JP4110223B2 - Ｐｎａプローブを用いる、溶液中でのヌクレオチドアッセイ法 - Google Patents
Ｐｎａプローブを用いる、溶液中でのヌクレオチドアッセイ法 Download PDFInfo
- Publication number
- JP4110223B2 JP4110223B2 JP53746398A JP53746398A JP4110223B2 JP 4110223 B2 JP4110223 B2 JP 4110223B2 JP 53746398 A JP53746398 A JP 53746398A JP 53746398 A JP53746398 A JP 53746398A JP 4110223 B2 JP4110223 B2 JP 4110223B2
- Authority
- JP
- Japan
- Prior art keywords
- target sequence
- nucleotide
- intensity
- probe
- fluorescence
- 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.)
- Expired - Fee Related
Links
- 239000000523 sample Substances 0.000 title claims abstract description 333
- 239000002773 nucleotide Substances 0.000 title claims abstract description 163
- 125000003729 nucleotide group Chemical group 0.000 title claims abstract description 162
- 238000003556 assay Methods 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 102
- 238000009396 hybridization Methods 0.000 claims abstract description 46
- 239000007788 liquid Substances 0.000 claims abstract description 45
- 239000007787 solid Substances 0.000 claims abstract description 13
- 108020004414 DNA Proteins 0.000 claims description 182
- 239000003550 marker Substances 0.000 claims description 51
- 230000000295 complement effect Effects 0.000 claims description 42
- 102000053602 DNA Human genes 0.000 claims description 27
- 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 claims description 18
- 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 claims description 17
- 238000012360 testing method Methods 0.000 claims description 14
- 238000001514 detection method Methods 0.000 claims description 12
- 239000013642 negative control Substances 0.000 claims description 9
- 238000000926 separation method Methods 0.000 claims description 9
- 238000005119 centrifugation Methods 0.000 claims description 6
- 230000005684 electric field Effects 0.000 claims description 5
- 239000013641 positive control Substances 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 4
- 230000001678 irradiating effect Effects 0.000 claims description 4
- 238000001962 electrophoresis Methods 0.000 claims description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N argon Substances [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- -1 argon ion Chemical class 0.000 claims description 2
- 238000012986 modification Methods 0.000 claims description 2
- 230000004048 modification Effects 0.000 claims description 2
- 238000001556 precipitation Methods 0.000 claims description 2
- 238000012544 monitoring process Methods 0.000 claims 6
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 238000010791 quenching Methods 0.000 claims 1
- 230000000171 quenching effect Effects 0.000 claims 1
- 238000012163 sequencing technique Methods 0.000 abstract description 3
- 108091093037 Peptide nucleic acid Proteins 0.000 description 92
- 239000000243 solution Substances 0.000 description 67
- 239000012634 fragment Substances 0.000 description 32
- 238000002189 fluorescence spectrum Methods 0.000 description 26
- 238000005259 measurement Methods 0.000 description 25
- OSBLTNPMIGYQGY-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;boric acid Chemical compound OB(O)O.OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O OSBLTNPMIGYQGY-UHFFFAOYSA-N 0.000 description 19
- 239000008051 TBE buffer Substances 0.000 description 19
- 239000000872 buffer Substances 0.000 description 19
- 108091028043 Nucleic acid sequence Proteins 0.000 description 12
- 150000007523 nucleic acids Chemical class 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 125000003275 alpha amino acid group Chemical group 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 102000039446 nucleic acids Human genes 0.000 description 9
- 108020004707 nucleic acids Proteins 0.000 description 9
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 8
- 230000035772 mutation Effects 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 8
- 239000000975 dye Substances 0.000 description 7
- 230000005284 excitation Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 5
- 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 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 108020004682 Single-Stranded DNA Proteins 0.000 description 4
- 238000004925 denaturation Methods 0.000 description 4
- 230000036425 denaturation Effects 0.000 description 4
- 238000001917 fluorescence detection Methods 0.000 description 4
- 239000007850 fluorescent dye Substances 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- 239000004952 Polyamide Substances 0.000 description 3
- 102000023732 binding proteins Human genes 0.000 description 3
- 108091008324 binding proteins Proteins 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 238000007405 data analysis Methods 0.000 description 3
- 229920002647 polyamide Polymers 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 238000007901 in situ hybridization Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-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
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 1
- PTDZLXBJOJLWKG-UHFFFAOYSA-N 5-(bromomethyl)-1h-pyrimidine-2,4-dione Chemical compound BrCC1=CNC(=O)NC1=O PTDZLXBJOJLWKG-UHFFFAOYSA-N 0.000 description 1
- GVUOPSNMFBICMM-UHFFFAOYSA-N 5-bromo-6-morpholin-4-yl-1h-pyrimidine-2,4-dione Chemical compound OC1=NC(O)=C(Br)C(N2CCOCC2)=N1 GVUOPSNMFBICMM-UHFFFAOYSA-N 0.000 description 1
- LPXQRXLUHJKZIE-UHFFFAOYSA-N 8-azaguanine Chemical compound NC1=NC(O)=C2NN=NC2=N1 LPXQRXLUHJKZIE-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 239000012625 DNA intercalator Substances 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- 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 1
- 108020005196 Mitochondrial DNA Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 102000001218 Rec A Recombinases Human genes 0.000 description 1
- 108010055016 Rec A Recombinases Proteins 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 101150104425 T4 gene Proteins 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 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 1
- 238000010521 absorption reaction Methods 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 239000012148 binding buffer Substances 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010291 electrical method Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 210000003917 human chromosome Anatomy 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- XDROKJSWHURZGO-UHFFFAOYSA-N isopsoralen Natural products C1=C2OC=CC2=C2OC(=O)C=CC2=C1 XDROKJSWHURZGO-UHFFFAOYSA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000001499 laser induced fluorescence spectroscopy Methods 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000001821 nucleic acid purification Methods 0.000 description 1
- 229920002114 octoxynol-9 Polymers 0.000 description 1
- 108700025694 p53 Genes Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- MLMVLVJMKDPYBM-UHFFFAOYSA-N pseudoisopsoralene Natural products C1=C2C=COC2=C2OC(=O)C=CC2=C1 MLMVLVJMKDPYBM-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012284 sample analysis method Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- ZEMGGZBWXRYJHK-UHFFFAOYSA-N thiouracil Chemical compound O=C1C=CNC(=S)N1 ZEMGGZBWXRYJHK-UHFFFAOYSA-N 0.000 description 1
- 229950000329 thiouracil Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
Images
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80790197A | 1997-02-27 | 1997-02-27 | |
| US08/807,901 | 1997-02-27 | ||
| US08/870,370 US6060242A (en) | 1997-02-27 | 1997-06-06 | PNA diagnostic methods |
| US08/870,370 | 1997-06-06 | ||
| PCT/IB1998/000521 WO1998038334A1 (en) | 1997-02-27 | 1998-02-23 | Assaying nucleotides in solution using pna probes |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2001514497A JP2001514497A (ja) | 2001-09-11 |
| JP2001514497A5 JP2001514497A5 (enExample) | 2005-01-13 |
| JP4110223B2 true JP4110223B2 (ja) | 2008-07-02 |
Family
ID=27123055
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP53746398A Expired - Fee Related JP4110223B2 (ja) | 1997-02-27 | 1998-02-23 | Ｐｎａプローブを用いる、溶液中でのヌクレオチドアッセイ法 |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP0975800B1 (enExample) |
| JP (1) | JP4110223B2 (enExample) |
| AT (1) | ATE241018T1 (enExample) |
| AU (1) | AU736701B2 (enExample) |
| CA (1) | CA2282704C (enExample) |
| CY (1) | CY2406B1 (enExample) |
| DE (1) | DE69814848T2 (enExample) |
| DK (1) | DK0975800T3 (enExample) |
| ES (1) | ES2202821T3 (enExample) |
| IN (1) | IN188176B (enExample) |
| PT (1) | PT975800E (enExample) |
| TW (1) | TW389791B (enExample) |
| WO (1) | WO1998038334A1 (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2288760T3 (es) | 1996-04-25 | 2008-01-16 | Bioarray Solutions Ltd. | Ensamblaje electrocinetico controlado por luz de particulas proximas a superficies. |
| US6251591B1 (en) | 1997-02-27 | 2001-06-26 | Lorne Park Research, Inc. | Quantitative method for detecting nucleotide concentration |
| US6046004A (en) * | 1997-02-27 | 2000-04-04 | Lorne Park Research, Inc. | Solution hybridization of nucleic acids with antisense probes having modified backbones |
| EP1536023B1 (en) * | 1998-12-08 | 2008-03-19 | Boston Probes, Inc. | Methods, kits and compositions for the identification of nucleic acids electrostatically bound to matrices |
| US6441152B1 (en) | 1998-12-08 | 2002-08-27 | Boston Probes, Inc. | Methods, kits and compositions for the identification of nucleic acids electrostatically bound to matrices |
| US6656692B2 (en) * | 1999-12-21 | 2003-12-02 | Ingeneus Corporation | Parallel or antiparallel, homologous or complementary binding of nucleic acids or analogues thereof to form duplex, triplex or quadruplex complexes |
| JP2003527075A (ja) * | 1999-03-25 | 2003-09-16 | ハイセック，インコーポレーテッド | ハイブリダイゼーションによる配列分析のための、溶液ベースの方法 |
| US6265170B1 (en) * | 2000-01-24 | 2001-07-24 | Ingeneus Corporation | Homogenous assay of duplex of triplex hybridization by means of multiple measurements under varied conditions |
| US7220541B2 (en) * | 2000-01-24 | 2007-05-22 | Ingeneus, Inc. | Homogeneous assay of biopolymer binding by means of multiple measurements under varied conditions |
| US9709559B2 (en) | 2000-06-21 | 2017-07-18 | Bioarray Solutions, Ltd. | Multianalyte molecular analysis using application-specific random particle arrays |
| US7264925B2 (en) | 2000-08-30 | 2007-09-04 | Avi Biopharma, Inc. | Method for analysis of oligonucleotide analogs |
| US7262063B2 (en) | 2001-06-21 | 2007-08-28 | Bio Array Solutions, Ltd. | Directed assembly of functional heterostructures |
| JP4377689B2 (ja) | 2001-10-15 | 2009-12-02 | バイオアレイ ソリューションズ リミテッド | 同時尋問及び酵素仲介検出による多型遺伝子座の複合分析 |
| US7810380B2 (en) | 2003-03-25 | 2010-10-12 | Tearlab Research, Inc. | Systems and methods for collecting tear film and measuring tear film osmolarity |
| US7041453B2 (en) | 2002-08-22 | 2006-05-09 | Bioarray Solutions Ltd. | Molecular constructs and methods of use for detection of biochemical reactions |
| WO2004047007A1 (en) | 2002-11-15 | 2004-06-03 | Bioarray Solutions, Ltd. | Analysis, secure access to, and transmission of array images |
| AU2004276761B2 (en) | 2003-09-22 | 2009-12-24 | Bioarray Solutions, Ltd. | Surface immobilized polyelectrolyte with multiple functional groups capable of covalently bonding to biomolecules |
| EP1678495A4 (en) * | 2003-10-20 | 2007-06-27 | Univ California | TRANSDUCTION SYSTEMS IN THE NANOMASSIC STATION FOR DETECTING MOLECULAR INTERACTIONS |
| CA2544041C (en) | 2003-10-28 | 2015-12-08 | Bioarray Solutions Ltd. | Optimization of gene expression analysis using immobilized capture probes |
| US7848889B2 (en) | 2004-08-02 | 2010-12-07 | Bioarray Solutions, Ltd. | Automated analysis of multiplexed probe-target interaction patterns: pattern matching and allele identification |
| ES2546743B1 (es) | 2014-03-28 | 2016-07-07 | Institut D'investigació Biomèdica De Bellvitge (Idibell) | Marcadores mitocondriales de enfermedades neurodegenerativas |
| BR112017005121A2 (pt) | 2014-09-23 | 2018-07-31 | Tearlab Res Inc | sistemas e métodos para integração de coleta de lágrima microfluídica e análise de fluxo lateral de analitos de interesse. |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0232967B1 (en) * | 1986-01-10 | 1993-04-28 | Amoco Corporation | Competitive homogeneous assay |
| WO1992018650A1 (en) * | 1991-04-11 | 1992-10-29 | Baxter Diagnostics Inc. | Detection of dna/rna by fluorescence polarization |
| US5539082A (en) * | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| DE4216949C2 (de) * | 1992-05-22 | 1997-07-24 | Christoph Prof Dr Dr Cremer | Nichtenzymatisches Verfahren zur In-situ-Hybridisierung bei spezifischen Proben |
| JPH11512617A (ja) * | 1995-10-06 | 1999-11-02 | パーセプテイブ・バイオシステムズ・インコーポレイテツド | ペプチド核酸プローブを用いるハイブリダイゼーション分析のための方法、装置及びキット |
-
1998
- 1998-02-23 PT PT98910911T patent/PT975800E/pt unknown
- 1998-02-23 ES ES98910911T patent/ES2202821T3/es not_active Expired - Lifetime
- 1998-02-23 EP EP98910911A patent/EP0975800B1/en not_active Expired - Lifetime
- 1998-02-23 AU AU65135/98A patent/AU736701B2/en not_active Ceased
- 1998-02-23 DE DE69814848T patent/DE69814848T2/de not_active Expired - Fee Related
- 1998-02-23 JP JP53746398A patent/JP4110223B2/ja not_active Expired - Fee Related
- 1998-02-23 WO PCT/IB1998/000521 patent/WO1998038334A1/en not_active Ceased
- 1998-02-23 DK DK98910911T patent/DK0975800T3/da active
- 1998-02-23 AT AT98910911T patent/ATE241018T1/de not_active IP Right Cessation
- 1998-02-23 CA CA002282704A patent/CA2282704C/en not_active Expired - Fee Related
- 1998-02-26 IN IN486DE1998 patent/IN188176B/en unknown
- 1998-03-12 TW TW087102841A patent/TW389791B/zh not_active IP Right Cessation
-
2004
- 2004-02-13 CY CY0400009A patent/CY2406B1/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2001514497A (ja) | 2001-09-11 |
| TW389791B (en) | 2000-05-11 |
| DE69814848D1 (de) | 2003-06-26 |
| AU6513598A (en) | 1998-09-18 |
| WO1998038334A1 (en) | 1998-09-03 |
| ATE241018T1 (de) | 2003-06-15 |
| IN188176B (enExample) | 2002-08-31 |
| DE69814848T2 (de) | 2004-05-06 |
| EP0975800A1 (en) | 2000-02-02 |
| CA2282704C (en) | 2007-11-13 |
| AU736701B2 (en) | 2001-08-02 |
| DK0975800T3 (da) | 2003-09-22 |
| PT975800E (pt) | 2003-10-31 |
| ES2202821T3 (es) | 2004-04-01 |
| CY2406B1 (en) | 2004-09-10 |
| CA2282704A1 (en) | 1998-09-03 |
| EP0975800B1 (en) | 2003-05-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4110223B2 (ja) | Ｐｎａプローブを用いる、溶液中でのヌクレオチドアッセイ法 | |
| US6060242A (en) | PNA diagnostic methods | |
| US5846729A (en) | Assaying nucleotides in solution using a fluorescent intensity quenching effect | |
| EP1242620B1 (en) | Fluorescent intensity assay for duplex and triplex nucleic acid hybridization in solution utilizing fluorescent intercalators | |
| US6046004A (en) | Solution hybridization of nucleic acids with antisense probes having modified backbones | |
| US5800994A (en) | Hybridization-ligation assays for the detection of specific nucleic acid sequences | |
| EP1250459B1 (en) | Homogenous assay of duplex or triplex hybridization by means of multiple measurements under varied conditions | |
| US6251591B1 (en) | Quantitative method for detecting nucleotide concentration | |
| JP2005525787A (ja) | プローブとの相互作用による遺伝子ハプロタイプの検出方法 | |
| KR100617427B1 (ko) | 다양한 조건하의 다중 측정에 의한 생중합체 결합의 균일분석 방법 | |
| WO2001068913A2 (en) | Nucleic acid detection method and system | |
| Corley-Smith et al. | Efficient detection of DNA polymorphisms by fluorescent RAPD analysis | |
| CA2170950A1 (en) | Method of quick screening and identification of specific dna sequences by a single nucleotide primer extension and kits thereof | |
| US20040203005A1 (en) | Dual hybridization of complex nucleic acid samples for sequencing and single-nucleotide polymorphism identification |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20040413 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040413 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20040916 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070612 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20070911 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20071022 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071212 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20080205 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20080306 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20080306 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110418 Year of fee payment: 3 |
|
| LAPS | Cancellation because of no payment of annual fees |