Method of fabrication of microparticle-based monolayer structures

Abstract

The present invention relates to a method for fabricating a single-layer structure based on microparticles, comprising the steps of: creating a hole chip body having a particle hole formed therein; injecting a mixture of a plurality of microparticles and a suspension into the particle hole; drying the mixture; and drying the suspension in the mixture to form a single layer of the plurality of microparticles, thereby enabling the easy fabrication of a single-layer structure formed of microparticles.

Description

Technology Field

[0001] The present invention relates to a method for fabricating a microparticle-based monolayer structure that can produce a monolayer microparticle structure by manufacturing a hole chip using 3D printing, injecting a suspension mixed with microparticles and a dispersion into the particle holes of the hole chip, and drying. Background Technology

[0003] In general, microparticles are spherical particles with a three-dimensional network structure having a micron size, and are used as supports for chromatography and flow cytometry, and as tools for high-speed high-throughput screening and immunoassays such as the detection and separation of DNA and proteins.

[0004] Optical measurement techniques are widely used to analyze the characteristics of microparticles themselves or their surfaces. For example, viruses and antibodies can be qualitatively or quantitatively measured by measuring the intensity of fluorescent substances (such as fluorescently labeled viruses and antibodies) attached to the surface of microparticles. Generally, to optically measure particles, they must be immobilized on the surface of a substrate, such as glass or plastic, or within a channel. If the material (substrate) on which the particles are immobilized emits autofluorescence with a wavelength similar to that of the particles, the signal sensitivity of the particles to be measured decreases. In other words, the background signal value relative to the signal becomes higher. Background signals exist even in transparent glass or plastic. The proposed airborne particle monolayer structure allows for the acquisition of high-sensitivity signals directly from the particles themselves, as background signals other than those from the air do not interfere. The problem to be solved

[0005] The present invention aims to provide a method for fabricating a microparticle-based single-layer structure, comprising a hole chip provided using 3D printing and an inverted truncated cone-shaped particle hole created in the hole chip, so as to facilitate the fabrication of a single-layer microparticle structure.

[0007] In addition, the present invention aims to provide a method for fabricating a microparticle-based single-layer structure by providing the ratio of the upper and lower surfaces of the particle holes and the thickness of the particle holes, so that a single-layer microparticle structure can be easily fabricated by drying a mixture of microparticles and a suspension.

[0009] The purposes of the embodiments of the present invention are not limited to those mentioned above, and other unmentioned purposes will be clearly understood by those skilled in the art from the description below. means of solving the problem

[0010] According to one embodiment of the present invention, a method for fabricating a microparticle-based monolayer structure may be provided, comprising the steps of: creating a hole chip body having a particle hole formed therein; injecting a mixture of a plurality of microparticles and a suspension into the particle hole; drying the mixture; and drying the suspension in the mixture to form a monolayer of the plurality of microparticles.

[0012] In addition, according to one embodiment of the present invention, a method for fabricating a microparticle-based monolayer structure may be provided, wherein the particle hole is provided in an inverted truncated cone shape such that the diameter of the upper surface is longer than the diameter of the lower surface.

[0014] In addition, according to one embodiment of the present invention, a method for fabricating a microparticle-based monolayer structure may be provided, wherein the step of forming the monolayer further comprises the step of measuring the components of the microparticles by irradiating the formed microparticle monolayer with fluorescence.

[0016] In addition, according to one embodiment of the present invention, a method for fabricating a microparticle-based monolayer structure may be provided, wherein the particle hole is formed such that the diameter of the upper surface is 1 mm and the diameter of the lower surface is 0.6 mm, and the thickness between the upper surface and the lower surface is 2 mm.

[0018] In addition, according to one embodiment of the present invention, a method for fabricating a microparticle-based monolayer structure may be provided, wherein the particle hole is formed such that the angle between the perpendicular of the lower end of the particle hole and the side of the particle hole is 5.7 to 5.8 degrees. Effects of the invention

[0019] In the present invention, a single-layer microparticle structure can be easily fabricated by providing a hole chip provided using 3D printing and an inverted truncated cone-shaped particle hole created in the hole chip.

[0020] In addition, in the present invention, by providing the ratio of the upper surface and the lower surface of the particle hole and the thickness of the particle hole, a single-layer microparticle structure can be easily produced by drying a mixture of microparticles and a suspension. Brief explanation of the drawing

[0021] FIG. 1 is a flowchart illustrating a method for fabricating a microparticle-based monolayer structure according to one embodiment of the present invention. FIG. 2 is a diagram illustrating a hole chip for creating a microparticle monolayer structure in a method for fabricating a microparticle-based monolayer structure according to one embodiment of the present invention. FIG. 3 is a diagram illustrating the specifications of a hole chip for creating a microparticle monolayer structure in a method for fabricating a microparticle-based monolayer structure according to one embodiment of the present invention. FIG. 4 is a diagram illustrating the process of generating a microparticle monolayer structure in a method for fabricating a microparticle-based monolayer structure according to one embodiment of the present invention. FIG. 5 is a diagram illustrating the shape of a structure generated according to the concentration of microparticles in a method for fabricating a microparticle-based monolayer structure according to one embodiment of the present invention. FIG. 6 is a diagram illustrating the shape of a structure produced according to the concentration of microparticles and the volume of a mixture in a method for producing a microparticle-based monolayer structure according to one embodiment of the present invention. FIG. 7 is a diagram illustrating particle images obtained from various materials in a method for fabricating a microparticle-based monolayer structure according to one embodiment of the present invention. Specific details for implementing the invention

[0022] The advantages and features of the embodiments of the present invention, and the methods for achieving them, will become clear by referring to the embodiments described below in detail together with the accompanying drawings. However, the present invention is not limited to the embodiments described below but may be implemented in various different forms. These embodiments are provided merely to ensure that the invention is complete and to fully inform those skilled in the art of the scope of the invention, and the invention is defined only by the scope of the claims. Throughout the specification, the same reference numerals refer to the same components.

[0023] In describing the embodiments of the present invention, specific descriptions of known functions or configurations will be omitted if it is determined that such detailed descriptions could unnecessarily obscure the essence of the invention. Furthermore, the terms described below are defined in consideration of their functions in the embodiments of the present invention, and these definitions may vary depending on the intentions or practices of the user or operator. Therefore, such definitions should be based on the content throughout this specification.

[0024] Hereinafter, embodiments of the present invention will be described in detail with reference to the attached drawings.

[0026] FIG. 1 is a flowchart illustrating a method for fabricating a microparticle-based single-layer structure according to an embodiment of the present invention; FIG. 2 is a diagram illustrating a hole chip for creating a microparticle single-layer structure in a method for fabricating a microparticle-based single-layer structure according to an embodiment of the present invention; FIG. 3 is a diagram illustrating the specifications of a hole chip for creating a microparticle single-layer structure in a method for fabricating a microparticle-based single-layer structure according to an embodiment of the present invention; FIG. 4 is a diagram illustrating the process of creating a microparticle single-layer structure in a method for fabricating a microparticle-based single-layer structure according to an embodiment of the present invention; FIG. 5 is a diagram illustrating the shape of a structure created according to the concentration of microparticles in a method for fabricating a microparticle-based single-layer structure according to an embodiment of the present invention; FIG. 6 is a diagram illustrating the shape of a structure created according to the concentration of microparticles and the volume of a mixture in a method for fabricating a microparticle-based single-layer structure according to an embodiment of the present invention; and FIG. 7 is a diagram illustrating particle images obtained from various materials in a method for fabricating a microparticle-based single-layer structure according to an embodiment of the present invention.

[0028] Referring to FIGS. 1 to 7, a method for fabricating a microparticle-based monolayer structure according to one embodiment of the present invention may include the step of creating a hole chip body having a particle hole formed therein (step 101), the step of injecting a mixture of a plurality of microparticles and a suspension into the particle hole (step 102), the step of drying the mixture (step 103), and the step of drying the suspension in the mixture to form a monolayer of a plurality of microparticles (step 104).

[0030] First, a step (step 101) of creating a hole chip body (201) having a particle hole (202) formed therein may be performed. The hole chip body (201) may be manufactured using a 3D printer, and a particle hole (202) may be formed in a part of the hole chip body (201). Here, the hole chip body (201) may be formed from a material such as plastic.

[0031] A particle hole (202) according to one embodiment of the present invention may be formed in the shape of an inverted truncated cone. That is, the cross-section of the particle hole (202) may be formed in the shape of an inverted trapezoid, and the upper and lower surfaces of the particle hole (202) may be formed in a circular shape. In addition, the diameter (D1) of the upper circle of the particle hole (202) may be formed to be larger than the diameter (D2) of the lower circle of the particle hole (202).

[0032] For example, if the height (or thickness) of the particle hole (202) is formed to be 2 mm, the diameter of the upper surface can be formed to be about 1 mm, and the diameter of the lower surface can be formed to be about 0.6 mm. When the particle hole (202) is formed in such a ratio, a single layer of microparticles can be formed as the mixture of microparticles and suspension injected into the particle hole (202) dries. Additionally, if the angle (θ) between the line connecting the lower end of the particle hole (202) (i.e., the lower surface edge end) and the upper surface edge end of the particle hole (202) (i.e., the length line of the side of the particle hole (202)) and the line perpendicular from the lower surface edge end of the particle hole (202) is formed to be about 5.71 degrees, a single layer of microparticles can be formed as the mixture of microparticles and suspension injected into the particle hole (202) dries. A detailed description regarding the structural form of the microparticles formed according to the shape of the particle hole (202) will be provided later.

[0034] Next, a step (step 102) of injecting a mixture of multiple microparticles and a suspension into the particle hole (202) may be performed. Here, the term "suspension" refers to a mixture in which small particles, such as mud, are dispersed in a liquid without being dissolved. When mixing microparticles and a suspension, the microparticles may not be dissolved, and the microparticles and the suspension may form a mixture.

[0035] A mixture of microparticles and a suspension according to one embodiment of the present invention can be injected into a particle hole (202). Here, even if the mixture is injected into the particle hole (202), the mixture has a certain viscosity and the diameter of the particle hole (202) becomes smaller as it goes toward the bottom of the particle hole (202), so the entire mixture does not pour out through the open bottom of the particle hole (202) but can remain stagnant at a certain position in the particle hole (202).

[0037] Next, a step (step 103) of drying the mixture may be performed. When the mixture is dried for a predetermined period of time, the suspension in the mixture continuously evaporates, and as the total volume of the mixture decreases, the distance between the multiple microparticles becomes closer.

[0038] Referring to FIG. 4, in a to d, the mixture injected into the hole chip body (201) is located inside the hole chip body (201), and as the suspension gradually dries, the volume of the entire mixture decreases, and the distance between multiple microparticles becomes closer. In particular, during the drying process, it can be seen that the central part of the mixture is formed to be relatively thinner than the edge part due to the tension of the edge part. Accordingly, the number of microparticles contained in the central part of the mixture may be less than the number of microparticles contained in the edge part of the mixture.

[0040] Next, a step (step 104) may be performed in which the suspension in the mixture is dried to form a monolayer of multiple microparticles. As the suspension in the mixture is dried, the suspension remains in trace amounts, and various forces may be applied to the multiple microparticles.

[0041] Referring to FIGS. 4e to FIGS. 4h, the process in which the microparticles in the central part of the plurality of microparticles form a monolayer (or mono-layer) while various forces are applied to the plurality of microparticles is as follows.

[0042] Referring to Figure 4e, it can be seen that equilibrium is achieved in the central part of the multiple microparticles due to lateral tension and vertical force acting on them. In this process, it can be seen that the multiple microparticles form multiple layers (or multi-layers) in the central part of the mixture.

[0043] Referring to f in Fig. 4, as the mixture dries, lateral resistance force may also act in addition to lateral tension and vertical force in the central part of the multiple microparticles. In this process, the vertical force acts relatively strongly, and as the mixture dries further, it can be seen that multiple microparticles form a single layer in the central part of the mixture.

[0044] Referring to Figures 4g to 4h, as the suspension in the central part of the mixture is completely dried, a monolayer of microparticles can be formed in the central part of the mixture. Additionally, as the lateral resistance force acts more significantly than the lateral tension force, the formed monolayer of microparticles can maintain its shape and be fixed.

[0045] Through the process described above, as the mixture dries, multiple microparticles in the central part of the mixture can form a monolayer. This monolayer form of microparticles can be referred to as a mono-layer and ring structure.

[0047] Meanwhile, in order to form a monolayer structure of microparticles, the ratio of the amount (or concentration) of microparticles to the mixture must be appropriately formed.

[0048] Referring to FIG. 5, a1 to a4 in FIG. 5 are drawings in which bright-field images were obtained after injecting and drying a mixture of various ratios, and b1 to b4 in FIG. 5 are drawings in which fluorescent images were obtained after injecting and drying a mixture of various ratios.

[0049] When the concentration of microparticles in the mixture is low, a 'Burst' structure may be formed, as shown in FIG. 5 a1 and FIG. 5 b1, where microparticles adhere only to the sides of the hole chip and the center of the hole chip is open. Additionally, when the concentration of microparticles in the mixture is relatively low, a 'Ring' structure may be formed, as shown in FIG. 5 a2 and FIG. 5 b2, where a small amount of microparticles grow from the sides to the center of the hole chip. Furthermore, when the concentration of microparticles in the mixture is appropriate, a 'Monolayer & Ring' structure may be formed, in which a single layer of microparticles is formed in the center of the mixture. Additionally, when the concentration of microparticles in the mixture is relatively high, a 'Multilayer' structure may be formed, in which a multilayer of microparticles is formed in the center of the mixture.

[0050] As described above, the structure of microparticles formed according to the relationship between the microparticle concentration and the volume of the mixture is classified as follows.

[0051] Referring to Fig. 6, the graph in Fig. 6 shows the structural form of microparticles according to the concentration of microparticles on the horizontal axis and the volume of the mixture on the vertical axis.

[0052] Referring to the graph in Fig. 6, a 'Monolayer & Ring' structure can be formed when the concentration of microparticles is approximately 600 (hereinafter, units are in Fig.) and the volume of the mixture is approximately 600 to 800. Additionally, it can be seen that a 'Monolayer & Ring' structure is formed when the volume of the mixture is approximately 600 and the concentration of microparticles is approximately 600 to 800. The conditions under which other 'Burst', 'Ring', and 'Multilayer' structures are formed can be confirmed by referring to Fig. 5.

[0054] Next, a step (step 105) of measuring the composition of microparticles by irradiating the formed microparticle monolayer with fluorescence can be performed.

[0055] Referring to Fig. 7, particle images can be obtained from various materials by irradiating with fluorescence, and the signal-to-noise (SN) ratio according to various materials can also be verified. In particular, viruses and antibodies can be qualitatively or quantitatively measured by measuring the intensity of fluorescent substances (such as fluorescently labeled viruses and antibodies) attached to the surface of microparticles. Generally, to optically measure particles, they must be fixed on the surface of a substrate, such as glass or plastic, or inside (e.g., a channel). If the material (substrate) on which the particles are fixed emits autofluorescence with a wavelength similar to the particle fluorescence, the signal sensitivity of the particle to be measured decreases. In other words, the background signal value relative to the signal increases. Even in transparent glass or plastic, background signals exist. The proposed air-suspended particle monolayer structure does not interfere with background signals other than air, so a high-sensitivity signal can be obtained from the particle itself.

[0057] Although various embodiments of the present invention have been presented and described in the above description, the present invention is not necessarily limited thereto, and those skilled in the art will readily understand that various substitutions, modifications, and changes are possible within the scope of the technical concept of the present invention. Explanation of the symbols

[0058] 201: Hole chip body 202: Particle hole 203 : Microparticles

Claims

Claim 1 A method for fabricating a microparticle-based monolayer structure comprising: a step of creating a hole chip body having a particle hole formed therein; a step of injecting a mixture of a plurality of microparticles and a suspension into the particle hole; a step of drying the mixture; and a step of drying the suspension in the mixture to form a monolayer of a plurality of microparticles, wherein the step of forming the monolayer comprises a step of irradiating the formed microparticle monolayer with fluorescence to measure the components of the microparticles. Claim 2 A method for fabricating a microparticle-based single-layer structure according to claim 1, wherein the particle hole is provided in an inverted truncated cone shape such that the diameter of the upper surface is longer than the diameter of the lower surface. Claim 3 delete Claim 4 A method for fabricating a microparticle-based monolayer structure according to claim 2, wherein the particle holes are formed such that the diameter of the upper surface is 1 mm and the diameter of the lower surface is 0.6 mm, and the thickness between the upper surface and the lower surface is 2 mm. Claim 5 A method for fabricating a microparticle-based monolayer structure according to claim 4, wherein the particle hole is formed such that the angle between the perpendicular of the lower end of the particle hole and the side of the particle hole is 5.7 to 5.8 degrees.

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