# US 12,181,390 B2 · Substance labeling patch, method and apparatus for tissue diagnosis using the same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,181,390 B2 - Document ID: US12181390B2 - Status: Granted - Kind: B2 - Application number: 18/364,392 - Filed: 2023-08-02 - Published: 2023-12-07 - Granted: 2024-12-31 - Earliest claimed: 2016-02-23 - Assignees: Noul Co., Ltd. - Applicants: Noul Co., Ltd. - Inventors: Dong Young Lee; Chan Yang Lim; Kyung Hwan Kim - Web page: https://patentgrep.com/patent/US12181390B2 ## CPC - G01N 1/312: {for samples mounted on planar substrates} - B01F 33/3039: with mixing achieved by diffusion between layers - B01L 3/00: Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers - C07K 16/3061: {Blood cells} - C12Q 1/6844: Nucleic acid amplification reactions - C12Q 1/6848: characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction - C12Q 1/686: Polymerase chain reaction [PCR] - C12Q 1/701: {Specific hybridization probes} - G01N 1/2813: {Producing thin layers of samples on a substrate, e.g. smearing, spinning-on (G01N1/30 takes precedence)} - G01N 1/30: Staining; Impregnating {; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis} - G01N 1/31: Apparatus therefor - G01N 15/06: Investigating concentration of particle suspensions (by weighing G01N5/00; investigating sedimentation of particle suspensions G01N15/04; investigating individual particles G01N15/10) - G01N 15/14: Optical investigation techniques, e.g. flow cytometry - G01N 21/77: by observing the effect on a chemical indicator - G01N 33/48: Biological material, e.g. blood, urine (G01N33/02, G01N33/26, G01N33/44, G01N33/46 take precedence); Haemocytometers (counting blood corpuscules distributed over a surface by scanning the surface G06M11/02) - G01N 33/4833: {of solid biological material, e.g. tissue samples, cell cultures (tissue in vivo A61B5/00; cell suspensions G01N33/48735)} - G01N 33/49: Blood {(chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80)} - G01N 33/5082: {Supracellular entities, e.g. tissue, organisms} - G01N 33/52: Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper {and including single- and multilayer analytical elements (immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72)} - G01N 33/53: Immunoassay; Biospecific binding assay; Materials therefor - G01N 33/5304: {Reaction vessels, e.g. agglutination plates (for solid-phase systems G01N33/543)} - G01N 33/533: with fluorescent label - G01N 33/543: with an insoluble carrier for immobilising immunochemicals - G01N 33/558: using diffusion or migration of antigen or antibody {(immunochromatographic test strips G01N33/54387)} - G01N 33/575: for cancer - G01N 33/58: involving labelled substances (G01N33/53 takes precedence) - G01N 33/60: involving radioactive labelled substances - G06T 7/0012: {Biomedical image inspection} - G06T 7/0014: {using an image reference approach} - B01L 3/505: {Flexible containers without fluid transport within} - B01L 7/52: {with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples} - G01N 15/01: specially adapted for biological cells, e.g. blood cells (investigating sedimentation of particle suspensions in blood G01N15/05) - G01N 15/075: by optical means - G01N 21/6428: {Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53)} - G01N 21/6458: {Fluorescence microscopy (fluorescence microscopes per se G02B21/0076 and G02B21/16)} - G01N 2001/302: {Stain compositions} - G01N 2021/7723: {Swelling part, also for adsorption sensor, i.e. without chemical reaction} - G01N 2021/7786: {Fluorescence} - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - Y02P 20/582: Recycling of unreacted starting or intermediate materials - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - B01F: MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING (mixing paints B44D3/06) - B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - G06T: IMAGE DATA PROCESSING OR GENERATION, IN GENERAL - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE - Y02P: CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS ## Abstract The present disclosure relates to a tissue diagnosis device including a plate supporter configured to support a plate on which a reaction region is placed and a sample is placed in the reaction region, a patch controller configured to support the patch which contains a labeling substance that specifically labels the target substance, and control a position of the patch relative to the reaction region so that the patch provides the labeling substance to the reaction region, and a target substance detector configured to detect the labeling substance and detect the target substance included in the tissue sample. ## Claims ### Claim 1 A tissue diagnosis method for detecting a target substance from a tissue sample by using a patch which includes a mesh structural body forming micro-cavities and is configured to contain a substance in the micro-cavities, the tissue diagnosis method comprising: placing the tissue sample in a reaction region; providing a fluorescence labeling substance for specifically labeling the target substance to the tissue sample by using the patch which contains the fluorescence labeling substance; and detecting the fluorescence-labeled target substance from the tissue sample. ### Claim 2 (depends on 1) The tissue diagnosis method of claim 1, wherein the fluorescence labeling substance is a fluorescence labeling complex that includes a reaction derivative that reacts specifically with the target substance and a fluorescence marker for detecting the target substance. ### Claim 3 (depends on 1) The tissue diagnosis method of claim 1, wherein the detecting of the fluorescence-labeled target substance is performed by acquiring a fluorescence image of the tissue sample. ### Claim 4 (depends on 1) The tissue diagnosis method of claim 1, wherein: the target substance is a target base sequence included in the tissue sample; and the fluorescence labeling substance includes a fluorescence-labeled nucleic acid probe, the nucleic acid probe binding complementarily to the target base sequence. ### Claim 5 (depends on 1) The tissue diagnosis method of claim 1, wherein: the target substance is a target protein included in the tissue sample; and the fluorescence labeling substance include a fluorescence-labeled antibody, the antibody binds specifically to the target protein. ### Claim 6 (depends on 1) The tissue diagnosis method of claim 1, wherein the providing of the fluorescence labeling substance to the tissue sample includes: contacting the patch containing the fluorescence labeling substance with the tissue sample; and when the patch is in contact with the tissue sample, the fluorescence labeling substance is allowed to move to the reaction region. ### Claim 7 (depends on 6) The tissue diagnosis method of claim 6, wherein: the providing of the fluorescence labeling substances to the tissue sample further includes separating the patch containing the fluorescence labeling substances from the tissue sample; and when the patch is separated from the tissue sample, a residual fluorescence labeling substance that has not bound to the target substance of the fluorescence labeling substance is removed from the reaction region. ### Claim 8 (depends on 1) The tissue diagnosis method of claim 1, wherein the detecting of the fluorescence-labeled target substance is performed by measuring an amount of fluorescence emitted from the target substance included in the tissue sample. ### Claim 9 (depends on 1) The tissue diagnosis method of claim 1, wherein the detecting of the fluorescence-labeled target substance includes obtaining information on distribution of the target substance in the tissue sample. ### Claim 10 A tissue diagnosis method for detecting a target substance from a tissue sample by using a patch which includes a mesh structural body forming micro-cavities and is configured to contain a substance in the micro-cavities, the tissue diagnosis method comprising: placing the tissue sample in a reaction region; providing a first fluorescence labeling substance for specifically labeling a first target substance to the tissue sample by using the patch which contains the first fluorescence labeling substance; and providing a second fluorescence labeling substance for specifically labeling a second target substance to the tissue sample by using a patch that contains the second fluorescence labeling substance. ### Claim 11 (depends on 10) The tissue diagnosis method of claim 10, wherein: a wavelength band from which fluorescence emitted from the first fluorescence labeling substance is detected and a wavelength band from which fluorescence emitted from the second fluorescence labeling substance is detected are different from each other; and the tissue diagnosis method further includes, after the providing of the second florescence labeling substance to the tissue sample, detecting the first target substance and the second target substance included in the tissue sample. ### Claim 12 (depends on 10) The tissue diagnosis method of claim 10, further comprising: after the providing of the first fluorescence labeling substance to the tissue sample, detecting the first target substance included in the tissue sample by detecting fluorescence emitted from the first fluorescence labeling substance; and after the providing of the second fluorescence labeling substance to the tissue sample, detecting the second target substance included in the tissue sample by detecting fluorescence emitted from the second fluorescence labeling substance. ### Claim 13 (depends on 12) The tissue diagnosis method of claim 12, wherein: a wavelength band from which the fluorescence emitted from the first fluorescence labeling substance is detected and a wavelength band from which the fluorescence is emitted from the second fluorescence labeling substance is detected at least partially overlap each other; and the detecting of the fluorescence emitted from the second fluorescence labeling substance is performed by comparing fluorescence detected from the tissue sample after the second fluorescence labeling substance is provided to the tissue sample and fluorescence detected from the tissue sample before the second fluorescence labeling substance is provided to the tissue sample.