KR20200042305A - Chip for analyzing fluids - Google Patents

Abstract

The present invention relates to a chip for analyzing a fluid. The chip for analyzing a fluid includes a fluid channel through which a fluid moves, so the movement of a subject material to be detected, contained in the fluid, may be observed or the subject material may be counted. The chip for analyzing a fluid includes: an upper plate formed with an inlet and outlet; and a lower plate disposed under the upper plate and having a plurality of cell-receiving grooves capable of receiving a fluid. According to the present invention, a plurality of cell-receiving grooves are formed on the lower plate and a plurality of air channels forming air walls are formed on both sides of the fluid channel. Accordingly, it is possible to observe the movement of a subject material to be detected, contained in the fluid, and to count the subject material. In addition, it is possible to stabilize the flow of the fluid, thereby preventing generation of air bubbles in the fluid, and to quantify the amount of the fluid in the fluid channel, thereby enabling precise fluid analysis.

Description

Chip for fluid analysis {CHIP FOR ANALYZING FLUIDS}

The present invention relates to a fluid analysis chip, and more particularly, to a fluid analysis chip capable of observing and counting cells and the like contained in a fluid sample.

In general, the analysis of fluid samples has been widely used not only in the chemical and biotechnology fields, but also in the diagnosis field through analysis of blood and body fluids collected from patients. In recent years, various types of miniaturized analysis and diagnostic equipment and technologies have been developed to perform the analysis of the fluid sample more conveniently and efficiently.

In particular, the lab-on-a-chip technology is a small-sized chip that utilizes microfluidics techniques to perform various experimental procedures performed in the laboratory, such as separation, purification, mixing, labeling, analysis, and cleaning of samples. Refers to the technology implemented on the platform.

In connection with this lab-on-a-chip technology, industries such as developing DNA analysis devices for portable personal identification that can perform the process from DNA extraction to analysis on a chip at a time are being developed. Its use is actively being made in the field.

In addition, in the field of in vitro diagnostics, a portable diagnostic tool, that is, a point of care testing (POCT) field that can be easily performed by an individual in the field for complex and precise examinations such as blood and body fluids performed in a hospital or a laboratory. Research has also been actively conducted.

POCT refers to a field diagnosis technology that can easily diagnose a disease in an emergency room, an operating room, or a general home, and is also an area where the need and demand for the aging and welfare society continue to increase. Currently, the diagnostic tool for measuring blood sugar occupies the mainstream of the market, but as the demand for POCT increases, the demand for a diagnostic tool for analyzing various biological substances such as lactic acid, cholesterol, urea and infectious pathogens is also rapidly increasing. .

These analysis or diagnostic techniques generally detect whether a fluid reacts with an antibody protein immobilized inside the chip or other samples while moving various fluid samples through a micro channel formed in the chip by various detection methods, It is done by analysis.

Lab-on-a-chip related to such detection and analysis can be used for various experiments performed in the laboratory, such as separation, purification, mixing, labeling, analysis, and washing of samples. It means implementing on a chip of size. In the design of the lab-on-a-chip, micro-fluidics and micro-LHS technologies are mainly used. In addition, in manufacturing a chip structure that implements microfluidics and microfluidic manipulation systems, chips are formed on the chip by using a semiconductor circuit design technology to form a fine channel inside the chip.

The plastic microchip used for the POCT or the lab-on-a-chip described above is polyethylene derivatives such as polycarbonate (PC), polystyrene (PS), polypropylene (PP), polyethylene terephthalate (PET), polymethyl meta It is made of acrylate (PMMA), or an acrylic-based plastic type material, and is used for disposable use.

The plastic microchip is manufactured by bonding the upper substrate and the lower substrate, and is provided with a space for a sample filling part of a predetermined height to fill a sample between the bonded upper substrate and the lower substrate, or a microstructure.

Since the plastic microchip must be precisely manufactured so that the sample filling section space has a volume of several μl to hundreds of μl, the plastic microchip is perfect only when the sample filling section space or the upper substrate and the lower substrate including the microstructure are precisely and accurately bonded. Can function.

However, as the conventional plastic microchip is formed in a structure capable of flowing in one direction along the inner wall of the upper substrate or the lower substrate, the flow rate of the sample is not uniform, as well as the sample during the flow of the sample There was a problem in that it was impossible to accurately analyze the amount of sample in the receiving space because air bubbles were generated in the chamber.

In addition, in the conventional plastic microchip, a fine grid having a line width of 0.5 to 10 μm capable of accommodating cells on one surface is formed for counting cells.

As such, a fine grid having a line width of 0.5 to 10 μm is imprinted with a pattern on a silicon wafer through semiconductor processing, and is plated with nickel, cobalt, iron, etc. on this mold to form a template for plastic injection (mirror plate steel core). Is produced.

However, a template (mirrored iron core) produced to form a fine grid having a line width of 0.5 to 10 μm transfers a substrate produced at a high cost of semiconductor processing, and has a thickness of 1 mm or less and a soft material due to the nature of plating. As it is limited, an expensive manufacturing cost is required, and there is a problem in that damage caused by stamping and resin infiltrate and bend when used.

In addition, the above-described template has a problem in that, due to heavy wear, frequent replacement is required when forming a grid and high pressure cannot be applied to increase production time.

Patent Publication No. 10-2011-0075448

The present invention has been devised to solve the above problems, and the object of the present invention is to form a micropattern directly on a mold core using an ultra-short laser, thereby forming embossed projections of a lattice structure, thereby forming a fluid sample. It is to provide a chip for fluid analysis capable of accurately observing and counting the movement of an object to be detected and quantifying the amount of fluid and allowing accurate fluid analysis by allowing the fluid to move at a uniform speed in the fluid channel. .

The problems of the present invention are not limited to the problems mentioned above, and other problems that are not mentioned will be clearly understood by those skilled in the art from the following description.

The chip for fluid analysis according to an embodiment of the present invention for solving the above-mentioned problem forms a fluid channel in which a fluid is movable, thereby observing the movement of the detection target material contained in the fluid or counting the detection target material A fluid analysis chip comprising: an upper plate on which an inlet and an outlet are formed; And a lower plate disposed on the lower side of the upper plate and having a plurality of cell receiving grooves capable of receiving the fluid on the upper surface.

The lower plate may include an embossed protrusion protruding from the upper surface of the lower plate to a predetermined length to form a lattice-like structure, and forming the plurality of cell receiving grooves inside.

The plurality of cell receiving grooves may be divided into a plurality of cell receiving regions according to the size of a single cell receiving groove.

The embossed protrusion may be formed in a structure in which the height gradually increases or decreases along at least one of the direction of movement of the fluid and the width of the lower plate.

The end of the embossed projection may be formed in a curved or inclined structure.

The embossed protrusion may be formed in a wedge structure in which the width of the cross section gradually narrows toward the end from the upper surface of the lower plate.

At the end of the embossed projection, a fine projection protruding from the end of the embossed projection to a predetermined length may be further formed.

Air channels forming air-walls for guiding the flow of the fluid introduced into the fluid channels may be further formed on both sides of the fluid channels.

The embossed protrusion may be formed on the upper surface of the lower plate using a mold having a fine pattern formed on the surface through femtosecond laser processing.

The ratio of the line width and the height of the embossed projection may be formed in a size of 1: 0.1 to 1: 2.

The line width of the embossed protrusions may be formed in a size of 1 to 3 μm, and the height of the embossed protrusions may be formed in a size of 0.5 to 2 μm.

According to an embodiment of the present invention, by forming a plurality of cell receiving grooves on the lower plate and a plurality of air channels forming air walls on both sides of the fluid channel, the mobility of the detection target substance contained in the fluid is observed or , It is possible to count the substance to be detected, and the flow of the fluid is stabilized to prevent the generation of bubbles in the fluid, and furthermore, the amount of fluid in the fluid channel is quantified to enable accurate fluid analysis.

In addition, by forming a plurality of cell receiving grooves through embossed protrusions forming a lattice-like structure, separating the detection target material accommodated in the cell receiving grooves from the external space, mixing of the external fluid into the detection target material received in the cell receiving grooves, It is possible to prevent the detection target material received in the cell receiving groove from being lost to the outside.

In addition, by forming the end of the embossed projection in a curved or inclined structure so that the detection target material is located on the surface of the embossed projection, the target material is accommodated in a plurality of cells by moving to one side or the other along the surface of the end. By blocking the remaining on the boundary between the grooves, it is possible to stably partition the detection target substance, thereby enabling accurate observation of cells.

1 is a perspective view showing a chip for fluid analysis according to an embodiment of the present invention.
2 is a cross-sectional view taken along line II-II of FIG. 1.
3 is a cross-sectional view taken along line III-III of FIG. 1.
4 is a plan view showing a chip for fluid analysis according to an embodiment of the present invention.
5 is a perspective view showing a top plate of a fluid analysis chip according to an embodiment of the present invention.
6 is an enlarged view showing a portion “A” of FIG. 3.
7 is an enlarged view showing a portion “B” of FIG. 2.
8 is a perspective view showing a lower plate of a chip for fluid analysis according to an embodiment of the present invention.
9 is an enlarged view showing a portion “C” of FIG. 4.
10 to 11 are cross-sectional views schematically showing various embodiments of embossed projections of a chip for fluid analysis according to an embodiment of the present invention.
12 to 15 are views illustrating a change in the flow of a sample according to a change in line width and height of embossed projections when 2 μl of fluid per second flows in one direction in a microfluidic line having a fluid channel height of 100 μm.
16 to 19 are diagrams showing the speed distribution based on the X-axis direction.
20 is a chart showing the height of the turbulence (turbulence) according to the change in the width and height of the embossed projection.
21 to 23 are views showing various embodiments of a plurality of cell receiving regions.

Hereinafter, various embodiments will be described in more detail with reference to the accompanying drawings. The embodiments described herein can be variously modified. Certain embodiments are depicted in the drawings and may be described in detail in the detailed description. However, the specific embodiments disclosed in the accompanying drawings are only for easy understanding of various embodiments. Accordingly, it is to be understood that the technical spirit is not limited by the specific embodiments disclosed in the accompanying drawings, and includes all equivalents or substitutes included in the spirit and technical scope of the invention.

Terms including ordinal numbers such as first and second may be used to describe various components, but these components are not limited by the above-described terms. The above-mentioned terms are used only for the purpose of distinguishing one component from other components.

In this specification, terms such as "comprises" or "have" are intended to indicate that there are features, numbers, steps, operations, components, parts, or combinations thereof described in the specification, and one or more other features. It should be understood that the existence or addition possibilities of fields or numbers, steps, operations, components, parts or combinations thereof are not excluded in advance. When an element is said to be "connected" or "connected" to another component, it is understood that other components may be directly connected to or connected to the other component, but other components may exist in the middle. It should be. On the other hand, when a component is said to be "directly connected" or "directly connected" to another component, it should be understood that no other component exists in the middle.

On the other hand, "module" or "unit" for a component used in the present specification performs at least one function or operation. And, the "module" or "unit" may perform a function or operation by hardware, software, or a combination of hardware and software. Also, a plurality of “modules” or a plurality of “parts” may be integrated into at least one module, excluding “modules” or “parts” that must be performed on specific hardware or performed on at least one processor. Singular expressions include plural expressions unless the context clearly indicates otherwise.

In addition, in describing the present invention, when it is determined that detailed descriptions of related known functions or configurations may unnecessarily obscure the subject matter of the present invention, detailed descriptions thereof are abbreviated or omitted.

1 is a perspective view showing a chip 1 for fluid analysis according to an embodiment of the present invention, and FIG. 2 is a cross-sectional view taken along line II-II of FIG. 1.

1 and 2, the fluid analysis chip 1 according to an embodiment of the present invention (hereinafter referred to as the 'fluid analysis chip 1)' is a fluid channel (C1) and the fluid can be moved therein By forming an air channel (C2) that guides the flow of the fluid, the movement of the detection target material contained in the fluid can be observed, the detection target material can be counted, and the fluid is moved at a uniform speed to generate bubbles in the fluid. In addition to suppressing, it is possible to quantify the amount of fluid in the fluid channel (C1). Here, the term “fluid” may mean a liquid or gas or a fluid sample that can freely flow in the fluid channel C1 by maintaining an intermediate state thereof. For example, the fluid may be cell lysate, whole blood, plasma, serum, saliva, ocular fluid, cerebrospinal fluid, sweat, urine, milk, ascites fluid, synovial fluid, and peritoneal fluid, but is not limited thereto. In addition, the detection target substance such as a cell or an antigen may be contained in the fluid. In addition, the term “channel” may mean a predetermined fluid movement space formed along the longitudinal direction inside the present fluid analysis chip 1. In addition, the motility of the detection target substance may be observed, or the count of the detection target substance may be performed using an analysis microscope equipped with an optical microscope or a CCD camera equipped with the present chip for fluid analysis 1.

In addition, the present fluid analysis chip 1 may be provided with at least two or more fluid analysis sections to simultaneously perform fluid analysis at a plurality of locations or to perform fluid analysis of different fluids separately.

4 is a plan view showing a chip 1 for fluid analysis according to an embodiment of the present invention.

Referring to FIG. 4, the fluid analysis chip 1 has a plurality of fluid analysis sections disposed opposite to each other along the longitudinal direction, and the plurality of fluid analysis sections are the first fluid analysis section T1 and the second fluid. It may include an analysis section (T2).

In addition, the present chip 1 for fluid analysis includes a top plate 10 and a bottom plate 20 that are stacked up and down to form a fluid channel C1 therein.

3 is a cross-sectional view taken along line III-III of FIG. 1, and FIG. 5 is a perspective view showing the top 10 of the fluid analysis chip 1 according to the embodiment of the present invention.

3 and 5, the top plate 10 is formed of a rectangular flat plate structure having a predetermined thickness. In addition, the upper plate 10 may be formed of a material such as a transparent plastic material or an acrylic material or glass so that the fluid flowing in the fluid channel C1 can be visually checked during fluid analysis.

In addition, an inlet 11 and an outlet 12 are formed in the top plate 10.

More specifically, the upper plate 10 is formed in a position opposite to the inlet 11 through which the fluid is injected and the inlet 11 along the longitudinal direction, when the fluid is introduced into the fluid channel C1, the fluid channel C1 ) To discharge the remaining air to smooth the flow of the fluid, and the outlet 12 through which the residual fluid is discharged may be formed. For example, the inlet 11 is formed in a circular or semi-circular shape so that the fluid can flow smoothly into the fluid channel (C1), it can be located on the upper portion of the fluid flow portion 22 formed on the lower plate 20 to be described later have. In addition, the outlet 12 is formed in a slit structure in which the size in the width direction is relatively larger than the size in the length direction so that proper air pressure can be maintained inside the fluid channel C1, and the lower plate described later ( 20) may be located in the upper portion of the depression groove (21) formed.

In addition, a guide surface 13 for guiding the fluid introduced through the inlet 11 to the fluid channel C1 may be formed on the top plate 10.

6 is an enlarged view showing a portion “A” of FIG. 3.

Referring to (a) of FIG. 6, the inner surface of the top plate 10 on which the inlet 11 is formed is in contact with the fluid that is introduced from the outside through the inlet 11, and a time difference is provided to guide the fluid to the fluid channel C1. The guide surface 13 may be formed. For example, the guide surface 13 may be formed in an inclined surface shape having a preset inclination angle with respect to the lower surface of the top plate 10.

Accordingly, the guide surface 13 prevents the fluid introduced into the inlet 11 from being directly dropped and scattered on the upper surface of the fluid flow part 22 to stably flow the fluid into the fluid channel C1.

In addition, a guide protrusion 14 may be further formed on the guide surface 13.

Referring to (b) of FIG. 6, the guide surface 13 protrudes from the surface of the guide surface 13 to a predetermined length so as to prevent fluid from remaining on the surface of the guide surface 13 and falls on the guide surface 13 Guide projections 14 for guiding the fluid to the fluid channel (C1) side may be formed. For example, a plurality of guide protrusions 14 are formed along the circumference of the guide surface 13, and are dropped in the vertical direction to the guide protrusions 14, so that the fluid contacting the surface flows toward the guide surface 13 and moves in a protruding direction. It can be formed in a wedge (wedge) structure that the width of the cross-section is narrowed along. In addition, the connecting portion between the guide projection 14 and the guide surface 13 may be curved to minimize the residual fluid.

In addition, the guide projection 14, the fluid moving toward the fluid channel (C1) along the surface of the guide projection 14 does not fall from the end of the guide projection 14, the lower surface of the top plate 10 by the surface tension To prevent it from being moved, it may be formed in a structure that protrudes more outward than the lower surface of the top plate 10. For example, the portion protruding outward from the guide protrusion 14 to the outside than the lower surface of the top plate 10 is formed in a form in which the width of the cross section gradually narrows toward the end so as to improve the drop rate of the fluid at the end, The end may be formed in a round hemisphere shape.

In addition, a support structure 15 may be formed on the lower surface of the top plate 10.

2, 4 and 5 (b), the support structure 15 is supported on the upper surface of the lower plate 20, is dissolved in the upper surface of the lower plate 20 to be bonded to the upper surface of the lower plate 20 You can.

More specifically, the support structure 15 is supported on the lower plate 20 to distribute the load acting in the vertical direction on the upper plate 10, a plurality of channels (C1, C2) inside the chip 1 for fluid analysis A boundary may be formed between the spaces outside the channel. In addition, the support structure 15 determines the height of the fluid channel (C1) formed between the upper plate 10 and the lower plate 20, sagging occurs in the upper plate 10, the upper plate 10 is the lower plate 20 In addition to preventing the phenomenon of being in close contact with, the size of the fluid channel C1 can be maintained in a constant state to maintain the fluid flow uniformly. For example, referring to FIG. 2, the height h1 of the support structure 15 may be formed to be larger than the height h2 of the embossed projection 24 to be described later. Accordingly, when the upper plate 10 is seated on the upper surface of the lower plate 20, a fluid channel C1 having a predetermined size may be formed between the embossed protrusion 24 and the lower surface of the upper plate 10.

In addition, the support structure 15 may include a support layer 151 and a solvent 152.

7 is an enlarged view showing a portion “B” of FIG. 2.

4 and 7, the support layer 151 protrudes from the lower surface of the upper plate 10 to a predetermined length and is supported on the upper surface of the lower plate 20, and between the upper plate 10 and the lower plate 20 on a plane. It may be formed in a structure surrounding the circumference of the formed fluid channel (C1).

Meanwhile, a diffusion surface 151a capable of diffusing the solvent 152 dissolved on the surface of the support layer 151 around the support layer 151 may be formed at a corner portion of the support layer 151. Accordingly, when the upper plate 10 and the lower plate 20 are joined, the solvent 152 leaked to the corner portion of the support layer 151 is evenly spread throughout the support layer 151 along the diffusion surface 151a, and the support layer 151 ) And the bonding performance of the lower plate 20 can be improved. For example, the diffusion surface 151a is formed in a curved structure at an edge portion of the support layer 151 as shown in FIG. 7 (a), or as shown in FIG. 7 (b), the edge of the support layer 151 It may be formed in an inclined structure on the site. However, the shape of the diffusion surface 151a is not necessarily limited to this, and can be changed to various structures within conditions that can implement the same function.

In addition, the support layer 151 may be formed in a structure in which the width of the cross section gradually decreases toward the protruding direction. Accordingly, the support layer 151 can minimize the contact with the lower plate 20 to simplify the structure and reduce the overall weight.

The solvent 152 is provided on the surface of the support layer 151, and when the upper plate 10 is stacked on the lower plate 20, it is dissolved in contact with the upper surface of the lower plate 20 to support the layer 151 and the lower plate 20. The upper surface of can be joined. For example, the solvent 152 may be applied as an organic solvent that dissolves when heat, ultrasound, or external force is applied, and then cures over a period of time. However, the support layer 151 is not necessarily bonded to the upper surface of the lower plate 20 through this method, and may be bonded through various bonding methods using thermal bonding, plasma, pressure, ultrasonic waves, and the like.

8 is a perspective view showing the lower plate 20 of the chip 1 for fluid analysis according to an embodiment of the present invention, FIG. 9 is an enlarged view showing a portion “C” of FIG. 4, and FIGS. 10 to 11 are It is a cross-sectional view schematically showing various embodiments of embossed protrusions 24 of the chip 1 for fluid analysis according to an embodiment of the invention.

4 and 8, the lower plate 20 is disposed on the lower side of the upper plate 10 and is formed in the shape of an outer shape corresponding to the upper plate 10, the same as the upper plate 10, or the upper plate 10 It is formed with a thicker thickness. In addition, the lower plate 20 may be formed of a material such as a transparent plastic material or an acrylic material or glass so that the fluid flowing in the fluid channel C1 can be visually checked during fluid analysis.

In addition, a plurality of support protrusions dispersing the load acting in the vertical direction on the chip 1 for fluid analysis by protruding at a predetermined length from the lower surface of the lower plate 20 to a predetermined length on the lower surface of the lower plate 20. 25 may be formed.

Also, referring to FIGS. 2 and 8 (a), the lower plate 20 receives a portion of the fluid that has passed through the fluid channel C1, and a recessed groove 21 that forms the air channel C2, and A fluid flow portion 22 through which fluid flows along one surface may be formed.

The recessed groove 21 is formed by being recessed to a predetermined depth along the vertical direction from the upper surface of the lower plate 20, and may be provided around the fluid flow part 22 to be described later. In addition, the recessed groove 21 may communicate with the fluid channel C1 when joining the upper plate 10 and the lower plate 20 to form air channels C2 on both sides of the fluid channel C1. The air channel C2 may form an air-wall inside to guide the flow of the fluid introduced into the fluid channel C1.

That is, the air channel (C2), when the fluid flows in the fluid channel (C1), the force acts in the direction of reducing the surface area of the whole by pulling water molecules to each other in the absence of a medium of solid, between the fluid and air Air walls may be formed on both sides of the fluid channel C1 so that the interface has a tension like a rubber band. Accordingly, the fluid flowing into the fluid channel C1 does not first move to both sides of the fluid channel C1 by the air wall, and the fluid flowing through the central portion of the fluid channel C1 is the side of the fluid channel C1. By maintaining a flow rate equal to the fluid flowing through, it is possible to prevent bubbles from occurring in the fluid. In addition, an accurate fluid analysis may be possible by quantifying the amount of fluid by uniformly filling the fluid in the entire fluid channel C1.

In addition, the air channel (C2) may serve as a guide in the flow of the fluid, as well as accepting a sample overflowing from the fluid channel (C1) (Overflow troughs) to quantify the sample in the fluid channel (C1).

On the other hand, in general, in order to maintain an error within 5% in a channel of 0.1 mm or less, a height adjustment of 0.005 mm is required. However, the plastic bonding method through the ultrasonic welding method has a problem in that a material has to be welded over a larger area in order to prevent a leak in a fluid, thereby causing a height change. So, in order to solve this, conventionally, a method of making a jaw that maintains the distance between the two plates without making plastic ultrasonic welding and infiltrating the liquid adhesive through the jaw was used. However, this method has a problem that the process is complicated and takes a long working time. Therefore, the present fluid analysis chip 1 serves as a guide for fluid through the above-described air channel C2 and quantifies a sample in the fluid channel C1 by receiving overflow samples through the fluid channel C1. As well as performing the role, the upper plate 10 and the lower plate 20 are not separated by a pressure difference and maintain a constant distance from each other, thereby minimizing the ultrasonic welding site and confining the liquid through ultrasonic welding. It can have a relatively thin thickness compared to the analytical chip, can significantly reduce the manufacturing time and cost of the product, and can simplify the manufacturing equipment.

For example, the depression depth of the depression groove 21 may be formed larger than the height of the support structure 15. Accordingly. The height h3 of the air channel C2 may be formed larger than the height h1 of the fluid channel C1, that is, the height h1 of the support structure 15.

The fluid flow portion 22 is formed inside the recessed groove 21 to form a plurality of cell receiving grooves 23 capable of receiving fluid on the upper surface, and is disposed opposite to the lower surface of the upper plate 10 to move the fluid The channel C1 can be formed.

In addition, the lower plate 20 may include embossed projections 24.

2 and 4, the embossed projection 24 protrudes from the upper surface of the lower plate 20 to a predetermined length along a vertical direction to form a lattice-like structure, and a plurality of cell receiving grooves 23 inside. Can form.

Here, the embossed protrusion 24 does not affect the flow of the sample, and the cells included in the sample do not span the end of the embossed protrusion 24 so that the dichotomous discrimination based on the embossed protrusion 24 can be objectively made. So, it can be formed in a size having a preset ratio of line width and height.

More specifically, the embossed projection 24 has a ratio of line width and height of 1:01 to 1: 2, and specifically, the embossed projection 24 has a line width of 1 to 3㎛. The height of the projection 24 may be formed to a size of 0.5 to 2㎛.

This will be described in more detail through the experimental results shown in FIGS. 12 to 20.

12 to 15 are experimental results showing changes in sample flow according to line width and height changes of embossed projections 24 when 2 μl of fluid per second flows in one direction in a microfluidic line having a fluid channel height of 100 μm. to be. Here, the embossed projections 24 are arranged in a plurality of spaced apart by 250 μm intervals along the X-axis direction, and each embossed projection 24 has a line width W of 1 μm, 3 μm, 5 μm, and 10 μm, 0.5 It is applied to heights (H) of μm, 2 μm, 4 μm and 6 μm, respectively. And, Figures 16 to 19 are experimental results showing the speed distribution based on the X-axis direction. Here, the non-red part means that a vortex is formed where the flow occurs in the opposite direction. In addition, Figure 20 is a chart showing the height of the vortex (turbulence) according to the width and height change of the embossed projection (24).

12 to 20, when the height of the embossed protrusion 24 is 4 μm or more, in all cases, a vortex having a height of 2 μm or more is generated at the rear of the embossed protrusion 24, and the height of the embossed protrusion 24 is When it is 2 μm or less, in all cases except for some cases (line widths of 5 μm and 10 μm), vortices having a height of 0.5 μm or less are generated at the rear of the embossed projection 24. That is, according to the experimental results, the vortex generated from the rear of the embossed projection 24 has a narrow line width of the embossed projection 24, and a larger height increases the size of the embossed projection 24 than the line width of the embossed projection 24. The height is more affected.

Therefore, based on the above-described experimental results, the maximum size of the embossed projection 24 that does not affect the flow of the fluid sample is a case where the height of the vortex is 0.5 μm or less, the height is 2 μm, and the line width is 3 μm, Accordingly, the embossed protrusion 24 may be applied in a size of 1 to 3 μm line width and 0.5 to 2 μm height.

In addition, the embossed protrusion 24 may be manufactured through an injection molding method using a mold having a fine pattern formed on its surface.

In more detail, the embossed protrusion 24 is formed of a lower plate through an injection molding method using a mold (injection core) in which a fine pattern of a lattice shape is formed on a surface through processing of micro-nano-level ultra-short lasers (femtoseconds 10-15). It can be formed on the upper surface. For reference, the fine pattern of the lattice shape, after polishing the surface of the mold, fixing the mold to the stage, placing the femtosecond regeneration amplifying device on the top of the mold fixed to the stage, and following the preset path of the mold Moving on the surface, irradiating a laser on the surface of the mold to form a fine pattern in a lattice shape, and performing post-treatment on the surface of the mold on which the fine pattern in a lattice shape is formed to remove deposits and burrs in the processing groove. It may be formed on the surface of the mold through the step of removing. Here, the femtosecond regeneration amplifier can perform laser processing from the pattern with the largest grid width to the pattern with the smallest grid width, and adjust the intensity and movement speed of the laser output according to each processing to control the surface of the mold. The width and depth of the processing groove formed in the can be adjusted.

Here, the injection core, which is imprinted with a fine pattern directly on the surface through ultra-short laser processing, is applied as a heat-treated steel material such as NAK55, NAK80, STAVAX, and has the advantage of being resistant to corrosion and not being caused by fine particles. In addition, the injection core has the advantages of resin penetration problem, shortened production time, and reduced manufacturing cost, and accordingly, it is possible to significantly reduce the production cost when producing the fluid analysis chip 1.

That is, the present fluid analysis chip 1 may form a lattice-shaped protruding structure on the upper surface of the lower plate 20 through the embossed protrusion 24, thereby forming a plurality of cell receiving grooves 23.

Meanwhile, the plurality of cell accommodating grooves 23 formed on the upper surface of the lower plate 20 may be divided into a plurality of cell accommodating regions according to the size of the plane of the single cell accommodating groove 23.

Referring to FIG. 9, the plurality of cell accommodating regions include a first cell accommodating region (A1) composed of a plurality of cell accommodating grooves 23 having the largest planar size among the plural cell accommodating grooves 23, and A second cell composed of a plurality of cell receiving grooves 23 formed in a size of 1/4 to 1/6 of the plane area of the single cell receiving groove 23 constituting the 1 cell receiving region A1 A plurality of cell receiving grooves (23) formed in a size of a flat area between 1/4 and 1/6 compared to the planar area of the single cell receiving grooves (23) constituting the receiving area (A2) and the second cell receiving area (A2) ) Is formed in a size of a flat area between 1/4 and 1/6 compared to the flat area of the single cell receiving groove 23 constituting the third cell receiving area A3 and the third cell receiving area A3. A fourth cell receiving region (A4) composed of a plurality of cell receiving grooves (23), and a fourth cell receiving region (A4) constituted It may include a fifth cell receiving region (A5) consisting of a plurality of cell receiving grooves 23 formed in a size of a flat area between 1/4 to 1/6 compared to the flat area of the single cell receiving groove 23 have. However, the plurality of cell receiving regions is not necessarily limited thereto, and the number of cell receiving regions may be increased or decreased as necessary.

In addition, the plurality of cell receiving regions may be formed in different sizes on the upper surface of the lower plate 20.

More specifically, the first cell receiving area (A1) is 84 to 86% of the total cell receiving area, the second cell receiving area (A2) is 10 to 12% of the total cell receiving area, and the third cell receiving area (A3) Is 1 to 2% of the total receiving area, the fourth cell receiving area (A4) is 0.5 to 1% of the total receiving area, and the fifth cell receiving area (A5) can occupy 0.1 to 0.5% of the total receiving area. . Here, the fifth cell accommodating region (A5) is disposed in the center of the entire cell accommodating region, the fourth cell accommodating region (A4) is cross-arranged around the fifth cell accommodating region (A5), and the third cell accommodating region is (A3) may be disposed between the cross-arranged fourth cell receiving region (A4). Through this, the fifth cell accommodating region (A5), the fourth cell accommodating region (A4) and the third cell accommodating region (A3) are the size of the single cell accommodating groove (23) constituting the first cell accommodating region (A1). A single receiving area of the same size can be formed. In addition, the second cell accommodating region A2 may be arranged to be cross-centered around the single accommodating region, and the first cell accommodating region A1 may be disposed around the second cell accommodating region A2.

However, the plurality of cell receiving regions are not necessarily limited thereto, and may be applied in various sizes and shapes as illustrated in FIGS. 21 to 23.

Meanwhile, the embossed protrusions 24 forming the plurality of cell accommodating grooves 23 may be formed at the same height as a whole or may be formed at different heights depending on the receiving area.

In addition, the embossed protrusion 24 may be formed in a structure in which the height gradually increases or decreases along at least one of the direction of the movement of the fluid and the width of the lower plate 20.

More specifically, the embossed projection 24 is formed in a structure in which the height is gradually increased along the direction of movement of the fluid as shown in Figure 10 (a), or as shown in Figure 10 (b) of the fluid It may be formed in a structure in which the height gradually decreases along the moving direction. In addition, although not shown in the drawing, the embossed projection 24 is formed to form a concavo-convex structure such as a waveform along the direction of movement of the fluid or the width of the lower plate 20, or the outer side from the center along the width direction of the lower plate 20 It may be formed in a half-type (harp) structure, the height of which gradually increases toward the. However, the embossed projection 24 is not necessarily limited to this, and may be changed and applied to various structures as necessary.

In addition, the embossed protrusion 24 may be formed in a structure capable of guiding the detection target material located on the surface to one side or the other side.

In more detail, the end of the embossed protrusion 24 may be formed in a curved structure to guide the detection target material seated on the surface to one side or the other side, as shown in FIG. 11A. In addition, although not shown in the drawing, the end of the embossed projection 24 may be formed in a structure of an inclined surface. In addition, the end of the embossed projection 24 may be formed in a structure that can guide the detection target material seated on the surface in only one direction.

In addition, as shown in (b) of FIG. 11, the embossed protrusion 24 gradually decreases in width of the cross-section toward the end from the upper surface of the lower plate 20 so as to minimize contact with the detection target material seated at the end. The paper may be formed in an oval-shaped wedge structure.

In addition, as shown in Fig. 11 (c), the end portion of the embossed projection 24 is preset in the vertical direction from the end of the embossed projection 24 formed in a curved shape so that the detection target material can be blocked. A fine protrusion 241 protruding to a length may be further formed. For example, the fine protrusions 241 may be formed with a wedge structure in which the width of the cross section gradually narrows toward the end, and may be formed with a smaller width and height than the embossed protrusion 24.

Thus, according to the embodiment of the present invention, by forming a plurality of cell receiving grooves 23 on the lower plate 20, by forming a plurality of air channels (C2) forming air walls on both sides of the fluid channel (C1) , It is possible to observe the motility of the substance to be detected contained in the fluid, or to count the substance to be detected, the flow of the fluid is stabilized to prevent the generation of bubbles in the fluid, and further, the amount of fluid in the fluid channel (C1) is quantified As such, accurate fluid analysis may be possible.

In addition, by forming a plurality of cell receiving grooves 23 through the embossed protrusions 24 forming a lattice-like structure, the detection target material accommodated in the cell receiving groove 23 is isolated from the external space, and the cell receiving groove 23 It is possible to prevent the incorporation of an external fluid into the detection target substance accommodated in, or the detection target substance accommodated in the cell receiving groove 23 to the outside.

In addition, by forming the end of the embossed protrusion 24 in a structure of a curved surface or an inclined surface, when the detection target material is located on the surface of the embossed protrusion 24, the object to be detected is moved to one side or the other along the surface of the end portion. The substance to be detected can be stably partitioned by blocking the substance from remaining at the boundary between the plurality of cell accommodating grooves 23, thereby enabling accurate observation of cells.

In the above, preferred embodiments of the present invention have been illustrated and described, but the present invention is not limited to the specific embodiments described above, and it is usually in the technical field to which the present invention belongs without departing from the gist of the present invention claimed in the claims. It is of course possible to perform various modifications by a person having knowledge of, and these modifications should not be individually understood from the technical idea or prospect of the present invention.

1. Fluid analysis chip
10. Tops
11. Inlet
12. Outlet
13. Guide surface
14. Guide projection
15. Support structure
151. Support layer
151a. Diffuser
152. Solvent
20. Bottom
21. Depressed Home
22. Fluid flow
23. Cell receiving groove
24. Embossed projection
241.
25. Protrusion
C1. Fluid channel
C2. Air channel

Claims (11)

A fluid analysis chip capable of observing the movement of a substance to be detected contained in the fluid by forming a fluid channel in which the fluid is movable, or counting the substance to be detected,
An upper plate on which an inlet and an outlet are formed; And
A lower plate disposed on the lower side of the upper plate and having a plurality of cell receiving grooves capable of receiving the fluid on the upper surface;
Chip for fluid analysis comprising a. According to claim 1,
The lower plate,
A fluid analysis chip including an embossed protrusion protruding from a top surface of the lower plate to a predetermined length to form a lattice-like structure, and forming the plurality of cell receiving grooves inside. According to claim 2,
The plurality of cell receiving grooves are fluid analysis chips that are divided into a plurality of cell receiving regions according to the size of a single cell receiving groove. According to claim 3,
The embossed projection is a fluid analysis chip formed in a structure in which the height gradually increases or decreases along at least one of the direction of movement of the fluid and the width of the lower plate. According to claim 2,
The end of the embossed projection is a fluid analysis chip formed of a curved or inclined structure. The method of claim 5,
The embossed projection,
A chip for fluid analysis formed from a wedge structure in which a width of a cross section gradually narrows from an upper surface of the lower plate toward an end. The method of claim 5,
At the end of the embossed projection, the fluid analysis chip is further formed a fine projection protruding from the end of the embossed to a predetermined length. According to claim 1,
A chip for fluid analysis wherein air channels forming air-walls for guiding the flow of the fluid introduced into the fluid channels are formed on both sides of the fluid channels. According to claim 2,
The embossed protrusion is a fluid analysis chip formed on the upper surface of the lower plate using a mold having a fine pattern formed on the surface through femtosecond laser processing. According to claim 2,
The ratio of the line width and height of the embossed projection is a fluid analysis chip formed to a size of 1: 0.1 ~ 1: 2. The method of claim 10,
The line width of the embossed projection is formed in a size of 1 to 3㎛, the height of the embossed projection is a fluid analysis chip formed in a size of 0.5 to 2㎛.

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