JP2018173324A - Method for manufacturing sample loading plate - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for manufacturing a sample loading plate on which a loaded sample can be properly wet and be spread.SOLUTION: The method for manufacturing a sample loading plate 1, which has a base plate to load a sample on, includes the steps of: forming a hydrophilic film 7a in the shape of an island on one surface of the base plate 2; forming a hydrophobic film 7b on another surface of the base plate where the hydrophilic film is not formed and on a surface of the hydrophilic film; and removing the hydrophobic film on the hydrophilic film.SELECTED DRAWING: Figure 2

Description

  The present invention relates to a method for manufacturing a sample loading plate.

  As one of ionization methods in mass spectrometry, Matrix Assisted Laser Desorption Ionization (MALDI method) is known. In the MALDI method, a substance (matrix) that easily absorbs laser light and is easily ionized in order to analyze an analyte that is difficult to absorb laser light or an analyte such as a protein that is easily damaged by laser light. Samples (matrix and analysis object) are ionized by irradiating the sample with a laser beam using a sample in which the analysis object is dispersed.

  In a mass spectrometer using the MALDI method, a sample is generally arranged on a metal sample loading plate called a sample plate (or target plate), and laser light is irradiated to the sample arranged on the plate. . At this time, a voltage is applied to the metal sample loading plate as necessary in order to accelerate ions generated with the irradiation of the laser beam.

  Patent Document 1 describes a conventional sample loading plate. FIG. 3 is a cross-sectional view of a conventional sample loading plate.

  As shown in FIG. 3, the sample stacking plate 100 includes a substrate 110 and a laminated film 120 formed so as to cover the surface of the substrate 110. The laminated film 120 includes a conductive interference layer 121 and a hydrophobic film 122. It is described that when the hydrophobic film 122 is formed in an island shape on the conductive interference layer 121 of the sample stacking plate 100, the hydrophobic surface by the hydrophobic film 122 and the hydrophilic surface from which the conductive interference layer 121 is exposed have appropriate wettability. ing. The sample loaded on the sample loading plate 100 has strong hydrophobicity on the sample loading plate 100 (the exposure of the conductive interference layer 121 is almost not exposed), and the contact surface between the sample and the sample loading plate 100 is small. It will be biased there. In addition, if the hydrophilicity is strong (the exposure of the conductive interference layer 121 is large), the sample becomes thin and spreads and the sample becomes dilute, making it difficult to perform an appropriate analysis. Therefore, it is necessary to make the wettability appropriate for the type of the sample to be loaded on the sample loading plate 100. (Note that FIG. 3 does not show the hydrophobic film 122 formed on the conductive interference layer 121 in an island shape for convenience.)

As a method of forming the island-like hydrophobic film 122 on the conductive interference layer 121 described above, a member including a hydrophobic material in steel wool is irradiated on the conductive interference layer 121 with an electron beam in a high vacuum. And a method of instantly vapor-depositing only a hydrophobic material contained in steel wool. The hydrophobic material to be included in the steel wool is a compound of Si (silicon), C (carbon) and F (fluorine). Then, by depositing a hydrophobic material evaporated from the steel wool on the conductive interference layer 121, a target hydrophobic film 122 can be obtained. Alternatively, an island-shaped mask made of metal or ceramics is placed on the hydrophobic film 122 formed on the conductive interference layer 121 _, and the hydrophobic film 122 is exposed to O _2, Ar, and a mixed plasma thereof in a vacuum. Describes that the desired hydrophobic film 122 can be obtained by removing the hydrophobic film 122.

Japanese Patent Laid-Open No. 2006-121968

  However, when a member containing a hydrophobic material in a conventional steel wool is irradiated with an electron beam in a high vacuum, the hydrophobic material included in the steel wool is instantly evaporated, and thus formed on the conductive interference layer. It was difficult to control the shape of the hydrophobic film in an island shape and deposit it, and there was a problem that the wettability of the sample loaded on the sample loading plate could not be made appropriate.

  An object of this invention is to provide the manufacturing method of the sample loading plate which can spread a sample appropriately on a sample loading plate.

  In the method for manufacturing a sample loading plate for loading a sample on a substrate, a step of forming a hydrophilic film on one surface of the substrate in an island shape, one surface of the substrate on which the hydrophilic film is not formed, and the surface of the hydrophilic film The method of manufacturing a sample stacking plate includes a step of forming a hydrophobic film on the surface and a step of removing the hydrophobic film formed on the surface of the hydrophilic film.

  The adhesion force between the hydrophilic film and the hydrophobic film is smaller than the adhesion force between the substrate and the hydrophobic film.

  A method for manufacturing a sample loading plate is provided in which an optical multilayer film is formed on one surface of a substrate to form a hydrophilic film and a hydrophobic film.

It is assumed that the outermost surface of one surface of the substrate on which the hydrophilic film and the hydrophobic film are formed is SiO ₂ , the hydrophilic film is MgF ₂ , and the hydrophobic film is a method for manufacturing a sample loading plate that is a fluorine compound.

  According to the method for manufacturing a sample loading plate of the present invention, it is possible to provide a sample loading plate capable of properly spreading a sample on the sample loading plate.

It is a figure of the sample loading plate which consists of the manufacturing method of the sample loading plate of this invention. It is a figure which shows the manufacturing method of the sample loading plate of this invention. It is a figure of the sample loading plate of a prior art.

  Embodiments of the present invention will be described below in detail with reference to the drawings.

  The sample loading plate of the present embodiment is mounted on a mass analyzer using the MALDI method, and is used for loading a sample on a sample loading spot and analyzing the mass. The form for carrying out the invention shown below exemplifies a sample loading plate manufacturing method for embodying the idea of the present invention and a sample loading plate comprising the manufacturing method. The present invention is described below. It is not specific to the method and configuration described. In particular, the manufacturing method and the shape, material, relative arrangement, etc. of the members described in the embodiments do not limit the scope of the present invention unless otherwise specified. In addition, the size, shape, positional relationship, and film layers to be formed shown in each drawing may be exaggerated for easy understanding.

First, the configuration of a sample stacking plate comprising a method for manufacturing a sample stacking plate according to an embodiment of the present invention will be described with reference to FIG.
FIG. 1A is a plan view of the sample stacking plate as viewed from the side of the surface on which the sample is loaded.

The substrate 2 of the sample loading plate 1 is an insulative and substantially rectangular flat plate having an outer diameter of about 50 mm × 40 mm. The sample loading plate 1 is made of a material such as Al ₂ O ₃ (alumina), for example. Can be made. For example, a notch is provided on the lower side for positioning or the like. The flatness of the sample loading plate 1 has an accuracy of 30 μm or less. The outer shape, thickness, etc. are not particularly limited as long as they meet the specifications of the mass spectrometer. The sample loading plate may be finished by a lapping process or a polishing process in order to ensure flatness. Although not shown, a serial number, a barcode, or the like given to the plate may be formed.

  The sample loading plate 1 includes a substrate 2 formed in a plate shape by having a front surface and a back surface, and a laminated film 3 formed so as to cover one surface of the substrate 2 and a part thereof Includes a laminated film 3 in which a plurality of grooves 4 are formed. In the sample loading plate 1, one surface of the substrate 2 is exposed to the outside at a portion where the groove 4 is formed in the laminated film 3. In this example, the width of the groove 4 is several tens μm to several hundreds μm.

  A plurality of island marks 5 each having a C-shape are formed in the sample stacking plate 1 by a plurality of grooves 4, but only two are shown for convenience. The area surrounded by the island mark 5 having a C-shape (the area surrounded by the groove 4 forming the C-shape) functions as a sample loading area (sample loading spot) for loading a sample on the sample loading plate 1. To do.

  FIG.1 (b) is a figure for demonstrating the sample loading plate 1, and is B section AA expanded sectional drawing of Fig.1 (a). As described above, the sample loading plate 1 of the present embodiment includes the substrate 2 and the laminated film 3 formed so as to cover one surface of the substrate 2, and a groove 4 is formed in a part thereof. And a laminated film 3 formed by forming. The laminated film 3 includes an optical multilayer film 6, a hydrophilic film 7a, and a hydrophobic film 7b. The optical multilayer film 6 is laminated on the first transparent layer 6b and the first transparent layer 6b laminated on the first metal layer 6a and the first metal layer 6a laminated on one surface of the substrate 2. On the optical multilayer film 6 which is composed of the second metal layer 6c and the second transparent layer 6d laminated on the second metal layer 6c and is formed so as to cover the substrate 2, a hydrophilic film 7a and A hydrophobic film 7b is formed. The hydrophilic film 7a has a substantially circular (diameter of 10 nm or less) island shape, and a hydrophobic film 7b is formed on the optical multilayer film 6 on which the hydrophilic film 7a is not formed. The gap between the islands of the hydrophilic film 7a is several nm. Unless the gap is sufficiently small with respect to the size of the sample loaded on the sample loading plate 1, the wettability of the sample loaded on the sample loading plate 1 cannot be made appropriate.

The first metal layer 6a is made of Ni (nickel) and its thickness is set to 80 nm. The first transparent layer 6b is made of Al ₂ O ₃ (alumina) and has a thickness of 80 nm. Further, the second metal layer 6c is made of Ti (titanium) and the thickness thereof is set to 10 nm. Further, the second transparent layer 6d is made of SiO ₂ (silica) and its thickness is set to 90 nm. The hydrophilic film 7a is a monomolecular layer made of MgF ₂ (magnesium fluoride), and the hydrophobic film 7b is made of a fluorine-based compound, and the thickness thereof is 1 to 3 nm.

  FIG.1 (c) is the figure which loaded the sample 200 on the surface of B section AA expanded sectional drawing (FIG.1 (b)) of Fig.1 (a). The liquid sample 200 supplied to the island mark 5 (sample loading region) tends to spread radially along the surface of the island mark 5 due to the influence of gravity. Here, in the present embodiment, island marks 5 having a C-shape are formed by the grooves 4. For this reason, the sample 200 loaded on the island mark 5 enters the inside of the groove 4 while spreading radially, and reaches the part that becomes the bottom of the groove 4, that is, the part where the substrate 2 is exposed. At this time, since the surface of the substrate 2 is hydrophilic, the sample 200 quickly wets and spreads inside the island mark 5 and the groove 4 and reaches the inside of the island mark 5 and the groove 4.

  In addition, the sample 200 wet and spread on the island mark 5 wets and spreads on the surface of the hydrophilic film 7a and the hydrophobic film 7b formed on the surface of the island mark 5, but the sample 200 stops being wet spread and the sample 200 On the surface of the mark 5, water droplets having a certain contact angle with respect to the surface of the island mark 5 are formed. This is because, since the hydrophobic film 7b is formed, the sample 200 wets and spreads to the point where the force for suppressing the radial spread of the sample 200 and the force for the sample 200 to spread radially are balanced. .

  Here, the board | substrate 2 is comprised with the ceramic material which has insulation. In the present embodiment, the substrate 2 is made of alumina ceramic with a purity of about 96%, the thickness is 800 μm, and the planarity of the front and back surfaces is 5 μm or less.

  As described above, since the hydrophilic film 7a and the hydrophobic film 7b are formed on the optical multilayer film 6 formed so as to cover the substrate 2, the (marked hydrophilic film) of the island mark 5 of the sample loading plate 1 is formed. The sample 200 properly spreads on the surface (of 7a and the hydrophobic film 7b).

  Next, the manufacturing process of the sample loading plate 1 shown in FIG. 1 will be described with reference to the main steps of FIGS. 2 (a) to 2 (e). In addition, unless there is a specific description in each step, it is natural to perform operations such as transfer, inspection, cleaning, drying, annealing, etc., which are necessary and general operations for each step, and explanations thereof are omitted. To do.

  First, the substrate 2 is formed. More specifically, the base material of the substrate 2 previously molded and fired into the shape shown in FIG. 1 was polished on the front and back surfaces, the thickness was set to 800 μm, and the flatness was set to 5 μm or less. A substrate 2 is obtained.

[Optical multilayer film forming step: FIG. 2 (a)]
Next, the optical multilayer film 6 is laminated on one surface of the substrate 2 obtained by the method described above. For example, the first metal layer 6a (Ni = nickel), the first transparent layer 6b (Al ₂ O ₃ = alumina), the second metal layer 6c (Ti = titanium), the second metal film 6a (Ni = nickel), the second metal layer 6c (Ti = titanium) The transparent layer 6d (SiO ₂ = silica) is formed in order. The thickness of each layer is 80 nm for the first metal layer 6a (Ni = nickel), 80 nm for the first transparent layer 6b (Al ₂ O ₃ = alumina), 10 nm for the second metal layer 6c (Ti = titanium), The second transparent layer 6d (SiO ₂ = silica) was 90 nm.

[Hydrophilic film 7a and hydrophobic film 7b forming step: FIG. 2 (b) to FIG. 2 (c)]
Next, a hydrophilic film 7a and a hydrophobic film 7b are formed so as to cover the optical multilayer film 6 with respect to the optical multilayer film 6 formed so as to cover one surface of the substrate 2 described above. In this embodiment, an example in which MgF ₂ is formed on the hydrophilic film 7a and a fluorine-based compound is formed on the hydrophobic film 7b will be described. On the optical multilayer film 6, a hydrophilic film 7a (MgF ₂ ) was formed in a substantially circular (diameter of 10 nm or less) island shape by a vapor deposition apparatus. Here, the gap 8 between the islands of the hydrophilic film 7a is made to be several nm by forming the hydrophilic film 7a (MgF ₂ ) thin so as not to cover the surface of the optical multilayer film 6. Can do. By setting the gap 8 to a few nanometers and sufficiently small with respect to the size of the sample loaded on the sample loading plate 1, the wettability of the sample loaded on the sample loading plate 1 can be made appropriate. . Gap 8 between the islands of the hydrophilic film 7a (MgF ₂₎ is to be determined by the thickness of the hydrophilic film 7a formed on the optical multilayer film 6 (MgF _2), hydrophilic film 7a (MgF It is possible to adjust the wettability of the sample loaded on the sample loading plate by changing the film thickness of ₂ ). This is because when the thickness of the hydrophilic film 7a (MgF ₂ ) formed on the optical multilayer film 6 is reduced, the gap 8 becomes wider, and when the thickness of the hydrophilic film 7a (MgF ₂ ) is increased, the gap 8 becomes narrower. It is. The method of forming the hydrophilic film 7a (MgF ₂ ) in an island shape on the optical multilayer film 6 is not limited to the above-described method. For example, the hydrophilic film 7a (MgF ₂ ) is formed on the surface of the optical multilayer film 6. Before this, a mask may be installed on the surface of the optical multilayer film 6 to form the hydrophilic film 7a (MgF ₂ ) in an island shape. As a result, the gap 8 between the islands of the hydrophilic film 7a (MgF ₂ ) formed on the surface of the optical multilayer film 6 can be formed with a target size and loaded on the sample loading plate 1. It becomes easy to control the wettability of the sample. The gap between the islands (a constant interval) is preferably several nm.

Next, as shown in FIG. 2C, a hydrophilic film 7a (MgF ₂ ) is formed in an island shape on the optical multilayer film 6, and then the surface of the hydrophilic film 7a (MgF ₂ ) and the hydrophilic film 7a (MgF ₂ ) are formed. ₂ ) A hydrophobic film 7b (fluorine compound) is vapor-deposited so as to cover the surface of the optical multilayer film 6 where the optical fiber film 6 is not formed.

[Hydrophobic film 7b removal step: FIG. 2 (d)]
Next, the substrate 2 obtained by the above-described method was formed on the surface of the hydrophilic film 7a (MgF ₂ ) by applying an impact such as ultrasonic vibration (not shown) to the substrate 2 as shown in FIG. 2D. The hydrophobic film 7b (fluorine compound) is removed, and the substrate 2 is formed with the hydrophobic film 7b (fluorine compound) formed in the gap 8 between the hydrophilic film 7a (MgF ₂ ) and the hydrophilic film 7a (MgF ₂ ). . Here, by applying an impact such as ultrasonic vibration to the substrate 2, the hydrophobic film 7 b (fluorine compound) formed on the surface of the hydrophilic film 7 a (MgF ₂ ) is removed and formed on the surface of the optical multilayer film 6. The reason why the hydrophobic film 7b (fluorine compound) thus formed is not removed will be described. This is because the adhesion between the hydrophilic film 7a (MgF ₂ ) and the hydrophobic film 7b (fluorine compound) is smaller than the adhesion between the surface of the optical multilayer film 6 and the hydrophobic film 7b (fluorine compound). The adhesion force of the hydrophobic film 7b (fluorine compound) formed on the surface of the hydrophilic film 7a (MgF ₂ ) is an extremely small adhesion force that can be removed by impact at the ultrasonic vibration level. As a result, a hydrophilic film 7a (MgF ₂ ) and a hydrophobic film 7b (fluorine compound) are formed on the optical multilayer film 6 so that the sample loaded on the sample loading plate 1 has an appropriate wettability. can do. The hydrophilic film 7a is not limited to MgF ₂ and the hydrophobic film 7b is not limited to a fluorine-based compound. The adhesion between the hydrophilic film 7a and the hydrophobic film 7b is the adhesion between the outermost surface of the optical multilayer film 6 and the hydrophobic film 7b. What is necessary is just to select so that it may become extremely smaller. For example, hydrophobic film 7b is a fluorine-based compound, when the outermost surface of the optical multilayer film 6 is SiO _2, the hydrophilic membrane 7a can be used AlF, the YF _3.

[Groove formation process: FIG. 2 (e)]
Finally, as shown in FIG. 2E, the groove 4 is formed in the sample stacking plate 1 in the groove forming step. For example, each film layer is peeled off by a processing method such as a laser marking method until the surface of the substrate 2 is exposed through the hydrophilic film 7a (MgF ₂ ), the hydrophobic film 7b (fluorine compound), and the optical multilayer film 6. . It is also desirable to process other address marks, bar code marks, etc. at the same time.

As described above, the embodiment of the sample loading plate and the manufacturing method thereof have been described. However, the present invention is not limited to the manufacturing method of the embodiment, and the concept of the present invention in terms of the detailed configuration, material, and quantity. Any change, addition, or deletion can be made without departing from the scope. For example, the order of the hydrophilic film 7a (MgF ₂ ) and hydrophobic film 7b (fluorine compound) forming process and the groove forming process of this embodiment may be changed. In this case, before forming the hydrophilic film 7a (MgF ₂ ) and the hydrophobic film 7b (fluorine compound), the surface of the groove is covered with a mask or the like, and the hydrophilic film 7a (MgF ₂ ) and the hydrophobic film 7b (fluorine compound) are covered. Need to form.

In the present embodiment, an example in which MgF ₂ as the hydrophilic film 7a is provided on the second transparent layer 6d (SiO ₂ ) on the outermost surface of the optical multilayer film 6 formed on one surface of the substrate is described. Even if the second transparent layer 6d (SiO ₂ ) on the outermost surface of the optical multilayer film 6 formed on one surface of the optical multilayer film 6 is not formed, MgF ₂ that is the hydrophilic film 7a is provided on the second metal layer 6c (Ti). The effects of the present invention can be obtained. This eliminates the need to form the second transparent layer 6d (SiO ₂ ) in the optical multilayer film 6, and thus has advantages such as cost and workability.

  In the present embodiment, the sample loading plate used in the MALDI method mass spectrometry is described as an example, and the sample loading plate comprising the sample loading plate manufacturing method of the present invention has been described. Since the sample mounted on the plate can be properly wetted and spread, it is not limited to the sample loading plate used for MALDI mass spectrometry, but is similar to the sample loading plate used for mass spectrometry of other methods Even if a simple structure is adopted, the same effect can be obtained. For example, laser desorption ionization without matrix (LDI), surface assisted laser desorption ionization (SALDI), secondary ion mass spectrometry (SIMS), desorption electrospray ionization (DESI), electrospray support / The present invention can also be applied to a sample loading plate used in laser desorption ionization (ELDI) or the like.

DESCRIPTION OF SYMBOLS 1,100 Sample loading plate 2,110 Substrate 3,120 Laminated film 4 Groove 5 Island mark 6 Optical multilayer film 6a 1st metal layer (Ni)
6b the first transparent layer _{(Al 2 O} 3)
6c Second metal layer (Ti)
6d the second transparent layer _(SiO 2)
7a Hydrophilic film 7b, 122 Hydrophobic film 8 Crevice 121 Conductive interference layer 200 Sample

Claims (4)

  In the method of manufacturing a sample loading plate for loading a sample on a substrate, a step of forming a hydrophilic film in an island shape on one surface of the substrate, the one surface of the substrate on which the hydrophilic film is not formed, and the A method for producing a sample loading plate, comprising: forming a hydrophobic film on a surface of the hydrophilic film; and removing the hydrophobic film formed on the surface of the hydrophilic film.   2. The method for manufacturing a sample loading plate according to claim 1, wherein an adhesion force between the hydrophilic film and the hydrophobic film is smaller than an adhesion force between the substrate and the hydrophobic film.   2. The method of manufacturing a sample stacking plate according to claim 1, wherein an optical multilayer film is formed on the one surface of the substrate, and the hydrophilic film and the hydrophobic film are formed. The outermost surface of the one surface of the substrate forming the hydrophilic film and the hydrophobic film is SiO ₂ , the hydrophilic film is MgF ₂ , and the hydrophobic film is a fluorine-based compound. Item 4. The method for producing a sample loading plate according to any one of Items 1 to 3.

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