ES2627063T3 - Detección de proteína a través de nanoinformadores - Google Patents
Detección de proteína a través de nanoinformadores Download PDFInfo
- Publication number
- ES2627063T3 ES2627063T3 ES10824048.2T ES10824048T ES2627063T3 ES 2627063 T3 ES2627063 T3 ES 2627063T3 ES 10824048 T ES10824048 T ES 10824048T ES 2627063 T3 ES2627063 T3 ES 2627063T3
- Authority
- ES
- Spain
- Prior art keywords
- protein
- probe
- oligo
- signal
- nanoinformer
- Prior art date
- Legal status (The legal status 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 status listed.)
- Active
Links
- 238000002331 protein detection Methods 0.000 title description 10
- 239000000523 sample Substances 0.000 claims abstract description 384
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 346
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 345
- 238000000034 method Methods 0.000 claims abstract description 177
- 230000027455 binding Effects 0.000 claims abstract description 98
- 239000011159 matrix material Substances 0.000 claims abstract description 31
- 239000003550 marker Substances 0.000 claims description 77
- 238000001514 detection method Methods 0.000 claims description 70
- 230000000295 complement effect Effects 0.000 claims description 61
- 150000007523 nucleic acids Chemical class 0.000 claims description 39
- 239000011324 bead Substances 0.000 claims description 35
- 102000039446 nucleic acids Human genes 0.000 claims description 33
- 108020004707 nucleic acids Proteins 0.000 claims description 33
- 108091033319 polynucleotide Proteins 0.000 claims description 16
- 102000040430 polynucleotide Human genes 0.000 claims description 16
- 239000002157 polynucleotide Substances 0.000 claims description 16
- 230000004224 protection Effects 0.000 claims description 16
- 239000002773 nucleotide Substances 0.000 claims description 10
- 125000003729 nucleotide group Chemical group 0.000 claims description 10
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 8
- 108010043958 Peptoids Proteins 0.000 claims description 7
- 108091081062 Repeated sequence (DNA) Proteins 0.000 claims description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 78
- 239000000203 mixture Substances 0.000 description 40
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 32
- 238000009396 hybridization Methods 0.000 description 32
- 239000000243 solution Substances 0.000 description 29
- 238000000746 purification Methods 0.000 description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 23
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 22
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 22
- 238000013459 approach Methods 0.000 description 20
- 238000011002 quantification Methods 0.000 description 20
- 238000003556 assay Methods 0.000 description 19
- 239000003153 chemical reaction reagent Substances 0.000 description 18
- 108091023037 Aptamer Proteins 0.000 description 17
- 238000005259 measurement Methods 0.000 description 17
- 238000004458 analytical method Methods 0.000 description 16
- 239000011616 biotin Substances 0.000 description 16
- 229960002685 biotin Drugs 0.000 description 16
- 235000020958 biotin Nutrition 0.000 description 16
- 238000010586 diagram Methods 0.000 description 16
- 239000000178 monomer Substances 0.000 description 16
- 230000035945 sensitivity Effects 0.000 description 16
- 201000010099 disease Diseases 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 102000000588 Interleukin-2 Human genes 0.000 description 14
- 108010002350 Interleukin-2 Proteins 0.000 description 14
- 230000008901 benefit Effects 0.000 description 14
- 108020004414 DNA Proteins 0.000 description 13
- 108010090804 Streptavidin Proteins 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 11
- 239000003599 detergent Substances 0.000 description 11
- 238000010828 elution Methods 0.000 description 11
- 241000700605 Viruses Species 0.000 description 10
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 10
- 150000001413 amino acids Chemical group 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- -1 but not limited to Chemical class 0.000 description 8
- 238000003745 diagnosis Methods 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 238000004393 prognosis Methods 0.000 description 8
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 7
- 108091005804 Peptidases Proteins 0.000 description 7
- 239000004365 Protease Substances 0.000 description 7
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 7
- 230000009977 dual effect Effects 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000002853 nucleic acid probe Substances 0.000 description 7
- 235000019419 proteases Nutrition 0.000 description 7
- 102000012410 DNA Ligases Human genes 0.000 description 6
- 108010061982 DNA Ligases Proteins 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 230000029087 digestion Effects 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000012678 infectious agent Substances 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 241000972773 Aulopiformes Species 0.000 description 5
- 241000282414 Homo sapiens Species 0.000 description 5
- 102000003960 Ligases Human genes 0.000 description 5
- 108090000364 Ligases Proteins 0.000 description 5
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 5
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 5
- 239000003086 colorant Substances 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 235000019515 salmon Nutrition 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- 101710086015 RNA ligase Proteins 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000000090 biomarker Substances 0.000 description 4
- 150000001718 carbodiimides Chemical class 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 4
- 238000010494 dissociation reaction Methods 0.000 description 4
- 230000005593 dissociations Effects 0.000 description 4
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 238000005304 joining Methods 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 241001515965 unidentified phage Species 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 108010067770 Endopeptidase K Proteins 0.000 description 3
- 206010018498 Goitre Diseases 0.000 description 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 108010079855 Peptide Aptamers Proteins 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 108020004682 Single-Stranded DNA Proteins 0.000 description 3
- 102100040247 Tumor necrosis factor Human genes 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 239000012472 biological sample Substances 0.000 description 3
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 3
- 238000012790 confirmation Methods 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 230000009260 cross reactivity Effects 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 208000026278 immune system disease Diseases 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 239000004005 microsphere Substances 0.000 description 3
- 108091008104 nucleic acid aptamers Proteins 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 238000004445 quantitative analysis Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 229940035893 uracil Drugs 0.000 description 3
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- 230000010777 Disulfide Reduction Effects 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 241000205156 Pyrococcus furiosus Species 0.000 description 2
- 241000194017 Streptococcus Species 0.000 description 2
- 241000589500 Thermus aquaticus Species 0.000 description 2
- 241000589499 Thermus thermophilus Species 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 210000000941 bile Anatomy 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- OOTFVKOQINZBBF-UHFFFAOYSA-N cystamine Chemical compound CCSSCCN OOTFVKOQINZBBF-UHFFFAOYSA-N 0.000 description 2
- 229940099500 cystamine Drugs 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 210000003722 extracellular fluid Anatomy 0.000 description 2
- 210000000416 exudates and transudate Anatomy 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 201000003872 goiter Diseases 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- SLPWXZZHNSOZPX-UHFFFAOYSA-N imidazole-1-carbonitrile Chemical compound N#CN1C=CN=C1 SLPWXZZHNSOZPX-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000003071 parasitic effect Effects 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000010069 protein adhesion Effects 0.000 description 2
- 238000000164 protein isolation Methods 0.000 description 2
- 230000009145 protein modification Effects 0.000 description 2
- 239000012521 purified sample Substances 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- VHYRHFNOWKMCHQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-formylbenzoate Chemical compound C1=CC(C=O)=CC=C1C(=O)ON1C(=O)CCC1=O VHYRHFNOWKMCHQ-UHFFFAOYSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- ODMSFJDLANJZHJ-UHFFFAOYSA-N 6-hydrazinylpyridine-3-carbohydrazide Chemical compound NNC(=O)C1=CC=C(NN)N=C1 ODMSFJDLANJZHJ-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 230000035502 ADME Effects 0.000 description 1
- 102100023157 AT-rich interactive domain-containing protein 2 Human genes 0.000 description 1
- 101710189264 AT-rich interactive domain-containing protein 2 Proteins 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 208000008190 Agammaglobulinemia Diseases 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 206010002961 Aplasia Diseases 0.000 description 1
- 206010053555 Arthritis bacterial Diseases 0.000 description 1
- 241000244185 Ascaris lumbricoides Species 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000004300 Atrophic Gastritis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 206010064539 Autoimmune myocarditis Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 241000206761 Bacillariophyta Species 0.000 description 1
- 241000228405 Blastomyces dermatitidis Species 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 241000589562 Brucella Species 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 241001112696 Clostridia Species 0.000 description 1
- 241000223205 Coccidioides immitis Species 0.000 description 1
- 206010010099 Combined immunodeficiency Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 201000007336 Cryptococcosis Diseases 0.000 description 1
- 241000221204 Cryptococcus neoformans Species 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 108060002063 Cyclotide Proteins 0.000 description 1
- 102100025621 Cytochrome b-245 heavy chain Human genes 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 241000199914 Dinophyceae Species 0.000 description 1
- 241000866683 Diphyllobothrium latum Species 0.000 description 1
- 235000003550 Dracunculus Nutrition 0.000 description 1
- 241000316827 Dracunculus <angiosperm> Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000224432 Entamoeba histolytica Species 0.000 description 1
- 241000498255 Enterobius vermicularis Species 0.000 description 1
- 241000194032 Enterococcus faecalis Species 0.000 description 1
- 241000194031 Enterococcus faecium Species 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000000571 Fibrocystic breast disease Diseases 0.000 description 1
- 208000004262 Food Hypersensitivity Diseases 0.000 description 1
- 206010016946 Food allergy Diseases 0.000 description 1
- 241000589601 Francisella Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 208000036495 Gastritis atrophic Diseases 0.000 description 1
- 241000224466 Giardia Species 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
- 208000003807 Graves Disease Diseases 0.000 description 1
- 208000003084 Graves Ophthalmopathy Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 241000711549 Hepacivirus C Species 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 241000228404 Histoplasma capsulatum Species 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 241000701806 Human papillomavirus Species 0.000 description 1
- 208000029422 Hypernatremia Diseases 0.000 description 1
- 206010020983 Hypogammaglobulinaemia Diseases 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 208000004575 Infectious Arthritis Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 241000222722 Leishmania <genus> Species 0.000 description 1
- 201000001779 Leukocyte adhesion deficiency Diseases 0.000 description 1
- 206010024434 Lichen sclerosus Diseases 0.000 description 1
- 241000186779 Listeria monocytogenes Species 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000545499 Mycobacterium avium-intracellulare Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 208000014767 Myeloproliferative disease Diseases 0.000 description 1
- 108010049175 N-substituted Glycines Proteins 0.000 description 1
- 241000498271 Necator Species 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 206010029379 Neutrophilia Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 241000713112 Orthobunyavirus Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 241000526686 Paracoccidioides brasiliensis Species 0.000 description 1
- 241000606860 Pasteurella Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000021161 Plasma cell disease Diseases 0.000 description 1
- 241000224016 Plasmodium Species 0.000 description 1
- 241000223960 Plasmodium falciparum Species 0.000 description 1
- 241001505293 Plasmodium ovale Species 0.000 description 1
- 241000223810 Plasmodium vivax Species 0.000 description 1
- 241000233872 Pneumocystis carinii Species 0.000 description 1
- 208000008601 Polycythemia Diseases 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108010026552 Proteome Proteins 0.000 description 1
- 241000588770 Proteus mirabilis Species 0.000 description 1
- 241000588767 Proteus vulgaris Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000702263 Reovirus sp. Species 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 241000235527 Rhizopus Species 0.000 description 1
- 241000702670 Rotavirus Species 0.000 description 1
- 241000710799 Rubella virus Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000242678 Schistosoma Species 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- 241000244155 Taenia Species 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000005485 Thrombocytosis Diseases 0.000 description 1
- 241000223996 Toxoplasma Species 0.000 description 1
- 241000869417 Trematodes Species 0.000 description 1
- 241000589886 Treponema Species 0.000 description 1
- 241001489145 Trichuris trichiura Species 0.000 description 1
- 241000223104 Trypanosoma Species 0.000 description 1
- 241000202898 Ureaplasma Species 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 108010059993 Vancomycin Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 206010047697 Volvulus Diseases 0.000 description 1
- 208000016025 Waldenstroem macroglobulinemia Diseases 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 241000607734 Yersinia <bacteria> Species 0.000 description 1
- CPGKMLVTFNUAHL-UHFFFAOYSA-N [Ca].[Ca] Chemical compound [Ca].[Ca] CPGKMLVTFNUAHL-UHFFFAOYSA-N 0.000 description 1
- 206010000269 abscess Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 238000003314 affinity selection Methods 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 208000024998 atopic conjunctivitis Diseases 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 230000006287 biotinylation Effects 0.000 description 1
- 238000007413 biotinylation Methods 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 208000016738 bone Paget disease Diseases 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 208000011803 breast fibrocystic disease Diseases 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 201000007455 central nervous system cancer Diseases 0.000 description 1
- 208000025997 central nervous system neoplasm Diseases 0.000 description 1
- 210000003756 cervix mucus Anatomy 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 208000016644 chronic atrophic gastritis Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000016532 chronic granulomatous disease Diseases 0.000 description 1
- 208000024207 chronic leukemia Diseases 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 208000007118 chronic progressive multiple sclerosis Diseases 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 210000003022 colostrum Anatomy 0.000 description 1
- 235000021277 colostrum Nutrition 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 239000003398 denaturant Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 238000000835 electrochemical detection Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 229940007078 entamoeba histolytica Drugs 0.000 description 1
- 229940032049 enterococcus faecalis Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000020932 food allergy Nutrition 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000008938 immune dysregulation Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940099472 immunoglobulin a Drugs 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 201000007647 intestinal volvulus Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000011379 keloid formation Diseases 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000029226 lipidation Effects 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000023707 liver extraskeletal osteosarcoma Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000002824 mRNA display Methods 0.000 description 1
- 238000002803 maceration Methods 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 238000002705 metabolomic analysis Methods 0.000 description 1
- 230000001431 metabolomic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 238000007837 multiplex assay Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 206010028537 myelofibrosis Diseases 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 238000011170 pharmaceutical development Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 201000006292 polyarteritis nodosa Diseases 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- 238000003498 protein array Methods 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 238000000575 proteomic method Methods 0.000 description 1
- 229940007042 proteus vulgaris Drugs 0.000 description 1
- 238000004451 qualitative analysis Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000002702 ribosome display Methods 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 201000001223 septic arthritis Diseases 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 238000013517 stratification Methods 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000004416 surface enhanced Raman spectroscopy Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/5306—Improving reaction conditions, e.g. reduction of non-specific binding, promotion of specific binding
-
- 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
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2537/00—Reactions characterised by the reaction format or use of a specific feature
- C12Q2537/10—Reactions characterised by the reaction format or use of a specific feature the purpose or use of
- C12Q2537/125—Sandwich assay format
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/54—Interleukins [IL]
- G01N2333/55—IL-2
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2458/00—Labels used in chemical analysis of biological material
- G01N2458/10—Oligonucleotides as tagging agents for labelling antibodies
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- General Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Analytical Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Bioinformatics & Computational Biology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US325224P | 2001-09-27 | ||
| US25119209P | 2009-10-13 | 2009-10-13 | |
| US251192P | 2009-10-13 | ||
| US32522410P | 2010-04-16 | 2010-04-16 | |
| US32678710P | 2010-04-22 | 2010-04-22 | |
| US326787P | 2010-04-22 | ||
| PCT/US2010/052556 WO2011047087A2 (en) | 2009-10-13 | 2010-10-13 | Protein detection via nanoreporters |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2627063T3 true ES2627063T3 (es) | 2017-07-26 |
Family
ID=43855316
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10824048.2T Active ES2627063T3 (es) | 2009-10-13 | 2010-10-13 | Detección de proteína a través de nanoinformadores |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US9714937B2 (enExample) |
| EP (2) | EP2488876B1 (enExample) |
| JP (3) | JP5954876B2 (enExample) |
| AU (1) | AU2010306862B2 (enExample) |
| CA (1) | CA2775613C (enExample) |
| ES (1) | ES2627063T3 (enExample) |
| HK (1) | HK1249580A1 (enExample) |
| WO (1) | WO2011047087A2 (enExample) |
Families Citing this family (140)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5954876B2 (ja) | 2009-10-13 | 2016-07-20 | ナノストリング テクノロジーズ， インコーポレイテッド | ナノレポーターによるタンパク質の検出 |
| EP2534174A4 (en) * | 2010-02-12 | 2015-02-25 | Solulink Inc | Preparation and / or purification of oligonucleotide conjugates |
| US10787701B2 (en) | 2010-04-05 | 2020-09-29 | Prognosys Biosciences, Inc. | Spatially encoded biological assays |
| US20190300945A1 (en) | 2010-04-05 | 2019-10-03 | Prognosys Biosciences, Inc. | Spatially Encoded Biological Assays |
| PT2556171E (pt) | 2010-04-05 | 2015-12-21 | Prognosys Biosciences Inc | Ensaios biológicos codificados espacialmente |
| US9523680B2 (en) * | 2010-06-30 | 2016-12-20 | Ambergen, Inc. | Global Proteomic screening of random bead arrays using mass spectrometry imaging |
| EP2622103B2 (en) | 2010-09-30 | 2022-11-16 | Bio-Rad Laboratories, Inc. | Sandwich assays in droplets |
| US9150852B2 (en) | 2011-02-18 | 2015-10-06 | Raindance Technologies, Inc. | Compositions and methods for molecular labeling |
| GB201106254D0 (en) | 2011-04-13 | 2011-05-25 | Frisen Jonas | Method and product |
| JP2014531908A (ja) | 2011-10-14 | 2014-12-04 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 構造アッセンブリによる配列決定 |
| US9410934B2 (en) | 2011-10-20 | 2016-08-09 | Exxonmobil Upstream Research Company | Nanoparticle probes, methods, and systems for use thereof |
| WO2013067489A1 (en) * | 2011-11-05 | 2013-05-10 | President And Fellows Of Harvard College | Nucleic acid-based linkers for detecting and measuring interactions |
| ES2700792T3 (es) | 2011-11-11 | 2019-02-19 | Eli N Glezer | Procedimientos de ensayo asistidos por coagente de unión |
| ES2991004T3 (es) | 2011-12-22 | 2024-12-02 | Harvard College | Métodos para la detección de analitos |
| ES2952728T3 (es) | 2011-12-22 | 2023-11-03 | Harvard College | Métodos para la detección de analitos |
| EP4361607A3 (en) | 2012-02-03 | 2024-07-17 | California Institute of Technology | Signal encoding and decoding in multiplexed biochemical assays |
| WO2013184754A2 (en) | 2012-06-05 | 2013-12-12 | President And Fellows Of Harvard College | Spatial sequencing of nucleic acids using dna origami probes |
| EP2880184B1 (en) | 2012-08-03 | 2021-03-31 | California Institute of Technology | Multiplexing and quantification in pcr with reduced hardware and requirements |
| DK3511423T4 (da) | 2012-10-17 | 2024-07-29 | Spatial Transcriptomics Ab | Fremgangsmåder og produkt til optimering af lokaliseret eller rumlig detektion af genekspression i en vævsprøve |
| US10829816B2 (en) | 2012-11-19 | 2020-11-10 | Apton Biosystems, Inc. | Methods of analyte detection |
| CA2891939C (en) | 2012-11-19 | 2020-10-27 | Apton Biosystems, Inc. | Digital analysis of molecular analytes using single molecule detection |
| US10138509B2 (en) | 2013-03-12 | 2018-11-27 | President And Fellows Of Harvard College | Method for generating a three-dimensional nucleic acid containing matrix |
| AU2014248759B2 (en) | 2013-03-13 | 2020-02-27 | Meso Scale Technologies, Llc. | Improved assay methods |
| US10114015B2 (en) | 2013-03-13 | 2018-10-30 | Meso Scale Technologies, Llc. | Assay methods |
| RU2690935C2 (ru) | 2013-06-04 | 2019-06-06 | Президент Энд Фэллоуз Оф Харвард Коллидж | Направляемая рнк регуляция транскрипции |
| EP3587585B1 (en) | 2013-06-12 | 2021-03-24 | The General Hospital Corporation | Methods, kits, and systems for multiplexed detection of target molecules and uses thereof |
| EP4234716A3 (en) | 2013-06-25 | 2023-12-06 | Prognosys Biosciences, Inc. | Methods for determining spatial patterns of biological targets in a sample |
| EP3143401A4 (en) | 2014-05-15 | 2017-10-11 | Meso Scale Technologies, LLC | Improved assay methods |
| EP3143165A4 (en) * | 2014-05-15 | 2018-05-16 | Two Pore Guys, Inc. | Scaffold data storage and target detection in a sample using a nanopore |
| WO2016007839A1 (en) | 2014-07-11 | 2016-01-14 | President And Fellows Of Harvard College | Methods for high-throughput labelling and detection of biological features in situ using microscopy |
| ES3014093T3 (en) | 2014-07-30 | 2025-04-16 | Harvard College | Method for determining nucleic acids |
| CN113403373B (zh) | 2014-11-21 | 2025-04-11 | 布鲁克空间生物学公司 | 无酶且无扩增的测序 |
| SG11201704177SA (en) | 2014-11-24 | 2017-06-29 | Nanostring Technologies Inc | Methods and apparatuses for gene purification and imaging |
| WO2016089588A1 (en) | 2014-12-06 | 2016-06-09 | Children's Medical Center Corporation | Nucleic acid-based linkers for detecting and measuring interactions |
| EP4119677B1 (en) | 2015-04-10 | 2023-06-28 | Spatial Transcriptomics AB | Spatially distinguished, multiplex nucleic acid analysis of biological specimens |
| WO2016196824A1 (en) | 2015-06-02 | 2016-12-08 | Children's Medical Center Corporation | Nucleic acid complexes for screening barcoded compounds |
| US12077807B2 (en) | 2015-06-27 | 2024-09-03 | The Research Foundation For The State University Of New York | Compositions and methods for analyte detection using nanoswitches |
| US20170002405A1 (en) * | 2015-06-30 | 2017-01-05 | Nanostring Technologies, Inc. | Methods and kits for simultaneously detecting gene or protein expression in a plurality of sample types using self-assembling fluorescent barcode nanoreporters |
| SG10202107055SA (en) | 2015-07-17 | 2021-08-30 | Nanostring Technologies Inc | Simultaneous quantification of a plurality of proteins in a user-defined region of a cross-sectioned tissue |
| US10640816B2 (en) | 2015-07-17 | 2020-05-05 | Nanostring Technologies, Inc. | Simultaneous quantification of gene expression in a user-defined region of a cross-sectioned tissue |
| CN105132533B (zh) * | 2015-07-24 | 2018-11-23 | 清华大学深圳研究生院 | 一种靶分子浓度的检测方法 |
| US20170081713A1 (en) * | 2015-09-03 | 2017-03-23 | Nanostring Technologies, Inc. | Multivalent probes having single nucleotide resolution |
| JP6882282B2 (ja) | 2015-11-03 | 2021-06-02 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 三次元核酸含有マトリックスの立体撮像のための方法と装置 |
| CN115369161A (zh) | 2015-12-04 | 2022-11-22 | 10X 基因组学有限公司 | 用于核酸分析的方法和组合物 |
| US11965891B2 (en) | 2015-12-30 | 2024-04-23 | Bio-Rad Laboratories, Inc. | Digital protein quantification |
| WO2017139409A1 (en) | 2016-02-09 | 2017-08-17 | Children's Medical Center Corporation | Method for detection of analytes via polymer complexes |
| US10919037B2 (en) | 2016-03-23 | 2021-02-16 | Children's Medical Center Corporation | Systems and apparatus for detecting compounds in human biological samples |
| WO2017165647A1 (en) | 2016-03-23 | 2017-09-28 | Children's Medical Center Corporation | Rapid and sensitive detection and quantification of analytes in complex samples using polymer-based methods |
| EP4613756A3 (en) | 2016-04-25 | 2025-11-12 | President And Fellows Of Harvard College | Hybridization chain reaction methods for in situ molecular detection |
| CN109715825B (zh) | 2016-05-16 | 2023-01-06 | 纳米线科技公司 | 用于检测样品中目标核酸的方法 |
| WO2017218777A1 (en) | 2016-06-17 | 2017-12-21 | California Institute Of Technology | Nucleic acid reactions and related methods and compositions |
| WO2017222453A1 (en) | 2016-06-21 | 2017-12-28 | Hauling Thomas | Nucleic acid sequencing |
| EP3264087B1 (en) * | 2016-06-27 | 2020-04-22 | Chimera Biotec GmbH | Method and device for quantification of target molecules |
| US9927441B1 (en) | 2016-07-29 | 2018-03-27 | X Development Llc | Combinatorial methods for aptamer based proteomics |
| EP3507364A4 (en) | 2016-08-31 | 2020-05-20 | President and Fellows of Harvard College | METHODS OF GENERATING NUCLEIC ACID SEQUENCE LIBRARIES FOR IN SITU FLUORESCENT SEQUENCING DETECTION |
| CN109923216B (zh) | 2016-08-31 | 2024-08-02 | 哈佛学院董事及会员团体 | 将生物分子的检测组合到使用荧光原位测序的单个试验的方法 |
| JP6730525B2 (ja) | 2016-11-21 | 2020-07-29 | ナノストリング テクノロジーズ，インコーポレイティド | 化学組成物とそれを利用する方法 |
| KR101968565B1 (ko) | 2017-03-16 | 2019-08-13 | 장준영 | 재킷 임시 걸이부를 구비한 옷걸이 |
| CN114921537A (zh) | 2017-03-17 | 2022-08-19 | 雅普顿生物系统公司 | 测序和高分辨率成像 |
| US11185568B2 (en) | 2017-04-14 | 2021-11-30 | President And Fellows Of Harvard College | Methods for generation of cell-derived microfilament network |
| US11788123B2 (en) | 2017-05-26 | 2023-10-17 | President And Fellows Of Harvard College | Systems and methods for high-throughput image-based screening |
| WO2019018394A1 (en) | 2017-07-17 | 2019-01-24 | The Brigham And Women's Hospital, Inc. | TREATMENT OF RHEUMATOID ARTHRITIS |
| CN120210336A (zh) | 2017-10-06 | 2025-06-27 | 10X基因组学有限公司 | Rna模板化连接 |
| US11591636B2 (en) | 2017-11-20 | 2023-02-28 | Children's Medical Center Corporation | Force-controlled nanoswitch assays for single-molecule detection in complex biological fluids |
| WO2019148001A1 (en) * | 2018-01-25 | 2019-08-01 | Apton Biosystems, Inc. | Methods and composition for high throughput single molecule protein detection systems |
| KR20250161650A (ko) | 2018-02-12 | 2025-11-17 | 브루커 스페이셜 바이올로지, 인크. | 유전자 및 단백질 발현을 검출하는 생체 분자 프로브 및 방법 |
| WO2019200326A1 (en) | 2018-04-13 | 2019-10-17 | Rarecyte, Inc. | Kits for labeling of biomarkers and methods of using the same |
| EP3781710A4 (en) | 2018-04-17 | 2022-01-05 | Chromacode, Inc. | METHODS AND SYSTEMS FOR MULTIPLEX ANALYSIS |
| WO2019213478A1 (en) | 2018-05-04 | 2019-11-07 | Nanostring Technologies, Inc. | Gene expression assay for measurement of dna mismatch repair deficiency |
| EP3794146B1 (en) | 2018-05-14 | 2025-12-10 | Bruker Spatial Biology, Inc. | Method for identifying a predetermined nucleotide sequence |
| CN112771177A (zh) | 2018-05-21 | 2021-05-07 | 纳米线科技公司 | 分子基因标签及其使用方法 |
| US12203129B2 (en) | 2018-07-03 | 2025-01-21 | ChromaCode, Inc. | Formulations and signal encoding and decoding methods for massively multiplexed biochemical assays |
| CN112770776B (zh) | 2018-07-30 | 2025-08-19 | 瑞德库尔有限责任公司 | 用于样品处理或分析的方法和系统 |
| US11519033B2 (en) | 2018-08-28 | 2022-12-06 | 10X Genomics, Inc. | Method for transposase-mediated spatial tagging and analyzing genomic DNA in a biological sample |
| WO2020061237A1 (en) | 2018-09-19 | 2020-03-26 | Apton Biosystems, Inc. | Densely-packed analyte layers and detection methods |
| WO2020076976A1 (en) | 2018-10-10 | 2020-04-16 | Readcoor, Inc. | Three-dimensional spatial molecular indexing |
| CN109337909B (zh) * | 2018-11-12 | 2020-10-13 | 湖南大学 | 一种检测肝癌耐药细胞株的核酸适体及其应用 |
| US12385083B2 (en) | 2018-12-10 | 2025-08-12 | 10X Genomics, Inc. | Methods of using master / copy arrays for spatial detection |
| CN113366116A (zh) | 2018-12-13 | 2021-09-07 | 哈佛学院院长及董事 | 用于merfish和其他应用的扩增方法和系统 |
| US11649485B2 (en) | 2019-01-06 | 2023-05-16 | 10X Genomics, Inc. | Generating capture probes for spatial analysis |
| US11926867B2 (en) | 2019-01-06 | 2024-03-12 | 10X Genomics, Inc. | Generating capture probes for spatial analysis |
| EP3976820A1 (en) | 2019-05-30 | 2022-04-06 | 10X Genomics, Inc. | Methods of detecting spatial heterogeneity of a biological sample |
| CN113906147B (zh) | 2019-05-31 | 2024-09-13 | 10X基因组学有限公司 | 检测目标核酸分子的方法 |
| EP4025711A2 (en) | 2019-11-08 | 2022-07-13 | 10X Genomics, Inc. | Enhancing specificity of analyte binding |
| IT201900024159A1 (it) | 2019-12-16 | 2021-06-16 | Menarini Silicon Biosystems Spa | Metodo e kit per amplificazione totale del genoma e analisi di molecole bersaglio in un campione biologico |
| GB201919032D0 (en) | 2019-12-20 | 2020-02-05 | Cartana Ab | Method of detecting an analyte |
| WO2021133842A1 (en) | 2019-12-23 | 2021-07-01 | 10X Genomics, Inc. | Compositions and methods for using fixed biological samples in partition-based assays |
| WO2021133849A1 (en) | 2019-12-23 | 2021-07-01 | 10X Genomics, Inc. | Methods for spatial analysis using rna-templated ligation |
| US12365942B2 (en) | 2020-01-13 | 2025-07-22 | 10X Genomics, Inc. | Methods of decreasing background on a spatial array |
| US12405264B2 (en) | 2020-01-17 | 2025-09-02 | 10X Genomics, Inc. | Electrophoretic system and method for analyte capture |
| US11732299B2 (en) | 2020-01-21 | 2023-08-22 | 10X Genomics, Inc. | Spatial assays with perturbed cells |
| US11702693B2 (en) | 2020-01-21 | 2023-07-18 | 10X Genomics, Inc. | Methods for printing cells and generating arrays of barcoded cells |
| US20210230681A1 (en) | 2020-01-24 | 2021-07-29 | 10X Genomics, Inc. | Methods for spatial analysis using proximity ligation |
| US12076701B2 (en) | 2020-01-31 | 2024-09-03 | 10X Genomics, Inc. | Capturing oligonucleotides in spatial transcriptomics |
| US12110548B2 (en) | 2020-02-03 | 2024-10-08 | 10X Genomics, Inc. | Bi-directional in situ analysis |
| US11898205B2 (en) | 2020-02-03 | 2024-02-13 | 10X Genomics, Inc. | Increasing capture efficiency of spatial assays |
| US12110541B2 (en) | 2020-02-03 | 2024-10-08 | 10X Genomics, Inc. | Methods for preparing high-resolution spatial arrays |
| US11732300B2 (en) | 2020-02-05 | 2023-08-22 | 10X Genomics, Inc. | Increasing efficiency of spatial analysis in a biological sample |
| US12129516B2 (en) | 2020-02-07 | 2024-10-29 | 10X Genomics, Inc. | Quantitative and automated permeabilization performance evaluation for spatial transcriptomics |
| US12281357B1 (en) | 2020-02-14 | 2025-04-22 | 10X Genomics, Inc. | In situ spatial barcoding |
| US12215379B2 (en) | 2020-02-17 | 2025-02-04 | 10X Genomics, Inc. | In situ analysis of chromatin interaction |
| JP2023514749A (ja) | 2020-02-21 | 2023-04-07 | １０エックス ジェノミクス インコーポレイテッド | 統合型インサイチュ空間的アッセイのための方法および組成物 |
| US11891654B2 (en) | 2020-02-24 | 2024-02-06 | 10X Genomics, Inc. | Methods of making gene expression libraries |
| US12188085B2 (en) | 2020-03-05 | 2025-01-07 | 10X Genomics, Inc. | Three-dimensional spatial transcriptomics with sequencing readout |
| EP4549582A3 (en) | 2020-04-22 | 2025-06-18 | 10x Genomics, Inc. | Methods for spatial analysis using targeted rna depletion |
| EP4553168A3 (en) | 2020-05-22 | 2025-08-27 | 10x Genomics, Inc. | Spatial analysis to detect sequence variants |
| WO2021236929A1 (en) | 2020-05-22 | 2021-11-25 | 10X Genomics, Inc. | Simultaneous spatio-temporal measurement of gene expression and cellular activity |
| US12031177B1 (en) | 2020-06-04 | 2024-07-09 | 10X Genomics, Inc. | Methods of enhancing spatial resolution of transcripts |
| ES2981265T3 (es) | 2020-06-08 | 2024-10-08 | 10X Genomics Inc | Métodos para determinar un margen quirúrgico y métodos de uso del mismo |
| US12209273B2 (en) | 2020-06-12 | 2025-01-28 | 10X Genomics, Inc. | Nucleic acid assays using click chemistry bioconjugation |
| EP4450639B1 (en) | 2020-06-25 | 2025-10-15 | 10X Genomics, Inc. | Spatial analysis of dna methylation |
| US11761038B1 (en) | 2020-07-06 | 2023-09-19 | 10X Genomics, Inc. | Methods for identifying a location of an RNA in a biological sample |
| US12209280B1 (en) | 2020-07-06 | 2025-01-28 | 10X Genomics, Inc. | Methods of identifying abundance and location of an analyte in a biological sample using second strand synthesis |
| US11981960B1 (en) | 2020-07-06 | 2024-05-14 | 10X Genomics, Inc. | Spatial analysis utilizing degradable hydrogels |
| US20220049303A1 (en) | 2020-08-17 | 2022-02-17 | Readcoor, Llc | Methods and systems for spatial mapping of genetic variants |
| US12297499B2 (en) | 2020-08-17 | 2025-05-13 | 10X Genomics, Inc. | Multicomponent nucleic acid probes for sample analysis |
| US11981958B1 (en) | 2020-08-20 | 2024-05-14 | 10X Genomics, Inc. | Methods for spatial analysis using DNA capture |
| US11926822B1 (en) | 2020-09-23 | 2024-03-12 | 10X Genomics, Inc. | Three-dimensional spatial analysis |
| US12071667B2 (en) | 2020-11-04 | 2024-08-27 | 10X Genomics, Inc. | Sequence analysis using meta-stable nucleic acid molecules |
| US11827935B1 (en) | 2020-11-19 | 2023-11-28 | 10X Genomics, Inc. | Methods for spatial analysis using rolling circle amplification and detection probes |
| EP4121555A1 (en) | 2020-12-21 | 2023-01-25 | 10X Genomics, Inc. | Methods, compositions, and systems for capturing probes and/or barcodes |
| US12060603B2 (en) | 2021-01-19 | 2024-08-13 | 10X Genomics, Inc. | Methods for internally controlled in situ assays using padlock probes |
| US12275984B2 (en) | 2021-03-02 | 2025-04-15 | 10X Genomics, Inc. | Sequential hybridization and quenching |
| WO2022221425A1 (en) | 2021-04-14 | 2022-10-20 | 10X Genomics, Inc. | Methods of measuring mislocalization of an analyte |
| WO2022236054A1 (en) | 2021-05-06 | 2022-11-10 | 10X Genomics, Inc. | Methods for increasing resolution of spatial analysis |
| EP4582555A3 (en) | 2021-06-03 | 2025-10-22 | 10X Genomics, Inc. | Methods, compositions, kits, and systems for enhancing analyte capture for spatial analysis |
| WO2023009842A1 (en) | 2021-07-30 | 2023-02-02 | 10X Genomics, Inc. | Methods and compositions for synchronizing reactions in situ |
| US12139751B2 (en) | 2021-07-30 | 2024-11-12 | 10X Genomics, Inc. | Circularizable probes for in situ analysis |
| US12391984B2 (en) | 2021-08-03 | 2025-08-19 | 10X Genomics, Inc. | Compositions and methods for rolling circle amplification |
| US12460251B2 (en) | 2021-08-03 | 2025-11-04 | 10X Genomics, Inc. | Stabilization and/or compaction of nucleic acid molecules |
| CN117858958A (zh) | 2021-08-16 | 2024-04-09 | 10X基因组学有限公司 | 包含分割条形码区的探针和使用方法 |
| EP4196605B1 (en) | 2021-09-01 | 2024-12-04 | 10X Genomics, Inc. | Methods for blocking a capture probe on a spatial array |
| EP4419707A1 (en) | 2021-11-10 | 2024-08-28 | 10X Genomics, Inc. | Methods, compositions, and kits for determining the location of an analyte in a biological sample |
| WO2023102118A2 (en) | 2021-12-01 | 2023-06-08 | 10X Genomics, Inc. | Methods, compositions, and systems for improved in situ detection of analytes and spatial analysis |
| CN118974836A (zh) | 2022-03-08 | 2024-11-15 | 10X基因组学有限公司 | 将光学拥挤最小化的原位代码设计方法 |
| EP4505177A1 (en) | 2022-04-01 | 2025-02-12 | 10x Genomics, Inc. | Compositions and methods for targeted masking of autofluorescence |
| CN119213143A (zh) | 2022-05-11 | 2024-12-27 | 10X基因组学有限公司 | 用于原位测序的组合物和方法 |
| WO2023245190A1 (en) | 2022-06-17 | 2023-12-21 | 10X Genomics, Inc. | Catalytic de-crosslinking of samples for in situ analysis |
| WO2024040060A1 (en) | 2022-08-16 | 2024-02-22 | 10X Genomics, Inc. | Ap50 polymerases and uses thereof |
| US12319956B2 (en) | 2023-07-31 | 2025-06-03 | 10X Genomics, Inc. | Methods and systems for targeted RNA cleavage and target RNA-primed rolling circle amplification |
Family Cites Families (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1323293C (en) | 1987-12-11 | 1993-10-19 | Keith C. Backman | Assay using template-dependent nucleic acid probe reorganization |
| JP2955759B2 (ja) | 1988-07-20 | 1999-10-04 | セゲブ・ダイアグノスティックス・インコーポレイテッド | 核酸配列を増幅及び検出する方法 |
| US5185243A (en) | 1988-08-25 | 1993-02-09 | Syntex (U.S.A.) Inc. | Method for detection of specific nucleic acid sequences |
| ES2089038T3 (es) | 1990-01-26 | 1996-10-01 | Abbott Lab | Procedimiento mejorado para amplificar acidos nucleicos blanco aplicable para la reaccion en cadena de polimerasa y ligasa. |
| US5320814A (en) | 1991-01-25 | 1994-06-14 | Trustees Of Tufts College | Fiber optic array sensors, apparatus, and methods for concurrently visualizing and chemically detecting multiple analytes of interest in a fluid sample |
| US5543838A (en) | 1993-08-31 | 1996-08-06 | Xerox Corporation | Signal multiplexing system for an image sensor array |
| SE9400088D0 (sv) | 1994-01-14 | 1994-01-14 | Kabi Pharmacia Ab | Bacterial receptor structures |
| AU6898296A (en) | 1995-08-14 | 1997-03-12 | Ely Michael Rabani | Methods and devices for parallel multiplex polynucleotide sequencing |
| EP0852004B1 (en) | 1995-10-11 | 2011-01-19 | Luminex Corporation | Multiplexed analysis of clinical specimens |
| US6387707B1 (en) | 1996-04-25 | 2002-05-14 | Bioarray Solutions | Array Cytometry |
| US7144119B2 (en) | 1996-04-25 | 2006-12-05 | Bioarray Solutions Ltd. | System and method for programmable illumination pattern generation |
| US6416960B1 (en) | 1996-08-08 | 2002-07-09 | Prolume, Ltd. | Detection and visualization of neoplastic tissues and other tissues |
| US6635452B1 (en) | 1996-12-10 | 2003-10-21 | Sequenom Inc. | Releasable nonvolatile mass label molecules |
| US20020034737A1 (en) | 1997-03-04 | 2002-03-21 | Hyseq, Inc. | Methods and compositions for detection or quantification of nucleic acid species |
| US6180415B1 (en) | 1997-02-20 | 2001-01-30 | The Regents Of The University Of California | Plasmon resonant particles, methods and apparatus |
| US20050037397A1 (en) * | 2001-03-28 | 2005-02-17 | Nanosphere, Inc. | Bio-barcode based detection of target analytes |
| US7348181B2 (en) | 1997-10-06 | 2008-03-25 | Trustees Of Tufts College | Self-encoding sensor with microspheres |
| US7115884B1 (en) | 1997-10-06 | 2006-10-03 | Trustees Of Tufts College | Self-encoding fiber optic sensor |
| IL135593A (en) | 1997-10-14 | 2004-06-01 | Luminex Corp | Precisely fluorescently painted polymeric microspheres and methods for making and using them |
| US6207392B1 (en) | 1997-11-25 | 2001-03-27 | The Regents Of The University Of California | Semiconductor nanocrystal probes for biological applications and process for making and using such probes |
| WO1999037663A1 (en) | 1998-01-27 | 1999-07-29 | California Institute Of Technology | Method of detecting a nucleic acid |
| WO1999067641A2 (en) | 1998-06-24 | 1999-12-29 | Illumina, Inc. | Decoding of array sensors with microspheres |
| EP0990903B1 (en) | 1998-09-18 | 2003-03-12 | Massachusetts Institute Of Technology | Biological applications of semiconductor nanocrystals |
| US7079241B2 (en) | 2000-04-06 | 2006-07-18 | Invitrogen Corp. | Spatial positioning of spectrally labeled beads |
| US6268147B1 (en) | 1998-11-02 | 2001-07-31 | Kenneth Loren Beattie | Nucleic acid analysis using sequence-targeted tandem hybridization |
| US6465193B2 (en) | 1998-12-11 | 2002-10-15 | The Regents Of The University Of California | Targeted molecular bar codes and methods for using the same |
| US6429027B1 (en) | 1998-12-28 | 2002-08-06 | Illumina, Inc. | Composite arrays utilizing microspheres |
| US6908737B2 (en) | 1999-04-15 | 2005-06-21 | Vitra Bioscience, Inc. | Systems and methods of conducting multiplexed experiments |
| US6355431B1 (en) | 1999-04-20 | 2002-03-12 | Illumina, Inc. | Detection of nucleic acid amplification reactions using bead arrays |
| AU4701200A (en) | 1999-05-07 | 2000-11-21 | Quantum Dot Corporation | A method of detecting an analyte using semiconductor nanocrystals |
| US20020051971A1 (en) | 1999-05-21 | 2002-05-02 | John R. Stuelpnagel | Use of microfluidic systems in the detection of target analytes using microsphere arrays |
| AU5764500A (en) | 1999-06-25 | 2001-01-31 | Motorola, Inc. | Novel methods and products for arrayed microsphere analysis |
| US7214477B1 (en) | 1999-07-26 | 2007-05-08 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Layered device with capture regions for cellular analysis |
| EP1218743B1 (en) | 1999-07-26 | 2006-05-31 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Layered device with capture regions for cellular analysis |
| AU2246601A (en) | 1999-08-30 | 2001-04-10 | Illumina, Inc. | Methods for improving signal detection from an array |
| AU2922701A (en) | 1999-11-04 | 2001-05-14 | Arcturus Engineering, Inc. | Automated laser capture microdissection |
| AU3806701A (en) | 2000-02-07 | 2001-08-14 | Illumina Inc | Nucleic acid detection methods using universal priming |
| CA2399908A1 (en) | 2000-02-10 | 2001-08-16 | Todd Dickinson | Array of individual arrays as substrate for bead-based simultaneous processing of samples and manufacturing method therefor |
| US20020028457A1 (en) | 2000-02-16 | 2002-03-07 | Quantum Dot Corporation | Single target counting assays using semiconductor nanocrystals |
| CN1416365A (zh) | 2000-02-22 | 2003-05-07 | 基因谱公司 | 微阵列制造技术及设备 |
| US20030186426A1 (en) | 2000-03-15 | 2003-10-02 | The Regents Of The University Of California | Multichannel flow cell for interacting single optically trapped, DNA molecules with different chemical species |
| WO2002009836A2 (en) | 2000-08-01 | 2002-02-07 | Surromed, Inc. | Methods for solid phase nanoextraction and desorption |
| US6777244B2 (en) | 2000-12-06 | 2004-08-17 | Hrl Laboratories, Llc | Compact sensor using microcavity structures |
| US7473767B2 (en) | 2001-07-03 | 2009-01-06 | The Institute For Systems Biology | Methods for detection and quantification of analytes in complex mixtures |
| US7553619B2 (en) | 2002-02-08 | 2009-06-30 | Qiagen Gmbh | Detection method using dissociated rolling circle amplification |
| US20040229294A1 (en) | 2002-05-21 | 2004-11-18 | Po-Ying Chan-Hui | ErbB surface receptor complexes as biomarkers |
| CN106337046B (zh) | 2002-10-30 | 2021-03-23 | 纽韦卢森公司 | 合成双功能复合物的方法 |
| AU2004254367B2 (en) | 2003-06-27 | 2008-06-19 | Nanosphere, Inc. | Bio-barcode based detection of target analytes |
| US7402398B2 (en) | 2003-07-17 | 2008-07-22 | Monogram Biosciences, Inc. | Measuring receptor homodimerization |
| US20050048498A1 (en) | 2003-08-29 | 2005-03-03 | Applera Corporation | Compositions, methods, and kits for assembling probes |
| EP1681983A4 (en) | 2003-10-14 | 2008-12-10 | Monogram Biosciences Inc | RECEPTOR TYROSINE KINASE SIGNAL PATH ANALYSIS FOR DIAGNOSIS AND THERAPY |
| US8637650B2 (en) | 2003-11-05 | 2014-01-28 | Genovoxx Gmbh | Macromolecular nucleotide compounds and methods for using the same |
| TW200526778A (en) | 2003-11-14 | 2005-08-16 | Sembiosys Genetics Inc | Methods for the production of apolipoproteins in transgenic plants |
| US7569392B2 (en) | 2004-01-08 | 2009-08-04 | Vanderbilt University | Multiplex spatial profiling of gene expression |
| WO2005071401A2 (en) * | 2004-01-15 | 2005-08-04 | Chiron Corporation | Homogeneous multiplex assay for nucleic acid targets |
| US7588906B2 (en) | 2004-02-24 | 2009-09-15 | Wisconsin Alumni Research Foundation | Hydrogels for biomolecule analysis and corresponding method to analyze biomolecules |
| JP2005257641A (ja) * | 2004-03-15 | 2005-09-22 | Geneticlab Co Ltd | Ｒｎａポリメラーゼを用いて複数の蛋白質を同時に検出する方法 |
| EP2322920B1 (en) | 2005-06-07 | 2014-12-10 | Centre National de la Recherche Scientifique (CNRS) | MALDI tissue imaging using conjugates cleavable by fast fragmentation |
| EP3211086B1 (en) * | 2005-09-20 | 2021-06-09 | Menarini Silicon Biosystems S.p.A. | Methods and composition to generate unique sequence dna probes, labeling of dna probes and the use of these probes |
| EP1963531B1 (en) * | 2005-12-23 | 2011-09-21 | Nanostring Technologies, Inc. | Nanoreporters and methods of manufacturing and use thereof |
| JP5700911B2 (ja) | 2005-12-23 | 2015-04-15 | ナノストリング テクノロジーズ，インコーポレーテッド | 配向され、固定化された巨大分子を含む組成物とその製造法 |
| US7855057B2 (en) | 2006-03-23 | 2010-12-21 | Millipore Corporation | Protein splice variant/isoform discrimination and quantitative measurements thereof |
| US8003312B2 (en) | 2007-02-16 | 2011-08-23 | The Board Of Trustees Of The Leland Stanford Junior University | Multiplex cellular assays using detectable cell barcodes |
| US7728287B2 (en) | 2007-03-01 | 2010-06-01 | Lawrence Livermore National Security, Llc | Imaging mass spectrometer with mass tags |
| WO2008122310A1 (en) * | 2007-04-04 | 2008-10-16 | Chimera Biotec Gmbh | Method for the detection of an analyte in biological matrix |
| CA2687292C (en) * | 2007-04-10 | 2017-07-04 | Nanostring Technologies, Inc. | Methods and computer systems for identifying target-specific sequences for use in nanoreporters |
| US8906700B2 (en) | 2007-11-06 | 2014-12-09 | Ambergen, Inc. | Methods and compositions for phototransfer |
| ES2614810T3 (es) | 2008-08-14 | 2017-06-02 | Nanostring Technologies, Inc | Nanoindicadores estables |
| EP2163900A1 (en) | 2008-09-04 | 2010-03-17 | Commissariat A L'energie Atomique | New method of imaging by mass spectrometry and new mass tag associated trityl derivatives |
| US8309306B2 (en) | 2008-11-12 | 2012-11-13 | Nodality, Inc. | Detection composition |
| DE102008062372B3 (de) | 2008-12-17 | 2010-06-17 | Medizinische Hochschule Hannover | Nachweiskonjugat und Verfahren zur Analyse |
| SG172983A1 (en) | 2009-01-15 | 2011-08-29 | Lab Corp America Holdings | Methods of determining patient response by measurement of her-3 |
| JP5457222B2 (ja) | 2009-02-25 | 2014-04-02 | エフ．ホフマン−ラ ロシュ アーゲー | 小型化ハイスループット核酸分析 |
| WO2010115089A2 (en) | 2009-04-03 | 2010-10-07 | University Of Virginia Patent Foundation | Serial multiple antigen colocalization in paraffin-embedded tissue |
| DE102009002653B3 (de) | 2009-04-27 | 2010-05-27 | Federal-Mogul Nürnberg GmbH | Verfahren und Vorrichtung zur Herstellung eines Kolbens für einen Verbrennungsmotor sowie Kolben für einen Verbrennungsmotor |
| JP5954876B2 (ja) | 2009-10-13 | 2016-07-20 | ナノストリング テクノロジーズ， インコーポレイテッド | ナノレポーターによるタンパク質の検出 |
| EP2542577A1 (en) | 2010-03-01 | 2013-01-09 | Lostam Biopharmaceuticals Ltd | Improved therapeutic antibodies against flagellated pseudomonas aeruginosa |
-
2010
- 2010-10-13 JP JP2012534336A patent/JP5954876B2/ja active Active
- 2010-10-13 US US12/904,078 patent/US9714937B2/en active Active
- 2010-10-13 EP EP10824048.2A patent/EP2488876B1/en active Active
- 2010-10-13 EP EP16201369.2A patent/EP3236264A3/en not_active Withdrawn
- 2010-10-13 AU AU2010306862A patent/AU2010306862B2/en active Active
- 2010-10-13 CA CA2775613A patent/CA2775613C/en active Active
- 2010-10-13 ES ES10824048.2T patent/ES2627063T3/es active Active
- 2010-10-13 WO PCT/US2010/052556 patent/WO2011047087A2/en not_active Ceased
-
2015
- 2015-07-30 US US14/814,216 patent/US9995739B2/en active Active
-
2016
- 2016-04-15 JP JP2016081762A patent/JP2016136161A/ja active Pending
- 2016-04-15 JP JP2016081763A patent/JP6225212B2/ja active Active
-
2018
- 2018-04-24 HK HK18105349.7A patent/HK1249580A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20110086774A1 (en) | 2011-04-14 |
| JP2013507642A (ja) | 2013-03-04 |
| AU2010306862B2 (en) | 2015-08-27 |
| AU2010306862A1 (en) | 2012-04-12 |
| CA2775613A1 (en) | 2011-04-21 |
| JP6225212B2 (ja) | 2017-11-01 |
| JP2016136161A (ja) | 2016-07-28 |
| WO2011047087A3 (en) | 2011-08-18 |
| US9995739B2 (en) | 2018-06-12 |
| US20160003809A1 (en) | 2016-01-07 |
| EP3236264A3 (en) | 2017-11-08 |
| US9714937B2 (en) | 2017-07-25 |
| EP2488876A2 (en) | 2012-08-22 |
| EP3236264A2 (en) | 2017-10-25 |
| EP2488876A4 (en) | 2013-03-20 |
| JP2016136162A (ja) | 2016-07-28 |
| CA2775613C (en) | 2018-06-12 |
| JP5954876B2 (ja) | 2016-07-20 |
| WO2011047087A2 (en) | 2011-04-21 |
| EP2488876B1 (en) | 2017-03-01 |
| HK1249580A1 (en) | 2018-11-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2627063T3 (es) | Detección de proteína a través de nanoinformadores | |
| US11932902B2 (en) | Barcoded beads and method for making the same by split-pool synthesis | |
| ES2963079T3 (es) | Detección de proteínas de células hospedadoras residuales en preparaciones de proteínas recombinantes | |
| US20110294135A1 (en) | Compositions and methods for analyte detection and quantitation | |
| US20220056515A1 (en) | Methods of identifying multiple epitopes in cells | |
| US11560585B2 (en) | Methods of identifying multiple epitopes in cells | |
| CA3029178C (en) | Double-stranded nucleic acid signal probe and method for detecting target molecule using same | |
| AU2015261558B2 (en) | Protein Detection Via Nanoreporters |