JP2007263600A - Sample target - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a sample target capable of realizing the laser dissociating ionization of a sample to be analyzed with high efficiency without using a matrix. <P>SOLUTION: In the sample target used in the ionization of a sample due to laser beam irradiation and having a substrate wherein at least the surface to be irradiated with a laser beam has a porous structure and a thin film comprising a metal or a semiconductor covering the surface to be irradiated with the laser beam, the heat conductivity of the surface layer participated in the ionizing reaction due to the laser beam of the substrate and that of a bulk part other than the surface layer are made equal or the heat conductivity of the bulk part is made lower than that of the surface layer part. For example, the sample target 10 is constituted of a substrate 20 comprising a silica monolithic plate having a double pore structure and the Pt thin film 30 which covers the surface to be irradiated with the laser beam of the substrate 20. By this constitution, the loss of energy due to the heat conduction from the surface layer part of the target substrate 20 to the bulk part is suppressed and ionization efficiency can be enhanced. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a sample target for holding a sample to be analyzed in mass spectrometry, and more particularly to a sample target that enables ionization of a sample to be analyzed by laser light irradiation without using a matrix.

  In recent years, mass spectrometry has been widely used as a qualitative / quantitative analysis technique for biological samples such as proteins, sugar chains, and DNA, and polymers such as synthetic polymers. This is a method of performing physical filtering using the mass / charge number ratio (m / z) of ions generated by ionizing and applying energy to a sample to be analyzed, and analyzing from the obtained mass spectrum. . There are various types of mass spectrometers. For example, ions generated by the ion generator are extracted by an electric field of a predetermined strength, introduced into a flight space that does not have an electric field and a magnetic field, and reach the ion detector. A time-of-flight mass spectrometer (TOFMS) that separates and detects various ions for each mass / charge number ratio according to the flight time until the time is known is known.

  As a sample ionization method in TOFMS, Matrix Assisted Laser Desorption / Ionization (MALDI) is generally used. MALDI is a method in which a sample to be analyzed is mixed with a compound called a matrix and coated on a metal plate called a sample target, and this is ionized by irradiating it with pulsed laser light in an ionization chamber, which absorbs the laser light. As the matrix is rapidly heated and vaporized, the sample molecules are desorbed and ionized. In other words, the MALDI method is a soft ionization method in which the sample indirectly receives the energy absorbed by the matrix, so that it becomes possible to ionize macromolecules without fragmenting them. However, measurement by MALDI requires time and effort to select an appropriate matrix and mix it with the sample, and background ions derived from the matrix are generated in the low molecular weight region, making it difficult to analyze the mass spectrum. is there.

  Therefore, desorption / ionization on (porous) Silicon: As a technique to achieve ionization of the sample by laser desorption / ionization without using a matrix by adding ionization capability to the sample target itself, A technique called the DIOS method has been developed. In this method, the sample to be analyzed is applied to a porous silica plate provided with a porous layer of submicron order by subjecting the surface of the Si substrate to electrochemical oxidation, and the sample is ionized by irradiation with laser light. is there. In addition, a technique called surface-assisted laser desorption / ionization (SALDI) based on materials other than Si has also been developed, and these matrix-free (such as DIOS and SALDI) (Not used) Laser desorption / ionization methods are being put into practical use in a form that complements MALDI.

  Furthermore, to improve the sample target in such a matrix-free ionization method, porous alumina whose surface is made porous by electrochemical oxidation is used as a base material, and this is a thin film made of noble metal or semiconductor. A coated one has also been devised, and it has been reported that the ionization ability of the sample target can be stabilized over a long period of time, and that a sample having a molecular weight of about 10,000 can be ionized (non-patented). Reference 1).

Analytical Chemistry, USA, 2005, 77, 16, pp.5364-5369

  As described above, in recent years, the application of mass spectrometry to qualitative and quantitative analysis of biological samples and polymer samples has been increasing, and along with this, further enhancement of the performance of matrix-free ionization methods, especially ionization efficiency. Improvement is strongly demanded. Therefore, the problem to be solved by the present invention is to realize higher ionization efficiency than before in a sample target used for laser desorption / ionization of a sample to be analyzed without using a matrix.

  In view of the above-mentioned problems, the inventors of the present invention have a structure in which the porous portion of the substrate surface layer is a covalently bonded oxide film in the conventional sample target, whereas the bulk remains as metal Al having high thermal conductivity. As a result, the thermal energy given to the sample target by the laser light is dissipated from the metal thin film coated on the surface through the bulk with high thermal conductivity, which is one of the causes of the decrease in ionization efficiency. And it came to this invention.

That is, the first aspect of the present invention made to solve the above problems is used for ionization of a sample by laser light irradiation, and at least a laser-irradiated surface having a porous structure, the laser A sample target having a thin film made of a metal or a semiconductor covering the irradiated surface,
The thermal conductivity of the surface layer part involved in the ionization reaction by laser light of the substrate and the bulk part other than the surface layer part is equal, or the thermal conductivity of the bulk part is lower than the surface layer part.

The second aspect of the present invention made to solve the above problems is used for ionization of a sample by laser light irradiation, at least a laser irradiated surface has a porous structure, and the laser irradiated A sample target having a metal or semiconductor thin film covering the surface,
A heat insulating layer is provided between the substrate and the thin film.

  According to the first aspect of the present invention having the above-described configuration, the thermal conductivity of the bulk portion in the sample target is equal to or less than that of the surface layer portion, so that the energy of heat conduction from the surface layer portion to the bulk portion is reduced. Loss can be suppressed. As a result, more ionization energy is supplied to the sample, and the ionization efficiency in matrix-free laser desorption ionization can be improved.

  According to the second aspect of the present invention, by providing a heat insulating layer between the base and the thin film covering the laser irradiated surface, the thermal energy given by the laser beam is transferred from the thin film to the base. As a result, ionization efficiency can be improved as in the first aspect.

  In the sample target of the present invention, the surface layer means a region contributing to an ionization reaction in laser desorption / ionization, and specifically refers to a region from the laser irradiated surface to a depth similar to the wavelength of the laser beam. . The bulk portion refers to a region other than the surface layer portion in the target substrate, and in the sample target using the conventional porous alumina, the thermal conductivity of the bulk portion is the surface layer portion (porous oxide film). It caused a loss of thermal energy because it was higher. On the other hand, in the present invention, by making the thermal conductivity of the bulk part equal to or less than that of the surface layer part, it is possible to prevent the heat energy absorbed in the surface layer part from being dissipated through the bulk part, Ionization efficiency is improved.

  Here, in the sample target of the present invention, it is desirable that the substrate is made of a nonmetal. Thereby, compared with the sample target whose bulk part consists of metals, such as Al like the past, the loss of ionization energy can be suppressed. Here, the nonmetal may be any material except carbon, and for example, a polymer or the like can be used. However, in view of heat resistance, it is desirable to use an inorganic material. For example, a ceramic material such as an oxide ceramic or a nitride ceramic can be suitably used. Here, ceramic means an inorganic solid material including glass and gel, and it is more preferable to use porous silica gel having a double pore structure as described later.

  In the sample target according to the present invention, it is desirable that the substrate is made of a porous body. This makes it possible to suppress the dissipation of thermal energy from the surface layer to the bulk due to the porous structural heat insulation, and more efficiently supply the thermal energy absorbed by the laser irradiated surface to the sample. It becomes. Here, the porous body may be made of any material, and it is desirable to use a nonmetal from the viewpoint of thermal conductivity, but a so-called metal porous material may be used. Furthermore, as the porous body, so-called double pores comprising mesoscale to macroscale (0.2 to 1 μm) pores and nanoscale (10 to 25 nm) micropores formed on the inner wall surface of the pores. It is desirable to use one having a structure. The porous body preferably has a porous structure as a whole. However, if a sufficient heat insulating effect is obtained during ionization, only the region close to the surface layer portion is made porous. May be.

  The coating with a thin film made of the metal or semiconductor may be applied only to the laser irradiated surface or may be applied to the entire substrate. In addition, the coating with the metal or semiconductor can be performed by a dry coating method such as sputtering, vapor deposition, ion plating, chemical vapor deposition (CVD), or by wet coating such as electrolytic plating or non-electrolytic plating. Any method may be used.

  In the second aspect of the present invention, the heat insulating layer only needs to have a thermal conductivity lower than that of at least the thin film, and for example, the above-mentioned nonmetal or porous material can be used. The heat insulating layer may be formed by any method, but for example, can be formed by the same method as the above thin film.

  A 30 × 20 × 1.2 mm silica monolith plate (manufactured by Kyoto Monotech Co., Ltd.) having mesoscale pores 22 having a diameter of about 500 nm and nanoscale micropores (not shown) having a diameter of about 12 nm is used as the substrate 20. A TOFMS sample target 10 is formed by coating the surface with Pt by ion beam sputtering to a thickness of 5 to 50 nm, preferably 20 to 50 nm, to form a thin film 30 (FIGS. 1 and 2). In the sample target 10 of this example obtained in this way, a region close to the laser irradiated surface 21 of the substrate 20 made of a silica monolith plate corresponds to the surface layer portion, and a region below it corresponds to the bulk portion. To do. As the Pt coating method, it is preferable to use an ion beam sputtering method that can expect a strong adhesion of the coating agent as described above, but any other method may be used. At this time, a sample holding portion (well) 31 as shown in FIG. 3 may be formed on the laser irradiated surface 21 by applying a partial coating using an appropriate mask.

A 30 × 20 × 1.2 mm Ag porous body having mesoscale pores with a diameter of about 500 nm is used as the substrate 20, and SiO ₂ (thermal conductivity: 0.07 to 0.12 kcal / m · hr · ° C.) is RF on the surface. The heat insulation layer 40 is formed by coating with a film thickness of 50 to 300 nm by diode sputtering or off-axis sputtering. Thereafter, the sample target 10 is fabricated by further coating the Pt with a film thickness of 20 to 50 nm by DC-sputtering to form the thin film 30 (FIG. 4). When a metal such as Ag is used as the substrate 20, the strength of the sample target 10 can be increased, but there is a drawback that ionization efficiency is lowered due to high thermal conductivity. However, in this embodiment, in addition to obtaining a structural heat insulating property by using a porous metal material constituting the substrate 20, the above-described structure is provided below the thin film 30 covering the laser irradiated surface 21. By providing such a heat insulating layer 40, it is possible to avoid the above-mentioned drawbacks and provide a sample target with high ionization ability.

Sectional drawing which shows the sample target which concerns on 1st Example of this invention. The expanded sectional view which shows the laser irradiated surface vicinity of the sample target which concerns on the Example. It is a figure which shows the case where the sample holding part is provided in the sample target which concerns on the Example, (a) is a top view, (b) is longitudinal direction sectional drawing. Sectional drawing which shows the sample target which concerns on the 2nd Example of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 ... Sample target 20 ... Base | substrate 21 ... Laser irradiated surface 22 ... Pore 30 ... Thin film 40 ... Heat insulation layer

Claims (5)

A sample target that is used for ionization of a sample by laser light irradiation and has a substrate having a porous structure at least on a laser irradiated surface, and a thin film made of a metal or a semiconductor that covers the laser irradiated surface,
A sample target characterized in that the thermal conductivity of the surface layer part involved in the ionization reaction by laser light of the substrate and the bulk part other than the surface layer part are equal, or the thermal conductivity of the bulk part is lower than the surface layer part.   The sample target according to claim 1, wherein the substrate is made of a nonmetal.   3. The sample target according to claim 1, wherein the substrate is made of a porous body.   The sample target according to any one of claims 1 to 3, wherein the substrate is made of porous silica gel having a double pore structure. A sample target that is used for ionization of a sample by laser light irradiation and has a substrate having a porous structure at least on a laser irradiated surface, and a thin film made of a metal or a semiconductor that covers the laser irradiated surface,
A sample target, wherein a heat insulating layer is provided between the substrate and the thin film.

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