WO2017146505A1

WO2017146505A1 - Substance-marking patch, and method and apparatus for tissue diagnosis using same

Info

Publication number: WO2017146505A1
Application number: PCT/KR2017/002029
Authority: WO
Inventors: 이동영; 임찬양; 김경환
Original assignee: 노을 주식회사
Priority date: 2016-02-23
Filing date: 2017-02-23
Publication date: 2017-08-31

Abstract

The present invention relates to a tissue diagnosis apparatus comprising: a plate support unit having a reaction area located therein and supporting a plate, in the reaction area, on which a tissue sample is placed; a patch control unit for supporting a patch storing a marker substance specifically marking a target substance, and controlling the location of the patch relative to the reaction area so that the patch transfers the marker substance thereto; and a target substance detection unit for detecting the target substance contained in the tissue sample by detecting the marker substance.

Description

Substance label patch, tissue diagnosis method and apparatus using same

The present invention relates to a substance label patch, a method and apparatus for diagnosing tissue using the same, and more particularly, to a patch for storing a label material and to label a portion of the tissue sample using the same, thereby performing a rapid and accurate diagnosis of the tissue sample. Method and apparatus.

Due to the rapidly aging population and the increasing demand for quality of life, the diagnostic market aiming at early diagnosis and early treatment has grown every year in the world, including Korea, and rapid and easy diagnosis is emerging as an important issue. Particularly, in-vitro diagnosis (IVD) or point-of-care testing (POCT), which is directly diagnosed next to the patient, is transferred to a form that can be performed without using large diagnostic equipment. There is a trend.

The histological diagnosis is a concept in charge of diagnosing pathology by using a sample of tissue, which is an aggregate of cells, as an intermediate step between cells and organs. In particular, the diagnosis using a tissue sample is mainly used for cancer diagnosis. If cancer is suspected through clinical or imaging diagnosis, a portion of the tissue suspected of cancer is collected from the patient by fine needle aspiration or the like. The collected tissue is used for diagnosis through tissue processing, and the diagnosis may be performed by observing the morphology of cells constituting the tissue or determining the presence of a specific protein.

Conventional tissue diagnostic methods require a washing process in which a large amount of washing solution is poured to rinse the plate or the like in order to remove a stained sample or fluorescent material that does not bind to the detection target material in the process of staining or fluorescently treating a sample. It became. At this time, there was a disadvantage in that a large amount of washing solution was consumed. In addition, in the conventional tissue diagnosis method, when the above-mentioned washing is not performed properly, the residual stained sample or the residual fluorescent substance interferes with the detection, thereby making it difficult to make an accurate diagnosis.

Accordingly, there is a need for a means for effectively removing the obstructive elements while minimizing the amount of sample required for diagnosis.

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

One object of the present invention is to provide a patch that can provide a reaction space of the material.

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

One object of the present invention is to provide a patch that can absorb a substance.

One object of the present invention is to provide a patch that can provide an environment.

One object of the present invention is to provide a patch for storing a labeling substance.

One object of the present invention is to provide a tissue diagnosis method using a patch.

According to an aspect of the present invention, a tissue diagnosis device for detecting a target material from a tissue sample by using a patch provided to store the material in the microcavities, including a net structure forming the microcavities, the reaction region, And a plate support for supporting a plate on which the tissue sample is located in the reaction zone, a patch for storing a labeling substance specifically labeled on the target material, and the patch being in contact with the reaction zone. And a patch control unit for controlling a relative position of the patch with respect to the reaction region so as to transfer the labeling substance to the reaction region, and a target substance detection unit for detecting the labeling substance and detecting the target substance included in the tissue sample. Tissue diagnostic devices may be provided.

The target substance detector may include an imaging module configured to capture an image of the reaction region in which the tissue sample is located. The target substance detection unit may include a measurement module for measuring the amount of the target substance included in the tissue sample.

According to another aspect of the present invention, a tissue diagnosis method for detecting a target substance from a tissue sample by using a patch provided to store a substance in the microcavities, the net structure forming the microcavities, the reaction region, Positioning a tissue sample in the cell, delivering the fluorescent label material to the tissue sample by using a patch for storing a fluorescent label material for specifically labeling the target material, and fluorescently labeling the target material from the tissue sample. The method of detecting tissue may be provided for the step of detecting.

The fluorescent label material may be a fluorescent label complex including a reaction derivative specifically reacting with the target material and a fluorescent label for detecting the target material.

The detecting of the fluorescently labeled target material may be performed by acquiring a fluorescent image of the tissue sample. The detecting of the fluorescently labeled target material may be performed by measuring the amount of fluorescence emitted from the target material included in the tissue sample. Detecting the fluorescently labeled target material may include obtaining distribution information in the tissue sample of the target material.

The target material is a target base sequence included in the tissue sample, and the fluorescent labeling material includes a fluorescently labeled nucleic acid probe, and the nucleic acid probe may complementarily bind to the target base sequence. Alternatively, the target material may be a target protein included in the tissue sample, and the fluorescent labeling material may include a fluorescently labeled antibody, and the antibody may specifically bind to the target protein.

The step of delivering the fluorescent label material to the tissue sample comprises contacting the tissue sample with a patch that stores the fluorescent label material, wherein the fluorescent label material is brought into the reaction region when the patch contacts the tissue sample. Can be made mobile.

In this case, the step of delivering the fluorescent labeling material to the tissue sample includes the step of separating the patch for storing the fluorescent labeling material from the tissue sample; if the patch is separated from the tissue sample of the fluorescent labeling material Excess fluorescent labeling material that does not bind to the target material may be removed from the reaction zone.

According to another aspect of the present invention, a tissue diagnostic method for detecting a target material from a tissue sample by using a patch comprising a net structure for forming the microcavities, the patch provided to store the material in the microcavities, Positioning a tissue sample in an area, transferring the dyeing material to the tissue sample by using a patch that stores a color labeling material for imparting a color to the object material, and detecting the colorated object material Tissue diagnostic methods can be provided comprising the steps.

The color labeling substance may be a color labeling complex including a reaction derivative specifically reacting with the target substance and a color label for detecting the target substance.

The detecting of the target substance to which the color is given may be performed by acquiring an image of the tissue sample. Detecting the color labeled target substance may include acquiring an amount labeled with the color in the tissue sample. Detecting the color-labeled target substance may include acquiring a distribution of the region labeled with the color in the tissue sample.

The target material is a target base sequence included in the tissue sample, and the color labeling substance may include a nucleic acid probe that complementarily binds to the target base sequence. The target material is a target protein included in the tissue sample, and the color labeling material includes an antibody to which a label that induces a color label is attached, and the antibody may specifically bind to the target protein.

The step of delivering the color labeling substance to the tissue sample comprises contacting the tissue sample with a patch that stores the color labeling substance, wherein the color labeling substance reacts when the patch contacts the tissue sample. It can be moved to an area.

The method may further include the step of separating the patch storing the color labeling material from the tissue sample. When the patch is separated from the tissue sample, the excess color labeling material that does not react with the target material among the color labeling materials may be used. It can be removed from the reaction zone.

According to another aspect of the present invention, a tissue diagnostic method for detecting a target material from a tissue sample by using a patch comprising a net structure for forming the microcavities, the patch provided to store the material in the microcavities, Positioning a tissue sample in a region, delivering the first fluorescent labeling material to the tissue sample using a patch that stores a first fluorescent labeling material for specifically labeling the first subject material and a second subject A tissue diagnostic method may be provided comprising delivering the second fluorescent labeling material to the tissue sample using a patch that stores a second fluorescent labeling material for specifically labeling the material.

The wavelength band at which fluorescence emitted from the first fluorescent label material is detected and the wavelength band at which fluorescence emitted from the second fluorescent label material are detected are different from each other, and after the step of delivering the second fluorescent label material to the tissue sample, The method may further include detecting the first target material and the second target material included in the tissue sample.

After the step of delivering the first fluorescent labeling material to the tissue sample, detecting the first target material included in the tissue sample by detecting fluorescence emitted from the first fluorescent labeling material; After the step of delivering the second fluorescent labeling material to the tissue sample, detecting the second target material included in the tissue sample by detecting the fluorescence emitted from the second fluorescent labeling material. have.

In this case, the wavelength band where the fluorescence emitted from the first fluorescent label material is detected and the wavelength band where the fluorescence emitted from the second fluorescent label material is detected at least partially overlap each other, and the fluorescence emitted from the second fluorescent label material is overlapped. The detecting may include comparing fluorescence detected from the tissue sample after delivering the second fluorescent labeling material to the tissue sample and fluorescence detected from the tissue sample before delivering the second fluorescent labeling material to the tissue sample. Can be performed.

According to another aspect of the present invention, the labeling material is bound to the target material contained in the tissue sample, and has a net structure to form a microcavity in which the labeling material is stored, and the target material in contact with the tissue sample A material label patch may be provided that includes a net structure that delivers the label material to a location in the reaction zone. The target material may be DNA included in the tissue sample.

The labeling material may be a fluorescent labeling material.

The fluorescent label material may include a fluorescently labeled antibody, and the target material may be a target protein included in the tissue sample. The fluorescent label material may include a fluorescently labeled nucleic acid probe, and the target material may be a target nucleotide sequence included in the tissue sample.

The labeling substance may be a color labeling substance.

The color labeling substance may include an antibody to which an enzyme is attached, and the target substance may be a target protein included in the sample. The color labeling substance may include hematoxylin, and the target substance may be a nucleus contained in the sample.

The technical solutions of the present invention are not limited to the above-mentioned solutions, and the solutions not mentioned may be clearly understood by those skilled in the art from the present specification and the accompanying drawings. There will be.

According to the present invention it is possible to easily store, transfer, and absorb the substance.

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

According to the present invention, the diagnosis using the tissue as a sample can be performed more easily, and the diagnosis result can be obtained quickly.

In addition, according to the invention, the delivery and absorption of the substance is properly controlled using the patch, so that the amount of the solution required for diagnosis can be significantly reduced.

According to the present invention, tissue diagnosis can be performed by simultaneously detecting a plurality of targets.

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

1 illustrates in detail an example of a patch according to the present application.

2 shows an example of a patch according to the present application in detail.

3 illustrates providing a reaction space as an example of the function of a patch according to the present application.

4 illustrates providing a reaction space as an example of the function of a patch according to the present application.

5 illustrates the delivery of a substance as an example of the function of a patch according to the present application.

6 illustrates the delivery of a substance as an example of the function of a patch according to the present application.

7 illustrates the delivery of a substance as an example of the function of a patch according to the present application.

8 illustrates the delivery of a substance as an example of the function of a patch according to the present application.

9 illustrates the delivery of a substance as an example of the function of a patch according to the present application.

10 illustrates the delivery of a substance as an example of the function of a patch according to the present application.

11 illustrates the delivery of a substance as an example of the function of a patch according to the present application.

12 illustrates the delivery of a substance as an example of the function of a patch according to the present application.

Figure 13 illustrates the delivery of material as an example of the function of the patch according to the present application.

14 illustrates absorbing material as an example of the function of a patch according to the present application.

15 illustrates absorbing material as an example of the function of a patch according to the present application.

16 illustrates absorbing material as an example of the function of a patch according to the present application.

17 illustrates absorbing material as an example of the function of a patch according to the present application.

18 illustrates absorbing material as an example of the function of a patch according to the present application.

19 illustrates absorption of a material as an example of the function of a patch according to the present application.

20 illustrates absorbing material as an example of the function of a patch according to the present application.

21 illustrates absorbing material as an example of the function of a patch according to the present application.

22 illustrates absorbing material as an example of the function of a patch according to the present application.

23 illustrates an example of providing an environment as one of the functions of a patch according to the present application.

24 illustrates providing an environment as an example of the functionality of a patch according to the present application.

25 illustrates providing an environment as an example of the functionality of a patch according to the present application.

FIG. 26 illustrates a case in which absorption and delivery of a material are performed as an embodiment of a patch according to the present application.

FIG. 27 illustrates a case of performing absorption and delivery of a material as an embodiment of a patch according to the present application.

FIG. 28 illustrates a case of performing absorption and delivery of a material as an embodiment of a patch according to the present application.

29 is a view illustrating a case of performing absorption and delivery of a material as an embodiment of a patch according to the present application.

30 illustrates a case of performing absorption and delivery of a material as an embodiment of a patch according to the present application.

FIG. 31 illustrates a case in which absorption, delivery of materials, and provision of an environment are performed as an embodiment of a patch according to the present application.

32 is a view illustrating a case of performing absorption, delivery, and provision of an environment as an embodiment of a patch according to the present application.

33 illustrates an embodiment of a plurality of patches as an embodiment of a patch according to the present application.

34 illustrates an embodiment of a plate having a plurality of patches and a plurality of target areas as one embodiment of a patch according to the present application.

35 is a flowchart illustrating an example of a tissue diagnosis method according to the present application.

36 is a flowchart illustrating an example of delivering a fluorescent label material to a tissue sample in a tissue diagnosis method according to an embodiment of the present application.

37 is a flowchart illustrating an example of a tissue diagnosis method according to the present application.

38 is a flowchart illustrating an example of delivering a color labeling substance to a tissue sample in a tissue diagnosis method according to an embodiment of the present application.

39 is a flowchart illustrating a case for detecting a plurality of target substances as an example of a tissue diagnosis method according to the present application.

40 is a flowchart illustrating a case for detecting a plurality of target substances as an example of a tissue diagnosis method according to the present application.

41 is a flowchart illustrating a case for sequentially detecting a plurality of target substances as an example of a tissue diagnosis method according to the present application.

42 illustrates an example of morphological diagnosis in an embodiment of a tissue diagnosis method according to the present application.

43 is a view schematically illustrating a case in which a plurality of target substances are to be detected as an example of a tissue diagnosis method according to the present application.

44 is a view schematically illustrating a case in which a plurality of target substances are to be detected as an example of a tissue diagnosis method according to the present application.

45 schematically illustrates a case where a plurality of target substances are to be detected as an example of a tissue diagnosis method according to the present application.

46 schematically illustrates a case in which a plurality of target substances are to be detected as an example of a tissue diagnosis method according to the present application.

FIG. 47 schematically illustrates a case in which a plurality of target substances are to be detected as an example of a tissue diagnosis method according to the present application.

48 illustrates an embodiment of a tissue diagnosis method according to the present application.

49 illustrates an embodiment of a tissue diagnosis method according to the present application.

50 illustrates an embodiment of a tissue diagnosis method according to the present application.

51 illustrates a case of using a probe as an embodiment of a tissue diagnosis method according to the present application.

52 illustrates the use of a probe as an embodiment of a tissue diagnosis method according to the present application.

53 illustrates a case of using a probe as an embodiment of a tissue diagnosis method according to the present application.

54 shows a case of using an antibody as an embodiment of a tissue diagnosis method according to the present application.

55 shows a case of using an antibody as an embodiment of a tissue diagnosis method according to the present application.

56 shows a case of using an antibody as an embodiment of a tissue diagnosis method according to the present application.

57 shows a case of using an antibody as an embodiment of a tissue diagnosis method according to the present application.

58 shows a case of using an antibody as an embodiment of a tissue diagnosis method according to the present application.

59 illustrates a case where a washing patch is used as an embodiment of a tissue diagnosis method according to the present application.

60 illustrates a case where a washing patch is used as an embodiment of a tissue diagnosis method according to the present application.

FIG. 61 illustrates a case where a washing patch is used as an embodiment of a tissue diagnosis method according to the present application.

62 illustrates an embodiment of a tissue diagnosis device according to the present application.

63 is a detailed diagram illustrating a target substance detection unit in an embodiment of a tissue diagnosis apparatus according to the present application.

The terminology used herein is a general term that has been widely used as far as possible in view of the functions of the present invention, but may vary according to the intention of a person of ordinary skill in the art to which the present invention belongs, custom or the emergence of a new technology. Can be. In contrast, when a specific term is defined and used in any meaning, the meaning of the term will be described separately. Therefore, the terms used in the present specification should be interpreted based on the actual meaning of the terms and the contents throughout the present specification, rather than simple names of the terms.

BRIEF DESCRIPTION OF THE DRAWINGS The drawings attached to the present specification are provided to easily explain the present invention, and the shapes shown in the drawings may be exaggerated and displayed as necessary to help understanding of the present invention, and thus the present invention is not limited to the drawings.

In the present specification, when it is determined that a detailed description of a known configuration or function related to the present invention may obscure the gist of the present invention, a detailed description thereof will be omitted as necessary.

1. Patch

What's in Patch 1.1

In this application, a patch for managing a liquid substance is disclosed.

The liquid material may mean a material in a liquid state as a material capable of flowing.

The liquid phase material may be a single component material having liquidity. Alternatively, the liquid substance may be a mixture including a plurality of substances.

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

When the liquid substance is a mixture, some of the plural components of the substance 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 material of the plurality of components constituting the mixture may be uniformly distributed. Alternatively, the mixture including the plurality of components may be a mixture mixed uniformly.

The material of the plurality of components may include a solvent and a material which is not dissolved in the solvent and is uniformly distributed.

On the other hand, some of the material of the plurality of components may be unevenly distributed. The non-uniformly distributed material may also include a particle component that is non-uniformly distributed in the solvent. In this case, the heterogeneously distributed particle component may be a solid phase.

For example, a material that can be handled using the patch may be in the form of 1) a single component liquid, 2) a solution, or 3) a colloid, and in some cases 4) solid particles are unevenly distributed in other liquid materials. It may be in a state where it is.

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

General nature of the 1.2 patch

1.2.1 Configuration

1 to 2 are diagrams 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.

Referring to FIG. 1, the patch PA according to the present application may include a net structure NS and a liquid material.

Here, the liquid substance may be considered by dividing the base material (BS) and the additive material (AS).

In addition, the patch PA may be a gel type. The patch PA may be implemented as a structure on a gel in which colloidal molecules are bonded to form a net tissue.

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 mesh structure in which a plurality of fine threads are entangled. However, the mesh structure NS is not limited to the shape of a network in which a plurality of fine threads are entangled, and may be implemented in any three-dimensional matrix form formed by connecting a plurality of fine structures. For example, the net structure NS may be a framework including a plurality of micro-cavities. In other words, the mesh structure NS may form a plurality of fine cavities MC.

2 shows the structure of another patch in one 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 may be used interchangeably with each other, and unless otherwise stated, the microcavities MC are defined as including the concept of the micropores MH.

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

The density of the mesh structure NS may have a value within a predetermined range. Preferably, the predetermined range may be determined within a limit in which the shape of the liquid substance SB captured in the patch PA is maintained in a form corresponding to the patch PA. The density may be defined as the density of the net structure NS to the mass ratio, the volume ratio, etc. of 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 network structure.

The patch PA according to the present application may include a liquid material SB, and the liquid material SB included in the patch PA is in the form of the net structure NS of the patch PA. By the fluidity of the liquid material (SB) may be limited.

The liquid substance SB may freely flow in the net structure NS. In other words, the liquid material SB is located in a plurality of microcavities formed by the mesh structure NS. Exchange of the liquid materials SB may occur between neighboring microcavities. At this time, the liquid material (SB), may be present in the form penetrating into the frame structure forming the net structure. In such a case, nano-sized pores may be formed in the frame structure to allow the liquid material SB to penetrate.

Further, depending on the molecular weight of the liquid material (SB) trapped in the patch (PA) to the size of the particles it can be determined whether the liquid material (SB) to the frame structure of the mesh structure. A material having a relatively high molecular weight may be trapped in the microcavity, and a material having a relatively low molecular weight may be injected into the microcavity and / or the frame structure of the mesh structure NS to be captured.

As used herein, the term "capture" refers to a state in which the liquid substance SB is located in a plurality of fine cavities and / or the nano-sized holes formed by the mesh structure NS. Can be defined In addition, the state in which the liquid substance SB is trapped in the patch PA, as described above, the liquid substance SB may flow between the microcavity and / or the nano-sized holes. It is defined to include the state that exists.

The liquid material SB may be considered as being 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 a material mixed with the base material BS and having fluidity. In other words, the base material BS may be a solvent. The additive material AS may be a solute dissolved in the solvent or particles insoluble in the solvent.

The base material BS may be a material that may flow 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), may be distributed only in a portion of the net structure (NS). The base material BS may be a liquid having a single component.

The additive material AS may be a material mixed with the base material BS or soluble in the base material BS. For example, the additive material AS can function as a solute using 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 minute particles that do not dissolve in the base material BS. For example, the additive material (AS) may contain microparticles such as colloidal molecules and microorganisms.

The additive material AS may include 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 included in the additive material AS, the fluidity of the additive material AS may be limited.

In addition, according to an embodiment, the additive material AS may include a component that is selectively included in the patch PA.

On the other hand, the additive material AS does not necessarily mean a material that is inferior in quantity or functionally inferior in relation to the base material BS described above.

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

1.2.2 characteristic

The patch PA according to the present application may include the net structure NS as described above. The patch PA may handle the liquid substance SB by the mesh structure NS. The patch PA may allow the liquid substance SB trapped in the patch PA to maintain at least some of its own characteristics.

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

The patch PA may provide a liquid environment in which a target material is diffused due to thermal movement, density, or concentration difference of the material. In general, 'diffusion' means that the particles that make up a substance are spread from the higher concentration to the lower concentration due to the difference in concentration. These diffusion phenomena can be understood basically as the resulting phenomena caused by the movement of molecules (translational movements in gases or liquids, vibrational movements in solids, etc.). In the present application, the term 'diffusion' refers to a phenomenon in which particles are spread from a high concentration to a low concentration due to a difference in concentration or density. The phenomenon of movement of particles by irregular motion is also referred to. In addition, the expression "irregular motion" of a particle is used in the same meaning as "diffusion", unless otherwise specified. The target material 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 patch PA may be diffused in the space provided by the patch PA. In other words, the additive material AS may diffuse in the space defined by the patch PA.

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

In addition, the concentration of the material or the additive material (AS) as a result of the non-uniformly distributed material or the additive material (AS) diffused in the patch (PA) or in an external region connected to the patch (PA). Even after is uniform, the material or the additive material AS may constantly move due to irregular movement of molecules in the interior of the patch PA and / or in the external region connected with the patch PA.

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

When the properties of the net structure NS and the liquid material SB are similar, the net structure NS may handle the liquid material SB more effectively.

The base material BS may be a hydrophilic material having polarity or a hydrophobic material having no polarity. In addition, the nature of the additive material (AS) may be hydrophilic or hydrophobic.

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

When both the polarity of the net structure NS and the polarity of the liquid material SB are hydrophilic or hydrophobic, an attractive force may act between the net structure NS and the liquid material SB. When the polarities 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. The repulsive force may act between the net structure NS and the liquid material SB.

Based on the properties described above, the patch PA may be used alone, in plurality, or in combination with other media to induce a desired reaction. Hereinafter, the functional aspects of the patch PA will be described.

However, hereinafter, for convenience of explanation, it is assumed that the patch PA is a gel phase that may contain a hydrophilic solution. In other words, unless otherwise stated, the mesh structure NS of the patch PA is assumed to have hydrophilic properties.

However, the scope of the present application should not be construed as being limited to patches on gels having hydrophilic properties, and patches on gels with solvent removed in addition to patches on gels containing solutions having hydrophobic properties. (PA) and, if possible to implement the functions according to the present application, the scope of the right can also extend to the patch (PA) on the sol.

2. Patch Functions

Patches according to the present application may have some useful functionality, due to the properties described above. In other words, the patch may be involved in the behavior of the liquid material SB by occupying the liquid material SB.

Accordingly, hereinafter, the reservoir function and the state of the material in which the state of the material is defined in a predetermined region formed by the patch PA according to the behavior of the material in relation to the patch PA are described. The channeling function in which the state of the material is defined including an external region will be described.

2.1 Reservoir

2.1.1 Significance

The patch PA according to the present application may capture the liquid substance SB as described above. In other words, the patch PA may function as 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 occupies at least a portion of the microcavities formed by the three-dimensional network structure NS of the patch PA, or a nano-sized hole formed in the network structure NS. Can penetrate

The liquid substance SB located in the patch PA does not lose the property of the liquid even if it is distributed in the plurality of microcavities. That is, the liquid substance SB has fluidity even in the patch PA, and the diffusion of the substance may occur in the liquid substance SB distributed in the patch PA, and an appropriate solute may be dissolved in the substance. 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 may capture a target material based on the above-described characteristics. The patch PA may be resistant to a change in the external environment within a predetermined range. Through this, the patch PA may keep the material in the captured state. The liquid substance SB, which is the target of the capture, may occupy the three-dimensional network structure NS.

Hereinafter, the function of the patch PA as described above is called storage for convenience.

However, the meaning that the patch PA stores the liquid substance means that the liquid substance is stored in the space formed by the mesh structure and / or to the frame structure constituting the mesh structure NS. It is defined as encompassing all that the liquid substance is stored.

The patch PA may store a liquid material SB. For example, due to the attractive force acting in the relationship between the net structure NS of the patch PA and the liquid substance SB, the patch PA may store the liquid substance SB. The liquid material SB may be stored in combination with the net structure NS with a attraction force of a predetermined intensity or more.

The properties of the liquid material SB stored in the patch PA may be classified according to the properties of the patch PA. More specifically, when the patch PA is hydrophilic, the hydrophilic liquid SB is combined with a polar hydrophilic liquid SB to form the three-dimensional fine particles. Can be stored in cavities. Alternatively, when the patch PA is hydrophobic, the hydrophobic liquid material SB may be stored in the microcavity of the three-dimensional network structure NS.

In addition, the amount of material that can be stored in the patch PA may be proportional to the volume of the patch PA. In other words, the amount of material stored in the patch PA may be proportional to the amount of the three-dimensional network structure NS as a support contributing to the shape of the patch PA. However, the volume relationship between the amount of the material that can be stored and the volume of the patch PA does not have a constant proportional constant, and the amount of the material that can be stored and the volume of the patch PA according to the design or manufacturing method of the mesh structure. Relationships can vary.

The amount of material stored in the patch PA may be reduced by evaporation, dropping, etc. over time. In addition, by adding a substance to the patch (PA) it can increase or maintain the content of the substance stored in the patch (PA). For example, a moisture preservative for suppressing evaporation of moisture may be added to the patch PA.

The patch PA may be embodied in an easy form for storing the liquid material SB. This means that the patch PA may be implemented to minimize the degeneration of the material when the material is affected by 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.

Meanwhile, the patch PA may store a liquid material SB having a plurality of components. At this time, the material of the plural components is placed together in the patch PA before the reference time point, or the material injected into the patch PA is first stored in the patch PA first, and then the secondary material is secondary to the patch PA after a predetermined time. It is also possible for the substance to be stored. For example, when two components of the liquid substance SB are stored in the patch PA, two components are stored in the patch PA or two components are produced in the patch PA. Only one component may be stored in the patch PA and the other one may be stored later, or two components may be sequentially stored after fabrication of the patch PA.

In addition, the material stored in the patch PA, as described above, may exhibit fluidity basically, and may also perform irregular or diffusion motion by molecular motion in the patch PA.

2.1.3 Provide reaction space

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

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

The patch PA may provide space for activities other than the diffusion of particles and / or irregular movement of the particles (hereinafter referred to as activities other than diffusion). Activities other than diffusion may refer to chemical reactions, but are not limited thereto and may also mean physical state changes. More specifically, activity other than diffusion means a chemical reaction in which the chemical composition of the substance changes before and after the activity, a specific binding reaction between components included in the substance, and a solute or particle contained in the substance and distributed unevenly. Homogenization, aggregation of some components contained in the material, or biological activity of a portion of the material.

Meanwhile, when a plurality of substances are involved in the activity, the plurality of substances may be located together in the patch PA before the reference time point. The plurality of materials may be sequentially added.

By changing the environmental conditions of the patch PA, the efficiency of the function of providing a space for activities other than the diffusion of the patch PA can be enhanced. For example, the temperature conditions of the patch PA may be changed or electrical conditions may be added to facilitate the activity or to initiate the activity.

3 and 4, the first material SB1 and the second material SB2 positioned in the patch PA react with the inside of the patch PA to be transformed into a third material SB3, or The third material SB3 may be generated.

2.2 Channel

2.2.1 Significance

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

The patch PA may form a path of movement of the material or may be involved in the movement of the material. More specifically, the patch PA is involved in the movement of the liquid substance SB trapped in the patch PA or through the liquid substance SB trapped in the patch PA. May be involved in the movement The base material BS or the additive material AS may exit from the patch PA, or an external material may flow into the patch PA from an external region.

The patch PA may provide a function of the movement passage of the material. That is, the patch PA may provide a channel function of material movement by participating in material movement. The patch PA may provide a channel of mass movement due to the inherent property of the liquid substance SB.

The patch PA may be in a state in which the liquid substance SB may move between the outer region or the outer region, depending on whether the patch PA is connected to the outer region. ) May be in a state where it is impossible to move. In addition, when channeling between the patch PA and the outer region is initiated, the patch PA may have unique functions.

Hereinafter, a state in which the material can be moved and a state in which the material cannot be moved will be described first. In the case where the patch PA performs specific functions, whether the patch PA is connected to the outer region and It is described in detail in conjunction.

Basically, between the patch PA and the outer region, the basic reason why the movement of the liquid material SB occurs is due to the irregular movement and / or diffusion of the material. However, in order to control the movement of the material between the patch PA and the external region, it has already been described that it is possible to control external environmental factors (eg, control of temperature conditions, control of electrical conditions, etc.). have.

2.2.2 movable state

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

For example, in the state where the substance is movable, the liquid substance SB or some components of the liquid substance SB may diffuse into the outer region or move by irregular movement. Alternatively, in the state in which the substance is movable, the foreign substance or some component of the foreign substance located in the outer region may diffuse into the liquid substance SB of the patch PA or move by irregular movement.

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

2.2.3 immovable state

In the state in which the material is not moved, movement of the material may not occur between the liquid material SB captured in the patch PA and the external region. However, the movement of the material may occur in each of the liquid material SB captured in the patch PA and the external material located in the external region.

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

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

The term "movable state" as defined herein has a meaning distinguished from "non-movable state", but transition between states may occur due to the passage of time, the environment, and the like. In other words, the patch PA may be in a movable state and may be in a non-movable state, may be in a non-movable state and may be in a movable state, and the patch PA may be in a movable state and then may not be moved. It is also possible to move back to a ready state.

2.2.4 Classification of Functions

2.2.4.1 Delivery

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

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

The predetermined condition for the delivery to occur may be determined by environmental conditions such as temperature change, pressure change, electrical property change, physical state change. For example, when the patch PA contacts an object having a stronger bonding force with the liquid substance SB than the net structure NS of the patch PA, the liquid substance SB is chemically reacted with the contacted substance. Can be combined, and as a result, at least a portion of the liquid material (SB) can be delivered to the object.

Hereinafter, the function of the patch (PA) as described above, for convenience, referred to as delivery.

The transfer may include moving the liquid substance SB between the patch PA and the outer region and moving the liquid substance SB between the patch PA and the outer region. It can happen via / through.

In more detail, when the liquid substance SB is in the movable state, the liquid substance SB may diffuse between the patch PA and the outer region or may move to the outer region by an irregular movement. In other words, the base solution and / or the additive material AS included in the liquid material SB may move from the patch PA to the outer region. In the state in which the liquid substance SB is not movable, movement between the patch PA and the outer region becomes impossible. In other words, some of the material that has been moved from the patch PA to the outer region due to the diffusion and / or irregular movement of the liquid material SB is due to the transition from the movable state to the non-movable state. It will not be possible to move back to the patch PA. Therefore, some of the liquid substance SB may be partially transferred to the outer region.

The transfer may be performed according to the difference between the attraction force between the liquid substance SB and the net structure NS and the attraction force between the liquid substance SB and the external region or the external substance. The attraction may result from the similarity or specific binding relationship of polarity.

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

The delivery of the liquid substance SB may optionally be performed. For example, when there is a specific binding relationship between some components included in the liquid substance (SB) and the external substance, the some components pass through the state in which the substance is movable and the state in which the substance cannot be moved. An optional delivery of may occur.

More specifically, assuming that the patch PA delivers the material to the outer plate PL in the form of a plate, a part of the liquid material SB captured in the patch PA (for example, a solute) A material that specifically binds to) may be applied to the outer plate PL. At this time, the patch PA passes through the movable state and the non-movable state, and the part of the solute that specifically binds to the material applied to the outer plate PL is attached to the plate PA. Can optionally be delivered.

Hereinafter, delivery as a function of the patch PA will be described, according to some examples of other areas in which the material is transported. However, in the specific description, the concept of “release” of the liquid substance SB and “delivery” of the liquid substance SB may be mixed.

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

As the patch PA contacts the plate PL, the liquid substance SB trapped in the patch PA diffuses into at least a portion of the plate PL or moves by irregular movement. Can be. When the contact between the patch PA and the plate PL is separated, some material (that is, a part of the liquid material SB) that has been moved from the patch PA to the plate PL is transferred to the patch ( You will not be able to move back to PA). As a result, the partial material may be transferred from the patch PA to the plate PL. At this time, the some material to be delivered may be the additive material (AS). In order for the material in the patch PA to be 'delivered' by the contact and separation, there must be a attraction force and / or a bonding force acting between the material and the plate PL, and the attraction force and / or the engagement force is It must be greater than the attraction force acting between the material and the patch PA. Therefore, when the aforementioned 'delivery condition' is not satisfied, the transfer of material between the patch PA and the plate PL may not occur.

In addition, the patch PA may be provided with a temperature or electrical condition to control the delivery of the substance.

The movement of material 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 may increase or decrease according to an area where the patch PA contacts the plate PL.

When the patch PA comprises a plurality of components, only some components may be selectively moved to the outer plate PL. In more detail, a material that specifically binds to some components of the plurality of components may be fixed to the outer plate PL. In this case, the material fixed to the outer plate PL may be in a liquid or solid state and may be fixed in the separate area. In this case, some materials of the plurality of components move to the plate PL to form a specific bond due to contact between the patch PA and the separate region, and the patch PA is connected to the plate PL. When separated from), only some components can be selectively released into the plate PL.

5 to 7 show the transfer of material from the patch PA to the outer plate PL as an example of the transfer of material during the function of the patch PA according to the present application. According to FIGS. 5 to 7, the patch PA may transfer a part of the material stored in the patch PA to the plate PL by contacting the outer plate PL. In this case, the transferring of the material may be enabled to move the material by contacting the plate. At this time, the water film WF may be formed near the contact surface between the plate and the patch PA, and the material may be moved through the formed water film WF.

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

As the patch PA comes into contact with the fluid material (for example, the patch PA is injected into the solution), the liquid material SB trapped in the patch PA has at least a part of the fluidity. The branch may diffuse and move to the material SL or may move by an irregular motion. When the patch PA and the flowable material are separated, some of the liquid material SB, which has been moved from the patch PA to the flowable material, cannot move back to the patch PA. In addition, some materials in the patch PA may be transferred to the fluid material.

Material movement between the patch PA and the flowable material SL may depend on the contact area between the patch PA and the flowable material SL. For example, the patch PA may have fluidity with the patch PA according to an area where the patch PA contacts the fluid material SL (for example, a depth into which the patch PA is injected into a solution or the like). The mass transfer efficiency of the material SL may be increased or decreased.

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

The distribution concentration of the additive material (AS) in the liquid material (SB) is different from the distribution concentration of the additive material (AS) in the flowable material, and thus from the patch (PA) to the flowable material. The additive material AS may also be delivered.

However, when the patch PA delivers the liquid material SB to the fluid SL, the physical separation between the patch PA and the fluid SL is essential. no. For example, when the driving force (causal force) that causes the mass movement from the patch (PA) to the fluid having a flow becomes smaller or less than the reference value, the movement of the substance can be stopped.

In the 'delivery' between the patch PA and the flowable material SL, the 'delivery conditions' between the patch PA and the flowable material SL may not be required. It may be. This means that the materials that have already moved to the fluid material SL are moved by diffusion and / or irregular motion in the fluid material SL, and the moving material and the patch PA are moved by the movement. When the distance between them is more than a certain distance it can be understood that the material is transferred to the fluid material (SL). This is because, in the case of the plate PL, since the movable range extended by the contact is a very limited range, the attraction force between the materials moved to the plate PL and the patch PA can act significantly. However, in the relation between the material having flowability and the patch PA, since the movable range extended by the contact between the patch PA and the plate PL is a relatively much wider range, the fluidity This is because the attraction between the materials moved to the material SL and the patch PA becomes meaningless.

8 to 10 show the transfer of material from the patch PA to a flowable material as an example of the transfer of material during the function of the patch PA according to the present application. 8 to 10, the patch PA may transfer a part of the material stored in the patch PA to an external fluid material. Delivering a portion of the stored material is that the patch (PA) is put into or in contact with the fluid material, the liquid material (SB) and the fluid material trapped in the patch (PA) of the material This may be achieved by having a state in which the movement is possible.

Here, the case where a substance moves from the said patch PA to another patch PA is assumed. 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 a portion of the other patch PA.

In the contact area, the liquid substance SB provided to each of the patches PA may diffuse and move to the other patch PA. At this time, due to the movement of the material, the concentration of the liquid material (SB) provided in each of the patches (PA) may be changed. Also in this embodiment, as described above, the patch PA and the other patch PA may be separated, and at this time, a part of the liquid material SB of the patch PA is different from the patch PA. Can be delivered.

Mass transfer between the patch PA and another patch PA can be performed by changes in environmental conditions, including physical state changes.

Material movement between the patch PA and the other patch PA may depend on the contact area of the patch PA and the other patch PA. For example, the mass transfer efficiency between the patch PA and the other patch PA may increase or decrease according to an area where the patch PA contacts the other patch PA.

11 to 13 illustrate the delivery of material from one patch PA1 to another patch PA2 as an example of the delivery of material during the function of the patch PA according to the present application. 11 to 13, the patch PA1 may transfer a part of the material stored in the patch PA1 to another patch PA2. Delivering a portion of the material is that the patch (PA1) in contact with the other patch (PA2), the liquid material (SB) trapped in the patch (PA1) and the material captured in the other patch (PA2) It can be achieved by having a state in which interchange with each other.

2.2.4.2 Absorption

Prior to the description, 'absorption' of the function of the patch PA according to the present application may be treated similarly to the 'delivery' described above in some embodiments. For example, when a movement of a substance due to a difference in concentration of a substance is assumed, the direction of movement of the moved substance can be controlled by changing the concentration of the liquid substance SB, in particular, the concentration of the additive substance AS. It may have a common aspect in that it is. In addition, the control of the movement of the material through the separation of the physical contact of the patch (PA), and the like can also be common, which will be clearly understood by those skilled in the art to which the present application belongs.

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

Hereinafter, the function of the patch PA as described above is called absorption for convenience. The absorption is a sub-concept of the channel function of the patch PA described above, and can be understood to define the movement of foreign material to the patch PA.

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

The material absorbed by the patch PA may be in a liquid or solid state. For example, when the patch PA comes into contact with an external material containing a solid material, the liquid material SB located in the patch PA and the solid material included in the external material may be separated from each other. Absorption of the material can be performed by the attraction force of. As another example, when the patch PA is in contact with a liquid external material, the patch PA may be performed by combining the liquid material SB located in the patch PA with the liquid external material.

The external material absorbed by the patch PA may move into the patch PA or may be distributed on the surface of the patch PA through a microcavity of the net structure NS forming the patch PA. can do. The distribution position of the foreign material may be determined from the molecular weight of the foreign material or the size of the particles.

The shape of the patch PA may be modified while the absorption is performed. For example, the volume, color, etc. of the patch PA may change. Meanwhile, while absorption is performed on the patch PA, external conditions such as temperature change and physical state change may be added to the absorption environment of the patch PA to activate or slow down the absorption of the patch PA.

Hereinafter, absorption will be described as a function of the patch PA, in accordance with some examples of the outer region providing the material absorbed into the patch PA when absorption occurs.

Hereinafter, assume a case in which the patch PA absorbs an external material from a separate outer plate PL. Here, the separate external substrate may exemplify a plate PL, etc., in which the external material may be located while not absorbing the external material.

A material may be applied to the outer plate PL. In particular, the plate PL may be coated with a material 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. In addition, the plate PL may be modified in shape to improve storage properties of the material. For example, it is possible to form a well to improve storage properties, to deform the surface of the plate PL in an engraved or embossed form, or to improve contact with the patch PA by using a patterned plate PL. It may be.

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

When the patch PA is separated from the plate PL by being separated by a predetermined distance or more, the water film WF moves along with the patch PA so that the material applied to the plate PL is applied to the patch PL. (PA) can be absorbed. The material applied to the plate PL may be absorbed into the patch PA as the patch PA is spaced apart from the plate PL by a predetermined distance or more. When the patch PA and the plate PL are separated from each other, the liquid substance SB provided to the patch PA does not move to the plate PL, or only a slight amount of the patch PA. Can be absorbed).

All or part of the material applied to the plate PL may specifically react with all or part of the material trapped in the patch PA. In this regard, the absorption of the material from the separate plate PL by the patch PA may be selectively performed. In particular, this may be the case when the patch PA has a stronger attraction force than the plate PL with respect to a part of the material trapped in the patch PA.

For example, some materials may be fixed to the plate PL. In other words, some materials are fixed to the plate PL and some materials are not fixed or may be applied with fluidity. In this case, when the patch PA and the plate PL are in contact with and separated from each other, only the material except for the fixed part of the material applied to the plate PL may be selectively absorbed into the patch PA. Alternatively, selective absorption may occur due to the polarity of the material located in the plate PL and the material trapped in the patch PA, regardless of fixation.

As another example, when the liquid material SB captured in the patch PA specifically binds to at least a portion of the material applied to the plate PL, the patch PA may be attached to the plate (P). When contacted with and separated from the material applied to PL), only at least a part of the specifically bound material of the material applied to the plate PL may be absorbed into the patch PA.

As another example, some of the material applied to the plate PL may specifically react with a material previously fixed to the plate PL. In this case, only the remainder of the material applied to the plate PL may be absorbed into the patch PA except for a material that specifically reacts with a material previously fixed to the plate PL.

14 to 16 show an example of absorption of a material during the function of the patch PA according to the present application, in which the patch PA absorbs the material from the outer plate PL. According to FIGS. 14 to 16, the patch PA may absorb a portion of the material located on the outer plate PL from the outer plate PL. Absorption of the material may include forming a water film WF near a contact area between the outer plate PL and the patch PA by contacting the outer plate PL with the patch PA. This can be achieved by allowing the material to move into the patch PA through WF).

It is assumed here that the material is absorbed into the patch PA from the material SL having fluidity. The material SL having fluidity may be a liquid external material contained in a separate storage space or flowing. More specifically, the fluid material SL and the liquid material SB trapped in the patch PA have an environment in which they can flow with each other, whereby a part or part of the fluid material SL is present. All may be absorbed into the patch PA. In this case, the mutually flowable environment may be formed by at least partially contacting the patch PA with the fluid SL.

As the patch PA contacts the fluid SL, the patch PA may be in a state where the material SL and the fluid may move. When the patch PA is separated from the flowable material SL, at least a part of the flowable material SL may be absorbed into the patch PA.

Absorption of the material into the patch PA from the fluid SL may depend on the concentration difference between the material trapped in the patch PA and the fluid SL. In other words, the liquid substance SB trapped in the patch PA is more concentrated in the predetermined additive substance AS than the concentration of the fluid SL in relation to the predetermined additive substance AS. When the concentration is low, the predetermined additive material AS may be absorbed into the patch PA.

On the other hand, when the material is absorbed from the fluid SL to the patch PA, in addition to depending on the concentration difference in the contacted state as described above, by adding an electrical factor or by changing the physical conditions The absorption of the patch PA can be controlled. Furthermore, the material captured by the patch PA and the material to be absorbed may not be directly contacted, but may be indirectly contacted through a medium to absorb the material.

17 to 19 show an example of absorption of a material during the function of the patch PA according to the present application, and shows that the patch PA absorbs the material from the fluid SL. 17 to 19, the patch PA may absorb a portion of the flowable material SL. Absorption of the material may include a liquid material SB captured by the patch PA by being injected into the material SL having the fluidity or contacting the material SL having the fluidity. The fluid SL may be made to move with each other.

It is assumed here that the patch PA absorbs an external substance from another patch PA.

Absorption of an external material from the patch PA by the patch PA may include absorption of the external material and the material trapped in the patch PA and the external material and the patch PA. By the difference in the bonding force between the foreign materials that are not. For example, the absorbent material is hydrophilic, the patch PA is hydrophilic, and the attraction force between the absorbed material and the patch PA is the attraction force between the other patch PA and the absorbed material. When the patch (PA) has a strong hydrophilic property compared to the other patch (PA), when the patch (PA) and the other patch (PA) is separated after contact The foreign material may be absorbed at least partially into the patch PA.

20 to 22 show an example of absorption of a material in the function of the patch PA according to the present application, and shows that the patch PA3 absorbs the material from another patch PA4. According to FIGS. 20 to 22, the patch PA3 may absorb a portion of the material located in the other patch PA4. Absorption of the substance may include the liquid substance SB captured by the patch PA3 and the liquid substance SB captured by the other patch PA4 by contacting the patch PA3 with another patch PA4. ) Can be achieved by interacting with each other.

Meanwhile, the binding force of the patch PA to the absorbed external material may vary according to the ratio of the total volume of the patch PA of the frame structure of the three-dimensional net structure NS constituting the patch PA. Can be. For example, as the volume ratio of the frame structure to the entire patch PA increases, the amount of the material trapped in the structure may decrease. In this case, the bonding force between the patch PA and the target material may decrease due to a decrease in contact area between the material captured in the patch PA and the target material.

In this regard, the polarity of the patch PA may be controlled by adjusting the proportion of the material forming the net structure NS in the manufacturing step of the patch PA. For example, in the case of the patch PA prepared using agarose, the degree of absorption may be adjusted by controlling the concentration of the agarose.

When the separate area has a weak bonding force with respect to the material provided from the patch PA compared to the patch PA, and the patch PA and the other patch PA are contacted and separated, the absorption is performed. The foreign material may be separated from the other patch PA together with the patch PA.

2.2.4.3 Provision of Environment

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

Environmental conditions resulting from the patch PA may depend on the liquid substance SB trapped in the patch PA. The patch PA may create a desired environment for the material located in the outer region so as to correspond to the properties of the material contained in the patch PA or to the properties of the material contained in the patch PA.

Adjusting the environment can be understood as changing the environmental conditions of the desired area. The changing of the environmental conditions of the target area may be performed in such a way that the area affected by the patch PA extends to include at least a part of the desired area or the environment of the patch PA with the target area. It may be implemented in a shared form.

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

The provision of the environment by the patch PA may be performed in a state in which the patch PA may move the material and the external area to provide the environment. The provision of the environment by the patch PA can be performed due to the contact. For example, when the patch PA contacts a target area (eg, an external material, a plate PL, etc.), the patch PA may provide a specific environment in the target area. .

The patch PA may provide an environment such as pH, osmotic pressure, humidity, concentration, temperature, and the like to adjust the environment of the target area TA. For example, the patch PA may impart liquidity to the target area TA or the target material. This impartation of fluidity can occur due to some movement of the material trapped in the patch PA. The wetting / moist environment may be provided to the target area TA through the liquid material SB to the base material BS captured by the patch PA.

Environmental factors provided by the patch PA may be kept constant according to the purpose. For example, the patch PA may provide homeostasis to the desired area. As another example, as a result of providing the environment, environmental conditions of the desired area may be adapted to the material captured in the patch PA.

Providing an environment by the patch PA may be a result of the diffusion of the liquid material SB included in the patch PA. That is, when the patch PA and the target region contact, the movement of the material may be possible through the contact region formed by the contact. In this regard, an environmental change due to osmotic pressure, an environmental change due to ion concentration, a wet environment, a change in pH, and the like may be implemented according to the diffusion direction of the material.

23 to 25 are examples of the provision of an environment among the functions of the patch PA according to the present application, and show that the patch PA provides a predetermined environment to the outer plate PL. According to FIGS. 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 to the plate PL. . Providing the environment, the water film (WF) is formed in the vicinity of the contact area by the patch (PA) in contact with the plate (PL) and the fourth material (SB4) and the fifth material in the formed water film (WF) (SB5) can be made by being captured.

3. Apply the patch

The patch PA according to the present application may be implemented to perform various functions by appropriately applying the functions of the above-described patch PA.

Hereinafter, by describing some embodiments, the technical spirit of the present application will be described. However, the technical range to which the function of the patch (PA) disclosed by the present application is applied or applied should be extended and interpreted within the range of easy derivation by those skilled in the art, and is limited by the embodiments described herein. The scope of rights should not be interpreted.

3.1 In-patch

The patch PA may provide a reaction zone of a material. In other words, the reaction of the material may occur in at least a part of the spatial region affected by the patch PA. At this time, the reaction of the substance, the reaction between the liquid substance (SB) trapped in the patch (PA), and / or the substance provided from the outside of the patch (PA) and the liquid substance (SB) trapped. Can be. Providing a reaction zone of the substance may be to activate or promote the reaction of the substance.

At this time, the liquid substance (SB) trapped in the patch (PA) is a substance introduced at the time of fabrication of the patch (PA), is added to the patch (PA) after fabrication and stored in the patch (PA) At least one of the material being and the material temporarily trapped in the patch (PA). In other words, as long as the material is captured in the patch PA at the time when the reaction in the patch PA is activated, it is irrespective of whether it is captured in the patch PA in any form. Can react. Furthermore, it is also possible for a material to be introduced after fabrication of the patch PA to act as a reaction initiator.

The provision of the reaction zone of the reaction involving the liquid substance SB trapped in the patch PA may be an exemplary sub-concept of the table of contents described above in 2.1.3 (ie, the provision of the reaction space). Or, it may be a multi-concept that performs the combined functions of the above-listed 2.1.3 and 2.2.4.2 (ie, absorption) tables of contents. In addition, the present invention is not limited thereto, and two or more functions may be implemented in a merged form.

3.1.1 Embodiment 1

Hereinafter, it is assumed that the absorption function of the patch PA and the provision function of the reaction space (hereinafter referred to as the provision function) are performed by one patch PA. In this case, the absorption function and the providing function may be a function that is performed at the same time, may be a function that is performed at different time points, or may be sequentially performed to perform another function. On the other hand, it can be seen that the patch PA further includes not only the absorbing and providing functions but also additional functions.

As described above, the patch PA may perform a function of capturing a material, and the material may be fluid even when the material is captured. If the distribution of some components of the liquid substance (SB) is non-uniform, the non-uniform components may diffuse. Even when the components of the liquid substance SB are uniformly distributed, the liquid substance SB may be in a state of mobility at a predetermined level due to irregular movement of particles. At this time, a reaction between materials, for example, specific binding between materials, may occur in the patch PA.

For example, in the patch PA, in addition to the reaction between the trapped materials, the fluid having a newly captured fluidity in the patch PA and the material trapped in the patch PA perform specific binding to each other. Form reactions may also be possible.

The reaction between the flowable material and the trapped material may be performed separately from any space in which the flowable material has been provided. For example, after the patch PA absorbs the flowable material from any space, the patch PA is separated from the random space, so that the absorbed material and the patch PA Reaction of the trapped material may occur in the patch PA.

In addition, the patch PA may perform an absorption function of the fluid material, so that the reaction of the trapped material may occur. In other words, a reaction between the absorbed material and the material trapped in the patch PA may occur by triggering the absorption of the fluid material of the patch PA. The reaction may be performed in a space defined by the patch PA.

In addition, due to the reaction occurring inside the patch PA, the composition of the liquid material SB captured in the patch PA may be changed. In particular, when the material trapped inside the patch PA is a compound, the chemical composition may be changed before and after the reaction. Alternatively, the composition distribution according to the position of the material in the patch PA may be changed. This can be exemplified by diffusion or by particles having specific attractive forces to other materials.

When the composition of the liquid material SB is changed due to the reaction inside the patch PA, the material outside the patch PA and the patch PA (if there is a contact material, the contacted material). Due to the difference in concentration, some materials may be absorbed into the patch PA, or the materials may be released from the patch PA to the external material.

3.1.2 Second Embodiment

Hereinafter, an embodiment in which the storage function of the patch PA and the function of providing a reaction space of the material are performed together for at least a predetermined time. More specifically, at least a portion of the liquid material SB stored in the patch PA may serve to provide a space for reacting.

The patch PA may store a material and provide a reaction space of the stored material. In this case, the reaction space provided by the patch PA may be a surface area of the microcavity or the patch PA formed by the mesh structure NS of the patch PA. In particular, when the material stored in the patch PA and the material applied to the surface of the patch PA react, the reaction space may be a surface area of the patch PA.

The reaction space provided by the patch PA may serve to provide a specific environmental condition. The patch PA may adjust the environmental conditions of the reaction while the reaction in the liquid substance SB located in the patch PA is in progress. For example, the patch PA can perform the function of a buffer solution.

The patch PA stores material through the net structure, and thus does not require a separate storage container. In addition, 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. To this end, the patch (PA) may be designed to be modified in a form that is easy to observe.

The liquid substance SB stored in the patch PA may be modified or react with other kinds of substances. The liquid substance SB stored in the patch PA may have a composition changed over time.

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

3.2 channeling

Hereinafter, a patch PA that performs a function of providing a movement path of a substance will be described. More specifically, the patch PA may capture, absorb, release, and / or store fluid material as described above. Each of the above-described functions of the patch PA, or a combination thereof, may implement various embodiments of the patch PA that perform a function of providing a path of movement of a material. However, some embodiments will be described for more specific understanding.

3.2.1 Third Embodiment

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

The patch PA may perform the absorption and delivery functions together to provide a path of movement of the material. In particular, it is possible to provide a movement path of the foreign material by absorbing the foreign material and delivering it to the external region.

Providing a path of movement of the foreign material by the patch PA may be performed by absorbing the foreign material and releasing the foreign material. In more detail, the patch PA may contact the external material to absorb the external material and contact the external area to transfer the external material to the external area. In this case, the patch PA captures the foreign material and delivers the external material to the absorption and delivery process similar to the above-described absorption and delivery.

The foreign substance absorbed and delivered to the patch PA may be a liquid phase or a solid phase.

Through this, the patch PA may allow some materials to be transferred from the external material to the other external material. The patch PA and the foreign material and other foreign material may be in contact at the same time. The patch PA and the foreign material and other foreign materials may contact the patch PA at different times.

The patch PA, the external material, and another external material may be contacted at different time points. When each of the external materials are in contact with each other at a different time point, the patch PA and the external material are contacted first, and after the external material and the patch PA are separated, the patch PA and the other external material are contacted. The material may be contacted. In this case, the patch PA may temporarily store a material captured from the external material.

The patch PA may additionally provide a delay in time while providing a path of movement of the material. In addition, the patch PA may perform a function of appropriately adjusting the amount and rate of delivery of the substance to other foreign substances.

On the other hand, such a series of processes may be performed in one direction based on the patch (PA). As a specific example, absorption of the material may be made through one surface of the patch PA, and an environment may be provided in the internal space of the patch PA, and the material may be released through the other surface facing the one side. Can be.

3.2.2 Fourth Embodiment

The patch PA may absorb and release the material among the functions of the patch PA and provide a reaction space of the material. At this time, the absorption, release and provision of the reaction space of the material may be performed simultaneously or sequentially.

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

The liquid substance SB trapped in the patch PA and the external substance trapped in the patch PA may react inside the patch PA. The foreign material absorbed by the patch PA may be affected by the environment provided by the patch PA. The material released from the patch PA may include at least a part of the material produced through the reaction. The external material may be released by changing the composition, properties, etc. from the patch (PA).

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

Absorption of the external material, reaction of the material, and delivery of the material may be performed in one direction. In other words, absorption of the material may be performed at one location of the patch PA, provision of the environment at another location, and release of the material at another location.

26 to 28 show an embodiment of a patch PA according to the present application, which provides a path of movement of material between two plates PL. According to FIGS. 26 to 28, the patch PA may 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 specific example, when the seventh material SB7 has a bond with the eighth material and the eighth material is fixed to the plate PL2, the patch PA may be attached to the plates PL1 and PL2. The seventh material SB7 may be moved through the patch PA to be combined with the eighth material SB8 by contacting them. The seventh material SB7 and the eighth material SB8 are connected to the patch PA in the water film WF formed by contacting the patches PA with the plates PL1 and PL2. You can.

29 and 30 illustrate an embodiment of a patch PA according to the present application, which provides 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 movement target material and the patch PA7 receiving the movement target material. The patch PA6 providing the movement path contacts the patch PA5 for storing the substance to be moved and the patch PA7 for receiving the substance to be moved. ) Can be moved. The movement of material between each patch can be achieved through the water film WF formed near the contact area between the patches.

31 and 32 illustrate an embodiment of a patch according to the present application, which provides a path of movement of material between two patches. 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 material. The patch PA9 providing the movement path may 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 from the patch PA9 providing the movement path to the patch PA10 receiving the material. The movement of the material between the patches PA may be performed through the water film WF formed near the contact area between the patches PA.

3.3 multi patch

The patch PA may be used alone, or a plurality of patches PA may be used together. In this case, that the plurality of patches PA may be used together includes not only the case where they are used simultaneously but also the case where they are used sequentially.

When the plurality of patches PA is used at the same time, each patch PA may perform a different function. 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, each patch PA is not in contact with each other so that the movement of the material between the patches PA may not occur, or the mutual exchange of materials stored in each patch PA may occur. It is also possible to perform the desired function in the possible state.

The plurality of patches PA used together may be manufactured in a similar shape or the same standard, but may be used together in the case of a plurality of patches PA having different shapes. In addition, each patch PA constituting the plurality of patches PA may have different densities of the net structure NS, or different components forming the net structure NS.

3.3.1 Multiple Patch Contacts

When using the plurality of patches PA, the plurality of patches PA may contact one target area TA. The plurality of patches PA may contact one target area TA to perform a desired function.

The plurality of patches PA may contact different target areas TA when the plurality of target areas TA is plural. When the plurality of target areas TA is present, the plurality of patches PA may contact the target areas TA corresponding to the plurality of patches PA to perform a desired function.

The plurality of patches PA may be in contact with a material applied to the target area TA. In this case, the material applied to the target area TA may be fixed or have fluidity.

The desired function may be a delivery or absorption function of a substance. However, each patch PA does not necessarily deliver the same material or absorb the same material, and each patch PA delivers a different material to the target area TA, or is located in 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 may perform a function of transferring a material to the target area TA, and the other patch PA may perform a function of absorbing a material from the target area TA.

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

According to one embodiment, when the plurality of patches (PA) comprises a material of different components and the material of the different components have different specific binding relationship, the material of the different components to the target region ( TA). The plurality of patches PA may be used to detect a plurality of specific bindings from a material applied to the target area TA by transferring materials of the different components.

According to another embodiment, the plurality of patches PA may include materials of the same component, and each patch PA may have a different concentration with respect to the materials of the same component. The plurality of patches PA including the materials of the same component may contact the target area TA and may be used to determine the influence of the concentration of the materials included in the plurality of patches PA.

On the other hand, when using a plurality of patches (PA) as described above, it is possible to modify the bundle of the patches (PA) in a more efficient form. In other words, the configuration of the plurality of patches PA to be used can be used differently each time. That is, the plurality of patches PA can be manufactured and used in the form of a cartridge. At this time, the shape of each patch PA used can also be suitably standardized and manufactured.

The plurality of patches PA in the form of cartridge may be suitable when a patch PA for storing a plurality of types of substances is prepared, and if desired, the selected patch PA is used.

In particular, when a plurality of kinds of substances are to be used to detect specific reactions of each substance from the target area TA, a combination of specific reactions to be detected may be configured and performed each time the detection is performed. There will be.

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

34 illustrates that a plurality of patches PA is used together, and the plate PL includes a plurality of target areas TA. According to FIG. 34, the plurality of patches PA according to the exemplary embodiment of the present application may be simultaneously in contact with the plurality of target areas TA positioned on the plate PL. The plurality of patches PA includes a first patch PA and a second patch PA, and the plurality of target areas TA includes a first target area and a second target area. The patch may contact the first target area and the second patch may contact the second target area.

3.3.2 Fifth Embodiment

The plurality of patches PA may perform a plurality of functions. As described above, each patch PA may perform a plurality of functions at the same time, and each patch PA may perform a different function at the same time. However, the present invention is not limited thereto, and each function may be performed in combination in a plurality of patches PA.

First, when each patch PA performs a plurality of functions simultaneously, each patch PA may perform both storage and release of the material. For example, each patch PA may store a different material and release each stored material in the target area TA. In this case, each stored material can be released simultaneously or sequentially.

Next, as each patch PA performs a different function at the same time, each patch PA may be performed by dividing the storage and release of the material. In this case, only some of the patches PA may be in contact with the target area TA, and may release the material into the target area TA.

3.3.3 Embodiment 6

When a plurality of patches PA is used, as described above, the plurality of patches PA may perform a plurality of functions. First, each patch PA can simultaneously perform storage, release and absorption of the material. Alternatively, each of the patches PA may be performed by dividing the storage, release and absorption of the material. However, the present invention is not limited thereto, and each function may be performed in combination in a plurality of patches PA.

For example, at least some of the plurality of patches PA may store a material and release the stored material to the target area TA. In this case, at least some other of the plurality of patches PA may absorb the material from the target area TA. Some of the plurality of patches PA may emit a material specifically binding to a material positioned in the target area TA. In this case, detection of specific binding may be performed by absorbing a material that does not form the specific binding among the materials located in the target region TA using another patch PA.

3.3.4 Seventh Embodiment

If multiple patches PA are used, each patch PA may simultaneously perform storage, release and provision of the environment at the same time. Alternatively, each of the patches PA may perform a separate storage, release and provision of the environment. However, the present invention is not limited thereto, and each function may be performed in combination in a plurality of patches PA.

For example, one patch PA among the plurality of patches PA may release the stored material to the target area TA. In this case, another patch PA may provide an environment to the target area TA. In this case, the providing of the environment may be implemented in a form of transferring the environmental conditions of the material stored in the other patch PA to the target area TA. More specifically, the reactant may be provided to the target area TA by one patch PA, and the other patch PA may contact the target area TA to provide a buffer environment.

As another example, the plurality of patches PA may be in contact with each other. In this case, the at least one patch PA may store the material and release the stored material as another patch PA providing the environment. In this embodiment, the patch PA providing the environment is in contact with at least one patch PA that releases the material and is not in contact with each other, and can absorb the material from each patch PA.

4. Tissue Diagnosis

The patch according to the present application described above may also be applied to the performance of a diagnosis for a tissue. Hereinafter, the tissue diagnosis to which the patch of the present application is applied will be described.

4.1 Introduction

4.1.1 Significance

In the present application, tissue diagnosis is a diagnosis / prediction / management of a disease / disease using a tissue as a sample to be diagnosed, and may be defined as a concept that is distinguished from performing a diagnosis using a body fluid or a cell as a sample.

The consultation tissue may refer to tissue collected from the human body. For example, it may mean some tissues, epithelial tissues, etc. constituting human organs. Broad tissue can be defined as including not only the human body but also tissues obtained from animals and plants, and further, artificial tissues. In the following, the term "organization" means an organization of consultation.

In applying the patch of the present application to the immunodiagnosis, the base material and the additive material described above may be appropriately changed depending on the application.

4.1.2 Classification of tissue diagnosis

Tissue diagnosis in the present application may be classified as follows according to some criteria.

Tissue diagnosis may be classified according to the preparation method of the specimen or the state of the specimen. The sample used for tissue diagnosis may be paraffin filled tissue thinning or frozen cutting.

Tissue diagnosis may be classified according to targets (ie, target substances) to which the diagnosis is based. In other words, the tissue diagnosis may be performed differently depending on the case where the target nucleotide sequence is to be detected and the target protein (especially the antigen) is detected and the diagnosis is desired. have. The target substance may include a target protein, a target nucleotide sequence, DNA, and the like included in the tissue sample.

Tissue diagnosis may be classified according to the manner of obtaining the diagnosis result. The tissue diagnosis may be performed by a method of acquiring an image or a method of acquiring a quantitative measurement of a target substance included in a specimen. The method of acquiring the image may mean a method of acquiring an image captured in a bright field or a method of acquiring a fluorescent image.

4.1.3 Methods of Tissue Diagnosis

4.1.3.1 Immunological Diagnosis

Tissue diagnosis according to the present application may be to perform a diagnosis by obtaining a distribution of a target protein from a tissue sample (SA). At this time, immunological methods may be used. In other words, the target protein can be detected by the antigen-antibody reaction, and the distribution of the target protein can be obtained.

Acquiring the distribution of the target protein may be performed using an antibody that specifically binds to the target protein. In other words, obtaining a distribution of the target protein may be performed by detecting a product (PD) according to a chemical reaction of a substrate catalyzed by an enzyme attached to an antibody that specifically binds to the target protein. Acquiring the distribution of the target protein may be performed using a first antibody specifically binding to the target protein and a second antibody specifically binding to the first antibody. At this time, the second antibody may be attached with a label to facilitate the identification of the distribution of the target protein.

Alternatively, the distribution of the target protein may be performed by detecting fluorescence emitted by a fluorophore attached to an antibody that specifically binds to the target protein.

As an example of the above-described immunological tissue diagnosis, the cancer sample may be detected by detecting a specific protein whose expression increases or decreases due to the onset of the cancer from the tissue sample (SA).

4.1.3.2 Morphological Diagnosis

The tissue diagnosis according to the present application may be performed by observing the form or distribution of cell and other substances constituting the tissue sample (SA). At this time, it may be accompanied by a staining process that makes the parts constituting the tissue color to facilitate the morphological diagnosis.

As an example of the morphological tissue diagnosis, the presence or absence of a tumor may be determined by detecting the characteristic forms of malignant cells by observing the morphology of cells constituting the tissue sample (SA).

4.1.3.3 DNA Diagnostics

Tissue diagnosis according to the present application, the diagnosis can be performed according to the configuration of the DNA contained in the tissue specimen (SA). The tissue diagnosis may be performed by detecting a specific base sequence from a tissue sample (SA).

As one example of diagnosing the DNA tissue, a tumor oncogene may be detected to predict a cancer occurrence probability. In addition, the DNA tissue diagnosis can be used for early detection of predisposed genetic diseases, prenatal tests, and the like.

4.2 Preparation of Tissue Diagnosis

In the tissue diagnosis according to the present application, diagnosis may be performed using the patch PA described above with respect to a tissue specimen SA.

4.2.1 Preparation of Sample to be Diagnosed

In the tissue diagnosis according to the present application, the diagnosis may be performed on a tissue collected from a human body. The tissue collected from the human body may be prepared in advance for easy diagnosis.

The tissue sample (SA) may be a paraffin filled and sliced tissue sample (SA) or frozen-sectioned tissue sample (SA). The frozen cut tissue sample (SA) may be embedded with gelatin. However, this is only an example, the tissue sample (SA) may be embedded with a medium such as celloidin, carbowax, other than paraffin.

The tissue sample (SA) is taken from the human body, fixed, washed, dehydrated, cleaned and infiltrated, embedded, and microtome. cutting). The prepared tissue sample SA may be dried.

The tissue sample (SA) may be fixed by formaldehyde (Formaldehyde), ethyl alcohol (Ethyl alcohol), acetone (Aceton) and the like.

The tissue sample (SA) may be formed of a thin tissue section of 3-5μm. The cut specimen SA may be manufactured using a separate slicer such as a rotary slicer or a frozen slicer.

Tissue specimen (SA) according to the present application, may be provided located on the plate (PL). The tissue sample SA may be prepared by being fixed to the plate PL.

The plate PL may mean a solid plate PL such as a plate PL made of a general slide glass, polystyrene, polypropyrene, or the like. In addition, the plate PL may have a different shape or transparency depending on a detection method. The plate PL may include a reaction region in contact with the patch PA or in which a desired reaction may occur.

Meanwhile, hereinafter, the above-described plate, a reaction region that may be located on the plate, and a tissue sample that may be located on the reaction region may be mixed according to context. In particular, in the subject in contact with the patch, the plate, the reaction zone, and the tissue sample are defined as being interchangeable.

The tissue sample SA may be a living body. However, in this application, unless otherwise specified, it is assumed that the diagnosis is performed on a tissue specimen (SA) prepared for histological analysis.

Hereinafter, a method of performing diagnosis using the tissue sample SA positioned on the plate PL will be described.

4.1.1 Preparation of Patches

Tissue diagnosis according to the present application may be performed using the above-described patch (PA).

The patch PA may store a staining reagent for staining the tissue sample (SA). The patch PA may store the staining reagent and deliver the stained reagent to the tissue sample SA. The staining reagent may include hematoxylin for staining the nucleus of the tissue or eosin for staining the cytoplasm. The staining reagent may be an immunostaining reagent for labeling a specific protein by antigen-antibody reaction. The immunostaining reagent may include an antibody to which a specific protein specifically binds.

The patch PA may store a fluorescent reagent for observing the tissue sample SA. The patch PA may store the fluorescent reagent and deliver the fluorescent reagent to the tissue sample SA. The fluorescent reagent may include a portion of the fluorescent material for labeling the target material, labeling the target protein, or labeling the target DNA. The patch PA may store labeling substances such as a color labeling substance (eg, hematoxylin), a fluorescent labeling substance (eg, an antibody to which a fluorophore is attached), and the like.

The patches PA may be used individually or in combination, depending on how the tissue diagnosis is performed.

4.2 Performing tissue diagnosis

Tissue diagnosis according to the present application may be performed differently depending on the detection aspect of the diagnosis result.

When a bright field image is to be obtained, some components of the tissue sample (SA) may be stained (that is, a color label) to perform a diagnosis. When a fluorescent image is to be obtained, a part of the tissue sample (SA) may be used. Diagnosis can be performed by labeling the components with fluorescence.

The diagnosis of staining some components of the tissue sample (SA) and the diagnosis of the fluorescent labeling of some components of the tissue sample (SA) will be described with reference to FIGS. 35 to 38. same.

According to FIG. 35, in the tissue diagnosis method according to the exemplary embodiment of the present application, a step of placing a tissue sample SA in a reaction area (S200) and delivering a fluorescent labeling material to a tissue sample SA (S300) And detecting the fluorescently labeled target material TS (S400). The tissue diagnosis method may detect a target material TS from a tissue sample SA by using a patch PA including a net structure forming microcavities and storing a material in the microcavities. have.

In this case, the target material (TS) is a target nucleotide sequence included in the tissue sample (SA), the fluorescent labeling material includes a fluorescently labeled nucleic acid probe, the nucleic acid probe is complementary to the target nucleotide sequence can do. Alternatively, the target material TS is a fluorescently labeled target protein, and the fluorescently labeled material includes a fluorescently labeled antibody, and the antibody may specifically bind to the target protein.

The fluorescent label material may be a fluorescent label complex including a reaction derivative specifically reacting with the target material TS and a fluorescent label for detecting the target material TS.

In this case, the reaction derivative may mean a portion that specifically binds to the target material. For example, the reaction derivative may include a probe that binds to the target nucleotide sequence complementarily or an antibody that specifically binds to the target protein.

In addition, the fluorescent label may mean a part attached to the reaction derivative to induce fluorescence detection. For example, the fluorescent label may include an enzyme that induces fluorescence emission by chemical reaction with a fluorophore attached to an antibody, a fluorophore attached to a probe or a substrate.

The fluorescently labeled probe may be a probe to which a fluorophore or the like capable of emitting fluorescence is attached. The fluorescently labeled probe may be a probe to which an enzyme is attached that reacts with a substrate to induce emission of fluorescence.

Positioning the tissue sample (SA) in the reaction zone (S200), may be to fix the tissue sample (SA) to the reaction zone or plate (PL). The tissue sample SA may be a tissue sample SA that has been cut through at least some treatment of fixation, washing, dehydration, transparency, infiltration, or embedding.

The step of delivering the fluorescent labeling material to the tissue sample (SA) (S300), the fluorescent labeling material for storing the fluorescent labeling material for specifically labeling the target material (TS) using the fluorescent labeling material It may be delivered to a tissue sample (SA).

The detecting of the fluorescently labeled target material TS (S400) may be to detect the fluorescently labeled target material TS from the tissue sample SA.

Detecting the fluorescent label may be performed by obtaining a fluorescent image of the tissue sample (SA). The fluorescence image may refer to an image in which fluorescence labeled on the target material is displayed to be distinguishable.

The detecting of the fluorescently labeled target material TS may be performed by measuring the amount of fluorescence emitted from the target material TS included in the tissue sample SA. The detecting of the fluorescently labeled target material TS may include acquiring distribution information of the target material TS from the tissue sample SA.

Acquiring the distribution in the tissue sample of the target material may include acquiring a position, a distribution area, a distribution form, or a distribution amount of the target material in the tissue sample.

According to FIG. 36, in the method of diagnosing tissue according to the present embodiment, the step of delivering the fluorescent labeling material to the tissue sample SA (S300) includes applying a patch PA storing the fluorescent labeling material to the tissue sample SA. It may include the step of contacting (S310) and separating the patch (PA) for storing the fluorescent labeling material from the tissue sample (S330).

In the step (S310) of contacting the patch PA storing the fluorescent labeling material with the tissue sample (SA), when the patch PA is in contact with the tissue sample (SA), the fluorescent labeling material to the reaction region It may be movable.

In the step (S330) of separating the patch PA storing the fluorescent labeling material from the tissue sample (SA), when the patch PA is separated from the tissue sample (SA), the target material of the fluorescent labeling material ( Excess fluorescent labeling material that does not bind to TS) can be removed from the reaction zone.

According to FIG. 37, according to an embodiment of the present invention, a method for diagnosing tissue may include placing a tissue sample (SA) in a reaction area (S500), and delivering a color labeling substance to the tissue sample (S600). And detecting the color-labeled target substance TS (S700). The tissue diagnosis method may include a net structure that forms microcavities, and detects a target substance TS from a tissue sample SA by using a patch PA configured to store a substance in the microcavities. Can be.

The color labeling substance may be a color labeling complex including a reaction derivative that specifically reacts with the target substance TS and a color marker for detecting the target substance TS. have.

In addition, the color label may mean a part attached to the reaction derivative to induce color detection. For example, the color label may include an enzyme attached to an antibody or a probe attached to an antibody and inducing fluorescence emission by chemical reaction with a substrate.

The target substance (TS) is a target base sequence included in the tissue sample (SA), and the color labeling substance may include a nucleic acid probe that complementarily binds to the target base sequence. Alternatively, the target substance (TS) is a target protein included in the tissue sample (SA), and the color labeling substance includes an antibody to which a label that induces a color label is attached, and the antibody is specific to the target protein. Can be combined. The target protein included in the tissue sample may be an antigen.

Positioning the tissue sample (SA) in the reaction region (S500), may be performed similarly to the above-described embodiment.

Delivering the color labeling material to the tissue specimen (SA) (S600), the staining material to the tissue sample using a patch (PA) for storing the color labeling material for imparting color to the target material (TS) May be delivered to (SA). Imparting the color may mean combining the colored particles with the target material, or infiltrating the colored material with the target material.

Detection of the target material TS given the color (S700) may be performed by acquiring an image of the tissue sample SA. In this case, the image of the tissue sample SA may be an image in which the color mark is displayed.

According to FIG. 38, in the method of diagnosing tissue according to the present embodiment, the step (S600) of delivering the color labeling substance to the tissue sample SA may include applying a patch PA storing the color labeling substance to the tissue sample SA. Contacting (S610) and separating the color labeling material from the tissue sample (SA) (S630).

In the step (S610) of contacting the patch (PA) for storing the color labeling material with the tissue sample (SA), when the patch (PA) is in contact with the tissue sample (SA) the color labeling material is the reaction region Can be made mobile.

In the step (S630) of separating the color labeling substance from the tissue sample SA, when the patch PA is separated from the tissue sample SA, the color labeling substance does not react with the target material TS among the color labeling substances. Excess color labeling material can be removed from the reaction zone.

48 to 50 schematically illustrate detecting a target material TS included in a tissue sample SA using a patch PA as an embodiment of a tissue diagnosis method according to the present application. According to FIGS. 48 to 50, the subject (SA) is placed on the plate (PL), the labeling agent (LA) is delivered to the tissue sample (SA), and the subject labeled by the labeling agent (LA) The substance TS can be detected. In the present exemplary embodiment, the labeling material LA may be a fluorescent labeling material or a color labeling material.

In this case, delivering the labeling material LA may be performed using a patch PA storing the labeling material LA.

Delivery of the labeling material LA may be performed by contacting and separating the patch PA storing the labeling material LA from the tissue sample SA (or reaction region) (S310, S330, and the like). S610, S630). The aqueous membrane WF may be formed near the contact area by contacting the patch PA storing the labeling material LA with the tissue sample SA (S310 and S610). The labeling material LA may be moved to the reaction region (or tissue sample SA) through the formed water film WF. The labeling material LA, which is movable to the reaction region, may specifically react with, bind to, or attach to the target material TS included in the tissue sample SA.

By separating the patch PA from the plate PL or the tissue sample SA (S330 and S630), the labeling material LA (that is, the surplus labeling material) that does not react with the target material TS may be It can be removed from the plate PL. When the patch PA is separated from the plate PL, the formed water film WF moves along with the patch PA, and the excess labeling material is trapped in the water film WF, so that the patch ( PA). The excess labeling substance may be removed from the plate PL when the patch PA is separated from the plate PL. The excess labeling material may be an excess color labeling material or an excess fluorescent labeling material.

The target material TS included in the tissue sample SA may be detected by detecting the labeling agent LA positioned on the plate PL by specifically reacting or binding with the target material TS. have.

51 to 53 illustrate a case where a target base sequence (TB) included in a tissue sample (SA) is detected using a probe (PR) as an embodiment of a tissue diagnosis method according to the present application. 51 to 53, a tissue sample (SA) is placed on the plate (PL), and a labeled probe (PR) having a complementary relationship with the target nucleotide sequence (TB) is transferred to the tissue sample (SA). The target nucleotide sequence (TB) labeled by the labeling probe (PR) may be detected. In this case, the delivering of the labeled probe PR may be performed using a patch PA that stores the labeled probe PR.

The delivering of the labeled probe PR may be performed by contacting and separating the patch PA storing the labeled probe PR from the tissue sample SA (S310, S330, S610, and S630). . The aqueous membrane WF may be formed near the contact area by contacting the patch PA storing the labeled probe PR with the tissue sample SA (S310 and S610). The label probe PR may be moved to the reaction region through the formed water film WF. The labeled probe (PR), which is movable to the reaction region, may complementarily bind to a target nucleotide sequence (TB) included in the tissue sample (SA).

The label probe PR (ie, a surplus label probe) that does not bind to the target nucleotide sequence TB by separating the patch PA from the plate PL or the tissue sample SA (S330, S630) is It may be removed from the plate PL. When the patch PA is separated from the plate PL, the formed water film WF moves along with the patch PA, and the surplus label probe is captured by the water film WF, and thus the patch ( PA). The excess label probe may be removed from the plate PL when the patch PA is separated from the plate PL.

51 to 53 schematically show target nucleotide sequence detection by a labeled probe, and the labeled probe substantially penetrates into cells of a tissue sample (SA) to specifically target the target nucleotide sequence (TB). Can be combined.

54 to 58 schematically show a case of detecting a target protein included in a tissue sample (SA) using an antibody (AB) as an embodiment of a tissue diagnosis method according to the present application. 54 to 58, a tissue sample (SA) is placed on the plate (PL), an antibody (AB) is delivered to the tissue sample (SA), and the target protein is detected from the tissue sample (SA). can do.

In this case, delivering the antibody (AB) may be performed using a patch (PA) that stores the antibody (AB). In addition, the antibody (AB) may be attached with a label for identification.

The antibody (AB) may be delivered by contacting and separating the patch (PA) storing the antibody (AB) from the tissue sample (SA). The aqueous membrane (WF) may be formed in the vicinity of the contact by contacting the tissue (SA) with the patch (PA) for storing the antibody (AB). The antibody AB may be moved to the reaction region through the formed water film WF. The antibody (AB), which is movable to the reaction region, may specifically bind to a target protein included in the tissue sample (SA).

By separating the patch (PA) from the plate (PL) or the tissue sample (SA), the antibody (AB) that does not bind the target protein (ie, the surplus antibody (AB)) can be removed from the plate (PL). Can be. When the patch PA is separated from the plate PL, the formed water film WF moves along with the patch PA, and the surplus antibody AB is trapped in the water film WF to allow the patch. (PA) can be absorbed. The excess antibody AB may be removed from the plate PL when the patch PA is separated from the plate PL.

As described above, when the antibody (AB) specifically binds to the target protein and the identification label is attached to the antibody (AB) itself, the identification label is detected by detecting only the antibody (AB). Target proteins can be detected. However, when an enzyme is attached to the antibody AB, a patch PA for storing the substrate SU may be separately provided and used. Using the patch PA to store the substrate SU, delivering the substrate SU to the reaction region may be applied similarly to the delivery of the antibody AB described above (FIGS. 57 and 58).

Meanwhile, in the present embodiment, a method of identifying a target protein using an antibody by a direct enzyme-linked immune sorbent assay (ELISA) method has been described. However, a method using an indirect ELISA is also possible. In this case, the indirect ELISA refers to detecting the target protein by using a first antibody that specifically binds to the target protein, and a second antibody that has a specific binding property to the first antibody and is attached with an identification label.

Hereinafter, the present invention will be divided into a case where the detection target material TS included in the tissue sample SA is diagnosed by staining, and a case where diagnosis is performed by fluorescence of the detection target material TS. However, each diagnostic method is not only to be performed separately, but may be applied together in one diagnostic process. In other words, the diagnostic methods disclosed in the present application do not have to be performed in a separate or independent relationship. For example, through one process, brightfield images and fluorescence images of the same tissue sample (SA) may be obtained together. When a plurality of diagnostic schemes are used in one diagnostic process, information obtained according to each diagnostic scheme may be different.

4.2.1 Performing staining diagnosis-acquisition of bright field images

Staining can be used to observe tissue specimens (SA). Since most of the elements constituting the tissue are not colored, the diagnosis may be performed by staining the tissue specimen (SA) so that the components of the tissue may be clearly distinguished and easily observed.

In the present application, dyeing is performed by using a label that can generate colored precipitates, in addition to coloring the target material TS by using a colored material. It also includes positioning the label. Specifically, the dyeing of the tissue may be used, such as biostaining, dyeing by selective dissolution, dyeing by chemical color reaction, metal penetration method, dyeing by dye.

Hereinafter, some embodiments of a method of staining a portion of a tissue sample (SA) to perform a tissue diagnosis are described.

Performing a tissue diagnosis according to the present application, positioning a tissue sample (SA) in the reaction area, using a patch (PA) to deliver a staining substance (staining substance) to the tissue sample (SA) and the And acquiring a bright field image of the tissue sample (SA) located in the reaction area.

Positioning the tissue sample SA in the reaction region may be placing the tissue sample SA on the plate PL. Positioning the tissue sample SA in the reaction region may be fixing the tissue sample SA to the reaction region or plate PL. Fixing the tissue sample SA may be performed by drying the tissue sample SA.

Delivering a staining material to the tissue sample (SA), may be to deliver a staining material for reading the shape of the cells constituting the tissue sample (SA). The patch PA may store a staining material for reading the morphology of cells constituting the tissue sample SA and deliver the stained material to the sample SA or the reaction region.

The staining material for reading the shape of the cells constituting the tissue sample (SA) may be an ionic staining material. In other words, the dyeing material may be acidic and impart color to the basic part of the tissue sample (SA). Alternatively, the dyeing material may be basic and impart color to an acidic portion of the tissue sample (SA).

The staining material for reading the morphology of the cells constituting the tissue sample (SA) may be an immunological staining material. The staining material may include an antibody that specifically binds to a target protein by an antigen-antibody reaction. An antibody that specifically binds to the target protein may indicate a region in which the target protein is distributed. Therefore, by analyzing the region in which the target protein is distributed, a morphological diagnosis of a tissue specimen (SA) may be performed.

Delivering a staining material to the tissue sample (SA), may be to deliver a dyeing material for labeling the target protein. The patch PA may store dyeing material for labeling the target protein and transfer the stained material to the sample or the reaction region.

The staining material for labeling the target protein may be a staining material using an antigen-antibody reaction. In other words, the target protein may be an antigen associated with a particular disease, and the delivery of the staining material specifically binds to the antigen and binds to the antibody to which the enzyme is attached, and to the colored precipitate catalyzed by the enzyme. It may include delivering a substrate (SU) to produce.

The staining material for labeling the target protein may induce a color reaction in the region where the target protein is located. In this case, the tissue diagnosis according to the present embodiment may be performed by measuring the colorimetric according to the color reaction and obtaining the presence or absence of the target protein, distribution information of the target protein, and the like.

Delivering the dyeing material to the tissue sample (SA), may be to deliver a dyeing material for labeling the target nucleotide sequence. The patch PA stores a staining material for labeling DNA (or a specific nucleotide sequence) included in the tissue sample (SA), and transfers the staining material to the tissue sample (SA) or the reaction region. .

In this case, the target nucleotide sequence to be detected may be a target nucleotide sequence for causing a disease to be diagnosed.

The dyeing material for labeling the target base sequence may be for detecting the target base sequence by in situ hybridization. The dyeing material for labeling the target sequence may be to detect the target base sequence using a nucleic acid probe (probe). Specifically, the dyeing material for labeling the target base sequence may include a probe that binds specifically (or complementarily) to the target base sequence and generates a color precipitated substance. The target nucleotide sequence may be detected by using chromogenic in situ hybridization (CISH).

The diagnostic method of detecting the target nucleotide sequence may be used to determine whether cancer (eg, breast cancer) has developed or whether human papillomarvirus is infected.

Delivering the dyeing material, the patch (PA) for storing the dyeing material is in contact with the reaction zone (hereinafter, the reaction zone, defined by the concept encompassing the sample (SA) or the reaction zone) The patch PA may be performed by separating from the reaction zone. According to the staining method of the tissue specimen (SA) according to the present application, compared to the conventional method of performing a staining of the tissue by applying a large amount of the staining sample, a significantly smaller amount of sample is required for staining, economic diagnosis This can be realized.

In this case, the dyeing material is transferred, the patch (PA) is in contact with the reaction zone, the dyeing material is able to move to the reaction zone, the dyeing material is a dyeing target material (TS) included in the reaction zone ) In combination with In this case, when the patch PA is separated from the reaction zone, the dye material which does not bind to the dyeing target material TS among the dyeing materials that have moved to the reaction zone may be absorbed into the patch PA.

Specifically, the dyeing material is transferred through the water film WF formed near the contact area by contacting the reaction area with the patch PA (the dyeing material may move to the reaction area, The dyeing material may be formed by binding to the dyeing target material TS included in the reaction zone, and when the patch PA is separated from the reaction zone, the dye is moved to the reaction zone through the water film WF. Among the materials, the dyeing material that does not bind to the dyeing material TS may be captured by the water film WF and absorbed into the patch PA.

As described above, in the case of transferring the dyeing material using the patch PA, the dyeing material that does not bind to the dyeing target material TS may be removed from the sample SA only by separating the patch PA from the reaction region. Can be. Therefore, in the tissue diagnosis method according to the present application, a washing process is performed using a separate washing solution to remove a substance (i.e., excess staining substance) that does not specifically bind to the dyeing target material (TS). Reagents are consumed less quickly and faster diagnosis can be performed than in the conventional method.

Acquiring a brightfield image of the tissue sample SA may be to acquire an image in which the target material (that is, the dyeing target material TS) on which the tissue diagnosis is based is dyed, colored, or colored. Alternatively, the bright field image may be an image obtained by combining color particles or pigments deposited on the target material TS. The brightfield image may be an image in which some elements, which are the basis for morphological analysis of the cells constituting the tissue sample (SA), are stained or colored. The brightfield image may be an image in which the target protein included in the tissue sample (SA) is color-labeled. The brightfield image may be a color-labeled image of DNA or a target nucleotide sequence included in the tissue specimen.

Acquiring a bright field image of the tissue specimen (SA) may be performed using bright field microscopy. Acquiring a bright field image of the tissue sample SA may use a light microscope. Acquiring the bright field image is obtained by recognizing light incident on one surface of the plate PL on which the tissue sample SA is located from a light source, and recognizing the light that has passed through the tissue sample SA. It may be. Acquiring a brightfield image of the tissue sample SA may be performed using an imaging module such as a CMOS (completary metal-oxide semiconductor) image sensor or a charged coupled device (CCD) image sensor. Acquiring the bright field image may be to acquire one image including the entire area of the tissue specimen (SA). Alternatively, the brightfield image may be obtained by capturing a tissue sample (SA) located in the reaction area for each of a plurality of unit regions to obtain a plurality of unit images and collecting the plurality of unit images. .

The tissue diagnosis according to the present embodiment may further include analyzing the obtained brightfield image.

Analyzing the acquired image may be to perform a morphological analysis.

For example, analyzing the acquired image may be performed to determine whether the cancer has developed from the sample SA. Specifically, whether or not the presence of an irregular shape of the nucleus from the form of the nucleus contained in the tissue sample (SA), or the adhesion between the cells from the junction state between the cells included in the tissue sample (SA) or By determining whether the arrangement of the cells included in the tissue sample (SA) is uniform, it may be determined whether the cancer is developed from the tissue sample (SA). However, the above judgments are only examples, and various morphological aspects for determining the presence or absence of cancer cells from tissue specimens (SA) may be applied.

For example, FIG. 42 schematically shows cancer cells and normal cells in one embodiment of tissue diagnosis according to the present application. Referring to FIG. 42, a general cell has a uniform form, has a large cytoplasm, has one nucleus per cell, and one nucleus has one nucleolus. Chromatin is tightly distributed. In contrast, cancer cells have an irregular shape, the cytoplasm is small, there may be a plurality of nuclei in one cell, a plurality of nucleolus in one nucleus, chromatin may be present in the nucleus. By using the morphological characteristics of the cancer cells and the normal cells, the presence or absence of cancer cells can be determined from the image of the tissue specimen (SA), or the distribution of cancer cells can be obtained.

Analyzing the acquired image may be to obtain a distribution of the detection target material TS. For example, distribution of the target protein can be obtained. In other words, the presence of a target antigen associated with the disease to be diagnosed or the position where the antigen is distributed in the tissue sample (SA) can be obtained. Alternatively, distribution of the target nucleotide sequence can be obtained. For example, from the tissue sample (SA), it is possible to obtain whether the target base sequence associated with the disease to be diagnosed is included and its distribution.

The analysis of the above-described image may be performed by artificial intelligence. In other words, detecting the diagnosis basis from the above-described image or obtaining the diagnosis result by analyzing the image may be performed by machine learning AI.

The acquired image is not only used for diagnosis of cancer or tumor, but may also be used for observing intracellular organelles, predicting a disease at risk of development, or managing a disease that has occurred in the past.

The tissue diagnosis according to the present embodiment may include measuring the amount of the target substance TS included in the tissue sample SA. The target substance (TS) may be a substance such as a target protein or a target nucleotide sequence to be diagnosed.

Measuring the amount of the target material (TS) may be performed by measuring the amount of the target material (TS) stained in the tissue sample (SA).

Alternatively, measuring the amount of the target material TS included in the tissue sample SA may be performed using an electrochemical method. In other words, measuring the amount of the target material (TS), in the delivery of the dyeing material to the tissue sample (SA) or the reaction region by using the patch (PA), it is included in the tissue sample (SA) The amount of material transferred from the patch PA to the reaction region may vary depending on the amount of the target material TS. In this case, as the material is transferred from the patch PA to the reaction region, a change in electrical characteristics of the patch PA or the plate PL on which the reaction region is located may be measured.

However, acquiring the amount of the target material TS is not necessarily performed independently from acquiring the image of the tissue sample SA described above, and obtaining the image to diagnose the sample SA and the sample. Measuring the amount of the target substance (TS) contained in (SA) may be parallel.

4.2.2 Performing Fluorescence Diagnostics-Acquisition of Fluorescence Images

Performing a tissue diagnosis according to the present application, positioning a tissue sample (SA) in the reaction area, delivering a fluorescent substance (fluorescent substance) to the tissue sample (SA) by using a patch (PA), the The method may include obtaining a fluorescence image of the tissue sample (SA) located in the reaction region.

Delivering the fluorescent material to the tissue sample (SA) by using the patch (PA), may be to deliver a fluorescent material for reading the shape of the cells constituting the tissue sample (SA). The patch PA may store fluorescent material for reading the morphology of cells constituting the tissue sample SA and deliver the fluorescent material to the sample SA or the reaction region.

The fluorescent material for reading the shape of the cells constituting the tissue sample (SA) may be an immunological fluorescent material. The fluorescent substance may include an antibody that specifically binds to a target protein by an antigen-antibody reaction. An antibody that specifically binds to the target protein may indicate a region in which the target protein is distributed. The region in which the target protein is distributed may be analyzed to perform a morphological diagnosis on the tissue sample (SA).

Delivering a fluorescent material to the tissue sample (SA) using the patch (PA), may be to deliver a fluorescent material for detecting a target protein from the tissue sample (SA). The fluorescent material may be a fluorescent material for labeling a target protein. The patch PA may store a fluorescent material for labeling the target protein and transfer the fluorescent material to the sample or the reaction region.

The fluorescent substance for labeling the target protein may be a fluorescent substance using an antigen-antibody reaction. The target protein may be an antigen associated with a particular disease. Delivering the fluorescent material may include delivering an antibody specifically bound to the antigen and attached to the enzyme and a substrate (SU) that is catalyzed by the enzyme to produce colored precipitates.

The fluorescent material for labeling the target protein may induce a color reaction in the region where the target protein is located. In this case, the tissue diagnosis according to the present embodiment may be performed by measuring the colorimetric according to the color reaction and obtaining the presence or absence of the target protein, distribution information of the target protein, and the like.

Delivering the fluorescent material to the tissue sample (SA) using the patch (PA), may be to deliver a fluorescent material for detecting DNA from the tissue sample (SA). The fluorescent material may be a fluorescent material for labeling DNA or a specific genetic sequence included in the tissue sample (SA). The patch PA stores a fluorescent material for labeling DNA (or a specific nucleotide sequence) included in the tissue sample (SA), and delivers the fluorescent material to the tissue sample (SA) or the reaction region. .

The fluorescent material may be a material for labeling DNA included in the tissue sample (SA). The fluorescent material may bind to DNA included in the tissue sample (SA) to facilitate identification of the distribution of DNA (ie, distribution of the nucleus) and the shape of the nucleus from the tissue sample (SA). The fluorescent material may be DAPI (4 ′, 6-diamidino-2-phenylindole).

The fluorescent substance for labeling the target base sequence may be for detecting the target base sequence by in situ hybridization. The fluorescent material for labeling the target sequence may be to detect the target base sequence using a nucleic acid probe (probe). Specifically, the fluorescent material for labeling the target base sequence may include a probe that binds specifically (or complementarily) to the target base sequence and generates a color precipitated substance. The target nucleotide sequence may be detected by using chromogenic in situ hybridization (FISH).

The delivering of the fluorescent material to the reaction region may be performed by contacting the patch PA storing the fluorescent material with the reaction area and separating the patch PA from the reaction area. According to the fluorescent labeling method according to the present application, a relatively small amount of sample may be consumed, as compared with a conventional method of performing fluorescent labeling by applying a large amount of fluorescent samples.

In this case, the fluorescent material is delivered, the patch (PA) is in contact with the reaction region, the fluorescent material can be moved to the reaction region, the fluorescent material is a label target material (TS) included in the reaction region ) In combination with In this case, when the patch PA is separated from the reaction region, the fluorescent substance which does not bind to the label target material TS among the fluorescent substances moved to the reaction region may be absorbed into the patch PA.

Specifically, the fluorescent material is transferred, the fluorescent material is able to move to the reaction region through the water film (WF) formed in the vicinity of the contact area by the patch (PA) in contact with the reaction region, the fluorescence The substance may be formed by binding to a target substance (TS) included in the reaction region. In this case, when the patch PA is separated from the reaction region, among the fluorescent materials that have moved to the reaction region through the water film WF, the fluorescent material that does not bind to the labeling material TS is added to the water film WF. It can be captured and absorbed into the patch PA.

In the conventional method of labeling the sample (SA) with fluorescence, a process of rinsing the sample (SA) by pouring a separate washing solution is necessary to remove the fluorescent material that does not bind to the labeling material (TS) from the sample (SA). Was required. In contrast, when the fluorescent material is delivered using the patch PA as in the present application, the fluorescent material that does not bind to the label target material TS may be separated from the sample by only separating the patch PA from the reaction region. Can be removed from (SA). Therefore, it is possible to label fluorescence on tissue specimens (SA) by an economical and convenient procedure compared to the conventional method.

Acquiring a fluorescence image of the tissue sample (SA) may be to obtain a fluorescently labeled image of the target material (TS) that is the basis of the tissue diagnosis. The fluorescence image may be an image in which some elements which are a standard for morphological analysis of cells constituting the tissue sample (SA) are fluorescently labeled. The fluorescent image may be an image in which a target protein included in the tissue sample (SA) is fluorescently labeled. The fluorescent image may be an image in which DNA or a target nucleotide sequence included in the tissue sample (SA) is fluorescently labeled.

Acquiring a fluorescent image of the tissue sample (SA) may be performed using a fluorescent microscope. Acquiring the fluorescence image is obtained by injecting light of a specific wavelength band into the reaction region or the tissue sample SA and detecting light of a specific wavelength band emitted from the reaction region or the tissue sample SA. It may be. In this case, a filter that passes only light of an appropriate wavelength band may be used. The detecting of the fluorescence may be performed by injecting light into the plate PL and measuring fluorescence emitted from the plate PL.

Acquiring a fluorescent image of the tissue sample SA may be performed by using an imaging module such as a CMOS image sensor or a CCD image sensor. Acquiring the fluorescence image may be obtained by obtaining one image including the entire area of the tissue sample (SA) or by acquiring unit images for each of the plurality of unit regions and collecting the unit images.

Measuring the fluorescence, in the case of measuring the fluorescence, preferably, the plate PL may be used that is opaque black or opaque white.

The tissue diagnosis according to the present embodiment may further include analyzing the obtained fluorescence image.

Analyzing the acquired image may be to perform a morphological analysis.

The determination of cancer cells may be applied similarly to that described above with respect to FIG. 42 in the embodiment of staining diagnosis. In other words, as shown in FIG. 42, the presence or absence of cancer cells or the distribution of cancer cells may be determined from the images of the tissue specimens (SA) by using characteristics that are contrasted with the cytoplasm, nucleus, chromatin, etc. of normal cells and cancer cells. Can be.

Measuring the amount of the target material TS may be performed by measuring the amount of fluorescence generated according to the amount of the target material TS. Or, the target material included in the tissue sample SA. Measuring the amount of (TS) can be performed using an electrochemical method. In other words, measuring the amount of the target material (TS), in the transfer of the dye or fluorescent material to the tissue sample (SA) or the reaction region by using the patch (PA), the tissue sample (SA) The amount of the material transferred from the patch PA to the reaction region may vary depending on the amount of the target material TS included in the target material TS. In this case, as the material is transferred from the patch PA to the reaction region, a change in electrical characteristics of the patch PA or the plate PL on which the reaction region is located may be measured.

However, measuring the amount of the target material TS included in the tissue sample SA is not necessarily performed independently from acquiring the fluorescence image of the sample SA, and diagnoses the sample SA. Acquiring an image and measuring an amount of the target material TS included in the sample SA may be performed in parallel.

4.2.3 Image acquisition by multiple targets

The tissue diagnosis method for detecting the plurality of target substances TS will now be described with reference to FIGS. 39 to 41.

39, a tissue diagnosis method for detecting a plurality of target substances TS as a tissue diagnosis method according to an embodiment of the present application may include placing a tissue sample SA in a reaction area (S20). And delivering the first fluorescent material to the tissue sample (S30) and delivering the second fluorescent material to the tissue sample (SA) (S40).

Positioning the tissue sample (SA) in the reaction region (S20), it may be carried out similarly to the above-described embodiments.

The step (S30) of delivering the first fluorescent material to the tissue sample (SA) is performed by using a patch (PA) for storing the first fluorescent labeling material for specifically labeling the first target material (TS). Can be.

The transferring of the second fluorescent substance to the tissue sample (S40) is performed by using a patch PA storing a second fluorescent labeling substance for specifically labeling the second target substance TS. Can be.

According to FIG. 40, the tissue diagnosis method for detecting the plurality of target substances TS according to the present embodiment further includes detecting the first target substance TS and the second target substance TS (S50). It may include. The detecting of the first target material TS and the second target material TS (S50) may be performed after delivering the second fluorescent labeling material to the tissue sample SA.

In this case, a wavelength band in which fluorescence emitted from the first fluorescent label material is detected and a wavelength band in which fluorescence emitted from the second fluorescent label material are detected may be different from each other, and the first target material TS and the second wavelength may be different from each other. The detecting of the target material TS (S50) may include detecting the first target material TS and the second target material TS included in the tissue sample SA (S50).

According to FIG. 41, in the tissue diagnosis method for detecting a plurality of target substances TS according to the present exemplary embodiment, placing a tissue sample SA in a reaction area (S20), and using the first fluorescent substance as a tissue sample ( SA (S30), detecting the first target material (TS) (S51), delivering the second fluorescent material to the tissue sample (S40) and the second target material (TS) It may include the step (S53).

Positioning the tissue sample (SA) in the reaction region (S20), delivering the first fluorescent material to the tissue sample (S30), and delivering the second fluorescent material to the tissue sample (SA) Step S40 may be performed similarly to the above-described embodiments.

Detecting a first target material (TS) (S51) is performed after the step of delivering the first fluorescent label material to the tissue sample (SA), by detecting the fluorescence emitted from the first fluorescent label material The first target material TS included in the tissue sample SA may be detected.

Detecting a second target material TS (S53) is performed after the step of delivering the second fluorescent label material to the tissue sample SA, and detecting fluorescence emitted from the second fluorescent label material. The second target substance TS included in the tissue sample SA may be detected.

In this case, the wavelength band where the fluorescence emitted from the first fluorescent label material is detected and the wavelength band where the fluorescence emitted from the second fluorescent label material is detected at least partially overlap each other, and the fluorescence emitted from the second fluorescent label material is overlapped. The detecting may include fluorescence detected from the tissue sample SA after delivering the second fluorescent labeling material to the tissue sample SA, and before delivering the second fluorescent labeling material to the tissue sample SA. It may be performed by comparing the fluorescence detected from the tissue specimen (SA).

Tissue diagnostics according to the present application can be used to detect a plurality of targets. The tissue diagnosis method for detecting the plurality of targets may be performed using a plurality of patches PA.

The target to be detected may mean a target substance (TS) that is the basis of tissue diagnosis. For example, the target may mean DNA, a specific nucleotide sequence, a specific protein, a cell component, or the like included in the tissue sample (SA). The tissue diagnosis may detect a plurality of targets through one process. The one process may mean using one plate PL. The one process may mean using one sample SA.

Tissue diagnostics in accordance with the present application may detect a plurality of targets from one bright field image acquisition process. In other words, according to the tissue diagnosis according to the present application, a plurality of targets can be detected from one bright field image. In this case, one image is an image obtained by photographing the entire tissue sample SA located on the plate PL, or by collecting a plurality of unit images captured by a plurality of unit regions included in the plate PL. It can mean an image.

The plurality of targets may be displayed in different colors on the bright field image. For example, the nucleus contained in the tissue sample (SA) may be represented by a blue line and the cytoplasm may be represented by a red line.

Tissue diagnosis according to the present application may detect a plurality of targets by one fluorescence image acquisition process. The plurality of targets may be detected from one fluorescence image. The plurality of targets may be detected from a plurality of fluorescent images obtained in one process. The plurality of targets may be labeled with fluorescence detected in a similar wavelength band.

The plurality of targets may be labeled with fluorescence detected in different wavelength bands. For example, the nucleus included in the tissue sample (SA) may be represented by fluorescence of a blue strain, and the microtubule may be displayed by fluorescence of a green strain.

In the present embodiment, the plurality of targets may be a plurality of target proteins. In other words, according to one embodiment of the present application, a plurality of target proteins may be detected by one fluorescence image acquisition process.

Hereinafter, as an example of tissue diagnosis for detecting a plurality of targets according to the present application, a tissue diagnosis for detecting a plurality of target proteins using an immunological method will be described.

As an example of tissue diagnosis according to the present application, a tissue diagnosis method for detecting a plurality of target proteins may include fixing a sample SA to a plate PL, and specifically, a plurality of target proteins to the plate PL. Delivering a plurality of types of fluorescent labeling material to bind, and detecting the plurality of target proteins. In the present embodiment, the fluorescent label material may mean an antibody to which the fluorescent label is attached. The fluorescent label may refer to an antibody to which an enzyme that reacts with a substrate (SU) to generate fluorescence is attached.

The fixing of the sample SA to the plate PL may be applied similarly to the above-described embodiments.

Delivering a plurality of types of fluorescent labeling material specifically binding to the plurality of target proteins to the plate PL, may be to deliver a first fluorescent labeling material and a second fluorescent labeling material. In other words, the plurality of target proteins include a first target protein and a second target protein, and the plurality of kinds of fluorescent labeling substances specifically bind to the first target protein and the first fluorescent labeling substance and the second target protein. It may include a second fluorescent labeling material that specifically binds to the protein. In this case, a wavelength band in which fluorescence emitted from the first fluorescent label material is detected and a wavelength band in which fluorescence emitted from the second fluorescent label material are detected may be different from each other.

The detecting of the plurality of targets may be performed by obtaining an image in which an area in which each target is distributed in the tissue sample SA is displayed. Alternatively, the detecting of the plurality of targets may include measuring an amount of the plurality of targets included in the tissue sample SA.

Detecting the plurality of target proteins may be to obtain a fluorescent image of the tissue sample (SA). Detecting the plurality of target proteins may be quantitative analysis of the plurality of target proteins.

The plurality of target protein detection methods described above may be performed using a plurality of patches PA. For example, the plurality of patches PA may include a first patch PA storing a first fluorescent label material and a second patch PA storing a second fluorescent label material.

Specifically, the target detection method using a plurality of patches (PA), the step of fixing the sample (SA) to the plate (PL), the first to store a first fluorescent labeling material that specifically reacts with the first target protein Delivering the first fluorescent labeling material to the plate PL using the patch PA, and storing the second fluorescent labeling material that specifically reacts with the second target protein. And transferring the second fluorescent labeling material to the plate PL. The wavelength band in which the fluorescence for labeling the first fluorescent label material is detected may be different from the wavelength band in which the fluorescence for labeling the second fluorescent label material is detected.

According to one embodiment, after the step of delivering the first fluorescent labeling material to the plate (PL) and before the step of delivering the second fluorescent labeling material to the plate (PL) included in the tissue sample (SA) And detecting the first target protein. The method may further include detecting the second target protein included in the tissue sample SA after delivering the second fluorescent labeling substance to the plate PL. In other words, the first target protein is detected when the first fluorescent label is delivered to the plate PL, and the second target protein is detected when the second fluorescent label is delivered to the plate PL. Can be.

According to another embodiment, after delivering the second fluorescent labeling material to the plate PL, detecting the first target protein and the second target protein included in the tissue sample SA. It may include. In other words, the first target protein and the second target protein may be detected after the first fluorescent labeling material and the second fluorescent labeling material are delivered to the plate PL.

When detecting a plurality of target proteins using a plurality of patches (PA) as in the present embodiment, the wavelength band at which fluorescence labeled on the first target protein is detected and labeled on the second target protein The wavelength bands in which fluorescence is detected may be similar to each other. In this case, when the first fluorescent labeling material is delivered to the plate PL, the first target protein is detected. When the second fluorescent labeling material is delivered to the plate PL, the second target protein is detected. The detecting of the second target protein may be performed by comparing the fluorescence obtained when detecting the first target protein with the fluorescence obtained for detecting the second target protein.

43 and 44 schematically illustrate a method of detecting a plurality of target substances TS as an example of a tissue diagnosis method according to the present application. 43 and 44, the tissue diagnosis method according to the present application may be used when the first target material TS1 and the second target material TS2 included in the tissue sample SA are to be detected. . A description with reference to FIG. 41 is as follows.

In the tissue diagnosis method of the present application, the sample SA is positioned in the reaction region (S20), the first fluorescent labeling substance is transferred to the tissue sample SA (S30), and the first target substance TS1 is detected ( S51) (FIG. 43). In addition, in the tissue diagnosis method of the present application, after detecting the first target material TS1 (S51), the second fluorescent label material is transferred to the tissue sample SA (S40), and the second target material TS2. ) Can be performed by detecting (S53) (FIG. 44). In the present embodiment, the wavelength band in which the first fluorescence emitted from the first target material TS fluorescently labeled by the first fluorescent label material is detected is the second target material fluorescently labeled by the second fluorescent label material. When the wavelength bands in which the second fluorescence emitted from the TS is detected overlap each other, it may be difficult to distinguish the fluorescence labeled on the first target material TS1 during the detection of the second target material TS2 (S53). . In this case, detecting the second target material TS may include fluorescence detected from the tissue sample SA after delivering the second fluorescent label material to the tissue sample SA, and the second fluorescent label material. The fluorescence detected from the tissue sample (SA) may be compared before delivery to the tissue sample (SA). For example, when the first target material TS1 is detected together when the second target material TS2 is detected, as shown in FIGS. 43 and 44, the fluorescent label detected before and after the second fluorescent label material is delivered to the plate PL. In comparison, the second target material TS2 may be detected. As described above, by detecting the first target material TS1 and the second target material TS2, respectively, the position where each target material TS is distributed in the tissue sample SA and the amount contained in the tissue sample SA. Can be obtained.

45 to 47 schematically illustrate a method of detecting a plurality of target substances TS as another example of a tissue diagnosis method according to the present application. 45 to 47, the tissue diagnosis method according to the present application may be used when the third target material TS3 and the fourth target material TS4 included in the tissue sample SA are to be detected. A description with reference to FIG. 41 is as follows.

In the tissue diagnosis method of the present application, the sample SA is positioned in the reaction region (S20), the first fluorescent label material FL1 is transferred to the tissue sample SA (S30), and the third target substance (TS3). It can be performed by detecting (S51) (FIG. 45). In addition, in the tissue diagnosis method of the present application, after detecting the third target material TS3 (S51), the second fluorescent label material FL2 is transferred to the tissue sample SA (S40), and the fourth target material is detected. It may be performed by detecting the material TS4 (S53) (FIG. 46). In the present exemplary embodiment, the wavelength band in which the first fluorescence emitted from the third target material TS3 fluorescently labeled by the first fluorescent label material FL1 is detected is fluorescent by the second fluorescent label material FL2. When the wavelength bands in which the second fluorescence emitted from the labeled fourth target material TS4 is detected overlap each other, upon detection of the fourth target material TS4 (S53), the fluorescence labeled on the third target material TS3 is applied. Identification may be difficult. In this case, detecting the fourth target material TS4 includes fluorescence detected from the tissue sample SA after delivering the second fluorescent label material FL2 to the tissue sample SA, and the second fluorescence. It may be performed by comparing the fluorescence detected from the tissue sample (SA) before delivering the labeling material (FL2) to the tissue sample (SA). For example, when the third target material TS3 is detected together when the fourth target material TS4 is detected as illustrated in FIGS. 45 and 46, the second target material TS3 is detected before and after the second fluorescent labeling material FL2 is delivered to the plate PL. By comparing the fluorescent labels, the fourth target material TS4 can be detected (FIG. 47). By detecting the third target material TS3 and the second target material TS4 as described above, the area in which each target material TS is distributed in the tissue sample SA and the amount contained in the tissue sample SA Can be obtained.

Meanwhile, the tissue diagnosis method for detecting the plurality of target substances TS may not be applicable only when the fluorescent label is used as in the above-described embodiments. The tissue diagnosis method for detecting the plurality of target substances TS may be widely applied when the identification labels for specifically identifying different target substances TS are the same kind of labels. In other words, in various cases where the first label that specifically reacts with the first target material TS and the second label that specifically reacts with the second target material TS generate similar signals, A method of detecting the plurality of target materials TS may be applied.

4.3 Patches Used to Diagnose Tissue

Hereinafter, an embodiment of a patch PA that can be used in the immunodiagnosis according to the present embodiment will be described. Each patch PA is described as having several components, and each component can be understood as the base material or additive material described above. However, components described as being able to be stored in each patch PA are not all components stored in each patch PA, and each patch PA may be stored together with additional components not specified.

According to the exemplary embodiment of the present application, the patch PA may include a labeling material that binds to and labeles the target material TS included in the tissue sample SA and a net structure that forms a microcavity in which the labeling material is stored. And a net structure in contact with the tissue sample SA to deliver the labeling substance to a reaction region in which the target material TS is located. The labeling material may be a fluorescent labeling material or a color labeling material (eg, a dyeing material).

When performing a tissue diagnosis using the patch, a large amount of reagent was applied to the tissue sample in order to stain the tissue or to label a part of the tissue in existing tissue test methods. It can be carried out simply by separating and separating, which leads to savings of reagents.

As described above, when the reagent is delivered using the patch, not only economic diagnosis can be performed as described above, but reagents that do not bind to the target material can be easily removed from the tissue, thereby significantly improving the accuracy of the diagnosis. In addition, an effect of preventing cross-contamination may also be expected by using a method of distinguishing and applying patches at each diagnosis. In addition, the patch is easier to store than the liquid sample, so that the sample can be more easily prevented from being exposed to harmful substances.

4.3.1 Dye Patch (H & E Patch)

Herein, a description will be given of a staining patch (PA) that stains portions of the tissue sample (SA) in various colors and intensities to facilitate observation. The patch can store staining material and deliver it to the tissue sample. The dyeing material may be a color labeling material.

The dyeing material stored in the dye patch PA may be an additive material stored in the patch PA. The patch PA may store a solution containing the dyeing material. In addition, the patch PA may store a separate base material or an additive material to allow the dyeing material to easily bind to the object to be dye together with the dyeing material.

The patch PA according to the present application may store an acidic or basic dyeing material. The acidic or basic dyeing material may be combined with the portions of the ionized state present in the tissue sample (SA) to have a color.

For example, the patch (PA) according to the present application may be used in a method of staining the tissue specimen (SA) using hematoxylin and eosin. Tissue staining with hematoxylin and eosin is one of the widely used staining methods for observing tissue. For example, in order to diagnose cancer, tissue sections prepared through pretreatment may be stained using hematoxylin and eosin, and morphology may be observed to determine whether cancer has developed.

Patch (PA) according to an embodiment of the present application may store a dyeing material for staining the nucleus contained in the tissue specimen (SA). The patch (PA) may store hematoxylin and deliver it to the tissue sample (SA). Hematoxylin is a basic substance that binds to basophilic (i.e. acidic to anionic) substances and stains them with a blue line. have. However, the present invention is not limited thereto, and the patch PA for staining the nucleus according to the present embodiment may store methylene blue, toluidine blue, and the like, and deliver the methane blue, toluidine blue, and the like to the specimen SA.

Patch (PA) according to another embodiment may store a staining material for staining the cytoplasm contained in the tissue sample (SA). The patch PA may store and deliver the eosin to the tissue sample. The eosin can bind to an acidophilic (ie, basic to cationic) material and stain with a red line. Therefore, the eosin can stain red or pink basic protein, muscle cells and the like. In particular, most of the cytoplasm is basic and eosin affinity. However, the patch for dyeing the cytoplasm (PA) may store acid fuchsin, orange G, etc. instead of eosin.

Patch PA according to another embodiment may store a neutral dyeing material. For example, the patch PA may store a dyeing material having both a + part and a − part. At this time, the + and the-portion of the tissue sample (SA) may be dyed to have a different color.

4.3.2 Antibody Patches

Here, the antibody patch (PA) used for the diagnosis of immunological tissue is described.

The antibody may be an additive substance stored in the patch PA. The patch PA may store a solution containing the antibody. In addition, the patch (PA) may store a separate base material or additive material to facilitate the specific binding of the antibody with the antibody.

Meanwhile, in the present application, the antibody used for diagnosing immunological tissue is 1) an antibody having specific binding to a target protein and having an identification label attached thereto, 2) a primary antibody having specific binding to a target protein, and 1 It may be a secondary antibody with specific binding to the secondary antibody and having an identifying label attached thereto.

4.3.2.1 Immunstaining Patches

The patch (PA) according to the present application can store an immunological staining material that facilitates the observation of portions of the tissue sample (SA) via an antigen-antibody reaction. The patch PA may store and deliver the immunological staining material to the reaction region or the tissue sample (SA). Tissue diagnosis according to the present application may include obtaining an image labeled with the target protein from the tissue sample (SA) using the immunological staining patch (PA).

The immunological staining material may include an antibody that specifically binds to a target protein by an antigen-antibody reaction. An antibody that specifically binds to the target protein may indicate a region in which the target protein is distributed. The antibody may be a color labeling substance. The antibody may be attached with an enzyme. The antibody to which the enzyme is attached may catalyze the chemical reaction of the substrate (SU). The product (PD) produced by the chemical reaction may color label the target protein.

The target protein may be an antigen associated with a particular disease, and the delivery of the staining material specifically binds to the antigen and the enzyme is attached and a substrate catalyzed by the enzyme to produce colored precipitates. (SU) may be included. The immunostaining substance may induce a color reaction in the region where the target protein is located. In other words, the patch (PA) for storing the immunostaining material may be dyed by generating colored precipitates or inducing a color reaction in the region where the target protein is located.

4.3.2.2 Immunofluorescence Patches / Immunochemical Fluorescence Patches

The patch (PA) according to the present application may store a fluorescent labeling material capable of fluorescence detection of a target protein through an antigen-antibody reaction, and deliver it to the tissue sample (SA). The tissue diagnosis according to the present application may include obtaining an image in which the target protein is fluorescently labeled from the tissue sample (SA) by using a patch (PA) for storing the fluorescent label material. Alternatively, the method may include measuring the amount of fluorescence labeled with the target protein from the tissue sample (SA).

The fluorescent label material may include an antibody to which a fluorescent label is attached as an antibody that specifically binds to the target protein. The antibody labeled with the fluorescent label may specifically bind to a target protein to be detected. The fluorescent label material may include an antibody to which an enzyme that emits fluorescence through a reaction with a substrate (SU) as an antibody that specifically binds to the target protein.

In this embodiment, for the fluorescence emission, a substrate patch for storing a substrate (SU) that forms fluorescence by a chemical reaction catalyzed by an enzyme attached to the separate antibody may be separately provided.

4.3.3 Integral Hybridization (ISH) Patch

Here, an in situ hybridization patch (PA) including a probe that specifically binds to a target nucleotide sequence and used for detection of the target nucleotide sequence will be described. Tissue diagnosis according to the present application may include obtaining an image labeled with the distribution of the target sequence from the tissue sample (SA) using the in situ hybridization patch (PA).

The probe may be an additive material stored in the patch PA. The patch PA may store a solution including the probe. In addition, the patch PA may store a separate base material or an additional material to facilitate the specific binding of the probe together with the probe.

4.3.3.1 FISH Patch

The patch (PA) according to the present application may store a fluorescent labeling material for labeling a target nucleotide sequence, and may be delivered to the tissue sample (SA). Tissue diagnosis according to the present application includes obtaining an image in which the target nucleotide sequence is fluorescently labeled from the tissue sample (SA) by using a patch (PA) that stores a fluorescent labeling substance for labeling the target nucleotide sequence. can do. Alternatively, the method may include measuring the amount of fluorescence labeled on the target nucleotide sequence from the tissue sample (SA).

The fluorescent label according to the present embodiment may include a probe that specifically binds to the target nucleotide sequence. The fluorescent label material may include a probe to which a fluorescent label is attached as a probe that specifically binds to the target base sequence. The fluorescent labeling substance may include a probe to which an enzyme that reacts with a substrate (SU) to emit fluorescence as a probe specifically binding to the target nucleotide sequence.

At this time, in the present embodiment, for the fluorescence emission, the substrate (SU) patch (PA) for storing the substrate (SU) to form fluorescence by a chemical reaction catalyzed by an enzyme attached to the separate probe is It may be provided separately.

4.3.3.2 CISH Patch

The patch (PA) according to the present application may store a staining material for labeling a target nucleotide sequence and deliver the stained material to the tissue sample (SA). Tissue diagnosis according to the present application may include obtaining an image labeled with the target nucleotide sequence from the tissue sample (SA) by using a patch (PA) that stores a staining material for labeling the target nucleotide sequence. have.

The dyeing material according to the present embodiment may include a probe specifically binding to the target nucleotide sequence. The dyeing material may include a probe to which a coloring material is attached as a probe specifically binding to the target base sequence.

4.3.4 DAPI Staining Patches

The patch (PA) according to the present application may store the fluorescent labeling material for labeling DNA and deliver it to the tissue sample (SA). Tissue diagnosis according to the present application may include obtaining a form and distribution of DNA included in the tissue sample (SA) by using a patch (PA) for storing the fluorescent labeling material for labeling the DNA.

The fluorescent label material according to the present embodiment may include a DAPI reagent penetrating the DNA. The patch PA may deliver a fluorescent label including the DAPI to the tissue sample, and the distribution of DNA contained in the tissue sample SA to which the DAPI is delivered may be detected by detecting blue fluorescence. Can be obtained. Therefore, the distribution or shape of the nucleus contained in the tissue sample SA may be obtained by detecting blue fluorescence.

On the other hand, identification of the nucleus by DAPI may be used alone in the observation of tissue specimens (SA), or may be used in conjunction with other techniques. For example, if you want to observe the endothelial tissue, in addition to the patch (PA) for storing the DAPI, TRITC (isothiocyanate derivative) for labeling the fine fibers in red fluorescence or FITC (fluorescein isothiocyanate) for fluorescent labeling the microtubules in green Using a separate patch (PA) for storing the back, it can be observed by multiple labeling the parts included in the tissue specimen (SA).

The DAPI may be an additive material stored in the patch PA. In addition to the DAPI, the patch PA may store a separate base material or an additive material to facilitate penetration of the DAPI into DNA.

As the DAPI reagent is stored in a patch according to the present application and delivered to the tissue, only an appropriate amount of reagent required for staining of the nucleus is transferred to the reaction zone, and the remaining DAPI not bound to the nucleus separates the patch from the tissue. It can be absorbed back into the patch alone. This may enable easier and faster fluorescence treatment.

4.3.5 Buffer Patch

The patch PA of the present application may store a substance that facilitates performing the tissue diagnosis and contact the reaction space to provide a predetermined environment in the reaction space or the tissue sample SA.

The patch PA according to an embodiment of the present application stores an environment in which a buffer solution for binding the dyeing material to the dyeing target material TS well and stores the binding solution easily in the reaction region. Can provide.

For example, according to one embodiment of the present application, the patch (PA) stores a buffer solution of pH 7.0, in the reaction zone, the environment suitable for binding the DNA contained in the sample (SA) with the DAPI sample Can be provided. Providing an environment in the reaction zone may be performed by the patch PA contacting the reaction zone. Since the DAPI sample has a light sensitive property, the patch PA may have a light blocking function.

4.3.6 Washing Patch

Tissue diagnostics in accordance with the present application can be performed using a wash patch (PA) that absorbs residues. In other words, the tissue diagnosis method according to the present embodiment may include absorbing the residue by contacting and separating the washing patch. The residue may comprise a fluorescent label (eg, an antibody) that is not bound to the target protein.

The wash patch may store a wash solution. The washing solution may include TBS and PBS to which tween-20 is partially added. The washing solution may be provided as a solution in which the residue may be dissolved, depending on the residue to be absorbed.

According to this embodiment, it is possible to easily remove the excess material non-specifically located on the plate PL by using the wash patch. Accordingly, the diagnosis can be performed economically as compared to the conventional method in which a process of washing the excess material by spraying a large amount of the washing solution onto the plate PL before and after application of each reagent used for detecting a specific reaction was required. And more accurate detection results can be derived.

In addition to the wash solution, the wash patch may store a separate base material or an additive material to increase washing efficiency.

59 to 61 briefly illustrate the removal of residue from the reaction zone using the washing patch PA as an embodiment of a tissue diagnosis method according to the present application. Here, the residue may mean a material that does not participate in the reaction for detecting the target material TS. The residue may be a surplus substance (eg, a surplus labeling substance) that does not participate in a specific reaction for detection of the target substance (TS).

59 to 61, the washing patch PA may absorb residue from the plate PL. According to the present exemplary embodiment, the residue may be removed from the reaction zone by contacting and separating the washing patch PA from the tissue sample SA. When the washing patch PA contacts the tissue sample SA, the water film WF may be formed near the contact area, and the residue may be dissolved in the water film WF. When the washing patch (PA) is separated from the tissue sample (SA), the meninges (WF) come with the patch (PA), and the residue antibody (AB2) is captured in the meninges (WF) and the patch (PA) can be absorbed. In this case, the antibody (AB1) bound to the target protein (TP) may not be absorbed by the patch.

However, in the present embodiment, but the antibody does not bind to the target protein as an example of the residue, but is not limited thereto. The residue may include a probe that does not bind to the target nucleotide sequence, a dye that does not bind to the target material (TS), and the like.

As described above, by washing the reaction area using the wash patch, the washing process used in the conventional tissue diagnosis can be replaced. Conventionally, in order to perform the washing, it was necessary to apply a large amount of the washing solution to the sample to wash the residue, and a large amount of the washing solution was consumed in the process. If washing of tissue is performed using the washing patch according to the present application instead of the conventional manner described above, the washing solution can be saved significantly.

4.3.7 Multiple Patches

Tissue diagnosis according to the present application can be performed using a plurality of patches (PA).

Tissue diagnostics using the plurality of patches can be used to detect a plurality of target substances. For example, when detecting a plurality of target proteins, it may be performed using a plurality of patches (PA).

The plurality of target proteins may include a first target substance (TS) and a second target substance (TS), and the plurality of patches PA may include a first patch PA and a second label that store a first labeling substance. It may include a second patch (PA) for storing the material. In this case, the first labeling substance may specifically bind to the first target substance TS and provide an identification label. The second labeling substance may specifically bind to the second target substance TS and provide an identification label. In this case, the identification label provided from the first label material and the identification label provided from the second label material may be different from each other.

For example, the plurality of target proteins may include a first target protein and a second target protein, and the plurality of patches PA may include a first patch PA and a second fluorescent label material for storing a first fluorescent label material. It may include a second patch (PA) for storing the. In this case, the first fluorescent label may specifically bind to the first target protein and emit fluorescence. The second fluorescent label may specifically bind to the second target protein and emit fluorescence. The fluorescence emitted from the first fluorescent label material and the fluorescence emitted from the second fluorescent label material may have different wavelength bands detected. The fluorescence emitted from the first fluorescent label and the fluorescence emitted from the second fluorescent label may have a similar wavelength band to each other.

As described above, by using a plurality of patches, a plurality of target substances can be detected simultaneously. Here, the simultaneous detection means that not only can be detected at the same time, but also that a plurality of target substances can be detected in one diagnostic process. In this case, the plurality of target substances simultaneously detected by using the plurality of patches may be mixed with proteins, nucleotide sequences, the configuration of the cells and the like. In addition, the manner in which the plurality of target substances are detected may be mixed with fluorescence detection, colorimetric detection, radiation detection, and the like.

4.4 Tissue Culture

Using a patch (PA) according to the present application, tissue specimens (SA) can be cultured. In particular, by culturing the tissue specimen (SA), it can be used to determine whether it is a malignant tumor. Specifically, the growth of the cells can be observed to determine the nature of the tumor.

Cultivating the tissue sample (SA) using the patch (PA) according to the present application, positioning the sample (SA) on the plate (PL), culturing the tissue sample (SA) on the sample (SA) Contacting the culture patch containing a nutritional substance for, may be performed by obtaining an image of the tissue specimen (SA). In this case, the specimen SA positioned on the plate PL may use a living body.

The culture patch for culturing the tissue sample (SA) may include a material required for growth of the tissue. For example, the culture patch may include some of a carbon source, an energy source, a nitrogen source, an inorganic salt, a vitamin, a trace element, a growth factor, a buffer, or a serum necessary for the tissue to grow.

Acquiring an image of the tissue sample SA may be applied similarly to acquiring an image of the reaction region, the plate PL, or the tissue sample SA in the above-described embodiments.

The acquired image, that is, the image of the cultured tissue sample (SA), may be used for morphological diagnosis. For example, the morphological characteristics of the cancer cells may be detected to determine whether the cancer cells are included in the tissue sample (SA). In this case, the cultured tissue sample (SA) may be stained to facilitate identification of the parts constituting the tissue sample (SA).

4.5 Tissue Diagnostic Device

According to FIG. 62, the tissue diagnosis apparatus 10 according to the present application may include a control unit 100, a plate support unit 200, a patch control unit 300, and a target substance detection unit 400. The tissue diagnosis apparatus 10 may include a net structure forming microcavities and may use a patch PA provided to store a substance in the microcavities, and may detect the target material TS from the tissue sample SA. Can be performed.

The control unit 100 may include a net structure forming microcavities and may perform tissue diagnosis by detecting a target substance from a tissue sample by using a patch provided to store a substance in the microcavities.

The controller 100 may place a tissue sample in the reaction region. The controller may deliver the fluorescent labeling material to the tissue sample by using a patch that stores a fluorescent labeling material for specifically labeling a target material. The controller 100 may detect a target material that is fluorescently labeled from the tissue sample. The controller 100 may transfer the dyeing material to the tissue sample by using a patch that stores a color labeling material for giving a color to the target material. The controller 100 may detect a target substance to which color is applied.

The plate support part 200 may support a plate in which a reaction region is located and the tissue sample SA is located in the reaction region.

The patch control unit 300 supports a patch PA for storing a labeling substance specifically labeled on the target material TS, and the patch PA contacts the reaction zone to contact the reaction zone. The relative position of the patch PA relative to the reaction region can be controlled to deliver the labeling substance.

The target substance detection unit 400 may detect the labeling substance and detect the target substance TS included in the tissue sample SA.

Referring to FIG. 63, in the tissue diagnosis apparatus 10 according to the present application, the target substance (TS) detection unit 400 may include an imaging module 410 and a measurement module 430.

The imaging module 410 may capture an image of the reaction region in which the tissue sample SA is located. The measurement module 430 may measure the amount of the target substance TS included in the tissue sample SA.

The above description is merely illustrative of the technical idea of the present invention, and those skilled in the art to which the present invention pertains may make various modifications and changes without departing from the essential characteristics of the present invention. Therefore, the embodiments of the present invention described above may be implemented separately or in combination with each other.

Therefore, the embodiments disclosed in the present invention are not intended to limit the technical idea of the present invention but to describe the present invention, and the scope of the technical idea of the present invention is not limited by these embodiments. The protection scope of the present invention should be interpreted by the following claims, and all technical ideas within the equivalent scope should be interpreted as being included in the scope of the present invention.

Claims

In the tissue diagnostic method for detecting a target material from a tissue sample by using a patch comprising a net structure for forming the fine cavities, the patch provided to store the material in the fine cavities

Placing a tissue sample in the reaction zone;

Delivering the fluorescent label to the tissue sample using a patch that stores a fluorescent label for specifically labeling the subject matter; And

Detecting a fluorescently labeled object from the tissue sample;

Containing

Tissue diagnostic method.
The method of claim 1,

The fluorescent label material is

A fluorescent label complex comprising a reactive derivative that specifically reacts with the target material and a fluorescent label for detecting the target material,

Tissue diagnostic method.
The method of claim 1,

Detecting the fluorescently labeled target material is performed by obtaining a fluorescent image of the tissue sample,

Tissue diagnostic method.
The method of claim 1,

The target material is a target nucleotide sequence included in the tissue sample,

The fluorescent label material includes a fluorescently labeled nucleic acid probe, wherein the nucleic acid probe binds complementarily to the target nucleotide sequence,

Tissue diagnostic method.
The method of claim 1,

The target substance is a target protein included in the tissue sample,

The fluorescent labeling material includes a fluorescently labeled antibody, wherein the antibody specifically binds to the target protein.

Tissue diagnostic method.
The method of claim 1,

Delivering the fluorescent label material to the tissue sample,

Contacting the tissue sample with a patch that stores the fluorescent label material;

When the patch is in contact with the tissue sample, the fluorescent label material is movable to the reaction region,

Tissue diagnostic method.
The method of claim 6,

Delivering the fluorescent label material to the tissue sample,

Separating the patch storing the fluorescent labeling material from the tissue sample;

When the patch is separated from the tissue sample, the excess fluorescent labeling material which does not bind to the target material among the fluorescent labeling material is removed from the reaction region.

Tissue diagnostic method.
The method of claim 1,

Detecting the fluorescently labeled target material,

Performed by measuring the amount of fluorescence emitted from the target material included in the tissue sample,

Tissue diagnostic method.
The method of claim 1,

Detecting the fluorescently labeled target material,

Obtaining distribution information in the tissue sample of the target substance,

Tissue diagnostic method.
In the tissue diagnostic method for detecting a target material from a tissue sample by using a patch comprising a net structure for forming the fine cavities, the patch provided to store the material in the fine cavities

Placing a tissue sample in the reaction zone;

Delivering the color labeling material to the tissue sample using a patch that stores a color labeling material for imparting color to the subject material; And

Detecting the target substance to which the color is applied;

Tissue diagnostic method.
The method of claim 10,

The color labeling substance is

Is a color labeling complex comprising a reaction derivative that specifically reacts with the target material and a color label for detecting the target material,

Tissue diagnostic method.
The method of claim 10,

Detecting the target substance to which the color is given is performed by acquiring an image of the tissue sample.

Tissue diagnostic method.
The method of claim 10,

The target material is a target nucleotide sequence included in the tissue sample,

The color labeling substance includes a nucleic acid probe that complementarily binds to the target base sequence,

Tissue diagnostic method.
The method of claim 10,

The target substance is a target protein included in the tissue sample,

The color labeling substance includes an antibody to which a label that induces a color label is attached, wherein the antibody specifically binds to the target protein.

Tissue diagnostic method.
The method of claim 10,

Delivering the color labeling material to the tissue sample,

Contacting the tissue sample with a patch that stores the color labeling substance,

When the patch is in contact with the tissue sample, the color labeling substance is movable to the reaction zone,

Tissue diagnostic method.
The method of claim 15,

Separating the patch storing the color labeling substance from the tissue sample;

When the patch is separated from the tissue sample, the excess color labeling material that does not react with the target material among the color labeling materials is removed from the reaction zone.

Tissue diagnostic method.
The method of claim 10,

Detecting the color labeled target substance includes acquiring an amount labeled with the color in the tissue sample.

Tissue diagnostic method.
The method of claim 10,

Detecting the color-labeled target substance includes acquiring a distribution of the region labeled with the color in the tissue sample.

Tissue diagnostic method.
In the tissue diagnostic method for detecting a target material from a tissue sample by using a patch comprising a net structure for forming the fine cavities, the patch provided to store the material in the fine cavities

Placing a tissue sample in the reaction zone;

Delivering the first fluorescent labeling material to the tissue sample using a patch that stores a first fluorescent labeling material for specifically labeling a first target material; And

Delivering the second fluorescent labeling material to the tissue sample using a patch that stores a second fluorescent labeling material for specifically labeling a second target material;

Containing

Tissue diagnostic method.
The method of claim 19,

A wavelength band at which fluorescence emitted from the first fluorescent label material is detected and a wavelength band at which fluorescence emitted from the second fluorescent label material are detected are different from each other,

Detecting the first target substance and the second target substance included in the tissue sample after the step of delivering the second fluorescent labeling substance to the tissue sample; Further comprising,

Tissue diagnostic method.
The method of claim 19,

After the step of delivering the first fluorescent labeling material to the tissue sample, detecting the first target material included in the tissue sample by detecting fluorescence emitted from the first fluorescent labeling material; More,

Detecting the second target material included in the tissue sample by detecting fluorescence emitted from the second fluorescent label material after delivering the second fluorescent label material to the tissue sample; Further comprising,

Tissue diagnostic method.
The method of claim 21,

A wavelength band at which fluorescence emitted from the first fluorescent label material is detected and a wavelength band at which fluorescence emitted from the second fluorescent label material are detected at least partially overlap each other,

Detecting fluorescence emitted from the second fluorescent labeling material includes fluorescence detected from the tissue sample after delivering the second fluorescent labeling material to the tissue sample, and delivering the second fluorescent labeling material to the tissue sample. Comparing the fluorescence detected from the tissue sample before,

Tissue diagnostic method.
A labeling substance that binds to and labels the target substance included in the tissue sample;

And a net structure that has a net structure for forming a microcavity in which the labeling substance is stored, and which delivers the labeling substance to a reaction region in which the target substance is located in contact with the tissue sample.

Substance logo patch
The method of claim 23, wherein

The labeling substance is a fluorescent labeling substance

Substance label patch.
The method of claim 24,

The fluorescent label material comprises a fluorescently labeled antibody,

The target substance is a target protein included in the tissue sample,

Substance label patch.
The method of claim 24,

The fluorescent label material comprises a fluorescently labeled nucleic acid probe,

The target material is a target nucleotide sequence included in the tissue sample,

Substance label patch.
The method of claim 23, wherein

The target material is DNA contained in the tissue sample,

Substance logo patch
The method of claim 23, wherein

The labeling substance is a color labeling substance,

Substance label patch.
The method of claim 28,

The color labeling substance includes an antibody to which an enzyme is attached, and the target substance is a target protein included in the sample.

Substance label patch.
The method of claim 28,

The color labeling substance includes hematoxylin, and the target substance is a nucleus contained in the sample.

Substance label patch.
In the tissue diagnostic apparatus for detecting a target material from a tissue sample using a patch comprising a net structure for forming the fine cavities, the patch provided to store the material in the fine cavities,

A plate support part on which a reaction region is located, and which supports a plate on which the tissue sample is located;

Support a patch for storing a labeling substance that specifically labels the subject material, and control the relative position of the patch relative to the reaction region such that the patch contacts the reaction region to deliver the labeling substance to the reaction region A patch control unit; And

And a target substance detection unit detecting the labeling substance and detecting the target substance included in the tissue sample.

Tissue diagnostic device.
The method of claim 31, wherein

The target substance detection unit,

And an imaging module configured to capture an image of the reaction region in which the tissue sample is located.

Tissue diagnostic device.
The method of claim 31, wherein

The target substance detection unit,

It includes a measurement module for measuring the amount of the target material contained in the tissue sample;

Tissue diagnostic device.