JP5122705B2 - 神経変性疾患における異常型タンパク質凝集の迅速かつ高感度の検出 - Google Patents
神経変性疾患における異常型タンパク質凝集の迅速かつ高感度の検出 Download PDFInfo
- Publication number
- JP5122705B2 JP5122705B2 JP2000595161A JP2000595161A JP5122705B2 JP 5122705 B2 JP5122705 B2 JP 5122705B2 JP 2000595161 A JP2000595161 A JP 2000595161A JP 2000595161 A JP2000595161 A JP 2000595161A JP 5122705 B2 JP5122705 B2 JP 5122705B2
- Authority
- JP
- Japan
- Prior art keywords
- species
- binding
- colloidal
- fibril
- particles
- 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
- 230000004770 neurodegeneration Effects 0.000 title description 67
- 208000015122 neurodegenerative disease Diseases 0.000 title description 67
- 238000011896 sensitive detection Methods 0.000 title description 3
- 230000004849 abnormal protein aggregation Effects 0.000 title 1
- 230000027455 binding Effects 0.000 claims description 152
- 239000000084 colloidal system Substances 0.000 claims description 122
- 238000000034 method Methods 0.000 claims description 117
- 239000002245 particle Substances 0.000 claims description 115
- 239000013545 self-assembled monolayer Substances 0.000 claims description 64
- 229910052751 metal Inorganic materials 0.000 claims description 53
- 239000002184 metal Substances 0.000 claims description 53
- 239000002094 self assembled monolayer Substances 0.000 claims description 48
- 102000004169 proteins and genes Human genes 0.000 claims description 37
- 108090000623 proteins and genes Proteins 0.000 claims description 37
- 230000003993 interaction Effects 0.000 claims description 31
- 230000000694 effects Effects 0.000 claims description 20
- 230000011664 signaling Effects 0.000 claims description 19
- 102000004190 Enzymes Human genes 0.000 claims description 15
- 108090000790 Enzymes Proteins 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 150000007942 carboxylates Chemical group 0.000 claims description 7
- 238000010521 absorption reaction Methods 0.000 claims description 6
- 238000013459 approach Methods 0.000 claims description 6
- 150000007523 nucleic acids Chemical group 0.000 claims description 5
- 230000005855 radiation Effects 0.000 claims description 4
- 239000002243 precursor Substances 0.000 claims description 3
- ZBKIUFWVEIBQRT-UHFFFAOYSA-N gold(1+) Chemical compound [Au+] ZBKIUFWVEIBQRT-UHFFFAOYSA-N 0.000 claims description 2
- 230000003100 immobilizing effect Effects 0.000 claims 5
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 2
- 239000012491 analyte Substances 0.000 claims 1
- 239000012620 biological material Substances 0.000 claims 1
- 239000002923 metal particle Substances 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 claims 1
- 241000894007 species Species 0.000 description 262
- 108090000765 processed proteins & peptides Proteins 0.000 description 138
- 239000000243 solution Substances 0.000 description 97
- 238000003556 assay Methods 0.000 description 68
- 230000002776 aggregation Effects 0.000 description 61
- 230000015572 biosynthetic process Effects 0.000 description 60
- 239000000523 sample Substances 0.000 description 58
- 102000004196 processed proteins & peptides Human genes 0.000 description 54
- 238000004220 aggregation Methods 0.000 description 49
- 239000011324 bead Substances 0.000 description 48
- 239000003814 drug Substances 0.000 description 43
- 238000001514 detection method Methods 0.000 description 41
- 229940079593 drug Drugs 0.000 description 39
- 235000018102 proteins Nutrition 0.000 description 35
- 108091000054 Prion Proteins 0.000 description 29
- 201000010099 disease Diseases 0.000 description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 25
- 102100034452 Alternative prion protein Human genes 0.000 description 24
- 229940000406 drug candidate Drugs 0.000 description 23
- 239000000126 substance Substances 0.000 description 23
- 150000001875 compounds Chemical class 0.000 description 21
- 239000000203 mixture Substances 0.000 description 20
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 19
- 150000003573 thiols Chemical class 0.000 description 19
- 238000002965 ELISA Methods 0.000 description 18
- 239000013642 negative control Substances 0.000 description 18
- 108010064397 amyloid beta-protein (1-40) Proteins 0.000 description 16
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 16
- 239000010931 gold Substances 0.000 description 16
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 15
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 15
- 229910052737 gold Inorganic materials 0.000 description 15
- 235000014304 histidine Nutrition 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 14
- 230000001965 increasing effect Effects 0.000 description 14
- 238000005054 agglomeration Methods 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 description 13
- 230000008569 process Effects 0.000 description 13
- 208000024827 Alzheimer disease Diseases 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 12
- 238000000149 argon plasma sintering Methods 0.000 description 12
- 230000008859 change Effects 0.000 description 12
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 12
- 239000006249 magnetic particle Substances 0.000 description 12
- 238000000682 scanning probe acoustic microscopy Methods 0.000 description 12
- 230000003321 amplification Effects 0.000 description 11
- 208000015181 infectious disease Diseases 0.000 description 11
- 230000002458 infectious effect Effects 0.000 description 11
- 238000005259 measurement Methods 0.000 description 11
- 238000003199 nucleic acid amplification method Methods 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 239000013522 chelant Substances 0.000 description 10
- 239000003446 ligand Substances 0.000 description 10
- 230000001717 pathogenic effect Effects 0.000 description 10
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 9
- 239000012091 fetal bovine serum Substances 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 8
- 230000003647 oxidation Effects 0.000 description 8
- 238000007254 oxidation reaction Methods 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- 238000013019 agitation Methods 0.000 description 7
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 7
- 125000005647 linker group Chemical group 0.000 description 7
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 6
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 6
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 102000029797 Prion Human genes 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 239000000412 dendrimer Substances 0.000 description 6
- 229920000736 dendritic polymer Polymers 0.000 description 6
- 238000007877 drug screening Methods 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 230000035945 sensitivity Effects 0.000 description 6
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 229910052723 transition metal Inorganic materials 0.000 description 6
- 150000003624 transition metals Chemical class 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 208000024777 Prion disease Diseases 0.000 description 5
- 230000004520 agglutination Effects 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 210000001124 body fluid Anatomy 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 5
- 230000005672 electromagnetic field Effects 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000007505 plaque formation Effects 0.000 description 5
- 239000002356 single layer Substances 0.000 description 5
- 239000004094 surface-active agent Substances 0.000 description 5
- 238000004832 voltammetry Methods 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
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- -1 antibacterials Substances 0.000 description 4
- 239000012472 biological sample Substances 0.000 description 4
- 239000010839 body fluid Substances 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 230000001747 exhibiting effect Effects 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- JADVWWSKYZXRGX-UHFFFAOYSA-M thioflavine T Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C1=[N+](C)C2=CC=C(C)C=C2S1 JADVWWSKYZXRGX-UHFFFAOYSA-M 0.000 description 4
- 238000011179 visual inspection Methods 0.000 description 4
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 3
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 3
- 241000699800 Cricetinae Species 0.000 description 3
- 241000699673 Mesocricetus auratus Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000004931 aggregating effect Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000004891 communication Methods 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 230000005670 electromagnetic radiation Effects 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 239000002070 nanowire Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 239000012488 sample solution Substances 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 125000006850 spacer group Chemical class 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- YXIWHUQXZSMYRE-UHFFFAOYSA-N 1,3-benzothiazole-2-thiol Chemical compound C1=CC=C2SC(S)=NC2=C1 YXIWHUQXZSMYRE-UHFFFAOYSA-N 0.000 description 2
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 2
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 2
- 102100022717 Atypical chemokine receptor 1 Human genes 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 101000678879 Homo sapiens Atypical chemokine receptor 1 Proteins 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 108090000189 Neuropeptides Proteins 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 238000004847 absorption spectroscopy Methods 0.000 description 2
- 150000001356 alkyl thiols Chemical class 0.000 description 2
- 230000003941 amyloidogenesis Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000005540 biological transmission Effects 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
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 150000004696 coordination complex Chemical class 0.000 description 2
- 238000002484 cyclic voltammetry Methods 0.000 description 2
- ZHYHKXNRKQTQFP-UHFFFAOYSA-N cyclopenta-1,3-diene cyclopenta-1,3-diene-1-thiol iron(2+) Chemical compound [Fe++].c1cc[cH-]c1.Sc1ccc[cH-]1 ZHYHKXNRKQTQFP-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000000151 deposition Methods 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 238000007878 drug screening assay Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 210000004126 nerve fiber Anatomy 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000013610 patient sample Substances 0.000 description 2
- 230000006919 peptide aggregation Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000003014 reinforcing effect Effects 0.000 description 2
- 238000007423 screening assay Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000012536 storage buffer Substances 0.000 description 2
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- CNDCQWGRLNGNNO-UHFFFAOYSA-N 2-(2-sulfanylethoxy)ethanethiol Chemical compound SCCOCCS CNDCQWGRLNGNNO-UHFFFAOYSA-N 0.000 description 1
- DYNBNOLIHUTXSO-UHFFFAOYSA-N 2-ethynylbenzenethiol Chemical compound SC1=CC=CC=C1C#C DYNBNOLIHUTXSO-UHFFFAOYSA-N 0.000 description 1
- ZMRFRBHYXOQLDK-UHFFFAOYSA-N 2-phenylethanethiol Chemical compound SCCC1=CC=CC=C1 ZMRFRBHYXOQLDK-UHFFFAOYSA-N 0.000 description 1
- 102000001049 Amyloid Human genes 0.000 description 1
- 108010094108 Amyloid Proteins 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 230000006980 Aβ overexpression Effects 0.000 description 1
- 229910000897 Babbitt (metal) Inorganic materials 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- KEZZLRJHEAOKLP-UHFFFAOYSA-N CC1=C(C(=C([CH-]1)C)C)C.[C-]1(C(=C(C(=C1C)C)C)C)S.[Fe+2] Chemical compound CC1=C(C(=C([CH-]1)C)C)C.[C-]1(C(=C(C(=C1C)C)C)C)S.[Fe+2] KEZZLRJHEAOKLP-UHFFFAOYSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 208000034846 Familial Amyloid Neuropathies Diseases 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 206010019889 Hereditary neuropathic amyloidosis Diseases 0.000 description 1
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 241000080590 Niso Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- SZKKRCSOSQAJDE-UHFFFAOYSA-N Schradan Chemical group CN(C)P(=O)(N(C)C)OP(=O)(N(C)C)N(C)C SZKKRCSOSQAJDE-UHFFFAOYSA-N 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 229910021607 Silver chloride Inorganic materials 0.000 description 1
- 102000019355 Synuclein Human genes 0.000 description 1
- 108050006783 Synuclein Proteins 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 description 1
- NNJWFWSBENPGEY-UHFFFAOYSA-N [2-(sulfanylmethyl)phenyl]methanethiol Chemical compound SCC1=CC=CC=C1CS NNJWFWSBENPGEY-UHFFFAOYSA-N 0.000 description 1
- 239000007801 affinity label Substances 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 230000004523 agglutinating effect Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 102000003802 alpha-Synuclein Human genes 0.000 description 1
- 108090000185 alpha-Synuclein Proteins 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004873 anchoring Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 208000005881 bovine spongiform encephalopathy Diseases 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 201000006061 fatal familial insomnia Diseases 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 125000003827 glycol group Chemical group 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 150000002343 gold Chemical class 0.000 description 1
- 150000002411 histidines Chemical class 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 208000010544 human prion disease Diseases 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- VSUTUDRPAASKEB-UHFFFAOYSA-N iron(2+);1,2,3,5-tetramethylcyclopenta-1,3-diene Chemical compound [Fe+2].CC=1[CH-]C(C)=C(C)C=1C.CC=1[CH-]C(C)=C(C)C=1C VSUTUDRPAASKEB-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 238000013188 needle biopsy Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- LCCNCVORNKJIRZ-UHFFFAOYSA-N parathion Chemical compound CCOP(=S)(OCC)OC1=CC=C([N+]([O-])=O)C=C1 LCCNCVORNKJIRZ-UHFFFAOYSA-N 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 238000003909 pattern recognition Methods 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- OGOOBRWCZLKZSV-UHFFFAOYSA-N phenanthro[9,10-b]thiophene Chemical compound C12=CC=CC=C2C2=CC=CC=C2C2=C1SC=C2 OGOOBRWCZLKZSV-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002940 repellent Effects 0.000 description 1
- 239000005871 repellent Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 230000009131 signaling function Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 210000001138 tear Anatomy 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000005382 thermal cycling Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 201000007905 transthyretin amyloidosis Diseases 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 239000012905 visible particle Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
-
- 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
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
Landscapes
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nanotechnology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- General Physics & Mathematics (AREA)
- Crystallography & Structural Chemistry (AREA)
- Hematology (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Urology & Nephrology (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Neurosurgery (AREA)
- Food Science & Technology (AREA)
- Neurology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Composite Materials (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- Materials Engineering (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11712699P | 1999-01-25 | 1999-01-25 | |
| US60/117,126 | 1999-01-25 | ||
| US13228899P | 1999-05-03 | 1999-05-03 | |
| US60/132,288 | 1999-05-03 | ||
| US15593799P | 1999-09-24 | 1999-09-24 | |
| US60/155,937 | 1999-09-24 | ||
| PCT/US2000/001997 WO2000043791A2 (en) | 1999-01-25 | 2000-01-25 | Rapid and sensitive detection of aberrant protein aggregation in neurodegenerative diseases |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012161791A Division JP2012230124A (ja) | 1999-01-25 | 2012-07-20 | 神経変性疾患における異常型タンパク質凝集の迅速かつ高感度の検出 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2002540383A JP2002540383A (ja) | 2002-11-26 |
| JP2002540383A5 JP2002540383A5 (enExample) | 2007-03-22 |
| JP5122705B2 true JP5122705B2 (ja) | 2013-01-16 |
Family
ID=27381935
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000595161A Expired - Fee Related JP5122705B2 (ja) | 1999-01-25 | 2000-01-25 | 神経変性疾患における異常型タンパク質凝集の迅速かつ高感度の検出 |
| JP2012161791A Pending JP2012230124A (ja) | 1999-01-25 | 2012-07-20 | 神経変性疾患における異常型タンパク質凝集の迅速かつ高感度の検出 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012161791A Pending JP2012230124A (ja) | 1999-01-25 | 2012-07-20 | 神経変性疾患における異常型タンパク質凝集の迅速かつ高感度の検出 |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1169646A2 (enExample) |
| JP (2) | JP5122705B2 (enExample) |
| AU (1) | AU3474100A (enExample) |
| CA (1) | CA2361013A1 (enExample) |
| WO (1) | WO2000043791A2 (enExample) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2413884A1 (en) * | 2000-06-23 | 2002-01-03 | Minerva Biotechnologies Corporation | Rapid and sensitive detection of protein aggregation |
| AU2002216614A1 (en) | 2000-10-03 | 2002-04-15 | Minerva Biotechnologies Corporation | Electronic detection of interaction based on the interruption of flow |
| EP1336104B1 (en) | 2000-11-01 | 2009-03-25 | Minerva Biotechnologies Corporation | Proteomics based drug comparison methods |
| EP1348034B1 (en) * | 2000-11-15 | 2016-07-20 | Minerva Biotechnologies Corporation | Oligonucleotide identifiers |
| US7700715B2 (en) | 2000-11-27 | 2010-04-20 | Minerva Biotechnologies Corporation | Diagnostic tumor markers, drug screening for tumorigenesis inhibition, and compositions and methods for treatment of cancer |
| US20030044843A1 (en) * | 2001-01-09 | 2003-03-06 | Mitsubishi Pharma Corporation | Novel proteome analysis method and devices therefor |
| US20060051741A1 (en) | 2002-10-04 | 2006-03-09 | Protosera Inc. | Plate for mass spectrometry, process for preparing the same and use thereof |
| US20050026165A1 (en) | 2001-05-31 | 2005-02-03 | Cindy Orser | Detection of conformationally altered proteins and prions |
| AU2002320045B2 (en) | 2001-05-31 | 2008-05-08 | Adlyfe, Inc. | Misfolded protein sensor method |
| EP1425016B1 (en) | 2001-09-05 | 2010-06-02 | Minerva Biotechnologies Corporation | Compositions and methods of treatment of cancer |
| JP2007531505A (ja) | 2002-11-27 | 2007-11-08 | ミネルバ バイオオテクノロジーズ コーポレーション | 癌（ｍｕｃ１）の診断および治療のための技術および組成物 |
| AU2003300371A1 (en) | 2002-12-20 | 2004-07-22 | Minerva Biotechnologies Corporation | Optical devices and methods involving nanoparticles |
| ES2398394T3 (es) | 2003-08-13 | 2013-03-15 | Novartis Vaccines And Diagnostics, Inc. | Reactivos peptídicos específicos de prión |
| DE602005016537D1 (de) | 2004-03-31 | 2009-10-22 | Anges Mg Inc | Testverfahren zur identifizierung eines kandidatenarzneistoffs |
| DE102004040119A1 (de) * | 2004-08-18 | 2006-04-27 | Heinrich-Heine-Universität Düsseldorf | Mittel zur Therapie und Prävention von Prionenerkrankungen |
| US20090130774A1 (en) * | 2005-01-13 | 2009-05-21 | David Peretz | Elisa assays using prion-specific peptide reagents |
| EP1853915B1 (en) | 2005-02-15 | 2011-10-12 | Adlyfe, Inc. | Method for detecting misfolded proteins and prions |
| WO2007030804A1 (en) | 2005-09-09 | 2007-03-15 | Novartis Ag | Prion-specific peptoid reagents |
| JP5097206B2 (ja) | 2006-07-28 | 2012-12-12 | エイディーライフ インコーポレイティッド | 診断および治療のためのペプチドプローブ |
| AU2009246397B2 (en) | 2008-05-13 | 2013-01-17 | University Of Kansas | Metal abstraction peptide (MAP) tag and associated methods |
| KR20160017117A (ko) | 2008-10-09 | 2016-02-15 | 미네르바 바이오테크놀로지 코포레이션 | 세포내에서 다능성을 유도하기 위한 방법 |
| WO2012017739A1 (ja) * | 2010-07-31 | 2012-02-09 | エレコン科学株式会社 | アミロイドアッセイ装置およびアミロイドアッセイ方法 |
| EP4086338A1 (en) | 2011-03-17 | 2022-11-09 | Minerva Biotechnologies Corporation | Method for making pluripotent stem cells |
| KR101352849B1 (ko) * | 2012-01-03 | 2014-01-21 | 주식회사 나노엔텍 | 멀티머-형성 폴리펩타이드의 멀티머형을 분별 검출하는 방법 |
| WO2013181461A2 (en) | 2012-06-01 | 2013-12-05 | University Of Kansas | Metal abstraction peptide with superoxide dismutase activity |
| JP2016520846A (ja) * | 2013-06-06 | 2016-07-14 | コーニンクレッカ フィリップス エヌ ヴェＫｏｎｉｎｋｌｉｊｋｅ Ｐｈｉｌｉｐｓ Ｎ．Ｖ． | 多量体の標的分子の検出に対する粒子ベースの試験において凝集を防ぐ試薬、方法及び装置 |
| EP3256494A4 (en) | 2015-02-10 | 2018-12-05 | Minerva Biotechnologies Corporation | Humanized anti-muc1* antibodies |
| JP6630972B2 (ja) * | 2015-03-24 | 2020-01-15 | 学校法人甲南学園 | アミロイドβペプチドを電気化学的に測定するためのバイオセンサ |
| WO2017138696A1 (ko) * | 2016-02-12 | 2017-08-17 | 주식회사 캔티스 | 단백질 응집형의 검출 방법, 전기화학적 검출 키트 및 이를 이용한 비정상 단백질 응집 관련 질병의 진단 방법 및 전기화학적 진단 키트 |
| US11167283B2 (en) | 2018-05-04 | 2021-11-09 | University Of South Carolina | Dot blot box and use thereof |
| CA3183682A1 (en) | 2020-06-26 | 2021-12-30 | Minerva Biotechnologies Corporation | Anti-nme antibody and method of treating cancer or cancer metastasis |
| CA3248038A1 (en) | 2022-04-12 | 2023-10-19 | Minerva Biotechnologies Corporation | ANTI-MUC1* VARIABLE ANTIBODIES AND RELATED USES |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8417301D0 (en) * | 1984-07-06 | 1984-08-08 | Serono Diagnostics Ltd | Assay |
| US5705402A (en) * | 1988-11-03 | 1998-01-06 | Igen International, Inc. | Method and apparatus for magnetic microparticulate based luminescence assay including plurality of magnets |
| GB9105031D0 (en) * | 1991-03-09 | 1991-04-24 | Fisons Plc | Processing analytical reagents |
| AU5358494A (en) | 1992-10-13 | 1994-05-09 | Duke University | Method of inhibiting binding of amyloid precursor protein to beta-amyloid protein |
| WO1994010569A1 (en) * | 1992-10-26 | 1994-05-11 | Schenk Dale B | METHODS AND COMPOSITIONS FOR THE DETECTION OF SOLUBLE β-AMYLOID PEPTIDE |
| AU690092B2 (en) * | 1992-12-14 | 1998-04-23 | N.V. Innogenetics S.A. | Monoclonal antibodies directed against the microtubule-associated protein tau, hybridomas secreting these antibodies, antigen recognition by these monoclonal antibodies and their applications |
| TW239881B (enExample) * | 1992-12-22 | 1995-02-01 | Sienna Biotech Inc | |
| EP0683234B2 (en) | 1993-01-25 | 2007-06-06 | Takeda Chemical Industries, Ltd. | Antibody against beta-amyloid or their derivative and use thereof |
| JPH06289020A (ja) * | 1993-04-06 | 1994-10-18 | Teijin Ltd | 歯槽骨由来タンパクの測定方法 |
| DE4430023A1 (de) * | 1994-08-24 | 1996-02-29 | Boehringer Mannheim Gmbh | Elektrochemischer Sensor |
| SE9403245D0 (sv) * | 1994-09-26 | 1994-09-26 | Pharmacia Biosensor Ab | Improvements relating to bilayer lipid membranes |
| US6207369B1 (en) * | 1995-03-10 | 2001-03-27 | Meso Scale Technologies, Llc | Multi-array, multi-specific electrochemiluminescence testing |
| EP1416280A3 (en) * | 1995-09-14 | 2005-08-10 | The Regents of the University of California | Antibodies specific for native PrPsc |
| JPH09275214A (ja) * | 1996-04-08 | 1997-10-21 | Hitachi Ltd | 微少電荷制御素子及びその作製法 |
| WO1998029727A2 (en) * | 1996-12-31 | 1998-07-09 | Stephon, Robert, L. | Microsphere-enhanced immunoassay for the detection of veterinary diseases |
| US6306584B1 (en) * | 1997-01-21 | 2001-10-23 | President And Fellows Of Harvard College | Electronic-property probing of biological molecules at surfaces |
| JPH10204350A (ja) * | 1997-01-27 | 1998-08-04 | Seiko Epson Corp | インクとインクジェットヘッドと印刷装置と配線基板 |
| JPH10217457A (ja) * | 1997-02-04 | 1998-08-18 | Seiko Epson Corp | インクジェットヘッドとその製造方法 |
| EP0861900A1 (en) | 1997-02-21 | 1998-09-02 | Erziehungsdirektion Of The Canton Zurich | Immunological detection of prions |
| EP0865078A1 (en) * | 1997-03-13 | 1998-09-16 | Hitachi Europe Limited | Method of depositing nanometre scale particles |
| US5998224A (en) * | 1997-05-16 | 1999-12-07 | Abbott Laboratories | Magnetically assisted binding assays utilizing a magnetically responsive reagent |
| EP0887645A1 (en) * | 1997-06-23 | 1998-12-30 | C.S.E.M. Centre Suisse D'electronique Et De Microtechnique Sa | Procedure and instrumentation for the ultrasensitive detection of prions, prion binding biomolecules and other biomolecules |
| SG75126A1 (en) | 1997-06-23 | 2000-09-19 | Gen Electric | Electrochemical sensor for detection of chlorine in phosgene |
-
2000
- 2000-01-25 JP JP2000595161A patent/JP5122705B2/ja not_active Expired - Fee Related
- 2000-01-25 CA CA002361013A patent/CA2361013A1/en not_active Abandoned
- 2000-01-25 EP EP00913266A patent/EP1169646A2/en not_active Withdrawn
- 2000-01-25 AU AU34741/00A patent/AU3474100A/en not_active Abandoned
- 2000-01-25 WO PCT/US2000/001997 patent/WO2000043791A2/en not_active Ceased
-
2012
- 2012-07-20 JP JP2012161791A patent/JP2012230124A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CA2361013A1 (en) | 2000-07-27 |
| JP2002540383A (ja) | 2002-11-26 |
| WO2000043791A3 (en) | 2001-07-26 |
| JP2012230124A (ja) | 2012-11-22 |
| WO2000043791A9 (en) | 2002-03-28 |
| WO2000043791A2 (en) | 2000-07-27 |
| EP1169646A2 (en) | 2002-01-09 |
| AU3474100A (en) | 2000-08-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2012230124A (ja) | 神経変性疾患における異常型タンパク質凝集の迅速かつ高感度の検出 | |
| JP6662797B2 (ja) | タンパク質凝集の迅速且つ高感度の検出 | |
| JP4223804B2 (ja) | 磁力でのＩｎＳｉｔｕ希釈法 | |
| JP4516273B2 (ja) | オリゴヌクレオチド識別子 | |
| US20050112607A1 (en) | Rapid and sensitive detection of protein aggregation | |
| JP5524812B2 (ja) | コロイド固定化種と非コロイド構造上の種との相互作用 | |
| JP2004526124A5 (enExample) | ||
| Nangare et al. | Nanoarchitectured bioconjugates and bioreceptors mediated surface plasmon resonance biosensor for in vitro diagnosis of Alzheimer’s disease: Development and future prospects | |
| JP2002540383A5 (enExample) | ||
| US20050148101A1 (en) | Interaction of colloid-immobilized species with species on non-colloidal structures | |
| JP2005501238A (ja) | アフィニティタグで改変された粒子 | |
| JP2004512497A (ja) | コロイドが固定された種と非コロイド構造上の種との相互作用 | |
| EP2401617A1 (en) | Detection of complexes of tau and amyloid | |
| JP4335526B2 (ja) | コロイド構造体および非コロイド構造体による結合スピーシーズの検出 | |
| US20060024230A1 (en) | Customized therapeutics and in situ diagnostics | |
| WO2002001225A2 (en) | Tandem signaling assay | |
| AU2002248159A1 (en) | Oligonucleotide identifiers |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070125 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070125 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090727 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20091016 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20091023 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100127 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100720 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20101013 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20101020 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110808 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20111104 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20111111 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120208 |
|
| RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20120307 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20120323 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120720 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20120727 |
|
| 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: 20120925 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20121025 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20151102 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 5122705 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |