructure layer 32 having a concave microstructure 35a and a protrusion 32a formed on the metal layer. The fine structure layer 32 has a structure having a fine hole 35a in which the hole diameter W1 is enlarged so as to leave the upper protrusion 32a. That is, the micro hole 35a in the present embodiment has a structure in which the opening 35b is narrowed by the protruding portion 32a. Here, the surface 32 s of the fine structure layer 32 becomes the sample supply surface 30 s of the device 30 for mass spectrometry. In the present embodiment, the diameter of the opening (15c in FIG. 2B) basically formed by anodic oxidation is the diameter W2 of the opening 35b of the fine hole 35a. Therefore, the value of the diameter W2 can be adjusted according to the anodizing conditions.

  Next, a method for manufacturing the mass spectrometry device 30 will be described. The device for mass spectrometry 30 is manufactured by anodizing from one surface 90s of the anodized material 90 (FIG. 2A), so that the anodized film 32 (having the fine holes 35a based on the anodized material 90). A porous oxide substance 33 composed of a microstructure layer) and a non-anodized portion 31 is formed, and a coating material is obliquely deposited from one or more directions on the opening surface of the porous oxide substance 33, thereby partially A coating layer is formed so as to enter the micropores 35a, the inner walls of the micropores 35a are etched, and then the coating layer is removed. That is, the mass spectrometric device 20 is formed, and the coating layer 24 in the mass spectrometric device 20 is removed. At this time, the upper portion 32a of the anodic oxide film 32 is left without being etched due to the presence of the protruding portion of the coating layer.

  The removal of the coating layer is not particularly limited, and wet etching or the like can be used. For example, when the coating layer is aluminum, it can be removed together with the etching of the inner wall of the micropore 25a by dissolution etching with a 5 wt% phosphoric acid solution having a liquid temperature of 30 ° C. Here, the coating layer may be completely removed or may remain partially. However, it is preferable to completely remove the residue because adhesion to the surface 32s of the anodic oxide film 32 is reduced and an interference peak derived from the residue is likely to occur.

  As described above, the mass spectrometric device 30 according to the present embodiment also has a concave microstructure, and the opening width W2 of the concave microstructure is larger than the structure width W1 of the concave microstructure, as in the first embodiment. Is also configured to be small. Therefore, by storing the ionization accelerator in the concave microstructure 35a in the LDI method, it is possible to prevent unnecessary ionization accelerator from being scattered by the laser irradiation. Thereby, the interference peak derived from an ionization promoter can be reduced, and mass spectrometry with high quantitative property is attained.

  Further, in the present embodiment, the microhole 35a is further enlarged by etching the inner wall of the microhole 35a. Therefore, more ionization promoter can be stored in the micropores 35a, and the efficiency of mass spectrometry can be improved. Furthermore, in this embodiment, it has a structure without the coating layer in the device for mass spectrometry (10, 20). Therefore, when the adhesion between the anodic oxide film 32 and the coating layer is low, an interference peak due to scattering of a part of the coating layer can be reduced, and mass spectrometry with higher quantitativeness can be performed.

<Fourth Embodiment of Device for Mass Spectrometry>
First, the configuration of the mass spectrometry device 40 according to the present embodiment will be described. FIG. 7 is a schematic front view showing the device 40 for mass spectrometry.

  As shown in FIG. 7, the mass spectrometry device 40 includes a metal layer 41, a microstructure layer 42 having a concave microstructure 45 a formed on the metal layer, and a microstructure layer 42. A covering layer 44 having a protruding portion 44a for narrowing the opening 45b of the micro hole 45a is provided. Here, the protrusion 44a has a tapered shape with a thick opening 45b that reaches the vicinity of the bottom of the concave microstructure 45a. That is, the micro hole 45a in the present embodiment has a structure in which the opening 45b is narrowed by the protruding portion 44a. Here, the surface 44 s of the coating layer 44 becomes the sample supply surface 40 s of the device for mass spectrometry 40. Further, in the present embodiment, the value of the diameter W2 is basically determined by the length of the opening (15c in FIG. 2B) and the thickness of the protruding portion 44a when formed by anodic oxidation. Therefore, the value of the diameter W2 can be adjusted by the conditions of anodization or oblique vapor deposition.

  Next, a manufacturing method of the device for mass spectrometry 40 will be described. The mass spectrometry device 40 is manufactured by anodizing from the one surface 90s of the anodized material 90 (FIG. 2A) so that the anode having a fine hole 45a having a large pore diameter W1 is formed on the basis of the anodized material 90. A porous oxide material 43 composed of an oxide film 42 (microstructure layer) and a non-anodized portion 41 is formed, and θ in FIG. 4 is fixed to the opening surface of the porous oxide material 43 to apply a coating material. By obliquely depositing from one or more directions, a coating layer is formed so that a part thereof enters the microhole 45a, and the process of oblique deposition is repeated a plurality of times while changing the value of θ. Here, when the width of the fine hole 45a is not constant as in the present embodiment, the hole diameter W1 of the fine hole 45a is set to the maximum value in the fine hole 45a.

  The method for manufacturing the microstructure layer is the same as that in the first embodiment. However, in order to narrow down the opening 45b by the taper shape of the protruding portion 44a, it is preferable to form the fine hole 45a as wide as possible.

  The material and manufacturing method of the coating layer 44 are substantially the same as those in the first embodiment. However, it is different in that the oblique deposition is repeated a plurality of times while changing the value of θ in FIG. The value of θ may be gradually increased or may be gradually decreased. By such a method, the protruding portion 44a having a tapered shape with a large opening 45b side can be formed.

  As described above, the mass spectrometric device 40 according to the present embodiment also has a concave microstructure as in the first embodiment, and the opening width W2 of the concave microstructure is larger than the structural width W1 of the concave microstructure. Is also configured to be small. Therefore, the same effect as the first embodiment can be obtained.

  Furthermore, the mass spectrometric device according to the present embodiment also provides an electric field enhancement effect by plasmons when the material of the coating layer 44 is a metal material. Therefore, the same effect as the first embodiment can be obtained.

<Fifth Embodiment of Device for Mass Spectrometry>
First, the configuration of the mass spectrometry device 50 according to the present embodiment will be described. FIG. 8 is a schematic front view showing the mass spectrometry device 50.

  As shown in FIG. 8, the mass spectrometric device 50 includes a metal layer 51 and a microstructure layer 52 formed on the metal layer and having a concave microstructure 55a and a protrusion 52a. Here, the protrusion 52a is an inner wall of the concave microstructure 55a, and has a tapered shape such that the width becomes narrower toward the opening 55b side. That is, the micro hole 55a in the present embodiment has a structure in which the opening 55b is narrowed by the protruding portion 52a. Here, the surface 52 s of the fine structure layer 52 becomes the sample supply surface 50 s of the device 50 for mass spectrometry.

  Next, a method for manufacturing the mass spectrometry device 50 will be described. The manufacturing method of the device 50 for mass spectrometry is shown below. First, anodization is progressed from one surface 90s of the anodized material 90 (FIG. 2A), so that the anodized film 52 (fine structure layer) having the fine holes 55a and the non-anodized oxide are formed based on the anodized material 90. A porous oxide material 53 comprising the portion 51 is formed. 4 is fixed to the opening surface of the porous oxide material 53 and the coating material is obliquely evaporated from one or more directions so that a coating layer is formed so that a part of the coating layer enters the micropores 55a. Form. Further, by etching the inside of the fine hole 55a, the portion not covered with the coating layer is etched, and when the etching is completed, the coating layer is removed. Thereafter, the step of oblique vapor deposition, the step of etching, and the step of removing the coating layer are sequentially repeated a plurality of times while changing the value of θ. Here, also in the present embodiment, as in the fourth embodiment, the maximum value of the width in the micro hole 55a is the hole diameter W1 of the micro hole 55a.

  The method for manufacturing the microstructure layer is the same as that in the first embodiment. In the present embodiment, the diameter of the opening (15c in FIG. 2B) basically formed by anodic oxidation is the diameter W2 of the opening 55b of the fine hole 55a. Therefore, the value of the diameter W2 can be adjusted according to the anodizing conditions.

  The material and manufacturing method of the coating layer are substantially the same as those in the first embodiment. However, it is different in that the oblique deposition is repeated a plurality of times while changing the value of θ in FIG. The value of θ may be gradually increased or may be gradually decreased.

  As described above, the mass spectrometry device 50 according to the present embodiment also has a concave microstructure, and the opening width W2 of the concave microstructure is larger than the structure width W1 of the concave microstructure, as in the first embodiment. Is also configured to be small. Therefore, by storing the ionization accelerator in the concave microstructure 55a in the LDI method, it is possible to prevent unnecessary ionization accelerator from being scattered by the laser irradiation. Thereby, the interference peak derived from an ionization promoter can be reduced, and mass spectrometry with high quantitative property is attained.

  Furthermore, also in the present embodiment, the coating layer is removed as in the third embodiment. Therefore, the same effect as the third embodiment can be obtained.

<Sixth Embodiment of Device for Mass Spectrometry>
First, the configuration of the mass spectrometry device 60 according to the present embodiment will be described. FIG. 9 is a schematic front view showing the device 60 for mass spectrometry. The device for mass spectrometry 60 is different from the device for mass spectrometry 30 in that the metal layer 31 in the device for mass spectrometry 30 according to the third embodiment is a heat insulating layer H. Therefore, the description of the same components as those of the mass spectrometry device 30 is omitted unless particularly necessary.

  Next, a method for manufacturing the mass spectrometry device 60 will be described. The mass spectrometric device 60 is manufactured by removing the metal layer 31 by dissolution and removal after the anodizing process in the mass spectrometric device 30 and forming the heat insulating layer H on the surface from which the metal layer 31 is removed. It is. Here, the manufacturing method of the device for mass spectrometry 30 is as described above.

  The heat insulating layer H is a layer having a thermal conductivity lower than that of the microstructure layer. Therefore, it is possible to prevent thermal diffusion downward of the mass spectrometry device 60 and efficiently confine heat generated by laser light irradiation in the fine structure layer 32. The material of the heat insulating layer H is not particularly limited, and for example, polystyrene foam, cellulose heat insulating material, or the like can be used. The method for forming the heat insulating layer H is not particularly limited, and vapor deposition methods such as a vacuum deposition method, a sputtering method, a CVD method, a laser deposition method, and a cluster ion beam method can be used. Moreover, the film-forming method of the heat insulation layer H may be a method of bonding a film or a plate-like heat insulating material using an adhesive. In this case, the adhesive preferably has conductivity. This is to make the voltage applied to the mass spectrometry device 60 uniform when a voltage is applied to the mass spectrometry device 60 in the mass spectrometry measurement.

  As described above, the mass spectrometric device 60 according to this embodiment also has a concave microstructure, and the opening width W2 of the concave microstructure is larger than the structure width W1 of the concave microstructure, as in the first embodiment. Is also configured to be small. Therefore, by storing the ionization accelerator in the concave microstructure 35a in the LDI method, it is possible to prevent unnecessary ionization accelerator from being scattered by the laser irradiation. Thereby, the interference peak derived from an ionization promoter can be reduced, and mass spectrometry with high quantitative property is attained.

  Furthermore, also in the present embodiment, the coating layer is removed as in the third embodiment. Therefore, the same effect as the third embodiment can be obtained.

  Furthermore, in this embodiment, the heat insulation layer H is formed in the part of the microstructure layer 32 where the metal layer 31 is removed. Therefore, it is possible to prevent thermal diffusion downward of the mass spectrometry device 60 and efficiently confine heat generated by laser light irradiation in the fine structure layer 32. As a result, the scattering efficiency of the sample can be improved, and mass analysis with higher quantification becomes possible.

<Seventh Embodiment of Device for Mass Spectrometry>
First, the configuration of the mass spectrometry device 70 according to the present embodiment will be described. FIG. 10 is a schematic front view showing the mass spectrometry device 70. The device for mass spectrometry 70 is configured to have the second metal layer M on the bottom surface of the device for mass spectrometry 60 according to the sixth embodiment. Therefore, the description of the same components as the mass spectrometry device 60 is omitted unless particularly necessary.

  Next, a manufacturing method of the device for mass spectrometry 70 will be described. The mass spectrometry device 70 is manufactured by forming the second metal layer M on the lower surface of the thermal insulation layer H (the bottom surface of the mass spectrometry device 60) after forming the thermal insulation layer H in the mass spectrometry device 60. It is. Here, the manufacturing method of the device for mass spectrometry 60 is as described above.

  The second metal layer M has a function of making the voltage applied to the mass spectrometry device 70 uniform when a voltage is applied to the mass spectrometry device 70. The material of the second metal layer M is not particularly limited, and for example, stainless steel, aluminum, copper, gold or the like can be used. The method for forming the second metal layer M is not particularly limited, and vapor deposition methods such as vacuum deposition, sputtering, CVD, laser deposition, and cluster ion beam can be used. it can. The film formation method of the second metal layer M may be a method of bonding a film or a plate-like conductive substance using an adhesive.

  As described above, the mass spectrometric device 70 according to the present embodiment also has a concave microstructure as in the first embodiment, and the opening width W2 of the concave microstructure is larger than the structure width W1 of the concave microstructure. Is also configured to be small. Therefore, by storing the ionization accelerator in the concave microstructure 35a in the LDI method, it is possible to prevent unnecessary ionization accelerator from being scattered by the laser irradiation. Thereby, the interference peak derived from an ionization promoter can be reduced, and mass spectrometry with high quantitative property is attained.

  Furthermore, also in the present embodiment, the coating layer is removed as in the third embodiment. Therefore, the same effect as the third embodiment can be obtained.

  Furthermore, also in the present embodiment, as in the sixth embodiment, the heat insulating layer H is formed on the portion of the microstructure layer 32 where the metal layer 31 is removed. Therefore, the same effect as in the sixth embodiment can be obtained.

  Furthermore, in the present embodiment, the second metal layer M is formed on the lower surface of the heat insulating layer H (the bottom surface of the mass spectrometry device 60). Therefore, when a voltage is applied to the device for mass spectrometry 70, the voltage applied to the device for mass spectrometry 70 can be made uniform. As a result, signal intensity unevenness due to applied voltage unevenness can be reduced.

<Eighth Embodiment of Device for Mass Spectrometry>
First, the configuration of the mass spectrometry device 80 according to the present embodiment will be described. FIG. 11 is a schematic perspective view showing the device 80 for mass spectrometry.

  As shown in FIG. 11, the mass spectrometric device 80 has a microstructure layer 82 having a concave microstructure 85a, and a protrusion 84a that is formed on the microstructure layer 82 and narrows the opening 85b of the concave microstructure 85a. A coating layer 84 is provided. Here, the protruding portion 84a is a part of the covering layer 84, and is formed so as to partially enter the concave microstructure 85a. That is, the concave microstructure 85a in the present embodiment has a structure in which the opening 85b is narrowed by the protruding portion 84a. Here, the surface 84 s of the coating layer 84 becomes the sample supply surface 80 s of the device 80 for mass spectrometry.

  Next, a manufacturing method of the device for mass spectrometry 80 will be described. The device for mass spectrometry 80 is manufactured by forming a stripe-shaped mask on one surface 90s of the microstructure layer precursor 90 (FIG. 2A) and performing dry etching on the surface to form a fine structure having a channel-type microstructure 85a. A structural layer 82 is formed, and a coating material is obliquely deposited from one or more directions on the opening surface of the fine structure layer 82 in the same manner as in the first embodiment, so that part of the structure layer 82 is formed on the channel-type fine structure 85a. The covering layer 84 is formed so as to enter.

  The fine structure layer 82 has a so-called channel-type fine structure in which an uneven structure extending in a line shape is repeated in a stripe shape. The material of the microstructure layer 82 is not particularly limited, and a metal material such as Al or a semiconductor material such as Si can be used. The manufacturing method of the fine structure layer 82 is not particularly limited. For example, a method of forming a stripe-shaped mask on the fine structure layer precursor and performing dry etching thereon, a focused ion beam (FIB) or an electron beam. (EB) etc. and the method by electronic drawing etc. are mentioned. In the present embodiment, the value of the diameter W2 is basically determined by the structure width W1 of the concave microstructure 85a and the thickness of the protruding portion 84a. Therefore, the value of the diameter W2 can be adjusted by the manufacturing method of the microstructure layer 82 or the conditions of oblique deposition.

  The material and manufacturing method of the coating layer 84 are substantially the same as those in the first embodiment.

  As described above, the mass spectrometry device 80 according to the present embodiment also has a concave microstructure, and the opening width W2 of the concave microstructure is larger than the structure width W1 of the concave microstructure, as in the first embodiment. Is also configured to be small. Therefore, the same effect as the first embodiment can be obtained.

  Furthermore, the mass spectrometric device according to the present embodiment also provides an electric field enhancement effect by plasmons when the material of the coating layer 84 is a metal material. Therefore, the same effect as the first embodiment can be obtained.

"Laser desorption ionization mass spectrometer and analysis method"
Next, a laser desorption / ionization mass spectrometry apparatus and an analysis method using the mass spectrometry device according to the present invention (for example, the mass spectrometry device 30 according to the third embodiment) will be described.

  With reference to FIG. 12, an embodiment of a mass spectrometer for carrying out the mass spectrometry method will be described. The mass spectrometer 100 of this embodiment is a time-of-flight mass spectrometer (TOF-MS). FIG. 12 is a schematic diagram showing the configuration of the mass spectrometer 100 of the present embodiment.

  As shown in the figure, a mass spectrometer 100 includes a mass analysis device 30 according to the above embodiment and a stage 102 having a substrate holding means for holding the mass analysis device 30 in a box 101 kept in a vacuum. Irradiating the sample supplied to the surface of the mass spectrometric device 30 with the laser beam L to desorb the analyte S from the surface of the mass spectrometric device 30, and the desorbed analyte Analyzing means 104 for detecting S and analyzing the mass of the analyte S, and disposed between the mass analyzing device 30 and the analyzing means 104 at a position facing the surface of the mass analyzing device 30. The drawing grid 105 and the end plate 106 arranged to face the surface of the drawing grid 105 opposite to the surface on the mass analysis device 30 side are provided.

The stage 102 is a moving stage capable of moving the mass spectrometry device 30 placed on the stage 102 in at least one direction (X direction in the figure). The light irradiation means 103 includes a laser light source. In addition, a light guide system such as a mirror for guiding light emitted from the light source may be provided. Examples of the light source include a pulse laser having a wavelength of 355 nm and a pulse width of about 50 ps to 50 ns.

  The analysis unit 104 detects a substance S to be analyzed that has been desorbed from the surface of the mass spectrometry device 30 by irradiation with the laser light L and has flown through the central hole of the extraction grid 105 and the end plate 106. 107, an amplifier 108 that amplifies the output of the detection unit 107, and a data processing unit 109 that processes an output signal from the amplifier 108.

  Hereinafter, mass spectrometry using the mass spectrometer 100 configured as described above will be described. Mass spectrometry is performed on the analyte S supplied on the mass spectrometry device 30. First, the voltage Vs is applied to the mass spectrometric device 30, and the surface of the mass spectrometric device 30 is irradiated with laser light L having a specific wavelength from the light irradiation means 103 by a predetermined start signal. By the irradiation with the laser beam L, the analyte S in the sample is ionized and desorbed from the surface. The analyte S may be desorbed after being ionized, or may be deionized after being desorbed. The desorbed analyte S is extracted and accelerated in the direction of the extraction grid 105 due to the potential difference Vs between the mass spectrometry device 30 and the extraction grid 105, and travels almost straight in the direction of the end plate 106 through the central hole. Then, it flies, passes through the hole of the end plate 106, reaches the detection unit 107, and is detected.

  An output signal from the detection unit 107 is amplified to a predetermined level by the amplifier 108 and then input to the data processing unit 109. In the data processing unit 109, a synchronization signal synchronized with the start signal is input, and the flight time of the analyte S can be obtained based on this synchronization signal and the output signal from the amplifier 108. The mass spectrum can be obtained by deriving the m / z value from the time.

  In the present embodiment, the case where the mass spectrometer 100 is a TOF-MS has been described as an example. However, the apparatus for performing mass analysis of ionized sample ions is not limited to the TOF type, and IT (Ion Trap; Ion trap type), FT (ICR) (Fourier-Transform Ion Cyclotron Resonance; Fourier transform type), QqTOF (Quadrupole-TOF; Quadrupole-TOF type), TOF- A mass spectrometer such as TOF (TOF connection type) can be used.

  As described above, in the laser desorption / ionization mass spectrometry apparatus and method according to this embodiment, the mass spectrometry device according to the present invention is used as the mass spectrometry device. Therefore, by storing the ionization accelerator in the concave microstructure in the LDI method, it is possible to prevent unnecessary ionization accelerators from being scattered by the laser irradiation. Thereby, the interference peak derived from an ionization promoter can be reduced, and mass spectrometry with high quantitative property is attained.

<Example>
Examples of a device for mass spectrometry according to the present invention and examples of a laser desorption ionization mass spectrometer and an analysis method performed using the device for mass spectrometry according to the present invention are shown below.

  The device 30 for mass spectrometry was manufactured by the following method. First, an aluminum plate was subjected to anodization for 60 s in a sulfuric acid solution (liquid temperature: 16 ° C., 0.3 M) under a voltage of 25 V to form a porous oxide material containing alumina. Then, an aluminum film having a thickness of 10 nm was formed by oblique deposition twice at an angle of (θ, φ) = (70 °, 90 °) and (70 °, 270 °). Next, the aluminum film and the alumina layer on the porous oxide material were dissolved with a 5 wt% phosphoric acid solution at a liquid temperature of 30 ° C., thereby removing the aluminum film and enlarging the pore diameter.

  The analysis conditions are as follows: analyzer: MALDI-TOFMS AXIMA manufactured by Shimadzu Corporation, excitation wavelength: 355 nm, measurement mode: positive mode and linear mode, sample: Angiotensin I manufactured by SIGMA-ALDRICH, sample concentration: 0.5 mM, amount of solution dropped : 0.5 ul, matrix used: α-cyano-4-hydroxycinnamic acid, device used: device for mass spectrometry 30 according to the present invention, control device: stainless steel plate. FIG. 13A shows an analysis result when a stainless steel plate is used, and FIG. 13B shows an analysis result when the mass spectrometry device 30 is used. FIG. 13A and FIG. 13B show that the interference peak derived from the ionization accelerator can be reduced by using the mass spectrometry device 30.

1 is a schematic perspective view showing a device for mass spectrometry according to a first embodiment. Schematic showing the device for mass spectrometry according to the first embodiment (No. 1) Schematic diagram showing the device for mass spectrometry according to the first embodiment (No. 2) Schematic perspective view showing the microstructure layer precursor Schematic perspective view showing porous oxide material Schematic which shows the formation process of the coating layer in the device for mass spectrometry which concerns on 1st Embodiment (the 1) Schematic which shows the formation process of the coating layer in the device for mass spectrometry which concerns on 1st Embodiment (the 2) The figure which shows the definition of the vapor deposition direction in the oblique vapor deposition of the coating material Schematic showing a device for mass spectrometry according to a second embodiment Schematic which shows the device for mass spectrometry which concerns on 3rd Embodiment Schematic which shows the device for mass spectrometry which concerns on 4th Embodiment Schematic which shows the device for mass spectrometry which concerns on 5th Embodiment Schematic which shows the device for mass spectrometry which concerns on 6th Embodiment Schematic which shows the device for mass spectrometry which concerns on 7th Embodiment Schematic which shows the device for mass spectrometry which concerns on 8th Embodiment 1 is a schematic view showing an embodiment of a laser desorption ionization mass spectrometer according to the present invention. Mass spectral data showing the results of laser desorption / ionization mass spectrometry using the conventional method Mass spectral data showing results of implementation of laser desorption ionization mass spectrometry method according to the present invention Schematic showing the vicinity of the device for mass spectrometry according to the present invention at the time of laser irradiation Schematic showing the vicinity of a conventional device for mass spectrometry during laser irradiation

Explanation of symbols

10. Device for mass spectrometry (first embodiment)
10s Sample supply surface 11 Metal layer (non-anodized portion)
12 Microstructure layer (anodized film)
13 Porous Oxidizing Material 14 Covering Layer 14a Projecting Part 14s Surface 15a of Covering Layer Concave Microstructure (Micropore)
15b Aperture 20 Device for Mass Spectrometry (Second Embodiment)
30 Device for Mass Spectrometry (Third Embodiment)
40 Device for mass spectrometry (fourth embodiment)
50 Mass spectrometry device (fifth embodiment)
60 Device for mass spectrometry (sixth embodiment)
70 Device for Mass Spectrometry (Seventh Embodiment)
80 Mass Spectrometer (Eighth Embodiment)
90 Anodized substance 100 Mass spectrometer H Thermal insulation layer I Ionization promoter L Laser light M Second metal layer S Analyte W1 Structure width (pore diameter)
W2 opening width (caliber)

Claims (10)

Laser desorption ionization mass spectrometry in which the analyte supplied on the supply surface of the mass analysis device is desorbed from the mass analysis device by laser light irradiation and the mass spectrum of the ionized analyte is measured. In the device for mass spectrometry used in the method,
Comprising a microstructure layer having a plurality of concave microstructures;
The plurality of concave microstructures have openings in the supply surface;
A device for mass spectrometry, wherein an opening width of the opening is smaller than a structure width of the concave microstructure.   The device for mass spectrometry according to claim 1, wherein the concave microstructure is a micropore.   The device for mass spectrometry according to claim 1 or 2, wherein the concave microstructure stores an ionization accelerator that promotes ionization of the analyte.   The device for mass spectrometry according to any one of claims 1 to 3, further comprising a heat insulating layer adjacent to a surface of the microstructure layer on a side opposite to the side on which the supply surface is provided.   The device for mass spectrometry according to any one of claims 1 to 4, further comprising a metal layer on a surface of the device for mass spectrometry opposite to the side on which the supply surface is provided. Used in a laser desorption ionization mass spectrometry method in which an analyte supplied on a mass spectrometry device is desorbed from the mass spectrometry device by laser light irradiation and a mass spectrum of the ionized analyte is measured. In a method for manufacturing a device for mass spectrometry to be obtained,
Forming a plurality of concave microstructures so as to have openings in one surface of the microstructure layer precursor;
A method for manufacturing a device for mass spectrometry, characterized in that a coating material is obliquely deposited from one or more directions with respect to a surface having the opening. The microstructure layer precursor is an anodized material;
The plurality of concave microstructures, wherein the anodized material is anodized to form a plurality of fine holes having openings in the anodized surface subjected to the anodization. 6. A method for producing a device for mass spectrometry according to 6.   8. The method for manufacturing a device for mass spectrometry according to claim 6, wherein the plurality of concave microstructures are subjected to an etching process after the oblique deposition. A device for mass spectrometry according to any one of claims 1 to 5,
A laser light source for irradiating the analyte supplied on the mass spectrometric device with laser light;
A device support that supports the device for mass spectrometry;
An analysis unit that separates the ionized analyte that has been desorbed and ionized from the device for mass spectrometry by irradiation with the laser light, according to the m / z value of the ionized analyte;
A detection unit for detecting the ionized analyte;
A laser desorption ionization mass spectrometer comprising: a data processing unit that forms a mass spectrum of the ionized analyte based on detection data obtained by the detection unit.
(Here, m is a dimensionless quantity obtained by dividing the mass of the ion by the unit of unified atomic mass, and z is the valence of the charge of the ionized analyte.) Using the device for mass spectrometry according to any one of claims 1 to 5,
Analyte supplied to the device for mass spectrometry is desorbed and ionized from the device for mass spectrometry by laser light irradiation,
According to the m / z value of the ionized analyte, the ionized analyte is separated and detected,
A laser desorption / ionization mass spectrometry method comprising forming a mass spectrum of the ionized analyte based on detection data obtained by detection.
(Here, m is a dimensionless quantity obtained by dividing the mass of the ion by the unit of unified atomic mass, and z is the valence of the charge of the ionized analyte.)

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