JP2010078346A - Mass analyzing device, mass analyzer using the same and mass analyzing method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To achieve the lowering of the power of measuring light and to enable the highly sensitive mass analysis of a hardly volatile substance or high-molecular weight substance in a surface support laser eliminating/ionizing mass analyzing method. <P>SOLUTION: This mass analyzing device 1 includes a base material 10 having a plurality of the micropores 20 opened in its surface 1s and constituted so as to irradiate the sample, which is brought into contact with the surface 1s with the measuring light L1 to eliminate the substance S to be analyzed contained in a sample from the surface 1s. This mass analyzing device includes a device structure wherein recessed parts 21 are formed to the sidewall surfaces 20a of the micropores 20. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  INDUSTRIAL APPLICABILITY The present invention is used in a method of irradiating a sample in contact with a device surface with measurement light, desorbing an analyte of mass analysis contained in the sample from the surface, and mass-analyzing the desorbed material. The present invention relates to a device for mass spectrometry, a mass spectrometer using the device, and a mass spectrometry method.

  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 depending on the chemical structure of the polymer chain, and even if the main chain 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 spectrometry device capable of mass spectrometry of a hardly volatile substance or a high molecular weight substance without causing deformation, a mass spectrometry apparatus and a mass spectrometry method including the same.

  The device for mass spectrometry of the present invention comprises a substrate having a plurality of micropores opened on the surface, and irradiates the sample brought into contact with the surface with measurement light, whereby the analyte contained in the sample is converted into the analyte. A device for mass spectrometry to be desorbed from the surface, wherein a concave portion is formed on a side wall surface of the micropore.

  In the present specification, the shape of the concave portion is not limited, and the concave portion in the case where the side wall surface of the microhole has a corrugated shape, the micropore formed in the side wall surface of the microhole, or the stripe shape And fine grooves formed in a lattice shape are also included. In addition, the recess has a sufficient depth and opening so that the analyte present in the recess is ionized after the analyte in the micropore other than the analyte is ionized. To do.

  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.

In the device for mass spectrometry of the present invention, a preferable embodiment of the substrate includes one in which at least the surface of the side wall surface of the fine hole is made of a dielectric. An example of such a dielectric is one made of SiO ₂ (which may contain inevitable impurities).

  Moreover, as another suitable aspect of the said base material, what is obtained by anodizing a to-be-anodized metal body is mentioned.

  Moreover, as another preferable aspect of the substrate, the bottomed hole formed by opening the first minute hole on the inner wall surface of the minute hole, wherein the minute hole is a first minute hole. And those having a plurality of second fine holes. The second fine hole can be formed on the side 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. As the metal to be anodized, Al is preferable.

  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 By irradiating light, using the plasmon generated in the metal microstructure by irradiation of the measurement light, the analyte contained in the sample is desorbed from the surface, and the desorbed analyte is captured. Mass spectrometry.

  The device for mass spectrometry of the present invention includes a base material having a plurality of fine holes opened on the surface, and has a structure in which concave portions are formed on the side wall surfaces of the fine holes. In such a configuration, the analyte in the micropores is desorbed by irradiation with the measurement light, but it is more than the analyte in the sample (hereinafter referred to as the second ionization portion) present in the concave portion of the side wall surface of the micropore. Since the analyte in the sample other than the second ionized portion existing in the micropore (hereinafter referred to as the first ionized portion) is easily ionized / desorbed, the analyte in the first ionized portion is first ionized / desorbed. After desorption, the analyte in the second ionized portion is ionized and desorbed. At this time, the analyte in the first ionized portion includes the interaction between the fine structure on the surface and the measurement light (first interaction), and the interaction between the concavo-convex structure on the micropore sidewall and the measurement light (second Ionization and desorption using the interaction), and ionization is performed with higher efficiency than conventional devices having a fine structure only on the surface. Furthermore, the analyte in the second ionized portion is ionized using the second interaction and jumps out of the recess, and the analyte that has not yet been ionized in the micropores and ions that have jumped out of another recess Since they collide and desorb with each other's energy, the ionization efficiency is further increased.

  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 of the present embodiment includes a base material 10 having a plurality of fine holes 20 opened at a surface 1 s (10 s), and a measurement light is applied to a sample brought into contact with the surface 1 s. A device for mass spectrometry in which a substance to be analyzed for mass spectrometry contained in a sample is desorbed from the surface 1s by irradiating L1, and has a device structure in which a recess 21 is formed on the side wall surface 20a of the micropore 20. Have.

  In the mass spectrometric device 1 of the present embodiment, the substrate 10 includes a dielectric 11 in which a large number of micro holes 20 having substantially the same shape in plan view are opened on the surface and arranged in a regular order on the conductor 12. (First fine structure).

  The micro-hole 20 is a non-penetrating hole that is opened substantially straight in the thickness direction from the surface of the dielectric 11 and closed without reaching the back surface while changing the hole diameter so that the side wall surface has corrugated irregularities. It is a hole and has a recess 21 on the side wall surface 20a.

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 20 is opened in a depth direction from the surface 40 s at a substantially central portion of each minute columnar body. Further, the bottom surfaces of the micro holes 20 and the fine columnar bodies have rounded shapes as shown in the drawing. 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. In the device for mass spectrometry 1 of the present embodiment, the hole diameter is changed so that the side wall surface 20a of the fine hole 20 has a waved shape. In anodic oxidation, the pore diameter of the micropores can be made arbitrary by changing the applied voltage, and any thickness (depth) can be made by changing the electrolysis time. Therefore, the anodic oxidation may be carried out by setting the applied voltage and electrolysis time so as to obtain the desired uneven shape.

  For example, in FIG. 2B, by increasing the applied voltage after the microhole 20 having a predetermined depth is formed, the micropore diameter is increased and the recess 21 is formed in the microhole 20 as shown in FIG. 2C. . By controlling the applied voltage and the electrolysis time so as to obtain desired irregularities and forming the micro holes 20 that are non-through holes, the device 1 for mass spectrometry of the present embodiment can be obtained (FIG. 2D).

  The recess 21 has a depth and an opening diameter sufficient to allow the analyte S present in the recess 21 to be ionized after the analyte in the micropore 20 other than the analyte is ionized. ing.

  It is preferable that the diameter of the opening part of the recessed part 21 exists in the range of 1-20 nm. The diameter of the opening can be changed depending on the pitch of the unevenness in the fine hole side wall 20a. According to the anodic oxidation, the pitch of the irregularities on the micro-hole sidewall 20a can be controlled on the order of about 10 nm, and in the present embodiment, it is preferably 10 to 300 nm.

  The depth of the concave portion 21 can be changed by the hole diameter of the fine hole 20a. According to the anodic oxidation, it can be controlled on the order of about 1 nm, preferably 5 to 100 nm, preferably 5 to 20 nm. More preferably.

  Moreover, it is preferable that the hole diameter and arrangement pitch of the micropores on the surface 10s have such a size 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 mass spectrometric device 1 has a concave portion on the side wall surface of the micropore, and considering the synergistic effect and the simplicity in manufacturing, the diameter of each micropore is 20 to 500 nm and adjacent to each other. The arrangement pitch between the micropores is preferably about 100 nm to 5 μm.

  In normal anodic oxidation, the pitch between adjacent fine holes 11a can be controlled in the range of 10 to 500 nm, and the diameter of the fine holes 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.

  In the present embodiment, the interaction between the fine structure on the surface 1s and the measurement light L1 (first interaction), and the interaction between the fine structure on the microhole sidewall (uneven structure) and the measurement light L1 (second interaction). And ionization / desorption of the analyte.

  When the microstructure surface is a dielectric as in this embodiment, when the measurement light L1 is irradiated onto the microstructure, the convex portion absorbs the measurement light L1 and the energy is confined in the convex portion. Due to this confinement effect, the energy of the measurement light L1 and the energy of the analyte S can be increased, and the ionization efficiency can be increased.

  As described above, the mass spectrometry device 1 includes the base material 10 having a plurality of fine holes 20 opened at the surface 1 s (10 s), and has a structure in which the concave portion 21 is formed on the side wall surface 20 a. When a sample containing the analyte S is brought into contact with the sample contact surface (surface) 1s of the device for mass spectrometry 1 and the sample is irradiated with the measurement light L1, the analyte S in the micropore 20 is desorbed. However, in the sample other than the second ionized portion present in the micropore 20 (hereinafter referred to as “analyzed substance S” in the sample (hereinafter referred to as “second ionized portion”) present in the recess 21 of the micropore side wall surface 20a (hereinafter referred to as “second ionized portion”). Since the analyte S of the first ionized portion is easily ionized / desorbed, the analyte S of the second ionized portion is first ionized / desorbed first. Are ionized and desorbed. At this time, the analyte S in the first ionized portion has an interaction between the fine structure on the surface 1s and the measurement light L1 (first interaction), and an interaction between the concavo-convex structure on the fine hole sidewall 20a and the measurement light L1. Since it is ionized and desorbed using the action (second interaction), it is ionized with higher efficiency than the conventional device having a fine structure only on the surface 1s. Further, the analyte S in the second ionized portion is ionized using the second interaction and jumps out of the recess 21, and from the analyte S not yet ionized in the micropore 20 or another recess 21. Since the ions collide with the ions that have jumped out and desorbed by increasing each other's energy, the ionization efficiency is further increased. 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.

  The mass spectrometric device 1 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 side 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 also be increased by the interaction resulting from the first microstructure and the second microstructure described above. 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 Technology” section, the MALDI method has been used so far for mass analysis of non-volatile substances and high molecular weight substances without chemical effects on 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 surface 20′a of the micropore 20 ′ of FIG. 3A. In order to facilitate visual recognition, the scale of the constituent elements is appropriately changed from the actual one.

  In the device for mass spectrometry 1 of the first embodiment, the unevenness of the side wall surface of the micropore was an uneven surface having a wave shape, whereas the device for mass spectrometry 2 is as shown in FIGS. A substrate 10 'having a plurality of first micro holes 20' opened at the surface 2s (10's) is provided, and the first micro holes 20 'open at the side wall surface 20'a. A plurality of second fine holes (recesses) 21 ′ that are bottomed holes formed in this manner are provided. In the figure, the number of the second fine holes 21 'is reduced for easy understanding.

  In the device 2 for mass spectrometry of the present embodiment, the base material 10 ′ anodizes the anodized metal body 40 ′ having a plurality of fine holes 43 opened at the surface 40 ′s as shown in FIG. 4A. The metal oxide body 41 ′ obtained in this way and the 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, anodization is performed by arranging an electrode so that anodization is started at least on the side wall surface 43a of the fine hole 43. Therefore, for the sake of clarity, FIG. 4 shows a case where only the side 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 micropore diameter and pitch may be used in consideration of the simplicity of manufacturing the second micropore 21 'on the micropore sidewall described below.

  In the present embodiment, the second fine hole 21 ′ corresponds to the concave portion 21 of the first embodiment. Therefore, the preferable diameter and depth of the opening are the same as those in the first embodiment. In the present embodiment, since the second micro holes 21 ′ are formed by anodic oxidation, their sizes can be controlled by changing the anodic oxidation conditions.

  When the anodized metal body 40 ′ shown in FIG. 4A is anodized, as shown in FIG. 4B, an oxidation reaction proceeds from the side 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 21 is opened from the side wall surface 20′a in the depth direction (see FIG. 3B). The mass spectrometric device 2 can be obtained as described above. Details of the anodic oxidation have already been described in the first embodiment, and a description thereof is omitted here.

  As described above, the mass spectrometric device 2 includes the base material 10 ′ having a plurality of first micropores 20 ′ opened at the surface 2s (10 ′s). A plurality of second fine holes (recesses) 21 ′, which are bottomed holes formed by opening on the wall surface 20′a, are provided. Therefore, the configuration is the same as that of the device for mass spectrometry of the first embodiment except that the shape of the concavo-convex structure of the side wall surface 20'a is different. In the present embodiment, since the second micro holes 21 ′ play the same role as the concave portion 21 of the first embodiment, the same operations and effects as the mass spectrometry device 1 of the first embodiment are exhibited.

  Also in this embodiment, as in the first embodiment, an ionization promoter is applied to the non-opening portion of the first micropore 20 ′ on the surface 2s and the side wall surface 20′a of the first micropore 20 ′. 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.

(Design changes)
In the first and second embodiments, only Al is cited as the main component of the anodized body, but any metal and semiconductor can be used as long as anodization is possible. For example, other than Al, Si, Ti, Ta, Hf, Zr, In, Zn, etc. can be used. The anodized body may contain two or more kinds of anodizable metals or semiconductors. Although the planar pattern of the micropores to be formed varies depending on the type of the anodized body to be used, it does not change that a dielectric having a structure in which micropores having substantially the same shape in plan view are arranged adjacent to each other is formed.

  In the first embodiment, since the entire surface can be collectively processed, it is possible to cope with an increase in area, and an expensive apparatus is not required, the above embodiment using anodization is preferable, but other methods may be used. For example, in the case of a resin base material that can serve as a resist agent, exposure light becomes a standing wave under certain conditions by exposing from above a mask that can obtain micropores with a predetermined pore diameter. Can be formed into an uneven shape corresponding to the waveform of the standing wave.

  In the case of forming the second micropore in the second embodiment, the method using the anodic oxidation is preferable. However, in the case of a resin base material that can be a resist agent, the micropore is formed by photolithography. A forming method or the like can be used.

  In each embodiment, the fine holes may or may not be regularly arranged.

  Moreover, although the said embodiment demonstrated the case where the surface of a base material or a micropore consisted of a dielectric material, it may not be restricted to this but semiconductors, such as Si, and a metal may be sufficient.

  Porous silicon is well known as a substrate for surface-assisted laser desorption / ionization. Porous silicon can be obtained by anodizing a Si substrate. When porous silicon is produced, the anodizing conditions are changed so as to have irregularities on the side wall surface of the micropores, so that the same shape as in the first embodiment is obtained. A device for mass spectrometry can be obtained.

  When the substrate is made of metal, in addition to the confinement effect described above, if the uneven structure has a size that the localized plasmon is effectively induced, the electric field enhancement effect by the localized plasmon can be obtained together. The ionization efficiency can be effectively increased. Examples of a method for forming fine holes having irregularities on a metal substrate include a nanoimprint method.

  In the said embodiment, although the recessed part was a recessed part when the side wall surface of a micropore has the unevenness | corrugation of the wave shape, and the case where it was a micropore formed in the side wall surface of a microhole, The shape is not limited to these, and the same effect can be obtained even if the groove is a fine groove formed in a stripe shape or a lattice shape.

"Mass spectrometer"
With reference to FIG. 5, 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. 5 is a schematic diagram showing the configuration of the mass spectrometer 3 of the present embodiment, and the configuration of the apparatus and the effects obtained are the same when the device 2 for mass spectrometry of the second embodiment is used.

  As shown in the drawing, the mass spectrometer 3 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 3 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 3 of the present embodiment is configured using the device 1 for mass spectrometry of the above embodiment, the same effect as the device 1 for mass spectrometry is achieved.

  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 3 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 view in the thickness direction of the device for mass spectrometry according to the second embodiment of the present invention 3A is an enlarged view of the side wall surface of the fine hole. 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) Schematic which shows the structure of the mass spectrometer of one Embodiment which concerns on this invention.

Explanation of symbols

1, 2 Device for mass spectrometry 1s, 2s Surface (sample contact surface)
10, 10 'substrate 10s, 10's substrate surface 11, 11' dielectric 12 conductor 20, 20 'fine hole 20a, 20'a fine hole side wall surface 21 recess 21' second fine hole 40 metal to be anodized Body 41 Metal oxide body 42 Non-anodized portion 43 Micropore 3 Mass spectrometer 61 Light irradiation means 64 Analysis means 76 Detection means (spectral means)
L1 Measuring light S Analyte I Ionization accelerator

Claims (12)

A device for mass spectrometry comprising a substrate having a plurality of micropores opened on the surface, and irradiating the sample brought into contact with the surface with measurement light to desorb an analyte contained in the sample from the surface Because
A device for mass spectrometry, wherein a concave portion is formed on a side wall surface of the fine hole.   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 claim 1, wherein at least a surface of the side wall surface is made of a dielectric. The device for mass spectrometry according to claim 4, wherein the dielectric is made of SiO ₂ (may contain inevitable impurities).   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 of the fine hole. The device for mass spectrometry according to any one of claims 1 to 3, wherein:   The second fine hole is formed on the side 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 device for mass spectrometry according to claim 7.   The device for mass spectrometry according to claim 6 or 8, wherein the metal to be anodized is Al. 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 desorbed from the surface,
An analysis method comprising capturing the desorbed analyte and performing mass spectrometry.

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