JP2010071949A - Device for mass spectrometry and mass spectrograph using the same, and mass spectrography - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To achieve high-sensitivity mass spectrometry of a hardly volatile substance and a high molecular weight substance by reducing power of measurement light in a surface support laser desorption ionization mass spectrography. <P>SOLUTION: A device 1 for mass spectrometry applies measurement light L1 to a sample abutting on a surface 1s to eliminate a substance S to be analyzed included in the sample from the surface 1s. The device 1 for mass spectrometry has a base material 10 having a plurality of micropores 13 open on the surface 1s, and has a metal fine structure at least on inner wall surfaces 13a of the micropores 13. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a method for irradiating a sample in contact with a device surface with measurement light, ionizing a substance to be analyzed for mass analysis contained in the sample, desorbing the substance from the surface, and mass analyzing the desorbed substance The present invention relates to a device for mass spectrometry used in the above, a mass spectrometry apparatus and a mass spectrometry method using the device.

  In mass spectrometry used for substance identification, etc., a mass that irradiates a sample that is in contact with a device for mass spectrometry with measurement light to desorb the analyte from the device, and detects the desorbed substance by mass Analytical methods are known. For example, Time of Flight Mass Spectroscopy (TOF-MS) is a method in which a substance desorbed from a device is caused to fly a predetermined distance and the mass of the substance is analyzed based on the time of flight.

  In such mass spectrometry, the analyte is usually ionized and desorbed. However, it is difficult to ionize and desorb analytes, especially if they are analytes that are low-volatility substances such as biological substances or high-molecular-weight substances such as synthetic polymers. Various methods have been studied.

  The matrix-assisted laser desorption / ionization method (MALDI method) uses an analyte to be mixed in sinapinic acid or glycerin, which is called a matrix, as a mixed crystal, and uses the light energy absorbed by the matrix for analysis. This is a method in which a substance is vaporized together with a matrix, and then a proton transfer occurs between the matrix and the analyte to ionize the analyte. The MALDI method is widely used for mass spectrometry of non-volatile substances, biomolecules, and high molecular weight substances such as synthetic polymers as a soft ionization method with little chemical influence on the analyte, such as fragmentation and denaturation. (Patent Document 1, etc.).

  However, when the analyte is a synthetic polymer or the like, the solubility in the solvent and the polarity of the polymer chain differ greatly due to the difference in the chemical structure of the polymer chain, and even if the main structure is the same, the average molecular weight and Since various characteristics differ depending on the chemical structure of the terminal group, it is necessary to optimize the type of matrix agent and the crystal preparation method according to the type of analyte.

On the other hand, surface-assisted laser desorption mass spectrometry (Surface-assisted laser desorption) that performs soft ionization by providing the mass spectrometry device itself with a function to support desorption / ionization of analytes without using a matrix agent / ionization-mass spectrometry: SALDI-MS) is being studied. For example, in Patent Document 2 and Patent Document 3, in a mass spectrometric device using a porous silicon substrate having a nano-order pore structure on the surface, soft ionization is performed using the interaction between the silicon nanostructure and measurement light. ing.
JP 9-320515 A US Patent No. 2008/0073512 US Patent No. 2006/0157648

  However, since the enhancement of ionization efficiency of SALDI-MS is not yet sufficient, high-power measurement light is required for mass spectrometry of hardly volatile substances and high molecular weight substances. Therefore, problems such as fragmentation and denaturation of the analyte and deformation of the substrate itself still remain.

  The present invention has been made in view of the above circumstances, and in surface-assisted laser desorption / ionization mass spectrometry, it is possible to reduce the power of measurement light, fragmentation or denaturation of an analyte, and the substrate itself. An object of the present invention is to provide a mass spectrometric device capable of mass spectrometry of a hardly volatile substance or a high molecular weight substance without causing deformation, and a mass spectroscope equipped with the device.

  The mass spectrometric device of the present invention is a mass spectrometric device for desorbing an analyte contained in a sample from the surface by irradiating the sample brought into contact with the surface with measurement light, And a substrate having a plurality of micropores opened at the above, and having a metal microstructure on at least an inner wall surface of the micropores.

  In the device for mass spectrometry of the present invention, an ionization accelerator is preferably fixed to at least a part of the surface or the micropore. The fine holes are preferably bottomed holes.

  As a suitable aspect of the device for mass spectrometry of the present invention, the metal fine structure may be one in which a plurality of metal particles are fixed to the inner wall surface.

  Further, as another preferred embodiment of the device for mass spectrometry of the invention, the micropore is a first micropore, and the first micropore is a bottomed hole formed by opening an inner wall surface. 2 having a plurality of fine holes, and the metal fine structure is formed so as to protrude from the inner wall surface on the filling portion and filled with the second fine hole, and is parallel to the inner wall surface. The thing which consists of a some metal body which consists of a protrusion part with the largest diameter of a direction larger than the diameter of the said filling part is mentioned. In this configuration, the second fine hole is formed on the inner wall surface of the fine hole by anodizing a metal body to be anodized having a plurality of bottomed fine holes opened on one surface. The plurality of metal bodies are preferably formed by performing a plating process in the second fine holes until a part of the metal bodies protrudes from the substrate surface. Moreover, it is preferable that the average separation distance between the protrusions adjacent to each other is 10 nm or less.

  Moreover, as another suitable aspect of the device for mass spectrometry of this invention, what the said metal fine structure consists of a metal layer by which the metal was patterned is mentioned.

  The mass spectrometric apparatus of the present invention irradiates the sample for mass spectrometry of the present invention and a sample in contact with the surface of the mass spectrometric device with the measurement light, and the analyte of mass spectrometry in the sample A light irradiation means for desorbing the substance from the surface, and an analysis means for detecting the desorbed analyte and analyzing the mass of the analyte. A preferred embodiment of the mass spectrometer of the present invention is a time-of-flight mass spectrometer.

  The mass spectrometric method of the present invention is an analysis method using the mass spectrometric device of the present invention, wherein after the sample is brought into contact with the surface of the mass spectrometric device, the measurement is performed on the surface of the sample in contact with the mass spectrometric method. Irradiating light, and using the plasmon generated in the metal microstructure by irradiation of the measurement light, the analyte contained in the sample is ionized and desorbed from the surface, and the desorbed analyte And mass spectrometry is performed.

  The device for mass spectrometry of the present invention includes a substrate having a plurality of fine holes opened at the sample contact surface, and has a metal microstructure on at least the inner wall surface of the fine holes. According to such a configuration, the interaction between the fine structure of the substrate surface that is the first fine structure and the measurement light, and the interaction between the metal fine structure in the fine hole that is the second fine structure and the measurement light, Can be used to efficiently ionize and desorb the analyte from the surface. In addition, since ionization by the second microstructure is performed in a local space in the micropore, the analytes that have been ionized and desorbed collide with the analytes that exist in the same micropores, increasing the energy of each other. Therefore, the ionization efficiency is higher. Therefore, according to the present invention, in the surface-assisted laser desorption / ionization mass spectrometry, the measurement light can be reduced in power, and even if the analyte is a hardly volatile substance or a high molecular weight substance, the analyte can be analyzed. Mass spectrometry can be performed with high sensitivity without causing fragmentation or denaturation of the substance and deformation of the substrate itself. Moreover, in the structure provided with the ionization accelerator, not only the energy of the measurement light but also the excitation efficiency of the ionization accelerator can be enhanced at the same time by the interaction with the measurement light in the first and second fine structures. Therefore, the ionization efficiency and the absolute intensity of the detected signal can be effectively enhanced by the above structure, the ionization accelerator and the synergistic effect thereof.

“First Embodiment of Device for Mass Spectrometry”
With reference to FIG. 1, the device for mass spectrometry of 1st Embodiment which concerns on this invention is demonstrated. FIG. 1 is a sectional view in the thickness direction, and FIG. 2 is a diagram showing the manufacturing process. In order to facilitate visual recognition, the scale of the constituent elements is appropriately changed from the actual one.

  As shown in FIG. 1, the mass spectrometric device 1 according to the present embodiment irradiates the sample 1 brought into contact with the surface 1s with the measurement light L1, so that the analyte of mass spectrometry contained in the sample is exposed to the surface 1s. A device for mass spectrometry to be desorbed from a substrate, comprising a substrate 10 having a plurality of bottomed micropores 13 opened at a surface 1s (10s), and a plurality of metal particles 20a on at least an inner wall surface 13a of the micropores 13. It has a device structure provided with a metal microstructure formed by bonding.

  In the mass spectrometric device 1 according to the present embodiment, the base material 10 includes a dielectric 11 in which a large number of micropores 13 having substantially the same shape in plan view are opened on the surface and arranged in a regular order on a conductor 12. (First fine structure).

  The micro hole 13 is a non-through hole that is opened substantially straight from the surface of the dielectric 11 in the thickness direction and is closed without reaching the back surface.

In the present embodiment, as shown in FIG. 2, the dielectric 11 is obtained by anodizing a part of the anodized metal body 40 that contains aluminum (Al) as a main component and may contain minute impurities. The resulting alumina (Al ₂ O ₃ ) layer (metal oxide layer) 41 is obtained. The conductor 12 is constituted by a non-anodized portion 42 of the anodized metal body 40 that remains without being anodized.

  The shape of the metal body 40 to be anodized is not limited, and examples thereof include a plate shape. Further, it may be used in a form with a support such as a layer in which the anodized metal body 40 is formed on a support.

  In anodizing, for example, the metal body 40 to be anodized 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. The electrolytic solution is not limited, and an acidic electrolytic solution containing one or more acids such as sulfuric acid, phosphoric acid, chromic acid, oxalic acid, sulfamic acid, and benzenesulfonic acid is preferably used.

  When the anodized metal body 40 shown in FIG. 2A is anodized, as shown in FIG. 2B, an oxidation reaction proceeds in a direction substantially perpendicular to the surface from the surface 40s (upper surface in the drawing), and the alumina layer 41 (11 ) Is generated.

  The alumina layer 41 (11) 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 13 is opened in the depth direction from the surface 40 s at a substantially central portion of each minute columnar body. Further, the bottom surface of each fine hole 13 and fine columnar body has a rounded shape as shown in the figure. The structure of the alumina layer produced by anodization is described in Hideki Masuda, “Preparation of mesoporous alumina by anodization and its application as a functional material”, Material Technology Vol.15, No.10, 1997, p.34, etc. Are listed.

  As an example of suitable conditions for anodization, when oxalic acid is used as the electrolytic solution, an electrolytic solution concentration of 0.5 M, a liquid temperature of 15 ° C., and an applied voltage of 40 V can be mentioned. By changing the electrolysis time, the alumina layer 41 (11) having an arbitrary layer thickness can be generated. If the thickness of the anodized metal body 40 before anodization is set thicker than the generated alumina layer 41 (11), the non-anodized part remains and the conductor 42 (12 comprising the non-anodized part) ), An alumina layer 41 (dielectric) (11) in which a large number of micropores 13 having substantially the same shape in plan view are opened on the surface and are generally regularly arranged can be obtained.

  The diameter of each micropore and the arrangement pitch between adjacent micropores are preferably such that the interaction with the measurement light L1 is effectively generated. In the porous silicon described in “Background Art”, in order to effectively obtain these interactions, the diameter of each micropore and the arrangement pitch between adjacent micropores are preferably on the order of submicron or less. It is said. On the other hand, the device 1 for mass spectrometry has a metal microstructure inside the micropores, and considering these synergistic effects and manufacturing simplicity, the diameter of each micropore and the micropores adjacent to each other The arrangement pitch is preferably about 100 nm to 5 μm.

  In normal anodization, the pitch between adjacent micropores 13 can be controlled in the range of 10 to 500 nm, and the pore diameter 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.

  Next, as shown in FIGS. 2C and 2D, a plurality of metal particles 20a are formed on the inner wall surface 13a of the micropore 13 (second microstructure) to obtain the device 1 for mass spectrometry (FIG. 2E). In the figure, the number of metal particles 20a is reduced for easy understanding.

  The method for forming the metal particles 20a is not particularly limited, and examples thereof include an oblique vapor deposition method and a method in which a metal fine particle dispersion is applied and annealed after film formation. 2C and 2D show an example in which the metal particles 20a are formed by oblique vapor deposition. When oblique deposition is performed, spherical or island-shaped metal particles 20a are naturally formed on the inner wall surface 13a.

  When the measurement light L1 is irradiated onto the metal particles 20a, the metal absorbs the measurement light L1 and energy is confined in the metal particles 20a. Due to this confinement effect, the energy of the measurement light L1 in the vicinity of the second fine structure and the energy of the analyte S can be increased, and the ionization efficiency can be increased.

  When the metal particle 20a has such a size that the localized plasmon is effectively induced, the electric field enhancement effect by the localized plasmon is obtained together, so that the ionization efficiency can be increased more effectively. In order to effectively obtain localized plasmons, the maximum diameter of the metal particles 20a is preferably less than the wavelength of the measurement light L1. Considering the wavelength of the measurement light L1 that is generally used, the metal particles 20a preferably have a maximum diameter in the range of 10 nm to 300 nm.

  When the metal particles 20a are large enough to induce localized plasmons, the metal particles 20a adjacent to each other are preferably separated, and the average separation distance is more preferably in the range of several nm to 10 nm. . When the average separation distance is within the above range, a region called a hot spot having a very high electric field enhancement effect due to the localized plasmon effect is generated in the vicinity thereof, which is preferable.

  The localized plasmon phenomenon is a phenomenon in which a free electric field in a convex portion oscillates in resonance with an electric field of light to generate a strong electric field around the convex portion. Therefore, the metal particle 20a may be any metal having free electrons. , Au, Ag, Cu, Pt, Ni, Ti and the like, and Au, Ag, etc., which have a high electric field enhancing effect, are particularly preferable.

  As described above, the device 1 for mass spectrometry includes the substrate 10 having a plurality of bottomed micropores 13 opened at the surface 1s (10s), and a plurality of metal particles 20a on at least the inner wall surface 13a of the micropores 13. Is provided with a metal fine structure formed by fixing. When a sample containing the analyte S is brought into contact with the sample contact surface (surface) 1s of the device 1 for mass spectrometry and the sample is irradiated with the measurement light L1, the microstructure of the surface 1s, which is the first microstructure ( And the measurement light L1 and the interaction between the measurement light L1 and the metal fine structure in which the plurality of metal particles 20a are fixed to the inner wall surface 13a, which is the second fine structure. By utilizing this, the analyte can be ionized with high efficiency and desorbed from the surface. In addition, since ionization by the second fine structure is performed in a local space in the micropore 13, the analytes that are ionized and desorbed collide with the analytes that exist in the same micropores, so that each other's energy is absorbed. The ionization efficiency becomes higher because of increasing each other. Therefore, according to the device 1 for mass spectrometry, in the surface assisted laser desorption / ionization mass spectrometry, the measurement light L1 can be reduced in power, and the analyte S is a hardly volatile substance or a high molecular weight substance. However, mass analysis can be performed with high sensitivity without causing fragmentation or denaturation of the analyte S and deformation of the substrate itself.

  The device 1 for mass spectrometry may have a configuration in which the ionization accelerator I is fixed to a non-opening portion of the micropore 13 on the surface 1s or the inner wall surface 13a of the micropore 13 (not shown). The ionization accelerator I is a substance that promotes ionization of the analyte by supplying protons and energy to the analyte by irradiation with the measuring light L1.

  The ionization promoter I is not particularly limited as long as it has the above function, but is preferably a substance that does not cause an interference peak that lowers the detection sensitivity of the analyte S. When a biomolecule or a synthetic polymer is an analyte, it is described in the document Nature Vol.449 1033-1037 (2007) (Supplementary Information, page 16), bis (tridecafluoro-1,1, 2,2-tetrahydrooctyl) tetramethyl-disiloxane, 1,3-dioctyltetramethyldisiloxane, 1,3-bis (hydroxybutyl) tetramethyldisiloxane, 1,3-bis (3-carboxypropyl) tetramethyl Organosilicon compounds such as disiloxane 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 matrix agent used in the MALDI method such as-[(2E) -3- (4-tret-butylphenyl) -2-methylprop-2-enylidene] malonitryl may also be used as the ionization accelerator I.

  The method for fixing the ionization accelerator I is not particularly limited, and examples thereof include a method in which an appropriate amount of a solution containing the ionization accelerator I is applied to the surface 10s, subjected to heat treatment in an oven or the like, and dried to remove the solvent. In order to prevent the excessive ionization accelerator I from being fixed, the process of removing the excess ionization accelerator I with an air gun or the like after the heat treatment and performing the heat treatment again may be repeated.

  The amount of the ionization accelerator I to be fixed is not particularly limited. However, if the amount is excessive, an excessive amount of measurement light L1 sufficient to induce localized plasmons in the fine metal body 20 cannot reach the fine metal body 20. The ionization accelerator I is desorbed and detected at the time of measurement, resulting in a decrease in detection sensitivity. If the amount is too small, effective ionization of the analyte cannot be performed. 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.

  In the device 1 for mass spectrometry, the excitation efficiency of the ionization promoter I can be increased by the interaction caused by the first fine structure and the enhanced electric field caused by the localized plasmon caused by the second fine structure. Therefore, if it is set as the structure provided with the ionization promoter I, it can make ionization efficiency higher and can implement | achieve further reduction in the power of measurement light.

  As described in the “Background” section, the MALDI method has been used so far for mass analysis of non-volatile substances and high molecular weight substances without chemically affecting the analyte. However, since these substances have complex chemical structures, it is essential to optimize the method for preparing the mixed crystal of the matrix agent and the sample according to the chemical properties of the analyte. It had to be complicated. As described above, according to the mass spectrometric device of the present embodiment, the surface-assisted laser desorption / ionization method does not cause fragmentation or denaturation of the analyte S and does not cause deformation of the substrate itself. Mass spectrometry of substances and high molecular weight substances can be made possible. In the surface-assisted laser desorption / ionization method, the sample is prepared simply by applying the sample solution onto the sample contact surface of the device for mass spectrometry. Therefore, according to the present invention, the sample is prepared in a simple manner and analyzed. Without causing fragmentation or denaturation of the substance S and deformation of the substrate itself, highly sensitive mass spectrometry of a hardly volatile substance or a high molecular weight substance can be performed.

“Second Embodiment of Device for Mass Spectrometry”
With reference to FIG. 3, the device 2 for mass spectrometry of 2nd Embodiment which concerns on this invention is demonstrated. 3A is a cross-sectional view in the thickness direction of the mass spectrometric device 2, and FIG. 3B is an enlarged view of the vicinity of the surface 13′a of the fine hole 13 ′ in FIG. 3A. In order to facilitate visual recognition, the scale of the constituent elements is appropriately changed from the actual one.

  In the device 1 for mass spectrometry of the first embodiment, the metal microstructure which is the second microstructure is a plurality of metal particles 20a fixed to the inner wall surface (surface) 13a of the micropore, whereas for the mass spectrometry As shown in the drawing, in the device 2, the base material 10 ′ having a plurality of bottomed first fine holes 13 ′ opened at the surface 2 s (10 ′s) is an inner wall surface 13 ′ a of the first fine holes. A plurality of second micropores 14 which are bottomed holes formed by opening the inner wall 13′a, and a filling portion 21 filled in the second micropore 14 on the inner wall surface 13′a, and a filling portion A metal microstructure composed of a plurality of metal bodies 20b formed on the upper surface 21 and projecting from the inner wall surface 13'a and having a protruding portion 22 whose maximum diameter in the direction parallel to the inner wall surface 13'a is larger than the diameter of the filling portion 21. It has a configuration with. In the figure, the number of the second fine holes 14 and the metal bodies 20b are reduced for easy understanding.

  In the mass spectrometric device 2 of the present embodiment, the base material 10 ′ has a portion of the anodized metal body 40 ′ having a plurality of bottomed fine holes 43 opened at the surface 40 ′ s shown in FIG. 4A halfway. It consists of a metal oxide body 41 ′ obtained by anodizing and a non-anodized portion 42 ′.

  Anodization proceeds on all exposed surfaces of the anodized metal body 40 'where an electric field is applied during anodization. In the present embodiment, the anodization is performed by arranging electrodes so that anodization is started at least on the inner wall surface 43a of the fine hole 43. Therefore, for the sake of clarity, FIG. 4 shows a case where only the inner wall surface of the fine hole 43 is anodized to form the second fine hole 14 (FIG. 4B).

  Since the fine holes 43 of the metal body 40 ′ to be anodized determine the uneven structure of the first fine structure in the present embodiment, the diameter of the fine holes 43 and the first fine holes 43 adjacent to each other are determined. As in the first embodiment, the arrangement pitch is preferably such a size that the interaction with the measuring light L1 is effectively generated. However, in the present embodiment, a relatively large fine pore diameter and pitch may be used in consideration of the convenience in manufacturing the second fine structure described below.

  When the anodized metal body 40 ′ shown in FIG. 4A is anodized, as shown in FIG. 4B, an oxidation reaction proceeds from the inner wall surface 43a of the fine hole 43 in a direction substantially perpendicular to the surface, and the alumina layer 41 '(11') is generated. As described in the first embodiment, the alumina layer 41 ′ (11 ′) has a structure in which fine columnar bodies having a substantially regular hexagonal shape in plan view are arranged adjacent to each other, and at a substantially central portion of each fine columnar body. The second fine hole 14 is opened from the inner wall surface 13'a in the depth direction.

  Since the details of the anodization are as described in the first embodiment, description thereof is omitted here. The second fine structure of the present embodiment includes a filling portion 21 filled in the second fine hole 14 and a protruding portion formed on the filling portion 21 from the inner wall surface 13'a in a direction parallel to the inner wall surface 13'a. Since the metal body 20b is composed of the plurality of metal bodies 20b each having the maximum diameter larger than the diameter of the filling portion 21, the local plasmon in the second microstructure has a depth at which the metal body 20b does not easily peel off. It is preferable to set the anodic oxidation conditions so as to have a fine pore diameter and a pitch that can effectively obtain the electric field enhancing effect due to.

  The method for forming the plurality of metal bodies 20b composed of the filling portion 21 and the protruding portion 22 is not particularly limited, but electroplating treatment or the like is performed until a part of the second fine hole 14 protrudes from the inner wall surface 13′a. It is formed by applying.

  When electroplating is performed, the conductor 12 'functions as an electrode, and the metal is preferentially deposited from the bottom of the fine hole 14 where the electric field is strong. By continuously performing this electroplating process, the metal is filled in the second fine holes 14 to form the filling portion 21 of the metal body 20b. If the electroplating process is further continued after the filling portion 21 is formed, the filling metal overflows from the second fine hole 14, but since the electric field near the second fine hole 14 is strong, the second fine hole 14. The metal continues to deposit around the periphery, and protrudes from the surface 13'a on the filling portion 21 to form a protruding portion 22 having a diameter larger than the diameter of the filling portion 21 to obtain the device 2 for mass spectrometry ( FIG. 4C).

  In the second fine structure composed of the plurality of metal bodies 20b, the same interaction as in the first embodiment is caused by irradiation with the measurement light L1, and the energy of the measurement light L1 in the vicinity of the second fine structure and the analyte S Energy can be increased and ionization efficiency can be increased.

  Similarly to the first embodiment, the metal body 20b is preferable if the protrusion 22 has a size that can induce localized plasmons because the electric field enhancement effect by the localized plasmons can be obtained together. . In order to effectively obtain localized plasmons, it is preferable that the maximum diameter of the protrusion 22 of the metal body 20b is less than the wavelength of the measurement light L1. Considering the wavelength of the measurement light L1 that is generally used, it is preferable that the maximum diameter of the projecting portion 22 be in the range of 10 nm to 300 nm.

In order to effectively obtain the electric field enhancement effect due to localized plasmons in the second microstructure, it is preferable that the separation distance w between adjacent metal particles is smaller, as described in the first embodiment, More preferably, it is 10 nm. Therefore, also in this embodiment, it is preferable that the separation distance between the adjacent protrusions 22 is several nm to 10 nm (FIG. 3B).
A preferable material of the metal body 20b is the same as that of the first embodiment.

  As described above, the mass spectrometric device 2 includes the substrate 10 ′ having a plurality of bottomed first micropores 13 ′ opened at the surface 2s (10 ′s), and the first micropores 13 ′. At least the inner wall surface 13'a is provided with a metal microstructure composed of a plurality of metal bodies 20b, and has the same configuration as that of the device for mass spectrometry of the first embodiment except that the configuration of the metal microstructure is different. Therefore, the same effect as the mass spectrometric device of the first embodiment can be obtained.

  Also in the present embodiment, as in the first embodiment, an ionization accelerator is applied to the non-opening portion of the first micropore 13 'on the surface 2s and the inner wall surface 13'a of the first micropore 13'. By making the structure fixed, ionization efficiency can be increased more effectively. Suitable materials for the ionization accelerator I are the same as those in the first embodiment.

“Third Embodiment of Device for Mass Spectrometry”
With reference to FIG. 5, the device 3 for mass spectrometry of 2nd Embodiment which concerns on this invention is demonstrated. 5A is a cross-sectional view in the thickness direction of the mass spectrometric device 3, and FIG. 5B is a partially enlarged view of the inner wall surface 13a of the fine hole 13 in FIG. 5A. In order to facilitate visual recognition, the scale of the constituent elements is appropriately changed from the actual one.

  As shown in the figure, the mass spectrometry device 3 has a metal microstructure that is the second microstructure, in which the fine metal wires 20c are formed on the inner wall surface 13a of the micropores in a regular lattice pattern (mesh shape). The structure is the same as that of the first embodiment except that the structure is different from that of the first metal layer.

  Since the board | substrate 10 is the same as that of 1st Embodiment, description is abbreviate | omitted about a preferable material, a shape, and a manufacturing method.

  The material of the metal thin wire 20c is not particularly limited, and the same material as the metal particle 20a of the first embodiment is exemplified.

  The pitch and line width of the fine metal wires 20c are not particularly limited as long as an energy confinement effect by light absorption can be obtained by irradiating the measurement light L1 on the fine metal wires 20c. Also in the present embodiment, it is preferable that the electric field enhancement effect by the localized plasmon is obtained in the metal fine structure composed of the fine metal wires 20c having the lattice pattern. Localized plasmon resonance is a phenomenon in which an electric field is generated when a metal free electron resonates with an electric field of light and vibrates. Therefore, in a metal layer having a fine concavo-convex structure like the metal microstructure of this embodiment. It is said that the free electrons in the convex portion vibrate in resonance with the electric field of light to generate a strong electric field around the convex portion, and local plasmon resonance effectively occurs. Accordingly, the pitch and line width of the fine metal wires 11 are preferably in the range of 10 nm or more and 300 nm or less, and preferably have a pattern gap.

  Examples of the method for forming the metal thin wire 11 include photolithography and nanoimprinting.

  As described above, the mass spectrometric device 3 includes the base material 10 having a plurality of bottomed micropores 13 opened at the surface 3s (10s), and at least the inner wall surface 13a of the micropores 13 has a thin metal wire (metal). 20c is provided with a metal microstructure composed of a patterned metal layer, and has the same configuration as that of the device for mass spectrometry of the first embodiment except that the configuration of the metal microstructure is different. Therefore, the same effect as the mass spectrometric device of the first embodiment can be obtained.

  In the present embodiment as well, as in the first embodiment, a more effective effect is obtained by configuring the non-opening portion of the fine hole 13 on the surface 3s or the inner wall surface 13a of the fine hole 13 to be fixed. In particular, the ionization efficiency can be increased. Suitable materials for the ionization accelerator I are the same as those in the first embodiment.

(Design changes)
In the first to third embodiments, only Al is cited as the main component of the anodized metal body. However, any metal can be used as long as the metal oxide that can be anodized is translucent. Can be used. Other than Al, Si, Ti, Ta, Hf, Zr, In, Zn, etc. can be used. The metal to be anodized may contain two or more types of metals that can be anodized. Depending on the type of metal to be anodized, the planar pattern of the micropores to be formed varies, but it does not change that a dielectric having a structure in which micropores having substantially the same shape in plan view are arranged adjacently is formed.

  In the first to third embodiments, the case where the fine holes are regularly arranged using anodic oxidation has been described. However, the method of forming the fine holes is not limited to anodic oxidation. In the case of producing the first microstructure, the above-described embodiment using anodization is preferable because the entire surface can be collectively processed, can cope with a large area, and does not require an expensive apparatus. In addition to the use of a laser, a plurality of concave portions regularly arranged by nanoimprint technology are formed on the surface of a substrate such as a resin, and an electron drawing such as a focused ion beam (FIB) or an electron beam (EB) is formed on the surface of a substrate such as a metal Examples include a fine processing technique such as drawing a plurality of concave portions regularly arranged by the technique.

  In the second embodiment, when forming a fine hole in the fine hole of the first fine structure, it is difficult to use the above processing technique, but when it is a resin base material that can be a resist agent, A method of forming micropores by a photolithography method can be used.

  Moreover, in each embodiment, although the case where the micropore (1st micropore) was a bottomed hole was demonstrated, as long as a sample can be hold | maintained in a sample contact surface or a micropore, it may be a through-hole. . Further, the fine holes may or may not be regularly arranged.

  Further, the metal microstructure is not limited to the structure shown in the first to third embodiments.

"Mass spectrometer"
With reference to FIG. 6, the mass spectrometer of the first embodiment according to the present invention will be described by taking as an example the case of using the mass spectrometry device 1 of the first embodiment. The mass spectrometer of this embodiment is a time-of-flight mass spectrometer (TOF-MS). FIG. 6 is a schematic diagram showing the configuration of the mass spectrometer 4 of the present embodiment, and the apparatus configuration and effects obtained are the same when the mass spectrometry devices 2 and 3 of the second and third embodiments are used. is there.

  As shown in the figure, the mass spectrometer 4 includes a device 68 for mass analysis, a device holding means 60 for holding the device 1 for mass analysis, and a device for mass spectrometry in a box 68 kept in a vacuum. The sample that is in contact with the surface 1 s of the first reflector 10 of the device 1 is irradiated with the measurement light L <b> 1 to desorb the analyte S for mass spectrometry in the sample from the surface 1 s of the first reflector 10. The first light irradiation means 61 and the analysis means 64 for detecting the desorbed analyte S and analyzing the mass of the analysis substance S are provided, and between the mass spectrometry device 1 and the analysis means 64, A lead grid 62 disposed at a position facing the surface 1 s of the first reflector 10, and an end plate 63 disposed facing the surface of the lead grid 62 opposite to the surface on the mass analysis device 1 side. It has a configuration with.

  The light irradiation means 61 includes a single wavelength light source such as a laser, and may include a light guide system such as a mirror that guides light emitted from the light source. Examples of the single wavelength light source include a pulse laser having a wavelength of 337 nm and a pulse width of about 50 ps to 50 ns.

  The analysis means 64 is desorbed from the surface of the first reflector 10 of the device for mass spectrometry 1 by irradiation with the measurement light L1, and is analyzed through the extraction grid 62 and the central hole of the end plate 63. The detection unit 65 that detects the substance S, an amplifier 66 that amplifies the output of the detection unit 65, and a data processing unit 67 that processes an output signal from the amplifier 66 are roughly configured.

Hereinafter, mass spectrometry using the mass spectrometer 4 configured as described above will be described.
First, the voltage Vs is applied to the mass spectrometry device 1 in contact with the sample, and the measurement light L1 of a specific wavelength is irradiated from the light irradiation means 61 to the surface 1s of the mass analysis device 1 by a predetermined start signal. By irradiating the measurement light L1, the electric field is enhanced on the surface 1s of the mass spectrometry device 1, and the analyte in the sample is generated by the light energy of the measurement light L1 enhanced by the electric field and the excited ionization accelerator. S is ionized and desorbed from the surface 1s.

  The desorbed analyte S is extracted and accelerated in the direction of the extraction grid 62 due to the potential difference Vs between the mass spectrometry device 1 and the extraction grid 62, and travels almost straight in the direction of the end plate 63 through the central hole. Then, it passes through the hole of the end plate 63 and reaches the detector 65 to be detected.

  The analyte S may be in a state in which another substance such as a part of the surface modification on the mass spectrometry device 1 is bound. The flying speed of the analyte S after desorption depends on the mass of the substance, and the smaller the mass, the faster the detection speed.

  An output signal from the detector 65 is amplified to a predetermined level by the amplifier 66 and then input to the data processing unit 67. In the data processing unit 67, a synchronization signal synchronized with the start signal is input, and the flight time of the analyte S can be obtained based on the synchronization signal and the output signal from the amplifier 66. A mass spectrum can be obtained by deriving mass from time.

  Since the mass spectrometer 4 of the present embodiment is configured by using the device 1 for mass spectrometry of the above embodiment, the same effect as the device 1 for mass spectrometry can be obtained.

  In the present embodiment, the configuration in which everything is provided in the box 68 has been described. However, if at least the mass spectrometry device 1, the drawer grid 62, the end plate 63, and the detector 65 are disposed in the box 68. Good.

  In this embodiment, although the case where the mass spectrometer 4 is TOF-MS was demonstrated to the example, it is applicable also to other mass spectrometry methods.

  The present invention can be applied to a mass spectrometer used for identification of substances.

Sectional view in thickness direction of the device for mass spectrometry of the first embodiment according to the present invention Sectional drawing which shows the manufacturing process of the device for mass spectrometry of FIG. 1 (the 1) Sectional drawing which shows the manufacturing process of the device for mass spectrometry of FIG. 1 (the 2) Sectional drawing which shows the manufacturing process of the device for mass spectrometry of FIG. 1 (the 3) Sectional drawing which shows the manufacturing process of the device for mass spectrometry of FIG. 1 (the 4) Sectional drawing which shows the manufacturing process of the device for mass spectrometry of FIG. 1 (the 5) Sectional view in the thickness direction of the device for mass spectrometry according to the second embodiment of the present invention Enlarged view of the inner wall of the fine hole in FIG. 3A Sectional drawing which shows the manufacturing process of the device for mass spectrometry of FIG. 3A (the 1) Sectional drawing which shows the manufacturing process of the device for mass spectrometry of FIG. 3A (the 2) Sectional drawing which shows the manufacturing process of the device for mass spectrometry of FIG. 3A (the 3) Sectional view in the thickness direction of the device for mass spectrometry according to the third embodiment of the present invention Enlarged view of the inner wall of the fine hole in FIG. 5A Schematic which shows the structure of the mass spectrometer of one Embodiment which concerns on this invention.

Explanation of symbols

1-3 Device for mass spectrometry 1s, 2s, 3s surface (sample contact surface)
10, 10 'substrate 10s, 10's substrate surface 11, 11' dielectric 13, 13 'minute hole 12 conductor 13a minute hole inner wall surface 14 second minute hole 20a metal particle (metal microstructure)
20b Metal body (metal microstructure)
20c fine metal wire (fine metal structure)
20s Translucent surface 21 Filling portion 22 Protruding portion 40 Anodized metal body 41 Metal oxide body 42 Non-anodized portion 4 Mass spectrometer 61 Light irradiation means 64 Analysis means 76 Detection means (spectral means)
L1 Measuring light S Analyte I Ionization accelerator w Separation distance between protrusions

Claims (12)

A device for mass spectrometry that detaches an analyte contained in a sample from the surface by irradiating the sample brought into contact with the surface with measurement light,
A device for mass spectrometry, comprising a substrate having a plurality of micropores opened on the surface, and having a metal microstructure on at least an inner wall surface of the micropores.   The device for mass spectrometry according to claim 1, wherein an ionization accelerator is fixed to at least a part of the surface or the micropores.   The device for mass spectrometry according to claim 1 or 2, wherein the fine hole is a bottomed hole.   The device for mass spectrometry according to any one of claims 1 to 3, wherein the metal microstructure has a plurality of metal particles fixed to the inner wall surface.   The device for mass spectrometry according to claim 4, wherein the base material is obtained by anodizing a metal body to be anodized.   The fine hole is a first fine hole, and the first fine hole has a plurality of second fine holes which are bottomed holes formed by opening on the inner wall surface, and the metal fine hole A filling portion filled with the second fine hole, and a protruding portion formed on the filling portion so as to protrude from the inner wall surface and having a maximum diameter parallel to the inner wall surface larger than the diameter of the filling portion. The device for mass spectrometry according to any one of claims 1 to 3, wherein the device comprises a plurality of metal bodies. The second fine hole is formed on the inner wall surface of the fine hole by anodizing a metal body to be anodized having a plurality of bottomed fine holes opened on one surface,
The plurality of metal bodies are formed by performing a plating process in the second fine holes until a part of the metal bodies protrudes from the surface of the base material. Device for mass spectrometry.   The device for mass spectrometry according to claim 6 or 7, wherein an average separation distance between the protrusions adjacent to each other is 10 nm or less.   The device for mass spectrometry according to any one of claims 1 to 3, wherein the metal microstructure is a metal layer in which a metal is patterned. A device for mass spectrometry according to any one of claims 1 to 9,
A light irradiation means for irradiating the sample in contact with the surface of the mass spectrometry device with the measurement light, and desorbing the analyte of mass spectrometry in the sample from the surface;
A mass spectrometer comprising: an analyzing means for detecting the desorbed analyte and analyzing the mass of the analyte.   The mass spectrometer according to claim 10, which is a time-of-flight mass spectrometer. An analysis method using the device for mass spectrometry according to claim 1,
After contacting the sample with the surface of the device for mass spectrometry, irradiating the surface with which the sample is contacted with measurement light
Utilizing plasmons generated in the metal microstructure by irradiation of the measurement light, the analyte contained in the sample is ionized and desorbed from the surface,
An analysis method comprising capturing the desorbed analyte and performing mass spectrometry.

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