CN104903465B - 基于寡核苷酸切割及延伸‑依赖性非‑杂交探测的靶核酸序列的检测 - Google Patents
基于寡核苷酸切割及延伸‑依赖性非‑杂交探测的靶核酸序列的检测 Download PDFInfo
- Publication number
- CN104903465B CN104903465B CN201380068241.3A CN201380068241A CN104903465B CN 104903465 B CN104903465 B CN 104903465B CN 201380068241 A CN201380068241 A CN 201380068241A CN 104903465 B CN104903465 B CN 104903465B
- Authority
- CN
- China
- Prior art keywords
- mentioned
- oligonucleotide
- hybridization
- nucleic acid
- oligonucleotides
- 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
- 238000009396 hybridization Methods 0.000 title claims abstract description 763
- 150000007523 nucleic acids Chemical group 0.000 title claims abstract description 429
- 238000001514 detection method Methods 0.000 title claims abstract description 341
- 108091028043 Nucleic acid sequence Proteins 0.000 title claims description 287
- 238000003776 cleavage reaction Methods 0.000 title abstract description 201
- 230000007017 scission Effects 0.000 title abstract description 192
- 238000003556 assay Methods 0.000 title abstract description 122
- 230000001419 dependent effect Effects 0.000 title abstract description 117
- 108091034117 Oligonucleotide Proteins 0.000 claims abstract description 1947
- 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 claims abstract description 773
- 238000002372 labelling Methods 0.000 claims abstract description 555
- 239000000539 dimer Substances 0.000 claims abstract description 134
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 80
- 239000002773 nucleotide Substances 0.000 claims description 393
- 125000003729 nucleotide group Chemical group 0.000 claims description 390
- 239000012634 fragment Substances 0.000 claims description 198
- 239000000523 sample Substances 0.000 claims description 196
- 238000011144 upstream manufacturing Methods 0.000 claims description 155
- 230000000295 complement effect Effects 0.000 claims description 145
- 108020004707 nucleic acids Proteins 0.000 claims description 137
- 102000039446 nucleic acids Human genes 0.000 claims description 137
- 238000000034 method Methods 0.000 claims description 129
- 239000000758 substrate Substances 0.000 claims description 92
- 238000002844 melting Methods 0.000 claims description 88
- 230000008018 melting Effects 0.000 claims description 88
- 239000007790 solid phase Substances 0.000 claims description 85
- 101710163270 Nuclease Proteins 0.000 claims description 69
- 102000004190 Enzymes Human genes 0.000 claims description 52
- 108090000790 Enzymes Proteins 0.000 claims description 52
- 238000004458 analytical method Methods 0.000 claims description 40
- 238000005520 cutting process Methods 0.000 claims description 36
- 239000002253 acid Substances 0.000 claims description 34
- 239000007787 solid Substances 0.000 claims description 33
- 230000003993 interaction Effects 0.000 claims description 31
- 108020004635 Complementary DNA Proteins 0.000 claims description 29
- 230000009977 dual effect Effects 0.000 claims description 23
- 238000010791 quenching Methods 0.000 claims description 15
- 230000000171 quenching effect Effects 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 230000001939 inductive effect Effects 0.000 claims description 5
- 239000012071 phase Substances 0.000 claims description 3
- 238000002474 experimental method Methods 0.000 claims 4
- 241000218636 Thuja Species 0.000 claims 2
- 230000001629 suppression Effects 0.000 claims 2
- 230000007850 degeneration Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 60
- 230000005764 inhibitory process Effects 0.000 abstract description 17
- 230000000694 effects Effects 0.000 description 64
- 239000002585 base Substances 0.000 description 46
- 230000002452 interceptive effect Effects 0.000 description 40
- 239000000047 product Substances 0.000 description 38
- 230000008569 process Effects 0.000 description 18
- 230000003321 amplification Effects 0.000 description 17
- 238000003199 nucleic acid amplification method Methods 0.000 description 17
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 16
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 16
- 230000002860 competitive effect Effects 0.000 description 14
- -1 label Chemical compound 0.000 description 14
- 230000002401 inhibitory effect Effects 0.000 description 13
- 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 12
- 238000000137 annealing Methods 0.000 description 11
- 230000008859 change Effects 0.000 description 11
- 230000036425 denaturation Effects 0.000 description 11
- 238000004925 denaturation Methods 0.000 description 11
- 238000003752 polymerase chain reaction Methods 0.000 description 11
- 238000011160 research Methods 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 9
- 241000589596 Thermus Species 0.000 description 8
- 238000013459 approach Methods 0.000 description 8
- 238000009830 intercalation Methods 0.000 description 8
- 238000003746 solid phase reaction Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 108091093037 Peptide nucleic acid Proteins 0.000 description 7
- 230000000903 blocking effect Effects 0.000 description 7
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 7
- 239000007850 fluorescent dye Substances 0.000 description 7
- 239000007791 liquid phase Substances 0.000 description 7
- 239000003550 marker Substances 0.000 description 7
- 230000035772 mutation Effects 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 7
- 108090000652 Flap endonucleases Proteins 0.000 description 6
- 102000004150 Flap endonucleases Human genes 0.000 description 6
- 241000589499 Thermus thermophilus Species 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 229960002685 biotin Drugs 0.000 description 6
- 235000020958 biotin Nutrition 0.000 description 6
- 239000011616 biotin Substances 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 230000002255 enzymatic effect Effects 0.000 description 6
- 230000001976 improved effect Effects 0.000 description 6
- 238000002493 microarray Methods 0.000 description 6
- 108010006785 Taq Polymerase Proteins 0.000 description 5
- 239000002981 blocking agent Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 230000007274 generation of a signal involved in cell-cell signaling Effects 0.000 description 5
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 5
- 239000010931 gold Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 238000006116 polymerization reaction Methods 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 241000205188 Thermococcus Species 0.000 description 4
- 241000206213 Thermosipho africanus Species 0.000 description 4
- 241000204666 Thermotoga maritima Species 0.000 description 4
- 241000204664 Thermotoga neapolitana Species 0.000 description 4
- 239000012472 biological sample Substances 0.000 description 4
- 238000006073 displacement reaction Methods 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 230000002349 favourable effect Effects 0.000 description 4
- 125000005647 linker group Chemical group 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 3
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 3
- 229930010555 Inosine Natural products 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 102100029684 Methylenetetrahydrofolate reductase Human genes 0.000 description 3
- 241000522615 Pyrococcus horikoshii Species 0.000 description 3
- 241001237851 Thermococcus gorgonarius Species 0.000 description 3
- 241000205180 Thermococcus litoralis Species 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- GRRMZXFOOGQMFA-UHFFFAOYSA-J YoYo-1 Chemical compound [I-].[I-].[I-].[I-].C12=CC=CC=C2C(C=C2N(C3=CC=CC=C3O2)C)=CC=[N+]1CCC[N+](C)(C)CCC[N+](C)(C)CCC[N+](C1=CC=CC=C11)=CC=C1C=C1N(C)C2=CC=CC=C2O1 GRRMZXFOOGQMFA-UHFFFAOYSA-J 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 description 3
- 238000006911 enzymatic reaction Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 229910052737 gold Inorganic materials 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 229960003786 inosine Drugs 0.000 description 3
- 238000011880 melting curve analysis Methods 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 238000001668 nucleic acid synthesis Methods 0.000 description 3
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- VGIRNWJSIRVFRT-UHFFFAOYSA-N 2',7'-difluorofluorescein Chemical compound OC(=O)C1=CC=CC=C1C1=C2C=C(F)C(=O)C=C2OC2=CC(O)=C(F)C=C21 VGIRNWJSIRVFRT-UHFFFAOYSA-N 0.000 description 2
- KHWCHTKSEGGWEX-RRKCRQDMSA-N 2'-deoxyadenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(O)=O)O1 KHWCHTKSEGGWEX-RRKCRQDMSA-N 0.000 description 2
- LTFMZDNNPPEQNG-KVQBGUIXSA-N 2'-deoxyguanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1C[C@H](O)[C@@H](COP(O)(O)=O)O1 LTFMZDNNPPEQNG-KVQBGUIXSA-N 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 229910001020 Au alloy Inorganic materials 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 108091093094 Glycol nucleic acid Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 241000508310 Meiothermus chliarophilus Species 0.000 description 2
- 241000589496 Meiothermus ruber Species 0.000 description 2
- 241000508289 Meiothermus silvanus Species 0.000 description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 2
- 108010030837 Methylenetetrahydrofolate Reductase (NADPH2) Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 241001148023 Pyrococcus abyssi Species 0.000 description 2
- 241000205192 Pyrococcus woesei Species 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 241000015345 Thermus antranikianii Species 0.000 description 2
- 241000589500 Thermus aquaticus Species 0.000 description 2
- 241000589501 Thermus caldophilus Species 0.000 description 2
- 241000589498 Thermus filiformis Species 0.000 description 2
- 241000015334 Thermus igniterrae Species 0.000 description 2
- 241000557726 Thermus oshimai Species 0.000 description 2
- 241001522143 Thermus scotoductus Species 0.000 description 2
- 108091046915 Threose nucleic acid Proteins 0.000 description 2
- MZZINWWGSYUHGU-UHFFFAOYSA-J ToTo-1 Chemical compound [I-].[I-].[I-].[I-].C12=CC=CC=C2C(C=C2N(C3=CC=CC=C3S2)C)=CC=[N+]1CCC[N+](C)(C)CCC[N+](C)(C)CCC[N+](C1=CC=CC=C11)=CC=C1C=C1N(C)C2=CC=CC=C2S1 MZZINWWGSYUHGU-UHFFFAOYSA-J 0.000 description 2
- 150000007513 acids Chemical group 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 238000003491 array Methods 0.000 description 2
- 238000010420 art technique Methods 0.000 description 2
- 238000002820 assay format Methods 0.000 description 2
- 102000005936 beta-Galactosidase Human genes 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 102000006995 beta-Glucosidase Human genes 0.000 description 2
- 108010047754 beta-Glucosidase Proteins 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- GYOZYWVXFNDGLU-XLPZGREQSA-N dTMP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 GYOZYWVXFNDGLU-XLPZGREQSA-N 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 239000005546 dideoxynucleotide Substances 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- 229930182470 glycoside Natural products 0.000 description 2
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 230000001293 nucleolytic effect Effects 0.000 description 2
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000037452 priming Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 108010068698 spleen exonuclease Proteins 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- ABZLKHKQJHEPAX-UHFFFAOYSA-N tetramethylrhodamine Chemical compound C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C([O-])=O ABZLKHKQJHEPAX-UHFFFAOYSA-N 0.000 description 2
- 238000010396 two-hybrid screening Methods 0.000 description 2
- WETFHJRYOTYZFD-YIZRAAEISA-N (2r,3s,5s)-2-(hydroxymethyl)-5-(3-nitropyrrol-1-yl)oxolan-3-ol Chemical compound C1[C@H](O)[C@@H](CO)O[C@@H]1N1C=C([N+]([O-])=O)C=C1 WETFHJRYOTYZFD-YIZRAAEISA-N 0.000 description 1
- 101150084750 1 gene Proteins 0.000 description 1
- NCMVOABPESMRCP-SHYZEUOFSA-N 2'-deoxycytosine 5'-monophosphate Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 NCMVOABPESMRCP-SHYZEUOFSA-N 0.000 description 1
- CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- LOJNBPNACKZWAI-UHFFFAOYSA-N 3-nitro-1h-pyrrole Chemical compound [O-][N+](=O)C=1C=CNC=1 LOJNBPNACKZWAI-UHFFFAOYSA-N 0.000 description 1
- WCKQPPQRFNHPRJ-UHFFFAOYSA-N 4-[[4-(dimethylamino)phenyl]diazenyl]benzoic acid Chemical compound C1=CC(N(C)C)=CC=C1N=NC1=CC=C(C(O)=O)C=C1 WCKQPPQRFNHPRJ-UHFFFAOYSA-N 0.000 description 1
- OZFPSOBLQZPIAV-UHFFFAOYSA-N 5-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NC=CC2=C1 OZFPSOBLQZPIAV-UHFFFAOYSA-N 0.000 description 1
- 241000726121 Acidianus Species 0.000 description 1
- 241000205069 Acidianus ambivalens Species 0.000 description 1
- 241000567139 Aeropyrum pernix Species 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 241000207208 Aquifex Species 0.000 description 1
- 241000207207 Aquifex pyrophilus Species 0.000 description 1
- JBRZTFJDHDCESZ-UHFFFAOYSA-N AsGa Chemical compound [As]#[Ga] JBRZTFJDHDCESZ-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000212384 Bifora Species 0.000 description 1
- 108010075254 C-Peptide Proteins 0.000 description 1
- 101150003340 CYP2C19 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 229910000881 Cu alloy Inorganic materials 0.000 description 1
- 101710085367 DNA polymerase I, thermostable Proteins 0.000 description 1
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 1
- 241000359383 Desulfurococcus amylolyticus Species 0.000 description 1
- 241000205229 Desulfurococcus mucosus Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 241000701832 Enterobacteria phage T3 Species 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108091092584 GDNA Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000587058 Homo sapiens Methylenetetrahydrofolate reductase Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000204641 Methanopyrus kandleri Species 0.000 description 1
- 241000203373 Methanotorris igneus Species 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 108010053210 Phycocyanin Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 241000736843 Pyrobaculum aerophilum Species 0.000 description 1
- 241000205156 Pyrococcus furiosus Species 0.000 description 1
- 241000204671 Pyrodictium Species 0.000 description 1
- 241001494984 Pyrodictium brockii Species 0.000 description 1
- 241000204670 Pyrodictium occultum Species 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 241000205091 Sulfolobus solfataricus Species 0.000 description 1
- 241000529868 Thermococcus zilligii Species 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 241000726445 Viroids Species 0.000 description 1
- PTDSBMOTWGZQRX-UHFFFAOYSA-N [N+](=O)([O-])C=1C=C2C=CNC2=CC1.[N+](=O)([O-])C=1C=C2C=CNC2=CC1 Chemical compound [N+](=O)([O-])C=1C=C2C=CNC2=CC1.[N+](=O)([O-])C=1C=C2C=CNC2=CC1 PTDSBMOTWGZQRX-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003570 air Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000005600 alkyl phosphonate group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- DEGAKNSWVGKMLS-UHFFFAOYSA-N calcein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(O)=O)CC(O)=O)=C(O)C=C1OC1=C2C=C(CN(CC(O)=O)CC(=O)O)C(O)=C1 DEGAKNSWVGKMLS-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- IDMLRIMDYVWWRJ-UHFFFAOYSA-N calcium crimson Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=CC=C1OCCOC1=CC(NS(=O)(=O)C=2C=C(C(C=3C4=CC=5CCCN6CCCC(C=56)=C4OC4=C5C6=[N+](CCC5)CCCC6=CC4=3)=CC=2)S([O-])(=O)=O)=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O IDMLRIMDYVWWRJ-UHFFFAOYSA-N 0.000 description 1
- NMUGYJRMGWBCPU-UHFFFAOYSA-N calcium orange Chemical compound C=12C=CC(=[N+](C)C)C=C2OC2=CC(N(C)C)=CC=C2C=1C(C(=C1)C([O-])=O)=CC=C1NC(=S)NC(C=1)=CC=C(N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)C=1OCCOC1=CC=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O NMUGYJRMGWBCPU-UHFFFAOYSA-N 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910021393 carbon nanotube Inorganic materials 0.000 description 1
- 239000002041 carbon nanotube Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 238000013211 curve analysis Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- LTFMZDNNPPEQNG-UHFFFAOYSA-N deoxyguanylic acid Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1CC(O)C(COP(O)(O)=O)O1 LTFMZDNNPPEQNG-UHFFFAOYSA-N 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 150000002009 diols Chemical group 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000012921 fluorescence analysis Methods 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- 238000002189 fluorescence spectrum Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 229910052732 germanium Inorganic materials 0.000 description 1
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 229940015043 glyoxal Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000007641 inkjet printing Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- NGCVJRFIBJVSFI-UHFFFAOYSA-I magnesium green Chemical compound [K+].[K+].[K+].[K+].[K+].C1=C(N(CC([O-])=O)CC([O-])=O)C(OCC(=O)[O-])=CC(NC(=O)C=2C=C3C(C4(C5=CC(Cl)=C([O-])C=C5OC5=CC([O-])=C(Cl)C=C54)OC3=O)=CC=2)=C1 NGCVJRFIBJVSFI-UHFFFAOYSA-I 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 150000004712 monophosphates Chemical class 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- VOFUROIFQGPCGE-UHFFFAOYSA-N nile red Chemical compound C1=CC=C2C3=NC4=CC=C(N(CC)CC)C=C4OC3=CC(=O)C2=C1 VOFUROIFQGPCGE-UHFFFAOYSA-N 0.000 description 1
- 238000012705 nitroxide-mediated radical polymerization Methods 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 229960002378 oftasceine Drugs 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 150000008298 phosphoramidates Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 238000000206 photolithography Methods 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- INCIMLINXXICKS-UHFFFAOYSA-M pyronin Y Chemical compound [Cl-].C1=CC(=[N+](C)C)C=C2OC3=CC(N(C)C)=CC=C3C=C21 INCIMLINXXICKS-UHFFFAOYSA-M 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 238000011897 real-time detection Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- MYIOYATURDILJN-UHFFFAOYSA-N rhodamine 110 Chemical compound [Cl-].C=12C=CC(N)=CC2=[O+]C2=CC(N)=CC=C2C=1C1=CC=CC=C1C(O)=O MYIOYATURDILJN-UHFFFAOYSA-N 0.000 description 1
- TUFFYSFVSYUHPA-UHFFFAOYSA-M rhodamine 123 Chemical compound [Cl-].COC(=O)C1=CC=CC=C1C1=C(C=CC(N)=C2)C2=[O+]C2=C1C=CC(N)=C2 TUFFYSFVSYUHPA-UHFFFAOYSA-M 0.000 description 1
- 229940043267 rhodamine b Drugs 0.000 description 1
- 239000001022 rhodamine dye Substances 0.000 description 1
- 108700038288 rhodamine-phalloidin Proteins 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000007727 signaling mechanism Effects 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- JGVWCANSWKRBCS-UHFFFAOYSA-N tetramethylrhodamine thiocyanate Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=C(SC#N)C=C1C(O)=O JGVWCANSWKRBCS-UHFFFAOYSA-N 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- ACOJCCLIDPZYJC-UHFFFAOYSA-M thiazole orange Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1.C1=CC=C2C(C=C3N(C4=CC=CC=C4S3)C)=CC=[N+](C)C2=C1 ACOJCCLIDPZYJC-UHFFFAOYSA-M 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6816—Hybridisation assays characterised by the detection means
-
- 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
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6816—Hybridisation assays characterised by the detection means
- C12Q1/6823—Release of bound markers
-
- 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
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
-
- 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
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/6851—Quantitative amplification
-
- 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
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/6853—Nucleic acid amplification reactions using modified primers or templates
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Health & Medical Sciences (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2012-0154834 | 2012-12-27 | ||
| KR20120154834 | 2012-12-27 | ||
| KR10-2013-0008580 | 2013-01-25 | ||
| KR20130008580 | 2013-01-25 | ||
| KR10-2013-0034670 | 2013-03-29 | ||
| KR20130034670 | 2013-03-29 | ||
| PCT/KR2013/012312 WO2014104818A1 (en) | 2012-12-27 | 2013-12-27 | Detection of target nucleic acid sequence by pto cleavage and extension-dependent non-hybridization assay |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104903465A CN104903465A (zh) | 2015-09-09 |
| CN104903465B true CN104903465B (zh) | 2017-04-26 |
Family
ID=51021756
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380068241.3A Active CN104903465B (zh) | 2012-12-27 | 2013-12-27 | 基于寡核苷酸切割及延伸‑依赖性非‑杂交探测的靶核酸序列的检测 |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US9783845B2 (enExample) |
| EP (1) | EP2943586B1 (enExample) |
| JP (1) | JP6178430B2 (enExample) |
| KR (1) | KR101760267B1 (enExample) |
| CN (1) | CN104903465B (enExample) |
| AU (1) | AU2013371128B2 (enExample) |
| BR (1) | BR112015014152B1 (enExample) |
| CA (1) | CA2896213C (enExample) |
| ES (1) | ES2653642T3 (enExample) |
| MX (1) | MX361191B (enExample) |
| RU (1) | RU2620958C2 (enExample) |
| WO (1) | WO2014104818A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3469100B1 (en) | 2016-06-10 | 2021-01-27 | Seegene, Inc. | Methods for preparing tagging oligonucleotides |
| KR102301305B1 (ko) | 2016-06-30 | 2021-09-13 | 주식회사 씨젠 | 핵산 증폭용 튜브 및 핵산 증폭용 반응 용기 |
| KR102239375B1 (ko) | 2016-10-06 | 2021-04-13 | 주식회사 씨젠 | 시료 내 타겟 핵산분자의 검출에 이용되는 올리고뉴클레오타이드의 제공방법 |
| WO2018114674A1 (de) * | 2016-12-23 | 2018-06-28 | Albert-Ludwigs-Universität Freiburg | Zweiteilige mediatorsonde |
| KR102651626B1 (ko) | 2016-12-29 | 2024-03-26 | 주식회사 씨젠 | 프라이머 다이머 형성을 감소시키고 증폭 효율을 증가시키는 방법 |
| KR102408564B1 (ko) | 2017-03-28 | 2022-06-14 | 주식회사 씨젠 | 타겟 핵산 서열의 존재를 결정하기 위한 분석 시그널 |
| CN108823287B (zh) | 2017-04-28 | 2019-04-12 | 厦门大学 | 一种检测靶核酸序列的方法 |
| CN107236815A (zh) * | 2017-07-18 | 2017-10-10 | 江西贤聚景欣医药生物科技有限公司 | 用于靶核酸序列检测的多重淬灭荧光探针及方法 |
| EP3676400A4 (en) | 2017-08-31 | 2021-06-02 | Seegene, Inc. | EVALUATING THE PERFORMANCE OF COMPONENTS USING A PAIR OF DIMERING PRIMERS |
| KR102345601B1 (ko) | 2017-09-29 | 2021-12-30 | 주식회사 씨젠 | Pto 절단 및 연장-의존적 연장 분석에 의한 타겟 핵산 서열의 검출 |
| WO2019135567A1 (en) | 2018-01-05 | 2019-07-11 | Seegene, Inc. . | Method for determining the presence or absence of m. tuberculosis, m. bovis and m. bovis bcg in a sample |
| AU2019255933B2 (en) | 2018-04-20 | 2022-08-25 | Seegene, Inc. . | Method and apparatus for detecting a plurality of target nucleic acid sequences in sample |
| US20220025449A1 (en) | 2018-12-14 | 2022-01-27 | Seegene, Inc. | Method for detecting a target analyte in a sample using an s-shaped function for a slope data set |
| EP3899035B1 (en) * | 2018-12-20 | 2025-04-16 | F. Hoffmann-La Roche AG | Detection of target nucleic acid by solid-phase molography |
| WO2023043280A1 (ko) | 2021-09-17 | 2023-03-23 | 주식회사 씨젠 | 합성 비자연 염기를 포함하는 태그 올리고뉴클레오타이드를 이용한 타겟 핵산 서열의 검출 |
| US20250340928A1 (en) * | 2022-04-22 | 2025-11-06 | Albert-Ludwigs-Universität Freiburg | Nucleic acid detection in a pcr by means of a target-sequence-unspecific modular reporter complex |
| EP4265734A1 (de) * | 2022-04-22 | 2023-10-25 | Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. | Nukleinsäurenachweis in einer pcr mittels eines zielsequenz-unspezifischem modularer reporterkomplexes |
| KR20250086619A (ko) | 2022-10-14 | 2025-06-13 | 주식회사 씨젠 | 상이한 tm 값을 가지는 2개의 프로브를 이용하여 샘플 내 타겟 핵산을 검출하는 방법 |
| EP4372100A1 (en) * | 2022-11-15 | 2024-05-22 | Stilla Technologies | Data analysis method for multiplex digital pcr using color-combination |
| WO2024106890A1 (ko) | 2022-11-16 | 2024-05-23 | 주식회사 씨젠 | 퀀칭-pto 절단 및 연장(quenching-pto cleavage and extension; q-ptoce) 어세이에 의한 타겟 핵산의 검출 |
| WO2025005717A1 (ko) * | 2023-06-30 | 2025-01-02 | 주식회사 씨젠 | Hto 절단 및 자기-연장 어세이에 의해 샘플 내의 타겟 핵산을 검출하는 방법 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101076537A (zh) * | 2003-11-19 | 2007-11-21 | 阿莱洛吉克生物科学公司 | 标记有多个荧光团的寡核苷酸 |
| US20090023151A1 (en) * | 2006-08-30 | 2009-01-22 | Dawson Elliott P | Method For The Labeling And Detection Of Small Polynucleotides |
| CN101506384A (zh) * | 2006-07-17 | 2009-08-12 | 布兰迪斯大学 | 专一性寡核苷酸和其在核酸扩增与检测中的用途 |
| US20100129812A1 (en) * | 2001-01-27 | 2010-05-27 | Jae Chern Yoo | Nucleic acid hybridization essay method |
| WO2012096523A2 (en) * | 2011-01-11 | 2012-07-19 | Seegene, Inc. | Detection of target nucleic acid sequences by pto cleavage and extension assay |
| WO2012134195A2 (en) * | 2011-03-29 | 2012-10-04 | Seegene, Inc. | Detection of target nucleic acid sequence by pto cleavage and extension-dependent cleavage |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5210015A (en) | 1990-08-06 | 1993-05-11 | Hoffman-La Roche Inc. | Homogeneous assay system using the nuclease activity of a nucleic acid polymerase |
| US5994069A (en) | 1996-01-24 | 1999-11-30 | Third Wave Technologies, Inc. | Detection of nucleic acids by multiple sequential invasive cleavages |
| US5541311A (en) | 1992-12-07 | 1996-07-30 | Third Wave Technologies, Inc. | Nucleic acid encoding synthesis-deficient thermostable DNA polymerase |
| US5538848A (en) | 1994-11-16 | 1996-07-23 | Applied Biosystems Division, Perkin-Elmer Corp. | Method for detecting nucleic acid amplification using self-quenching fluorescence probe |
| GB9812768D0 (en) | 1998-06-13 | 1998-08-12 | Zeneca Ltd | Methods |
| US7381532B2 (en) | 1999-10-29 | 2008-06-03 | Stratagene California | Compositions and methods for the detection of a nucleic acid using a cleavage reaction |
| US6893819B1 (en) | 2000-11-21 | 2005-05-17 | Stratagene California | Methods for detection of a nucleic acid by sequential amplification |
| US7601497B2 (en) * | 2000-06-15 | 2009-10-13 | Qiagen Gaithersburg, Inc. | Detection of nucleic acids by target-specific hybrid capture method |
| US7309573B2 (en) | 2000-11-21 | 2007-12-18 | Stratagene California | Methods for detection of a nucleic acid by sequential amplification |
| GB0205455D0 (en) * | 2002-03-07 | 2002-04-24 | Molecular Sensing Plc | Nucleic acid probes, their synthesis and use |
| WO2008083261A1 (en) | 2006-12-29 | 2008-07-10 | Applera Corporation | Systems and methods for detecting nucleic acids |
| MX342067B (es) * | 2011-05-04 | 2016-09-09 | Seegene Inc | Detección de secuencias de ácido nucleico objetivo por desdoblamiento e hibridización de oligonucleótido de sonda. |
-
2013
- 2013-12-27 JP JP2015550327A patent/JP6178430B2/ja active Active
- 2013-12-27 MX MX2015008494A patent/MX361191B/es active IP Right Grant
- 2013-12-27 US US14/655,847 patent/US9783845B2/en active Active
- 2013-12-27 KR KR1020157017974A patent/KR101760267B1/ko active Active
- 2013-12-27 CA CA2896213A patent/CA2896213C/en active Active
- 2013-12-27 ES ES13868457.6T patent/ES2653642T3/es active Active
- 2013-12-27 CN CN201380068241.3A patent/CN104903465B/zh active Active
- 2013-12-27 RU RU2015130335A patent/RU2620958C2/ru active
- 2013-12-27 BR BR112015014152-8A patent/BR112015014152B1/pt active IP Right Grant
- 2013-12-27 EP EP13868457.6A patent/EP2943586B1/en active Active
- 2013-12-27 WO PCT/KR2013/012312 patent/WO2014104818A1/en not_active Ceased
- 2013-12-27 AU AU2013371128A patent/AU2013371128B2/en active Active
-
2017
- 2017-09-07 US US15/697,617 patent/US20180057869A1/en not_active Abandoned
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100129812A1 (en) * | 2001-01-27 | 2010-05-27 | Jae Chern Yoo | Nucleic acid hybridization essay method |
| CN101076537A (zh) * | 2003-11-19 | 2007-11-21 | 阿莱洛吉克生物科学公司 | 标记有多个荧光团的寡核苷酸 |
| CN101506384A (zh) * | 2006-07-17 | 2009-08-12 | 布兰迪斯大学 | 专一性寡核苷酸和其在核酸扩增与检测中的用途 |
| US20090023151A1 (en) * | 2006-08-30 | 2009-01-22 | Dawson Elliott P | Method For The Labeling And Detection Of Small Polynucleotides |
| WO2012096523A2 (en) * | 2011-01-11 | 2012-07-19 | Seegene, Inc. | Detection of target nucleic acid sequences by pto cleavage and extension assay |
| WO2012134195A2 (en) * | 2011-03-29 | 2012-10-04 | Seegene, Inc. | Detection of target nucleic acid sequence by pto cleavage and extension-dependent cleavage |
Also Published As
| Publication number | Publication date |
|---|---|
| MX361191B (es) | 2018-11-29 |
| EP2943586A4 (en) | 2016-09-28 |
| KR20150093766A (ko) | 2015-08-18 |
| KR101760267B1 (ko) | 2017-07-24 |
| MX2015008494A (es) | 2015-09-10 |
| US20180057869A1 (en) | 2018-03-01 |
| CN104903465A (zh) | 2015-09-09 |
| US20160060690A1 (en) | 2016-03-03 |
| ES2653642T3 (es) | 2018-02-08 |
| EP2943586B1 (en) | 2017-09-20 |
| AU2013371128B2 (en) | 2017-08-10 |
| CA2896213C (en) | 2018-12-11 |
| US9783845B2 (en) | 2017-10-10 |
| RU2015130335A (ru) | 2017-01-30 |
| BR112015014152A2 (enExample) | 2017-08-22 |
| EP2943586A1 (en) | 2015-11-18 |
| JP2016502861A (ja) | 2016-02-01 |
| CA2896213A1 (en) | 2014-07-03 |
| JP6178430B2 (ja) | 2017-08-09 |
| RU2620958C2 (ru) | 2017-05-30 |
| AU2013371128A1 (en) | 2015-08-13 |
| BR112015014152B1 (pt) | 2023-01-24 |
| WO2014104818A1 (en) | 2014-07-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104903465B (zh) | 基于寡核苷酸切割及延伸‑依赖性非‑杂交探测的靶核酸序列的检测 | |
| JP6244440B2 (ja) | Ｐｔｏ切断及び伸長アッセイによるターゲット核酸配列の検出 | |
| CN103534358B (zh) | 基于pto切割以及延伸-依赖性切割的靶核酸序列的检测 | |
| CN104145029B (zh) | 利用探测和标记寡核苷酸切割及延伸-依赖性信号传导寡核苷酸杂交的靶核酸序列的检测 | |
| CN104245959B (zh) | 基于探测和标记寡核苷酸切割及延伸试验的从靶核酸序列的核苷酸变异检测 | |
| JP6529934B2 (ja) | Ｐｏ切断及びハイブリダイゼーションによるターゲット核酸配列の検出 | |
| JP6096885B2 (ja) | ＰＴＯ切断及び伸長依存的なシグナリングオリゴヌクレオチド切断を用いたターゲット核酸配列の検出｛ＤｅｔｅｃｔｉｏｎｏｆＴａｒｇｅｔＮｕｃｌｅｉｃＡｃｉｄＳｅｑｕｅｎｃｅｂｙＰＴＯＣｌｅａｖａｇｅａｎｄＥｘｔｅｎｓｉｏｎ−ＤｅｐｅｎｄｅｎｔＳｉｇｎａｌｉｎｇＯｌｉｇｏｎｕｃｌｅｏｔｉｄｅＣｌｅａｖａｇｅ｝ | |
| CN105705657B (zh) | 基于利用杂交-捕捉和模板化寡核苷酸的探测和标记寡核苷酸切割及延伸分析的在固相中的靶核酸序列检测 | |
| AU2015203677B2 (en) | Detection of Target Nucleic Acid Sequences by PTO Cleavage and Extension | |
| KR20170142128A (ko) | Cto 세트를 사용한 pto 절단 및 연장 어세이에 의한 타겟 핵산서열의 검출 | |
| RU2588457C2 (ru) | Определение целевых нуклеиновокислотных последовательностей путем расщепления зондирующего олигонуклеотида и гибридизации |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |