WO2018151556A1 - Sample plate for maldi mass spectrometry and manufacturing method therefor - Google Patents

Abstract

A sample plate for MALDI mass spectrometry, according to the present invention, enables separately positioning, by means of a plastic insulation plate, metal wiring and metal dots onto which an analyte sample is to be loaded, and electrically connecting same by means of a via or a metal portion, and thus the energy transferred into the plate when radiating a laser beam on the target (metal dots) may be reduced compared to a sample plate using a base metal, and thus laser energy may be concentrated on the target, and an effect may be achieved whereby heat loss is minimized.

Description

Sample plate for MALDI mass spectrometry and its manufacturing method

The present invention relates to a sample plate for MALDI mass spectrometry, a method of manufacturing the same, and a MALDI mass spectrometry method using the same.

Since mass spectrometry was first used in the early 1900s, various ionization methods have been developed. In general, EI (Electron Impact) has been widely used as a standard ionization method. However, this method has the disadvantage that it can be used only for volatile samples and cannot be used for samples that are unstable to heat, and its application has been mainly limited to organic small molecules.

For this reason, chemical ionization (CI), electro-spray ionization (ESI), secondary ion mass spectrometry (SIMS), field desorption (FD), fast atom bombardment (FAB), Several ionization methods have been developed, including Atmospheric Pressure Chemical Ionization (APCI) and Matrix Assisted Laser Desorption Ionization (MALDI).

Among them, MALDI is a method that can vaporize / ionize a polymer material without decomposition of a sample, and is generally known as a method that can be ideally applied to a biomass or a synthetic polymer that is large in mass and thermally unstable.

The principle of sampling in MALDI is called the dried droplet method, which mixes a laser-absorbing matrix and analyte in a solvent, and then dissolves it in a sample plate. D) and drying the solvent to produce a target, and then irradiating the laser to the target, the energy of the irradiated laser is transferred to the analyte through a crystallized matrix to ionize the analyte. As a result, the ionized analyte molecules are accelerated into an electric field and reach a detector of a time-of-flight mass spectrometer (TOF-MS), where the mass-to-charge (m / z) ratio is small. The mass of molecules (ions) is measured using the principle that ions reach the detector faster than ions with large mass-to-charge ratios.

MALDI can measure the molecular weight of materials with high molecular weight, such as polymers, proteins, peptides, and deoxyribonucleic acid (DNA), and can be analyzed even when several kinds of components are mixed instead of one. Samples can also be analyzed and the analysis time is short.

However, even if you use the same MALDI mass spectrometer and obtain mass spectra for the same analyte, how to prepare the target, where the laser reaches the target, the wavelength of the laser used, the pulse energy of the laser, and the point where the laser reaches It is well known that the mass spectral pattern obtained is not the same depending on the size of the spot, the number of times of laser irradiation on the same spot, and the like. The lack of reproducibility of such spectral patterns is a serious problem in basic research, precise analysis, and standardization using MALDI mass spectrometry.

Thus, if the reproducibility of the spectral pattern of MALDI can be improved, its applicability is expected to be greatly expanded.

As similar documents for the sample plate for MALDI mass spectrometry, Korean Patent Registration No. 10-1204342 and Korean Patent Application Publication No. 10-2010-0051318 have been presented, but there is still a need for improvement of the aforementioned problem.

[Patent Documents]

Korea Patent Publication No. 10-1204342 (2012.11.19.)

Korean Patent Publication No. 10-2010-0051318 (2010.05.17.)

An object of the present invention is to provide a sample plate for MALDI mass spectrometry, which has excellent sensitivity and excellent reproducibility of the MALDI mass spectrum.

Another object of the present invention is to provide a method for producing a sample plate for MALDI mass spectrometry, which has excellent sensitivity and excellent reproducibility of the MALDI mass spectrum.

Another object of the present invention is to provide a MALDI mass spectrometry method using a sample plate for MALDI mass spectrometry, which has excellent sensitivity and excellent reproducibility of MALDI mass spectra.

MALDI mass spectrometry sample plate according to the present invention, the plastic insulating plate; And a metal dot formed on one surface of the plastic insulating plate to allow a sample to be loaded on the surface thereof. In this case, the metal dot may be electrically connected to the sample plate voltage applying unit of the MALDI mass spectrometer.

The sample plate for MALDI mass spectrometry according to an embodiment of the present invention may further include one or two or more metal layers formed in contact with the side surfaces, the bottom surfaces, the top surfaces, or these surfaces of the plastic insulation plate, and the metal layers may include the metal dot. It may be electrically connected with the. In this case, the metal dot may be electrically connected to the sample plate voltage applying unit of the MALDI mass spectrometer through the metal layer during mass spectrometry.

MALDI mass spectrometry sample plate according to an embodiment of the present invention, the plastic insulating plate; A metal dot formed on one surface of the plastic insulating plate to allow a sample to be loaded on a surface thereof; A lower metal layer formed on the other surface of the plastic insulating plate; And a metal dot via formed through the plastic insulating plate and electrically connected to the metal dot and the bottom metal layer.

The sample plate for MALDI mass spectrometry according to an embodiment of the present invention may further include an upper metal layer formed on one surface of the plastic insulation plate on which the metal dot is formed.

In one example of the present invention, the upper metal layer may be electrically connected to the metal dot, or may not be electrically connected to the metal dot. As a specific example, when the metal layer is electrically connected to the metal dot, one surface of the plastic insulating plate on which the metal dot is formed may include an insulating part spaced apart from the metal dot and the upper metal layer; And a connection part adjacent to the insulating part and formed by contacting the metal dot and the upper metal layer, or the entire circumference of the metal dot and the upper metal layer may contact the insulating part. As a specific example, when the metal layer is not electrically connected to the metal dot, one surface of the plastic insulation plate on which the metal dot is formed may be spaced apart from the entire circumference of the metal dot and the upper metal layer, and adjacent to the entire circumference of the metal dot. It may include; insulating portion surrounding it.

The sample plate for MALDI mass spectrometry according to an embodiment of the present invention may further include a metal layer via formed through the plastic insulating plate and electrically connected to the upper metal layer and the lower metal layer. One surface of the formed plastic insulating plate may include an insulating portion surrounding the entire circumference of the metal dot and the upper surface metal layer and adjacent to the entire circumference of the metal dot.

MALDI mass spectrometry sample plate according to an embodiment of the present invention, the plastic insulating plate; A metal dot formed on one surface of the plastic insulating plate; An upper metal layer formed on one surface of the plastic insulating plate on which the metal dots are formed and electrically connected to the metal dots; A lower metal layer formed on the other surface of the plastic insulating plate; And a metal layer via formed through the plastic insulating plate and electrically connected to the upper metal layer and the lower metal layer.

In one embodiment of the present invention, one surface of the plastic insulating plate on which the metal dot is formed, the insulating portion formed between the metal dot and the upper metal layer spaced apart; And a connection part adjacent to the insulating part and formed by contacting the metal dot and the upper metal layer, or the entire circumference of the metal dot and the upper metal layer may be in contact with each other.

MALDI mass spectrometry sample plate according to an embodiment of the present invention, the plastic insulating plate; A metal dot formed on one surface of the plastic insulating plate; An upper metal layer formed on one surface of the plastic insulating plate on which the metal dots are formed and electrically connected to the metal dots; And a side metal layer formed on a side surface of the plastic insulating plate and electrically connected to the upper metal layer.

In one embodiment of the present invention, one surface of the plastic insulating plate on which the metal dot is formed, the insulating portion formed between the metal dot and the upper metal layer spaced apart; And a connection part adjacent to the insulating part and formed by contacting the metal dot and the upper metal layer, or the entire circumference of the metal dot and the upper metal layer may be in contact with each other.

The sample plate for MALDI mass spectrometry according to an embodiment of the present invention may further include a lower surface metal layer formed on the other surface of the plastic insulation plate and electrically connected to the upper surface metal layer.

In one embodiment of the present invention, one surface of the plastic insulating plate on which the metal dot is formed, the entire circumference of the metal dot and the upper metal layer spaced apart, the insulating portion adjacent to surround the entire circumference of the metal dot; And a metal dot via formed through the plastic insulating plate and electrically connected to the metal dot and the bottom metal layer.

In one embodiment of the present invention, the metal dot may have a diameter of 100 ㎛ to 5 mm.

In one embodiment of the present invention, the metal dot and the metal layer are independently of each other gold (Au), silver (Ag), copper (Cu), chromium (Cr), aluminum (Al), tungsten (W), zinc ( Zn), nickel (Ni), iron (Fe) and alloys thereof may include any one or two or more selected from.

In one embodiment of the present invention, the plastic insulating plate may have a hydrophobic surface property, the metal dot may have a hydrophilic surface property.

In one embodiment of the present invention, the surface of the metal dot, the sample seating surface portion located in the center of the metal dot surface; And a hydrophobic surface portion surrounding the sample seating portion, wherein the hydrophobic surface portion may have a greater hydrophobicity than the sample seating surface portion.

The sample plate for MALDI mass spectrometry according to an embodiment of the present invention may further include a sample reservoir substrate attached to one surface of the plastic insulating plate, surrounding the metal dot, and provided with a through hole.

In one example of the present invention, the sample reservoir substrate may be provided with a gas passage for discharging the inert gas to the through-hole.

In one embodiment of the present invention, the sample reservoir substrate may have a structure that can be attached to one surface of the plastic insulating plate.

Method for producing a sample plate for MALDI mass spectrometry according to an embodiment of the present invention, forming a metal thin film on both sides of the plastic insulating plate; Forming a via penetrating the plastic insulating plate; And selectively etching both sides of the metal thin film of the plastic insulation plate to form a metal dot on one surface and a bottom metal layer on the other surface thereof. In this case, the metal dot and the bottom metal layer may be electrically connected through vias.

Method for producing a sample plate for MALDI mass spectrometry according to an embodiment of the present invention, forming a metal thin film on both sides of the plastic insulating plate; Selectively etching both sides of the metal thin film of the plastic insulating plate, forming a metal dot and an upper metal layer on one surface, and forming a lower metal layer on the other surface; And forming a metal thin film in contact with a side surface of the plastic insulating plate to form a side metal layer. In this case, the metal dot and the top metal layer may be electrically connected, the top metal layer and the side metal layer may be electrically connected, and the side metal layer and the bottom metal layer may be electrically connected.

Method for producing a sample plate for MALDI mass spectrometry according to an embodiment of the present invention, forming a metal thin film on both sides of the plastic insulating plate; Selectively etching both sides of the metal thin film of the plastic insulating plate, forming a metal dot and an upper metal layer on one surface, and forming a lower metal layer on the other surface; Forming a metal dot via or a metal layer via penetrating the plastic insulating plate; And forming a metal thin film in contact with a side surface of the plastic insulating plate to form a side metal layer. In this case, the metal dot and the top metal layer are electrically connected, the top metal layer and the side metal layer are electrically connected, the side metal layer and the bottom metal layer are electrically connected, and the metal dot and the bottom metal layer are vias. It may be to be electrically connected through.

MALDI mass spectrometry method according to an embodiment of the present invention, the mass of the sample to be analyzed by loading the sample to be analyzed on a metal dot of the MALDI mass spectrometry sample plate according to the present invention and irradiating a laser to desorb and ionize the sample. It may be to analyze.

In the MALDI mass spectrometry sample plate according to the present invention, the metal dot to be loaded with the sample to be analyzed and the metal wiring are separated from each other through a plastic insulating plate, and electrically connected to each other through a via or a metal part, thereby lasering the target (metal dot). When irradiating to the sample plate using the metal matrix to reduce the energy transmitted to the inside of the plate to focus the laser energy to the target, there is an effect that can minimize the heat loss.

Accordingly, the MALDI mass spectrometry sample plate according to the present invention is capable of homogeneous heating of the sample to be analyzed, and thus has an effect of obtaining a reproducible MALDI mass spectrum when the laser is irradiated to the same spot several times.

Even if the effects are not explicitly mentioned in the present invention, the effects described in the specification and the inherent effects expected by the technical features of the present invention are treated as described in the specification of the present invention.

1 and 2 are cross-sectional and top views, respectively, of a side of a sample plate for MALDI mass spectrometry according to an aspect of the present invention.

3 is a cross-sectional view of a side surface of a sample plate for MALDI mass spectrometry including a metal layer according to an aspect of the present invention, and FIGS. 5 and 6 are top views of the sample plate for MALDI mass spectrometry.

7 is a cross-sectional view of a side of a sample plate for MALDI mass spectrometry comprising a metal dot having a hydrophobic surface portion according to an aspect of the present invention.

8 and 9 are cross-sectional and top views, respectively, of a side of a sample plate for MALDI mass spectrometry provided with a sample reservoir substrate according to one aspect of the present invention.

10 is a cross-sectional view and a perspective top view of a side of a sample plate for MALDI mass spectrometry comprising a sample reservoir substrate having a gas passage, in accordance with an aspect of the present invention.

 And top view.

11 is a cross-sectional view of a side surface of a sample plate for MALDI mass spectrometry further comprising a side metal layer on a side portion according to another embodiment of the present invention.

12 and 13 are top views of a sample plate for MALDI mass spectrometry further comprising a side metal layer at a side portion according to another embodiment of the present invention.

14 shows an actual image of a sample plate for MALDI mass spectrometry according to an embodiment of the present invention, showing the front surface of the sample plate.

Hereinafter, a sample plate for MALDI mass spectrometry, a method for preparing the same, and a MALDI mass spectrometry method using the same will be described in detail with reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS The drawings described herein are provided by way of example in order to fully convey the spirit of the invention to those skilled in the art. Therefore, the present invention is not limited to the drawings presented and may be embodied in other forms, and the drawings may be exaggerated to clarify the spirit of the present invention.

Unless otherwise defined in the technical and scientific terms used herein, it has the meaning commonly understood by those of ordinary skill in the art to which this invention belongs, and the gist of the invention in the following description and the accompanying drawings. The description of well-known functions and configurations that may unnecessarily obscure them will be omitted.

As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the specification indicates otherwise.

As used herein, unless stated otherwise, unit of% means weight% unless otherwise defined.

In the present specification, the term "electrically connected" refers to a case in which two objects to be electrically connected are directly connected to each other or indirectly connected to each other through separate connection means.

MALDI mass spectrometry sample plate according to the present invention, the plastic insulating plate; And a metal dot formed on one surface of the plastic insulating plate to allow a sample to be loaded on the surface thereof. In this case, the metal dot may be electrically connected to the sample plate voltage applying unit of the MALDI mass spectrometer.

The sample plate for MALDI mass spectrometry according to an embodiment of the present invention may further include one or two or more metal layers formed in contact with the side surfaces, the bottom surfaces, the top surfaces, or these surfaces of the plastic insulation plate, and the metal layers may include the metal dot. It may be electrically connected with the. In this case, the metal dot may be electrically connected to the sample plate voltage applying unit of the MALDI mass spectrometer through the metal layer during mass spectrometry.

The sample plate for MALDI mass spectrometry according to an embodiment of the present invention may further include an upper metal layer formed on one surface of the plastic insulation plate on which the metal dot is formed.

In one example of the present invention, the upper metal layer may be electrically connected to the metal dot, or may not be electrically connected to the metal dot.

As a specific example, when the metal layer is electrically connected to the metal dot, one surface of the plastic insulating plate on which the metal dot is formed may include an insulating part spaced apart from the metal dot and the upper metal layer; And a connection part adjacent to the insulating part and formed by contacting the metal dot and the upper metal layer, or the entire circumference of the metal dot and the upper metal layer may contact the insulating part.

As a specific example, when the metal layer is not electrically connected to the metal dot, one surface of the plastic insulation plate on which the metal dot is formed may be spaced apart from the entire circumference of the metal dot and the upper metal layer, and adjacent to the entire circumference of the metal dot. It may include; insulating portion surrounding it.

The sample plate for MALDI mass spectrometry according to an embodiment of the present invention may further include a lower metal layer formed on the other surface of the plastic insulation plate.

The sample plate for MALDI mass spectrometry according to an embodiment of the present invention may further include a side metal layer formed on the side of the plastic insulating plate and electrically connected to the upper metal layer.

The MALDI mass spectrometry sample plate according to an embodiment of the present invention may further include a metal dot via formed through the plastic insulating plate and electrically connected to the metal dot and the bottom metal layer.

The MALDI mass spectrometry sample plate according to an embodiment of the present invention may further include a metal layer via formed through the plastic insulating plate and electrically connected to the upper metal layer and the lower metal layer.

Hereinafter, a sample plate for MALDI mass spectrometry according to the present invention, which may be more preferable, will be described in detail as the first to third aspects. However, this is only to distinguish the sample plate for MALDI mass spectrometry according to the present invention more effectively, whereby the present invention is not limited to a specific embodiment, or should be interpreted as different inventions. In addition, although the components described in each aspect are not separately described in other aspects, the components described in each aspect may be shared and applied to other aspects.

The sample plate for MALDI mass spectrometry of the first aspect according to an embodiment of the present invention, as shown in Figures 1 and 2, a plastic insulating plate; A metal dot formed on one surface of the plastic insulating plate to allow a sample to be loaded on a surface thereof; A lower metal layer formed on the other surface of the plastic insulating plate; And a metal dot via formed through the plastic insulating plate and electrically connected to the metal dot and the bottom metal layer.

As such, the metal dot to be loaded with the sample to be analyzed and the bottom metal layer are separated from each other through a plastic insulating plate and electrically connected to each other through vias. By reducing the transmitted (thermal) energy, the laser energy can be concentrated on the target, minimizing heat loss. Accordingly, the homogeneous heating of the sample to be analyzed is possible, so that the MALDI mass spectrum having excellent reproducibility can be obtained even when the laser is irradiated to the same spot several times.

MALDI mass spectrometry sample plate according to the first aspect of the present invention, as shown in Figure 3, is formed on one surface of the plastic insulating plate on which the metal dot is formed, the upper metal layer electrically connected to the metal dot; Can be. When the upper metal layer is formed, the potential of the plastic insulating plate is determined by surface charge, etc., so it is very easy to predict the electric field around it, and the uncertainty of the electric field due to the presence of the insulator around the metal dot is reduced. It can be expected that the electric field around the dot will be formed uniformly without distortion.

In the MALDI mass spectrometry sample plate of the first aspect of the present invention, the upper metal layer may be electrically connected to the metal dot, or may not be electrically connected to the metal dot.

As a specific example of the first embodiment, when the metal layer is electrically connected to the metal dot, as shown in FIG. 6, one surface of the plastic insulating plate on which the metal dot is formed is spaced apart from the metal dot and the upper metal layer therebetween. Insulating section; And a connection part adjacent to the insulating part and formed by contacting the metal dot and the upper metal layer, or the entire circumference of the metal dot and the upper metal layer may contact the insulating part. As a non-limiting example, the case including the insulation part and the connection part may be described as an example illustrated in FIG. 6. More specifically, the width of the connection portion may be 1 to 20% of the width of the insulation portion. As a non-limiting example, when the entire circumference of the metal dot and the upper surface metal layer contact each other, the entire circumference of the metal dot may contact the metal layer or the metal dot may be integrated with the metal layer. However, this is only a preferred example, and the present invention is not limited thereto.

As another specific example of the first embodiment, when the metal layer is not electrically connected to the metal dot, as shown in FIG. 5, one surface of the plastic insulation plate on which the metal dot is formed may have the entire circumference of the metal dot and the upper metal layer. Spaced apart, the insulating portion adjacent to surround the entire circumference of the metal dot; may include. The insulating portion may be spaced apart from the metal dot so as to surround the circumference thereof. For example, the insulating portion may have a circular shape, and may have a thickness of 0.2 to 20 mm, but the shape and size thereof are not limited thereto. The insulating part may refer to an insulating layer that divides a region of the metal dot and the upper metal layer, or may mean a surface of the plastic insulating plate exposed to the outside of the sample plate. When the insulating portion refers to the surface of the plastic insulating plate exposed to the outside of the sample plate, the upper metal layer is not electrically connected to the lower metal layer, the sample plate for MALDI mass spectrometry of the second embodiment according to the present invention, Figure 4 (top In the bottom order in the first drawing), the metal layer via is electrically connected to the upper metal layer and the lower surface metal layer and penetrated through the plastic insulating plate; may further include. When this is satisfied, as shown in FIG. 5, the upper metal layer and the metal dot are electrically connected to each other through the metal layer via without contacting the metal dot, thereby minimizing the transfer of thermal energy and easily applying voltage.

The sample plate for MALDI mass spectrometry of the second aspect according to an embodiment of the present invention is as shown in Fig. 3 (second drawing from top to bottom), Fig. 4 (first, second and fourth drawings from top to bottom). Like, plastic insulation plate; A metal dot formed on one surface of the plastic insulating plate; An upper metal layer formed on one surface of the plastic insulating plate on which the metal dots are formed and electrically connected to the metal dots; A lower metal layer formed on the other surface of the plastic insulating plate; And a metal layer via formed through the plastic insulating plate and electrically connected to the upper metal layer and the lower metal layer.

That is, in the MALDI mass spectrometry sample plate of the second aspect, as shown in FIG. 3 (second from top to bottom), the metal layer vias penetrating the plastic insulation plate are electrically connected to the upper metal layer and the lower metal layer. The upper metal layer and the metal dot may have a structure electrically connected to each other. In this case, the upper metal layer and the metal dot are sufficient to have an electrically connected structure. For example, the upper metal layer and the metal dot may be electrically connected to each other by contacting the upper metal layer, as shown in FIG. 6, and FIG. The metal dot and the upper metal layer may be electrically connected to the metal dot via described above.

As such, the sample plate using the metal matrix when the laser is irradiated to the target by placing the metal dot on which the sample to be analyzed and the lower surface metal layer are separated from each other through the plastic insulating plate and electrically connecting them through vias formed through the plastic insulating plate. By reducing the (heat) energy delivered to the interior of the contrast plate, the laser energy can be concentrated on the target and the heat loss can be minimized. Accordingly, the homogeneous heating of the sample to be analyzed is possible, so that the MALDI mass spectrum having excellent reproducibility can be obtained even when the laser is irradiated to the same spot several times.

In one non-limiting example, the upper metal layer and the metal dot may be in contact with and electrically connected to each other. For example, the entire circumference of the metal dot and the upper metal layer may contact each other, or one surface of the plastic insulating plate on which the metal dot is formed, An insulating part spaced apart from the metal dot and the upper metal layer; And a connection part adjacent to the insulation part and formed to be in contact with the metal dot and the upper metal layer. As a non-limiting example, when the entire circumference of the metal dot and the upper surface metal layer contact each other, the entire circumference of the metal dot may contact the metal layer or the metal dot may be integrated with the metal layer. As a non-limiting example, as shown in FIG. 6, the width of the connection portion may be 1 to 20% of the width of the insulation portion. However, this is only a preferred example, and the present invention is not limited thereto.

The sample plate for MALDI mass spectrometry of the third embodiment according to an embodiment of the present invention is shown in FIGS. 11 to 13, 3 (third drawing in the order from the top to the bottom), and FIG. 4 (2, 3, Fourth drawing) plastic insulation plate; A metal dot formed on one surface of the plastic insulating plate; An upper metal layer formed on one surface of the plastic insulating plate on which the metal dots are formed and electrically connected to the metal dots; And a side metal layer formed on a side surface of the plastic insulating plate and electrically connected to the upper metal layer.

In the third aspect, the metal dot is electrically connected to the lower surface metal layer by the side metal layer formed on the side surface of the plastic insulating plate. The side metal layer may be formed in contact with a side portion of the plastic insulation plate, specifically, the side surface of the plastic insulation plate. Specifically, as shown in FIG. 11 (first drawing in the top to bottom order), the side metal layer may be formed in contact with the side surface of the bottom plastic insulator of the top metal layer, and as shown in FIG. 11 (the second drawing in the top to bottom order), It may be formed in contact with the side of the upper metal layer and the side of the plastic insulating plate. In addition, as shown in FIG. 12, the side metal layer may be formed on one side portion of the plastic insulation plate, and as shown in FIG. 13, a plurality of side metal layers may be formed on the plurality of side parts of the plastic insulation plate, respectively. In this case, the size and shape of the side metal layer is not limited as long as voltage is applied and the objects can be electrically connected to each other. For example, the side metal layer may have various shapes and sizes such as a plate shape and a wire shape. For example, in terms of minimizing the transfer of thermal energy, the side metal layer may be formed in an area of 0.1 to 10%, specifically 0.5 to 5%, with respect to the entire side of the plastic insulation plate. In addition, in terms of minimizing the transfer of thermal energy, it may be preferable that a plurality of side metal layers are formed in a smaller unit size on the side of the plastic insulation plate. However, this is only a preferred example, and the present invention is not limited thereto.

As such, the upper metal layer electrically connected to the metal dot through the plastic insulating plate is electrically connected to the side metal layer formed on the side portion of the plastic insulating plate, so that when the laser is irradiated to the target, the upper metal layer is transferred to the inside of the plate compared with the sample plate using the metal matrix. By reducing the (heat) energy, the laser energy can be concentrated on the target, minimizing heat loss. Accordingly, the homogeneous heating of the sample to be analyzed is possible, so that the MALDI mass spectrum having excellent reproducibility can be obtained even when the laser is irradiated to the same spot several times.

The MALDI mass spectrometry sample plate according to the third aspect of the present invention may further include a lower surface metal layer formed on the other surface of the plastic insulation plate and electrically connected to the upper surface metal layer in some cases. .

In the MALDI mass spectrometry sample plate according to the third aspect of the present invention, in some cases, one surface of the plastic insulation plate on which the metal dot is formed may be spaced apart from the entire circumference of the metal dot and the upper metal layer, An insulation part adjacent to and surrounding the entire circumference of the dot; And a metal dot via formed through the plastic insulating plate and electrically connected to the metal dot and the bottom metal layer.

In a third aspect, the bottom metal layer and the metal dot via may be used for the electrical connection between the metal dot and another metal layer, and the metal layer may be for connection with a voltage applying unit.

In the third aspect, the connection structure to the top metal layer electrically connected to the metal dot may be any structure in which they can be electrically connected. As a specific example, as shown in FIG. 6, the upper metal layer and the metal dot may be in direct contact with each other, and may be electrically connected to each other. Alternatively, the upper metal layer and the metal dot may not be in contact with each other and may be indirectly connected through other connecting means. As an example of the indirect electrical connection structure, as shown in FIG. 4 (third view from top to bottom), the metal dot contacts the metal dot via, the metal dot via contacts the lower metal layer, and the lower metal layer contacts the side metal layer. The upper metal layer and the metal dot may be indirectly electrically connected by the upper metal layer contacting the side metal layer.

As described above, in the MALDI mass spectrometry sample plate according to the present invention, the upper metal layer may be spaced apart from the metal dot, or may be positioned in contact with the metal dot. As a non-limiting example, the top metal layer may be located in contact with the entire circumference of the metal dot, that is, formed as a single metal plate (metal dot + top metal layer) without a plastic insulating plate or an insulating portion between the top metal layer and the metal dot. May be

As described above, the present invention may include various aspects, such as the first to third aspects, wherein components described in each aspect may be shared and applied to other aspects, even if there is a component that is not separately described in each aspect. Of course it can. That is, the combination of the components for the sample plate for MALDI mass spectrometry according to the above-described example is specifically described as it is more preferable in the present invention, and other possible combinations of the aforementioned components may also be used as the configuration of the present invention. Of course it is included.

The via is for electrically connecting the metal dot and the metal layer, and may be formed in the through hole penetrating the plastic insulation plate, and the diameter and the shape of the via are not particularly limited as long as they can connect the metal dot and the metal layer. . Specifically, it may be desirable for the via diameter to be smaller than the diameter of the metal dot so that the metal dot can be stably bound to one surface of the plastic insulating plate. In one embodiment, the diameter of the via may be 10 μm to 1 mm, more preferably 50 to 500 μm, but is not limited thereto.

The via is not particularly limited as long as the via penetrates the plastic insulating plate to electrically connect the metal layer to the bottom metal layer. However, the inner surface of the through hole penetrating the plastic insulation plate is coated with metal so that the metal layer is electrically connected to the bottom metal layer. Or it may be in the form of a metal plug pressed into the through-hole.

In this case, the metal coating or the metal plug may be formed of the same or different metal as the lower metal layer, and may be, for example, a metal element material. As a more specific example, the via is gold (Au), silver (Ag), copper (Cu), chromium (Cr), aluminum (Al), tungsten (W), zinc (Zn), nickel (Ni), iron (Fe) And any one or two or more selected from these alloys and the like. In addition, the via may include copper (Cu) or a copper alloy in terms of reducing costs while ensuring excellent electrical conductivity. However, this is only a preferred example, and the present invention is not limited thereto.

The plastic insulating plate is an insulating plastic substrate, and is not particularly limited as long as it can relatively reduce heat transfer as compared to, for example, a metal dot, a lower metal layer, a via, and the like. As one non-limiting example, the plastic insulating plate may be epoxy, paper-phenolic resin, polyimide (PI), polyethylene terephthalate (PET), polyethylenenaphthalate (PEN), Polymethylmethacrylate (PMMA), polyetheretherketone (PEEK), polycarbonate (PC), polyethersulfone (PES), polyarylite or cyclic olefin copolymer It may be a substrate such as (cyclicolefincopolymer, COC), but is not limited thereto. The thickness may be sufficient as the thickness of a commonly used sample plate that is not easily deformed while providing sufficient insulation, and in one embodiment may be 2 to 5 mm, but is not limited thereto. In this case, the paper-phenolic resin substrate may mean that the phenol resin penetrates the paper and is manufactured by heating and compressing a plurality of sheets. However, this is only a preferred example, and the present invention is not limited thereto.

The metal dot is a portion in which an analyte sample to be mass analyzed is substantially loaded, and is a point where a laser is irradiated during MALDI analysis. The metal dot may be formed in a required shape on one surface of the plastic insulating plate, and one or more metal dots may be formed on one surface of the plastic insulating plate, and when a plurality of metal dots are formed, periodic and regular arrangement Or aperiodic and irregular arrangements.

The material of the metal dot according to an embodiment of the present invention is a material that allows a sample to be analyzed in the art to be loaded, and is not particularly limited as long as it is an electrically conductive material, and may be, for example, a metal element material. As a non-limiting example, the metal dot may be gold (Au), silver (Ag), copper (Cu), chromium (Cr), aluminum (Al), tungsten (W), zinc (Zn), nickel (Ni), It may include any one or two or more selected from iron (Fe) and alloys thereof, but does not exclude other materials commonly used in the art.

As mentioned above, the metal dot is a component that is loaded with the sample to be analyzed, and therefore, it is preferable to have an appropriate size so that the sample to be analyzed can be well aggregated, and similar to the sample to be analyzed.

In one embodiment, the diameter of the metal dot may be 100 μm to 5 mm, specifically 100 μm to 2 mm, more specifically 300 μm to 1 mm. When forming a target by dropping the sample solution to be analyzed in such a range, the effect of aggregation of the target into the metal dot may be excellent, and heat dissipation is suppressed as the size of the metal dot is small, thereby minimizing heat loss. have.

In addition, in order to further increase the effect of the sample to be aggregated into the metal dot, the metal dot may be similar in nature to the sample or analyte sample solution, and the plastic insulating plate may have the opposite properties.

As a non-limiting example, when the sample solution to be analyzed is hydrophilic, the plastic insulating plate or the metal layer to be described later may have a hydrophobic surface property, and the metal dot has a hydrophilic surface property to aggregate the analyte sample with the metal dot. Can be effective. To this end, in the manufacture of a plastic insulating plate, a plastic insulating plate is manufactured by using a hydrophobic polymer, or as shown in FIG. 7, after the substrate is manufactured, the surface is treated with a hydrophobic material to prepare a plastic insulating plate having hydrophobic surface properties. can do. In contrast, in the case of a metal dot, the surface of the metal dot may be treated with a hydrophilic material to prepare a metal dot having a hydrophilic surface.

As a more preferable example, the surface of the metal dot is a sample seating surface portion located in the center of the metal dot surface, as shown in Figure 7; And a hydrophobic surface portion surrounding the sample seating portion, wherein the hydrophobic surface portion may have a greater hydrophobicity than the sample seating surface portion. The sample seating surface portion is a portion where the sample to be actually analyzed is seated, and the hydrophobic surface portion allows the sample to be analyzed to aggregate onto the sample seating surface portion. The sample seating surface portion may have a diameter enough to allow the sample to be seated, for example, 100 μm or more and smaller than the diameter of the metal dot. In addition, as shown in Figure 9, the hydrophobic surface portion may be formed on the surface of the upper metal layer. However, this is only a preferred example, and the present invention is not limited thereto.

In addition, in one embodiment of the present invention, when there is an insulating portion such as a plastic insulating plate between the upper metal layer and the metal dot, as shown in Figure 7, the hydrophobic surface portion may be located in the insulating portion.

In one embodiment of the invention, the hydrophobic surface portion tetrafluoroethylene, hexafluoropropylene, chlorotrifluoroethylene, trifluoroethylene, vinylidene fluoride, octafluorobutylene, pentafluorophenyl tri Fluorine-based compounds including any one or two or more selected from fluoroethylene, pentafluorophenylethylene, polymers including repeating units derived therefrom, fluorine-containing acrylate polymers and perfluoropolyethers; Silane compounds having an alkyl group including any one or two or more selected from alkyltrichlorosilane, alkyltrimethoxysilane, alkyltriethoxysilane, dichlorodialkylsilane and the like; Silicone oil containing a silane compound having an amine group and any one or more selected from dimethicone and methicone; Oxide / polymer nanocomposites including any one or more selected from manganese oxide / polystyrene (MnO ₂ / PS) nanocomposites and zinc oxide / polystyrene (ZnO / PS) nanocomposites exhibiting superhydrophobicity; A composition comprising carbon nanotubes; And silica nano coatings; It may include any one or two or more selected from. However, this is only a preferred example, of course, the present invention is not limited thereto.

As a non-limiting example, when the sample solution to be analyzed is hydrophobic, the plastic insulating plate or the metal layer to be described later may have a hydrophilic surface property, and the metal dot has a hydrophobic surface property to aggregate the sample to be analyzed with a metal dot. Can be effective.

As described above, when the sample to be analyzed is agglomerated in a very narrow region and has a high degree of integration, mass analysis can be performed with high sensitivity even with a small volume of sample, and MALDI mass spectrum having excellent reproducibility can be obtained.

In the present invention, the voltage is finally applied to the metal dot to allow mass analysis, and various known methods or methods described below for applying the voltage to the metal dot may be used. As a specific example, to enable the operation of the MALDI mass spectrometer, the MALDI mass spectrometer may include a voltage applying unit for applying a voltage to the sample plate, from which the voltage is applied to the metal dot. If you can, it's fine. As an example of a specific means for allowing a voltage to be applied to the metal dot, the voltage applying unit may be electrically connected to the metal dot of the sample plate for MALDI mass spectrometry according to the present invention, but may be electrically connected to the metal layer or via. It may be desirable to ensure that the voltage applying portion is not directly connected to the metal dot. As a specific example, the voltage applying unit may be electrically connected in direct contact with any one or two or more selected from a metal dot via, a metal layer via, an upper metal layer, a lower metal layer, and a side metal layer. More preferably, when the voltage applying unit is electrically connected to the metal dot, it may be preferable to directly connect the metal layer.

The metal layer provides an electrical connection through the above-described structure so that the operation of the MALDI mass spectrometer can be more smoothly performed even though the metal dot is formed in a dot or a circular shape on one surface of the plastic insulating plate, and the metal layer is the MALDI mass. The analysis equipment may be designed to be in contact with a voltage applying unit for applying a voltage to a sample plate. In addition, the actual electrical connection with the metal dot may be through a via or a metal layer. For example, the lower metal layer may cover one end of the side via of the plastic insulation plate on which the lower metal layer is formed, or contact the side metal layer. It may be desirable to form. As a non-limiting example, MALDI mass spectrometry can be difficult to apply voltage to the metal dot if the metal layer is not connected to one end of the via or in contact with the side metal layer, that is, in one non-limiting example According to the present invention, the metal layer has a structure that is connected to a voltage applying part supplying voltage to the sample plate and connected to a metal dot through vias in the step of inserting and analyzing the sample plate into the mass spectrometer. The effect of minimizing the reproducibility deterioration due to the temperature variation according to the number of times of irradiation can be further improved.

The material of the metal layer may be used without particular limitation as long as it is known to have excellent electrical conductivity. For example, the metal layer may be a metal element material. As a more specific example, the metal layer is gold (Au), silver (Ag), copper (Cu), chromium (Cr), aluminum (Al), tungsten (W), zinc (Zn), nickel (Ni), iron (Fe) ) And alloys thereof, and the like. It may be more preferable that the metal layer includes copper (Cu) or a copper alloy in terms of reducing costs while ensuring excellent electrical conductivity. However, this is only a preferred example, and the present invention is not limited thereto.

As used herein, the "metal layer" is not limited in its form and may be, for example, in the form of a plate, specifically, in the form of a coating film.

The size of the 'metal dot', 'metal layer' referred to in the present specification may be appropriately adjusted according to the size, and is not particularly limited. For example, the average thickness thereof may be 10 μm to 200 μm, but the present invention is not limited thereto. Of course not. In addition, the size of the 'plastic insulating plate' referred to in the present specification may be appropriately adjusted according to the size, and is not greatly limited. For example, the average thickness thereof may be 0.5 mm to 3 mm, but the present invention is not limited thereto. .

The sample plate for MALDI mass spectrometry according to the present invention may further include an identification marking area adjacent to the circumference of the metal dot. The metal dot region, which is a region in which the sample is loaded, may be identified by the above-described insulation, and in order to make it difficult to further identify or supplement the region, an identification marking region adjacent to the circumference of the metal dot may be further provided. have. This marking area can be performed by various known methods such as coating, painting and the like.

The sample plate for MALDI mass spectrometry according to an embodiment of the present invention is attached to one surface of the plastic insulating plate, as shown in Figure 8 to 10, the sample reservoir substrate having a through-hole surrounding the metal dot It may further include. In this case, unlike the metal layer surrounding the circumference of the metal dot to be spaced apart from the circumference of the metal dot, the sample reservoir substrate may have a form in which the inner surface of the through hole of the sample reservoir substrate is in contact with the circumference of the metal dot.

As such, since the sample reservoir substrate may be provided, the sample solution may be directly deposited on the sample plate, and the sample may be loaded on the metal dot, thereby providing extremely uniform and detailed analysis. Samples can be sampled to ensure better reproducibility during mass spectrometry.

In one embodiment of the present invention, the sample reservoir substrate is loaded with the sample to be analyzed to form a target, and then separated from the sample plate for MALDI mass spectrometry for efficient laser irradiation during mass analysis, the sample leisure The burr substrate may be detachable from one surface of the plastic insulating plate.

As such, since the sample reservoir substrate is separated from the MALDI mass spectrometry sample plate, the sample reservoir substrate may not be particularly limited as long as the sample reservoir substrate is manufactured to have a desired shape, and may be any metal, metal oxide, ceramic, or polymer. Although a material may be used, it is preferable that the through hole has a hydrophobic surface property on its inner surface in order to enhance the effect of aggregating the sample to be analyzed with a metal dot. However, this is only a preferred example, and the present invention is not limited thereto.

In addition, as mentioned above, the through-hole of the sample reservoir substrate is a shape in which the inner surface of the through-hole of the sample reservoir substrate is in contact with the circumference of the metal dot, and the shape of the through-hole itself is not particularly limited, and specifically, for example, a cylinder Shape or funnel shape or the like. However, this is only a preferred example, and the present invention is not limited thereto.

In addition, the sample reservoir substrate according to an embodiment of the present invention, as shown in Figure 10, in order to quickly dry the solvent in the sample solution to be injected into the through hole, a gas passage for discharging the inert gas to the through hole may be provided have. The gas passage is not limited to the shape, size, etc., if the gas can be transported through the through-hole, and also does not limit the number of passages, as an example of the gas passage is shown by the dotted line shown in the left figure of FIG. 10 is a perspective top view, which is a top view of a sample plate, and the gas passages shown are in a perspective state as dotted lines. In this case, the inert gas may be helium (He), neon (Ne), nitrogen (N 2) or argon (Ar), but is not limited thereto.

In addition, the sample reservoir substrate according to an embodiment of the present invention, as shown in Figure 10, may be provided with a magnet inside the sample reservoir substrate to be detachable from the sample plate for MALDI mass spectrometry, wherein the magnet is permanent It may mean a magnet. To this end, an attachment aid may be further provided which is attached to the bottom surface of the sample plate for MALDI mass spectrometry, that is, the opposite surface of the surface to which the sample reservoir substrate is attached, and the attachment aid may also be provided with a magnet. . By attaching the sample plate for MALDI mass spectrometry on the attachment aid and adjusting the displacement of the magnet provided in the attachment aid, the magnet provided in the attachment aid and the magnet in the sample reservoir substrate are attracted to each other. Alternatively, the sample reservoir substrate may be detached or attached to the sample plate for MALDI mass spectrometry. However, this is only a preferred example, and the present invention is not limited thereto.

Hereinafter, a method of manufacturing a sample plate for MALDI mass spectrometry according to the present invention will be described in detail. However, this is only for effectively explaining a method for producing a sample plate for MALDI mass spectrometry according to the present invention by way of example, whereby the present invention is limited to a specific embodiment should not be interpreted. In addition, each component of the method for producing a sample plate for ALDI mass spectrometry described below can be shared and applied to the components of the above-described ALDI mass spectrometry sample plate.

Method for producing a sample plate for MALDI mass spectrometry according to an aspect of the present invention, forming a metal thin film on both sides of the plastic insulating plate; Forming a via penetrating the plastic insulating plate; And selectively etching both sides of the metal thin film of the plastic insulation plate to form a metal dot on one surface and a bottom metal layer on the other surface thereof. In this case, the metal dot and the bottom metal layer may be electrically connected through vias.

Method for producing a sample plate for MALDI mass spectrometry according to an aspect of the present invention, forming a metal thin film on both sides of the plastic insulating plate; Selectively etching both sides of the metal thin film of the plastic insulating plate, forming a metal dot and an upper metal layer on one surface, and forming a lower metal layer on the other surface; And forming a metal thin film in contact with a side surface of the plastic insulating plate to form a side metal layer. In this case, the metal dot and the top metal layer may be electrically connected, the top metal layer and the side metal layer may be electrically connected, and the side metal layer and the bottom metal layer may be electrically connected.

Method for producing a sample plate for MALDI mass spectrometry according to an aspect of the present invention, forming a metal thin film on both sides of the plastic insulating plate; Selectively etching both sides of the metal thin film of the plastic insulating plate, forming a metal dot and an upper metal layer on one surface, and forming a lower metal layer on the other surface; Forming a metal dot via or a metal layer via penetrating the plastic insulating plate; And forming a metal thin film in contact with a side surface of the plastic insulating plate to form a side metal layer. In this case, the metal dot and the top metal layer are electrically connected, the top metal layer and the side metal layer are electrically connected, the side metal layer and the bottom metal layer are electrically connected, and the metal dot and the bottom metal layer are vias. It may be to be electrically connected through.

As a specific example, the sample plate for MALDI mass spectrometry may be manufactured based on a printed circuit board (PCB), that is, the metal layer and vias formed on the plastic insulating plate are used when manufacturing the printed circuit board. It may be formed through a conventional method.

First, the step of forming a metal thin film on both sides of the plastic insulating plate will be described, wherein the plastic insulating plate may be prepared from the same material as described above.

In the present invention, the method of forming the metal thin film may be a method commonly used in a printed circuit board (PCB) process, and for example, chemical vapor deposition, physical vapor deposition, or a mixture thereof may be used. More specific examples include electroless plating, electroplating, DC sputtering, magnetron sputtering, electron beam evaporation, thermal evaporation, thermal molecular vapor deposition, LMBE, Laser Molecular Beam Epitaxy, pulse Metal thin film in combination with one or more methods selected from laser deposition (PLD, PulsedLaser Deposition), vacuum deposition, atomic layer deposition (ALD) and plasma assisted chemical vapor deposition (PECVD) It may be formed, but is not necessarily limited thereto. At this time, the thickness of the metal thin film can be adjusted as desired, specifically, for example, may be 0.1 to 30 ㎛, but is not limited thereto.

Next, a step of forming a via penetrating the plastic insulating plate will be described.

In one embodiment of the present invention, the via is not particularly limited as long as the via penetrates the plastic insulating plate and can be electrically connected to the metal dot or the metal layer. However, after forming the through hole penetrating the plastic insulating plate, the via penetrates the plastic insulating plate. It may be formed by coating the inner surface of the through hole with a metal or pressing a metal plug into the through hole.

In one example of the present invention, the method of forming the through hole is not particularly limited as long as it is commonly used in the art, and may be formed using, for example, drilling or laser direct ablation (LDA).

In one embodiment of the present invention, the metal coating of the inner surface of the through hole is not particularly limited, but may be performed by electroless plating, electroplating, or sputtering, and the metal plug indentation fills the through hole with a conductive material. Alternatively, the method may be performed by inserting a metal plug manufactured in the shape of a through hole into the through hole, but is not limited as long as it can fill the inner surface of the through hole or the entire through hole to enable electrical connection.

In this case, the metal coating or the metal plug may be the same or different metal as the metal layer, for example, may be a metal element material, and the like, and more specifically, gold (Au), silver (Ag), copper (Cu), and chromium ( It may include any one or two or more selected from Cr), aluminum (Al), tungsten (W), zinc (Zn), nickel (Ni), iron (Fe) and alloys thereof. Preferably, while securing excellent electrical conductivity, it may include copper (Cu) or a copper alloy in terms of reducing the cost.

In one specific embodiment, before forming the through-holes for forming the vias, the metal dot, the metal layer and the metal dot and the lower surface metal layer in each case, including the case where the metal dot and the lower metal layer should be electrically connected through the metal dot via, and the like. It is desirable to design the location and pattern of the vias in advance.

Next, a step of selectively etching the metal thin films on both sides of the plastic insulating plate will be described.

In one example of the present invention, a method of forming a metal dot, a metal layer, etc. may be used without particular limitation as long as it is a method used in a PCB process. For example, a metal thin film of a region designed as a metal dot, a metal layer, etc. may be used through photolithography. After masking, the metal thin film of the unmasked region may be etched to form a metal dot, a metal layer, or the like.

At this time, as described above, the location and pattern of the bottom metal layer, the metal dot is preferably designed in advance to enable electrical connection. For example, the sample plate according to the present invention comprises a metal dot-via-bottom metal layer connection structure; Metal dot-via-bottom metal layer-side metal layer-top metal layer connection structure; Metal dot-top metal layer-side metal layer-bottom metal layer connection structure; Metal dot-top metal layer-metal layer via-bottom metal layer connection structure; It may have a connection structure of various aspects, such as, and the sample plate can be prepared by appropriately designing the position and pattern of the metal layer, the metal dot according to the connection structure of the various aspects.

In one embodiment of the present invention, the photolithography may be performed through a conventional method, and is not particularly limited, but may be applied to a dry film on a metal thin film, exposed and developed to mask a region designed with a metal dot or a metal layer. Can be.

In one example of the present invention, the etching method is not particularly limited, but dry etching, wet etching, or a mixture thereof may be used. As a specific example, the dry etching may be plasma etching or the like, and the wet etching may be etching using an etchant.

In addition, a process of removing the resist used for masking a specific region after forming a metal dot, a metal layer, or the like may be further performed.

Using the MALDI mass spectrometry sample plate thus prepared, it is possible to analyze the mass of the analyte sample according to a conventional MALDI mass spectrometry method. Specifically, the mass of the sample to be analyzed may be analyzed by loading the sample to be analyzed on a metal dot of a sample plate for MALDI mass spectrometry and irradiating a laser to desorb and ionize the sample.

Although the preferred embodiment of the present invention has been described above, it is clear that the present invention may use various changes, modifications, and equivalents, and that the above embodiments may be appropriately modified and applied in the same manner. Accordingly, the above description does not limit the scope of the invention as defined by the limitations of the following claims.

[Description of the code]

100: plastic insulation plate, 200: metal dot,

210: sample seating surface portion, 220: hydrophobic surface portion,

300: bottom metal layer, 400 (410): metal dot via,

420: metal layer via, 500 (510): top metal layer,

520: side metal layer, 600: sample reservoir substrate,

700: gas passage, 800: magnet, 900: hydrophobic surface portion

Claims (23)

1. Plastic insulation plate; And

   A metal dot formed on one surface of the plastic insulating plate to allow a sample to be loaded on a surface thereof;

   Including;

   The metal dot is a MALDI mass spectrometry sample plate electrically connected to the sample plate voltage applying unit of the MALDI mass spectrometer during mass spectrometry.
2. The method of claim 1,

   The MALDI mass spectrometry sample plate,

   One or more metal layers formed on side surfaces, bottom surfaces, upper surfaces of the plastic insulating plates, or in contact with these surfaces;

   More,

   The metal layer is electrically connected to the metal dot,

   The sample plate for MALDI mass spectrometry that the metal dot is electrically connected to the sample plate voltage applying unit of the MALDI mass spectrometer through the metal layer during mass spectrometry.
3. Plastic insulation plate;

   A metal dot formed on one surface of the plastic insulating plate to allow a sample to be loaded on a surface thereof;

   A lower metal layer formed on the other surface of the plastic insulating plate; And

   A metal dot via formed through the plastic insulating plate and electrically connected to the metal dot and the bottom metal layer;

   MALDI mass spectrometry sample plate comprising a.
4. The method of claim 3,

   The MALDI mass spectrometry sample plate,

   An upper metal layer formed on one surface of the plastic insulation plate on which the metal dot is formed;

   MALDI mass spectrometry sample plate further comprising.
5. The method of claim 4, wherein

   The upper metal layer is not electrically connected to the metal dot or spaced apart from the metal dot,

   When the metal layer is electrically connected to the metal dot, one surface of the plastic insulating plate on which the metal dot is formed is an insulating part spaced apart from the metal dot and the upper metal layer; And a connection part adjacent to the insulating part and formed by contacting the metal dot and the upper metal layer, or the entire circumference of the metal dot and the upper metal layer are in contact with each other.

   When the metal layer is not electrically connected to the metal dot, one surface of the plastic insulating plate on which the metal dot is formed is insulated from the entire circumference of the metal dot and the upper metal layer, and surrounded and surrounded by the entire circumference of the metal dot. MALDI mass spectrometry sample plate comprising a.
6. The method of claim 5,

   The MALDI mass spectrometry sample plate,

   A metal layer via formed through the plastic insulating plate and electrically connected to the upper metal layer and the lower metal layer;

   More,

   One surface of the plastic insulating plate on which the metal dot is formed, the entire circumference of the metal dot and the upper metal layer spaced apart, the insulating portion adjacent to the entire circumference of the metal dot; includes;
7. Plastic insulation plate;

   A metal dot formed on one surface of the plastic insulating plate;

   An upper metal layer formed on one surface of the plastic insulating plate on which the metal dots are formed and electrically connected to the metal dots;

   A lower metal layer formed on the other surface of the plastic insulating plate; And

   A metal layer via formed through the plastic insulating plate and electrically connected to the upper metal layer and the lower metal layer;

   MALDI mass spectrometry sample plate comprising a.
8. The method of claim 7, wherein

   One surface of the plastic insulating plate on which the metal dot is formed,

   An insulating part spaced apart from the metal dot and the upper metal layer; And

   A connection part adjacent to the insulation part and formed to be in contact with the metal dot and the upper metal layer;

   A MALDI mass spectrometry sample plate comprising or in contact with the entire circumference of the metal dot and the upper metal layer.
9. Plastic insulation plate;

   A metal dot formed on one surface of the plastic insulating plate;

   An upper metal layer formed on one surface of the plastic insulating plate on which the metal dots are formed and electrically connected to the metal dots; And

   A side metal layer formed on a side surface of the plastic insulating plate and electrically connected to the upper metal layer;

   Sample plate for MALDI mass spectrometry comprising a.
10. The method of claim 9,

    One surface of the plastic insulating plate on which the metal dot is formed,

    An insulating part spaced apart from the metal dot and the upper metal layer; And

    A connection part adjacent to the insulation part and formed to be in contact with the metal dot and the upper metal layer;

    A MALDI mass spectrometry sample plate comprising or in contact with the entire circumference of the metal dot and the upper metal layer.
11. The method of claim 9,

    The MALDI mass spectrometry sample plate,

    A lower metal layer formed on the other surface of the plastic insulating plate and electrically connected to the upper metal layer;

    MALDI mass spectrometry sample plate further comprising.
12. The method of claim 11,

    One surface of the plastic insulating plate on which the metal dot is formed,

    An insulation part spaced apart from the entire circumference of the metal dot and the upper surface metal layer and adjacent to the entire circumference of the metal dot; And

    A metal dot via formed through the plastic insulating plate and electrically connected to the metal dot and the bottom metal layer;

    MALDI mass spectrometry sample plate comprising a.
13. The method according to any one of claims 2 to 12,

    The metal dot has a diameter of 100 ㎛ to 5 mm MALDI mass spectrometry sample plate.
14. The method according to any one of claims 2 to 12,

    The metal dot and the metal layer are independently of each other gold (Au), silver (Ag), copper (Cu), chromium (Cr), aluminum (Al), tungsten (W), zinc (Zn), nickel (Ni), Sample plate for MALDI mass spectrometry comprising at least one selected from iron (Fe) and alloys thereof.
15. The method according to any one of claims 2 to 12,

    The plastic insulating plate has a hydrophobic surface property, the metal dot has a hydrophilic surface property sample plate for MALDI mass spectrometry.
16. The method according to any one of claims 2 to 12,

    The surface of the metal dot,

    A sample seating surface portion located at the center of the metal dot surface; And

    A hydrophobic surface portion surrounding the sample seating portion;

    Including;

    MALDI mass spectrometry sample plate wherein the hydrophobic surface portion is greater hydrophobic than the sample seating surface portion.
17. The method according to any one of claims 2 to 12,

    The MALDI mass spectrometry sample plate,

    A sample reservoir substrate attached to one surface of the plastic insulating plate, surrounding a circumference of the metal dot, and having a through hole;

    MALDI mass spectrometry sample plate further comprising.
18. The method according to any one of claims 2 to 12,

    The sample reservoir substrate MALDI mass spectrometry sample plate is provided with a gas passage for discharging the inert gas through the through-hole.
19. The method of claim 18,

    The sample reservoir substrate MALDI mass spectrometry sample plate that can be attached to one side of the plastic insulating plate.
20. Forming a metal thin film on both sides of the plastic insulating plate;

    Forming a via penetrating the plastic insulating plate; And

    Selectively etching the metal thin films on both sides of the plastic insulation plate to form a metal dot on one surface and a bottom metal layer on the other surface;

    Including;

    The metal dot and the bottom metal layer is a method of manufacturing a sample plate for MALDI mass spectrometry is electrically connected via vias.
21. Forming a metal thin film on both sides of the plastic insulating plate;

    Selectively etching both sides of the metal thin film of the plastic insulating plate, forming a metal dot and an upper metal layer on one surface, and forming a lower metal layer on the other surface; And

    Forming a side metal layer by forming a metal thin film in contact with a side surface of the plastic insulating plate;

    Including;

    And the metal dot and the upper metal layer are electrically connected, the upper metal layer and the side metal layer are electrically connected, and the side metal layer and the lower metal layer are electrically connected.
22. Forming a metal thin film on both sides of the plastic insulating plate;

    Selectively etching both sides of the metal thin film of the plastic insulating plate, forming a metal dot and an upper metal layer on one surface, and forming a lower metal layer on the other surface;

    Forming a metal dot via or a metal layer via penetrating the plastic insulating plate; And

    Forming a side metal layer by forming a metal thin film in contact with a side surface of the plastic insulating plate;

    Including;

    The metal dot and the top metal layer are electrically connected, the top metal layer and the side metal layer are electrically connected, and the side metal layer and the bottom metal layer are electrically connected,

    And the metal dot and the bottom metal layer are electrically connected to each other via vias.
23. The mass of the sample to be analyzed is loaded by loading the sample to be analyzed on a metal dot of the MALDI mass spectrometry sample plate selected from any one of claims 2 to 12 and irradiating a laser to desorb and ionize the sample. MALDI mass spectrometry method.

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