WO2017146502A1 - Timbre de réaction en chaîne par polymérase, et procédé et appareil de diagnostic l'utilisant - Google Patents

Timbre de réaction en chaîne par polymérase, et procédé et appareil de diagnostic l'utilisant Download PDF

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Publication number
WO2017146502A1
WO2017146502A1 PCT/KR2017/002026 KR2017002026W WO2017146502A1 WO 2017146502 A1 WO2017146502 A1 WO 2017146502A1 KR 2017002026 W KR2017002026 W KR 2017002026W WO 2017146502 A1 WO2017146502 A1 WO 2017146502A1
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WO
WIPO (PCT)
Prior art keywords
patch
plate
sample
temperature
reagent
Prior art date
Application number
PCT/KR2017/002026
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English (en)
Korean (ko)
Inventor
이동영
임찬양
김경환
Original Assignee
노을 주식회사
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from KR1020160069936A external-priority patent/KR20170099737A/ko
Application filed by 노을 주식회사 filed Critical 노을 주식회사
Priority to US16/079,360 priority Critical patent/US11808677B2/en
Priority to CN201780025053.0A priority patent/CN109073627B/zh
Priority to EP17756840.9A priority patent/EP3421991A4/fr
Priority claimed from KR1020170024387A external-priority patent/KR102045068B1/ko
Publication of WO2017146502A1 publication Critical patent/WO2017146502A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G01N1/31—Apparatus therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/49—Blood
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/60—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances involving radioactive labelled substances

Definitions

  • the present application relates to a polymerase chain reaction patch, a diagnostic method and apparatus using the same, and more particularly, a patch for amplifying a target gene included in a sample by contacting a sample such as blood, and a polymerase chain reaction using the same.
  • a diagnostic method and apparatus for performing the same relates to a polymerase chain reaction patch, a diagnostic method and apparatus using the same, and more particularly, a patch for amplifying a target gene included in a sample by contacting a sample such as blood, and a polymerase chain reaction using the same.
  • a polymerase chain reaction is a method of amplifying a specific target genetic material to be detected, and is a test method for a more accurate diagnosis by amplifying a small amount of genetic material having the same base sequence.
  • the PCR test is not only used to diagnose genetic diseases by amplifying human DNA, but also applied to DNA of bacteria, viruses, and fungi, and may be used to diagnose infectious diseases.
  • the failure of the initial response can be a national problem.
  • the MERS virus started as an early infected person, resulting in more than 100 confirmed patients and about 30 deaths. Therefore, it is essential that the diagnosis of the subject is promptly performed and accurate diagnosis is made in order to prevent the increase of the infected person by the method of self-isolation of the infected person.
  • the conventional PCR diagnostic method was performed by inserting a sample into a tube for PCR test, mixing with a reagent used for PCR test, and adjusting the temperature of the sample mixed with the reagent. Accordingly, the reagent must be metered in the process of mixing the reagent with the sample, and there is a problem in that a lot of time is required to control the temperature of the sample mixed with the reagent.
  • 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 reagent used for the polymerase chain reaction.
  • One object of the present invention is to provide a polymerase chain reaction method using a patch.
  • a PCR patch provided on a mesh-like gel forming a micro-cavity
  • at least some of the reagents used for the polymerase chain reaction may be added to the microcavity.
  • the reagent stored in the microcavity moves to at least a portion of the outer region, and the target DNA contained in the sample located in the outer region.
  • PCR polymerase chain reaction of the polymerase may be provided.
  • a PCR patch set including a plurality of the patches used for the progress of the polymerase chain reaction of the patches provided on the gel of the network structure forming a micro-cavity
  • a first patch in which at least a first reagent of a plurality of reagents used in the polymerase chain reaction is stored in the microcavity;
  • a second patch in which at least a second reagent of the plurality of reagents used in the polymerase chain reaction is stored in the microcavity, wherein the first reagent is a reagent different from the second reagent.
  • the polymerase chain Providing a reagent stored in the first patch to a sample provided on the plate, using a first patch storing at least some of the plurality of reagents used in the reaction in the microcavity; And controlling the temperature of the sample to cause the polymerase chain reaction; PCR methods comprising a can be provided.
  • a target DNA included in a sample is provided by using a patch provided on a gel of a network structure forming a micro-cavity and storing a reagent used for a polymerase chain reaction.
  • a diagnostic apparatus for performing the polymerase chain reaction of a target DNA comprising: a relative movement control unit for relatively moving a region provided with the sample and the patch to provide a reagent stored in the patch to the sample; A temperature controller for controlling the temperature of the sample to a temperature such that the polymerase chain reaction can be induced; And an image acquisition unit for acquiring an image of the sample to detect a target DNA included in the sample.
  • reaction zone of a substance it is possible to provide a reaction zone of a substance or to provide a predetermined environment in a target zone.
  • the PCR test can be performed more simply, and the diagnostic result can be obtained quickly.
  • the delivery and absorption of the substance is properly controlled by using the patch, so that the amount of the solution for diagnosis can be significantly reduced.
  • amplification of a plurality of target DNAs can be simultaneously performed and detected.
  • FIG. 1 illustrates in detail an example of a patch according to the present application.
  • FIG. 2 shows an example of a patch according to the present application in detail.
  • FIG 3 illustrates providing a reaction space as an example of the function of a patch according to the present application.
  • FIG. 4 illustrates providing a reaction space as an example of the function of a patch according to the present application.
  • FIG. 5 illustrates the delivery of a substance as an example of the function of a patch according to the present application.
  • FIG. 6 illustrates the delivery of a substance as an example of the function of a patch according to the present application.
  • FIG. 7 illustrates the delivery of a substance as an example of the function of a patch according to the present application.
  • FIG. 8 illustrates the delivery of a substance as an example of the function of a patch according to the present application.
  • FIG 9 illustrates the delivery of a substance as an example of the function of a patch according to the present application.
  • FIG. 10 illustrates the delivery of a substance as an example of the function of a patch according to the present application.
  • FIG. 11 illustrates the delivery of a substance as an example of the function of a patch according to the present application.
  • FIG. 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.
  • FIG. 14 illustrates absorbing material as an example of the function of a patch according to the present application.
  • FIG. 16 illustrates absorbing material as an example of the function of a patch according to the present application.
  • FIG 17 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.
  • FIG. 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.
  • FIG. 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.
  • FIG. 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.
  • FIG. 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 graph for explaining a PCR process according to the present application.
  • 36 is a diagram for explaining provision of a target sample according to the present application.
  • 37 is a view for explaining contact between the patch and the plate according to the embodiment of the present application.
  • 38 is a view for explaining separation of a patch and a plate according to an embodiment of the present application.
  • 39 is a view for explaining separation of the patch and the plate when the sample is not fixed to the plate according to one embodiment of the present application.
  • 40 is a view for explaining contact between the patch and the plate through the medium, according to an embodiment of the present application.
  • 41 is a view for explaining that the contact through the medium between the patch and the plate according to an embodiment of the present application.
  • 43 is a view for explaining a contact section between a patch and a plate according to an embodiment of the present application.
  • 44 is a view for explaining the number of contact between the patch and the plate according to an embodiment of the present application.
  • 45 is a view for explaining a contact between the plurality of patches and the plate according to an embodiment of the present application.
  • 46 is a view for explaining a contact point of the patch and the plate according to an embodiment of the present application in comparison with the step.
  • 47 is a view illustrating a contact point of a patch and a plate according to an embodiment of the present application in comparison with a step.
  • 48 is a diagram for describing a method of obtaining an image of a sample according to an embodiment of the present application.
  • 49 is a diagram for describing a method of obtaining an image of a sample according to an embodiment of the present application.
  • 50 is a diagram for describing a time point of obtaining an image for a sample according to an embodiment of the present application.
  • FIG. 51 is a diagram illustrating a time point at which an image of a sample is acquired according to an embodiment of the present application.
  • FIG. 52 is a block diagram of a diagnostic apparatus according to an embodiment of the present application.
  • 53 is a conceptual diagram illustrating an example in which a structure of a diagnosis apparatus is moved by a relative movement operation of the relative position adjusting unit 100 according to an embodiment of the present application.
  • 54 is a flowchart illustrating a PCR process according to an embodiment of the present application.
  • 55 is a flowchart illustrating amplification of DNA included in a sample according to an embodiment of the present application.
  • 56 is a flowchart illustrating amplifying the DNA included in the sample according to an embodiment of the present application.
  • 57 is a diagram illustrating a PCR process for a plurality of target genetic material according to an embodiment of the present application.
  • 58 is a diagram illustrating a PCR process for a plurality of target genetic material according to one embodiment of the present application.
  • 59 is a diagram illustrating a PCR process for a plurality of target genetic material according to an embodiment of the present application.
  • 60 is a view for explaining a PCR process using a plate and a patch provided with a reagent according to an embodiment of the present application.
  • 61 is a view for explaining a PCR process using a plate and a patch provided with a reagent according to an embodiment of the present application.
  • FIG. 62 is a flowchart illustrating a PCR process using a plate and a patch provided with a reagent according to an embodiment of the present application.
  • 63 is a flowchart of a method of controlling contact between a patch and a plate according to an embodiment of the present application.
  • 64 is a view for explaining a contact time between a patch and a plate according to an embodiment of the present application.
  • 65 is a flowchart illustrating a method of controlling the temperature of a sample by adjusting the temperature of a patch according to an embodiment of the present application.
  • 66 is a view for explaining the effect of adjusting the temperature of a sample using a plurality of patches according to an embodiment of the present application.
  • 67 is a flowchart illustrating a process of performing a PCR process on an RNA sample according to an embodiment of the present application.
  • a PCR patch provided on a mesh-like gel forming a micro-cavity
  • at least some of the reagents used for the polymerase chain reaction are added to the microcavity.
  • the reagent stored in the microcavity moves to at least a portion of the outer region, and the target DNA contained in the sample located in the outer region.
  • PCR polymerase chain reaction of the polymerase may be provided.
  • Reagents stored in the microcavity of the patch may be provided with a PCR patch comprising a first substance that specifically reacts with the target DNA.
  • the reagent stored in the microcavity of the patch includes a second material that reacts with DNA bound to the first material, and a third material that creates an environment for the polymerase chain reaction of the second material PCR patches may be provided.
  • the first material may be provided with a PCR patch coupled to the fluorescent material.
  • the first substance may be provided with a PCR patch comprising a fourth substance specifically reacting with the first target DNA and a fifth substance specifically reacting with the second target DNA.
  • the patch includes a first region and a second region, wherein the reagent stored in the first region does not move to the second region, and the reagent stored in the second region does not move to the first region May be provided.
  • the first region may include a fourth substance that specifically reacts with the first target DNA, and the second region may be provided with a PCR patch including a fifth substance that specifically reacts with the second target DNA. Can be.
  • the outer region is a plate on which the sample may be provided, and the plate may be provided with a PCR patch in which the sample is provided as a monolayer.
  • At least a part of a plurality of reagents used for the polymerase chain reaction is applied to the plate, and when the patch and the plate come into contact with each other, the reagent applied to the plate is contained in the sample.
  • PCR patches may be provided that participate in the polymerase chain reaction.
  • the reagent applied to the plate includes a second material that reacts with the DNA bound to the primer, and the reagent stored in the microcavity of the patch includes an environment for the polymerase chain reaction of the second material.
  • a PCR patch comprising the third material to make up may be provided.
  • a PCR patch set including a plurality of the patches used for the progress of the polymerase chain reaction of the patches provided on the gel of the network structure forming a micro-cavity
  • a first patch in which at least a first reagent of a plurality of reagents used in the polymerase chain reaction is stored in the microcavity;
  • a second patch in which at least a second reagent of the plurality of reagents used in the polymerase chain reaction is stored in the microcavity, wherein the first reagent is a reagent different from the second reagent.
  • the first reagent comprises a first substance that specifically reacts with the target DNA
  • the second reagent is a PCR patch that specifically reacts with the target DNA but has a base sequence complementary to the first substance.
  • the first reagent includes a first substance that specifically reacts with a target DNA
  • the second reagent is provided by a PCR patch set including a second substance that reacts with DNA bound to the first substance. Can be.
  • the first reagent includes a second material that reacts with DNA bound to a primer, and the second reagent includes a third material that creates an environment for the polymerase chain reaction of the second material.
  • PCR patch sets can be provided.
  • the polymerase chain Providing a reagent stored in the first patch to a sample provided on the plate, using a first patch storing at least some of the plurality of reagents used in the reaction in the microcavity; And controlling the temperature of the sample to cause the polymerase chain reaction; PCR methods comprising a can be provided.
  • Providing the reagent stored in the first patch may be provided with a PCR method comprising the step of contacting the plate and the first patch.
  • Adjusting the temperature of the sample may be provided with a PCR method comprising adjusting the temperature of the plate, in order to adjust the temperature of the sample provided on the plate.
  • PCR method When the temperature of the plate is greater than or equal to a reference temperature, separating the contact between the plate and the first patch; PCR method may further be provided.
  • Adjusting the temperature of the sample may be provided with a PCR method comprising adjusting the temperature of the first patch, in order to adjust the temperature of the sample.
  • the adjusting of the temperature of the first patch may be provided by a PCR method performed before the step of contacting the plate with the first patch.
  • Adjusting the temperature of the sample may be provided with a PCR method comprising the step of contacting the temperature-controlled metal material with the plate to adjust the temperature of the sample.
  • the first reagent stored in the first patch may be provided with a PCR method which is not stored in the second patch.
  • a PCR method stored in the first patch may be provided.
  • Providing the reagent stored in the second patch may be provided with a PCR method comprising the step of contacting the plate with the second patch.
  • Adjusting the temperature of the sample may be provided with a PCR method comprising at least one of adjusting the temperature of the first patch and adjusting the temperature of the second patch.
  • Adjusting the temperature of the first patch is followed by providing a reagent stored in the first patch and adjusting the temperature of the second patch is followed by providing a reagent stored in the second patch.
  • a PCR method may be provided in which a step is performed.
  • the reagent stored in the first patch includes a first substance that specifically reacts with the target DNA, and the reagent stored in the second patch includes a second substance that reacts with the DNA bound to the first substance.
  • PCR may be provided comprising a.
  • Providing the reagent stored in the second patch may be provided with a PCR method comprising the step of contacting the second patch and the first patch.
  • Providing the reagent stored in the first patch may be provided with a PCR method comprising the step of performing the contact of the plate with the first patch a plurality of times.
  • the target DNA included in the sample using a patch provided on the mesh of the network forming the micro-cavity to store the reagent used for the polymerase chain reaction A diagnostic apparatus for performing the polymerase chain reaction of a target DNA, comprising: a relative movement control unit for relatively moving a region provided with the sample and the patch to provide a reagent stored in the patch to the sample; A temperature controller for controlling the temperature of the sample to a temperature such that the polymerase chain reaction can be induced; And an image acquisition unit for acquiring an image of the sample to detect a target DNA included in the sample.
  • 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.
  • the liquid substance may be a mixture including a plurality of substances.
  • the liquid substance 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.
  • the liquid substance 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.
  • the material of the plurality of components constituting the mixture may be uniformly distributed.
  • 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.
  • the non-uniformly distributed material may also include a particle component that is non-uniformly distributed in the solvent.
  • the heterogeneously distributed particle component may be a solid phase.
  • 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.
  • FIGS. 1 and 2 are diagrams showing an example of a patch according to the present application.
  • a patch according to the present application will be described with reference to FIGS. 1 and 2.
  • the patch PA may include a net structure NS and a liquid material.
  • the liquid substance may be considered by dividing the base material (BS) and the additive material (AS).
  • 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.
  • 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.
  • 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.
  • the net structure of the patch PA may have a sponge structure SS.
  • the net structure of the sponge structure SS may include a plurality of fine holes (MH).
  • MH fine holes
  • 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.
  • the net structure NS may have a regular or irregular pattern.
  • 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.
  • 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.
  • the fluidity of the liquid material (SB) may be limited.
  • the liquid substance SB may freely flow in the net structure NS.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the additive material AS may include a component that is selectively included in the patch PA.
  • 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.
  • 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.
  • 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.
  • 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.
  • '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 gas or liquid, vibrational movements in solids, etc.).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the net structure NS of the patch PA may be hydrophilic or hydrophobic.
  • 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.
  • 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.
  • the liquid material SB may be hydrophilic
  • both the base material BS and the additive material AS may be hydrophilic
  • the liquid material (SB) may be hydrophobic
  • 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.
  • 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.
  • 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.
  • the patch PA may be used alone, in plurality, or in combination with other media to induce a desired reaction.
  • the functional aspects of the patch PA will be described.
  • the patch PA is a gel phase that may contain a hydrophilic solution.
  • the mesh structure NS of the patch PA is assumed to have hydrophilic properties.
  • Patches according to the present application may have some useful functionality, due to the properties described above.
  • the patch may be involved in the behavior of the liquid material SB by occupying the liquid material SB.
  • 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.
  • the patch PA according to the present application may capture the liquid substance SB as described above.
  • 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.
  • 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.
  • 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.
  • 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.
  • the amount of material that can be stored in the patch PA may be proportional to the volume of the patch PA.
  • 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.
  • 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.
  • a substance to the patch (PA) it can increase or maintain the content of the substance stored in the patch (PA).
  • 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.
  • the patch PA may store a liquid material SB having a plurality of components.
  • 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.
  • the substance it is also possible for the substance to be stored.
  • 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.
  • the material stored in the patch PA may exhibit fluidity basically, and may also perform irregular or diffusion motion by molecular motion in the patch PA.
  • 3 and 4 are diagrams for providing a reaction space as an example of the function of the patch according to the present application.
  • the patch PA according to the present application may perform a function of providing a space.
  • 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.
  • the plurality of substances 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.
  • the efficiency of the function of providing a space for activities other than the diffusion of the patch PA can be enhanced.
  • 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.
  • 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.
  • Movement of material may occur between the patch PA and the outer region.
  • 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.
  • the patch PA may have unique functions.
  • the basic reason why the movement of the liquid material SB occurs is due to the irregular movement and / or diffusion of the material.
  • external environmental factors eg, control of temperature conditions, control of electrical conditions, etc.
  • the liquid substance SB or some components of the liquid substance SB may diffuse into the outer region or move by irregular movement.
  • 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.
  • 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.
  • movement of the material may not occur between the liquid material SB captured in the patch PA and the external region.
  • 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.
  • the liquid material SB remaining in the patch PA and the outer region or the outer substance may not move. .
  • 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.
  • a state in which the movement of the material is impossible may be caused by separation of the patch PA and the external region.
  • 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.
  • 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.
  • 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.
  • environmental conditions such as temperature change, pressure change, electrical property change, physical state change.
  • 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.
  • the liquid substance SB 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.
  • 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.
  • movement between the patch PA and the outer region becomes impossible.
  • 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.
  • 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.
  • 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.
  • 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.
  • liquid material SB is transferred from the patch PA to a separate outer plate PL.
  • the case where the material is moved from the patch PA to the plate PL such as slide glass may be considered.
  • 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.
  • some material that is, a part of the liquid material SB
  • the partial material may be transferred from the patch PA to the plate PL.
  • the some material to be delivered may be the additive material (AS).
  • 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.
  • 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.
  • the patch PA comprises a plurality of components
  • only some components may be selectively moved to the outer plate PL.
  • a material that specifically binds to some components of the plurality of components may be fixed to the outer plate PL.
  • the material fixed to the outer plate PL may be in a liquid or solid state and may be fixed in the separate area.
  • 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.
  • only some components can be selectively released into the plate PL.
  • 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.
  • the transferring of the material may be enabled to move the material by contacting the plate.
  • 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.
  • the material SL having fluidity may be a liquid material contained in a separate storage space or flowing.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the physical separation between the patch PA and the fluid SL is essential. no.
  • 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.
  • 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.
  • 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.
  • the liquid material SB provided to the patch PA may move to at least a portion of the other patch PA.
  • the liquid substance SB provided to each of the patches PA may diffuse and move to the other patch PA.
  • the concentration of the liquid material (SB) provided in each of the patches (PA) may be changed.
  • 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.
  • 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.
  • 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.
  • 'absorption' of the function of the patch PA may be treated similarly to the 'delivery' described above in some embodiments.
  • 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.
  • 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 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.
  • 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.
  • 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.
  • 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.
  • the patch PA 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.
  • the volume, color, etc. of the patch PA may change.
  • 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.
  • 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.
  • the patch PA absorbs an external material from a separate outer plate PL.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • some materials may be fixed to the plate PL.
  • some materials are fixed to the plate PL and some materials are not fixed or may be applied with fluidity.
  • 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.
  • 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.
  • the patch PA 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.
  • 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.
  • the patch PA absorbs the material from the outer plate PL.
  • 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).
  • 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.
  • the patch PA may be in a state where the material SL and the fluid may move.
  • 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.
  • 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.
  • the concentration is low, the predetermined additive material AS may be absorbed into the patch PA.
  • the material 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.
  • 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.
  • 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.
  • the absorbent material is hydrophilic
  • the patch PA is hydrophilic
  • the attraction force between the absorbed material and the patch PA is the attraction force between the other patch PA and the absorbed material.
  • 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.
  • 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.
  • 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.
  • the degree of absorption may be adjusted by controlling the concentration of the agarose.
  • 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.
  • 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.
  • 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. .
  • a target area eg, an external material, a plate PL, etc.
  • 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.
  • 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.
  • the patch PA may provide homeostasis to the desired area.
  • 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.
  • 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.
  • 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.
  • 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. .
  • 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.
  • 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.
  • the patch PA may provide a reaction zone of a material.
  • the reaction of the material may occur in at least a part of the spatial region affected by the patch PA.
  • 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.
  • 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).
  • 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.
  • 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-mentioned 2.1.3 table of contents and 2.2.4.2 (ie, absorption) table of contents.
  • the present invention is not limited thereto, and two or more functions may be implemented in a merged form.
  • the absorption function of the patch PA and the provision function of the reaction space are performed by one patch PA.
  • 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.
  • the patch PA further includes not only the absorbing and providing functions but also additional functions.
  • 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.
  • 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.
  • 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.
  • the patch PA may perform an absorption function of the fluid material, so that the reaction of the trapped material may occur.
  • 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.
  • the composition of the liquid material SB captured in the patch PA may be changed.
  • the chemical composition may be changed before and after the reaction.
  • 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.
  • 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.
  • the patch PA may store a material and provide a reaction space of the stored material.
  • the reaction space provided by the patch PA may be a surface area of the microcavity or the patch PA formed by the mesh structure NS of the patch PA.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the patch PA may capture, absorb, release, and / or store fluid material as described above.
  • the patch PA 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the patch PA may perform a function of appropriately adjusting the amount and rate of delivery of the substance to other foreign substances.
  • such a series of processes may be performed in one direction based on the patch (PA).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the patch PA may be used alone, or a plurality of patches PA may be used together.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • one patch PA may perform a function of transferring a material to the target area TA
  • 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.
  • 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.
  • the material of the different components 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.
  • 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.
  • 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.
  • a combination of specific reactions to be detected may be configured and performed each time the detection is performed. There will be.
  • FIG. 33 illustrates an embodiment of a patch PA according to the present application, in which a plurality of patches PA are used together.
  • 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.
  • the plate PL includes a plurality of target areas TA.
  • 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.
  • 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.
  • each patch PA may perform both storage and release of the material.
  • 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.
  • 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.
  • each patch PA can simultaneously perform storage, release and absorption of the material.
  • each of the patches PA may be performed by dividing the storage, release and absorption of the material.
  • the present invention is not limited thereto, and each function may be performed in combination in a plurality of patches PA.
  • 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.
  • each patch PA may simultaneously perform storage, release and provision of the environment at the same time.
  • each of the patches PA may perform a separate storage, release and provision of the environment.
  • the present invention is not limited thereto, and each function may be performed in combination in a plurality of patches PA.
  • one patch PA among the plurality of patches PA may release the stored material to the target area TA.
  • another patch PA may provide an environment to the target area TA.
  • 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.
  • 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.
  • the plurality of patches PA may be in contact with each other.
  • the at least one patch PA may store the material and release the stored material as another patch PA providing the environment.
  • 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.
  • PCR polymerase chain reaction
  • PCR means a polymerase chain reaction, and is a method of amplifying a target genetic material to be detected. PCR has been used in various fields such as diagnosis of diseases (eg cancer diagnosis, AIDS diagnosis, tuberculosis diagnosis), gene duplication, forensic evidence, gene identification.
  • 35 is a graph for explaining a PCR process according to the present application.
  • PCR may be performed in three steps. Specifically, the general PCR is a heat denaturation step for separating DNA having a double helix structure using heat, 1) a denaturation step, 2) annealing step for the primer (binmer) to bind to the sequence ends of the DNA to be amplified ( annealing step), and 3) a polymerization step (extension step) to extend the DNA to which the primer is bound.
  • the general PCR is a heat denaturation step for separating DNA having a double helix structure using heat, 1) a denaturation step, 2) annealing step for the primer (binmer) to bind to the sequence ends of the DNA to be amplified ( annealing step), and 3) a polymerization step (extension step) to extend the DNA to which the primer is bound.
  • the thermal denaturation step is a process of separating two strands of DNA having a double helix structure into one strand of DNA.
  • the test object hereinafter, a sample
  • the test object is usually heated to 95 ° C. to separate hydrogen bonds formed between the complementary bases of the two DNA strands, thereby converting the two DNA strands into one DNA pair. Can be separated.
  • the temperature at which the two strands of DNA can be separated into one strand of DNA is defined as a heat denaturation temperature.
  • the annealing step is a process of binding primers complementary to the base sequence of one strand of DNA.
  • the annealing step is usually performed at 55 ⁇ 65 °C, primers corresponding to some sequences of the target genetic material can be used.
  • the primer may include a forward primer and a reverse primer, the forward primer and the reverse primer may have a base sequence complementary to each other.
  • the primer may be in a state in which a fluorescent material is labeled.
  • the temperature eg, 55-65 ° C.
  • the primer complementary to the base sequence of the single strand of DNA can be bound is defined as an annealing temperature.
  • a base complementary to one strand of DNA to which the primer is bound is synthesized and extended to two strands of DNA.
  • the polymerization step is usually performed at 70 °C, DNA complementary base fragment (deoxyribonucleotide or less, dNTP) and the DNA polymerase (synthesis) that synthesizes the dNTP to the DNA can be used.
  • a temperature eg, 70 ° C.
  • a polymerization reaction temperature eg, 70 ° C.
  • a coenzyme for stable activity of the DNA polymerase, a coenzyme may be used.
  • the above-described DNA polymerase is Taq polymerase having high heat resistance
  • magnesium ion for stable activity of the Taq enzyme may be added.
  • the magnesium ions may be added in the form of MgCl 2 or MgSO 4 aqueous solution.
  • a buffer may be used to provide an optimal pH and / or salt concentration for the DNA amplification reaction.
  • PCR may be carried out the above-described heat denaturation step, annealing step, and polymerization reaction step. In addition, the above-described three steps may be performed sequentially sequentially. By repeating the PCR reaction, the amplification amount of the target genetic material may increase.
  • the PCR process using the patch PA may be performed by testing a sample SA containing a target genetic material.
  • a PCR process using the patch PA may be performed on the extracted genetic material.
  • the genetic material may be detected in the field for gene identification or extracted using tissue or blood of a diagnosis subject.
  • a process using a PCR preprocessor, or a lysozyme for cell wall degradation and a sodium dodecyl sulfate (SDS) reagent for washing may be used.
  • a PCR process using the patch PA may be performed on blood that has not undergone a separate pretreatment.
  • the target genetic material to be detected may be DNA or RNA of the virus. Therefore, the PCR process may be performed on a sample (SA) containing the genetic material of the virus.
  • SA sample
  • Blood infected with the virus may contain the DNA and / or RNA of the virus.
  • the blood of a patient infected with Zika virus may be suspended with viral RNA (ie, VIRAL RNA).
  • the PCR process for diagnosing a viral disease may be performed on a blood sample (SA) not subjected to pretreatment by targeting a genetic material of a virus present in blood.
  • SA blood sample
  • 36 is a diagram for explaining provision of a target sample SA according to the present application.
  • a sample (SA) is provided to a PCR tube so that the reagent (RA) and the sample (SA) in an aqueous solution can be mixed.
  • the sample (SA) is plated.
  • PL eg, slide glass
  • the sample SA may be provided as a mono layer on the plate PL.
  • a method of printing may be used.
  • the sample SA ie, blood
  • some cells eg, white blood cells and red blood cells
  • the sample SA are provided as a monolayer on the plate PL
  • the cells arranged in overlap may be reduced. . Therefore, when the sample SA is provided in the mono layer, the effect of analyzing the sample SA (eg, the image of the sample SA) may be more accurate.
  • the sample SA provided on the plate PL may be fixed.
  • the sample SA smeared on the plate PL may be fixed to the plate PL.
  • the sample SA printed on the plate PL may be fixed to the plate PL.
  • the sample SA discharged using the eyedropper may be fixed to the plate.
  • the fixing of the sample SA to the plate PL refers to a state in which a resistance is generated so that the sample SA stays on the plate PL until a force of reference strength is applied to the sample SA. do. As a result, even when the patch PA is in contact with or separated from the plate PL, the sample SA may not be absorbed into the patch PA.
  • the method for fixing the sample SA to the plate PL may be any method used in the art to which the present application belongs.
  • a method of providing and volatilizing methanol to the sample SA may be used.
  • RNA sample (SA) substantially containing RNA and a PCR process using a DNA sample (SA) containing DNA proceed similarly. Therefore, it is assumed that the sample SA is DNA, and the PCR process will be described.
  • the PCR process using the RNA sample SA will be compared with the PCR process using the DNA sample SA, based on the difference. This will be explained in.
  • Patches (PA) can be used in a PCR process.
  • the patch PA may include at least some of the reagents RA used in the PCR process.
  • the patch PA may store the reagent RA.
  • the reagent RA captured in the patch PA may be stored in the patch PA due to the polarity of the patch PA. For example, when the polarity of the mesh structure and the polarity of the reagent (RA) are the same, the reagent (RA) is maintained in the patch (PA) for a predetermined time due to the attraction force between the mesh structure and the reagent (RA). Can be.
  • the patch PA may store a plurality of types of reagents RA used in a 1-cycle PCR process.
  • the patch (PA) may be stored dNTP, DNA polymerase, primers, buffers and coenzymes.
  • PA patch
  • PA all-in-one patch
  • the all-in-one patch (PA) is applied to the sample SA.
  • One cycle of the PCR process i.e., the heat denaturation step, the annealing step and the polymerization reaction step proceeds sequentially
  • the patch PA may store some types of reagents RA among a plurality of types of reagents RA used in a 1-cycle PCR process.
  • the patch PA stores some types of reagents RA among the reagents RA used in the PCR process
  • the remaining reagents RA may be stored in another patch PA.
  • the other patch PA means a separate patch PA separated from the patch PA, and the reagent RA stored in the patch PA and the reagent RA stored in the other patch PA. This does not mean that the reagents contained in are different.
  • the patch PA when the patch PA stores some kinds of reagents RA among the reagents RA used in the PCR process, the remaining reagents RA may be applied to the plate PL provided with the sample.
  • the patch PA when the patch PA stores some kinds of reagents RA among the reagents RA used in the PCR process, the remaining reagents RA may be provided to the sample SA on the PCR process.
  • the medium may be paper, thread, or other material that contains a reagent (RA) that can be dissolved in contact with the liquid.
  • the patch PA stores some types of reagents RA among the reagents RA used in the PCR process
  • at least some of the remaining reagents RA are stored in another patch, and the remaining reagents RA At least a portion of may be applied to the plate PL on which the sample SA is provided.
  • Reagents (RA) used in a PCR process that can be stored in a variety of ways can be sorted by a combination of reagents (RA) stored together, through some of the methods described above.
  • reagent RA used for PCR is assumed to be stored separately in the first patch PA and the second patch PA unless otherwise noted.
  • some kinds of reagents (RA) stored in the first patch (PA) are first reagents (RA)
  • some kinds of reagents (RA) stored in the second patch (PA) are second reagents. It is assumed to be (RA).
  • the reagents may be stored in the first patch PA and the second patch PA in consideration of the relationship between the reagents RA that may cause nonspecific binding among the plurality of reagents.
  • the forward primer may be stored in the first patch, and the reverse primer may be stored in the second patch.
  • the reagents may be added to the first patch PA and the second patch PA.
  • RA can be stored.
  • the DNA polymerase may be stored in the first patch PA and the coenzyme may be stored in the second patch PA.
  • the buffer solution is stored in the first patch (PA) to prevent the DNA polymerase and dNTP from being provided with the polymerization reaction activity condition of the PCR process by the buffer solution before the polymerization step.
  • dNTP and DNA polymerase may be stored in the second patch (PA).
  • dNTP, primer, DNA polymerase can be applied to the plate (PL), the buffer solution and the coenzyme can be stored in the first patch (PA).
  • the reagents RA may be stored in the first patch PA and the second patch PA.
  • the primers are stored in the first patch (PA) to provide reagents (RA), which should be provided in the same step, at once, and the DNA polymerase, dNTP, and buffers.
  • RA reagents
  • the solution and coenzyme can be stored in the second patch (PA).
  • the PCR process which is different from the above-described embodiment, consists of a separate patch (PA) of primers that must be changed according to the sequence of the target genetic material, so that the primers may be changed if a change of the primer is required to diagnose a disease different from the previous PCR test.
  • PA patch
  • RA reagents
  • the reagents RA may be stored in the first patch PA and the second patch PA in consideration of the reagents RA consumed. .
  • the reagent (RA) consumed as the PCR process proceeds in a region capable of storing a large amount Can be stored.
  • the DNA polymerase is applied to the plate, primers, dNTP that is consumed after one cycle is a patch Can be stored in
  • the forward primer may be stored in the first patch (PA), and the reverse primer may be stored in the second patch (PA).
  • dNTPs, DNA polymerases, buffers and coenzymes may be stored in the third patch PA, taking into account the time when reagent RA should be provided to the sample SA.
  • a patch PA including the above-described lysozyme (hereinafter referred to as a lysis patch PA) may be used.
  • the lysis patch PA is not always required to be applied in a PCR process to be described later, but may be additionally used as necessary.
  • the lysis patch PA may be used to deform a structure such as a cell wall included in the sample SA provided on the plate PL, or may be used for the sample SA. It may be used at some point where the pretreatment process is performed.
  • a patch PA (hereinafter, referred to as an empty patch PA) that does not contain the reagent RA may be used.
  • the empty patch PA like the lysis patch PA, may be additionally used but not always applied in a PCR process to be described later.
  • the empty patch PA may be used for absorbing and removing a material provided on the plate PL, or absorbing the sample SA provided on the plate PL to absorb the sample SA. ) May be used to provide a space for reaction.
  • the patch PA may provide the reagent RA to the plate PL.
  • the patch PA may contact the plate PL, and may provide the reagent RA stored in the patch PA by the contact to the plate PL.
  • the final destination of the reagent RA provided in the plate PL may be an area provided with the sample SA on the plate PL.
  • the patch PA may contact a region in which the sample SA of the plate PL is provided.
  • the contact between the plate PL and the patch PA may be released. Due to the contact release of the plate PL and the patch PA, the reagent RA provided to the plate PL may be absorbed into the patch PA.
  • 37 is a view for explaining contact between the patch PA and the plate PL according to an embodiment of the present application.
  • the contact between the patch PA and the plate PL allows the reagent RA (ie, a liquid substance) contained in the patch PA to move to the plate PL.
  • reagent RA ie, a liquid substance
  • By the contact of the patch PA and the plate PL it may be possible to move the material on the plate PL to the patch PA.
  • the function of this patch (PA) has been described in detail in the above-mentioned delivery of the patch.
  • the reagent RA may be provided to the sample SA while the patch PA is in contact with the plate PL.
  • reagent (RA) While the reagent (RA) is provided, some reagents (RA) moved from the patch (PA) to the plate (PL) may be closer to or less than a reference distance from the sample (SA), and the sample (SA) If there are some substances in which binding force acts with the reagent (RA), at least some of the reagents (RA) may bind to the some substances. For example, if some reagents (RA) moved to the plate (PL) by the patch (PA) is a primer, the primer may bind to the DNA contained in the sample (SA) in the annealing step.
  • the reagent RA transferred to the plate may provide a specific environment to the sample SA.
  • the specific environment may be pH conditions, salt concentrations and / or ion concentrations.
  • a patch PA including a buffer solution may provide an environment for providing a pH suitable for the polymerization reaction step to the sample SA.
  • FIG. 38 is a view for explaining separation of a patch PA and a plate PL according to an embodiment of the present application.
  • the reagent RA provided to the plate PL by the patch PA may be captured back into the patch PA.
  • the liquid substance including the reagent RA provided to the plate PL by the patch PA may be captured back into the patch PA.
  • the liquid material captured again may be in a state where some materials are lost, compared to the liquid material provided to the sample SA by the patch PA.
  • a liquid material including the primer may be provided to the sample SA when the patch PA contacts the plate SA.
  • some of the primers captured in the patch PA may bind to DNA contained in the sample SA.
  • a liquid material except for some primers combined with the sample SA may be introduced back into the patch PA.
  • the liquid material captured again, compared to the liquid material provided on the plate PL may be a state in which some primers are lost.
  • the patch PA can maintain its original function.
  • the material trapped in the patch PA may be diffused in the patch PA.
  • FIG. 39 is a diagram for describing separation of the patch PA and the plate PL when the sample SA is not fixed to the plate PL according to one embodiment of the present application.
  • the sample SA provided on the plate PL When the sample SA provided on the plate PL is not fixed, when the patch PA contacts the plate PL, the sample SA may move to the patch PA.
  • the patch PA may capture the sample SA.
  • the sample SA captured in the patch PA may flow in the patch PA. Due to the diffusion motion of the sample SA, the position of the sample SA may be changed.
  • the reagent RA stored in the patch PA may move to the plate PL by contact between the patch PA and the plate PL.
  • the reagent RA may diffuse in the patch PA.
  • the sample SA is introduced into the patch PA, and a PCR reaction may be performed.
  • the patch PA may capture the sample SA to provide a reaction space.
  • the sample SA may react with the reagent RA stored in the patch PA.
  • the sample SA may react with a material absorbed together with the sample SA.
  • the reagent RA stored in the patch PA may perform a function of providing a specific environment to the sample SA.
  • the patch PA can maintain its original function.
  • the material trapped in the patch PA may diffuse in the patch PA. Accordingly, the sample SA may flow in the patch PA, and the reagent RA and the sample SA captured together even after the contact of the patch PA and the plate PL are released. Can react.
  • 40 is a diagram for explaining contact between the patch PA and the plate PL through a medium according to one embodiment of the present application.
  • the patch PA and the plate PL may be contacted using separate mediators which channelize each other, instead of directly contacting each other. Even when the patch PA and the plate PL are connected through a medium, the patch PA may provide a reagent RA to the plate PL.
  • the mediator may be a patch (PA2).
  • the patch PA2 may be a separate patch PA separate from the patch PA1 storing the reagent RA.
  • the patch PA2 serving as a medium is defined as the second patch PA2 and the patch PA1 storing the reagent as the first patch PA1.
  • the medium may be a medium embodied to be provided to the sample (SA) in a PCR process.
  • the medium may be provided between the plate PL and the patch PA to provide a wet environment from the patch PA.
  • the reagent RA stored in the medium may be transferred to the plate PL.
  • the direct contact between the patch (PA) and the plate (PL) and the patch (PA) and the plate ( PL) is defined to include all contact by using a medium.
  • the reagent RA stored in the first patch PA1 may move to the plate PL.
  • the material included in the first patch PA1 may move to the second patch PA2 through contact between the first patch PA1 and the second patch PA2 and the second patch. This is due to the ability of the material included in the second patch PA2 to move to the plate PL through contact between the plate PA2 and the plate PL.
  • the patch PA and the plate PL directly contact each other.
  • a function similar to the case may be performed.
  • 41 and 42 are views for explaining the release of contact through the medium between the patch PA and the plate PL according to an embodiment of the present application.
  • the contact between the patch PA and the plate PL using the above-described medium can be separated by releasing the contact between the medium and the plate PL.
  • the medium is a patch
  • the first patch PA1 is separated from the plate PL by releasing contact between the second patch PA2 and the plate PL, a reagent provided to the sample SA is released. This may be absorbed into the first patch and the second patch again.
  • the reagent RA stored in the first patch PA1 may no longer move to the plate PL.
  • the sample SA and the plate PL are in direct contact. And similar functions as in the case of separation and separation can be performed.
  • the release of contact between the patch PA and the plate PL releases direct contact between the patch PA and the plate PL and releases the patch PA and the plate PL. It is defined as including all the release of the contact using the mediator of). In addition, the separation of contacts can be used in confusion with the release of the contacts described above.
  • the contact between the patch PA and the plate PL using the above-described medium may be separated by releasing the contact between the medium and the patch PA.
  • the medium may be maintained in contact with the plate PL.
  • the medium is a patch
  • the first patch PA1 Reagent (RA) stored in the can no longer move to the second patch (PA2) or plate (PL).
  • the second patch PA2 is in contact with the plate PL, and the reagent RA stored in the second patch PA2 may move to the plate PL.
  • reagents RA may be captured in the second patch PA2 through the contact between the first patch PA1 and the second patch PA2.
  • the patch PA used for contact between the patch PA and the plate PL may be obtained even after the patch PA providing the reagent RA is separated from the patch PA used for the contact. In this case, there may be an advantage of continuously providing the reagent RA to the sample SA.
  • the unfixed sample SA may be introduced into the patch PA.
  • This process can be easily understood by those skilled in the art, but when separating the media and the patch (PA), the disadvantage that some samples (SA) with the patch (PA) can be separated, a small amount of the sample (SA) is lost Therefore, detailed description thereof will be omitted.
  • the contact between the plate PL and the patch PA is defined as including all of the above-described various embodiments.
  • 43 is a view for explaining a contact section between the patch PA and the plate PL according to an embodiment of the present application.
  • the patch PA may be in contact with the plate PL in a section in which a reagent RA needs to be provided.
  • the patch PA may provide the reagent RA to the plate PL by contact between the patch PA and the plate PL.
  • the patch PA may contact the plate PL before the section requiring the provision of the reagent RA, and may separate the contact with the plate PL after the section requiring the provision of the reagent RA. have.
  • the patch PA may be in contact with the plate PL in some of the sections in which the reagent RA needs to be provided.
  • the reagent RA is provided while the patch PA and the plate PL are in contact with each other, in order to control the amount of the reagent RA provided to the patch PA, the plate ( PL) and the contact timing of the patch PA can be adjusted.
  • the patch PA may be in contact with the plate PL at any point in the section requiring the provision of the reagent RA, and the plate PL at any point in the section requiring the provision of the reagent RA. ) Contact can be separated.
  • the patch PA may not be in contact with the plate PL in a section requiring provision of the reagent RA.
  • the patch PA may be contacted and separated before the section where the reagent RA is required.
  • the patch PA and the plate are provided in a section requiring the provision of the reagent RA. (PL) may be separated.
  • the contact between the patch PA and the plate PL is separated by contact separation between the medium and the patch PA. Provision of the reagent RA may be maintained.
  • the patch PA and the plate PL contact each other and the sample SA is introduced into the patch PA, even if the patch PA and the plate PL are separated, the reagent RA ) Can be maintained.
  • the patch PA may be separated from the plate PL at any point in the section in which the reagent RA is required.
  • Reagents may be provided to the sample (SA) in the section (RA) is required.
  • FIG. 44 is a view for explaining a contact number of a patch PA and a plate PL according to an embodiment of the present application.
  • the patch PA and the plate PL may be contacted once to provide the reagent RA.
  • the patch PA and the plate PL may be contacted once during the heat denaturation step, the annealing step, and the polymerization reaction step. It can mean.
  • One contact to provide reagent (RA) has the advantage that the process procedure is monotonous by eliminating unnecessary contact and separation.
  • the all-in-one patch PA and the plate PL are contacted to amplify DNA by controlling temperature, and after the DNA amplification is completed, the all-in-one patch ( PA) and the plate PL may be separated.
  • the patch PA and the plate PL may be contacted a plurality of times to provide the reagent RA.
  • the patch PA may include a primer used in the annealing step and a DNA polymerase used in the polymerization reaction step
  • the patch PA may be contacted at least once in the annealing step and at least once in the polymerization step.
  • the patch PA may be contacted a plurality of times in the annealing step.
  • the patch PA may be contacted a plurality of times in the polymerization reaction step. Contacting a plurality of times to provide a reagent (RA) may cause an effect of preventing denaturation of the patch (PA).
  • RA reagent
  • the patch PA and the plate PL are separated when the reagent RA does not need to be provided so that the reagent RA in the patch PA is affected by the plate PL. You can stop receiving. This may prevent the patch PA from being heated, cooled, or storing other materials by the plate PL.
  • the sixth embodiment will be described in more detail below.
  • 45 is a view for explaining contact between the plurality of patches PA and the plate PL according to an embodiment of the present application.
  • the reagent RA is provided to the plate PL using a plurality of patches PA in performing a process using the patch PA
  • one patch PA is used. Contacts the plate PL to provide a reagent RA, and after the patch PA is separated from the plate PL, the other patch PA may contact the plate PL. .
  • the sample SA provided on the plate PL may be separated from the other patch (PA).
  • Reagent (RA) entrapped in PA) can be provided.
  • the reagent RA captured in the one patch PA cannot move to the patch PA. That is, the reagent (RA) provided with the sample (SA) may be limited to the reagent (RA) captured in the other patch (PA) in contact with. As a result, it is possible to prevent some substances of the reagents RA contained in the separated patch PA and some substances of the reagents RA contained in the other patch PA contacted thereafter.
  • the provision of the reagent RA is not terminated (for example, the patch PA contacts and separates the medium located on the plate PL).
  • the patch PA may also be provided with some reagents RA captured in the separated patch PA.
  • a function similar to the case in which the plurality of patches PA, which will be described below, is simultaneously provided to the plate PL for a predetermined period may be performed.
  • the plate PL may be in contact with the plurality of patches PA simultaneously.
  • Simultaneous contact of the plurality of patches PA may be performed by direct contact between the plate PL and the first patch PA and direct contact between the plate PL and the second patch PA.
  • the direct contact may mean that the patch PA and the plate PL are contacted without other media.
  • simultaneous contact of the plurality of patches PA may be performed by direct contact of the first patch PA with the plate PL and indirect contact of the second patch PA.
  • the indirect contact means that the patch PA and the plate PL are contacted through a medium, and the second patch PA contacts the first patch PA so that the second patch PA contacts the first patch PA.
  • the reagent RA stored in the patch PA may refer to a contact that may be provided to the plate PL.
  • primers and coenzymes may be included in the first patch PA, and dNTP, DNA polymerase, and buffer may be included in the second patch PA.
  • dNTP DNA polymerase
  • buffer may be included in the second patch PA.
  • the reagents RA are provided by the plurality of patches PA
  • at least some of the patches PA may be in contact with the plate PL a plurality of times. This may be performed in a similar manner as the one patch PA contacts the plate PL a plurality of times, and thus detailed description thereof will be omitted.
  • Patches (PA) can be used in a PCR process.
  • Each step of the PCR process requires that the temperature of the sample SA be maintained at an appropriate temperature.
  • the temperature of the sample SA may be maintained at the thermal denaturation temperature, the annealing temperature or the polymerization reaction temperature.
  • the plate PL may be heated or cooled or maintained at a target temperature.
  • the patch PA may be heated or cooled, or maintained at a target temperature.
  • both the plate PL and the patch PA may be heated or cooled, or maintained at a target temperature.
  • the temperature of the sample SA may be controlled by adjusting the temperature of the plate PL.
  • the temperature of the sample SA may be controlled by adjusting the temperature of the plate PL.
  • the temperature of the patch PA is adjusted when the patch PA and the plate PL are in contact with each other. It is possible to control the temperature of the sample SA, but when the patch PA and the plate PL are separated, the temperature of the patch SA is controlled by adjusting the temperature of the patch PA. Can't. Considering that the thermal equilibrium is a phenomenon in which heat transfer is caused by contact between two objects, when the patch PA and the plate PL are separated, the temperature of the patch PA is adjusted to adjust the temperature. It will not be possible to adjust the temperature of the sample SA.
  • the temperature of the sample SA may be controlled by controlling the temperatures of the patch PA and the plate PL.
  • controlling the temperature of the patch (PA) and the plate (PL) it is possible to control the temperature of any one of the entities compared to the case of adjusting the temperature of the sample (SA).
  • FIG. 46 is a view illustrating a contact point of a patch PA and a plate PL according to an embodiment of the present application in comparison with a step.
  • the patch PA may be in contact with the plate PL before the DNA amplification process starts, and may maintain contact with the plate PL until the DNA amplification process is completed. This has the advantage that the PCR process can be carried out through the simplest process procedure.
  • the temperature of the thermal denaturation step is about 95 ° C.
  • whether or not the patch PA is thermally denatured may be a problem. More specifically, if the patch PA is made of a material that is thermally deformed, in order to prevent denaturation of the patch PA, the patch PA is separated from the sample SA in the thermal denaturation step. It is understood that it would be desirable. In this regard, the contact point of the patch PA and the sample SA and / or the separation point of the contact may be determined.
  • the patch PA may contact the sample SA in a temperature control section.
  • the temperature control section is a section in which the temperature of the sample SA is changed by heating before the heat denaturation step, a section in which the temperature of the sample SA is changed by cooling before the annealing step, and before the polymerization reaction step. It is defined as a section in which the temperature of the sample SA is changed by heating.
  • the temperature of the sample SA and the patch PA are similar by thermal equilibrium, so that the patch PA ) And a sudden change in the temperature of the sample SA in the temperature maintenance section due to the temperature difference between the sample and the SA. Therefore, when the patch PA contacts the temperature control section with the sample SA, it may be possible to perform a more stable PCR process.
  • the patch PA may be separated from the sample SA in a temperature control section.
  • the temperature of the sample SA may be heated or cooled.
  • the sample (SA) and the patch (PA) may be separated in a temperature control section.
  • the patch PA may contact the sample SA in a temperature maintenance section.
  • the temperature maintenance section is a section in which the temperature of the sample SA is maintained at a thermal denaturation temperature, a section in which the temperature of the sample SA is maintained at an annealing temperature, and the temperature of the sample SA is polymerized. It is defined as the interval maintained at the reaction temperature.
  • the temperature of the sample SA and the patch PA are different, so that the sample SA is adjusted to an appropriate temperature.
  • the temperature of) may change. This may be improved through a method of heating or cooling the temperature of the patch PA before contacting the patch PA and the plate PL. A more detailed description thereof will be given in the eighth embodiment.
  • the patch PA may be separated from the sample SA in a temperature maintenance section.
  • the reagent SA stored in the patch PA is provided to the sample SA, so that the patch PA and the plate PL are provided.
  • the reagent RA provided to the sample SA may be blocked. This function can be applied, in particular, to control the length of the DNA amplified in the polymerization step.
  • the patch PA may contact the plate PL in a temperature control section, and may be separated from the plate PL in a temperature control section.
  • the patch PA may be in contact with the plate PL in a temperature maintaining section, and may be separated from the plate PL in a temperature maintaining section.
  • the patch PA may contact the patch PA in a temperature control section, and may be separated from the patch PA in a temperature maintenance section.
  • the patch PA may be in contact with the patch PA in a temperature maintenance section, and may be separated from the patch PA in a temperature control section.
  • the patch PA is the all-in-one patch (ie, a patch including dNTP, DNA polymerase, primer, buffer, and coenzyme).
  • the patch PA may be in contact with the plate PL during the DNA amplification process.
  • the patch PA and the plate PL may contact each other in a section controlled by the thermal denaturation temperature or a section maintained at the thermal denaturation temperature.
  • the plate PL may be provided with the reagent RA stored in the patch PA.
  • the temperature of the sample SA may be sequentially adjusted to a thermal denaturation temperature, an annealing temperature and a polymerization reaction temperature.
  • the temperature control may be performed by adjusting the temperature of the patch PA and / or adjusting the temperature of the plate PL.
  • the patch PA may be separated from the plate PL in a section maintained at the polymerization reaction temperature or a section controlled by a thermal denaturation step of another cycle.
  • the patch PA may be in contact with the plate PL during the annealing step and the polymerization reaction step.
  • the patch PA may contact the plate PL in a section in which the temperature of the sample SA is adjusted to the annealing temperature.
  • the plate PL may be provided with the reagent RA stored in the patch PA by the contact.
  • the temperature of the sample SA may be maintained at an annealing temperature and then adjusted to a polymerization reaction temperature.
  • the patch PA may be separated from the plate PL in a section in which the temperature of the sample SA is controlled again from the polymerization reaction temperature to the thermal denaturation temperature.
  • the patch PA may be in contact with the plate PL in the annealing step and the polymerization reaction step.
  • the patch PA may contact the plate PL a plurality of times in one cycle of the PCR process.
  • the patch PA may contact the plate PL in a section in which the temperature of the sample SA is maintained at the annealing temperature.
  • the plate PL may be provided with the reagent RA stored in the patch PA by the contact.
  • the patch PA may be separated from the plate PL while being in contact with the plate PL for a certain period in a section in which the temperature of the sample SA is maintained at the annealing temperature.
  • the reagent RA provided to the plate PL may be blocked by the separation.
  • the temperature of the sample SA may be controlled and maintained at a polymerization reaction temperature.
  • the patch PA may be contacted with and separated from the plate PL in a section where the polymerization temperature is maintained. By this contact as well, the plate PL may be provided with the reagent RA stored in the patch PA.
  • the PCR process using the plurality of patches PA is a PCR process in which one of the plurality of patches PA is used, at least one patch PA of the plurality of patches PA is the temperature control.
  • the plate PL may be in contact with the section, or may be in contact with the plate PL in the temperature maintaining section.
  • the contact between the one or more patches (PA) of the plurality of patches (PA) and the plate (PL) may be separated in the temperature control section, or may be separated in the temperature holding section.
  • One or more patches PA of the plurality of patches PA are independent of each other. In other words, contacting and detaching the first patch does not affect the ability of contacting and detaching the second patch.
  • the plurality of patches PA may be in contact with the plate PL together for a certain period of time.
  • the plurality of patches includes a first patch PA and a second patch PA.
  • the first patch PA includes a primer
  • the second patch PA includes dNTP, a DNA polymerase, a buffer solution, and a coenzyme.
  • FIG. 47 is a view illustrating a contact point of a patch PA and a plate PL according to an embodiment of the present application in comparison with a step.
  • the first patch PA may contact the plate PL in a section controlled by an annealing temperature.
  • the sample SA may be supplied by the contact with the reagent RA stored in the first patch PA.
  • the temperature of the sample SA may be maintained for a predetermined time at the annealing temperature.
  • the first patch PA may be separated from the plate PL, and the second patch PA may contact the plate PL.
  • the plate PL may receive the reagent RA stored in the second patch PA by the contact.
  • the temperature of the sample SA may be maintained at a polymerization reaction temperature for a predetermined time. After a certain time, the second patch PA may be separated from the plate PL.
  • the first patch PA may contact the plate PL in a section maintained at an annealing temperature.
  • the sample SA may be supplied with the reagent RA stored in the first patch PA by the contact.
  • the temperature of the sample SA may be maintained at the annealing temperature for a predetermined time and then adjusted to the polymerization reaction temperature.
  • the second patch PA may contact the plate PL.
  • the first patch PA may be in contact with the plate PL.
  • the sample SA may be supplied with the reagent RA stored in the second patch PA.
  • the reagent RA stored in the first patch PA may also be provided as the sample SA.
  • the first patch PA and the second patch PA may be separated from the plate PL at any time.
  • the arbitrary time point may be a section in which the temperature of the sample SA is maintained at the polymerization reaction temperature, and may be a section in which the polymerization reaction temperature is adjusted to a thermal denaturation temperature of the next cycle.
  • the contact method, timing and frequency described in detail in the provision of the reagent RA may be applied to the contact of the patch PA and the plate PL disclosed in the control of the temperature.
  • the patch PA and the plate PL may contact a plurality of times in one cycle of a PCR process.
  • an image of the sample SA may be obtained.
  • the sample SA may be in an amplified state of DNA.
  • the image may be obtained by imaging light rays emitted by the light emitted through the light source through the sample SA. That is, transmitted light may be obtained for the amplified sample SA through a PCR process using the patch PA according to the present application.
  • a conventional image of the sample SA may be obtained.
  • a visible light image may be obtained from the sample SA that has undergone the PCR process.
  • Fluorescence images of DNA included in the sample SA may be obtained.
  • the fluorescent image may be obtained by changing a wavelength band of light irradiated from a light source.
  • the fluorescence image may be obtained by selectively detecting light transmitted through the sample SA.
  • a primer to which a fluorescent material is bound may be used.
  • the primer may bind to DNA through a PCR process, and the amplified DNA may be fluoresced by a fluorescent material bound to the primer.
  • the fluorescent material may be provided in a form in which a blocking material that blocks color development is combined as necessary.
  • the fluorescent material may be designed to emit light when the sample SA and the primer are combined with a material for blocking fluorescence.
  • a method of measuring the amount of fluorescence emission may be used. More specifically, quantitative analysis of DNA may be performed by analyzing an increase in the amount of fluorescence emission.
  • 48 and 49 illustrate a method of obtaining an image of a sample SA according to an embodiment of the present application.
  • the image of the sample SA may be obtained in a state in which the plate PL and the patch PA are not in contact with each other.
  • an image of at least a partial area of the plate PL may be obtained.
  • the transmitted light may be obtained through the light beam transmitted through the plate PL.
  • the sample SA and the plate PL may be separated before the image acquisition of the sample SA.
  • the remaining reagents (RA) except for the sample (SA) provided on the plate (PL) and some reagents (RA) bound to the sample (SA). May be absorbed into the patch PA.
  • the sample SA provided on the plate PL may be fixed.
  • the patch PA and the plate PL When the patch PA and the plate PL are separated, the patch PA may be removed from the path of the light beam for acquiring the image. Therefore, the problem that light may be scattered while passing through the patch PA may be solved. As a result, a clearer image can be obtained with respect to the sample SA.
  • an image of the sample SA may be obtained while the plate PL and the patch PA are in contact with each other.
  • an image of at least a partial area of the plate PL may be obtained.
  • the transmitted light may be obtained through the light beam transmitted through the plate PL.
  • the light rays transmitted through the plate PL may pass through the patch PA in contact with the plate PL.
  • the reagent RA stored in the patch PA may move to the sample SA. Therefore, it may be possible to acquire an image of the sample SA while the sample SA is reacting.
  • Acquiring an image of the sample SA while the sample SA is in contact with the plate PL may be more suitably applied when performing a real-time analysis of the sample SA.
  • an image of at least a partial area of the patch PA may be obtained. That is, the light beams that do not pass through the plate PL may be designed to pass through the patch PA, so that the transmitted light may be obtained through the light beams passing through the patch PA.
  • 50 and 51 are views for explaining a point in time at which an image of a sample SA is acquired according to an embodiment of the present application.
  • an image may be acquired for a sample SA on which a plurality of cycles of a PCR process are performed. For example, an image of a sample SA on which a desired PCR process is completed may be obtained.
  • the image may be obtained at any point in the PCR process. Rather than an image for measuring the change over time of the sample SA, a single image for analyzing the amplified target DNA of the sample SA detected at one time point may be obtained.
  • an image of the sample SA may be continuously acquired for one cycle.
  • the image of the sample SA may be obtained at any point in time when one cycle of the PCR process is performed.
  • the image of the sample SA may be obtained when one cycle of the PCR process is completed.
  • the image of the sample SA may be obtained at a plurality of time points during one cycle of the PCR process.
  • the sample SA has a predetermined period and an image may be obtained.
  • an image may be obtained.
  • FIG. 52 is a block diagram of a diagnostic apparatus according to an embodiment of the present application.
  • Diagnostic apparatus may be composed of a relative position control unit 100, the temperature control unit 200 and the image acquisition unit 300.
  • the diagnostic device according to the present application may comprise more components or fewer components.
  • the relative position adjusting unit 100 may perform a function of relatively moving the patch PA and the plate PL.
  • the relative position adjusting unit 100 may relatively move the patch PA and the plate PL in a horizontal direction and / or a vertical direction.
  • the horizontal direction may mean a direction parallel to one surface of the plate PL and the patch PA contact.
  • the vertical direction may mean a direction perpendicular to one surface where the plate PL and the patch PA contact each other.
  • 53 is a conceptual diagram illustrating an example in which a structure of a diagnosis apparatus is moved by a relative movement operation of the relative position adjusting unit 100 according to an embodiment of the present application.
  • the relative position adjusting unit 100 relatively moves the patch PA and the plate PL in a horizontal direction, so that the patch PA on the plate PL is moved. You can change the relative position.
  • the relative position adjusting unit 100 by moving the patch (PA) and the plate (PL) in the horizontal direction relative to change the patch (PA) disposed so as to be in contact with the sample (SA). Can be done. Altering the patch PA positioned to be in contact with the sample SA may enable delivery of a liquid material provided from another patch PA to the sample SA.
  • the relative position adjusting unit 100 relatively moves the patch PA and the plate PL in the vertical direction, so that the plate PL and the sample SA may be moved.
  • the contact can be controlled. Contacting the patch PA with the sample SA may be involved in transferring a substance captured in the patch PA to the sample SA.
  • the relative position adjusting unit 100 is a power source for relatively moving the patch (PA) and the plate (PL) in the horizontal direction and a power source for relatively moving the patch (PA) and the plate (PL) in the vertical direction. It can be provided separately. Alternatively, the relative position adjusting unit 100 may move the patch PA and the plate PL in a horizontal and / or vertical direction by using a single power source.
  • the temperature control unit 200 may perform a function of controlling the temperature.
  • the temperature control part 200 may perform heating or cooling of the plate PL and / or the patch PA.
  • the temperature control unit 200 may perform a function of adjusting the temperature of the sample SA and maintaining a constant temperature.
  • the temperature controller 200 may be used to adjust the sample SA to the above-described heat denaturation temperature, annealing temperature and / or polymerization reaction temperature.
  • the temperature control unit 200 may perform an exothermic reaction and an endothermic reaction.
  • the temperature control unit 200 may include a heating element, or may include a thermoelectric element.
  • the present invention is not limited thereto, and any material capable of generating heat may be used as the temperature controller 200 without limitation.
  • the temperature control unit 200 may further include a temperature sensor.
  • the temperature sensor may be used to check the current temperature of the temperature control object.
  • the image acquisition unit 300 may perform a function of acquiring an image of the sample SA. That is, the image acquisition unit 300 may perform a function of acquiring an image of the sample SA, in which the PCR process is completed, in order to analyze the genetic material amplified through the PCR process.
  • the acquiring of the image may include obtaining an image of part or all of the plate PL, obtaining an image of part or all of the patch PA, or directly obtaining an image of the sample SA. It can be carried out through the acquisition method.
  • the image acquisition unit 300 may acquire an image of the sample SA in a state where the PCR process is completed, and may acquire an image of the sample SA in the state where the PCR process is performed.
  • the image acquisition unit 300 may include a means for obtaining an image.
  • the image acquisition unit 300 may include image generating means for generating an image, such as an image sensor such as a CMOS or CCD, predetermined light generating means capable of generating a light ray passing through the sample SA, and / Or an optical system for forming an image of light transmitted through the sample SA.
  • the image acquisition unit 300 may detect fluorescence or acquire a fluorescence image for quantitative and / or qualitative analysis of the sample SA.
  • the image generated from the image acquisition unit 300 may have various magnifications.
  • the image may be an image of an enlarged magnification with respect to the sample SA, an image of a positive magnification, or may be an image of a magnified magnification as necessary.
  • the image acquisition unit 300 includes a power member for moving the plate PL on which the sample SA is located, or for moving the components of the image acquisition unit 300 to the sample SA. Image may be obtained.
  • 54 is a flowchart illustrating a PCR process according to an embodiment of the present application.
  • the DNA sample SA may be provided on the plate PL (S1000). As described above, the sample SA may be provided as a mono layer on the plate PL. In addition, the sample SA provided in the mono layer may be fixed to the plate PL in a conventional manner.
  • a procedure for amplifying the DNA included in the sample SA may be performed.
  • the reagent (RA) and temperature conditions required for the heat denaturation step, the annealing step, and the polymerization step should be provided to the sample (SA).
  • the PCR process when a single patch (PA) is used in the PCR process, the PCR process may be performed in the following order.
  • PA single patch
  • the temperature of the sample SA may be adjusted to a thermal denaturation temperature (S2110).
  • the first patch PA may be contacted with the heated plate PL (S2220).
  • the first patch PA is merely meant to refer to any patch PA that can be used in the PCR process, and is not limited to the first patch PA.
  • the reagents RA used in the annealing step may be stored in the first patch PA.
  • the first patch PA may store a liquid material to provide a wet environment to the plate PL.
  • the reagent RA stored in the first patch PA may be provided to the plate PL.
  • the temperature of the sample SA may be adjusted to an annealing temperature (S2130).
  • the temperature of the sample SA may be cooled to an annealing temperature and maintained at the annealing temperature.
  • the temperature of the sample SA may be adjusted to the polymerization reaction temperature (S2140).
  • the temperature of the sample SA may be heated to a polymerization reaction temperature and maintained at a polymerization reaction temperature.
  • the patch PA and / or the plate PL may be heated or cooled, and the sample SA may be directly heated or It can also cool.
  • the heat treatment process of the aforementioned PCR may be repeated any number of times. This may be to increase the amount of amplification of the DNA included in the sample SA.
  • the contact between the plate PL and the first patch PA may be separated (S2150).
  • the contact between the first patch PA and the plate PL is performed while the temperature of the sample SA is being heated to the annealing temperature or the temperature of the sample SA is increased. It can be carried out while maintaining the annealing temperature.
  • the contact between the first patch PA and the plate PL may be performed while the temperature of the sample SA is adjusted to a thermal denaturation temperature or the temperature of the sample SA is maintained at a thermal denaturation temperature. It can also be performed during.
  • the contact between the first patch PA and the plate PL may be performed a plurality of times during one cycle (that is, during the heat denaturation step, the annealing step, and the polymerization reaction step once).
  • the PCR process may be performed in the following order.
  • the temperature of the sample SA may be adjusted to a thermal denaturation temperature (S2210).
  • the temperature of the plate PL may be adjusted.
  • the first patch PA may be contacted (S2220) with the plate PL on which the sample SA is located.
  • the first patch PA may include some or all of the reagents RA required in the annealing step. Through contact between the sample SA and the patch PA, some or all of the reagents RA stored in the patch PA may be transferred to the plate PL. This is due to the function of the patch PA due to the expansion of the movable area of the material due to the contact of the patch PA with the plate PL.
  • the temperature of the sample SA may be adjusted to an annealing temperature (S2230). While the temperature of the sample SA is maintained at the annealing temperature, some of the reagents RA transferred from the patch PA may bind to the DNA included in the sample SA.
  • the contact between the first patch PA and the plate PL may be released (S2240).
  • S2240 The contact between the first patch PA and the plate PL may be released (S2240).
  • a part of the reagent RA provided by the first patch PA may be transferred to the plate PL.
  • the reagent RA delivered to the plate PL may be coupled to the sample SA.
  • the second patch PA may contact the plate PL (S2250).
  • the second patch PA may include some or all of the reagents RA required in the polymerization reaction step. Some or all of the reagents RA stored in the second patch PA may move to the plate PL.
  • the temperature of the sample SA may be adjusted to a polymerization reaction temperature (S2260).
  • the temperature of the sample SA may be heated and maintained at a desired temperature in order to be adjusted to the polymerization reaction temperature. While the temperature of the sample SA is maintained at the polymerization reaction temperature, the dNTP may bind to the DNA.
  • the second patch PA and the plate PL may be separated (S2270).
  • the heat treatment process of the aforementioned PCR can be repeated any number of times.
  • the contact between the first patch PA and the plate PL and the contact between the second patch PA and the plate PL are performed for one cycle (that is, a heat denaturation step, an annealing step, and a polymerization reaction). May be performed multiple times).
  • the contact between the first patch PA and the plate PL is performed while the temperature of the sample SA is adjusted to the annealing temperature or the temperature of the sample SA is annealed. It can be carried out while maintaining the temperature.
  • the contact between the first patch PA and the plate PL may be performed while the temperature of the sample SA is adjusted to a thermal denaturation temperature or the temperature of the sample SA is maintained at a thermal denaturation temperature. It can also be performed during.
  • the contact between the second patch PA and the plate PL may be maintained while the temperature of the sample SA is adjusted to the polymerization reaction temperature or the temperature of the sample SA is maintained at the polymerization reaction temperature. May be performed during the process.
  • the contact between the second patch PA and the plate PL may be performed while the temperature of the sample SA is adjusted to the annealing temperature or while the temperature of the sample SA is maintained at the annealing temperature. Can be performed.
  • the first patch PA and the second patch PA are merely meant to refer to any patch PA that can be used in the PCR process, and the above-described first patch PA or the first patch PA may be used. It is not limited to 2 patches PA.
  • the first patch PA and the second patch PA mean a separate patch PA, and the first patch PA and the second patch PA are different from each other. ) Does not have to be stored.
  • the separation of the first patch PA and the second patch PA from the plate PL may be omitted.
  • the second patch (PA) by contacting the first patch (PA) and the second patch (PA) in a state that the first patch (PA) and the plate (PL) is not separated (S2240).
  • Reagent (RA) stored in PA) can be transferred to the plate (PL).
  • the PCR process according to an embodiment of the present application may perform diagnosis for various diseases through a single PCR process.
  • PCR processes for various genetic materials can be performed using patched regions (PAs).
  • PAs patched regions
  • the patch PA may be divided into at least two areas.
  • the patch PA according to the present application forms a water film through contact with the sample SA, and a liquid substance captured in the patch PA may move inside the water film. Using this feature, the patch PA can transfer material to the outer region.
  • the patch PA maintains the form of the material stored in the patch PA even after contact with an external material, while delivering the material in an area similar to the contact area of the patch PA.
  • one patch PA may be divided so that material cannot be moved between the divided regions, and different reagents RA may be transferred to different regions.
  • 57 is a diagram illustrating a PCR process for a plurality of target genetic material according to an embodiment of the present application.
  • primers for different target DNAs may be stored in the first region and the second region.
  • a patch PA
  • primers corresponding to different target DNAs are separately stored in a first region and a second region
  • an image of the sample SA is obtained to obtain a plurality of targets.
  • Diagnosis of genetic material can be performed.
  • the presence or absence of a dielectric material corresponding to a primer stored in the first region for the sample SA is determined by detecting whether the fluorescence is detected in one region of the sample SA corresponding to the first region through a fluorescence image. Can be determined.
  • the presence or absence of a genetic material corresponding to the primer stored in the second region for the sample SA may be determined. .
  • the PCR process using the divided patch PA may be applied to both the PCR process using the single patch PA and the PCR process using the plurality of patches PA.
  • the PCR process can be used to perform a more accurate diagnosis. This is because an independent water film is generated in the region of the sample SA corresponding to the first region and the region of the sample SA corresponding to the second region until the PCR process is completed.
  • a patch PA containing a plurality of types of primers to which different types of coloring reagents RA are attached may be used.
  • the sample SA of the PCR process using a plurality of primers to which different types of coloring reagents (RA) are attached may have various dielectric properties by varying the wavelength band of the light irradiated onto the sample (SA) at the time of image acquisition. Analysis of the substance may be possible.
  • 58 and 59 are views for explaining a PCR process for a plurality of target genetic material according to an embodiment of the present application.
  • one patch PA may include various primers corresponding to sequences of some specific genetic materials.
  • the various primers may be combined with one fluorescent material corresponding to one sequence. That is, a fluorescent material having a wavelength band may be coupled to a primer corresponding to the A genetic sequence, and a fluorescent material having a b wavelength band may be coupled to a primer corresponding to the B genetic sequence.
  • the PCR process may be performed using the patch (PA) containing the various primers.
  • the above-described PCR process using a single patch (PA) or a PCR process method using a plurality of patches (PA) may be applied.
  • the patch (PA) containing the various primers may further include dNTP, DNA polymerase, coenzyme and / or buffer solution.
  • a patch according to an embodiment of the present application may include a primer corresponding to a sequence of a specific genetic material.
  • the primer may be associated with a fluorescent material that develops a different color when the target dielectric material is different.
  • the patch comprising the primer may be one or more.
  • a PCR process may be performed using a first patch including a first primer (primary primer corresponding to A genetic sequence) and a second patch including second primer (primary primer corresponding to B genetic sequence). .
  • the patch may be in contact with the sample SA at a point in time when a primer should be provided to the sample SA.
  • the first patch PA1 may be provided to the sample SA and the second patch PA2 may contact the first patch PA1 when a primer is to be provided to the sample SA. .
  • the second patch PA2 is provided to the sample SA and the first patch PA1 is in contact with the second patch PA2 when the primer SA is to be provided to the sample SA. Can be.
  • An image may be acquired for the sample SA in which the PCR process is completed or progressed.
  • the image of the sample SA may acquire each image for a plurality of wavelength bands.
  • Multiple excitation filters can be used for image acquisition for multiple wavelength bands.
  • the presence of a dielectric material corresponding to the primer coupled to the fluorescent material having a wavelength band by irradiating the light of the wavelength band it is possible to check the presence of the dielectric material corresponding to the primer having a b wavelength band by irradiating the light of the wavelength band b The presence or absence of the corresponding genetic material can be confirmed. Through this, even a PCR process using the one patch can perform a diagnosis for a plurality of diseases.
  • 60 and 61 are views for explaining a PCR process using a plate (PL) and a patch (PA) is provided with a reagent (RA) according to an embodiment of the present application.
  • the plate PL may be coated with some or all of the reagents RA used in the PCR process.
  • the reagent RA applied to the plate PL may be coated. .
  • the plate PL provided with the reagent RA in advance may be manufactured by applying the reagent RA to the plate PL and freeze-drying it. Through this process, the reagent RA may have a constant resistance and maintain a predetermined position on the plate PL.
  • the plate PL coated with the reagent RA may be provided with a wet environment from the patch PA.
  • the patch PA When the patch PA is in contact with the plate PL, the liquid substance trapped in the patch PA may move to the plate PL, and the plate PL may move to the plate PL.
  • Wet environments can be provided.
  • the reagent RA coated on the plate PL is provided with a wet environment by the patch PA, a condition under which the sample SA provided on the plate PL may react with the reagent is established.
  • the temperature of the sample SA is adjusted to an appropriate temperature, the sample SA may undergo a heat denaturation step, an annealing step, or a polymerization reaction step.
  • the condition under which the reagent RA and the sample SA react by the contact of the patch PA and the plate PL is established.
  • the plate PL lead to a similar effect to that of the reagent RA provided to the sample SA.
  • a PCR process using a patch (PA) in a variety of ways that can be easily disclosed or derived by the present application, using the plate (PL) to which the reagent (RA) is applied and the sample (SA)
  • the reagent (RA) may provide a condition for reacting, and the PCR process may be performed using the plate (PL) to which the reagent (RA) is applied.
  • a PCR process may be performed by using a plate PL to which the above-described reagent RA is applied and a patch PA that may provide a wet environment.
  • FIG. 62 is a flowchart illustrating a PCR process using a plate PL and a patch PA provided with a reagent RA according to an embodiment of the present application.
  • the sample SA may be provided to the plate PL to which the reagent RA is applied (S2310).
  • the reagent RA (hereinafter, referred to as a first material) applied to the plate PL may mean a part or all of the reagent RA used in the PCR process.
  • the sample SA provided on the plate PL may be fixed to the plate PL to prevent the patch PA from being absorbed into the patch PA when the contact between the patch PA and the plate PL is separated. Can be.
  • the sample SA provided on the plate PL and the patch PA may contact each other (S2320).
  • the first material provided with the wet environment by the contact is mobile. Accordingly, the first material may move within the region where the sample SA is applied, and may move to the patch PA.
  • the liquid material (hereinafter, the second material) provided on the plate PL may move to the sample SA by the patch PA. Will be.
  • the temperature of the sample SA may be adjusted (S2330).
  • the temperature of the sample SA may be sequentially adjusted to a heat denaturation step, an annealing step and a polymerization reaction step. While the temperature of the sample SA is controlled and maintained at an appropriate temperature, the DNA included in the sample SA and the first material may bind. Alternatively, the DNA included in the sample SA and the second material may bind to each other. Alternatively, the second material may bind to the first material.
  • DNA contained in the sample (SA) can be amplified.
  • the sample (SA) and the patch (PA) may be separated (S2340).
  • the liquid material on the plate except for some of the material (SA) and the sample (SA) bonded to the plate (PL) to the patch (PA) can be absorbed again.
  • the sample SA and the patch PA the sample SA and the material provided on the plate PL may be absorbed into the patch PA.
  • FIG. 63 is a flowchart illustrating a method of controlling contact between a patch PA and a plate PL according to an embodiment of the present application.
  • This embodiment may be applied in the process of adjusting the temperature of the plate PL to a thermal denaturation temperature.
  • the thermal denaturation temperature is generally high compared to the temperature of the sample (SA) provided or the polymerization reaction temperature in the previous cycle. Therefore, in order to adjust the temperature of the sample SA to a thermal denaturation temperature, it may be required to heat the plate PL (S2410). The heating may be performed by the temperature control unit 200.
  • the temperature of the plate PL may be checked at any time or continuously (S2420).
  • the checked temperature of the plate PL is higher than or equal to a preset reference temperature, whether the patch PA is in contact with the plate PL may be adjusted (S2430).
  • the patch PA when the patch PA is made of a material that is denatured to heat, there is a problem that the patch PA may be modified if the temperature of the plate PL is higher than that of the patch PA. .
  • the temperature of the plate PL is checked, and when the temperature of the plate PL is higher than the reference temperature (that is, the temperature at which the patch PA is denatured).
  • the plate PL and the patch PA may be separated. Contact between the patch PA and the plate PL may be controlled by the relative position adjusting unit 100.
  • the contact between the patch PA and the plate PL may be controlled according to the temperature of the sample SA.
  • the temperature of the sample SA provided to the plate PL may be checked at any time or continuously while the plate PL is heated.
  • the confirmed temperature of the sample SA is higher than or equal to a preset reference temperature, whether the patch PA contacts the plate PL may be adjusted.
  • the sample SA may be heated in a process of adjusting to a thermal denaturation temperature.
  • the patch PA eg, the patch PA including the primer
  • the plate PL By controlling the contact of the patch (PA) and the plate (PL) to provide the reagent (RA) to the sample (SA) when the temperature of the sample (SA) is above the reference temperature, similar to the general Hot-start PCR process Enable effects. This has the meaning that the same effect can be obtained by omitting the inconvenient process of separating the upper and lower materials by using wax in the existing Hot-start PCR.
  • the temperature of the patch PA and / or the plate PL may be controlled. have.
  • 65 is a flowchart illustrating a method of controlling the temperature of the sample SA by adjusting the temperature of the patch PA according to an embodiment of the present application.
  • the temperature of the patch PA may be adjusted (S2510).
  • the temperature of at least a portion of the area in contact with the patch PA may be adjusted. Temperature control of the patch PA may be performed by the temperature control unit 200.
  • the temperature of the patch PA is adjusted to a temperature suitable for the current step (for example, in the case of the annealing step, the temperature of the patch PA is adjusted to a temperature for adjusting the temperature of the sample SA to the annealing temperature).
  • the patch PA and the plate PL may contact each other.
  • the patch PA may include some or all of the reagents RA required for the current step.
  • the patch PA and the plate PL may be in contact with each other and maintained for a predetermined time. This may be to provide time for the sample SA to be adjusted to the appropriate temperature in each step.
  • the plate PL and the patch PA may be separated (S2530).
  • the plate PL and the patch PA may be separated to heat or cool the patch PA.
  • the temperature of some or all of the plurality of patches PA may be adjusted.
  • the sample ( The temperature of SA) may be adjusted and the temperature of the third patch PA may not be adjusted.
  • At least some of the patches PA may be adjusted to different temperatures.
  • the plurality of patches PA may be adjusted to temperatures appropriate for each step.
  • the first patch PA is heated to a proper temperature to adjust the temperature of the sample SA in contact with the first patch PA
  • the second patch PA is adjusted to a proper temperature in the annealing step.
  • the third patch PA is heated to an appropriate temperature to contact the third patch PA.
  • the temperature of the sample SA may be adjusted.
  • At least some of the patches PA may be sequentially adjusted in temperature. At least a portion of the plurality of patches PA may be adjusted at the same time.
  • FIG. 66 is a view for explaining the effect of adjusting the temperature of the sample SA by using the plurality of patches PA according to an embodiment of the present application.
  • each step by using a different patch (PA) in each step, at least some of the reagents (RA) used in each step is stored in each patch (PA), and the temperature of each patch (PA) is adjusted. .
  • the PCR process according to the present embodiment can reduce the time spent for temperature control. More specifically, the time of ⁇ t2 is reduced in the period controlled by the annealing temperature, and the time of ⁇ t3 is reduced in the interval controlled by the polymerization reaction temperature, thereby enabling a faster PCR process.
  • the plate (PL) may be further used to adjust the temperature of the sample (SA). have. Temperature control by the patch PA and temperature control by the plate PL may be performed sequentially or simultaneously. In this case, the efficiency of temperature control of the sample SA using the plurality of patches PA may be significantly improved compared to a conventional PCR process.
  • the separate material may be a metal material. That is, in the step of adjusting the temperature of the patch PA (S2510), the temperature of the metal material may be adjusted, and the plate PL and the metal material may contact with each other to adjust the temperature of the sample SA. have.
  • Temperature control of the sample SA using the metal material may be performed in a process in which the temperature of the sample SA is adjusted to a thermal denaturation temperature. This may be advantageous considering that there is no reagent (RA) to be provided to the sample (SA) in the heat denaturation step, and that the temperature of the sample (SA) should be adjusted to about 90 ° C or more. In other words, there is no need to deliver reagent (RA) to the sample (SA) by using the transfer function of the patch (PA), there is no possibility of denaturation in the heat of about 90 °C, metal material has a good thermal conductivity PCR process Can reduce the time spent.
  • the temperature control unit 200 may include a thermoelectric element.
  • a thermoelectric element eg, a Peltier element
  • an electric current ie, a Peltier effect
  • Controlling the temperature using the thermoelectric element has advantages in that not only the heating of the temperature control target but also the cooling is possible, the endotherm and the heat generation are freely switched according to the current direction, and the constant temperature is excellent.
  • the PCR process according to the embodiment of the present application may be performed on an RNA sample (SA).
  • SA RNA sample
  • the RNA sample (SA) may be synthesized into DNA through a reverse transcription PCR process. Conventional PCR can be performed on the synthesized DNA.
  • 67 is a flowchart illustrating a process of performing a PCR process on an RNA sample (SA) according to an embodiment of the present application.
  • the RNA sample SA may be provided to the plate PL (S4000).
  • the step of providing the RNA sample SA to the plate PL (S4000) may be performed similarly to the step of providing the DNA sample SA to the plate PL (S1000).
  • RNA sample SA provided on the plate PL may be synthesized with DNA (S5000). MRNA contained in the RNA sample (SA) can be synthesized by cDNA.
  • RNA contained in the sample (SA) into DNA reverse transcriptase, a primer, dNTP may be used.
  • the procedure by which RNA is synthesized into DNA may be similar to the procedure by which DNA is amplified, although the reagent (RA) used must be altered by the DNA polymerase to reverse transcriptase. Therefore, even if the sample (SA) is RNA, it is a matter of course that the technical spirit and embodiments disclosed herein can be applied.
  • the patch (PA) used in the DNA synthesis process may be a first patch (PA) including a primer and a second patch (PA) including a dNTP and a reverse transcriptase. Therefore, the process may be similar to the PCR process described with reference to FIG. 56.
  • RNA sample (SA) can be heated.
  • the RNA sample (SA) may be maintained at a temperature for a predetermined time after heating. Preferred temperatures can be varied depending on the manual of the reagent (RA) used.
  • the plate PL and the first patch PA may contact each other.
  • the RNA sample SA is in contact with the first patch PA, and primers captured in the first patch PA may be moved to the RNA sample SA by the first patch PA. .
  • the temperature of the RNA sample (SA) can be adjusted to allow the primer to bind to the RNA.
  • the primer and a part of the sample (SA) may be combined. Thereafter, the plate PL and the first patch PA may be separated.
  • the plate PL and the second patch PA may contact each other.
  • the reagent RA stored in the second patch PA may move to the RNA sample SA.
  • the moving reagent (RA) may be dNTP and reverse transcriptase.
  • the temperature of the sample may be adjusted to allow dNTP to be bound to RNA and synthesized into DNA. If the temperature of the RNA is maintained for a certain time, DNA can be synthesized.
  • the RNA sample (SA) may be cooled for a certain time before the transfer of dNTP and reverse transcriptase to the RNA sample (SA). For example, this process may be performed when the reaction temperature of the reverse transcriptase is lower than that of 55-60 °C.
  • PCR may be performed on the synthesized DNA. That is, the synthesized DNA can be amplified (S6000).
  • the process of amplifying the DNA may be a PCR process using a patch (PA) that can be performed by the present specification, or may be a general PCR process.
  • PA patch
  • An image may be acquired (S7000) from the sample SA on which the DNA amplification is completed.
  • the patch PA may not only be used in a PCR process for amplifying DNA, but also used to determine whether a target DNA is included in a sample (SA), which is already randomly amplified. Can be.
  • the patch (PA) may have a primer corresponding to the sequence of the target DNA to be detected.
  • a label such as a fluorescent substance may be attached to the primer.
  • the patch (PA) storing the primer and the plate (PL) may be contacted and separated. Through the contact and separation of the patch (PA) and the plate (PL), the primers stored in the patch (PA) can bind to some DNA of the DNA contained in the sample (SA), it can not bind The remaining primer can be absorbed back into the patch (PA).
  • the sample SA subjected to the PCR process may be stored in the patch PA.
  • a label such as a fluorescent substance may be attached to the DNA (or RNA) included in the sample SA.
  • the plate PL in contact with the patch PA may be coated with a strand of DNA molecules (eg, a DNA probe).
  • the plate PL and the patch PA may be contacted and separated.
  • the DNA molecules coated on the plate PL may bind to the DNA (or RNA) stored in the patch PA.
  • the sample (SA) except for the DNA (or RNA) bound to the DNA molecule may be absorbed back into the patch (PA).
  • sample SA has DNA (or RNA) that complementarily binds to the DNA molecule, fluorescence may be detected in the region where the DNA molecule is located. Therefore, whether or not the target DNA is included in the sample SA may be confirmed.
  • first patch (PA) means that they are separate patches (PA) that are physically separated, It does not necessarily mean a patch (PA) that stores different reagents (RA).
  • the diagnostic apparatus may perform the PCR process described so far. Even if the details are not repeated, it will be easily understood by those skilled in the art of the present application, and thus, the description of the process in the mechanical aspect is omitted.

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Abstract

L'invention concerne un timbre de réaction en chaîne par polymérase (PCR), se présentant sous la forme d'un gel structuré en réseau ayant des micro-cavités qui, selon un mode de réalisation de la présente invention, stocke une partie d'une pluralité de réactifs utilisés dans une réaction en chaîne par polymérase dans les micro-cavités, et démarre une réaction en chaîne par polymérase avec un ADN cible contenu dans un échantillon situé dans une région externe lorsque le timbre entre en contact avec ce dernier et le réactif stocké dans les micro-cavités se déplace vers au moins une partie de la région externe.
PCT/KR2017/002026 2016-02-23 2017-02-23 Timbre de réaction en chaîne par polymérase, et procédé et appareil de diagnostic l'utilisant WO2017146502A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US16/079,360 US11808677B2 (en) 2016-02-23 2017-02-23 Polymerase chain reaction patch, method and device for diagnosis using the same
CN201780025053.0A CN109073627B (zh) 2016-02-23 2017-02-23 聚合酶链式反应贴片以及使用该贴片进行诊断的方法和装置
EP17756840.9A EP3421991A4 (fr) 2016-02-23 2017-02-23 Timbre de réaction en chaîne par polymérase, et procédé et appareil de diagnostic l'utilisant

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US201662298959P 2016-02-23 2016-02-23
US62/298,959 2016-02-23
KR1020160069936A KR20170099737A (ko) 2016-02-23 2016-06-04 접촉식 염색 패치 및 이를 이용하는 염색 방법
KR10-2016-0069938 2016-06-04
KR1020160069937A KR20170099738A (ko) 2016-02-23 2016-06-04 접촉식 염색 패치 및 그 제조 방법
KR10-2016-0069937 2016-06-04
KR1020160069938A KR20170099739A (ko) 2016-02-23 2016-06-04 접촉식 염색 보조 패치, 그 제조 방법 및 이를 이용하는 염색 방법
KR10-2016-0069936 2016-06-04
KR10-2016-0095739 2016-07-27
KR1020160095739A KR20170099741A (ko) 2016-02-23 2016-07-27 테스트 키트
KR10-2016-0118462 2016-09-13
KR1020160118462A KR20170099742A (ko) 2016-02-23 2016-09-13 테스트 키트 및 이를 이용하는 염색 방법
KR10-2016-0144551 2016-11-01
KR1020160144551A KR20170099745A (ko) 2016-02-23 2016-11-01 진단 방법 및 이를 수행하는 기기
KR10-2017-0024387 2017-02-23
KR1020170024387A KR102045068B1 (ko) 2016-02-23 2017-02-23 중합 효소 연쇄 반응 패치, 이를 이용하는 진단 방법 및 장치

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