KR20170099785A - Circulating tumor cell diagnosis method using the patch and device using the same - Google Patents

Abstract

One embodiment of the present invention may provide a diagnostic method for diagnosing cancer cells contained in a sample by means of a patch provided as a networked gel having micro-cavities, wherein the method comprises the following steps: placing the sample on a plate; and providing a reagent stored in the patch to the plate by means of the patch in which a reagent used for detecting cancer is stored.

Description

TECHNICAL FIELD [0001] The present invention relates to a CTC diagnosis method and apparatus using a patch,

The present invention relates to a CTC diagnostic method and apparatus using a patch, and more particularly, to a CTC diagnostic method and apparatus using a patch for detecting cancer cells floating in blood and performing cancer diagnosis.

The CTC test (circulating tumor cell diagnosis) is intended to detect blood circulating cancer cells floating in the blood, and various diagnostic methods for blood can be used.

In the case of conventional cancer diagnosis, various diagnoses were performed using a biopsy of a part of the tissue of the subject to be diagnosed. In general, the biopsy obtained through surgery sometimes causes the subject to be rejected. These complex procedures and psychological burdens made it more difficult to find the early stages of cancer.

The CTC test is a noninvasive test that can be used to diagnose cancer using the blood collected from the subject's blood. Therefore, a simple cancer diagnosis can be made without a procedure like surgery. In addition, the CTC test has the advantage of being able to predict whether or not a cancer has arisen, and research has been conducted more actively.

In the conventional CTC test, general immunodiagnosis was performed on blood, and it was confirmed whether or not cancer occurred. For example, in the process of detecting an antigen to be diagnosed by injecting an antibody into blood, it is essential to perform a washing process of washing a plate or the like by pouring a large amount of washing solution to remove unbound antibodies or other elements that interfere with detection . As a result, a large amount of wash solution is wasted, and there is a problem that the binding of the antibody and the antigen is separated again by washing.

Therefore, the CTC test requires measures to improve the accuracy of diagnosis while minimizing the amount of reagent used for diagnosis.

An object of the present invention is to provide a patch capable of storing a substance.

An object of the present invention is to provide a patch capable of providing a reaction space of a substance.

An object of the present invention is to provide a patch capable of delivering a substance.

An object of the present invention is to provide a patch capable of absorbing a substance.

An object of the present invention is to provide a patch capable of providing an environment.

An object of the present invention is to provide a CTC inspection method using a patch.

According to one aspect of the present invention, there is provided a method of diagnosing cancer cells contained in a specimen using a patch provided in a gel-like net structure forming a micro-cavity, Placing the sample; And providing the reagent stored in the patch to the plate using the patch that stores the reagent used to detect the cancer.

According to another aspect of the present application, there is provided a method of diagnosing cancer cells contained in a specimen using a patch provided in a gel form of a net structure forming a micro-cavity, Placing the sample; Providing a reagent stored in the first patch to the plate using a first patch that stores a first reagent used to detect cancer; And providing a reagent stored in the second patch to the plate using a second patch storing a second reagent used for detecting the arm.

According to another aspect of the present application, there is provided a method of detecting a cancer, comprising the steps of: providing a gel-like net structure forming a micro-cavity, using a patch storing a reagent used for detecting cancer; A relative movement regulator for relatively moving the patch and the patch in a region where the specimen is provided to provide the reagent stored in the patch to the specimen; And an image acquiring unit for acquiring an image of the specimen for the cancer diagnosis.

According to the present invention, storage, transmission, and absorption of a substance can be easily performed.

According to the present invention, it is possible to provide a reaction region of a substance or to provide a predetermined environment to a target region.

According to the present invention, the delivery and absorption of a substance can be appropriately controlled by using a patch, whereby the amount of reagent used for diagnosis can be remarkably reduced.

According to the present invention, more accurate diagnosis results can be obtained by performing a plurality of diagnostic methods.

The effects of the present invention are not limited to the above-mentioned effects, and the effects not mentioned can be clearly understood by those skilled in the art from the present specification and the accompanying drawings.

1 shows an example of a patch according to the present application in detail.
2 shows an example of a patch according to the present application in detail.
FIG. 3 illustrates providing a reaction space as an example of the function of the patch according to the present application.
Fig. 4 shows the provision of a reaction space as an example of the function of the patch according to the present application.
FIG. 5 shows the transfer of material as an example of the function of the patch according to the present application.
FIG. 6 shows the transfer of a substance as an example of the function of the patch according to the present application.
FIG. 7 shows the transfer of material as an example of the function of the patch according to the present application.
FIG. 8 shows the transfer of material as an example of the function of the patch according to the present application.
FIG. 9 shows the transfer of material as an example of the function of the patch according to the present application.
FIG. 10 shows the transfer of material as an example of the function of the patch according to the present application.
Fig. 11 shows the transfer of a substance as an example of the function of the patch according to the present application.
FIG. 12 shows the transfer of a substance as an example of the function of the patch according to the present application.
Fig. 13 shows the delivery of a substance as an example of the function of the patch according to the present application.
Fig. 14 shows absorption of a substance as an example of the function of the patch according to the present application.
Fig. 15 shows absorption of a substance as an example of the function of the patch according to the present application.
Fig. 16 shows absorption of a substance as an example of the function of the patch according to the present application.
Fig. 17 shows absorption of a substance as an example of the function of the patch according to the present application.
FIG. 18 shows absorption of a substance as an example of the function of the patch according to the present application.
Fig. 19 shows absorption of a substance as an example of the function of the patch according to the present application.
Fig. 20 shows absorption of a substance as an example of the function of the patch according to the present application.
FIG. 21 shows absorption of a substance as an example of the function of the patch according to the present application.
Fig. 22 shows absorption of a substance as an example of the function of the patch according to the present application.
Fig. 23 illustrates providing an environment as an example of the function of the patch according to the present application.
Fig. 24 illustrates providing an environment as an example of the function of the patch according to the present application.
FIG. 25 illustrates providing an environment as an example of the function of the patch according to the present application.
26 shows an example of the patch according to the present application, in which absorption and transmission of the substance are performed.
27 shows an example of a patch according to the present application, in which absorption and transmission of a substance are performed.
Fig. 28 shows an example of the patch according to the present application, in which absorption and transfer of a substance are performed. Fig.
29 shows an example of a patch according to the present application, in which absorption and transmission of a substance are performed.
30 shows an example of a patch according to the present application, in which absorption and transmission of a substance are performed.
Fig. 31 shows an example of a patch according to the present application, in which absorption, transmission, and provision of environment are performed.
FIG. 32 shows an example of a patch according to the present application, in which the absorption, transmission, and provision of environment are performed.
FIG. 33 shows an embodiment of a patch according to the present application, showing an example of a plurality of patches.
34 illustrates an embodiment of a patch having a plurality of patches and a plurality of target regions, according to one embodiment of the patch according to the present application.
FIG. 35 is a diagram for explaining the morphological diagnosis using the staining method in the cancer diagnosis according to the embodiment of the present application. FIG.
FIG. 36 is a diagram for explaining the morphological diagnosis by using a staining method using a plurality of stained samples in the cancer diagnosis according to the embodiment of the present application. FIG.
FIG. 37 is a diagram for explaining the morphological diagnosis using the DAPI staining method in cancer diagnosis according to one embodiment of the present application. FIG.
FIG. 38 is a diagram for explaining performing immunological diagnosis in cancer diagnosis according to one embodiment of the present application. FIG.
FIG. 39 is a diagram for explaining a method of detecting cancer using a substrate-enzyme reaction when immunodiagnosis is performed in cancer diagnosis according to an embodiment of the present application. FIG.
40 is a diagram for explaining a method of detecting cancer using a substrate-enzyme reaction when immunodiagnosis is performed in cancer diagnosis according to an embodiment of the present application;
FIG. 41 is a diagram for explaining a method of detecting cancer using a fluorescent substance when immunodiagnosis is performed in cancer diagnosis according to an embodiment of the present application. FIG.
42 is a view for explaining a method of performing immunodiagnosis using a plurality of types of antibodies in cancer diagnosis according to an embodiment of the present application.
FIG. 43 is a diagram for explaining a method of performing immunodiagnosis using the primary antibody and the secondary antibody in cancer diagnosis according to an embodiment of the present application. FIG.
44 is a diagram for explaining a method of performing immunodiagnosis using a first antibody coated on a plate and a second antibody provided on a specimen in cancer diagnosis according to an embodiment of the present application;
FIG. 45 is a diagram for explaining that cell culture is performed in cancer diagnosis according to one embodiment of the present application. FIG.
46 is a view for explaining a process of proliferating cells contained in a specimen in cancer diagnosis according to an embodiment of the present application.
47 is a diagram for explaining a process of proliferating cells contained in a specimen in cancer diagnosis according to an embodiment of the present application.
FIG. 48 is a view for explaining that a PCR process is performed in cancer diagnosis according to an embodiment of the present application. FIG.
FIG. 49 is a diagram for explaining a method of decomposing a cell membrane of a cell contained in a specimen by using a patch when performing a PCR process in cancer diagnosis according to an embodiment of the present application. FIG.
50 is a view for explaining that a PCR process is performed in cancer diagnosis according to an embodiment of the present application.
51 is a diagram for explaining a plurality of kinds of diagnostic methods for a specimen in cancer diagnosis according to an embodiment of the present application.
52 is a diagram for explaining a plurality of kinds of diagnostic methods for a specimen in cancer diagnosis according to an embodiment of the present application.
53 is a diagram for explaining a plurality of kinds of diagnostic methods for a specimen in cancer diagnosis according to an embodiment of the present application.
54 is a diagram for explaining a plurality of kinds of diagnostic methods for a specimen in cancer diagnosis according to an embodiment of the present application.
55 is a diagram for explaining a plurality of kinds of diagnostic methods for a specimen in cancer diagnosis according to an embodiment of the present application.
56 is a diagram for explaining a plurality of kinds of diagnostic methods for a specimen in cancer diagnosis according to an embodiment of the present application.
FIG. 57 is a diagram for explaining a plurality of types of diagnostic methods for a specimen in cancer diagnosis according to an embodiment of the present application. FIG.
58 is a diagram for explaining a plurality of kinds of diagnostic methods for a specimen in cancer diagnosis according to an embodiment of the present application.
59 is a block diagram of a diagnostic apparatus according to an embodiment of the present application.
FIG. 60 is a conceptual diagram showing an example in which the structure of the diagnostic apparatus is moved by a relative movement operation of the relative position adjusting unit according to an embodiment of the present application.

It is to be understood that the embodiments described herein are for illustrative purposes only and are not intended to limit the scope of the present application to the embodiments described herein, Are to be construed as including modifications or variations that do not depart from the spirit of the present application.

Although the terms used in the present specification have been selected based on the general functions of the present application, the present invention is not limited to the intention of the person skilled in the art to which the present invention belongs. . However, if a specific term is defined as an arbitrary meaning, the meaning of the term will be described separately. Accordingly, the terms used herein should be interpreted based on the actual meaning of the term rather than on the name of the term, and on the content throughout the description.

The drawings attached hereto are intended to illustrate the present application easily, and the shapes shown in the drawings may be exaggerated as necessary to facilitate understanding of the present application, and thus the present application is not limited to the drawings.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS In the following description, a detailed description of known configurations or functions related to the present application will be omitted when it is determined that the gist of the present application may be obscured.

According to one aspect of the present invention, there is provided a method of diagnosing cancer cells contained in a specimen using a patch provided in a gel-like net structure forming a micro-cavity, Placing the sample; And providing the reagent stored in the patch to the plate using the patch that stores the reagent used to detect the cancer.

The step of positioning the specimen on the plate may include providing the specimen as a monolayer on the plate.

The diagnostic method may be provided, wherein the specimen is blood.

The step of positioning the specimen on the plate may include fixing the specimen to the plate.

The reagent stored in the patch may be provided with a diagnostic method comprising an antibody that specifically reacts with the cancer cells.

Providing a substrate to the plate may be provided to identify antibodies bound to the cancer cells.

The plate may be provided with a diagnostic method in which an antibody specifically reactive with the cancer cells is applied.

The reagent stored in the patch may be provided with a diagnostic method including a staining reagent used for staining cells to stain the cancer cells.

The dyeing reagent may be provided with a diagnostic method for targeting at least one of the cell nucleus of the cell, the cytoplasm of the cell, and DNA distributed in the cell.

A diagnostic method comprising the step of adjusting the temperature of the specimen to form the reaction environment of the staining reagent may be provided.

The reagent stored in the patch may be provided with a diagnostic method including a nutrient reagent used for culturing the cells for culturing the cancer cells to diagnose the cancer.

Providing the reagent stored in the patch may be provided with a diagnostic method comprising the step of contacting the plate with the patch.

And obtaining an image of the plate on which the specimen is placed, for diagnosis of the cancer cells.

A diagnostic method may be provided wherein the image of the plate on which the specimen is located is a fluorescence image.

The reagent stored in the patch may be provided with a diagnostic method including a reagent used for cell membrane removal of cells to extract the DNA of the cancer cells.

According to another aspect of the present application, there is provided a method of diagnosing cancer cells contained in a specimen using a patch provided in a gel form of a net structure forming a micro-cavity, Placing the sample; Providing a reagent stored in the first patch to the plate using a first patch that stores a first reagent used to detect cancer; And providing a reagent stored in the second patch to the plate using a second patch storing a second reagent used for detecting the arm.

The step of providing the reagent stored in the first patch may be performed before the step of providing the reagent stored in the second patch.

The first reagent may include an antibody that specifically reacts with the cancer cells, and the second reagent may include an antibody that binds to an antibody that specifically reacts with the cancer cells.

Wherein the first reagent comprises an antibody that specifically reacts with the cancer cells, and the second reagent is a diagnostic reagent comprising a nutrient reagent used for culturing the cells for culturing the cancer cells to diagnose the cancer Can be provided.

Wherein the first reagent comprises an antibody that specifically reacts with the cancer cells,

The second reagent may be provided with a diagnostic method comprising a staining reagent used for staining cells to stain the cancer cells.

The first reagent may include an antibody that specifically reacts with the cancer cells, and the second reagent may include an antibody that specifically reacts with leukocytes.

An image is obtained for the specimen between the step of providing the reagent stored in the first patch and the step of providing the reagent stored in the second patch; A diagnostic method may be further provided.

The first reagent includes a reagent used for cell membrane removal of cells to extract the DNA of the cancer cells and the second reagent can be provided with a diagnostic method including a reagent used for a polymerase chain reaction have.

And adjusting the temperature of the specimen so as to induce the polymerase chain reaction.

According to another aspect of the present application, there is provided a method of detecting a cancer, comprising the steps of: providing a gel-like net structure forming a micro-cavity, using a patch storing a reagent used for detecting cancer; A relative movement regulator for relatively moving the patch and the patch in a region where the specimen is provided to provide the reagent stored in the patch to the specimen; And an image acquiring unit for acquiring an image of the specimen for the cancer diagnosis.

And a temperature controller for controlling the temperature of the specimen.

1. Patch

Significance of the 1.1 patch

The present application discloses a patch for managing a liquid substance.

The liquid material may refer to a material that is in a liquid state as a flowable material.

The liquid material may be a single component material having a liquidity. Alternatively, the liquid material may be a mixture comprising a plurality of ingredients.

When the liquid substance is a single component substance, the liquid substance may be a substance consisting of a single element or a compound including a plurality of chemical elements.

When the liquid substance is a mixture, some of the substances of the plural components may function as a solvent and others may function as a solute. That is, the mixture may be a solution.

On the other hand, the plural component materials constituting the mixture can be uniformly distributed. Alternatively, the mixture comprising the multiple component materials may be a homogeneously mixed mixture.

The multi-component material may include a solvent and a material that is not dissolved in the solvent and is uniformly distributed.

On the other hand, some of the substances of the plural components may be non-uniformly distributed. It is also possible that the non-uniformly distributed material comprises a particle component that is non-uniformly distributed in the solvent. At this time, the nonuniformly distributed particle component may be a solid phase.

For example, the material that can be handled using the patch may be 1) a single component liquid, 2) a solution or 3) a colloid state, and 4) the solid particles may be unevenly distributed It may be in a state where

Hereinafter, the patch according to the present application will be described in more detail.

The general nature of 1.2 patches

1.2.1  Configuration

1 and 2 are views showing an example of a patch according to the present application. Hereinafter, a patch according to the present application will be described with reference to Figs. 1 and 2. Fig.

Referring to Fig. 1, the patch PA according to the present application may comprise a net structure (NS) and a liquid substance.

Here, the liquid material can be considered as divided into a base material (BS) and an additive material (AS).

Also, the patch PA may be a gel type. The patch PA may be realized as a gel-like structure in which colloidal molecules are bonded to form a net structure.

The patch PA according to the present application may include a three-dimensional net structure (NS) as a structure for handling the liquid material SB. The net structure NS may be a solid structure that is continuously distributed. The mesh structure NS may have a net-like mesh structure in which a plurality of fine threads are intertwined. However, the net structure NS is not limited to a mesh-like net shape, but may be embodied as any three-dimensional matrix formed by connecting a plurality of microstructures. For example, the net structure NS may be a skeleton containing a plurality of micro-cavities. In other words, the net structure NS can form a plurality of microcavities MC.

2 shows the structure of another patch according to an embodiment of the present application. Referring to FIG. 2, the net structure of the patch PA may have a sponge structure SS. At this time, the net structure of the sponge structure SS may include a plurality of fine holes MH. Hereinafter, the micropores and the microcavities MC can be used in combination with each other, and unless otherwise stated, the microcavities MC are defined to include the concept of micropores (MH).

In addition, the net structure NS may have a regular or irregular pattern. Furthermore, the net structure NS may include both a region having a regular pattern and a region having an irregular pattern.

The density of the net structure NS may have a value within a predetermined range. Preferably, the predetermined range may be determined to the extent that the shape of the liquid material SB captured by the patch PA is maintained in a shape corresponding to the patch PA. The density may be defined as a degree of compactness of the net structure NS or a mass ratio, a volume ratio, etc. occupied by the net structure NS in the patch.

The patch according to the present application can handle the liquid substance SB by having a three-dimensional net structure.

The patch PA according to the present application may comprise a liquid substance SB and the liquid substance SB contained in the patch PA may be in the form of the net structure NS of the patch PA The fluidity of the liquid material SB can be limited.

The liquid material SB can freely flow in the net structure NS. In other words, the liquid material SB is located in a plurality of microcavities formed by the net structure NS. Alternating currents of the liquid materials SB may occur between adjacent microcavities. At this time, the liquid material SB may exist in a form permeating the frame structure forming the net structure. In this case, nano-sized pores capable of penetrating the liquid material SB may be formed in the frame structure.

Further, depending on the molecular weight or particle size of the liquid substance SB captured in the patch PA, whether or not the liquid substance SB is injected into the frame structure of the net structure can be determined. A substance having a relatively high molecular weight is caught in the microcavity and a substance having a relatively small molecular weight can be injected into the microcavities and / or the frame structure of the net structure NS and captured.

The term "captured" herein refers to a state in which the liquid material SB is located in a plurality of microcavities and / or nano-sized holes formed by the net structure NS Can be defined. In addition, the state in which the liquid substance SB is trapped in the patch PA is such that the liquid substance SB can flow between the microcavity and / or the nano-sized hole Is defined as including a state that exists.

The liquid material SB can be considered as divided into a base material BS and an additive material AS as follows.

The base material BS may be a liquid material SB having fluidity.

The additive material AS may be mixed with the base material BS to have a fluidity. In other words, the base material (BS) can be used everyday. The additive material AS may be a solute dissolved in the solvent or a particle not soluble in the solvent.

The base material BS may be a material capable of flowing in the matrix formed by the net structure NS. On the other hand, the base material BS may be uniformly distributed in the net structure NS and may be distributed only in a partial region of the net structure NS. The base material BS may be a liquid having a single component.

The additive substance AS may be a substance which is mixed with the base substance (BS) or dissolves in the base substance (BS). For example, the additive material AS may function as a solute with the base material (BS) as a solvent. The additive material AS may be uniformly distributed in the base material BS.

The additive material AS may be fine particles which do not dissolve in the base material BS. For example, the additive substance AS may include microparticles such as colloidal molecules, microorganisms, and the like.

The additive material AS may comprise particles larger than the microcavities formed by the net structure NS. If the size of the microcavities is smaller than the size of the particles contained in the additive material AS, the flowability of the additive material AS may be limited.

Also, according to one embodiment, the additive material AS may comprise a component optionally contained in the patch PA.

On the other hand, the additive material AS does not necessarily mean a material which is not necessarily defective in terms of quantities in terms of the above-mentioned base material (BS), or is functionally inferior.

Hereinafter, the characteristics of the liquid material SB captured in the patches PA can be regarded as characteristics of the patches PA. That is, the characteristics of the patch PA may depend on the characteristics of the material trapped in the patch PA.

1.2.2 characteristic

The patch PA according to the present application may include a net structure NS as described above. The patch PA can handle the liquid material SB by the net structure NS. The patches PA can cause the liquid material SB captured in the patches PA to at least partially maintain their inherent characteristics.

For example, diffusion of material may occur in the region of the patch PA in which the liquid material SB is distributed, and a force such as surface tension may act.

The patches PA may provide a liquid environment in which the subject material diffuses due to thermal motion, density or concentration difference of the material. In general, 'diffusion' means that the particles forming the substance are spread from the higher concentration side to the lower concentration side due to the difference in concentration. This diffusion phenomenon can be understood as a result phenomenon that is basically caused by the motion of a molecule (translational motion in gas or liquid, oscillation motion in solid, etc.). In the present application, the term "diffusion" refers to a phenomenon in which particles are diffused to a lower concentration at a higher concentration due to a difference in concentration or density, It also refers to the phenomenon of movement of particles due to irregular motion. Also, the expression 'irregular motion' of particles is used in the same meaning as 'diffusion' unless otherwise noted. The substance to be diffused may be a solute dissolved in the liquid material SB, and the solute may be provided in a solid, liquid or gaseous state.

More specifically, non-uniformly distributed material in the liquid material SB captured by the patches PA can be diffused in the space provided by the patches PA. In other words, the additive material AS can diffuse in the space defined by the patch PA.

The nonuniformly distributed substance or the additive substance AS in the liquid substance SB handled by the patch PA diffuses in the microcavities provided by the net structure NS of the patch PA can do. In addition, the non-uniformly distributed material or the region where the additive material AS can diffuse can be changed by contacting or connecting the patch PA with another material.

It is also preferred that the non-uniformly distributed substance or the additive substance AS is diffused in the patch PA or in an outer region connected to the patch PA and the concentration of the substance or the additive substance AS The material or the additive material AS can be constantly moved by the irregular movement of the molecules inside the patch PA and / or in the outer region connected with the patch PA.

The patch PA may be formed to have hydrophilic or hydrophobic properties. In other words, the mesh structure NS of the patch PA may have hydrophilic or hydrophobic properties.

If the nature of the net structure NS is similar to that of the liquid substance SB, the net structure NS can more effectively handle the liquid substance SB.

The properties of the base material BS may be polar, hydrophilic, or non-polar, hydrophobic. In addition, the nature of the additive material (AS) may be hydrophilic or hydrophobic.

The nature of the liquid material SB may be related to the base material BS and / or the additive material AS. For example, when the base material BS and the additive material AS are both hydrophilic, the liquid material SB may be hydrophilic, and both the base material BS and the additive material AS may be hydrophilic. In the case of hydrophobicity, the liquid substance SB may be hydrophobic. When the polarity of the base material BS and the additive material AS are different from each other, the liquid material SB may be hydrophilic or hydrophobic.

If both the polarity of the net structure NS and the polarity of the liquid material SB are both hydrophilic or hydrophobic, attraction may be applied between the net structure NS and the liquid material SB. For example, when the polarity of the net structure NS and the liquid material SB are opposite to each other, for example, when the polarity of the net structure NS is hydrophobic and the liquid material SB is hydrophilic , A repulsive force may act between the net structure NS and the liquid material SB.

Based on the above-mentioned properties, the patches PA can be used alone, in plural, or in combination with other mediums to induce a desired reaction. Hereinafter, functional aspects of the patch PA will be described.

Hereinafter, for convenience of explanation, it is assumed that the patch PA is a gel phase in which a hydrophilic solution can be contained. In other words, the net structure NS of the patch PA is assumed to have a hydrophilic property unless otherwise specified.

However, in addition to a gel patch (PA) containing a solution which is hydrophobic in nature, the scope of the present application should not be limited to gel patches (PA) having hydrophilic properties, (PA) on the sol and the patch PA on the sol if it is possible to implement the function according to the present application.

2. Features of the patch

The patches according to the present application may have some useful functions due to the above-mentioned characteristics. In other words, the patch can occupy the liquid material SB, thereby contributing to the behavior of the liquid material SB.

Hereinafter, a reservoir function in which the state of the substance is defined in a predetermined region formed by the patch PA according to the behavior of the substance in relation to the patch PA, And a channeling function in which the state of the substance is defined including an outer region.

2.1 Reservoir

2.1.1 Significance

The patch PA according to the present application can capture the liquid substance SB as described above. In other words, the patch PA can perform a function of a reservoir.

The patch PA may capture a liquid material SB in a plurality of microcavities formed in the mesh structure NS through the mesh structure NS. The liquid material SB may occupy at least a part of the microcavities formed by the three dimensional net structure NS of the patch PA or may be formed into nano sized pores or the like formed in the net structure NS It can penetrate.

Even if the liquid material SB located in the patch PA is distributed in the plurality of microcavities, the property of the liquid is not lost. That is, the liquid substance SB has fluidity even in the patch PA, and diffusion of the substance can occur in the liquid substance SB distributed in the patch PA, and a proper solute can be dissolved in the substance PA have.

Hereinafter, the reservoir function of the patch PA will be described in more detail.

2.1.2 contain

In the present application, the patch (PA) can capture the target substance by the above-described characteristics. The patches PA may have resistivity within a certain range with respect to changes in the external environment. Thereby, the patch PA can keep the material in a trapped state. The liquid material SB to be captured may occupy the three-dimensional net structure NS.

Hereinafter, the function of the above-described patch PA is referred to as storage for the sake of convenience.

However, the meaning of the patch PA storing the liquid material is that the liquid material is stored in a space formed by the net structure and / or the frame structure constituting the net structure NS And the storage of the liquid material.

The patches PA may store a liquid substance SB. For example, the patch PA can store the liquid substance SB by the attraction force acting in the relationship between the net structure NS of the patch PA and the liquid substance SB. The liquid material SB may be stored in association with the net structure NS with a force of a predetermined strength or more.

The property of the liquid material SB stored in the patch PA may be classified according to the property of the patch PA. More specifically, when the patch PA has a hydrophilic property, the patch PA is combined with a generally hydrophilic liquid material SB having polarity, and the hydrophilic liquid material SB is mixed with the three- It can be stored in communities. Alternatively, when the patch PA is hydrophobic, a hydrophobic liquid material SB may be stored in the microcavities of the three-dimensional network structure NS.

Also, the amount of material that can be stored in the patches PA can be proportional to the volume of the patches PA. In other words, the amount of material stored in the patch PA can be proportional to the amount of the three-dimensional mesh structure NS as a support contributing to the shape of the patch PA. However, the amount of the material that can be stored and the volume of the patch PA do not have a constant proportional constant, and the amount of the material that can be stored according to the design or manufacturing method of the net structure and the volume of the patch PA Relationships can be different.

The amount of the substance stored in the patch PA can be reduced by evaporation, dropout, etc. over time. In addition, a substance may be added to the patch PA to increase or maintain the content of the substance stored in the patch PA. For example, a water retention agent or the like for suppressing the evaporation of water may be added to the patch PA.

The patch PA can be realized in a form easy to store the liquid material SB. This means that the patch PA can be implemented to minimize denaturation of the material when the material is affected by the environment such as humidity, light quantity, temperature, and the like. For example, in order to prevent the patch PA from being denatured by an external factor such as bacteria, the patch PA may be treated with a bacterial inhibitor or the like.

On the other hand, the patch PA may store a liquid substance SB having a plurality of components. At this time, the plural-component material is placed in the patch PA before the reference time point, or the material to be primarily charged is first stored in the patch PA, It is also possible that the material is stored. For example, when a two-component liquid material SB is stored in the patch PA, two components are stored in the patch PA when the patch PA is manufactured, Only one component may be stored in the patch PA and the remaining one may be stored, or two components may be sequentially stored after the manufacture of the patch PA.

In addition, the substance stored in the patch PA can exhibit fluidity basically as described above, and can perform irregular or diffuse motion due to molecular motion in the patch PA.

2.1.3  Provide reaction space

FIGS. 3 and 4 are diagrams for providing a reaction space as an example of the function of the patch according to the present application. FIG.

As shown in Figs. 3 and 4, the patch PA according to the present application can perform a function of providing space. In other words, the patch PA can provide a space through which the liquid material SB can move through the space formed by the net structure NS and / or the space constituting the net structure NS have.

The patches PA can provide space for diffusion of particles and / or activities other than irregular movement of particles (hereinafter referred to as activities other than diffusion). Activities other than diffusion can mean a chemical reaction, but are not limited to physical changes. More specifically, activity other than diffusion refers to a chemical reaction in which the chemical composition of the material changes before and after the action, a specific binding reaction between the ingredients contained in the material, a solute or particle , Coagulation of some of the components contained in the material, or biological activity of a portion of the material.

On the other hand, when a plurality of substances are involved in the activity, a plurality of substances may be placed together in the patch PA before the reference time point. The plurality of materials may be sequentially introduced.

By changing the environmental conditions of the patches PA, the efficiency of the function of providing space for activities other than the diffusion of the patches PA can be improved. For example, the temperature condition of the patch PA may be changed or an electrical condition may be added to promote the activity or induce the initiation of activity.

3 and 4, the first material SB1 and the second material SB2 located in the patch PA react within the patch PA to be deformed into the third material SB3, The third material SB3 can be produced.

2.2 Channel

2.2.1  Righteousness

Material movement may occur between the patch PA and the outer region. In addition, material may be moved from the patch PA to the outer region of the patch PA, or material may be transferred from the outer region to the patch PA.

The patches PA can form a movement path of the material or can participate in the movement of the material. More specifically, the patch PA is a part of the patch PA, which is involved in the movement of the liquid substance SB captured by the patch PA, Can be involved in movement. The base material BS or the additive material AS may escape from the patch PA or foreign matter may be introduced from the outer region into the patch PA.

The patches PA can provide the function of the passage of material. That is, the patch PA may participate in the movement of the material to provide a channel function of material movement. The patches PA can provide a channel of mass transfer due to the inherent properties of the liquid substance SB.

The patch PA may be configured to allow movement of the liquid material SB between the outer region and the state of the liquid material SB Can not be moved. In addition, when channeling between the patch PA and the outer region is started, the patch PA may have unique functions.

Hereinafter, a state in which the material can move and a state in which the material can not be moved will be described first. In performing the functions peculiar to the patch PA, whether or not the patch PA is connected to the outer region, Describe in detail.

Basically, the primary reason for the movement of the liquid material SB between the patch PA and the outer region is due to irregular movement and / or diffusion of the material. However, it is possible to control external environmental factors (for example, control of temperature conditions, control of electrical conditions, etc.) in order to control the movement of a substance between the patch PA and the external region have.

2.2.2  Movable state

In the movable state of the material, flow between the liquid material SB captured by the patch PA and / or the material located in the outer region may occur. When the material is in a movable state, movement of a substance between the liquid material SB captured in the patch PA and the outer region may occur.

For example, when the material is movable, some of the liquid material SB or some of the liquid material SB may diffuse to the outer region or may move by irregular movement. Alternatively, when the material is movable, an external material located in the outer region or a part of the outer material may diffuse into the liquid material SB of the patch PA or may move by irregular movement.

The state in which the substance is movable may be caused through contact. The contact may mean that the liquid material SB captured by the patch PA is connected to the outer region. The contact may mean that the flow region of the liquid material SB overlaps at least partially with the outer region. The contact may mean that the external material is connected to at least part of the patch PA. The state in which the substance is movable can be understood as extending the range in which the captured liquid substance SB can flow. In other words, in the movable state of the substance, the liquid phase can be expanded so that the flowable range of the substance includes at least a part of the outer region of the captured liquid substance SB. For example, when the liquid material SB is in contact with the outer region, the range in which the captured liquid material SB can flow may be expanded to include at least a portion of the outer region contacted. More specifically, when the outer region is an outer plate, an area in which the liquid material SB can flow may be extended to include an area in contact with the liquid material SB of the outer plate.

2.2.3 immovable state

In the unmovable state of the substance, movement of the substance between the liquid substance SB captured in the patch PA and the external region may not occur. However, it goes without saying that material may migrate in each of the liquid material SB captured in the patch PA and the external material positioned in the outer region.

The state in which the substance is immovable may be a state in which the contact is released. In other words, in the state where the patch PA is released from contact with the outer region, the material can not move in the liquid material SB remaining in the patch PA and the outer region or the outer material .

More specifically, the state in which the contact is released may mean that the liquid material SB captured by the patch PA is not connected to the outer region. The state in which the contact is released may mean that the liquid material SB is not connected to an external material located in the outer region. For example, a state in which the material can not be moved can be caused by the separation of the patch PA and the outer region.

The 'movable state' defined in the present specification has a meaning distinct from the 'non-movable state', but transition between states may occur due to time flow, environmental change, and the like. In other words, the patch PA can be moved to a non-movable state, the non-movable state can be moved to a movable state, and the state in which the patch PA is movable, It is also possible to move back to a state ready for movement.

2.2.4  Classification of functions

2.2.4.1 Forwarding

In the present application, the patches PA can transfer at least a part of the liquid substances SB occupied in the patches PA to the desired outer region due to the above-described characteristics. The transfer of the material may mean that a part of the liquid material SB captured by the patch PA is separated from the patch PA as a certain condition is satisfied. Partial separation of the liquid material SB may mean that some material is extracted or released or released from the area affected by the patch PA. This can be understood as a sub-concept of the channel function of the patch PA described above, which defines the delivery of the substance located in the patch PA to the outside of the patch PA.

The desired outer region may be another patch (PA), a dried region, or a liquid region.

The predetermined condition for generating the transfer may be defined as environmental conditions such as a temperature change, a pressure change, an electrical property change, and a physical state change. For example, when the patch PA comes into contact with an object stronger in binding force with the liquid substance SB than the net structure NS of the patch PA, the liquid substance SB is chemically And as a result at least a part of the liquid substance SB can be transferred to the object.

Hereinafter, the function of the above-described patch PA is referred to as " transmission " for the sake of convenience.

Wherein the transfer is performed between a state in which the liquid SB is movable between the patch PA and the outer region and a state in which the liquid SB moves between the patch PA and the outer region, It can happen via via / through.

More specifically, when the liquid material SB is in the movable state, it may diffuse between the patch PA and the outer region, or may move to the outer region by irregular movement. In other words, the base solution and / or the additive substance AS contained in the liquid material SB can move from the patch PA to the outer region. When the liquid material SB is in the non-movable state, movement between the patch PA and the outer region becomes impossible. In other words, some of the material that has migrated from the patch PA to the outer region due to the diffusion and / or irregular movement of the liquid material SB may be caused by the transition from the movable state to the immovable state , It is impossible to move back to the patch PA. As a result, some of the liquid substances SB may be partially transferred to the outer region.

The transfer may be performed according to the difference between the attractive force between the liquid material SB and the net structure NS and the attractive force between the liquid material SB and the outer region or the external material. The attractive force can be attributed to polarity similarity or a specific coupling relationship.

More specifically, when the liquid substance SB is hydrophilic and the outer region or the foreign substance is more hydrophilic than the mesh structure NS of the patch PA, the movable state and the non-movable state At least a part of the liquid material SB captured in the patch PA may be transferred to the outer region.

The transfer of the liquid material SB can also be carried out selectively. For example, if there is a specific binding relationship between some of the components contained in the liquid substance SB and the external substance, the state of the substance can not be shifted, May be generated.

More specifically, assuming that the patch PA transfers a substance to an outer plate PL in the form of a plate, a part of the liquid substances SB captured in the patch PA (for example, solute May be applied to the outer plate (PL). At this time, the patch PA passes a part of the solute that specifically binds to the substance applied to the outer plate PL through the movable state and the non-movable state to the plate (PA) PL).

Hereinafter, the delivery as a function of the patch PA will be described according to some examples of other regions where the material is moved. However, the concept of "release" of the liquid substance SB and "transfer" of the liquid substance SB may be mixed in a specific explanation.

Here, a case where a liquid substance SB is transferred from the patch PA to a separate outer plate PL will be described. For example, the material may be moved from the patch PA to a plate PL such as a slide glass.

As the patch PA and the plate PL come into contact with each other, the liquid material SB trapped in the patch PA diffuses and moves at least partially to the plate PL or moves by irregular movement . Some of the substances (that is, some of the liquid substances SB) which have been transferred from the patches PA to the plates PL are separated from the patches PL by separating the contact between the patches PA and the plate PL, PA. ≪ / RTI > As a result, some of the material may be transferred from the patch PA to the plate PL. At this time, the substance to be delivered may be the additive substance AS. In order for the substance in the patch PA to be 'transferred' by the contact and separation, a force and / or a binding force acting between the substance and the plate PL must exist and the attractive force and / Must be greater than the attractive force acting between the material and the patch (PA). Therefore, when the above-described 'transfer condition' is not satisfied, transfer of the substance between the patch PA and the plate PL may not occur.

In addition, temperature or electrical conditions may be provided to the patch PA to control the delivery of the material.

The mass transfer from the patch PA to the plate PL may depend on the contact area between the patch PA and the plate PL. For example, the mass transfer efficiency of the patch PA and the plate PL can be increased or decreased according to the area of contact between the patch PA and the plate PL.

In the case where the patch PA includes a plurality of components, only some of the components may be selectively moved to the outer plate PL. More specifically, the outer plate PL may be fixed with a substance that specifically binds to some of the plurality of components. At this time, the substance fixed to the outer plate PL may be in a liquid or solid state, and may be fixed in the separate region. In this case, a part of the plurality of components moves to the plate PL by the contact of the patch PA and the other region, thereby forming a specific coupling, and the patch PA is moved to the plate PL , Only some of the components may be selectively released to the plate PL.

Figures 5-7 illustrate the transfer of material from the patch PA to the outer plate PL as an example of the transfer of material among the functions of the patch PA according to the present application. 5 to 7, the patch PA can transfer a part of the substance stored in the patch PA to the plate PL by contacting the outer plate PL. At this time, the transfer of the substance may be made possible by the contact with the plate. At this time, a water film WF can be formed near the contact surface where the plate and the patch PA come in contact with each other, and the material can be moved through the formed water film WF.

Here, a case where the liquid material SB is transferred from the patch PA to a material SL having fluidity will be described. Here, the material SL having fluidity may be a liquid material in a state of being contained or flowing in a separate storage space.

As the patch PA and the fluid material are brought into contact with each other (for example, by applying a patch PA to the solution), the liquid material SB captured in the patch PA at least partially has the fluidity The branch may diffuse and migrate into the material SL or may move by irregular motion. When the patch PA and the fluid material are separated from each other, a part of the liquid material SB which has been transferred from the patch PA to the fluid material can not be moved back to the patch PA , Some material in the patch PA may be transferred to the fluid material.

The mass transfer between the patch PA and the material SL having fluidity may depend on the contact area between the patch PA and the material SL having fluidity. For example, depending on the area of contact between the patch PA and the material SL having fluidity (for example, the depth at which the patch PA is charged into the solution or the like) The mass transfer efficiency of the material SL can be increased or decreased.

In addition, the mass transfer between the patch PA and the fluid material SL can be controlled through physical separation of the patch PA and the fluid material.

Wherein the distribution concentration of the additive substance (AS) in the liquid substance (SB) differs from the distribution concentration of the additive substance (AS) in the flowable substance, The additive material AS may be delivered.

However, when the patch PA transfers the liquid material SB to the material SL having fluidity, it is essential that the physical separation between the patch PA and the material SL having fluidity is required no. For example, when the driving force / causal force causing the mass transfer from the patch PA to the fluid having a fluidity becomes smaller than or equal to the reference value, the movement of the substance may be stopped.

In the 'transfer' between the patch PA and the material SL having fluidity, a 'transfer condition' between the patch PA and the material SL having the fluidity described above is not required It is possible. This is because the substances already migrated to the material SL having fluidity are moved by diffusion and / or irregular movement in the material SL having the fluidity, It is understood that the material is transferred to the material SL having the fluidity. This is because, in the case of the plate PL, the movable range extending by the contact is in a very limited range, so that the attraction between the substances moved to the plate PL and the patch PA can be significant However, in the relationship between the material having fluidity and the patch PA, since the movable range extended by the contact between the patch PA and the plate PL is in a relatively wide range, Because the attraction between the patch PA and the materials moved to the material SL having the noble metal particles becomes meaningless.

Figures 8-10 illustrate the transfer of material from the patch PA to a fluid material as an example of the transfer of material among the functions of the patch PA according to the present application. According to Figures 8 to 10, the patches PA can convey a part of the substance stored in the patches PA with an external flowable substance. The transfer of a portion of the stored material may be performed such that the patch (PA) is charged or contacted with the flowable material so that the liquid material (SB) captured by the patch (PA) So that it can be moved.

Here, it is assumed that a material moves from the patch PA to another patch PA. In the contact area where the patch PA contacts the other patch PA, the liquid material SB provided to the patch PA may move to at least some of the other patches PA.

In the contact area, the liquid substances SB provided in the respective patches PA can diffuse and move to the other patches PA. At this time, due to the movement of the material, the concentration of the liquid substance SB provided to each of the patches PA may be varied. Also in this embodiment, as described above, the patch PA and the other patches PA can be separated, and at this time, a part of the liquid matter SB of the patches PA is transferred to the other patches PA ). ≪ / RTI >

The mass transfer between the patches PA and the other patches PA can be performed by changing the environmental conditions including physical state changes.

The mass transfer between the patch PA and the another patch PA may depend on the contact area between the patch PA and the other patch PA. For example, the mass transfer efficiency between the patch PA and the other patch PA can be increased or decreased according to the area of contact between the patch PA and the other patch PA.

Figures 11-13 illustrate the transfer of material from the patch PA1 to another patch PA2 as an example of the transfer of material among the functions of the patch PA according to the present application. According to Figures 11 to 13, the patch PA1 can transfer a part of the substance stored in the patch PA1 to another patch PA2. The transfer of a part of the material is performed when the patch PA1 comes into contact with the other patch PA2 so that the liquid SB captured in the patch PA1 and the material trapped in the other patch PA2 So that they can be exchanged with each other.

2.2.4.2 Absorption

Prior to the description, the 'absorption' of the function of the patch PA according to the present application can be handled similarly to the above-mentioned 'transmission' in some embodiments. For example, when the movement of a substance due to the concentration difference of a substance is assumed, it is possible to control the moving direction of the moving substance by varying the concentration of the liquid substance SB, particularly the concentration of the additive substance AS It can have a common aspect. Also, the control of the movement of the material through the separation of the physical contact of the patches PA and the selective absorption can be likewise common, which can be clearly understood by those skilled in the art to which the present application belongs.

The patch PA according to the present application can capture foreign matter by the above-described characteristics. The patch PA may pull an external substance existing outside the region defined by the patch PA into an area where the influence of the patch PA acts. The foreign substance introduced may be captured as the liquid substance SB of the patch PA. The introduction of the foreign substance may be attributed to the attraction between the liquid substance SB trapped in the patch PA and the foreign substance. Alternatively, the introduction of the foreign substance may be attributed to an attraction between the external material and a region not occupied by the liquid substance SB of the net structure NS. The introduction of the foreign substance can be attributed to the force of the surface tension.

Hereinafter, the function of the patch PA is referred to as absorption for the sake of convenience. The absorption can be understood as a sub-concept of the channel function of the above-mentioned patch PA, which defines the movement of foreign matter to the patch PA.

The absorption may occur via the patch PA through a state in which the material is movable and a state in which movement of the material is impossible.

The material that the patch PA can absorb may be in a liquid or solid state. For example, when the patches PA are in contact with a foreign substance including a solid material, the liquid material SB located in the patch PA and the solid material contained in the foreign material The absorption of the material can be carried out with the force of. As another example, when the patches PA are in contact with a foreign substance in the liquid phase, they can be performed by combining a liquid substance SB located in the patches PA and a liquid external substance.

The foreign matter absorbed by the patch PA moves into the interior of the patch PA through the microcavity of the net structure NS constituting the patch PA or is distributed on the surface of the patch PA can do. The distribution position of the foreign substance may be determined from the molecular weight of the external substance or the particle size.

The shape of the patch PA may be deformed during the absorption. For example, the volume, color, etc. of the patches PA may vary. Meanwhile, external conditions such as a temperature change and a physical state change may be added to the absorption environment of the patch PA during absorption of the patch PA to activate or retard the absorption of the patch PA.

Absorption will now be described as a function of the patch PA, according to some examples of the outer region providing the material to be absorbed into the patch PA when absorption occurs.

Hereinafter, it is assumed that the patch PA absorbs foreign matter from a separate outer plate PL. Here, the separate external substrate may be a plate (PL) or the like, which does not absorb the external material, but in which the external material can be positioned.

The outer plate PL may be coated with a substance. Particularly, the plate PL may be coated with a substance in powder form. The material applied to the plate PL may be a single component or a mixture of multiple components

The plate PL may have a flat plate shape. The shape of the plate PL may be modified to improve the storage stability of the material. For example, a well may be formed to improve storage stability, or the surface of the plate PL may be deformed with a negative or positive angle, or the contact with the patch PA may be improved by using a patterned plate PL It is possible.

The patch PA according to the present invention absorbs the substance from the plate PL by the contact between the plate PL and the patch PA. At this time, in the contact area near the contact surface between the plate PL and the patch PA, the liquid material SB captured by the patch PA and / or the water film SB due to the material applied to the plate PL, (WF) may be formed. When a water film (WF, aquaplane) is formed in the contact area, the substance applied to the plate PL can be captured in the water film WF. The material trapped in the water film WF can freely flow in the patch PA.

When the patch PA is separated from the plate PL by a predetermined distance or more and the water film WF moves with the patch PA, (PA). The material applied to the plate PL can be absorbed by the patch PA as the patch PA is separated from the plate PL by a predetermined distance or more. When the patch PA and the plate PL are separated and separated from each other, the liquid SB provided to the patch PA is not moved to the plate PL or only a small amount of the material SB is transferred to the patch PA ). ≪ / RTI >

All or a part of the substance applied to the plate PL may specifically react with all or a part of the substance trapped in the patch PA. In this regard, it is optional to allow the patch PA to absorb material from the separate plate PL. In particular, the patch PA may have a stronger attractive force than the plate PL for a portion of the material trapped in the patch PA.

For example, some material may be fixed to the plate PL. In other words, some of the materials are fixed to the plate PL, and some of the materials are not fixed or can be applied with fluidity. At this time, when the patch PA and the plate PL are brought into contact with and separated from each other, only a part of the materials applied to the plate PL excluding the fixed substances may be selectively absorbed into the patch PA. Alternatively, selective absorption may occur due to the polarity of the material positioned on the plate PL and the material trapped on the patch PA regardless of whether it is fixed or not.

As another example, when the liquid substance SB captured by the patch PA specifically binds to at least a part of the substance applied to the plate PL, the patch PA is applied to the plate PL, at least a portion of the material specifically applied to the plate PL may be absorbed by the patch PA when the material is contacted with and separated from the material applied to the plate PL.

As another example, some of the materials applied to the plate PL may specifically react with the material previously fixed to the plate PL. In this case, only the substance applied to the plate PL, other than the substance specifically reacting with the substance previously fixed to the plate PL, can be absorbed by the patch PA.

14 to 16 show an example of the absorption of a substance among the functions of the patch PA according to the present application, in which the patch PA absorbs the substance from the outer plate PL. 14 to 16, the patch PA can absorb a part of the material positioned on the outer plate PL from the outer plate PL. The material is absorbed when the water film WF is formed near the contact area between the outer plate PL and the patch PA by the contact of the patch PA with the outer plate PL, WF to allow the material to move to the patch PA.

Here, it is assumed that the material is absorbed from the material SL having fluidity to the patch PA. The material SL having fluidity may be a liquid external substance contained in a separate storage space or in a flowing state. More specifically, the liquid material SL having the fluidity and the liquid material SB captured by the patch PA have an environment in which they can flow with each other, All can be absorbed by the patch PA. At this time, the interflowing environment can be formed by at least partially contacting the patch PA with the material SL having fluidity.

The patch PA is brought into contact with the material SL having the fluidity so that the material PA and the material SL having the fluidity can move. When the patch PA is separated from the material SL having fluidity, at least a part of the material SL having fluidity can be absorbed into the patch PA.

The absorption of the material from the fluid material SL to the patch PA may depend on the difference in the concentration of the substance trapped in the patch PA and the material SL having fluidity. In other words, the liquid substance SB captured by the patch PA is higher than the concentration of the liquid substance SL with respect to the predetermined additive substance AS, The predetermined additive material AS can be absorbed into the patch PA.

On the other hand, when the substance is absorbed from the material SL having fluidity to the patch PA, depending on the concentration difference in the contact state as described above, an electric factor is added, The absorption of the patch PA can be controlled. Further, the substance captured by the patch PA and the substance to be absorbed may not be in direct contact with each other, but may be indirectly contacted through the medium to perform absorption of the substance.

Figs. 17-19 illustrate that the patch PA absorbs material from a material SL having fluidity, as an example of the absorption of material among the functions of the patch PA according to the present application. 17 to 19, the patch PA can absorb a part of the material SL having fluidity. The absorbing of the material can be achieved by the fact that the patch PA is charged into the material SL having the fluidity or comes into contact with the material SL having the fluidity, And the material SL having fluidity can be moved with respect to each other.

Here, it is assumed that the patch PA absorbs foreign matter from another patch PA.

It is preferable that the patch PA absorbs the foreign matter from the other patch PA by absorbing the absorbed foreign matter and the substance trapped in the patch PA and the absorbed foreign matter and the patch PA By the difference in the bonding force between the external substances. For example, if the absorbent material is hydrophilic, the patch PA is hydrophilic, and the attracting force of the absorbent material and the patch PA is the attraction force between the other patch PA and the absorbent material When the patch PA is separated from the other patch PA after the patch PA is contacted with the patch PA, that is, when the patch PA is stronger than the other patch PA The foreign material may be at least partially absorbed by the patch PA.

Figs. 20 to 22 illustrate that the patch PA3 absorbs material from another patch PA4, as an example of the absorption of a substance among the functions of the patch PA according to the present application. According to Figs. 20 to 22, the patch PA3 can partially absorb the substance that was located in the other patch PA4. The absorbing of the substance is performed by absorbing the liquid substance SB captured in the patch PA3 and the liquid substance SB captured in the other patch PA4 by the patch PA3 contacting the other patch PA4, Can be exchanged with each other.

On the other hand, depending on the ratio of the frame structure of the three-dimensional net structure NS constituting the patch PA to the total volume of the patches PA, the binding force of the patches PA to the absorbed foreign substances changes . For example, as the volume percentage occupied by the frame structure in the entire patch PA is increased, the amount of material trapped in the structure can be reduced. In this case, the binding force between the patch PA and the target material may be reduced due to a decrease in contact area between the material trapped by the patch PA and the target material.

In this regard, the polarity of the patch PA can be controlled by adjusting the ratio of the material forming the net structure NS in the manufacturing process of the patch PA. For example, in the case of a patch (PA) fabricated using agarose, the concentration of the agarose can be controlled to control the extent of the absorption.

When the patch PA and the other patch PA are brought into contact with and separated from each other, the separate area has a weaker binding force than the patch PA with respect to the material provided from the patch PA, Can be separated from the other patches (PA) together with the patches (PA).

2.2.4.3 Providing the Environment

The patch PA according to the present application can perform the function of adjusting the environmental condition of the target area by the above-described characteristics. The patches PA can provide an environment resulting from the patches PA in a desired area.

The environmental conditions resulting from the patches PA may depend on the liquid substance SB captured in the patches PA. The patches PA can create the desired environment for the material located in the outer region so as to correspond to the characteristics of the material contained in the patches PA or to the characteristics of the materials contained in the patches PA.

Regulating the environment may be understood as altering the environmental conditions of the desired region. The changing of the environmental condition of the target area may be performed in such a manner that an area affected by the patch PA is expanded to include at least a part of the target area or a configuration in which the environment of the patch PA is divided into the target area And can be implemented in a shared form.

Hereinafter, the function of the above-described patch PA is referred to as provision of environment for the sake of convenience.

The provision of the environment by the patches PA may be performed in a state in which the patches PA are capable of moving the outer region and the material to which the environment is to be provided. The provision of the environment by the patches PA can be performed due to the contact. For example, when the patch PA is in contact with a desired area (e.g., a foreign material, a plate PL, etc.), the patch PA can provide a specific environment for the desired area .

The patch PA can adjust the environment of the target area TA by providing an appropriate pH, osmotic pressure, humidity, concentration, and temperature environment. For example, the patch PA may impart liquidity to the target area TA or the target material. This imparting of fluidity can occur due to some movement of the material trapped in the patches PA. It is possible to provide a wetting / moist environment to the target area TA through the liquid material SB to base material BS captured in the patch PA.

The environmental factors provided by the patch PA can be kept constant depending on the purpose. For example, the patch PA may provide homeostasis in the desired region. As another example, as a result of provision of the environment, the environmental condition of the desired region can be adapted to the material trapped in the patch PA.

The provision of the environment by the patches PA may be a result of diffusion of the liquid substances SB contained in the patches PA. That is, when the patch PA and the target region come into contact with each other, movement of the material through the contact region formed due to the contact can be made possible. In this regard, depending on the diffusion direction of the substance, the environment change due to osmotic pressure, the environment change depending on the ion concentration, the provision of the wetting environment, and the change in pH can be realized.

23 to 25 show an example of the provision of the function of the function of the patch PA according to the present application, in which the patch PA provides a predetermined environment to the outer plate PL. 23 to 25, the patch PA may provide a predetermined environment to the outer plate PL on which the fourth material SB4 and the fifth material SB5 are located. For example, the patch PA may provide a predetermined environment for forming the sixth material SB6 by reacting the fourth material SB4 and the fifth material SB5 on the plate PL . Providing the environment is that the water film WF is formed in the vicinity of the contact region by the contact of the patch PA with the plate PL and the fourth material SB4 and the fifth material WF are formed in the formed water film WF, (SB5) is captured.

3. Apply patches

The patch PA according to the present application can be implemented to perform various functions by suitably applying the function of the patch PA described above.

Hereinafter, the technical idea of the present application will be described by disclosing some embodiments. However, the technical scope to which the function of the patch (PA) disclosed by the present application is applied or applied should be expanded within the range of convenience of those skilled in the art, and is limited by the embodiment described in this specification, Should not be interpreted.

3.1 In-patch

The patches PA may provide a reactive area of the material. In other words, a reaction of the material may occur in at least part of the spatial region affected by the patch PA. At this time, the reaction of the substance is carried out by a reaction between the liquid substance SB captured in the patch PA, and / or between the trapped liquid substance SB and the substance provided from the outside of the patch PA Lt; / RTI > Providing the reaction zone of the substance may be to activate or promote the reaction of the substance.

In this case, the liquid substance SB captured in the patch PA refers to a material SB introduced into the patch PA at the time of manufacture of the patch PA, And a material temporarily trapped in the patch PA. In other words, if the material is trapped in the patch PA at the time when the reaction in the patch PA is activated, whether the material is trapped in the patch PA or not, Can react. Further, it is also possible that the material to be introduced after the production of the patches PA acts as a reaction initiator.

The provision of the reaction zone of the reaction in which the liquid substance SB captured in the patch PA is involved can be an embodiment sub-concept of the above-mentioned 2.1.3 (i.e., provision of the reaction space) table. Or a multi-concept that performs the combined function of the above-described Table of Contents 2.1.3 and 2.2.4.2 (i. E., Absorption) table of contents. However, the present invention is not limited to this, and two or more functions may be combined.

3.1.1 Example 1

Hereinafter, it is assumed that the function of absorbing the patch PA and the function of providing a reaction space (hereinafter referred to as providing function) are performed by one patch PA. In this case, the absorption function and the providing function may be functions performed simultaneously, or may be functions performed at different points in time, and may be sequentially performed to perform another function. On the other hand, it can be seen that the patch PA further includes other functions in addition to the absorbing and providing function.

The patches PA can perform the function of capturing the material, as described above, and the material can be fluid even when captured. If the distribution of some components of the liquid material SB is non-uniform, the non-uniform components may diffuse. Even when the components of the liquid material SB are uniformly distributed, the liquid material SB may have a certain level of mobility due to irregular movement of the particles. At this time, reactions between materials, for example, specific binding between materials, can occur within the patch PA.

For example, in the patch PA, in addition to the reaction between the trapped substances, a substance having fluidity newly caught in the patch PA and a substance trapped in the patch PA are subjected to specific binding The reaction of the form can also be possible.

It is also possible that the reaction between the fluid substance and the trapped substance is performed separately from any space in which the fluid substance is provided. For example, after the patch PA has absorbed the flowable material from an arbitrary space, the patch PA is separated from the arbitrary space so that the absorbed material and the patch PA The reaction of the entrapped material may occur in the patch PA.

In addition, the patch PA can perform an absorption function with respect to a fluid material, so that the reaction of the trapped material can take place. In other words, the absorption of the fluid material in the patch PA can trigger the reaction of the absorbed material and the material trapped in the patch PA. The reaction may be performed within a space defined by the patch PA.

Further, due to the reaction occurring inside the patch PA, the composition of the liquid material SB captured in the patch PA can be changed. This is because the chemical composition can be changed before and after the reaction, especially when the substance trapped inside the patch (PA) is a compound. Alternatively, the composition distribution depending on the position of the substance in the patch PA may be changed. This can be exemplified by diffusion or by particles having a specific attraction to other materials.

When the composition of the liquid material SB is changed due to the reaction in the patch PA, the material PA (the contact material in the presence of the contact material, if any) Some material may be absorbed into the patch PA by the difference in concentration between the patch PA and the material may be released from the patch PA to the external material.

3.1.2 Example 2

Hereinafter, an embodiment in which the storage function of the patch PA and the function of providing the reaction space of the material are performed together for at least a predetermined time will be described. More specifically, at least a portion of the liquid substance SB stored in the patches PA can function to provide space for reaction.

The patches PA can store material and provide a reaction space for the stored material. The reaction space provided by the patch PA may be a surface area of the microcavity or the patch PA formed by the net structure NS of the patch PA. Particularly, when the material stored in the patch PA and the material coated on the surface of the patch PA react, the reaction space may be the surface area of the patch PA.

The reaction space provided by the patches PA can serve to provide specific environmental conditions. The patch PA can adjust the environmental conditions of the reaction during the reaction in the liquid material SB located in the patch PA. For example, the patches PA can perform the function of a buffer solution.

The patches PA do not require a separate storage vessel by storing material through the netting structure. Further, when the reaction space of the patch PA is the surface of the patch PA, it can be easily observed through the surface of the patch PA. For this purpose, the shape of the patch PA can be modified and designed in a form that can be easily observed.

The liquid material SB stored in the patches PA may be denatured or react with other kinds of materials. The liquid material SB stored in the patch PA can be changed in composition over time.

On the other hand, the reaction may be a chemical reaction in which the chemical formula is changed, a physical state change or a biological reaction. At this time, the liquid material SB stored in the patch PA may be a single component material or a mixture containing a plurality of components.

3.2 channeling

Hereinafter, a patch PA that performs a function of providing a material movement path will be described. More specifically, the patch PA can capture, absorb, emit, and / or store a fluid material or the like as described above. As the function of each of the above-described patches PA, it is possible to implement various embodiments of the patches PA that perform the function of providing the movement path of the material. However, some embodiments will be described for the sake of more specific understanding.

3.2.1 Example 3

The patch PA may be implemented to perform 2.2.4.1 (i.e., a table of contents for delivery) and 2.2.4.2 (i.e., a table of contents for absorption) of the functions of the above-described patch PA. At this time, the absorption function and the transfer function may be provided together, and may be sequentially provided.

The patches PA may perform the absorption and the transfer function together to provide a path of movement of the material. Particularly, a foreign substance can be absorbed and transferred to an external region, thereby providing a path for moving the foreign substance.

The patch PA provides a path of movement of the foreign material can be performed by absorbing the external material and discharging the foreign material. More specifically, the patch PA may contact the external material to absorb the foreign material, and may contact the outer area to transfer the external material to the outer area. At this time, the patch PA captures the foreign substance and transfers it to the external region can proceed with a process similar to the above-described absorption and transmission.

The foreign matter absorbed and transferred to the patches PA may be liquid or solid.

In this way, the patch PA can allow some material from the external material to be transferred to the other external material. The foreign matter and other foreign matter may be in contact with the patch PA at the same time. The patch PA and the foreign matter and other foreign matter may be contacted to the patch PA at different points in time.

The patch PA and the foreign matter and other foreign matter may be contacted at different points in time. In the case where each of the external materials comes into contact with each other at a different point in time, the patch PA and the external material first come into contact with each other. After the external material and the patch PA are separated, The material may be contacted. At this time, the patch PA may temporarily store the substance trapped by the foreign substance.

The patches PA can additionally provide a time delay while providing a path of movement of the material. In addition, the patch PA may perform a function of appropriately adjusting the amount of the substance to be transferred to the foreign substance and the delivery speed.

Meanwhile, the series of processes may be performed in one direction based on the patch PA. As a specific example, the absorption of material through one side of the patch PA can be provided and an environment can be provided in the inner space of the patch PA, and the material can be discharged through the other side facing the one side .

3.2.2  Fourth Embodiment

The patches PA are capable of absorbing and releasing the substance of the function of the patches PA described above and providing the reaction space of the substance. At this time, the absorption, release and provision of the reaction space of the material can be performed simultaneously or sequentially.

According to one embodiment, the patch PA may provide a reaction space in the absorbed foreign material for at least a part of the time in performing the process of absorbing and releasing the external material. The patches PA may provide a specific environment for the liquid material SB captured in the patches PA containing the absorbed foreign material for at least some time.

The liquid material SB captured in the patch PA and the foreign material captured in the patch PA may react inside the patch PA. The foreign matter absorbed by the patch PA may be influenced by the environment provided by the patch PA. The material released from the patch PA may comprise at least some of the material produced through the reaction. The external material may be discharged from the patch PA by changing its composition, characteristics, and the like.

The absorbed material may be released from the patch PA. It can be understood that the external material is absorbed by the patch PA and emitted from the patch PA through the patch PA. The foreign matter passing through the patch PA may lose the identity due to the reaction in the patch PA or the environment provided by the patch PA.

The absorption of the foreign substance, the reaction of the substance and the transferring process of the substance described above can proceed in one direction. In other words, absorption of the substance is performed at one position of the patch PA, provision of the environment at another position is performed, and release of the substance is performed at another position.

Figs. 26-28 illustrate providing a path of movement of material between two plates PL, according to one embodiment of a patch PA according to the present application. According to Figures 26 to 28, the patch PA can provide a path of movement of the material between the plate PL1 coated with the seventh material SB7 and the plate PL2 coated with the eighth material SB8 have. As a concrete example, when the seventh material SB7 has binding properties with the eighth material and the eighth material is fixed to the plate PL2, the patch PA is attached to the plates PL1 and PL2, The seventh material SB7 can move through the patch PA and be combined with the eighth material SB8. The reason why the seventh material SB7 and the eighth material SB8 are connected to the patch PA is that the patch PA is formed on the water film WF formed by contacting the plates PL1 and PL2 Can be done.

29 and 30 show one embodiment of a patch PA according to the present application, providing a path of movement of material between two patches. 29 and 30, the patch PA6 providing the movement path may be in contact with the patch PA5 storing the moving target material and the patch PA7 receiving the moving target material. The patch PA6 providing the movement path comes into contact with the patch PA5 storing the moving object material and the patch PA7 receiving the moving object material, ). ≪ / RTI > Movement of the material between each patch can be accomplished through a water film (WF) formed near the contact area between each patch.

FIGS. 31 and 32 show one embodiment of a patch according to the present application, providing a path of movement of material between two patches. According to Figs. 29 and 30, the patch PA9 providing the movement path may be in contact with the patch PA8 storing the ninth material SB9 and the patch PA10 receiving the substance. The patch PA9 providing the movement path can absorb the ninth material SB9 by contacting the patch PA8 storing the ninth material SB9. The absorbed ninth material SB9 may react with the tenth material SB10 stored in the patch PA9 providing the movement path to form the eleventh material. The eleventh material SB11 may be transferred to a patch PA10 that receives the material from the patch PA9 providing the movement path. The movement of the material between the patches PA can be made through the water film WF formed near the contact area between the patches PA.

3.3 multi patch

The patches PA can be used alone, and a plurality of patches PA can be used together. Here, the plurality of patches PA can be used together, as well as the case where the patches PA are used simultaneously, and the case where the patches PA are used sequentially.

When the plurality of patches PA are used at the same time, each of the patches PA can perform different functions. Each patch PA of the plurality of patches PA may store the same material, but may store different materials.

When the plurality of patches PA are used at the same time, the respective patches PA are not in contact with each other and the movement of the material between the patches PA may not occur, or alternatively, It is also possible to perform a desired function in a state in which it is possible.

The plurality of patches PA to be used together can be formed in a shape similar to or the same size as each other, but can also be used in the case of a plurality of patches PA having different shapes. Each of the patches PA constituting the plurality of patches PA may have different densities of the net structure NS or different components constituting the net structure NS.

3.3.1 Multiple patch contact

When a plurality of patches PA are used, a plurality of patches PA can contact one target area TA. The plurality of patches PA can perform a desired function by contacting one target area TA.

The plurality of patches PA may be in contact with different target areas TA when a plurality of target areas TA are present. The plurality of patches PA can perform a desired function by contacting a corresponding target area TA when a plurality of target areas TA are provided.

The plurality of patches (PA) may be in contact with a material applied to the target area (TA). At this time, the material applied to the target area TA may be fixed or fluid.

The desired function may be a substance transfer or absorption function. However, it is needless to say that each patch PA does not necessarily transmit the same material or absorb the same material, but each patch PA transfers different materials to the target area TA, It can absorb different components from the material.

The desired function may be different for each patch PA constituting the plurality of patches PA. For example, one patch PA performs the function of transferring the material to the target area TA, and the other patch PA functions to absorb the material from the target area TA.

The plurality of patches PA may include different materials, and the different materials may be transferred to one target area TA to induce a desired reaction. When a plurality of components are required for the purpose of the reaction to occur, a plurality of the components of the plurality of components may be respectively stored in the patch PA and transferred to the target region TA. The use of such a plurality of patches (PA) may be particularly useful when the substances required for the reaction are mixed for reasons such as being stored in a single patch (PA), or the properties of the material required for the desired reaction are lost or altered have.

According to one embodiment, when a plurality of patches PA comprise materials of different components and the materials of the different components have different specific binding relationships, TA). The plurality of patches (PA) may be used to detect a plurality of specific binding from a substance applied to the target area (TA) by transferring the substance of the different component.

According to another embodiment, the plurality of patches PA comprise materials of the same component to each other, and each patch PA may have a different concentration for the same component of the material. A plurality of patches (PA) including materials having the same components can be used to determine the influence of the concentration of the substance contained in the plurality of patches (PA) in contact with the target area (TA).

On the other hand, in the case of using a plurality of patches PA as described above, the bundles of patches PA can be modified and utilized in a more efficient manner. In other words, the configuration of a plurality of patches PA to be used can be used differently each time it is performed. That is, a plurality of patches PA can be manufactured in the form of a cartridge and used. At this time, the shape of each patch PA to be used may be appropriately standardized.

The plurality of patches PA in the form of a cartridge may be suitable for manufacturing a patch PA for storing a plurality of kinds of materials, respectively, and selecting and using the patches as necessary.

Particularly, when a plurality of kinds of substances are used to detect the specific reaction of each substance from the target region TA, the combination of the specific reactions to be detected can be carried out at each time of detection, There will be.

33 shows an example of a patch PA according to the present application, in which a plurality of patches PA are used together. According to FIG. 33, a plurality of patches PA according to an embodiment of the present application can simultaneously contact a target area TA located on the plate PL. Each of the patches PA constituting the plurality of patches PA may have a standardized form. The plurality of patches PA include a first patch and a second patch, and the material stored in the first patch may be different from the material stored in the second patch.

Fig. 34 shows that a plurality of patches PA are used together, and the plate PL includes a plurality of target areas TA. According to FIG. 34, a plurality of patches PA according to an embodiment of the present application can simultaneously contact a plurality of target areas TA located on the plate PL. Wherein the plurality of patches PA comprise a first patch PA and a second patch PA and the plurality of target areas TA comprise a first target area and a second target area, The patch may be in contact with the first target area and the second patch may be in contact with the second target area.

3.3.2 Fifth Embodiment

The plurality of patches PA can perform a plurality of functions. As described above, not only can each of the patches PA perform a plurality of functions simultaneously, but each of the patches PA can perform different functions at the same time. However, the present invention is not limited to the above case, and it is also possible that the respective functions are performed in combination in a plurality of patches PA.

First, when each of the patches PA performs a plurality of functions at the same time, each of the patches PA can perform both storage and discharge of the substance. As an example, each patch PA may store different materials and release each stored material in the target area TA. In this case, each stored substance may be released simultaneously or sequentially.

Next, in the case where each of the patches PA performs a different function at the same time, each of the patches PA may perform storage and discharge of a substance separately. In this case, only a part of each of the patches PA may contact the target area TA and release the material into the target area TA.

3.3.3 Sixth Embodiment

When a plurality of patches PA are used, as described above, the plurality of patches PA can perform a plurality of functions. First, each patch PA can simultaneously perform storage, release, and absorption of material. Alternatively, it is possible that each of the patches PA divides storage, release and absorption of a substance. However, the present invention is not limited to this, and it is also possible that the respective functions are performed in combination in a plurality of patches PA.

In one example, at least some of the plurality of patches PA may store material and release the stored material to a target area TA. At least some of the plurality of patches PA may absorb material from the target area TA. Some of the plurality of patches PA may emit a material that specifically binds to the material located in the target area TA. At this time, detection of the specific binding may be performed by absorbing the substance not forming the specific binding among the substances located in the target region TA using another patch PA.

3.3.4  Seventh Embodiment

In the case where a plurality of patches PA are used, each of the patches PA can simultaneously perform storage, emission, and provision of material at the same time. Alternatively, each patch (PA) can be performed separately for storage, release, and provision of environment. However, the present invention is not limited to this, and it is also possible that the respective functions are performed in combination in a plurality of patches PA.

In one example, a patch PA of a plurality of patches PA may release the stored material into the target area TA. At this time, another patch PA may provide an environment to the target area TA. Here, providing the environment may be realized by transferring the environmental condition of the substance stored in the another patch PA to the target area TA. More specifically, a reactive material is provided to a target area TA by a patch PA, which can contact the target area TA to provide a buffering environment.

As another example, the plurality of patches PA may be in contact with each other. At this time, at least one patch (PA) can store the substance and release the stored substance to another patch (PA) providing the environment. In this embodiment, the patches PA providing the environment are each capable of contacting the at least one patch PA that emits the material and is not in contact with each other, and can absorb the material from each patch PA.

4. Circulating Tumor Cell diagnosis

4.1 CTC (Circulating Tumor Cell)

The patch (PA) according to the present application can be used for cancer diagnosis. In particular, the patch PA can be used for CTC inspection.

The cancer cells CE are known to break down normal cells (CE) and transit through blood vessels or lymphatic vessels. The blood vessels and the lymph vessels are connected to organs located in the human body. The cancer cells CE migrate to tissues (for example, lymph nodes, liver, lungs) that are spaced apart from each other in accordance with the flow of blood or lymph to form new cancer tissues.

In this regard, the CTC test is performed on cancer cells (CE) floating in the blood of a subject to be diagnosed (hereinafter referred to as blood circulating cancer cells (CE)). The blood circulating cancer cell (CE) refers to a cancer cell (CE) that moves along the above-described blood or lymph.

The CTC test has the advantage of being able to detect cancer cells (CE) even when no cancer cells (CE) are detected in CT or imaging studies. That is, even when the transferred cancer tissue is not yet formed to such an extent that image sensing is possible, CTC examination can detect cancer cells (CE) migrating through the blood for metastasis.

In addition, the CTC test has an advantage that cancer can be diagnosed simply by using blood without taking a biopsy. With regard to the fact that cancer is a disease that requires continuous monitoring even after cure, cancer diagnosis through a simple procedure is a very important advantage.

Hereinafter, a method for diagnosing the blood circulation cancer cell CE will be described in advance, before explaining various embodiments of the method for detecting blood circulation cancer cells CE using the patch PA.

4.2 Diagnostic Methods

In order to detect blood circulating cancer cells (CE) and diagnose cancer, general diagnostic methods performed to detect cells (CE) can be applied.

For example, there is a method of detecting the morphology of the blood circulating cancer cells (CE). Cells (CE) distributed in the blood can be identified and the presence of cancer cells (CE) and the risk of cancer cells (CE) can be selected in consideration of the size and shape of the cells (CE).

In addition, for more accurate detection of cancer cells (CE), staining for cells (CE) distributed in the blood may proceed further. For example, the cell (CE) in the blood may be stained for cytoplasmic staining or the cell (CE) staining for the cell may proceed.

As another example, there is a method of performing immunodiagnosis for the blood circulating cancer cells (CE). Detection of the presence or absence of cancer cells (CE) in the blood can be performed using a tumor marker for the cancer cells (CE). The tumor marker may be an antibody (AB) that specifically reacts with epithelial cells (CE) or cancer cells (CE).

As another example, there is a method of performing a culture on the blood circulating cancer cells (CE).

Cells (CE) generally cease cell apoptosis at any point and apoptosis, while cancer cells (CE) have the property of infinitely proliferating. Further, the cancer cell (CE) is known to have a higher cleavage rate than a normal cell (CE).

Due to this difference, cancer cells (CE) in the blood can be detected by culturing the blood. More specifically, the cancer cell CE can be detected by confirming the cleavage rate of the cells (CE) contained in blood and the end point of cleavage.

As another example, there is a method in which DNA is extracted from the blood circulating cancer cells (CE) and the PCR process is performed using the extracted DNA.

Cancer diagnosis can be performed by amplifying the target DNA using a primer reflecting the nucleotide sequence of the DNA expressed in the cancer tissue, and confirming whether or not the extracted DNA is amplified with the markers mentioned above. In some cases, the detection of cancer using the DNA may be used to examine the type of cancer expressed in the specimen (SA).

5. Performing Diagnostics

5.1 Preparation of sample (SA)

5.1.1 Delivery of sample (SA)

The cancer diagnosis according to the present application can be performed on blood for detection of blood circulating cancer cells (CE). Considering the average rate of circulating cancer cells (CE) found in the blood of a cancer patient, about 60 ml of blood can be used for an effective cancer diagnosis, although this is not required.

The specimen SA may be provided on the plate PL. In addition, if necessary, the specimen SA may be provided as a monolayer on the plate PL. In order to provide the specimen SA as a monolayer, a method may be used in which the specimen SA is applied to the plate PL or the inflow speed and the outflow position of the specimen SA are adjusted and printed.

When the specimen SA is provided as a monolayer, some cells CE (e.g., leukocytes, erythrocytes) contained in the specimen SA may be arranged in a two-dimensional array.

When the specimen SA is provided as a monolayer on the plate PL, compared with the case where the specimen SA is discharged onto the plate PL by using a syringe or provided in a multilayer, . As a result, providing the sample (SA) as a monolayer can produce an effect that the cell-counting result of the cancer cells CE contained in the specimen SA becomes more accurate.

The sample (SA) provided on the plate PL can be fixed. For example, the specimen SA applied to the plate PL may be fixed to the plate PL. As another example, the specimen SA printed on the plate PL may be fixed to the plate PL. As another example, the specimen SA discharged using the syringe may be fixed to the plate PL.

The fixing of the specimen SA to the plate PL means a state in which the specimen SA is resistant to allow the specimen SA to stay on the plate PL until a force of a reference strength is applied to the specimen SA do. As a result, even when the patch PA and the plate PL come into contact with or separate from each other, the sample SA may not be absorbed into the patch PA.

The method of fixing the specimen SA to the plate PL may be any method used in the technical field to which the present application belongs. For example, in order to fix the specimen SA to the plate PL, methanol may be supplied to the specimen SA and volatilized.

The cancer diagnosis according to the present application can be performed on a DNA sample extracted from the blood. The extracted DNA may include DNA obtained by degrading a cell membrane of blood circulating cancer cells (CE) floating in the blood.

In this connection, a lysic patch (PA) containing a lysozyme for decomposing a cell membrane can be used for DNA extraction, which will be described in more detail below.

The cancer diagnosis according to the present application may be performed to detect DNA (hereinafter referred to as CtDNA) of cancer cells (CE) floating in the blood.

The CtDNA may be released from cancer cells (CE) that have been ruptured and killed. Some of the CtDNA released into the blood can not be removed by macrophages and drift into the blood due to their rapid and large-scale properties. CtDNA, which drifts in the blood, can be used to diagnose cancer through DNA detection of blood.

The detection of the DNA of cancer cells (CE) floating in the blood is the same in that the DNA of the cancer cell (CE) is detected from the extracted DNA sample and the diagnosis of cancer is performed using the DNA. Therefore, the detection of the DNA of the cancer cell (CE) floating in the blood described above can proceed similar to the detection of the DNA of the cancer cell (CE) from the extracted DNA sample.

Hereinafter, a method of performing cancer diagnosis on blood in order to detect circulating cancer cells (CE) will be described in detail. In the following description, it is assumed that the specimen SA is provided on the plate PL.

Further, in explaining detection of DNA for cancer diagnosis, a method of pre-treating the blood to detect DNA of blood circulating cancer cells (CE) will be described in detail. However, a method of detecting DNA floating in blood for detecting the CtDNA may be easily understood by a method of detecting DNA by pretreatment of the blood.

5.1.2  Cell filtering

The diagnosis of cancer according to the present application can be performed on a specimen (SA) subjected to filtering. In carrying out the cancer diagnosis, a filtering procedure may be further performed by using a size, a density, or a specific marker of the cancer cell CE, and the like.

Considering that blood circulating cancer cells (CE) to be detected in the cancer diagnosis according to the present application are distributed in a very small specific gravity in the blood, the above-mentioned filtering has an advantage in that detection efficiency can be increased through selection of a cancer cell (CE) This can be.

However, the above description is made to clarify that the cancer diagnosis according to the present application can be performed on a specimen (SA) subjected to a filtering procedure if necessary, and it means that a filtering procedure is necessarily performed no.

Hereinafter, a patch PA that can be used in performing cancer diagnosis according to the present application will be described.

5.2 Preparing the Patch

5.2.1 Morphology

In order to diagnose cancer according to the present application, the patch (PA) may be used in analyzing the shape of cells (CE) contained in blood. The patch PA may cause the substance stored in the patch PA to move to the plate PL due to the contact with the plate PL.

By analyzing the shape of the sample (SA), cancer diagnosis can be performed. More specifically, the cancer diagnosis can be performed by confirming the size of the cells (CE) contained in the blood and the shape of the nucleus.

However, for more accurate morphological analysis, cancer cells (CE) can be stained.

The patch can store a dye sample. Here, the dye sample can be variously changed according to the purpose of the blood test or the staining method to be performed. Representative examples of the dyed samples include Romanowsky stain such as acetic acid carmine, methylene blue, eosin, acidic hopsin, sapranin, janus green B, hemotoxylin, Kimchi juice, Dye solutions used, reshuman dyes, gram stain solutions, carboulocins, Ziehl solutions, and the like.

Of course, the dyed samples in the present invention are not limited to the examples described above, and various materials for staining blood may be used as the dyed samples. For example, the dye sample may be fluorescent DAPI.

The patch (PA) can store a single dye sample. Alternatively, the patch PA may store two or more dye samples together. In this regard, in the staining method using a plurality of types of staining samples, only a part of the plurality of types of staining samples may be stored.

The patch PA may store a washing solution. As an example, the washing solution may be TBS or PBS to which tween-20 is added. The patch PA storing the washing solution can absorb the substance in the plate PL by contacting and separating the plate PL.

The patch PA may store the buffer solution. The patch PA may function to provide an environment by contacting the plate PL and an environment suitable for the dyeing may be formed in the specimen SA located on the plate PL. The buffer solution may be a solution having an intellectual pH per staining method.

5.2.2 Immunochemistry

In order to diagnose cancer according to the present application, the patch PA may be used in performing immunological diagnosis on blood. The patch PA may cause the substance stored in the patch PA to move to the plate PL due to the contact with the plate PL.

The patch (PA) may store an antigen. The patch PA may store a biological sample containing an antigen (i.e., a sample (SA)).

The patch PA may store the antibody AB. For example, the antigen to be detected by the antibody (AB) may be EpCAM or cytokeratin known to be distributed on the surface of the cancer cell (CE).

According to the indirect method, the antibody AB stored in the patch PA may be the primary antibody AB or the secondary antibody AB. The patch PA may store the primary antibody AB or may store the secondary antibody AB or may store the primary antibody AB and the secondary antibody AB together Can be.

The patch PA may store a substrate SU. The substrate (SU) can perform a reaction catalyzed by an enzyme, and the substrate (SU) used can be changed according to an enzyme to be used and a detection method. For example, the substrate SU may be ABTS (3-ethylbenzothiazoline-6-sulphonic acid), TMB (3,3 ', 5,5'-Tetramethylbenzidine) or the like.

The patch PA may store a washing solution. As described above, the patch PA storing the washing solution is able to absorb the substance in the plate PL by contacting and separating the plate PL. At this time, the sample (SA) fixed to the plate (PL) and some substances combined with the sample (SA) may not be absorbed.

The patch PA may store the buffer solution. The patch PA may perform a function of providing an environment by contacting the plate PL and an environment suitable for each step of the immunodiagnosis may be provided to the sample SA located on the plate PL . As an example of the buffer solution, a peroxide buffer may be used to detect chemiluminescence.

The patch PA storing the washing solution (hereinafter referred to as the wash patch PA) and the patch PA storing the buffer solution (hereinafter referred to as the buffer patch PA) And the buffer patch PA.

5.2.3  Culture

For cancer diagnosis according to the present application, a patch (PA) may be used in carrying out the method of culturing the cells (CE). The patch PA may cause the substance stored in the patch PA to move to the plate PL due to the contact with the plate PL.

The patch PA may store a nutrient sample NT (hereinafter referred to as a nutrient patch PA). The nutrient sample (NT) may be a component necessary for culturing the cell (CE). For example, the patch PA may contain amino acids, vitamins, trace elements, and the like. As another example, the patch PA may contain proteins, peptides, hormones, minerals, and the like.

The patch PA may store a washing solution. As described above, the patch PA storing the washing solution is able to absorb the substance in the plate PL by contacting and separating the plate PL.

The patch PA may store the buffer solution. The patches PA may function to provide an environment by contacting the plate PL. In other words, by the contact of the patches PA, an environment suitable for the cell culture can be established in the sample (SA) placed on the plate PL. As an example, the patch PA may be used to control the pH composition of a specimen that changes as the cell CE is cultured.

The patch PA storing the washing solution (hereinafter referred to as the wash patch PA) and the patch PA storing the buffer solution (hereinafter referred to as the buffer patch PA) (PA) and buffer patch (PA).

5.2.4 PCR (Polymerase chain reaction)

In order to diagnose cancer according to the present application, a patch (PA) may be used in performing a PCR method for amplifying DNA. The patch PA may cause the substance stored in the patch PA to move to the plate PL due to the contact with the plate PL.

The patch (PA) may store lysozyme. The patch PA can move the lysozyme stored in the patch PA to the specimen SA by contacting the plate PL and consequently the blood circulation Cell membranes of cancer cells (CE) can be destroyed.

When the cell membrane of the blood circulation cancer cell (CE) is destroyed, the DNA in the cancer cell (CE) can be leaked to the specimen. Therefore, the patch PA may allow the DNA of the blood circulation cancer cells CE to flow out to the plate PL.

The patch (PA) can store a primer. The primers can be made to correspond to some previously known sequences of cancer patients. The primer moves from the patch PA to the plate PL and in the annealing step a partial sequence of the DNA contained in the specimen SA can bind to the primer.

The patch PA may store dNTPs. The dNTP moves from the patch PA to the plate PL and the target DNA of the specimen SA can be bound to the dNTP in a polymerisation extension step.

The patch (PA) can store a DNA polymerase. The DNA polymerase can perform the function of binding the dNTP to the DNA bound to the primer. For example, the DNA polymerase may be taq polymerase.

The patch PA may store the buffer solution. The patch PA may perform a function of providing an environment by contacting the plate PL and an environment suitable for each step of the PCR may be provided in the sample SA located on the plate PL have.

The buffer PA (hereinafter referred to as the buffer patch PA) storing the buffer solution may be somewhat similar to the buffer patch PA used in the morphological diagnosis, immunodiagnosis and cell culture diagnosis.

The patch PA can store the coenzyme. The coenzyme can be changed according to the DNA polymerase. For example, when the DNA polymerase is taq polymerase, the coenzyme may be MgCl2. The patches PA may contact the plate PL to provide an environment for activation of the DNA polymerase.

Hereinafter, some diagnostic methods performed for cancer diagnosis according to the present application will be described.

5.3 Diagnostic Methods

5.3.1 Morphology

In the cancer diagnosis according to the present application, the shape diagnosis using the patches PA and PL can be performed.

More specifically, the cancer cell (CE) can diagnose cancer through the shape of the nucleus of the cancer cell (CE) in consideration of the fact that the cancer cell (CE) has a different nucleus shape from the normal cell (CE). Alternatively, considering the fact that the size of the cancer cells CE is larger than the size of the normal cells CE, cancer can be diagnosed through the outline of the cancer cells CE.

In the case of cancer diagnosis for performing the morphological analysis, it can be performed by smearing the specimen (SA), taking an image, and analyzing the image of the specimen (SA) taken. However, for more accurate diagnosis, staining for the specimen (SA) can be performed.

Hereinafter, a method of performing staining for the specimen (SA) will be briefly described.

The morphological diagnosis using the patch PA and the plate PL can be performed by dyeing. The sample (SA) provided on the plate (PL) can be fixed and a dye can be provided. The provision of the dye may be performed by a patch PA (hereinafter referred to as a dye patch PA) that stores a dye sample.

When the dye sample contained in the patch PA moves to the specimen, the cytoplasm or nucleus of the cell (CE) contained in the specimen can be stained. Alternatively, if the dye sample contained in the patch PA moves to the blood, the DNA located inside the cell (CE) contained in the sample may be stained.

More specifically, a patch (PA) containing a nuclear staining sample can stain nuclei of cells (CE) contained in blood. As the nuclear dye sample, a basic dye sample is mainly used. Typical examples thereof include methylene blue, toluidine blue, and hymatoxylin.

A patch (PA) containing a cytoplasmic staining sample can stain the cytoplasm of the cell (CE) contained in blood or the outer structure of the cell (CE). As the cytoplasmic staining specimen, mainly an acid dye sample is used, and representative examples thereof include eosin, acid fuchsin, and orange G (oreng G).

Furthermore, the DNA in the cells (CE) contained in the blood can be stained to confirm the shape of the stained cells (CE) and / or the nucleus position. To this end, the patch PA may store DAPI with membrane permeability. The DAPI penetrates the cell membrane and binds to the DNA distributed in the cell membrane, so that the cell (CE) can be stained.

After the dye sample is provided to the sample (SA), a buffer solution is provided to the sample (SA), so that an appropriate environment for dyeing can be provided. The provision of the buffer solution may be performed by a buffer patch (PA) storing the buffer solution. This may be for enhancing the dyeing efficiency of the sample (SA).

After the dye sample is provided to the sample (SA), the sample (SA) is provided with a washing solution to remove unnecessary dye after dyeing. The provision of the washing solution may be performed by a washing patch (PA) storing the washing solution. This may be to obtain a clearer image of the specimen (SA).

The morphological diagnosis using the stained blood can be performed in various ways. As an example, it can be performed by capturing an image of the stained blood and analyzing the captured image. The analysis of the image may be performed by counting the number of cancer risky cells in the photographed image and analyzing and classifying the type of the cancer cells.

Here, it is preferable that the plate PL is prepared as a material that allows light emitted from a light source to pass through as much as possible. The light source may emit white light or emit a specific wavelength of light.

5.3.2  Immunochemistry

In cancer diagnosis according to the present application, immunodiagnosis using the patches (PA) and the plate (PL) can be performed. The antibody (AB) described below can bind specifically to a protein attached to the surface of blood circulating cancer cells (CE), unless otherwise specified.

Immunodiagnosis using the patches (PA) and the plate (PL) can be performed according to a direct method. The sample (SA) (or antigen) provided on the plate PL may be immobilized to provide an antibody (AB) specifically binding to the antigen to be detected. This can be performed by a patch PA (hereinafter referred to as an antibody patch PA) storing the antibody AB described above. The antibody (AB) may be labeled with a label for identification. After the antibody (AB) is provided, a procedure for removing the antibody (AB) which is not bound to the antigen provided to the plate (PL) can be performed. This can be performed by a patch PA (hereinafter referred to as a wash patch PA) storing the above-described washer solution.

Immunodiagnosis using the patches (PA) and the plate (PL) can be performed according to an indirect method. The sample (SA) (or antigen) provided on the plate PL may be fixed and a primary antibody (AB) specifically binding to the antigen to be detected may be provided. This can be performed by the above-described antibody patch (PA). The primary antibody (AB) may not have a marker for identification. After the primary antibody (AB) is provided, a secondary antibody (AB) that specifically binds to the primary antibody (AB) may be provided to the plate (PL). This can be performed by the above-described antibody patch (PA). The secondary antibody (AB) may be labeled with a marker for identification. After the secondary antibody (AB) is provided, the primary antibody (AB) that is not bound to the antigen provided to the plate (PL) and the secondary antibody (AB) that is not bound to the primary antibody A procedure can be performed. This can be performed by the above-described washer patch PA.

Immunodiagnosis using the patches (PA) and the plate (PL) can be carried out according to the sandwich method. The plate (PL) may be provided with an antibody (AB) specifically binding to an antigen to be detected. The sample (SA) may be provided on the plate (PL) on which the antibody (AB) is provided. After the sample (SA) is provided, an antibody (AB) that specifically binds to the antigen can be provided to the plate (PL). This can be performed by the above-described antibody patch (PA). After the antibody AB is provided, a procedure may be performed in which the antibody AB that is not bound to the antigen provided to the plate PL is removed. This can be performed by a patch PA (hereinafter referred to as a wash patch PA) storing the above-described washer solution. The antibody (AB) may be labeled with a marker for identification.

Cancer detection through immunodiagnostic methods can be performed in a variety of ways. For example, it is possible to detect color development through an enzyme-substrate (SU) reaction, to detect fluorescence of a fluorescent marker, and to detect light through a chemical reaction.

Hereinafter, a method of using an enzyme-substrate (SU) reaction or using a fluorescent marker will be described in more detail.

For example, color development through the enzyme-substrate (SU) reaction can be detected to confirm the presence or absence of the antigen of the sample (SA). The antibody (AB) in the direct method described above or the secondary antibody (AB) in the indirect method may have an enzyme attached thereto as a marker. Once the antibody (AB) is provided to the sample (SA), the sample (SA) can be provided with a substrate (SU). This can be performed by a patch PA (hereinafter referred to as a substrate patch PA) including a substrate SU. The enzyme attached to the antibody (AB) can catalyze the chemical reaction of the substrate (SU) to generate a product. By the generated product, color development can be detected in the specimen.

When color development is detected by the generated product, the specific binding between the antibody (AB) and the antigen can be quantitatively measured by measuring the color development. The measurement of color development may be performed by a method of detecting light emitted from the light source and passing through the plate PL. In other words, measuring color development can be performed in a manner that measures the absorption. When measuring the color development, a spectrophotometer can be used. At this time, it is preferable that the plate PL is transparent and flat.

As another example, fluorescence can be detected through the fluorescence marker and the presence or absence of the antigen of the sample (SA) can be confirmed. The antibody (AB) in the direct method described above or the secondary antibody (AB) in the indirect method may have a fluorescent substance attached thereto as a marker.

When the fluorescence detection method is used, fluorescence of the sample (SA) can be measured to quantitatively measure the specific binding of the antigen (AB) to the antigen. The measurement of the fluorescence can be performed in a manner that light is incident on the plate PL and fluorescence emitted from the plate PL is measured. When measuring the fluorescence, a fluorometer equipped with a filter may be used. When the fluorescence is measured, it is preferable that the plate PL is opaque black or opaque white.

The above-described coloring or fluorescence can be detected through an image. The image can be photographed partly, and the photographed image can be collected into one. From the image, the location of the target antigen / antibody (AB) distribution, the shape of the cell (CE), the distribution of the target protein, and the like can be confirmed.

5.3.3  Culture

In cancer diagnosis according to the present application, culturing of cells (CE) can be carried out using the patches (PA) and the plates (PL). The nutritional patches (PA) described below may store nutrients required for culturing the cancer cells (CE).

In the cell culture using the patch PA and the plate PL, the sample SA is provided on the plate PL, and the nutrient sample NT can be provided on the sample SA . The sample (SA) can be provided with the nutritional sample (NT) by the above-described nutritional patch (PA).

When a predetermined time has elapsed since the sample (SA) is provided with the nutrient sample, the cell (CE) contained in the sample can proliferate.

Analysis on proliferated cells (CE) can be performed in a variety of ways. As an example, an image of a specimen (SA) in which cell (CE) cultivation has been completed for a certain period of time can be obtained, and the image can be analyzed. As another example, an image of a specimen (SA) undergoing cell (CE) culture can be obtained and the image can be analyzed.

The analysis on the image can be performed in consideration of the cleavage rate of the cell CE and the termination time of the cleavage of the cell CE. In other words, while the cleavage rate of cancer cells (CE) is higher than the cleavage rate of normal cells (CE) and the cleavage of normal cells (CE) ends at an arbitrary point, cancer cells (CE) , It is possible to identify the cell (CE) that continuously divides and divides at a relatively high rate, thereby confirming whether or not the cancer has occurred.

Also in this case, it may be preferable that the plate PL is prepared as a material through which light emitted from a light source is transmitted as much as possible.

5.3.4  PCR

In cancer diagnosis according to the present application, PCR can be performed using the patches (PA) and the plate (PL). The primers described below can be made to correspond to the DNA sequence of a cancer patient.

PCR using the patch PA and the plate PL can be performed on the specimen SA provided on the plate PL. The sample (SA) may be a sample obtained by extracting DNA from blood. The DNA sample can be heated at a temperature at which two strands of DNA contained in the sample are separated (hereinafter referred to as heat denaturation temperature).

The heated DNA sample may be provided with a primer. The provision of the primer can be performed by a patch (PA) including a primer. The DNA sample provided with the primer can be adjusted to a temperature at which the primer can bind to the DNA (hereinafter, annealing temperature). The primer may be provided with a marker for identification.

After the primer binds to the DNA, the sample may be provided with dNTP, DNA polymerase, buffer solution and coenzyme. This can be performed by a patch (PA) for storing the dNTP, a patch (PA) for storing the DNA polymerase, a patch (PA) for storing the buffer solution, and a patch (PA) for storing the coenzyme. Alternatively, it can be carried out by a patch (PA) storing at least two of dNTPs, DNA polymerase, buffer solution and coenzyme described above. If the temperature of the sample is adjusted to a temperature at which the DNA bound to the primer can be extended (hereinafter referred to as a polymerization reaction temperature), the DNA bound to the primer can be extended.

Cancer diagnosis through the PCR process can be performed in various ways. For example, fluorescence of a fluorescent marker can be detected, and electrophoresis can be used. In addition, the target DNA can be detected on the sample (SA) subjected to the PCR process according to the analysis time of the sample (SA), or the sample (SA) on the way of the PCR process can be detected DNA detection can proceed.

The identification marker attached to the above-mentioned primer may be a fluorescent substance. In addition, the fluorescent material may be a substance that fluoresces until the fluorescence is consumed, or may be a substance designed to fluoresce when the primer and the DNA are combined.

Immunodiagnosis has already been described in detail for detection methods using fluorescent markers, and a detailed description thereof will be omitted.

As described so far, cancer diagnosis according to one embodiment of the present application can be performed through morphological diagnosis, immunological diagnosis, culture progress diagnosis and DNA diagnosis (i.e., PCR test).

Hereinafter, in order to facilitate understanding, a method of performing cancer diagnosis using a patch (PA) for each diagnosis method will be described in detail with some embodiments.

6. Examples of diagnostic processes using patches

6.1 Morphology

FIG. 35 is a diagram for explaining the morphological diagnosis using the staining method in the cancer diagnosis according to the embodiment of the present application. FIG. The morphological diagnosis according to an embodiment of the present application may include providing a sample SA to a plate PL, providing S1100 to a plate PL, (S1300) of taking an image of the subject. This may correspond to the execution of morphological diagnosis through simple staining.

In the morphological diagnosis for cancer diagnosis according to the present application, as described above, nuclei and / or cytoplasm of cancer cells (CE) can be stained.

Providing the specimen SA to the plate PL (S1100) may mean placing the specimen SA on the plate PL. As an example, the specimen SA may be plated or printed on the plate PL. In addition, the specimen SA may be fixed to the plate PL. The specimen SA has a certain resistance and is fixed to the plate PL so that the specimen SA is not absorbed into the patch PA by the contact or separation of the patch PA and the plate PL. .

In order to provide a dye sample to the plate PL (S1200), a dye patch PA may be used. In the patch PA, a single dye sample may be stored.

The dye reagent stored in the patch PA by the contact between the patch PA and the plate PL can be moved to the plate PL. In order to provide a dye sample to the plate PL, the patch PA and the plate PL may be in contact with each other. In addition, the patch PA and the plate PL can be separated after contact.

In this step, if necessary, the buffer patch PA may be used to implement a predetermined environment in the specimen SA.

Also, in this step, washing may be performed to remove an unnecessary dye reagent provided in the specimen (SA). The washing may be performed by a washing patch PA storing the washing solution.

After the staining sample is provided, an image of the stained specimen (SA) located on the plate (PL) can be taken (S1300). When the image of the specimen SA is photographed, analysis of the image can be performed.

The image may be analyzed to compare the size and shape of the cells (CE) contained in the blood. The cancer cells CE are larger in size and different in shape than general cells CE, and can detect cancer cells CE through image analysis and count the number of cancer cells CE.

FIG. 36 is a diagram for explaining the morphological diagnosis by using a staining method using a plurality of stained samples in the cancer diagnosis according to the embodiment of the present application. FIG.

In the step of providing the dye sample to the plate PL (S 1200), at least two dye samples can be delivered. At this time, in order to deliver the at least two dyed samples to the specimen (SA), a plurality of dyed patches (PA) storing one of the plurality of dyed samples may be used.

Hereinafter, for convenience of description, two dyeing patches (PA), namely, a first staining patch (PA) and a second staining patch (PA) are used to stain specimens using two staining samples Explain.

However, in this embodiment, the number of dye patches PA is not limited to two, and three or more dye patches PA may be used. Variations using three or more staining patches (PA) in the following description should be understood to be included in this embodiment as they are applicable to those skilled in the art without inventive thought.

The step S1200 of providing a dye sample to the plate PL may include providing a first dye sample to the plate PL and providing a second dye sample to the plate PL . ≪ / RTI >

Here, the first staining sample and the second staining sample can stain different target substances in the blood. For example, the first staining sample may be one of a basic staining sample staining the nucleus and an acid staining sample staining the cytoplasm, and the second staining sample may be the other staining sample. Or vice versa. Specifically, the first staining sample may be methylene blue, and the second staining sample may be eosin. Of course, it should be noted that the types of the first dye sample and the second dye sample are not limited by the above-described examples.

When the first staining patch PA comes into contact with the plate PL, the first staining sample can move to the plate PL. Therefore, the staining patch PA for storing the first stained sample may stain the first target material contained in the specimen SA. When the second staining patch PA comes into contact with the plate PL, the second staining sample can move to the plate PL. Therefore, the dyeing patch PA storing the second stained sample can stain the second target material contained in the specimen SA. Here, the first target material may be any one of a cell (CE) nucleus and a cytoplasm, and the second target material may be another one of a cell (CE) nucleus and a cytoplasm.

FIG. 37 is a diagram for explaining the morphological diagnosis using the DAPI staining method in cancer diagnosis according to one embodiment of the present application. FIG.

In step S1240 of providing a dye sample to the plate PL, a fluorescent dye sample may be provided on the plate PL. For example, the dye sample may be DAPI (4 ', 6-diamidino-2-phenylindole).

A patch PA for storing the dye sample can contact the plate PL and a dye sample stored in the patch PA by contact between the patch PA and the plate PL is transferred to the plate PL).

The stained sample can permeate through the cell membrane and enter the cell (CE). When the cell membrane is destroyed, the DAPI staining efficiency can be further improved. However, in the DAPI staining method, the staining sample can be introduced into the cell even when the cell membrane is present.

If necessary, the pH value of the sample (SA) can be adjusted. The pH of the sample (SA) can be performed by a buffer patch (PA) storing the buffer solution.

In addition, the temperature of the sample (SA) can be adjusted. Preferably, after the dye sample is provided to the sample (SA), the temperature of the sample (SA) is maintained at about 37 for 15 minutes to provide a sufficient reaction time for the sample (SA).

The image of the stained specimen SA can be photographed (S1300). However, in this embodiment, considering that the dyeing reagent used is a fluorescent reagent, a fluorescence image can be taken. Therefore, in order to capture the fluorescence image, light of an arbitrary wavelength band may have to be provided to the specimen SA.

Fluorescent images using the DAPI staining method have a high resolution and may be advantageous in performing more accurate cancer diagnosis.

6.2 Immunochemistry

FIG. 38 is a diagram for explaining performing immunological diagnosis in cancer diagnosis according to one embodiment of the present application. FIG. The method of immunodiagnostics according to one embodiment of the present application includes the steps of providing a sample (SA) to a plate (PL) (S2100), providing an antibody (AB) to a plate (PL) (Step S2300). In step S2300, the antibody AB is detected. This may correspond to performing an immunodiagnosis through a direct method.

In the immunoassay for cancer diagnosis according to the present application, as described above, an antibody (AB) that specifically binds to EpCAM or cytokeratin can be used.

The step of providing the specimen SA to the plate PL (S2100) may be similar to the step S1100.

To provide the antibody AB to the plate PL (S2200), an antibody patch PA may be used. The contact between the patch PA and the plate PL allows the antibody AB stored in the patch PA to move to the plate PL. The antibody (AB) can bind specifically to an antigen contained in a specimen (SA) provided in the plate (PL).

When the antibody (AB) is provided to the plate (PL), the antibody (AB) specifically binding to the antigen can be identified (S2300). Prior to this step, as required, a washing patch PA may be used to remove the antibody AB that has not bound to the sample (SA).

The antibody (AB) specifically binding to the antigen can be identified through various methods.

In one example, an antibody (AB) specifically binding to the antigen can be identified using a substrate (SU) -enzyme reaction.

39 and 40 are diagrams for explaining a method of detecting cancer using a substrate-enzyme reaction when immunodiagnosis is performed in cancer diagnosis according to an embodiment of the present application.

When the antibody (AB) is provided by the patch (PA), the antibody (AB) may have an enzyme bound thereto. The marker bound to the antibody (AB) may be an enzyme. The sample (SA) provided with the antibody (AB) by the patch (PA) may be in a state of being coupled with some antibodies (AB) provided by the patch (PA).

 The sample (SA) may be provided with a substrate patch (PA). When the substrate (PA) is provided on the specimen (SA), the substrate (SU) can react with the enzyme attached to the antibody (AB) bound to the specimen. More specifically, the product may be produced due to the reaction catalyzed by the substrate. The presence or absence of the blood circulating cancer cells (CE) can be confirmed in the sample (SA) through the presence or absence of the production of the product.

At this time, the substrate patch (PA) can perform a function of providing a reaction space in which the enzyme and the substrate (SU) can react. In this regard, the function of the aforementioned patches (PA) has been described in detail.

As another example, using a fluorescent substance, an antibody (AB) specifically binding to the antigen can be identified.

FIG. 41 is a diagram for explaining a method of detecting cancer using a fluorescent substance when immunodiagnosis is performed in cancer diagnosis according to an embodiment of the present application. FIG.

When the antibody (AB) is provided by the patch (PA), the antibody (AB) may have a fluorescent substance bound thereto. The marker bound to the antibody (AB) may be a fluorescent substance. The sample (SA) provided with the antibody (AB) by the patch (PA) may be a state in which some of the antibodies (AB) provided by the patch (PA) are bound.

The contact between the patch PA and the plate PL can be released. This may be to prevent the fluorescence from being developed by the antibody AB (that is, the antibody AB that has not yet bound to the sample SA) stored in the patch PA.

After the contact between the patch PA and the plate PL is released, depending on whether or not the fluorescent substance attached to the antibody AB associated with the sample SA is emitted, CE).

When the antibody (AB) specifically binding to the antigen is identified by using the fluorescent substance, fluorescence images of the sample (SA) can be photographed to confirm the position where the antibody (AB) is attached. The cancer cell (CE) distributed in the blood can be cell-counted by analyzing the position where the antibody (AB) is attached.

A plurality of images for the specimen SA can be obtained with the passage of time. By comparing the changes of the previous shot image and the subsequent shot image among the plurality of images, diagnosis can be performed for a plurality of targets.

42 is a diagram for explaining a method of performing immunodiagnosis using a plurality of types of antibodies AB in cancer diagnosis according to an embodiment of the present application.

For example, when the sample (SA) is provided to the plate (PL) (S2100), the sample (SA) is provided with a third antibody (AB) (for example, CD45) specifically binding to leukocytes (S2250) can do. The provision of the third antibody AB may be performed by a patch PA in which the third antibody AB is stored.

After the third antibody AB is provided to the sample SA, the antigen specifically binding to the third antibody AB can be identified (S2350). That is, after the third antibody AB is provided, an image of the specimen SA may be acquired, and the image may be analyzed to count the number of white blood cells contained in the specimen SA.

The fourth antibody AB for the cancer cells CE may be provided to the plate PL (S2260). The provision of the fourth antibody AB may be performed by a patch PA in which the fourth antibody AB is stored.

After the fourth antibody AB is provided to the specimen SA, the antigen specifically binding to the fourth antibody AB can be identified (S2360). That is, after the provision of the fourth antibody AB, an image for the specimen SA can be obtained, and the image can be analyzed. The number of cancer cells CE included in the specimen SA can be counted by analyzing the image with consideration of the position where the fluorescence is displayed in the previously acquired image after confirming the position where the fluorescence is displayed in the currently obtained image .

FIG. 43 is a diagram for explaining a method of performing immunodiagnosis using the primary antibody (AB) and the secondary antibody (AB) in cancer diagnosis according to an embodiment of the present application. This may correspond to performing immunodiagnosis through indirect methods.

(S2200) of providing the antibody (AB) to the plate PL may include the step of providing the first antibody AB to the plate PL and the step (S2220) of the second antibody (AB) to the second antibody (AB).

The first antibody (AB) may be an antibody (AB) that specifically binds to cancer cells (CE). The second antibody (AB) may be an antibody (AB) that specifically binds to the first antibody (AB). Here, the specific binding between the first antibody (AB) and the second antibody (AB) may be a species-specific binding rather than an epitope-specific binding. Immunodiagnostic methods using the first antibody (AB) and the second antibody (AB) can be used for the convenience of producing a specific antibody (AB).

The first antibody (AB) may be provided by a patch (PA) storing the first antibody (AB). The second antibody (AB) may be provided by a patch (PA) storing the second antibody (AB). Alternatively, the first antibody AB and the second antibody AB may be provided by a patch PA that stores both the first antibody AB and the second antibody AB.

In order to provide the first antibody AB to the plate PL, a patch PA storing the first antibody AB may be in contact with the plate PL. In order to provide the second antibody AB to the plate PL, a patch PA for storing the second antibody AB may be in contact with the plate PL.

Alternatively, in order to provide the first antibody (AB) and the second antibody (AB) to the plate (PL), the patch (PA) storing the first antibody (AB) and the second antibody And can be in contact with the plate PL. In order to provide a first antibody (AB) and a second antibody (AB) to the plate (PL), the patch (PA) storing the first antibody (AB) contacts the plate (PL) The patch PA storing the antibody AB may be in contact with the first antibody AB.

After the step of providing the antibody AB to the plate PL, a washing patch (not shown) may be provided to remove the antibody AB provided by the patch PA, PA) may be used.

Figure 44 is a graph showing the results of immunodiagnosis using the first antibody (AB) coated on the plate (PL) and the second antibody (AB) provided on the specimen (SA) in cancer diagnosis according to an embodiment of the present application And FIG. This may correspond to performing immunodiagnosis through the sandwich method.

The first antibody AB can be positioned (S2020) on the plate PL by a conventional method. For example, a method of applying the first antibody to the plate and freeze-drying can be applied. The first antibody (AB) may be an antibody (AB) that specifically binds to cancer cells (CE).

The first antibody AB may be fixed to the plate PL. The immobilization of the first antibody (AB) can be carried out by drying the antibody (AB) or by using a coating buffer solution. Alternatively, the fixing of the antibody AB to the plate PL may be performed by forming a thin film on the plate PL. The thin film may be prepared by previously manufacturing and attaching to the plate PL.

The sample SA may be provided to the plate PL on which the first antibody AB is placed (S2100). Providing the sample (SA) to the plate (PL) may be to apply the blood. In addition, the application of the blood can be applied thinly in consideration of the reaction area with the antibody (AB) fixed to the plate (PL). Preferably, the blood can be applied as a mono-layer.

The second antibody AB may be provided (S2200) to the plate PL. The second antibody (AB) may be an antibody (AB) that specifically binds to leukocytes. Alternatively, the second antibody (AB) may be an antibody (AB) that specifically binds to cancer cells (CE). At this time, the second antibody (AB) may be different from the first antibody (AB).

The second antibody (AB) can be performed by the direct method or the indirect method described above. In other words, providing the second antibody (AB) to the plate (PL) may be to provide an antibody (AB) that binds specifically to the antigen to be detected, and specifically to the antigen to be detected To provide a primary antibody (AB) that binds and a second antibody (AB) that specifically binds to the primary antibody (AB).

As described above, the first antibody AB and / or the second antibody AB can be provided by the patch PA. At this time, the immunological diagnosis method according to the direct method or the indirect method described above can be applied.

The sample (SA) can not bind to the sample (SA) as needed after the step of providing the sample (SA) to the plate (PL) and / or after the step of providing the antibody (AB) A washing patch PA may be used to remove the antibody AB provided by the patch PA.

6.3 Culture

45 is a diagram for explaining that cell (CE) culture is performed in cancer diagnosis according to an embodiment of the present application.

The cell culturing process according to an embodiment of the present invention includes a step S3100 of providing a sample SA to a plate PL and a step S3200 of providing a nutrient sample NT to the plate PL. And taking an image of the specimen SA (S3300). This may be for detecting blood circulating cancer cells (CE) contained in the specimen (SA).

The step of providing the specimen SA to the plate PL (S3100) may be similar to the step S1100.

The specimen SA placed on the plate PL may be provided with a nutrient sample NT (S3200). The nutrient sample (NT) may be provided by a patch (PA) storing at least a part of reagents used for culturing the cancer cells (CE).

As described above, the patch PA may contain amino acids, vitamins, trace elements, and the like. Alternatively, the patch PA may contain proteins, peptides, hormones, minerals, and the like in other examples.

The contact between the patch PA and the plate PL allows the nutrient sample NT stored in the patch PA to move to the plate PL. When the nutrient sample (NT) is provided, the cells (CE) contained in the sample (SA) located on the plate (PL) can propagate.

If necessary, a washing process may be performed on the plate PL in this step. This may be a procedure performed by the wash patch PA described above.

For analysis of the proliferated cells (CE), an image may be taken 3300 for the specimen (SA). As described above, an image of the sample (SA) in which the cell (CE) culture has been completed or the sample (SA) in which the culture of the cell (CE) is in progress can be obtained.

A plurality of images for the cells CE can be obtained. The image of the sample (SA) is obtained once before the start of culturing of the cell (CE), and can be obtained at least once at a desired time point. The image acquired before the start of culturing of the cells (CE) may be for the purpose of estimating the cell proliferation rate using images prior to cell culture in the analysis of images.

46 and 47 are diagrams for explaining the process of proliferation of cells (CE) contained in a specimen in cancer diagnosis according to one embodiment of the present application.

Referring to Figure 46, in cell culture (CE) according to one embodiment of the present application, a specimen (SA) may be applied to a plate PL. The applied sample (SA) may contain some cells (CE). The contact between the nutrition patch PA and the plate PL makes it possible to move the nutrient sample NT stored in the nutrition patch PA to the plate PL.

When the nutrient sample NT stored in the nutrient patch PA is supplied to the sample SA applied to the plate PL, the cells CE contained in the sample SA can propagate.

As shown in FIG. 47, the proliferation rate of the cells CE may be partly different. The cleavage rate of cancer cells (CE) may be faster than that of normal cells (CE). By comparison, the cancer cells CE contained in the specimen SA can be detected. This can be a way of estimating highly dividing cells (CE) as cancer cells (CE).

6.4 PCR

FIG. 48 is a view for explaining that a PCR process is performed in cancer diagnosis according to an embodiment of the present application. FIG. The PCR process according to an embodiment of the present application includes the steps of providing a sample SA to a plate PL (S4100), providing a reagent to the plate PL (S4200), changing the temperature of the sample SA (Step S4300), and analyzing the sample SA (step S4400). This may be for detecting the DNA of blood circulating cancer cells (CE) contained in the specimen (SA).

The step of providing the specimen SA to the plate PL (S4100) may be similar to the step S1100. However, a specimen (SA) that has been subjected to a pre-treatment for extracting DNA from the blood may be used.

A reagent may be provided (S4200) to the plate PL provided with the sample (SA). The reagent may be provided by a patch (PA) storing a reagent of at least a part of a plurality of reagents used in the PCR process.

The patch PA may be a patch PA for storing a dNTP, a patch PA for storing a primer, and a patch PA for storing a DNA polymerase. Also, the patch PA may be a patch PA for storing a buffer solution, and may be a patch PA for storing a coenzyme. Alternatively, the patch (PA) may be a patch (PA) for storing at least two reagents among the above-mentioned dNTPs, primers, DNA polymerase, buffer solution and coenzyme.

The patch PA and the plate PL may be in contact with each other so that the reagent contained in the patch PA is provided to the plate PL. By the contact between the patch PA and the plate PL, the reagent stored in the patch PA can move to the plate PL.

When reagents are supplied to the plate PL using a plurality of patches PA, the plurality of patches PA are sequentially brought into contact with the plate PL, The patch PA may be brought into contact with the plate PL and the one patch PA and the other patch PA may be brought into contact with the one patch PA.

When the reagent is supplied to the plate PL, the temperature of the sample SA may be adjusted (S4300). The temperature of the sample (SA) can be adjusted by heating, cooling, or maintaining the temperature of the plate (PL) at the target temperature. The temperature of the specimen SA can be adjusted by heating, cooling or keeping the temperature of the patch PA at the target temperature. The temperature of the specimen SA can be adjusted by heating, cooling, or maintaining the temperature of the patches PA and PL.

The temperature of the sample (SA) can be adjusted to the aforementioned heat denaturation temperature, annealing temperature and polymerization reaction temperature. By adjusting the temperature of the specimen (SA), the DNA contained in the specimen (SA) can be separated into a double helical structure, a primer can be bound to the separated DNA, and dNTP DNA can be lengthened by binding.

When the temperature of the specimen SA is adjusted (S4300), the specimen (SA) can be analyzed (S4400). Here, analyzing the specimen (SA) may be performed by detecting a fluorescent substance attached to the primer. Alternatively, analyzing the specimen (SA) may be for imaging an image of the specimen (SA).

The analysis may be performed after completion of the PCR process for the sample (SA). This enables more accurate data to be obtained by analysis in a state where DNA amplification of the specimen (SA) is completed.

The analysis may be performed during the PCR process on the sample (SA). More specifically, analysis of the sample (SA) can be continuously performed during the PCR process, and one cycle of the PCR process (for example, thermal denaturation step, annealing step, , It can be repeatedly performed for each cycle at an arbitrary point in time. This type of analysis allows quantitative analysis of target DNA in real time by comparing amplification amounts of DNA with time.

49 illustrates a method of decomposing a cell membrane of a cell (CE) contained in a sample (SA) using a patch (PA) in the case of performing a PCR process in cancer diagnosis according to an embodiment of the present application FIG.

In the modification of the embodiment described above, the step of providing the reagent to the plate PL (S4120) and the step of fixing the sample (SA) located on the plate PL (S4140) May be further performed after step S4100 of providing SA.

After the sample SA is supplied to the plate PL (S4100), the reagent may be supplied to the plate PL (S4120). The sample (SA) may be blood that has not undergone the pretreatment. The reagent may be a substance for decomposing the cell membrane of blood circulating cancer cells (CE) floating in the blood. For example, the reagent may be a lysozyme that destroys the membrane of the cell (CE). The reagent may be provided by the patch PA. The reagent may be stored in the patch PA.

After the reagent is supplied to the plate PL in step S4120, the sample SA located on the plate PL may be fixed in step S4140. The specimen (SA) located on the plate PL may be the DNA of the cells (CE) contained in the blood and the blood. In addition, the sample (SA) may be a state in which a part of the cell membrane of the cell (CE) floats.

After the specimen SA is fixed to the plate PL (S4140), the PCR process for the specimen SA may proceed. The subsequent PCR process can be performed irrespective of the PCR process process disclosed herein or the PCR process process performed by a typical technician.

50 is a view for explaining that a PCR process is performed in cancer diagnosis according to an embodiment of the present application. In the present embodiment, it is assumed that the reagent supplied to the plate PL is based on a plurality of patches PA.

When the specimen SA is supplied to the plate PL (S4100), the temperature of the specimen SA can be adjusted to the thermodetection temperature (S4310). The temperature of the specimen SA can be adjusted by adjusting the temperature of the plate PL and / or the patch PA, as described above. When the temperature of the specimen SA is maintained at the heat denaturation temperature for a predetermined time, the DNA contained in the specimen SA can be separated from the double helical structure.

An annealing reagent may be provided to the plate PL (S4310). Here, the annealing reagent may be at least a part of the reagents used in the annealing step. For example, the annealing reagent may be a primer.

The annealing reagent may be provided by a patch PA. The reagent stored in the patch PA can be moved to the plate PL by the contact between the patch PA and the plate PL, The reagent may be provided with the plate PL.

The patch (PA) may be storing an annealing reagent. As an example, the patch PA may be storing a primer. At this time, the primers can be produced so as to correspond to sequences commonly contained in DNA of cancer patients.

When the annealing reagent is provided to the plate PL (S4310), the reagent may be provided to the sample (SA) located on the plate PL.

The temperature of the specimen SA may be adjusted to the annealing temperature (S4320). In order for the temperature of the specimen SA to be adjusted to the annealing temperature, the temperature of the plate PL and / or the patch PA may be adjusted as described above.

The subject whose temperature is adjusted so that the temperature of the specimen SA is adjusted to the annealing temperature may be different from the subject whose temperature is controlled so that the temperature of the specimen SA is controlled to the polymerization reaction temperature. For example, in order to adjust the temperature of the specimen SA to the thermal denaturation temperature, even if the plate PL is heated, the temperature of the specimen SA may be adjusted to the annealing temperature, And may be brought into contact with the plate PL.

When the temperature of the specimen SA is adjusted to the annealing temperature (S4320), the DNA contained in the specimen SA can react with the annealing reagent. For example, the DNA contained in the specimen (SA) can bind to the primer.

After the temperature of the sample SA is maintained at the annealing temperature for a predetermined time, a polymerization reaction reagent may be provided to the plate PL (S4220). Here, the polymerization reaction reagent may be a part of the reagent used in the polymerization reaction step. For example, the annealing reagent may be dNTP, DNA polymerase, buffer solution, and coenzyme.

The polymerization reaction reagent may be provided by the patch PA.

The reagent stored in the patch PA can be moved to the plate PL by the contact between the patch PA and the plate PL, ) To the plate (PL).

As another example, the patch PA contacts another patch PA already in contact with the plate PL so that the reagent stored in the patch PA can be moved to the other patch PA . Thus, the reagent may be provided on the plate PL in contact with the another patch PA.

The patch (PA) may contain a polymerization reaction reagent. In one example, the patch (PA) may contain dNTPs, DNA polymerase, buffer solution and coenzyme.

The temperature of the sample (SA) may be adjusted to the polymerization reaction temperature (S4330). The temperature of the specimen SA can be adjusted by adjusting the temperature of the patch PA and / or the plate PL. When the temperature of the sample (SA) is adjusted to the polymerization reaction temperature, the sample (SA) can react with the polymerization reaction reagent. For example, the DNA associated with the primer can be extended.

7. Multi-test

7.1 Significance

Cancer is an incurable disease in which no complete treatment has yet been developed, and the survival rate between the early stage of cancer, the middle stage of cancer and the end stage of cancer is remarkably different. Therefore, accurate diagnosis of the onset in cancer diagnosis is a critical factor.

In this regard, cancer diagnosis according to the present application can perform a plurality of diagnoses on one specimen (SA) for accuracy of diagnosis.

Hereinafter, an embodiment in which a plurality of diagnostic steps for the sample (SA) proceeds and its effect will be described in detail.

7.2 Example for Multi-test

7.2.1 Embodiment 1

51 is a diagram for explaining a plurality of kinds of diagnostic methods for a specimen (SA) in cancer diagnosis according to an embodiment of the present application.

The diagnosis of cancer according to one embodiment of the present application can be performed through a method of analyzing the morphology of the specimen (SA) (S5100) and analyzing the progress of the specimen (SA) (S5200).

In the morphological analysis for the sample (SA), the above-described morphological analysis examples can be applied.

For the analysis of the culture time for the specimen (SA), the above-described embodiments of the analysis of the culture progress can be applied.

The morphology analysis of the sample (SA) means that the morphology of the cell (CE) contained in the sample (SA) is analyzed. Cells (CE) estimated as cancer cells (CE) can be identified by analyzing the shape of the cells (CE) contained in the specimen (SA).

If necessary, dyeing can be performed on the specimen (SA). However, in the morphological analysis described in this embodiment, it is assumed that an image of the specimen (SA) which is not stained is photographed.

The analysis of the culture after the morphological analysis of the specimen (SA) means that the specimen (SA) undergoing the morphological analysis is cultured.

In the culture analysis, cells (CE) suspected of being cancer cells (CE) can be identified through culture of the sample (SA). At this time, the location of the cell (CE) identified as a cancer cell (CE) risk group can be determined through the morphological analysis of the specimen (SA), and the cell culture progress of the cell (CE) at the corresponding position can be confirmed.

The analysis of the culture progress of the sample (SA) may be performed to confirm whether or not the cell (CE) included in the specimen (SA) is continuously fragmented. In other words, due to the feature of infinite proliferation of cancer cells (CE), it is to detect cancer cells (CE) continuously progressing cell (CE) cleavage.

Hereinafter, a cancer diagnosis method according to the present embodiment will be described in more detail.

FIG. 52 is a diagram for explaining a plurality of kinds of diagnostic methods for a specimen (SA) in cancer diagnosis according to an embodiment of the present application.

When the specimen SA is provided to the plate PL (S5110), an image of the specimen SA can be taken (S5120).

The step S5110 may be similar to the step S1100. The step S5120 may be similar to the step S1300.

As described above, the sample (SA) may be coated on the plate (PL) as a mono layer. The specimen (SA) may be in an unstained state. This may be to inhibit the unwanted sample (for example, a staining sample) from being allowed to incubate the provided sample (SA), although this is not essential, in a subsequent culture analysis to be performed later.

Further, if necessary, the sample (SA) provided on the plate in this embodiment may not be fixed. This may be to prevent the membrane of the cell (CE) from breaking during the fixing process.

The image for the specimen (SA) can be analyzed. It is possible to identify a cell CE estimated to be a circulating cancer cell CE through an image of the specimen SA and attempt a precise analysis on the cell CE.

The precise analysis may be performed by a method of performing a culture progress analysis on the cell (CE).

The specimen SA may be provided with nutrition (S5210). The nutrition may be provided by contact between the patch PA and the sample SA. The patch PA may be a nutrient patch PA in which a nutrient sample (NT) is stored as described above.

When the specimen SA is supplied with nutrition, an image of the specimen SA may be taken (S5220).

The step S5210 may be similar to the step S3200. The step S5220 may be similar to the step S3300.

The image of the sample (SA) can be photographed in real time while the sample (SA) is supplied with nutrition. In this case, the image photographed in real time is advantageous in that an immediate change of the cell CE can be observed.

Alternatively, the image for the specimen SA may be photographed after the specimen SA has been supplied with nutrition and some time has elapsed. The image for the specimen (SA) can be compared with the image for the above-described morphological analysis. For example, cancer cells (CE) contained in the specimen (SA) can be detected by analyzing the size change of the specific cell (CE) and the difference in the culture rate relative to other cells (CE) of the specific cell .

7.2.2  Second Embodiment

53 is a diagram for explaining a plurality of kinds of diagnostic methods for a specimen (SA) in cancer diagnosis according to an embodiment of the present application.

The diagnosis of cancer according to one embodiment of the present application can be performed by performing an immunodiagnostic analysis of the sample (SA) (S6100) and a method of analyzing the culture (SA) of the sample (S6200).

For the immunodiagnostic analysis for the sample (SA), the embodiments for immunodiagnostic analysis described above can be applied.

For the analysis of the culture time for the specimen (SA), the above-described embodiments of the analysis of the culture progress can be applied.

The meaning of performing the immunodiagnostic analysis on the sample (SA) means that the immune system of the cell (CE) contained in the sample (SA) is analyzed. (For example, the presence or absence of cancer cells (CE)) of the cell (CE) using an antibody (AB) for a protein distributed on the surface of the cell (CE) contained in the sample (SA) .

In some cases, it is also possible to analyze the morphology of the cell (CE) using an antibody (AB) bound to the surface protein of the cell (CE) by binding of the antibody (AB) with an antigen. This corresponds to a method of estimating the outline of the cell (CE) outlined by the marker bound to the antibody (AB).

Performing the culture progress analysis for the sample (SA) is to carry out culture for the sample (SA) in which the above-described immunodiagnostic analysis has been performed. The analysis of the culture progress of the sample (SA) has already been described above, and a more detailed description thereof will be omitted.

Hereinafter, a cancer diagnosis method according to the present embodiment will be described in more detail.

54 is a diagram for explaining a plurality of kinds of diagnostic methods for a specimen (SA) in cancer diagnosis according to an embodiment of the present application.

When the specimen SA is provided to the plate PL (S6110), the antibody AB may be provided (S6120) to the plate PL. The antibody (AB) provided on the plate (PL) can specifically bind to the antigen contained in the specimen (SA). In the patch PA, the antibody AB may be stored. The antibody AB may be provided to the plate PL by a patch PA.

The provision of the antibody (AB) may be carried out by any of the direct method, indirect method and sandwich method described above.

Once the antibody (AB) is provided to the plate (PL), the antibody (AB) specifically binding to the antigen can be identified (S6130). For example, fluorescence of the sample (SA) can be detected if the fluorescent substance is attached to the antibody (AB). As another example, if the enzyme (AB) is attached to the enzyme (SA), the color of the specimen (SA) can be detected by providing the specimen (SA) with a substrate (SU). Through the above-described method, the presence or absence of the antibody (AB) specifically binding to the antigen contained in the specimen (SA) can be confirmed, thereby confirming whether or not the cancer has occurred.

The step S6110 may be similar to the step S2100, the step S6120, the step S2200, and the step S6130 may be similar to the step S2300.

The step S6210 of supplying the sample SA to the plate PL and the step S6220 of photographing the sample SA may be performed in a similar manner to the steps S5210 and S5220 described above Therefore, detailed description will be omitted.

7.2.3  Third Embodiment

55 is a diagram for explaining a plurality of kinds of diagnostic methods for a specimen (SA) in cancer diagnosis according to an embodiment of the present application.

After the progress of the culture for the sample (SA), any one of the morphological analysis for the sample (SA), the immunodiagnosis analysis for the sample (SA) and the DNA analysis for the sample (SA) .

When the culture progress analysis is performed, the cell (CE) contained in the specimen (SA) may proliferate. Therefore, when cancer diagnosis is performed through other methods after the above-described analysis of the culture progress, analysis of the specimen (SA) including the proliferated cells (CE) becomes possible, and more accurate cancer diagnosis can be possible.

Hereinafter, for the sake of understanding, an example of performing immunodiagnostic analysis (S7200) on the specimen (SA) after the progress of culture (S7100) on the specimen (SA) .

56 is a diagram for explaining a plurality of types of diagnostic methods for a specimen (SA) in cancer diagnosis according to an embodiment of the present application.

When the specimen SA is supplied to the plate PL in step S7110, a nutrient sample NT may be supplied to the plate PL in step S7120. The provision of the nutrient sample (NT) can be performed by a patch (PA). The patch PA may store the nutrient sample (NT).

The nutrient sample NT provided to the plate PL is also provided to the sample SA located on the plate PL so that the cell CE contained in the sample SA can be proliferated Environment can be provided.

In addition, a buffer patch (PA) may be used to appropriately adjust the pH and / or the salt concentration of the sample (SA). The buffer patch PA may be in contact with the plate PL or with the nutrition patch PA.

After the nutrient sample (NT) is supplied to the plate (PL) for a certain period of time, an image of the sample (SA) is taken (S7130) and analyzed.

Alternatively, during the supply of the nutrient sample (NT) to the plate (PL), an image of the sample (SA) is taken (S7130), and the cell (CE) contained in the sample .

Alternatively, the image of the specimen SA may not be photographed. That is, the analysis of the culture progress of the sample (SA) is not a procedure for acquiring an image of the sample (SA), but a method of propagating a cell (CE) of a sample (SA) Lt; / RTI > Thus, by performing various diagnoses using the proliferated cells (CE), the detection efficiency of blood circulating cancer cells (CE) distributed in the blood can be increased.

The step S7210 of providing the antibody AB to the plate PL and the step S7220 of identifying the antibody AB specifically binding to the antigen may be performed in a similar manner to the steps S6120 and S6130 described above Therefore, detailed description will be omitted.

7.2.4 Fourth Embodiment

FIG. 57 is a diagram for explaining a plurality of kinds of diagnostic methods for a specimen (SA) in cancer diagnosis according to an embodiment of the present application.

The diagnosis of cancer according to one embodiment of the present application can be performed by a method of performing immunodiagnosis analysis of a specimen (SA) (S8100) and proceeding a morphological analysis of a specimen (S8200).

For the immunodiagnostic analysis for the sample (SA), the embodiments for immunodiagnostic analysis described above can be applied.

In the morphological analysis for the sample (SA), as described above, the morphological analysis examples can be applied.

The specimen (SA) may be first subjected to morphological analysis, and the immunoassay analysis may be performed on the specimen (SA). Alternatively, as in the present embodiment, the immunoassay analysis for the sample (SA) can be performed first, and the morphological analysis for the sample (SA) can proceed.

When the staining for the sample (SA) is performed when the specimen (SA) is subjected to morphological analysis, some of the cells (CE) contained in the specimen (SA) may be destroyed. This is related to the fact that the cell (CE) can be necrosed by the dye. Accordingly, it is understood that, when the staining for the specimen SA is proceeded during the morphological analysis, the specimen SA can be more accurately examined by performing the immunodiagnostic analysis on the specimen SA first.

The immunodiagnosis analysis (S8100) for the sample (SA) can be performed by using any one of the direct method, the indirect method and the sandwich method described above.

The morphological analysis (S8200) for the specimen (SA) can be performed on the specimen (SA) stained by any one of the above-described method for obtaining an image of an unstained specimen (SA), simple staining, Romanovskia and DAPI staining For example.

However, the present invention is not limited to this, and even in the case of dyeing using the staining method not disclosed in the present application, it can be used in the above-described morphological analysis.

Up to now, an embodiment has been described in which a plurality of kinds of diagnoses are performed on the specimen (SA) in performing the cancer diagnosis according to the present application.

It should be understood, however, that the above-described embodiments are illustrative of some embodiments that may be advantageously practiced and do not imply a limitation on the scope of the present application.

For convenience of explanation, the embodiment has been described in which two types of diagnoses are sequentially performed. However, even when cancer diagnosis is performed using three or more types of diagnoses, it is easy for a technician belonging to the technical field of the present application to easily Lt; / RTI >

8. Multi-region

In the cancer diagnosis according to the present application, when a plurality of kinds of diagnostic methods are applied to one specimen (SA), the plurality of types of diagnostic methods can be performed simultaneously.

58 is a diagram for explaining a plurality of types of diagnostic methods for a specimen (SA) in cancer diagnosis according to an embodiment of the present application.

A plurality of patches PA may be in contact with the plate PL. Different reagents may be stored in the plurality of patches PA.

For example, the plurality of patches PA may include a first patch PA, a second patch PA, and a third patch PA.

The first patch PA may store a dye sample. The staining sample may be a sample for staining the nucleus and / or cytoplasm of the cell (CE) contained in the specimen (SA).

The second patch PA may store the antibody AB. The antibody (AB) may be an antibody (AB) that specifically reacts with cancer cells (CE) contained in the specimen (SA).

The third patch PA may store a nutrient sample (NT). The nutrient sample (NT) may be a sample used for propagating the cell (CE) contained in the sample (SA) through cleavage.

The first patch PA may contact the first region of the plate PL. The second patch PA may contact the second region of the plate PL. The third patch PA may contact the third region of the plate PL. As a result, the cell (CE) contained in the specimen (SA) located in the first region can be stained, and the antibody (CE) contained in the specimen (SA) And the cell (CE) contained in the sample (SA) located in the third patch (PA) can propagate.

Images for the first area, the second area and the third area of the plate PL can be obtained. The images of the first area, the second area and the third area may be photographed respectively, or may be photographed in one frame. Alternatively, the images of the first region, the second region, and the third region may be acquired in a form such that they are captured and collected partly.

The plurality of kinds of diagnosis methods disclosed in the Multi-region and the plurality of types of diagnosis methods disclosed in the Multi-test can be combined with each other. For example, after the cell (CE) culture analysis is performed on the region provided with the sample (SA), the region of the sample (SA) subjected to the cell culture analysis analysis is divided, Can proceed.

9. Diagnostic device

59 is a block diagram of a diagnostic apparatus according to an embodiment of the present application.

The diagnostic apparatus according to the present application may include a relative position adjusting unit 100, a temperature adjusting unit 200, and an image obtaining unit 300. The diagnostic device according to the present application may comprise more or fewer components.

The relative position adjusting unit 100 may perform a function of moving the patch PA and the plate PL relatively. The relative position adjustment unit 100 may relatively move the patch PA and the plate PL in the horizontal direction and / or the vertical direction.

The horizontal direction may mean a direction parallel to one surface of the plate PL and the patch PA. The vertical direction may mean a direction perpendicular to one surface of the plate PL and the patch PA.

FIG. 60 is a conceptual diagram showing an example in which the structure of the diagnostic apparatus is moved by a relative movement operation of the relative position adjustment unit 100 according to an embodiment of the present application.

60 (a), the relative position adjusting unit 100 relatively moves the patch PA and the plate PL in the horizontal direction, and moves the relative position of the patch PA on the plate PL The relative position can be changed.

The relative position adjustment unit 100 also has a function of changing the patch PA disposed so as to contact the specimen SA by relatively moving the patch PA and the plate PL in the horizontal direction Can be performed. Changing the patch PA positioned so as to be in contact with the specimen SA enables the specimen SA to transfer the liquid material provided from the other patch PA.

60 (b), the relative position adjusting unit 100 relatively moves the patch PA and the plate PL in the vertical direction, and moves the plate PL and the sample SA Contact can be controlled. Contacting the patch PA with the specimen SA may involve transferring the substance trapped in the patch PA to the specimen SA.

The relative position adjustment unit 100 includes a power source for relatively moving the patch PA and the plate PL in the horizontal direction and a power source for relatively moving the patch PA and the plate PL in the vertical direction. May be separately provided. Alternatively, the relative position adjuster 100 may move the patch PA and the plate PL horizontally and / or vertically using a single power source.

The temperature controller 200 may perform a function of controlling the temperature. The temperature regulator 200 may perform heating or cooling of the plate PL and / or the patch PA. In addition, the temperature controller 200 may control the temperature of the specimen SA and maintain a constant temperature.

For example, the temperature controller 200 may be used to adjust the specimen SA to the thermal denaturation temperature, the annealing temperature, and / or the polymerization reaction temperature.

The temperature controller 200 may perform an exothermic reaction and an endothermic reaction. Accordingly, the temperature regulating unit 200 may include a heating element, or may include a thermoelectric element. However, the present invention is not limited thereto, and any material capable of generating heat can be used as the temperature regulator 200 without limitation.

Further, if necessary, the temperature controller 200 may further include a temperature sensor. The temperature sensor can be used to confirm the current temperature of the temperature control object.

The image obtaining unit 300 may perform a function of obtaining an image of the specimen SA. Acquisition of the image may include, for example, a method of acquiring an image of part or all of the plate PL, a method of acquiring an image of part or all of the patch PA, And the like.

The image obtaining unit 300 may include means for obtaining an image. For example, the image obtaining unit 300 may include image generating means for generating an image such as an image sensor such as a CMOS or a CCD, predetermined light generating means capable of generating a light beam transmitting the specimen SA, and / Or an optical system for imaging the light beam transmitted through the specimen SA.

The image obtaining unit 300 can directly pick up the specimen SA stained on the plate PL. Here, the image acquiring unit 300 may acquire an image of the specimen SA by receiving light transmitted through the plate PL irradiated from the light source and coated with the specimen SA.

For example, the image acquiring unit 300 may be configured such that the specimen SA of the slide glass is disposed on the smoothed surface (hereinafter referred to as "front side") and the light source is disposed on the opposite side of the front surface of the slide glass, have. According to this arrangement, the image obtaining unit 300 can obtain the image of the specimen SA by irradiating light from the light source at the back side of the slide glass and passing through the slide glass.

As another example, the image acquiring unit 300 may be disposed on the back surface of the slide glass, and the light source may be disposed on the front surface of the slide glass. According to this arrangement, the image acquiring unit 300 can acquire the image of the specimen SA by irradiating light from the light source at the front side of the slide glass and passing through the slide glass.

The image obtaining unit 300 may detect fluorescence or acquire a fluorescence image for quantitative and / or qualitative analysis of the specimen SA.

The image generated from the image acquiring unit 300 may have various magnifications. For example, the image may be an image of an enlarged magnification for the specimen SA, may be an image of a magnification factor, and may be an image of a reduced magnification as required.

The image acquiring unit 300 includes a power member for moving the plate PL on which the specimen SA is placed or moving the components of the image acquiring unit 300, It is possible to acquire an image of the user.

The diagnostic apparatus according to the present application can perform the PCR process described so far. It will be understood by those skilled in the art to which the present invention pertains that the details of the process steps in the mechanical aspects will be omitted.

It will be understood by those skilled in the art that various modifications and variations can be made in the present invention without departing from the essential characteristics thereof. Accordingly, the embodiments of the present application described above may be implemented separately or in combination.

Therefore, the embodiments disclosed in the present application are intended to illustrate rather than limit the technical idea of the present application, and the scope of the technical idea of the present application is not limited by these embodiments. The scope of protection of the present application should be construed according to the following claims, and all technical ideas within the scope of equivalents should be construed as being included in the scope of the present application.

PA: Patch PL: Plate
SL: Material with fluidity WF: Water film
SB: Liquid substance CE: Cell
SA: sample SU: substrate
AB: antibody NT: nutritional sample

Claims (26)

1. A method for diagnosing cancer cells contained in a specimen using a patch provided in a gel-like net structure forming a micro-cavity,
Placing the specimen on a plate; And
Providing said plate with a reagent stored in said patch, using said patch to store a reagent used to detect cancer;
Diagnostic method.
The method according to claim 1,
Wherein positioning the specimen on the plate comprises providing the specimen as a monolayer to the plate
Diagnostic method.
The method according to claim 1,
Characterized in that the specimen is blood
Diagnostic method.
3. The method of claim 2,
Wherein positioning the specimen on the plate comprises securing the specimen to the plate
Diagnostic method.
The method according to claim 1,
The reagent stored in the patch includes an antibody specifically reactive with the cancer cells
Diagnostic method.
6. The method of claim 5,
Providing a substrate to the plate to identify antibodies bound to the cancer cells
Diagnostic method.
6. The method of claim 5,
The plate is coated with an antibody that specifically reacts with the cancer cells
Diagnostic method.
The method according to claim 1,
The reagent stored in the patch,
In order to stain the cancer cells, a staining solution containing a staining reagent used for staining of cells
Diagnostic method.
9. The method of claim 8,
Wherein the staining reagent targets at least one of the cell nucleus of the cell, the cytoplasm of the cell, and the DNA distributed in the cell
Diagnostic method.
10. The method of claim 9,
Controlling the temperature of the specimen to form a reaction environment of the staining reagent,
Diagnostic method.
The method according to claim 1,
The reagent stored in the patch,
In order to diagnose the cancer by culturing the cancer cells,
Diagnostic method.
The method according to claim 1,
Wherein providing the reagent stored in the patch comprises contacting the plate with the patch
Diagnostic method.
The method according to claim 1,
And obtaining an image of the plate on which the specimen is located, for diagnosis of the cancer cells
Diagnostic method.
14. The method of claim 13,
The image of the plate on which the specimen is placed is a fluorescence image
Diagnostic method.
The method according to claim 1,
The reagent stored in the patch,
In order to extract the DNA of the cancer cells,
Diagnostic method.
1. A method for diagnosing cancer cells contained in a specimen using a patch provided in a gel-like net structure forming a micro-cavity,
Placing the specimen on a plate;
Providing a reagent stored in the first patch to the plate using a first patch that stores a first reagent used to detect cancer; And
Providing a reagent stored in the second patch to the plate using a second patch that stores a second reagent used to detect the arm;
Diagnostic method.
17. The method of claim 16,
The step of providing the reagent stored in the first patch may be performed before the step of providing the reagent stored in the second patch
Diagnostic method.
17. The method of claim 16,
Wherein the first reagent comprises an antibody that specifically reacts with the cancer cells,
Wherein the second reagent comprises an antibody that specifically binds to an antibody that specifically reacts with the cancer cell
Diagnostic method.
17. The method of claim 16,
Wherein the first reagent comprises an antibody that specifically reacts with the cancer cells,
The second reagent may include a nutrient reagent used for culturing the cells for culturing the cancer cells to diagnose the cancer
Diagnostic method.
17. The method of claim 16,
Wherein the first reagent comprises an antibody that specifically reacts with the cancer cells,
The second reagent may include a staining reagent used for staining the cells to stain the cancer cells
Diagnostic method.
17. The method of claim 16,
Wherein the first reagent comprises an antibody that specifically reacts with the cancer cells,
Wherein the second reagent comprises an antibody that specifically reacts with leukocytes
Diagnostic method.
22. The method of claim 21,
Between the step of providing the reagent stored in the first patch and the step of providing the reagent stored in the second patch,
Obtaining an image for the specimen; Further comprising
Diagnostic method.
17. The method of claim 16,
The first reagent includes a reagent used for cell membrane removal to extract the DNA of the cancer cell,
Wherein the second reagent comprises a reagent used in a polymerase chain reaction
Diagnostic method.
24. The method of claim 23,
And adjusting the temperature of the specimen to cause the polymerase chain reaction
Diagnostic method.
A diagnostic device is provided which is provided as a gel-like net structure forming a micro-cavity to perform a diagnosis on cancer cells contained in the sample using a patch for storing a reagent used for detecting cancer As a result,
A relative movement regulator for relatively moving the patch and the region where the specimen is provided to provide the reagent stored in the patch to the specimen; And
And an image obtaining unit for obtaining an image of the specimen for the cancer diagnosis
Diagnostic device.
26. The method of claim 25,
And a temperature controller for controlling the temperature of the specimen
Diagnostic device.

Images